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Biomedical subjects

E Haber

Publications and source records attributed to E Haber.

At least 325 records · Page 18Linked to original sources
PubMed1972

Inhibition of angiotensin conversion in experimental renovascular hypertension.

Constriction of the renal artery and controlled reduction of renal perfusion pressure is followed by a prompt increase in systemic renin activity and a concomitant rise in blood pressure in trained, unanesthetized dogs. The elevated blood pressure induced by the renal artery stenosis can be prevented by prior treatment with the nonapeptide Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro, which blocks conversion of angiotensin I to angiotensin II. Further, the nonapeptide can restore systemic pressure to normnal in the early phase of renovascular hypertension. These results offer strong evidence that the renin-angiotensin system is responsible for the initiation of hypertension in the unilaterally nephrectomized dog with renal artery constriction.

Angiotensin II↗
PubMed1972

Identification of the cardiac beta-adrenergic receptor protein: solubilization and purification by affinity chromatography.

A protein that binds catecholamines with a specificity parallel to that of their in vivo effects on cardiac contractility (isoproterenol > epinephrine or norepinephrine > dopamine > dihydroxyphenylalanine) was solubilized from a microsomal fraction of canine ventricular myocardium. The binding protein was purified 500 to 800-fold by solubilization and subsequent affinity chromatography with conjugates of norepinephrine linked to agarose beads. Purified beta-adrenergic binding protein exists in two forms, corresponding to molecular weights of 40,000 and 160,000. The purified material has a single association constant, 2.3 x 10(5) liters/mol (as compared to two association constants, 10(7) and 10(6) liters/mol, for the binding protein in particulate form) but retains the identical binding specificity for beta-adrenergic drugs and antagonists.

Amination↗
PubMed1972

Changes in intrinsic circular dichroism of several homogeneous anti-type 3 pneumococcal antibodies on binding of a small hapten.

Three homogeneous antibodies against the capsular polysaccharide of Type III pneumococci of similar specificities and affinities were purified from a single bleeding of an individual rabbit and fractionated by isoelectric focusing. A comparison of the circular dichroic spectra of the three antibodies revealed differences among them, although the spectra were generally similar to those obtained previously for heterogeneous rabbit antibodies [Cathou, R. E., Kulcycki, A., Jr. & Haber, E. (1968) Biochemistry 7, 3958]. On binding of the hexasaccharide, -[-->3)-beta-D-glucuronic acid-(1-->4)-beta-D-glucose-(1-](3)-->, significant changes in all three circular dichroic spectra were observed. Since the oligosaccharide alone shows no transitions above 220 nm, these spectral changes can be attributed to changes in the intrinsic optical activity of the antibodies. Calculated difference circular dichroism spectra (of antibody minus that of antibody-hapten complex) of the three antibodies are different from each other, and resemble spectra of tryptophan and tyrosine derivatives. These changes in optical activity can be ascribed to changes in the asymmetric environments of aromatic chromophores directly in the combining site and/or to changes in orientation inside or beyond the site. Since the hapten-antibody interactions are different in the three antibodies, as shown by the difference spectra, the structures of the combining sites are presumably also different. We have interpreted these observations to mean that a relatively simple ligand may be bound by several different complementary sites.

Animals↗
PubMed1972

An active derivative of rabbit antibody light chain composed of the constant and the variable domains held together only by a native disulfide bond.

The immunoglobulin light chain is thought to be organized into two structural domains, the constant and the variable regions, linked by a switch region of lesser tertiary organization. Light chains of homogeneous rabbit antibodies to pneumococcal polysaccharides labeled with (125)I were subjected to trypsin digestion at different temperatures. At 43 degrees molecular size (as determined by gel filtration) remained unchanged until the chain was subjected to full reduction and alkylation, when half molecules were demonstrated. One light chain resisted tryptic digestion at 43 degrees . At 50 degrees extensive digestion to small peptides occurred. These experiments confirm the susceptibility of the switch region to enzymatic attack as well as the relative resistance of the constant and variable region domains. They also demonstrate that the third disulfide bridge in rabbit light chain extends between the two structural domains and maintains the integrity of the molecule even when a peptide bond in the switch region is cleaved. When the light chain was subjected to dilute acid hydrolysis [10% acetic acid-pyridine (pH 2.5) in 7 M guanidine-HCl for 24-90 hr] selective cleavage at the switch region was demonstrated in yields up to 90%. The site of cleavage was shown to be the acid labile Asp 109-Pro 110 bond by automated Edman degradation. After cleavage the molecule remained intact until full reduction and alkylation, when half molecules were again demonstrated. A light chain cleaved in this way with its interdomain disulfide bond intact, was able to recombine with a homologous heavy chain and restore antigen binding. This indicates that an intact switch region is not needed for antibody activity. The availability of a functional variable region now allows for planning an examination of the antibody combining site by the technique of peptide synthesis.

Acetamides↗