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Biomedical subjects

S Blumberg

Publications and source records attributed to S Blumberg.

At least 73 records · Page 4Linked to original sources
PubMed1980

Substance P and analogues: biological activity and degradation.

A series of C-terminal partial sequences of Substance P, either free or blocked at the amino terminus, has been synthesized. The peptides were examined for their relative potencies as smooth muscle contracting agents and for their rates of degradation by rat brain synaptosomes. The C-terminal hexapeptide in both the free and blocked forms displays activity comparable to that of the longer C-terminal peptides as well as to that of the native undecapeptide. The blocked peptides, however, are much more stable than the corresponding free peptides. Among the free peptides Substance P is degraded virtually at the same rate as the C-terminal octapeptide but significantly more slowly than the C-terminal hexa- or heptapeptides. These patterns of inactivation together with the response to inhibition by various protease inhibitors indicate that both endopeptidase(s) are involved in the degradation of Substance P. Degradation of the Substance P molecule at Substance P synapses may occur in two steps, first by a specific endopeptidase splitting the molecule into an N-terminal tetrapeptide and a C-terminal heptapeptide, the latter being degraded in a second step by aminopeptidases.

Animals↗
PubMed1980

A possible association between influenza vaccination and small-vessel vasculitis.

We describe two patients who experienced small-vessel vasculitic syndromes after influenza immunization. Their illnesses were characterized by fever, arthralgias, and myalgias; uveitis and optic neuritis occurred in one patient, while the other had palpable purpura, which histologically was proved to be a cutaneous necrotizing venulitis. No viral or bacterial infection, medications, or underlying systemic rheumatic disease could be implicated. To our knowledge, small-vessel vasculitis occurring after influenza vaccination has not been previously reported.

Adult↗
PubMed1979

The psychological effects of differential treatment of a high risk sample in a randomized clinical trial.

A study was carried out using 616 participants in a randomized clinical trial at the Harvard MRFIT (Multiple Risk Factor Intervention Trial) Clinical Center, to test if there were differences in the psychological dimensions of anxiety, depression, and functional heart symptoms in groups given different levels of treatment in a CHD (Coronary Heart Disease) Intervention Program. A theoretical framework was given to justify a number of hypotheses as to the induction of adverse psychological effects. At the end of two years in the MRFIT Program there were no significant differences between the special intervention group (SI) and the usual care group (UC) in the selected psychological variables.

Anxiety↗
PubMed1978

Modulation of the catalytic properties of alpha-chymotrypsin by chemical modification at Tyr 146.

alpha--Chymotrypsin was modified with three different diazonium salts derived from D--phenylalanine. All three reagents react selectively with tyrosine 146 on the surface of the enzyme. The spectral and enzymatic properties of the azochymotrypsins are characteristic for each of the proteins. Dependent on the structure of the reagent employed for modification, the activity towards rho-nitroanilide substrate can be higher or about the same as that of the native enzyme.

Amino Acid Sequence↗
PubMed1976

Effect of divalent metal ions on the digestibility of concanavalin A by endopeptidases.

Demetallized concanavalin A is degraded rapidly at pH 7.0 and 8.2 by alpha-chymotrypsin, thermolysin or trypsin, yielding peptide fragments devoid of ability to bind to Sephadex G-75. Addition of Ni2+ and of Ca2+ confers on concanavalin A high resistance towards proteolytic attack so that even after long periods of exposure to the enzymes, almost all of the saccharide-binding capacity is preserved. Ni2+ alone protects strongly at pH 7.0 but not at pH 8.2. Apparently, both the transition metal ion and Ca2+ play an important role in stabilizing the native conformation of the protein molecule. Digestion of demetallized concanavalin A with alpha-chymotrypsin or thermolysin readily yields small peptide fragments (Mr less than 10 000), while trypsin yields as the major product(s) larger peptide(s) (Mr approximately 20 000) of appreciable resistance to further fragmentation.

Calcium↗
PubMed1976

Superactivation of neutral proteases: acylation with N-hydroxysuccinimide esters.

A series N-hydroxysuccinimide esters of acylamino acids previously shown to acylate and thereby increase the activity of thermolysin by several orders of magnitude (Blumberg, S., and Vallee, B. L. (1975), Biochemistry 14, 2410) has been used to modify the related neutral proteases from Bacillus subtilis, Bacillus megaterium, and Aeromonas proteolytica. Each of these enzymes is activated to a level characteristic of the particular protein and the particular acyl group incorpporated when monitored with the substrate furylacryloyl-Gly-Leu-NH2. Thus, for the modification of B. megaterium, B. subtilis, and A. proteolytica proteases with Ac-Trp-ONSu, kcat/Km increases 11-, 2.5-, and 18-fold whereas those of the Ac-Phe(4-DnpNH)-ONSu modified enzymes before and after deacylation with hydroxylamine indicate that from 1 to 2 residues are modified. The rate of removal of the Ac-Phe(4-DnpNH) label by 0.1 M hydroxylamine correlates directly with that of the return of native enzymatic activity, at a rate comparable with the rate of deacylation of O-acyltyrosine models. The competitive inhibitors Zn2+ and beta-phenyl-propionyl-Phe do not prevent activation indicating that modification occurs at a site(s) distinct from that at which inhibitors bind. The degree of activation depends also on the substrate employed, generally being greater for substrates which the native enzymes hydrolyze slowly. These data are interpreted to indicate the modification of a residue near the active site, but which serves as a subsite for substrate interaction.

Aeromonas↗
PubMed1975

Superactivation of thermolysin by acylation with amino acid N-hydroxysuccinimide esters.

Synthesis of a series of active N-hydroxysuccinimide esters of aliphatic and aromatic amino acids has yielded a new class of reagents for the covalent modification of proteolytic enzymes such as thermolysin. The activities of aliphatic acyl amino acid thermolysins are from 1.7 to 3.6 times greater than that of the native enzyme when hydrolyzing durylacryloyl-Gly-Leu-NH2, the substrate employed most widely. By comparison, the aromatic acylamino acid derivatives are "superactive," their activities being as much as 70-fold greater. Apparently, the aromatic character of the amino acid introduced is a critical variable in the determination of the functional response. The increased activity is completely restored to that of the native enzyme by deacylation with nucleophiles, such as hydroxylamine, and the rate of restoration of native activity is a function of the particular acyl group incorporated. Preliminary evidence regarding the chemical properties of the modified enzyme suggests that tyrosine, rather than lysine, histidine, or arginine, may be the residue modified. The functional consequences of successive modification with different reagents, moreover, indicate that each of them reacts with the same protein residue. The competitive inhibitors beta-phenyl-propionyl-Phe and Zn-2+ do not prevent modification with these active esters. Hence, the site(s) of their inhibitory action differ(s) from that at which modification occurs. The structure of the substrate is also a significant variable which determines the rate at which each acyl amino acid thermolysin hydrolyzes peptides. Depending on the particular substrate, the activity of aromatic derivatives can be as much as 400-fold greater than that of the native enzyme, and the resultant activity patterns can be ordered in a series characteristic for each enzyme derivative.

Acylation↗
PubMed1972

Purification by affinity chromatography of the molecular forms of acetylcholinesterase present in fresh electric-organ tissue of electric eel.

An acetylcholinesterase inhibitor-Sepharose conjugate was prepared by coupling a derivative of the powerful acetylcholinesterase inhibitor, N-methylacridinium, to CNBr-activated Sepharose. Use of this conjugate permitted direct purification, by affinity chromatography, of the two molecular forms of acetylcholinesterase, 14 and 18 S, present in fresh electric organ tissue. The purified 14S and 18S acetylcholinesterases retained the capacity to aggregate at low ionic strength displayed by crude extracts of the enzyme. The major polypeptide components of the 14S and 18S enzymes, as revealed by acrylamide gel electrophoresis, closely resemble those observed in the 11S form of acetylcholinesterase, previously purified after tryptic digestion of electric-organ tissue.

Acetylcholinesterase↗