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Biomedical subjects

B F Erlanger

Publications and source records attributed to B F Erlanger.

At least 145 records · Page 8Linked to original sources
PubMed1971

Photochromic activators of the acetylcholine receptor.

Two photochromic activators of the electrogenic membrane of the electroplax of Electrophorus electricus are described. Trans-3,3'-bis[alpha-(trimethylammonium)methyl]azobenzene dibromide (Bis-Q), one of the most potent ever reported, is active at concentrations of less than 10(-7) M. Its cis isomer, which is obtained from the trans by exposure to light of 330 nm, is practically devoid of activity. Photoregulation of the potential of the membrane takes place in the presence of Bis-Q, presumably because of the conversion of the active trans isomer to the inactive cis isomer in the single-cell electroplax system. The second activator, 3-(alpha-bromomethyl)-3'-[alpha-(trimethylammonium)methyl]azobenzene bromide (QBr) can be covalently attached to the electroplax membrane after reduction of the membrane with dithiothreitol. Activation of the membrane is induced by the covalently linked reagent. Its cis isomer, obtained from the trans by exposure to light of 330 nm, is, like cis-Bis-Q, of very low activity. Both isomers of Bis-Q are equally active as inhibitors of acetylcholinesterase, 50% inhibition occurring at a concentration of 10(-5) M. The possibility of using trans-Bis-Q and trans-QBr to characterize and isolate the receptor protein is discussed.

Acetylcholine↗
PubMed1970

Phenothiazine-N-carbonyl chloride, a specific inactivator of chymotrypsin.

Phenothiazine-N-carbonyl chloride inactivated chymotrypsin and trypsin by means of a 1:1 stoicheiometric reaction. Its reaction with chymotrypsin was 29 times as fast as that with trypsin and was inhibited by indole. The reaction of phenothiazine-N-carbonyl chloride with chymotrypsin resembled an enzyme-substrate reaction in which the deacylation step is rate-limiting. Slow deacylation occurred, resulting in complete regeneration of active enzyme in 15h. The pH-rate profile of the inactivation process had a maximum at pH7.8. These data and other evidence indicate that the reaction of phenothiazine-N-carbonyl chloride with chymotrypsin exhibits ;kinetic specificity'. Therefore any hypothesis that attempts to describe the topography of the active site of chymotrypsin should take into account the reactivity of phenothiazine-N-carbonyl chloride. The above findings, as well as recent reports of others, are examined within the context of a hypothesis given in an earlier paper (Erlanger, 1967).

Binding Sites↗
PubMed1970

Photoregulation of biological activity by photochromic reagents, IV. A model for diurnal variation of enzymic activity.

Levels of acetylcholinesterase activity can be made to vary in response to the presence or absence of sunlight in a system that can be considered as a model for photoperiodic processes found in nature. The enzyme is rendered photosensitive by the presence of a photochromic inhibitor, N-p-phenylazophenylcarbamyl choline, which changes from a trans to a cis isomer under the influence of the light of the sun and reverts back to the trans isomer in the dark. The two isomers differ in their ability acetylcholinesterase, thus rendering the enzyme system responsive to sunlight. The relationship of this system to photoresponsive processes in nature is discussed, and a possible role in photoregulation is suggested for naturally occurring carotenoids.

Acetylcholinesterase↗
PubMed1970

Localization of fluorescein-labeled antinucleoside antibodies in glomeruli of patients with active systemic lupus erythematosus nephritis.

Renal tissues from two groups of patients were studied with fluorescein-labeled (Fl-) antibodies (Abs) to immunoglobulins, complement, and antibodies prepared in rabbits against BSA conjugate of 5-methyluridine (T) and cytidine (C), the latter two of which react specifically with denatured DNA. The first group consisted of 13 SLE patients, and the second consisted of 53 patients with non-SLE nephropathies. The data obtained from the two groups of patients were used for comparison, and they showed the following:(a) Fl-Abs to immunoglobulins and complement were bound in the glomeruli of tissues from all patients with active SLE glomerulonephritis characterized by deposits of foreign material in glomerular capillary walls (GCW). The fluorescent pattern was granular, corresponding to the distribution of the glomerular deposits, as seen by electron microscopy. Fl-Abs reactive with thymine and cytosine were bound in the GCW of eight of the nine patients with active SLE glomerulonephritis and showed the same granular distribution. The capacity of these latter Fl-Abs to stain the GCW was removed by absorption with the homologous antigen or denatured DNA.(b) Fl-Abs to immunoglobulins, complement, and pyrimidine bases of DNA did not react with the GCW of two SLE patients without clinical and histologic evidence of glomerulonephritis or with the sclerotic glomeruli of two uremic patients with chronic "burned out" lupus nephritis.(c) The glomeruli of 47 of the 53 patients with other nephropathies bound Fl-Abs to immunoglobulins and complement to some extent, and in 26, the localization appeared as marked as in the patients with active SLE glomerulonephritis. Fl-Abs reactive with thymine and cytosine were bound in the GCW of only one of the renal tissues from the 53 non-SLE patients. In the remaining 52, no binding was seen.(d) The findings are consistent with the hypothesis that antigen-antibody complexes, formed by denatured DNA, specific antibody, and complement, are present in the deposits of foreign material accumulated in the GCW of patients with active SLE glomerulonephritis, and that they may contribute to the pathogenesis of this renal disease.

Adolescent↗
PubMed1969

Immunologic studies of autoimmune disease in NZB-NZW F1 mice. I. Binding of fluorescein-labeled antinucleoside antibodies in lesions of lupus-like nephritis.

For the past 3 years NZB and NZW mice have been maintained by sister-brother matings from English breeder stock. NZB/NZW F(1) hybrids developed lupus-like nephritis during the 6th to 7th month and few survived beyond the 8th month. Renal tissues of these animals were examined with fluorescein-labeled antinucleoside sera, specific for thymine and cytosine, for the presence of denatured DNA in GCW, and with labeled antibody to mouse IgG for the presence of excess host globulin in the same areas. The following results have been obtained: (a) All 51 hybrids, over 5 months of age, had an excess of mouse globulin in GCW. 40 animals between the ages of 5 and 12 months showed, in the same areas, antigens which bound one or both of the antinucleoside antibodies. (b) Renal tissues of 19 NZB mice, 5-19 months old, and 27 NZW mice, 2-18 months old, were examined. Excess host globulin was seen in GCW of 13 NZB and 20 NZW animals. The tissues of only two old NZB mice, 14 months of age, bound antinucleoside antibody but none of the other animals did. The association of rapidly fatal lupus-like nephritis in NZB/NZW F(1) mice with denatured DNA and mouse globulin in GCW supports the hypothesis involving this antigen-antibody complex in the pathogenesis of the disease.

Animals↗
PubMed1969

Photoregulation of biological activity by photocromic reagents. II. Inhibitors of acetylcholinesterase.

The enzymic activity of acetylcholinesterase can be photoregulated through the mediation of photochromic inhibitors of the enzyme. N-p-phenylazophenyl-N-phenylcarbamyl fluoride, an irreversible inhibitor of acetylcholinesterase, exists as two geometric isomers which are interconvertible through the action of light. The cis isomer, which predominates after exposure to light of 320 nm, is more active than the trans isomer, which results from exposure to light of 420 nm. It was possible, therefore, to use light energy to regulate the inactivation of the enzyme. Similarly, levels of acetylcholinesterase activity could be photo-regulated in a completely reversible manner by means of the photochromic reversible inhibitor p-phenylazophenyltrimethylammonium chloride. These experiments can serve as models for similar phenomena observed in nature, particularly in photoperiodic rhythms of higher animals.

Acetylcholinesterase↗
PubMed1969

Photoregulation of biological activity by photochromic reagents. 3. Photoregulation of bioelectricity by acetylcholine receptor inhibitors.

The photochromic compounds N-p-phenylazophenyl-N-phenylcarbamylcholine chloride and p-phenylazophenyltrimethylammonium chloride inhibit the carbamylcholine-produced depolarization of the excitable membrane of the monocellular electroplax preparation of Electrophorus. The trans isomer of each predominates in the light of a photoflood (420 mmu) lamp; they are stronger inhibitors than the cis isomers, which predominate under ultraviolet (320 mmu) irradiation. The potential difference across the excitable membrane may be photoregulated by exposing an electroplax in the presence of a solution of carbamylcholine and either of the two compounds to light of appropriate wavelengths, since light shifts the cis-trans equilibrium. The system may be considered as a model illustrating how one may link a cis-trans isomerization, the first step in the initiation of a visual impulse, with substantial changes (20-30 mv) in the potential difference across an excitable membrane.

Acetylcholine↗
PubMed1968

Photoregulation of an enzymic process by means of a light-sensitive ligand.

A specific inactivator of chymotrypsin, p-azophenyldiphenylcarbamyl chloride, exists as two geometric isomers, cis and trans, which are interconvertible by means of light. The cis-isomer is five times more reactive than the more stable trans-isomer, and is obtained by exposure of the latter to light of 320 nanometer wavelength. The trans-isomer can be regained by exposure of the cis-isomer to light of 420 nanometer wavelength. This interconversion can be made to occur in aqueous solution in the presence of the enzyme under conditions in which the trans-isomer reacts relatively slowly with chymotrypsin. Thus, it is possible to regulate the rate of inactivation of chymotrypsin by using light of the appropriate wavelength. This system is presented as a model for some of the light-sensitive metabolic systems present in living organisms.

Adenosine Triphosphate↗
PubMed1967

Nuclear fluorescence employing antinucleoside immunoglobulins.

Fluoresceinated antinucleoside globulins were shown to react with the nuclei of L cells. The pattern of nuclear fluorescence was similar to the distribution of nuclear DNA. This reaction was shown to be specific by the following control experiments: 1. Absorption of the specific antibody from an antiadenosine globulin eliminated all fluorescence. 2. Treatment of the cells with nonfluorescent antiadenosine globulin, followed by staining with the fluorescent antiadenosine eliminated almost all of the fluorescence of the nucleus. 3. Treatment of the cells with DNase destroyed the ability of the nucleus to react with antiuridine fluorescent antibodies. 4. Fluoresceinated anti-BSA did not produce nuclear fluorescence. Nuclear fluorescence occurred only in cells harvested during the period of maximum DNA synthesis as measured by the uptake of thymidine. This correlates with the previously demonstrated specificity of the antibodies for denatured DNA.

Animals↗