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Biomedical subjects

B Weiss

Publications and source records attributed to B Weiss.

At least 325 records · Page 18Linked to original sources

Microwaves: effect on thermoregulatory behavior in rats.

Rats, with their fur clipped, pressed a lever to turn on an infrared lamp while in a cold chamber. When they were exposed to continuous-wave microwaves at 2450 megahertz for 15-minute periods, the rate at which they turned on the infrared lamp decreased as a function of the microwave power density, which ranged between 5 and 20 milliwatts per square centimeter. This result indicates that behaviorally significant levels of heating may occur at an exposure duration and intensities that do not produce measurable changes in many other behavioral measures or in colonic temperature. Further study of how microwaves affect thermoregulatory behavior may help us understand such phenomena as the reported "nonthermal" behavioral effects of microwaves.

Animals↗

Purification and covalent coupling of calf brain prolidase.

We have investigated methods of stabilizing prolidase by chemical modification and covalent coupling to various supports, for use in protein hydrolysis and possible use in enzyme replacement therapy. Purified acetone powder of calf brain prolidase was further purified by gel filtration on Sephadex G-200 and chromatography on DEAE-Sephadex A25. Polyacrylamide gel electrophoresis showed that the number of bands was reduced from 11 to 2. Since yields were low, the purified (NH4)2SO4 fraction was used in all experiments. Thiolation of the enzyme reduced the amount of protein coupled to AH- or CH-Sepharose 4B. Activities were highest when the protein was linked through its carboxyl groups. The coupled enzyme showed much greater thermal stability than its free counterpart. Of the bound preparations, the thiolated was less stable than the untreated. Untreated and thiolated enzymes bound to either matrix showed higher activity at low pH and less at high pH than the free material. Thiolation shifted the pH maximum from 6.8 to 7.5. The free thiolated enzyme and that bound to activated SH-Sepharose 4B showed greater thermal stability and a broader pH range of optimal activity than the bound untreated enzyme. These results show that prolidase can be immobilized by coupling to an insoluble matrix through various types of covalent bonds with retention of activity and increased stability.

Animals↗

Behavioral toxicology of carbon disulfide and toluene.

Organic solvents are pervasive in the communal and industrial environments. Although many are potent central nervous system agents, clearly delineated behavioral effects have played only a minor role in the formation of exposure standards. A comprehensive behavioral pharmacology and toxicology of these compounds is one aim of US/USSR collaboration. The current report describes some actions of carbon disulfide and toulene. Earlier data about the actions of carbon disulfide on pigeon operant performance indicated disruption of schedule-controlled key-pecking. Primate data are now described from a situation designed to determine aversive thresholds to electrical stimulation. Effective concentrations of carbon disulfide produced both a rise in the amount of electric shock tolerated and a diminution of the response force exerted by the monkeys. In experiments with toluene, pigeons were shown to elevate key-pecking rate in an operant situation at certain concentrations. Toluene also was studied for its capacity to maintain self-administration in the same way as drugs of abuse. Monkeys worked to gain access to toulene vapor just as they work for opiates or amphetamines. The current experiments demonstrate how comprehensive the range of behavioral toxicology needs to be to deal with environmental health issues.

Animals↗

V. Efforts at stabilization of rat liver phenylalanine hydroxylase.

The best from a series of matrices for the covalent coupling of rat liver phenylalanine (Phe H) was activated thiol-Sepharose 4B. An average of 0.38 mumoles of enzyme thiol was coupled per mumole of matrix thiol, representing 21 mg of protein per g of carrier. After thiolation with N-acetylhomocysteine thiolactone the enzyme, bound to the same matrix, was thermally more stable with a broad pH range of optimal activity. Thiolation with S-acetylmercaptosuccinic anhydride markedly reduced hydroxylase activity whereas succinylation with succinic anhydride had little or no effect. Treatment of the thiolated enzyme with various oxidants to form disulfide bridges did not increase the thermal stability. Efforts to improve stability by formation of new linkages while the enzyme was still bound to the matrix were unsuccessful. The untreated or thiolated enzyme was inactivated upon reaction with glutaraldehyde.

Animals↗

Age-related alterations in the development of adrenergic denervation supersensitivity.

The density of beta-adrenergic receptors in the central nervous system exhibits marked age-related changes. In general, there is an initial increase in receptors soon after birth followed by a decline with advancing age; the specific pattern of the development and loss of receptors is dependent upon the brain area. The ontogenetic increase in the density of adrenergic receptors coincides temporally with the development of responsiveness to catecholamines but can proceed without an adrenergic innervation. This suggests that the biosynthesis of receptors is genetically predetermined and does not require an adrenergic input for initiation. Decreasing adrenergic activity produces an increased number of beta-receptors and a supersensitive response to adrenergic agonists. The decline in beta-receptors with advanced age appears to be related to this phenomenon of denervation supersensitivity since certain aged tissues have a diminished capacity to develop an increased number of receptors in response to a reduced sympathetic input. We conclude that the decline in beta-adrenergic receptors with age may explain the age-related decrease in the sensitivity of adenylate cyclase to catecholamines, and, consequently, the reduced physiological response to adrenergic stimuli. The mechanism for this loss of receptors may be the inability of aged tissue to develop a supersensitivity response in reaction to diminished sympathetic activity.

Adenylyl Cyclases↗

Ability of aged rats to alter beta adrenergic receptors of brain in response to repeated administration of reserpine and desmethylimipramine.

Repeated administration of reserpine to 3-month-old rats produced dose-related increases in [3H]dihydroalprenolol (DHA) binding in pineal gland, cerebral cortex and cerebellum. Reserpine increased DHA binding by increasing the density of beta adrenergic receptors. Brain tissue from 24-month-old rats, however, had an impaired ability to increase receptor density in response to reserpine treatment, even in the pineal gland where the concentration of reserpine was nearly 7 times that found in the glands of young rats given the same dose on the basis of body weight. Repeated administration of desmethylimipramine decreased DHA binding in pineal glands by about 50% and in cerebral cortices by about 25%, but did not alter DHA binding in the cerebellum. The magnitude of these changes was similar in the 3- and 24-month-old rats, although the concentration of desmethylimipramine in the pineal glands and cerebral cortices of the aged rats was significantly higher than that of the young animals. The results indicate that the reserpine-induced decrease in noradrenergic input causes a compensatory increase in beta adrenergic receptor density in rat brain. They suggest further that although aged rats can decrease receptor density in response to increased adrenergic input, they have an impaired ability to increase beta adrenergic receptor density in response to decreased adrenergic input. This finding may explain the decreased density of beta adrenergic receptor found in aged rat brain.

Aging↗

Behavioral epidemiology of food additives.

Behavioral toxicology in the natural environment can be considered a special branch of epidemiology. Behavioral epidemiology, because it typically relies on complex functional criteria, faces all of the problems of behavior measurement posed by uncontrollable variation, and amplified even further by chemical exposure. Many such issues arose in a study of behavioral responses to artificial food colors in children. Difficulties in employing Applied Behavioral Analysis in such a context run the gamut from selection of retrospective criteria to appropriate statistical models.

Child↗

Assays for behavioral toxicity: a strategy for the Environmental Protection Agency.

Broad agreement on specific approaches or standardized test batteries for assessing behavioral toxicity is unlikely to emerge in the foreseeable future. EPA should reject test standardization in any case, however; standardization stifles progress and, in addition, may bypass unique properties of new types of substances. The optimal strategy is to prescribe a set of functions, such as sensory, motor, and complex performance processes, leaving it to the manufacturer to select adequate tasks. Adequacy would be judged by EPA staff, in consultation with advisory panels, and resolved, in most cases, by a dialogue with the manufacturer.

Animals↗

beta-Adrenergic receptors in aged rat brain: reduced number and capacity of pineal gland to develop supersensitivity.

The density but not the affinity of beta-adrenergic receptors declined significantly with age in rat pineal gland, corpus striatum, and cerebellum, as determined by the binding of tritiated dihydroalprenolol. Exposing rats to light for 12 hours increased the binding of this radioligand in 3-month-old but not in 24-month-old rats. The reduced responsiveness to catecholamines seen in aging may be due to a decrease in the number of beta-adrenergic receptors which, in turn, may be caused by an impaired capacity of receptors in aged animals to adapt to changes in adrenergic neuronal input.

Aging↗

Dyskinesias evoked in monkeys by weekly administration of haloperidol.

In two cebus (Cebus albifrons) monkeys given weekly oral doses of 0.25 milligram of haloperidol per kilogram, movement disorders appeared 1 to 8 hours after drug administration following the tenth weekly dose. These disorders included oral movements, peculiar postures, writhing, and stretching. Such reactions faded in intensity after the next two doses. Increasing the dose to 0.5 milligram per kilogram has elicited the disorders reliably after each weekly dose for almost 2 years. Similar reactions also developed in a squirrel monkey (Saimiri sciurea) treated weekly with haloperidol and in a third cebus monkey previously maintained for a year on a regimen of 0.25 milligram of haloperidol per kilogram on 5 days per week. These findings suggest an experimental model for determining the etiology of drug-induced movement disorders. They also suggest an unrecognized clinical problem.

Animals↗

A DNase for apurinic/apyrimidinic sites associated with exonuclease III of Hemophilus influenzae.

An endonuclease purified from Hemophilus influenzae made single strand breaks in DNA containing apurinic or apyrimidinic sites but had no detectable endonuclease activity on untreated native DNA. The new 5'-termini created at the cleavage sites were base-free deoxyribose 5-phosphate residues. The enzyme preparation also catalyzed the exonucleolytic release of 5'-mononucleotides from bihelical DNA and the hydrolysis of DNA 3'-terminal phosphomonoesters. The phosphatase-exonuclease activity was indistinguishable from that reported by Gunther and Goodgal (J. Biol. Chem. (1970) 245, 5341-5349) and resembled that of exonuclease III of Escherichia coli. The endonucleolytic and exonucleolytic activities could not be separated by electrophoresis, sedimentation, or gel filtration, and they were also affected simultaneously by mutation. The enzymatic activities appear to be functions of a single monomeric protein (M(r) = 30,000).

Apurinic Acid↗