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H D Brown

Publications and source records attributed to H D Brown.

At least 37 records · Page 2Linked to original sources
PubMed1988

Electromagnetic-field exposure and cancer.

Electromagnetic fields are a ubiquitous part of man's environment. Natural sources of energy have been present, and possibly have contributed to the processes of the evolution of living forms. In very recent time, however, exploitation of the properties of the electromagnetic spectrum, has added variables in intensity, frequency, modulation frequency, and alterations in contributions of electrical and magnetic components. Biological impact has been little studied and poorly defined. Animal carcinogenesis studies and human epidemiological data indicate that exposure to nonionizing radiation can play a role in cancer causation. Numerous effects at the physiological and biochemical level have been reported; many are of such a nature that a relationship to the causation of neoplastic transformation can rationally be hypothesized. Many bioeffects of electromagnetic fields can be adequately and economically explained in terms of heat effects alone. However, observations of frequency-, pulse form or modulation-, and intensity-specificity as well as effects opposite to that known for temperature-rise, imply direct interaction of radiant energy with biomolecules. The possibility of such direct interaction has been shown in quantum mechanical models.

Animals↗
PubMed1987

Energetics of ligand and inhibitor interactions with acetylcholinesterase.

Acetylcholinesterase (AChE, EC 3.1.1.7) from Electrophorus electricus, purified by affinity chromatography to a specific activity of 7000-10,000 U/mg protein, was studied at 27 degrees C in conduction-type microcalorimeters for the heats of reaction, with the subsite-specific cationic ligands edrophonium and propidium and with the irreversible inhibitor diisopropylfluorophosphate (DFP), in an ion-free aqueous medium. Edrophonium and propidium, each at 0.5 x 10(-5) M, yielded reaction heats of +3.2 and -1.5 kcal/mol (1 kcal = 4.184 J) respectively, with 1.3 x 10(-5) M AChE active sites. DFP (1.3 x 10(-5) M) reacted exothermically yielding -0.5 kcal/mol at stoichiometric level with AchE active sites. Circular dichroic spectra showed that a ternary complex of AChE (6.5 x 10(-7) M active sites) and the two ligands (each at 1 x 10(-3) M) in 1 mM Tris-HCl buffer (pH 8.0) had a positive Cotton effect at 235 nm. Neither DFP nor phosphoric acid 2,2-dichloroethenyl dimethyl ester (DDVP) caused any appreciable change. DFP-AChE, however, behaved like a normal enzyme in showing a positive Cotton effect in association with the two ligands. DDVP-AChE showed an increase in negative ellipticity at 287 nm in the presence of the two ligands. Another cationic ligand, d-tubocurarine, when present together with edrophonium, increased negative ellipticity at 302 nm and blue-shifted a 265-nm peak of the normal AChE. DFP interactions with AChE appear to be energetically different from those of edrophonium, the latter of which is believed to associate with the acetylcholine-binding subsite.

Acetylcholinesterase↗
PubMed1986

Substrate-ligand interactions with acetylcholinesterase and energetics of binding.

Ester hydrolysis by acetylcholinesterase (from electric eel, Electrophorus electricus) increased in the presence of low concentrations (ca 10(-7) M) of edrophonium, propidium, d-tubocurarine, gallamine, decamethonium or bis-N-methylacridinium, and decreased at higher concentrations. The overall sensitivity of the substrates to inhibition by the ligands was acetylcholine (Ach) greater than phenylacetate (PA) greater than indophenylacetate (IPA). Complete (saturable) inhibition was unattainable with edrophonium or gallamine for IPA and, to a lesser degree, with propidium for PA. Reaction heats between the enzyme and the ligands (edrophonium, propidium and decamethonium) measured directly in a microcalorimeter revealed binding sites that are different from each other in their interaction energetics.

Acetylcholinesterase↗
PubMed1985

Enthalpy of acetylcholine hydrolysis by acetylcholinesterase.

Direct microcalorimetric measurements were made of the reaction between acetylcholine chloride and acetylcholinesterase (EC 3.1.1.7) that was extracted from electric eel (Electrophorus electricus) and purified by affinity chromatography. Tris-HCl, sodium phosphate and potassium phosphate were used as buffers and sources of ions for the reaction. At pH 7.2 and in 0.1-0.2 M phosphate buffer, the delta H for acetylcholine hydrolysis was found to be -0.107 kcal/mol (under buffered conditions) and -0.931 kcal/mol under unbuffered conditions (water). At pH 8.0 in 0.1 M Tris-HCl buffer, values greater than -2.5 kcal/mol were obtained, with the highest value of -9.2 kcal/mol being seen with bovine erythrocyte acetylcholinesterase. Tris-HCl buffer at 4 X 10(-2) M enhanced the reaction velocity by 51.2% over that of 4 X 10(-3) M buffer. Enzyme purity, pH and ionic milieu of reaction mixture, and substrate concentration affected the measured delta H value.

Acetylcholine↗
PubMed1985

Clinical and biochemical effects of aflatoxin in feed ration of chicks.

Aflatoxin carcinogenesis appears to relate to multiple factors. This includes bulky adduct formation at DNA guanine N-7. The process also requires more extensive physiological degradation, possibly by the toxin alone as the active principle, but in instances also involving other assaults (e.g., hepatitis B virus). Since aflatoxin carcinogenesis involves complex effects, we have undertaken to define the range of influence of this common food contaminant upon a susceptible model, the broiler-type chick. Aflatoxicosis in two treated groups was indicated by jaundice, coagulopathy, dehydration of combs and shanks, retardation of body weight, and decrease in bursa weight. Blood clotting time, hemoglobin content, erythrocyte and packed-cell volume were affected. Hepatocytes were swollen and had undergone fatty degeneration. Bile duct hyperplasia was evident. Total serum protein, alkaline phosphatase, creatine, lactate dehydrogenase, serum glutamic oxalacetic transaminase and glutamyl transpeptidase were similarly abnormal in birds receiving the contaminated (0.5 and 2.5 micrograms/g aflatoxin B1) feed rations. The aflatoxin B1 and its metabolites were isolated by HPLC from chick serum, liver and muscle.

Aflatoxin B1↗
PubMed1984

Information requirements for chemists in the pharmaceutical industry.

The principal information needs of chemists in the pharmaceutical industry center around a substance, methods used for its characterization, its reactions, its physicochemical and biomedical properties, and its metabolic fate in biological media. Novelty searches for a specific chemical are critical because of the need for patent protection for product candidates. Chemical relatives are important, necessitating substructure searching. Therapeutic neighbors may give insight into its biological mode of action. The phases of drug discovery and development are used to indicate the diversity of the information needs of chemists and to emphasize the dual process of generation and use of information.

Animals↗
PubMed1983

Microcalorimetric determination of binding sites of acetylcholinesterase.

Acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7), phosphorylated with dichlorvos, showed relatively more reactivity toward the substrate indophenyl acetate than the enzyme that was carbamylated with carbaryl. When the anionic subsite of the phosphorylated or carbamylated enzyme was alkylated with an aziridinium ion, the reaction velocity toward indophenyl acetate increased in the phosphorylated enzyme but not in the carbamylated enzyme. The organophosphate binding site--which appears to be different from that of carbamate or indophenyl acetate, but probably the same as that of acetylcholine -- is apparently alkylated in such a way that the modified (phosphorylated) enzyme is better-fit for the binding (and hydrolysis) of indophenyl acetate. The modified conformation presumably results in the release of the phosphoryl group from the esteratic subsite.

Acetylcholinesterase↗
PubMed1983

Exposure of professional pest control operator to dichlorvos (DDVP) and residue on house structures.

Each of the 13 human volunteers carried out a 1-day urban pest control work in 4 homes using 10-14 aerosol cans (230-330 g dichlorvos (DDVP] and 18-22 pints of 0.5% emulsion spray (40-50 g DDVP). Average residue levels of 75.85 micrograms/ft2, 40.9 micrograms/ft2 were found on the applicator's back, chest and respirator filter, respectively. Residue on the house structure was 219.7 micrograms/ft2 on the first day, which fell to 50.9 micrograms/ft2 by the end of 5 days. Blood and urine analyses revealed no changes in various clinical parameters, including serum cholinesterase levels.

Acetylcholinesterase↗
PubMed1983

A pharmaceutical information manager's viewpoint on R & D information resource management.

An overview of the environment (from my perspective) related to information resource management in pharmaceutical R & D has been presented. Some notions of organizational preference (functional), employee selection (chemist turned information scientist), automation (user friendly, cost effective), and the value of project teams (information transfer) have been noted. Difficulties associated with keeping our innovative tools sharp were observed. Finally, we noted that our bottom line--productivity--should first consider what is useful (effectiveness) and then learn how to do it well--efficiency. Success in the management of information resources depends on the proactive delivery of information packets which find their way into problem solving and decision support for scientists or line managers.

Chemistry, Pharmaceutical↗
PubMed1983

Energetics of the oxidase activity of NADPH-cytochrome P-450 reductase.

Oxidase activity of rat liver microsomes has been evaluated microcalorimetrically. delta H for the oxidation of reduced nicotine adenine dinucleotide phosphate was measured to be -39.33 (uncertainty 2.18) kcal/mol. The contribution of peroxide reduction and NADPH ring opening heats to this value have been considered. Calorimetric assay of the hydroxylase activity of the P-450-reductase-hydroxylase enzymatic complex has been demonstrated using the organocarbamate, Isolan (1-isopropyl-3-methyl-5-pyrazolyl dimethylcarbamate), as substrate.

Animals↗
PubMed1980

Microcalorimetric assay of acetylcholinesterase.

Comparative assays were made in a spectrophotometer and a microcalorimeter for the reaction between acetylcholinesterase (EC 3.1.1.7) and acetylthiocholine. The rate of light absorbance change and the rate of heat flow were measured from similar and simultaneous reactions in spectrophotometer and microcalorimeter, respectively. At the enzyme activity levels studied, i.e., 0.05-0.15 I.U. in calorimetry and 1-4 I.U. in spectrophotometry, the reaction rates were linear and showed first-order kinetics A highly significant positive correlation was seen between the two methods (r = 0.997). More importantly, spectrophotometric assay with acetylthiocholine (which utilized a secondary reaction with chromagen, dithiobisnitrobenzoic acid) stood in highly significant positive correlation with calorimetric assays (which did not require a chromagen) either with the same substrate (r = 0.976) or with acetylcholine (r = 0.900). It appears that microcalorimetry can be used in preference to spectrophotometry for enzyme kinetic studies to overcome the complexity of reaction mixture and interference problems and with the advantage of using natural substrates.

Acetylcholine↗
PubMed1978

Cholesterol oxidase: thermochemical studies and the influence of hydroorganic solvents on enzyme activity.

Thermal and binary cosolvent studies of the cholesterol oxidase (cholesterol: oxygen oxidoreductase, EC 1.1.3.6) reaction have been carried out using batch microcalorimetry and ultraviolet spectrophotometry respectively. Heat conduction measurements are shown to provide the basis for a serum cholesterol assay yielding results comparable to conventional automated clinical assay. The enthalpy of the reaction for cholesterol oxidation, measured with different sources of the enzyme in the presence and absence of catalase is -113 +/- 7.2 mJ/mumol. The value is agreement with calculated estimates based on bond energies, enthalpies of formation and trigonal additivity contribution calculations. From this heat of reaction the deltaHf0 of cholestenone (c) is calculated to be -490 kJ . mol-1. No evidence for the reverse reaction could be adduced. Enzyme activation with detergent (Surfal) is attributed to the formation of mixed micelles of cholesterol with detergent molecules. The detergent concentration at which the enzyme is half activated corresponds to the critical micelle concentration of Surfal. The enhanced enzyme activity found when ethanol, acetonitrile and dioxane were examined as binary cosolvents with water is ascribed to a conformational change in the enzyme mediated through the altered structuredness of water. This cosolvent effect is abolished in the presence of 0.18% Surfal due to the formation of inverted mixed micelles of detergent with cholesterol.

3-Hydroxysteroid Dehydrogenases↗
PubMed1978

"The Merck Index": the merits of using computers in publishing.

"The Merck Index", an internationally recognized encyclopedia of drugs, chemicals, and biologicals was produced by the traditional method for eight consecutive editions. Owing to the rapidly increasing volume of information and escalating costs of book production, it became desirable to design a computer-assisted production method for preparation of the recently published ninth edition. The method that was developed and used as well as the philosophy behind its use are described.

Computers↗
PubMed1977

Ectopic production of antidiuretic hormone (adh), adrenocorticotrophic hormone (ACTH) and beta-melanocyte stimulating hormone (beta-MSH) by an oat cell carcinoma of the lung.

A 61 year old woman presented with profound hyponatremia and markedly low serum osmolality. Urine osmolality was greater than the serum osmolality, an abnormality that was corrected by water restriction, suggesting inappropriate ADH secretion. Although there were no physical signs of Cushing's syndrome, her serum potassium level was low and markedly elevated levels of plasma and urine corticosteroids were not altered by the administration of large amounts of dexamethasone, suggesting the ectopic ACTH-MSH syndrome. Plasma levels of immunoreactive ACTH and beta-MSH were elevated. At autopsy, a metastastic oat cell carcinoma of the lung, not detected antemortem by chest roentgenograms and bronchoscopy, was found. Immunoreactive ADH, ACTH and beta-MSH were detected in the primary tumor and in metastases to the liver. beta-MSH was also detected in the spleen, in which metastases were observed. This is the first documented case of the simultaneous production of ADH, ACTH and beta-MSH by neoplastic tissue associated with clinical manifestations of the syndrome of inappropriate ADH secretion and the ectopic ACTH-MSH syndrome.

Adrenocorticotropic Hormone↗
PubMed1977

Calorimetry of cholinesterase activity in serum.

Cholinesterase activity in human serum was measured calorimetrically and compared to values obtained with the spectrophotometric method of Rappaport et al. [Clin. Chim. Acta 4, 227 (1959)]. The response of the calorimeter upon mixing serum with acetylcholine corresponded to the cholinesterase activity of the serum, the thermogram peak height being linearly related to enzyme activity at serum dilution volumes at which interference heat was negligible. The interference heat contributed by the dilution mixing characteristics of serum, studied separately, was found to be similar for heat-denatured, aged, or lyophilized samples. In all cases, heat of mixing was negligible when 1 ml of serum in buffer (2/3 by vol) was mixed with 1 ml of buffer. When this amount of serum was assayed with acetylcholine, cholinesterase activities of 2 and 3 kU/liter were recorded as thermograms with peak heights of 2.3 and 3.5 cm, respectively.

Acetylcholine↗