PubMed Health⌕ Search

Biomedical subjects

B J Abbott

Publications and source records attributed to B J Abbott.

At least 37 records · Page 2Linked to original sources
PubMed1982

Calorie restriction: effect on growth of human tumors heterotransplanted in nude mice.

The presence of 4 human malignant tumors (1 breast, 1 lung, and 2 colon carcinomas) growing subcutaneously as heterotransplants in nude mice did not significantly affect the body weights of adult animals until the tumors reached very large dimensions (tumor wt greater than 15% of the body wt). However, a colon carcinoma (HT 29) induced a cessation of the natural rate of body weight increase when it grew in young adults (animals weighing approximately equal to 25 g which will gain 6 g or approximately equal to 25% body wt in 1 mo). Calorie restriction at all the levels tested (8, 6, 4, and 2 g/day/mouse) with standard pelletized mouse food produced both weight loss in the animals (with and without tumor) and a lowering of the growth rate of all the 4 tumors tested growing at a subcutaneous site and/or under the kidney capsule. Each tumor responded differently to the calorie restriction. The 4 tumors tested grew equally in both male and female nude mice. Young animals weighing 20 g inoculated with a fifth tumor (MeWo melanoma) exhibited tumor growth inhibition proportional to restriction of calorie intake. Their survival, however, did not improve.

Adenocarcinoma, Mucinous↗
PubMed1981

Periodontal ligament injection: a clinical evaluation.

Attaining profound local anesthesia is frequently difficult. Standard block or infiltration injections often are not sufficient; a supplementary injection is often necessary. The purpose of this study was to examine the effectiveness of the periodontal ligament injection in patients who did not have adequate pulpal anesthesia. Information was obtained by questionnaire after 120 periodontal ligament injections. The frequency and rapidity of onset of anesthesia was determined as well as the factors that might affect the technique. The following conclusions were obtained from this study. -Mandibular molars required supplementary anesthesia more frequently than other types of teeth. -Injecting under strong backpressure was important; the greatest frequency of success was attained when injecting under pressure. Injecting without strong pressure on both mesial and distal surfaces resulted in the lowest frequency of anesthesia. -Onset of anesthesia was generally very rapid, usually immediate. -The length and gauge of needle were unimportant in attaining anesthesia. -Rejection was frequently successful if the first periodontal ligament injection failed. -The overall frequency of success in attaining anesthesia with this injection was 92%. This rate included situations in which the injection was administered more than once. -The most critical factor was to inject under strong resistance. This necessitates wedging the finger supported needle into the interproximal space between root surface and bone and applying maximum pressure to the syringe handle.

Anesthesia, Dental↗
PubMed1979

Microbial transformation of A23187, a divalent cation ionophore antibiotic.

A23187 is an ionophore antibiotic that forms dimeric complexes with divalent cations such an Mn2+ and Ca2+. Over 200 randomly selected soil microorganisms were incubated with A23187. None of these cultures was capable of transforming this compound. In contrast, many microorganisms were able to modify the methyl ester of A23187. The transformation products produced by one culture, Streptomyces chartreusis, were isolated and identified as 16-hydroxy-N-demethyl A23187 methyl ester, 16-hydroxy-A23187 methyl ester, and N-demethyl A23187 methyl ester. These ester derivatives lack most of the ionophore properties of the acids and cannot readily form dimeric complexes with divalent cations. However, they could be hydrolyzed by a mild treatment with ethanolic KOH to free acids that possess good ionophore activity. The use of the ester substrate in conjunction with the hydrolysis procedure is, at the present time, the only known method for microbiologically producing A23187 derivatives.

Anti-Bacterial Agents↗
PubMed1979

Microbiological transformations of nabilone, a synthetic cannabinoid.

A screening program was conducted to find microorganisms that modify the synthetic cannabinoid nabilone. After purification, the products from three cultures were analyzed by spectral methods to determine their chemical structures. An optically active 9S-hydroxy-6aR,10aR-trans cannabinoid was isolated from a culture of an unidentified soil bacterium designated A24007. From Bacillus cereus cultures were isolated a 9S,6'-dihydroxy-6aR,10aR-trans cannabinoid, a 9S-hydroxy-6'-keto-6aR,10aR-trans cannabinoid, a 9-keto-6'-hydroxy-6aS,10aS-trans cannabinoid, and a 6',9-diketo-6aS,10aS-trans cannabinoid. All of these products were optically active, as was a 9S-hydroxy-6aS,10AS-trans cannabinoid also isolated from B. cereus cultures. A series of acidic products were isolated from cultures of Nocardia salmonicolor. All of these products contained a carboxylic acid group at the terminal end of three-position alkyl side chains having varying numbers of carbon atoms. Two of the acidic products contained a 9-keto group, whereas all other carboxylic acid products were 9-hydroxy cannabinoids. The array of products obtained from incubation of nabilone indicates the usefulness of microbial transformations in the preparation of new cannabinoids.

Actinomycetales↗
PubMed1978

Incorporation of 14C-labeled compounds into sinefungin (A9145), a nucleoside antifungal antibiotic.

Streptomyces griseolus produces a complex of antifungal nucleoside antibiotics that contain an ornithine residue linked to the ribose moiety of adenosine. 14C-Labeled compounds were added to cultures of S. griseolus (approximately 0.5 muCi/ml culture broth) and the amount of label incorporated into the two major antifungal components (sinefungin and factor C) was measured. Substantial incorporation (16 approximately 52%) was obtained with adenosine [8-14C], ATP [14C(u)], adenine [8-14C], L-ornithine [14C(u)], and DL-citrulline [5-14C]. Glycine glucose L-arginine, and acetate were incorporated to the extent of 1.7 approximately 4.7%. Studies were conducted on the fermentation time course and on the time dependence of label incorporation in order to optimize the incorporation of labeled adenine into sinefungin. Adenine [8-14C] incorporation and sinefungin specific activity were highest 48 hours after label addition and both declined during subsequent incubation. As much as 43% of the labeled adenine was incorporated into the antibiotic and sinefungin was produced with a specific activity of 24.8 muCi/mg. The labeling experiments suggest that a performed adenine derivative (e.g., an adenine nucleotide) and ornithine (or a closely related metabolite) are direct biosynthetic precursors of sinefungin.

Adenine↗
PubMed1977

Microbiological transformation of cannabinoids.

Microorganisms were screened for their ability to modify 2 synthetic cannabinoid substrates (I and II). Structure analyses revealed that microorganisms transformed the substrates by (a) primary oxidation of the side chain, beta-oxidation of the side chain, ketone formation on the side chain or cyclohexene ring, (b) secondary hydroxylation on the side chain, (c) aromatization of the cyclohexene ring, and (d) tertiary hydroxylation at the b/c ring juncture.

Actinomycetales↗
PubMed1977

Microbiological transformations of delta6a10a-tetrahydrocannabinol.

A screening program was conducted to find microorganisms that catalyze transformation reactions with cannabinoids. Three hundred fifty-eight cultures, consisting of 97 bacteria, 175 actinomycetes, and 86 molds, were incubated in media containing 0.5 mg of Delta(6a,10a)-tetrahydrocannabinol (Delta(6a,10a)-THC) per ml. After 120 h of cultivation, ethyl acetate extracts of the cultures were examined by thin-layer chromatography (TLC) for transformation products. About 18% of the cultures modified Delta(6a,10a)-THC. The ability to modify the substrate did not predominate among any particular group of microorganisms. After purification, the products from three cultures were analyzed by high-resolution mass spectrometry, 100-mHz proton magnetic resonance spectrometry, ultraviolet spectrometry, and infrared spectrometry. These spectral data indicated that a Mycobacterium sp. oxidized Delta(6a,10a)-THC to cannabinol and a diastereomeric pair of 6a-hydroxy-Delta(10,10a)-THC isomers; a Streptomyces sp. and a Bacillus sp. oxidized Delta(6a,10a)-THC to 7-keto-Delta(6a,10a)-THC and 4'-hydroxy-Delta(6a,10a)-THC, respectively. The occurrence of these products and the presence of others that have not yet been isolated or identified indicate that microbial transformation may be a useful tool for the preparation of new cannabinoids that have desirable pharmacological properties.

Actinomycetales↗
PubMed1976

Immobilization of a cephalosporin acetylesterase by containment within an ultrafiltration device.

A cephalosporin acetylesterase produced by Bacillus subtilis catalyzes the deacetylation of 7-aminocephalosporanic acid (7-ACA). Previous reports from our laboratory described the kinetic constants that characterize the reaction: Km = 2.8 X 10(-3)M, Kia acetate = 5 X 10(-2)M, and Kid deacetyl-7-ACA = 3.6 X 10(-2)M. These constants were used to predict the time course of the reaction using the following equation for dual competitive product inhibition. (see article) where St =mg/ml 7-ACA, At =mg/ml acetate, Dt =mg/ml deacetyl-7-ACA. The predicted time course closely matched the time course measured experimentally. The equation also was solved without the inhibition terms and the solution indicated that product inhibition caused about a 30% increase in the time required for complete (greater than 97%) hydrolysis of a 24 mg/ml 7-ACA solution. The esterase was immobilized by containment within an ultrafiltration device. With this technique the enzyme was reused 20 times over an 11 day span to deacetylate 7-ACA solutions containing 4 to 24 mg/ml 7-ACA. The specific activity after the 20th use was the same as the activity prior to the first use, indicating little enzyme inactiviation occurred.

Acetylesterase↗
PubMed1976

Bioassay of plant extracts for anticancer activity.

Crude plant products were first tested in the Drug Research and Development Program, Division of Cancer Treatment, NCI, in 1956. The first materials were voluntarily submitted and later materials were acquired through various contracts. A review is given of the tumor systems which have been used for the evaluation of these plant products and of in vitro assays utilized to expedite fractionation and isolation.

Adenocarcinoma↗
PubMed1975

Structural effects on the reactivity of substrates and inhibitors in the epoxidation system of Pseudomonas oleovorans.

The epoxidation reaction catalyzed by an enzyme system of Pseudomonas oleovorans exhibits a substrate specificity different from that expected on the basis of chemical reactivity in non-enzymatic epoxidation reactions. Cyclic and internal olefins, aromatic compounds and styrene are not epoxidated. The reactivity of straight chain diolefins is maximal for octadiene and falls off rapidly as the carbon chain is shortened, but decreases only slightly as the chain is lengthened. In contrast, methyl group hydroxylation is less sensitive to decreasing chain length. As a consequence, propylene and 1-butene are hydroxylated but not epoxidated by this enzyme system. With the substrate 1-decene, which is capable of undergoing both epoxidation and hydroxylation, the former reaction predominates. Methyl imidoesters were found to be inhibitors of enzymatic epoxidation, and the potency of a homologous series of imidoester inhibitors was examined. The results parallel the substrate specificity patterns observed, and support the conclusion that the mode of substrate binding severely moderates the inherent chemical reactivity of the activated oxygen in this system. The effect of the bifunctional imidoester, dimethyladipimidate, was also examined and the results compared with those obtained in other investigations.

Alcohols↗
PubMed1975

Preparation and properties of a cephalosporin acetylesterase adsorbed onto bentonite.

A cephalosporin acetylesterase produced by Bacillus subtilis was immobilized by adsorption onto bentonite. The immobilized enzyme (E(I)) and the soluble enzyme (E(S)) exhibited Michaelis-Menton kinetics with 7-aminocephalosporanic acid (7-ACA): K(m) = 2.8 x 10(-3) M and K(m) = 3.2 x 10(-3) M, respectively. Similar kinetics were observed with 7-(thiophene-2-acetamido)cephalosporanic acid (cephalothin), but the K(m) value measured with E(I) (3.7 x 10(-3) M) was less than one-half that measured with this substrate and E(S). The reduction in K(m) value was correlated with the ability of bentonite to adsorb cephalothin. The reaction products, acetate and deacetyl-7-ACA, were weak competitive inhibitors of E(S) and E(I). The K(i) values for E(I) were 5.0 x 10(-2) M for acetate and 3.6 x 10(-2) M for deacetyl-7-ACA. Similar values were measured with E(S) and these substrates. E(I) retained about 80% of its initial activity after 3 weeks of storage in solution at 25 C. However, the enzyme dissociated from the bentonite particles during the deacetylation reaction. This dissociation was minimized by cross-linking E(I) with glutaraldehyde or bis-dimethyladipimidate, or by adding Al(OH)(3) to the suspension. With the latter addition, E(I) was stabilized so that it could be reused nine times before one-half of the initial activity was lost.

Acetylesterase↗
PubMed1975

Physical properties and kinetic behavior of a cephalosporin acetylesterase produced by Bacillus subtilis.

An esterase that deacetylates cephalosporins was recovered from the supernatant of a Bacillus subtilis culture. It was partially purified by ammonium sulfate fractionation and ultrafiltration. The enzyme had a temperature optimum between 40 and 50 C and a pH optimum of 7.0. The molecular weight was estimated by gel filtration to be 190,000. The enzyme was very stable and retained greater than 80% of its activity after storage in solution at 25 C for 1 month. The esterase exhibited Michaelis-Menton kinetics with the substrates 7-aminocephalosporanic acid (7-ACA) and 7-(thiophene-2-acetamido)cephalosporanic acid (cephalothin); the K(m) values were 2.8 X 10(-3) and 8.3 X 10(-3) M, respectively. The products of 7-ACA deacetylation were weak competitive inhibitors, and a K(i) value of 5.0 X 10(-2) M was determined for acetate and of 3.6 X 10-2 M for deacetyl-7-ACA. Weak product inhibition did not prevent the deacetylation reaction from going to completion. A 5-mg/ml solution of partially purified esterase completely hydrolyzed (greater than 99.5%) a 24-mg/ml solution of 7-ACA in 3 h. Because of the kinetic properties and excellent stability, this enzyme may be useful in an immobilized form to prepare large quantities of deacetylated cephalosporin derivatives.

Acetylesterase↗
PubMed1975

Antitumor activity of macromomycin B (NSC 170105) against murine leukemias, melanoma, and lung carcinoma.

Mice bearing either of the two rapidly growing mouse leukemias, L1210 or P388, or the slow-growing B16 melanoma responded to i.p. injections of Macromomycin B (NSC 170105) with significant increases in life-span. The maximal increases in life-span obtained in these experiments were 37% for L1210, 68% for P388, and 120% for B16. In addition, there were 7 of 30 cures for varying doses of Macromomycin in the B16 melanoma. Activity of over 50% increase in life-span in B16 was obtained with a daily i.p. injection on Days 1 to 9 of 16 to 40 mg/kg. Animals that had received s.c. implanted Lewis lung tumors responded to either single or repeated injections (8 to 16 mg/kg) given at the site of tumor implant by a marked reduction in growth of the primary tumor, increased life-span, and some cures. The same doses were without effect when administered i.p. The reported activity of Macromomycin against L1210, P388 leukemias, B16 melanoma, and Lewis lung carcinoma make it a good candidate for development for clinical trial against human solid tumors. A new method of evaluating activity against solid tumors, "responder analysis," is also presented.

Animals↗
PubMed1974

Effect of growth rate and nutrient limitation on the composition and biomass yield of Acinetobacter calcoaceticus.

Acinetobacter calcoaceticus was grown on ethanol in a chemostat as a model system for single-cell protein production. The substrate yield coefficient (Y(s), grams of biomass/gram of ethanol), protein yield coefficient (Y(p), grams of protein/gram of ethanol), and biomass composition were measured as a function of the specific growth rate. Nucleic acid, protein, Y(p), and Y(s) all increased at higher growth rates. Although protein content increased only 14% (from 53 to 67%), Y(p) almost doubled over the same range of growth rates. The increase in Y(p) was due to the higher protein content of the biomass and to higher values of Y(s). The higher values of Y(s) were attributed to maintenance metabolism, and the value of the maintenance coefficient was found to be 0.11 g of ethanol per g of cell per h. When A. calcoaceticus was cultivated under a phosphorus limitation protein content, Y(p) and Y(s) were lower than in carbon-limited cultures. It was concluded that a single-cell protein fermentation using A. calcoaceticus should be operated at a high growth rate under ethanol-limiting conditions in order to maximize both the protein content of the biomass and the amount of biomass and/or protein made from the substrate.

Alcaligenes↗