Antitrust assaults tail competition.
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Biomedical subjects
Publications and source records attributed to M J Thompson.
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Brassinolide (2 alpha, 3 alpha, 22 alpha, 23 alpha-tetrahydroxy-24 alpha-methyl -B-homo-7-oxa-5 alpha-cholestan-6-one), a novel plant growth-promoting steroid isolated from rape pollen, and its hitherto unknown 22 beta, 23 beta-isomer were synthesized from a C-24 epimeric 60:40 mixture of 22-dehydroxampesterol (24 alpha-methyl) and brassicasterol (24 beta-methyl) from oysters. The method of synthesis favored the formation of the 22 beta, 23 beta-isomer by better than 4:1. Comparative plant growth-promoting capabilities of brassinolide, both natural and synthetic, and its three side chain cis-glycolic isomers in the bean second internode bioassay showed that the natural and synthetic brassinolides were equally active and caused splitting of the internode at the 0.1 microgram level. The least active was the 22 beta, 23 beta-isomer of brassinolide. The isomers with the 22 alpha, 23 alpha and 24 alpha, and the 22 beta, 23 beta and 24 beta configurations were highly active and were required at about 10 times the concentration of brassinolide to cause the same physiological response. In the bean first internode bioassay, an auxin-induced growth test system which employs isolated bean plant segments, the isomer with 22 beta, 23 beta and 24 beta configuration caused a greater response than brassinolide. Two of the four tetrahydroxy ketones obtained in the synthesis of the isomers were also active in both assays.
Central and regional hemodynamic studies were performed before and after the oral administration of 75 mg of hydralazine and/or 20 mg of isosorbide dinitrate in 15 patients with low-output congestive heart failure. Hydralazine increased mean cardiac output 17-25%, mean renal blood flow 19%, and limb blood flow 17% (all p < 0.05). Mean hepatic blood flow did not change significantly with hydralazine. Except for a small increase in cardiac output (6%, p < 0.05) at 30 minutes, isosorbide dinitrate did not significantly alter central, renal, hepatic or limb blood flow. Combining isosorbide dinitrate and hydralazine effected similar increases in cardiac output (17-24%, p < 0.05), renal (17%, p < 0.05) and limb (20%, p < 0.05) blood flow as those elicited by hydralazine alone. The combination did not significantly alter mean hepatic blood flow. Hydralazine, alone or combined with isosorbide dinitrate, increases renal and limb blood flow in congestive heart failure in proportion to the augmented cardiac output; isosorbide dinitrate alone does not alter blood flow to these regions. Neither drug (or combination) changes hepatic blood flow in this clinical setting.
Decanamine hydrochloride (a C10 primary amine), N-methylundecanamine (a C11 secondary amine) and N, N-dimethyldodecanamine (a C12 tertiary amine) were tested for their effects upon in vitro cellulose digestibility by unadapted ruminal microorganisms. The three amines exhibited similar patterns of inhibition of cellulose digestibility in 48-hr in vitro incubations. Cellulose digestion was depressed to 97, 89, 31, 11 and 12% of the control value by 5, 10, 25, 50 and 100 ppm of the amines, respectively. Total volatile fatty acid production was depressed to 89, 85, 61, 40 and 32% of the control value by 5, 10, 25, 50 and 100 ppm of the amines, respectively. Propionate production was inhibited to a greater extent than was acetate production, and acetate to propionate ratios increased in the presence of the amines. The results demonstrate that these primary, secondary and tertiary amines inhibit those microorganisms which digest cellulose in the rumen.
Six branched and straight chain secondary or tertiary amines with chain lengths of 12 to 18 carbons and two azasteroids, 25-aza-5 alpha-cholestane and 25-azacoprostane, were fed to mature White Leghorn hens, and their effectiveness was compared with 20,25-diazacholesterol dihydrochloride (SC-12937), an azasteroid known to lower egg cholesterol. Feed consumption, body weight, egg production, egg and plasma cholesterol and desmosterol, and plasma total lipid were measured. The 6 amines were fed at 200 ppm, and only the C12 branched chain amine N,N,3,711-pentamethyldodecanamine reduced plasma and egg cholesterol with a concomitant increase in desmosterol. After 4 weeks, plasma desmosterol was 0, 13, 60, and 75% of total sterol for control, 200 ppm C12 branched chain amine, 5 ppm diazacholesterol, and 5 ppm azacholestane, respectively. Egg production was severely reduced to 6 and 0% by feeding 5 ppm azacholestane for 2 and 4 weeks, respectively, and to 69 and 36% by feeding 5 ppm diazacholesterol. After 4 weeks egg cholesterol was 79 and 36% of the total sterol for the 200 ppm C12 branched chain amine and 5 ppm diazacholesterol, respectively. Concomitant increases in desmosterol accompanied all reductions in cholesterol. The depletion and repletion rates of egg cholesterol were measured in a subsequent experiment. After 2-1/2 weeks of feeding the test substances, egg cholesterol was reduced with concomitant increases in desmosterol. Egg cholesterol was 100, 71, and 50% of the total egg sterol for control, 200 ppm, and 400 ppm C12 branched chain amine, respectively: 58, 13, and 3% for .1, .5, and 1.0 ppm azacholestane; 28, 29, and 18% for 1, 2.5, and 5 ppm azacholesterol; and 23% for 1 ppm azacoprostane. The experimental diets were then withdrawn, and egg cholesterol repletion was studied biweekly. Egg cholesterol was repleted to 100% of the total sterol after withdrawal times of 2 weeks for C12 branched chain amine, 8 weeks for azacoprpostane, 14 to 16 weeks for diazacholesterol, 10 to 16 weeks for the lower levels of azacholestane, and longer than 16 weeks for 1 ppm azacholestane. The increase in desmosterol accompaning the demonstrated reduction in egg cholesterol, particularly with azasteroids, causes one to question the usefulness of this approach to lower cholesterol.
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26-Hydroxyecdysone, which is the major free recoverable ecdysteroid of older age groups of embryonated eggs of the tobacco hornworm was also the major component in 4- to 18-hour-old embryonated eggs. The other 3 beta-ecdysteroids, ecdysone, 20-hydroxyecdysone, and 20,26-dihydroxy-ecdysone, were also present and accounted for all the molting hormone activity; 26-hydroxyecdysone was devoid of molting hormone activity in the house fly assay. 20-Hydroxyecdysone was a minor component, which confirms the earlier observations that the main metabolic route for ecdysteroids during embryonic development is that leading to 26-hydroxyecdysone, whereas formation of 20-hydroxyecdysone is a minor pathway. A new 3 alpha-ecdysteroid, 3-epi-26-hydroxyecdysone, also devoid of molting hormone activity, was the second major ecdysteroid isolated from the eggs. 3-Epi-20,26-dihydroxyecdysone was detected in very minute amounts. In addition to the six 3 beta-and 3 alpha-ecdysteroids there were at least an equivalent number of unknown ecdysteroids all of which lacked molting hormone activity. Their physical properties including chromatographic behavior are discussed.
Butopamine is chemically similar to dobutamine but, unlike dobutamine, it is not a catecholamine. Preclinical studies on dogs show that butopamine is inotropic intravenously and orally. We gave butopamine intravenously to eight patients with congestive heart failure using a progressive dose-response protocol ranging from 0.02 to 0.17 mcg/kg/min. The mean cardiac index and stroke volume index increased at doses greater than or equal to 0.06 mcg/kg/min; there was also an increase in heart rate at greater than or equal to 0.06 mcg/kg/min. At greater than or equal to 0.08 mcg/kg/min the augmented stroke volume tended to plateau so that additional increases in the cardiac index were secondary to the elevated heart rate. Improved ventricular performance, measured by systolic time intervals, left ventricular stroke work index, and the calculated mean rate of left ventricular pressure development during isovolumetric contraction (delta P/delta t/PCWP), was noted at greater than or equal to 0.06 mcg/kg/min. Systemic systolic blood pressure increased at greater than or equal to 0.04 mcg/kg/min but diastolic and mean arterial pressures and pulmonary artery and pulmonary capillary wedge pressures did not change. The progressive increase in cardiac output was accompanied by a reduction in pulmonary and systemic vascular resistances. Although mean premature ventricular contractions per minute did not change, two patients experienced a substantial increase in ventricular ectopy at 0.10 and 0.12 mcg/kg/min. Butopamine induces a positive inotropic response in patients with congestive heart failure but for equal increments in cardiac output, butopamine increases heart rate more than dobutamine.
Recent proposals by the Food and Drug Administration to regulate teat dips as drugs have led to a search for safer teat dip ingredients. Primary, secondary, and tertiary alkyl amines (carbon-10 to -18 chain length) inhibit growth of mastitic bacteria (Streptococcus agalactiae, Streptococcus uberis, Staphylococcus aureus, Escherichi coli, Klebsiella pneumoniae) in a broth tube culture assay. Since carbon-13 compounds were active, a carbon-13 primary (tridecanamine hydrochloride), secondary methyl (N-methyltridecanamine), secondary ethyl (N-ethyltridecanamine), tertiary dimethyl amine (N, N-dimethyltridecanamine), and carbon-12 quaternary amine (N, N, -trimethyldodecaneammonium chloride) were tested for their ability to reduce experimentally applied populations of S. agalactiae or E. coli on the bovine teat surface. The five compounds were compared at concentrations of 100, 500, 1,000, 3,000, 7,000, and 10,000 ppm. Activity was greater against the gram-positive S. agalactiae than against the gram-negative E. coli. The tertiary amine was most active, producing a log reduction of 4 (reduction of bacterial number from 10(6) to 10(2)) at a concentration of 3,000 ppm in the teat dip. The relative order of effectiveness for the amines was: dimethyl tertiary greater than methyl secondary greater than ethyl secondary greater than primary = quaternary. The results suggest that these amines may be useful as potent, effective antibacterial agents for incorporation into teat dips.
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Six naturally occurring C27 ecdysteroids were isolated and identified from the tobacco hornworm during pupal-adult development five days after peak titer of molting hormone activity. In order of decreasing quantities the hormones were: 20,26-dihydroxyecdysone, 3-epi-20-hydroxyecdysone, 20hydroxyecdysone, 3-epi-20,26-dihydroxyecdysone, 3-epi-ecdysone, and ecdysone. 20-Hydroxyecdysone, in an earlier study, was the major molting hormone present at peak titer during pupal-adult development. The major ecdysteroid present during embryonic development in this insect, 26-hydroxyecdysone, was not detected. The copresence of all six of these ecdysteroids from a single developmental stage of an insect provides information on the metabolic interrelationships that exist among these steroids and on their possible function(s) in insects. The 3alpha-ecdysteroids were far less active than the 3 beta-epimers in the house fly assay. The significance of epimerization is discussed.
The activities of branched and straight chain amines (10 to 18 carbons chain length) were compared in inhibiting the growth of five microorganisms that cause about 95% of bovine mastitis. Three gram-positive (Streptococcus agalactiae, Streptococcus uberis, Staphylococcus aureus) and two gram-negative (Escherichia coli, Klebsiella pneumoniae) bacteria were used in a trypticase soy broth tube culture growth assay. Sixty-two compounds were screened at concentrations of 200, 100, 50, 25, 10, 5, and 1 ppm in broth culture to determine the effective minimum inhibitory concentration. Alkyl secondary N-substituted monoethyl [CH3(CH2)nNHCH2CH3] and tertiary N,N-substituted dimethyl [CH3(CH2) nN(CH3)2] amines with chain lengths of 11 to 14 carbon atoms were active against both gram-positive and gram-negative organisms. Antimicrobial activity against gram-positive organisms increased with increasing chain length and carbon-14 to 18 amines were active at 1 to 5 ppm. The carbon-11 to 13 alkyl amines were most active against gram-positive organisms; longer chain amines (more than 14 carbons) were inactive. Branching of the alkyl chain caused a loss of activity against gram-negative but not against gram-positive bacteria. Antimicrobial testing of monoamines, polyamines, and the influence of order substituents were investigated to correlate structure-acitivity relationships.
The cells which produce the procoagulant part of antihaemophilic factor (factor VIII-C) in normal people have remained unknown. Normal blood leucocytes cultured in vitro with phytohaemagglutinin synthesised a procoagulant with the properties of factor VIII-C. The procoagulant was inhibited by human VIII-C inhibitor and itself absorbed human VIII-C inhibitor--properties which are regarded as specific for factor VIII-C. Unexpectedly, cultured leucocytes from haemophiliacs also synthesised the procoagulant in similar amounts. Possible explanations and implications of these findings are briefly considered.
During commissioning of the medical gas system of a new hospital, fourteen connection defects were found; six of these were potentially lethal cross-connections. A major contaminant was also detected throughout the medical gas system. The methods of testing a new medical gas system described in this report highlight the need for up-grading of existing standards.
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