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Biomedical subjects

M J Thompson

Publications and source records attributed to M J Thompson.

At least 73 records · Page 4Linked to original sources
PubMed1987

Metabolism of sterols of varying ring unsaturation and methylation by Caenorhabditis elegans.

The metabolism of three dietary 4,4-desmethylsterols and two 4 alpha-methylsterols was investigated in the free-living nematode Caenorhabditis elegans. Dietary cholestanol was converted mostly to lathosterol. Dietary lathosterol, 7-dehydrocholesterol, 4 alpha-methylcholest-7-enol and 4 alpha-methylcholest-8(14)-enol each remained largely unchanged. An absolute requirement for a substantial quantity of 7-dehydrocholesterol in C. elegans did not exist. C. elegans was unable to remove a 4 alpha-methyl group or introduce a double bond at C-5 and also demonstrated the lack of a delta 7-reductase. Its nutritional sterol requirement was satisfied by cholestanol, lathosterol or 7-dehydrocholesterol; growth was comparable to that obtained previously in media containing delta 5-sterols. However, the two 4 alpha-methylsterols appeared to be unsatisfactory sterol nutrients. The possible physiological importance of 4 alpha-methylsterols is discussed briefly.

Animals↗
PubMed1985

Biosynthesis of a C21 steroid conjugate in an insect. The conversion of [14C]cholesterol to 5-[14C]pregnen-3 beta,20 beta-diol glucoside in the tobacco hornworm, Manduca sexta.

Following injection into Manduca sexta (L.) female pupae (day 16), [14C]cholesterol was converted to a C21 steroid conjugate, 5-[14C]pregnen-3 beta,20 beta-diol glucoside. The conjugate was isolated from ovaries and eggs and contained three glucose units at least one of which is attached to C-20. The distribution of the other two glucose units remains to be determined. Other than the dealkylation of C-24 alkane or alkene substituents, side-chain cleavage of sterols is uncommon to insects. Here we report the first definitive proof of the biosynthesis of a C21 steroid conjugate from cholesterol in an insect species. The capability of M. sexta to so readily convert cholesterol to a C21 steroid suggests a physiological role for 5-pregnen-3 beta,20 beta-diol in this species.

Animals↗
PubMed1985

Inhibition of C28 and C29 phytosterol metabolism by N,N-dimethyldodecanamine in the nematode Caenorhabditis elegans.

Effects on the metabolism of campesterol and stigmasterol in Caenorhabditis elegans were investigated using N,N-dimethyldodecanamine, a known inhibitor of growth, reproduction and the delta 24-sterol reductase of this nematode. 7-Dehydrocholesterol was the predominant sterol (51%) of C. elegans grown in stigmasterol-supplemented media, whereas addition of 25 ppm amine resulted in a large decrease in the relative percentage of 7-dehydrocholesterol (23%) and the accumulation of a substantial proportion (33%) of delta 24-sterols (e.g., cholesta-5,7,24-trienol) and delta 22,24-sterols (e.g., cholesta-5,7,22, 24-tetraenol) but yielded no delta 22-sterols. Dealkylation of stigmasterol by C. elegans proceeded in the presence of the delta 22-bond; reduction of the delta 22-bond occurred prior to delta 24-reduction. Addition of 25 ppm amine to campesterol-supplemented media altered the sterol composition of C. elegans by increasing the percentage of unmetabolized dietary campesterol from 39 to 60%, decreasing the percentage of 7-dehydrocholesterol from 26 to 12%, and causing the accumulation of several delta 24-sterols (6%). C. elegans also was shown to be capable of dealkylating a delta 24 (28)-sterol as it converted 24-methylenecholesterol to mostly 7-dehydrocholesterol. The proposed role of 24-methylenecholesterol as an intermediate between campesterol and 7-dehydrocholesterol was supported by the results.

Amines↗
PubMed1985

Effects of an azasteroid on growth, development and reproduction of the free-living nematodes Caenorhabditis briggsae and Panagrellus redivivus.

The azasteroid, 25-azacoprostane (ASA-6), was evaluated for its effects on the growth, development and reproduction of the free-living nematodes, Caenorhabditis briggsae and Panagrellus redivivus. The axenic culture medium for either species of nematode consisted of Caenorhabditis briggsae Maintenance Medium (CbMM): formalin-killed Escherichia coli (1:1) with or without the addition of 5 micrograms cholesterol per ml and/or 25 micrograms ASA-6 per ml medium. All cultures also contained 50 micrograms Tween 80 per ml medium. After two generations of growth in sterol-deficient media, both species displayed a decrease in mean length, a decrease in the percent development to the adult stage and an inhibition of reproductive capability. These effects were more apparent in the sterol-deficient medium containing ASA-6. In the presence of cholesterol and ASA-6, growth and reproduction of C. briggsae, but not of P. redivivus, was inhibited after five generations. Morphologic abnormalities of azasteroid-inhibited worms were similar to those shown by worms cultured in sterol-deficient medium. These results suggest that different species of nematodes may exhibit different responses to azasteroid and that sterol utilization and metabolism may vary between nematode species. In addition, the similarities between the known effects of azasteroid inhibition in insects and those presented in this study on nematodes suggest a similar mechanism of action by the inhibitor in both groups of organisms.

Animals↗
PubMed1984

Ecdysteroids in developing ovaries and eggs of the tobacco hornworm.

Ecdysteroids of ovaries and newly-laid eggs (0- to 1-hour-old) of the tobacco hornworm are present mainly as conjugates (greater than 95%). Newly-laid eggs contain ecdysteroid conjugates equivalent to 21 micrograms of 26-hydroxyecdysone and 0.73 micrograms of ecdysone per gram of eggs. These levels are similar in ovaries of 93-hour-old adult females. In 1- to 18-hour-old eggs more than 63% of the ecdysteroids exist in the free form and the proportion is similar in 48- to 64-hour-old eggs. The ratio of 26-hydroxyecdysone to ecdysone in the conjugated form remains constant during oocyte maturation and embryogenesis. Though 26-hydroxyecdysone is without molting hormone activity in the house fly assay, the exceptionally high concentration of 26-hydroxyecdysone conjugate(s) in ovaries and newly-laid eggs, together with the fact that it is being released during embryogenesis, indicate some physiological role for 26-hydroxyecdysone.

Animals↗
PubMed1984

Effects of azasteroids on growth and development of the free-living stages of Nippostrongylus brasiliensis and Nematospiroides dubius.

25-Azasteroids were evaluated for their effects on the growth and development of the free-living stages of Nippostrongylus brasiliensis and Nematospiroides dubius. Increasing the concentration of 25-azasteroids in axenic cultures of either species resulted in a decrease in the percentage and mean length of larvae that developed to the third stage. Morphologic abnormalities of inhibited larvae were similar to those shown by larvae cultured in sterol-deficient medium. Addition of cholesterol to the culture medium reversed the inhibitive effects of azasteroid. Azasteroid completely inhibited growth and development of N. brasiliensis when the only sterol present in the culture medium was sitosterol. These results suggest similar pathways of sterol metabolism and similar mechanisms of action by azasteroids in the nematodes and insects that have been studied.

Animals↗
PubMed1984

Comparative effects of growth inhibitors on sterol metabolism in the nematode Caenorhabditis elegans.

An analogous series of dimethylalkyl compounds, consisting of four amines, an amide, and a phosphonate ester, inhibited motility and reproduction of the nematode Caenorhabditis elegans. Dimethylamines with straight-chain lengths of 12, 14, or 16 carbon atoms were equally active nematicides, causing greater than 80% population growth inhibition at a concentration of 25 ppm. The C12 straight-chain amine and its corresponding amide produced similar inhibition and were much more potent than either the corresponding C12 phosphonate or a C12 branched-chain amine. Inhibition of the delta 24-sterol reductase system was exhibited by all four amines, but not by the amide or phosphonate, in the following order of activity: C12 branched-chain amine greater than C12 straight-chain amine greater than C14 amine greater than C16 amine. The C12 branched amine also blocked the C-24(28)-dehydrogenase system in the conversion of sitosterol to fucosterol, the initial step in sitosterol dealkylation.

Amides↗
PubMed1984

Free erythrocyte protoporphyrin as an index of perinatal iron status.

The relationship between free erythrocyte protoporphyrin and conventional indices of iron status was studied in 49 mothers and their infants. Maternal venous blood samples were collected at 34 weeks gestation and at delivery. The corresponding infant blood samples were collected from the umbilical cord and at age 6 weeks. In each case free erythrocyte protoporphyrin, serum iron, total iron binding capacity, and serum ferritin were determined. Cord free erythrocyte protoporphyrin was negatively correlated with maternal ferritin at 34 weeks gestation (p = 0.016) and at delivery (p = 0.014), and with transferrin saturation at delivery (p = 0.026). The infants' haemoglobin concentrations at 6 weeks were significantly negatively related to maternal free erythrocyte protoporphyrin at 34 weeks (p = 0.026) and at delivery (p = 0.026). Cord free erythrocyte protoporphyrin is an index of maternal iron status in the last trimester. Maternal free erythrocyte protoporphyrin in the last trimester predicts the magnitude of physiological anaemia of the infant at age 6 weeks.

Adult↗
PubMed1984

The Minnesota Diabetes Complications Clinical Trial cognitive functions under long-term maximized and standard metabolic controls.

We have studied memory (Wechsler Memory Scale) and mood states in 20 insulin dependent diabetics under maximized metabolic control (treated with multiple insulin injections daily or insulin pumps) and 12 patients under standard control (treated with one or more injections of insulin daily). Both groups of patients have been enrolled in the Minnesota Diabetes Complications Clinical Trial for two years or longer. The patients in the maximized control group (mean +/- SD) blood glucose 130 +/- 9 mg/dl) had hypoglycemic episodes much more frequently than the patients in the standard control group (mean +/- SD blood glucose 242 +/- 22 mg/dl). Both groups of patients had normal cognitive functions, including a few patients with numerous hypoglycemic episodes. Only one patient who developed a hypoglycemic coma for several weeks has had lasting abnormal cognitive functions including a few patients with numerous hypoglycemic episodes. We conclude that long-term maximized diabetic control (at least 2 years), although not devoid of danger, does not seem to affect cognitive functions in the patients tested according to the parameters used.

Adult↗
PubMed1983

Novel nuclear methylation of sterols by the nematode Caenorhabditis elegans.

Caenorhabditis elegans possesses a unique sterol methylation pathway not reported to occur in any other organism and also removes the C-24 ethyl group of sitosterol (a plant sterol). This nematode produced substantial quantities of 4 alpha-methyl-5 alpha-cholest-8(14)-en-3 beta-ol and smaller amounts of lophenol from dietary cholesterol, desmosterol or sitosterol. When C. elegans was propagated in media containing sitosterol plus 25-azacoprostane hydrochloride (25-aza-5 beta-cholestane hydrochloride), an inhibitor of delta 24-sterol reductase in insects, its 4 alpha-methylsterol fraction largely consisted of equal amounts of 4 alpha-methyl-5 alpha-cholesta-7,24-dien-3 beta-ol and 4 alpha-methyl-5 alpha-cholesta-8(14),24-dien-3 beta-ol. Thus 25-azacoprostane hydrochloride inhibited both a delta 24-sterol reductase and a delta 7-sterol isomerase in C. elegans.

Animals↗
PubMed1982

Utilization and metabolism of dietary sterols in the honey bee and the yellow fever mosquito.

The honey bee, Apis mellifera, does not convert C28 and C29 phytosterols to cholesterol as found in most previous studies of phytophagous or omnivorous insects, but instead the workers and queens selectively transfer 24-methylenecholesterol, sitosterol and isofucosterol from their endogenous sterol pools to the brood larvae regardless of the sterol in the worker diet. Administering radiolabeled sterols by feeding and injection has made it possible to trace this selective transfer through a second generation of the honey bee. In further comparative sterol metabolism studies, the yellow fever mosquito, Aedes aegypti, was shown to be capable of dealkylating and converting a radiolabeled C29 dietary sterol ([14C]sitosterol) to cholesterol. Metabolic studies with several radiolabeled dietary sterols and an inhibitor of steroid metabolism in the yellow fever mosquito further verified this capability.

Aedes↗
PubMed1982

Synthesis of brassinosteroids and relationship of structure to plant growth-promoting effects.

A number of brassinosteroids with and without hydroxyl groups or an alkyl substituent in their side chain were synthesized. The alkyl substituent at C-24 highly influenced the oxidation of the C-22 double bond with osmium tetroxide and, hence the ratio of the 22 beta,23 beta- and 22 alpha,23 alpha-glycolic isomers obtained. Two different bean bioassays used to compare the plant growth-promoting capabilities of these compounds and of brassinolide and its three side chain 22,23-cis-glycolic isomers showed that brassinolide was the most active. The next most active brassinosteroids were generally those with 22 alpha-OH, 23 alpha-OH orientation and a beta-methyl or alpha-ethyl substituent at C-24. Similarly, of the synthetic precursor tetrahydroxy ketones of the brassinosteroids, those with 22 alpha-OH, 23 alpha-OH orientation (like brassinolide) and an alkyl group at C-24 were also the most active in both bioassays. The results indicate stringent structural features are required for a steroid to induce brassin activity. The structural requirements are: a trans A/B ring system (5alpha-hydrogen), a 6-ketone or a 7-oxa-6-ketone system in ring B, cis alpha-oriented hydroxyl groups at C-2 and C-3, cis hydroxy groups at C-22 and C-23 as well as a methyl or ethyl substituent at C-24.

Biological Assay↗
PubMed1982

Comparison of N,N-dimethyldodecanamine with antibiotics on in vitro cellulose digestion and volatile fatty acid production by ruminal microorganisms.

Eleven antibiotic compounds used in animal production, were compared with N,N-dimethyldodecanamine for their effects on in vitro cellulose digestibility and VFA production. Dose-response data were analyzed statistically to determine the concentration for each compound which would inhibit cellulose digestion of VFA production by 50%, thereby providing a convenient reference point for evaluation of the amine with respect to the antibiotics. Chlortetracycline, oxytetracycline and penicillin inhibited cellulose digestion by 17 to 35% and VFA production by 18 to 26% at concentrations of 2.5 micrograms/ml, while N,N-dimethyldodecanamine and dihydrostreptomycin at concentrations of 10 micrograms/ml inhibited cellulose digestion and VFA production by 5 to 19%. For similar inhibitive effects, bacitracin, chloramphenicol, kanamycin, sulfanilamide and sulfathiazole were required in concentrations of 25 micrograms/ml. Tylosin at a concentration of 1 microgram/ml inhibited cellulose digestion and VFA production by about 80 and 50%, respectively, and monensin was effective at 5 micrograms/ml. In general, compounds of lesser importance for growth promotion in ruminants (sulfathiazole, sulfanilamide and kanamycin) had a less inhibitory effect on cellular digestion and VFA production in vitro. N,N-dimethyldodecanamine was more effective than these compounds but repressed cellulolytic activity less than those antibiotics (chlortetracycline, oxytetraxycline and monensin) that are most effective in improving feed efficiency.

Amines↗
PubMed1982

Mastitis: effect of pH, temperature, and emollients on disinfecting action of N,N-dimethyldodecanamine.

Growth inhibition of bacteria over time by N,N-dimethyldodecanamine, a tertiary alkyl amine, was studied to evaluate disinfecting action with changes in pH and temperature and with addition of emollients. Because alkyl amines have limited solubility in aqueous solutions, the effect of pH on solubility of the tertiary amine was determined. Non-growing cultures of Streptococcus agalactiae or Escherichia coli were added to sterile buffer or buffer containing the amine, and at specific intervals aliquots were removed, neutralized in a lecithin/Tween 80 quencher, and then plated to determine the number of surviving bacteria per plate. Survival curves were used to determine the effect of changing environmental conditions on antimicrobial activity. Antimicrobial activity was greater at pH 7 than at pH 8 and was least at pH 6. Increases in temperature from 20 to 40 degrees C caused a corresponding increase in antimicrobial activity. Addition of up to 10% glycerin or propylene glycol caused no significant decrease in antimicrobial activity of the tertiary amine.

Amines↗
PubMed1982

Vasodilators and prostaglandin inhibitors in primary pulmonary hypertension.

Ten women with primary pulmonary hypertension had resting hemodynamic measurements taken before and after the nonparenteral administration of various vasodilators and prostaglandin inhibitors. Only sublingual isoproterenol, alone or combined with sublingual isosorbide dinitrate, effected a substantial (greater than 20%) drop in pulmonary vascular resistance; this decrease was accompanied by little change in pulmonary artery pressure. Isosorbide dinitrate was the only drug that elicited any reduction in pulmonary artery pressure; pulmonary vascular resistance decreased modestly. The oral administration of diazoxide, hydralazine, phentolamine, and tolazoline elicited little change in pulmonary artery pressure or resistance. Except for tolazoline, all these agents significantly decreased systemic blood pressure and resistance. Prostaglandin inhibition by indomethacin (acute and chronic dosing) increased pulmonary and systemic vascular resistances and reduced cardiac output. Aspirin combined with dipyridamole elicited no changes. The vasodilators and prostaglandin inhibitors studied evoked little improvement in resting pulmonary hemodynamic abnormalities in primary pulmonary hypertension.

Adolescent↗