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Biomedical subjects

D A Otto

Publications and source records attributed to D A Otto.

At least 37 records · Page 2Linked to original sources
PubMed1985

Reciprocal effects of 5-(tetradecyloxy)-2-furoic acid on fatty acid oxidation.

Under certain incubation conditions 5-(tetradecyloxy)-2-furoic acid (TOFA) stimulated the oxidation of palmitate by hepatocytes, as observed by others. A decrease in malonyl-CoA concentration accompanied the stimulation of oxidation. Under other conditions, however, TOFA inhibited fatty acid oxidation. The observed effects of TOFA depended on the TOFA and fatty acid concentrations, the cell concentration, the time of TOFA addition relative to the addition of fatty acid, and the nutritional state of the animal (fed or starved). The data indicate that only under limited incubation conditions may TOFA be used as an inhibitor of fatty acid synthesis without inhibition of fatty acid oxidation. When rat liver mitochondria were preincubated with TOFA, ketogenesis from palmitate was slightly inhibited (up to 20%) at TOFA concentrations that were less than that of CoA, but the inhibition became almost complete (up to 90%) when TOFA was greater than or equal to the CoA concentration. TOFA had only slight or no inhibitory effects on the oxidation of palmitoyl-CoA, palmitoyl(-)carnitine, or butyrate. Since TOFA can be converted to TOFyl-CoA, the data suggest that the inhibition of fatty acid oxidation from palmitate results from the decreased availability of CoA for extramitochondrial activation of fatty acids. These data, along with previous data of others, indicate that inhibition of fatty acid oxidation by CoA sequestration is a common mechanism of a group of carboxylic acid inhibitors. A general caution is appropriate with regard to the interpretation of results when using TOFA in studies of fatty acid oxidation.

Animals↗
PubMed1985

Separating the effects of lead and social factors on IQ.

Initial evaluations of 104 low-socioeconomic status black children screened by the local community health departments in North Carolina showed significant effects of lead in the range 6-59 micrograms/dl on IQ after controlling for concomitant social factors, such as socioeconomic status, home environment, and maternal IQ. The main concomitant variable was socioeconomic status, which was multicolinear with other social factors. Five years later, when all blood lead levels were 30 micrograms/dl or less, lead effects on IQ were no longer significant. The correlation between maternal and child IQ, which had been suppressed initially in children with higher lead levels, returned to expected levels when decreases in blood lead level occurred, while concomitant variables remained stable over the 5-year period.

Child↗
PubMed1984

Relationship of the ATP/ADP ratio to the site of octanoate activation.

Following preincubation of isolated rat liver mitochondria in the absence of substrate, the carnitine-independent oxidation of octanoate or butyrate was markedly depressed when compared to rates observed with nonpreincubated mitochondria. Carnitine addition prevented the inhibition of octanoate oxidation but not that of butyrate. 2-Tetradecylglycidic acid or Zwittergent 3-08 (Z3-08) completely blocked the effect of carnitine. Replacement of ATP in the nonpreincubated incubation system with ADP mimicked the effect of preincubation by inhibiting octanoate and butyrate oxidation. This inhibition of octanoate oxidation was also prevented by carnitine addition. There was a direct and causal relationship between the ATP/ADP ratio of the total adenine nucleotide pool and the rate of carnitine-independent octanoate oxidation in mitochondria. The depression of octanoate oxidation was associated with a decrease in the intramitochondrial AMP content and intra- and extramitochondrial ATP/ADP ratios. In a cellular system, incubating isolated hepatocytes with fructose or glycerol to lower the ATP/ADP ratio resulted in greater inhibition of octanoate oxidation by 2-tetradecylglycidic acid. The data suggest that the ATP/ADP ratio may have a role in determining the site of octanoate activation and subsequent route of oxidation.

Adenosine Diphosphate↗
PubMed1982

Structure-function relations between fatty acid oxidation and the mitochondrial inner-membrane--matrix region.

Decreasing the osmolarity of the incubation media for rat liver mitochondria, by lowering the KCl or sucrose content, greatly increased the oxidation of palmitate, palmitoyl-CoA, palmitoyl-(-)-carnitine, octanoate and butyrate, but only slightly affected the oxidation of succinate, glutamate plus malate, and 3-hydroxybutyrate. Kinetic studies indicated that the increased rate of fatty acid oxidation commenced at the onset of incubation in the hypotonic media and remained relatively constant. This was accompanied by an increase in the 3-hydroxybutyrate: acetoacetate ratio, a higher rate of oxygen consumption, an increase in the extramitochondrial adenine-nucleotide phosphorylation-state ratio, and a greater state of reduction of the respiratory chain cytochromes b, c, and oxidase. Incubation of mitochondria in the hypotonic media caused a rapid decrease in the intermembrane and intracrystal spaces and concurrent expansion of the matrix, without changing the volume of the mitochondria. These observations indicate that expansion of the inner-membrane-matrix compartment of mitochondria in vitro specifically activates fatty acid oxidation at the site of beta-oxidation or at the site of its interaction with the respiratory chain, with a consequent increase in the states of reduction and phosphorylation of the mitochondria. Evidence is also presented which suggests that the activation of mitochondrial fatty acid oxidation by Ca2+ is initiated by a Ca2+-induced alteration of the structure or volume of the inner-membrane-matrix region.

Animals↗
PubMed1981

Effects of age and body lead burden on CNS function in young children. I. slow cortical potentials.

The effects of body Pb burden on slow cortical potentials were studied in 63 children aged 13-75 months. Slow wave (SW) voltage during sensory conditioning varied as a linear function of blood lead (PbB) level. The slope of this function, moreover, changed systematically with age. For children under 5 years of age, SW voltage tended to be positive at low PbBs and to be negative above 30 micrograms/dl. For children over 5 years of age, SW voltage tended to be negative at low PbBs and to be less negative (or positive) above 30 micrograms/dl. These results provide evidence of altered CNS function at the lowest Pb effect level ever reported.

Aging↗
PubMed1981

Effects of age and body lead burden on CNS function in young children. II. EEG spectra.

This study explored the effects of age and PbB upon EEG power spectra and various measures of hemispheric laterality in children, aged 13-75 months, watching a display (cartoon). The following are the principle conclusions: (1) The delta- and theta-band amplitude decreased with age. (2) When only bilaterally synchronized EEG between P3 and P4 was considered, the amplitude of P3 was estimated as greater than P4 in all frequency bands and for all ages. Previous reports have not shown lateral EEG dominance in children below 75 months. (3) When lateral dominance measures consider only the relationship between synchronized EEG at P3 and P4, bilateral communality in the delta band increased with age. (4) Increased PbB generally produced an increase in the relative amplitude of synchronized EEG between P3 and P4 in all frequency bands. This was true for PbB levels well below 15 micrograms/dl, among the lowest level PbB effects previously reported. No clinical or behavioral effects of PbB values have been reported below 15 micrograms/dl. It appears to be theoretically and practically important to understand the functional significance of bilaterally synchronized activity. The signal processing of the CNS can be explored using these methods. Greater understanding of these data would help define the extent and etiology of PbB effects on the CNS

Aging↗
PubMed1980

Differential inhibition of ketogenesis by malonyl-CoA in mitochondria from fed and starved rats.

Rates of ketogenesis in mitochondria from fed or starved rats were identical at optimal substrate concentrations, but responded differently to inhibition by malonyl-CoA. Kinetic data suggest that the K1 for malonyl-CoA is greater in the starved animal. These results indicate that, for the regulation of ketogenesis in the starved state, the lower sensitivity of carnitine palmitoyltransferase to inhibition by malonyl-CoA may be more important than the concentration of malonyl-CoA.

Acyl Coenzyme A↗
PubMed1980

Isolation of a lipocyte-rich fraction from rat liver nonparenchymal cells.

A modified pronase digestion procedure is described for isolating nonparenchymal liver cells from vitamin A treated rats, which yielded a 15-23% population of lipocytes in the total cell suspension. The criteria for defining a lipocyte was the appearance of vitamin A containing cells as determined by fluorescent microscopy. Measurement of alcohol dehydrogenase and retinol dehydrogenase activities indicated that these enzyme activities were not present in the isolated nonparenchymal cells. A lipocyte-rich fraction of nonparenchymal cells was obtained by centrifugation of purified nonparenchymal cells in a linear Metrizamide gradient. Vitamin A fluorescence and chemical assay of vitamin A in the cell fractions indicated a four-fold enrichment of lipocytes in the cell fraction with d = 1.043 g/ml. Fractions high in vitamin A also had numerous cells with fat droplets as shown by transmission electron microscopy.

Adipose Tissue↗
PubMed1979

Carbon monoxide and human time discrimination: failure to replicate Beard-Wertheim experiments.

Beard and Wertheium described a dose-related deficit in human time perception during low level CO exposure. Two other laboratories were unable to replicate this finding, although methodological differences could explain these failures. This study more precisely repeated the original experiment, but failed again to obtain any CO-related deficit. The bulk of evidence, therefore, does not indicate any adverse effect of low level CO exposure on time perception in healthy young adults.

Acoustic Stimulation↗
PubMed1977

Lack of effects of carbon monoxide on human vigilance.

Previous publications on the effects of low levels of carbon monoxide (CO) on human vigilance performance have found conflicting results. While several studies have found statistically reliable effects, none have gone unchallenged. This article presents a critical review of the literature and the results of a study employing 52 human male subjects performing a numeric monitoring task. CO levels were 0, 100, and 200 ppm which produced mean carboxyhemoglobin levels 0.01, 4.61 and 12.62 percent respectively. No CO-exposure levels produced any effect on vigilance performance. The power of the statistical test for CO effects was shown to be quite high, even for fairly trivial possible decrements of performance.

Adult↗
PubMed1975

Effect of low-frequency random noises on performance of a numeric monitoring task.

Previous findings indicate that continuous low-frequency noises at moderate sound-pressure levels do not produce decrements in vigilance performance. Such noises are commonly found in urban environments, however; and it is important to explore their effects carefully. This study employed 27 human males in a numeric monitoring task to evaluate the effects of low-frequency (11.5 to 350 Hz) noise at moderate sound-pressure levels (80 db). More numeric signals were missed during noise than during control runs. The effect was small but statistically reliable (P smaller than .033), in disagreement with previous research. The possible environmental impact of these findings is discussed.

Acoustic Stimulation↗