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Biomedical subjects

P Eriksson

Publications and source records attributed to P Eriksson.

At least 163 records · Page 9Linked to original sources
PubMed1993

Altered behaviour in adult mice orally exposed to tri- and tetrachloroethylene as neonates.

Male NMRI mice were orally exposed to trichloroethylene (TRI, 50 and 290 mg/kg per day) and tetrachloroethylene (PER, 5 and 320 mg/kg per day) between days 10 and 16 postnatally. Spontaneous activity, observed as locomotion, rearing and total activity, was measured over three 20-min periods at an age of 17 and 60 days. Compared to controls, mice at 17 days of age were unaffected, while at 60 days of age mice exposed to PER showed changes in all three spontaneous motor activity variables, while TRI-exposed mice only were affected in rearing. This indicates a neonatal susceptibility of brain maturation to these chlorinated organic solvents in achieving long-lasting changes in adult behaviour.

Administration, Oral↗
PubMed1993

A gene encoding sn-glycerol 3-phosphate dehydrogenase (NAD+) complements an osmosensitive mutant of Saccharomyces cerevisiae.

Osmoregulatory mutants of Saccharomyces cerevisiae with a defect in their capacity to readjust the cell volume/buoyant density after osmotically induced dehydration were enriched by density gradient centrifugation. Colonies derived from cells that remained dense after dehydration were screened for sensitivity to high concentrations of NaCl and defects in their osmotically induced production and intracellular accumulation of glycerol. The isolated osg (osmosensitive glycerol defective) mutants were recessive in heterozygous diploids and fell into four complementation groups (osg1-osg4). The osg1-1 mutant, described in this work, is unable to grow at low water potential and shows a decreased capacity for glycerol production and a strongly reduced activity of NAD(+)-dependent sn-glycerol 3-phosphate dehydrogenase (GPD), an enzyme in the glycerol-producing pathway. Complementation of the osg1-1 salt sensitivity defect with a low copy yeast genomic library led to the cloning of GPD1, encoding an S. cerevisiae GPD consisting of 391 amino acids and sharing 47-50% identity with GPD from other sources. Micro-sequencing of the N-terminus of purified S. cerevisiae GPD revealed a 20-amino-acid sequence that was identical to a nucleotide-deduced amino acid sequence in GPD1, but indicated that the enzyme is produced with an N-terminal extension that is removed from the functional enzyme. Subcellular fractionation does not indicate, however, that the putative pre-sequence targets GPD to any organelle; the enzyme appears to be located in the cytoplasm. Chromoblot and tetrad analysis were used to position the GPD1 gene to chromosome IV, with a distance of about 18 cM from trp1.

Amino Acid Sequence↗
PubMed1992

[Astrocytes are of vital significance for the central nervous system].

The tissue of the CNS (central nervous system) is composed of neurons and neuroglia. Whereas neurons develop an ability for the rapid transduction of specific signals, astrocytes develop an ability to modulate the extracellular neuronal environment, and in mature CNS tissue manifest a capacity for active uptake of amino acids and ions. Astrocytes can control extracellular volume by regulation of their own volume, and are intimately involved in the neuronal exchange of trophic substances and metabolites. Astrocytic processes extend to blood vessel walls, the brain surface, the ventricular wall, neuronal cell bodies and synapses. Astrocytes are abundantly supplied with membrane receptors for various neurotransmitters, coupled to such second messenger systems as cyclic AMP (adenosine monophosphate) or the phosphatidylinositol cycle. Activation of the receptors results in changes in oxidative metabolism, cell morphology, cell volume, and immunocompetence: and recent findings have shown the occurrence of receptor-mediated changes in amino acid uptake. Thus, by modulating the extracellular environment, astrocytes can simultaneously modulate the sensitivity and/or excitability of large numbers of neurons. In the article are presented recent research findings suggesting astroglial cells to be targets for neurotransmitters, and probably to be actively involved in higher cognitive functions. Advances in our knowledge of astroglial cell characteristics might improve our understanding of behavioural disturbances and diseases of the CNS.

Astrocytes↗
PubMed1992

Exposure to DDT during a defined period in neonatal life induces permanent changes in brain muscarinic receptors and behaviour in adult mice.

DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] is a potent neurotoxicant in both vertebrate and invertebrate species. We have previously reported that neonatal exposure to DDT affects the muscarinic cholinergic receptors (MAChR) in the cerebral cortex in the neonatal mouse, leading to permanent disturbances in the cholinergic system and behaviour of the animals as adults. In order to determine if there is a critical period for these effects, mice at the ages of 3-days, 10-days and 19-days were given a single low oral dose of DDT (0.5 mg/kg b.wt.). At adult age (4 months) the mice were tested for spontaneous behaviour: 'locomotion', 'rearing' and 'total activity', and were subsequently sacrificed for measurement of the density of MAChR and subpopulations of MAChR in the cerebral cortex by using the muscarinic antagonist quinuclidinyl benzilate, [3H]QNB, and agonist carbachol, respectively. A significant increase in spontaneous motor behaviour and a significant decrease in MAChR density in the cerebral cortex was only observed in adult mice receiving DDT at the age of 10 days. The induction of these disturbances is limited to peaks in the development of spontaneous behavioural activity and MAChR in the neonatal rodent.

Animals↗
PubMed1992

Behavioural effects of neonatal metallic mercury exposure in rats.

The effect of neonatal exposure of rats to mercury vapour (Hg0), at the concentration 0.05 mg/m3, 1 h (low dose) or 4 h (high dose), on the behaviour in adulthood were studied. Exposure occurred on days 11-17 (the period of rapid brain growth). Tests for spontaneous motor activity were performed at the ages of 2 and 4 months. Rats exposed to the high dose Hg0 showed a marked increase in variables locomotion and total activity but a decrease for rearing when tested at 2 months of age. At 4 months of age these rats showed a marked hypoactivity with respect to all three variables. Rats exposed to the low dose showed no significant differences at 2 months compared to controls. However, at the age of 4 months the same pattern (increase in variables locomotion and total activity but a decrease for rearing) already noticed in the high dose group at 2 months was observed. In the spatial learning tasks applied, the radial arm maze and circular swim maze, neonatally exposed pups showed a retarded acquisition to the former, while there was no difference compared to controls in the latter. These data indicate that neonatal exposure to mercury vapour results in similar behaviour changes as reported from offspring prenatally exposed to mercury vapour or methylmercury. Furthermore, exposure for 1 week to concentrations around Swedish threshold values (TLV) for 1 or 4 h resulted in dose and age-related behavioural changes.

Age Factors↗
PubMed1992

Quantitative assessment of aortic regurgitation by combined two-dimensional, continuous-wave and colour flow Doppler measurements.

The width of the regurgitant jet at the aortic valve plane, i.e. the core flow diameter, the ratio of the jet width to the left ventricular outflow diameter, the regurgitant volume and regurgitant fraction were determined using two-dimensional, continuous wave and colour flow Doppler echocardiography. The relationship between the non-invasive measurements and semiquantitative angiographic grading of the regurgitant flow (1 + to 4+) was examined in a primary group of 20 patients with chronic aortic regurgitation. Cut-off points for the non-invasive measurements were selected so as to separate patients with mild or moderate regurgitation (1+ or 2+) from patients with moderately severe or severe regurgitation (3+ or 4+). These cut-off points were prospectively applied in a new group of 35 patients with aortic regurgitation to predict the angiographic grading. Jet width correctly predicted the angiographic grading in 86% of cases, the ratio of the jet width to the outflow diameter in 83% of cases, the regurgitant volume in 86% of cases and the regurgitant fraction in 91% of cases. We conclude that the severity of aortic regurgitation as determined by angiographic grading can be estimated with reasonable accuracy by non-invasive techniques based on colour flow imaging.

Adult↗
PubMed1991

Neonatal nicotine exposure induces permanent changes in brain nicotinic receptors and behaviour in adult mice.

The effects of neonatal nicotine exposure on spontaneous and nicotine-induced behaviour in 4-month-old mice and on the development of brain nicotinic receptors were studied. The behaviour study showed that mice treated with nicotine 66 micrograms (-)nicotine base/kg body weight (bw) s.c. twice daily between 10 and 16 days postnatally displayed a hypoactive condition, whereas mice treated with saline displayed a hyperactive condition. When the nicotinic receptors in the brain cortex were analyzed, the displacement curves for [3H]nicotine(-)nicotine revealed an almost equal proportion of high- and low-affinity binding sites in 17-day-old mice, while the high-affinity sites predominated in 4-month-old mice, with affinity constants for both high- and low-affinity binding sites 10 times higher in 4-month-old mice than in 17-day-old-mice. A decrease in the number of nicotinic receptors was observed from day 17 to 4 months, mainly of the low-affinity nicotinic type. Interestingly, the displacement curves in neonatally nicotine-treated mice showed only one population of high-affinity binding sites in 17-day- and 4-month-old mice though the total binding sites in 4-month-old mice were the same for the neonatally nicotine-treated and saline-treated mice. These results indicate that neonatal nicotine treatment prevents the development of low-affinity nicotinic sites in the brain and this earlier exposure to nicotine induces a different behaviour response in adult animals to a test dose of nicotine. Days 10-16 postnatally appear to be a critical period for the effects of nicotine on the brain.

Aging↗
PubMed1991

Neurotoxic effects of two different pyrethroids, bioallethrin and deltamethrin, on immature and adult mice: changes in behavioral and muscarinic receptor variables.

We have recently shown that two pyrethroids, bioallethrin and deltamethrin, affect muscarinic cholinergic receptors (MAChR) in the neonatal mouse brain when given to suckling mice during the period of rapid brain growth. Such early exposure to these pyrethroids can also lead to permanent changes in the MAChR and behavior in the mice as adults. In the present study, male NMRI mice were given bioallethrin (0.7 mg), deltamethrin (0.7 mg), or a 20% fat emulsion vehicle (10 ml) per kilogram of body weight per os once daily between the 10th and 16th postnatal day. The mice were subjected to behavioral tests upon reaching the age of 17 days and at 4 months. Within 1-2 weeks after the behavioral tests the mice were killed by decapitation and crude synaptosomal fractions (P2) were prepared from the cerebral cortex, hippocampus, and striatum. The densities of MAChR were assayed by measuring the amounts of quinuclidinyl benzilate ([3H]QNB) specifically bound in the P2 fraction. The proportions of high-affinity (HA) and low-affinity (LA) binding sites of MAChR were assayed in a displacement study using [3H]QNB/carbachol. The behavioral tests at an adult age of 4 months indicated a significant increase in spontaneous motor behavior in both bioallethrin- and deltamethrin-treated mice. There was also a significant decrease and a tendency toward a decrease in the density of MAChR in the cerebral cortex in mice receiving bioallethrin and deltamethrin, respectively. The proportions of HA- and LA-binding sites of MAChR were not changed. This study further supports that disturbances of the cholinergic system during rapid development in the neonatal mouse can lead to permanent changes in cholinergic and behavioral variables in the animals as adults.

Allethrins↗
PubMed1991

Neonatal exposure to 3,3',4,4'-tetrachlorobiphenyl: changes in spontaneous behaviour and cholinergic muscarinic receptors in the adult mouse.

We have previously reported that 3,3',4,4'-tetrachlorobiphenyl (TCB) affects muscarinic cholinergic receptors (MAChR) in the neonatal mouse brain when given to suckling mice at the age of 10 days. As shown in the present study, such early exposure to TCB may also lead to a permanent change in the MAChR and disturbed behaviour of the mice as adults. Male NMRI mice were given two single oral doses of TCB, 0.41 or 41 mg/kg body wt, and a 20% fat emulsion vehicle (10 ml)/kg body wt. The behavioural test at adult age of 4 months indicated a significant change in spontaneous motor behaviour in the TCB-treated mice. In mice receiving the highest dose of TCB there was also a minor increase (5%), although significant, in the density of MAChR in the hippocampus, assayed by using the tritium-labeled muscarinic antagonist, quinuclidinyl benzilate [( 3H]QNB). As previously reported, this part of the brain was affected in the neonatal mouse, which shows that the cholinergic system during rapid development in the neonatal mouse brain is sensitive to disturbance. This may lead to permanent changes in the animals as adults, accompanied by behavioural changes.

Animals↗
PubMed1991

DDT and pyrethroids--ecotoxicological considerations.

1. DDT, and a DDT metabolite, DDOH, conjugated to palmitic acid, DDOH-PA, as well as bioallethrin and deltamethrin have all been shown to affect muscarinic cholinergic receptors (MAChR) in the neonatal mouse brain after administration to 10-day-old mice during the period of rapid brain growth. 2. This early exposure has also been shown to lead to permanent changes in cholinergic and behavioural variables in the animals as adults.

Acetylcholine↗
PubMed1991

The glucocorticoid receptor in homodimeric and monomeric form visualised by electron microscopy.

The purified glucocorticoid receptor (GR) from rat liver has been visualised by electron microscopy. The specimens were prepared by spreading on thin carbon support and negatively stained using uranyl acetate. Two forms of GR, the monomeric and the dimeric forms, were identified based on size, chromatographic distribution, and DNA binding properties. The GR monomer consists of two globular domains of slightly different size with a thinner connecting domain in between. In the absence of DNA the dimeric GR has a characteristic four-leaf clover structure. The size and appearance of this structure is consistent with two GR subunits arranged in a side-by-side fashion. Monomeric and dimeric GR specifically bound to DNA are also shown.

Animals↗
PubMed1991

Transfer effects of endurance training with the arms and legs.

The purpose of this study was to examine whether endurance training in the form of arm or leg cycling resulted in significant transfer effects when exercise was performed with the untrained muscle group. Sixteen middle-aged male volunteers completed 24 training sessions over 8 wk on either an arm cycle ergometer (AG, N = 8, mean age = 35.2 +/- 6.6 yr) or a leg cycle ergometer (LG, N = 8, mean age = 41.0 +/- 4.7 yr). The two groups were initially equated for their pre-training peak oxygen uptake (pVO2) determined during leg cycling (44.5 +/- 5.0 and 43.8 +/- 7.7 ml.kg-1.min-1 for the AG and LG, respectively). Training was performed at an intensity that was mid-way between the pre-training ventilatory threshold (VT) and the pVO2 for both cycling methods. Significant increases (P less than .05) were observed in the relative values of the oxygen uptake at the VT and the pVO2 as a result of both these methods of training, but these elevations were specific to the muscle groups that were trained. This specificity of training was also evident in the cardiorespiratory and metabolic measurements obtained during submaximal steady state exercise performed at the power output corresponding to the pre-training VT during arm and leg exercise. Hence, it was concluded that improvements in exercise performance resulting from short-term aerobic training with the arms or legs in middle-aged males with relatively high aerobic powers are due primarily to peripheral adaptations in the trained muscles.

Adult↗
PubMed1991

Reliability of peak physiological responses during wheelchair ergometry in persons with spinal cord injury.

This study examined the test-retest reliability of peak physiological responses during wheelchair ergometry (WE) in individuals with spinal cord injury (SCI). Seven wheelchair dependent subjects, two with paraplegia (T10-11 and T11-12 lesions) and five with quadriplegia (all with C6-7 lesions), were given two incremental exercise tests to volitional fatigue on separate occasions within a one-week period. Each subject wheeled his or her personal wheelchair, which was mounted on a set of frictionless rollers with side-mounted flywheels. Metabolic and cardiorespiratory responses were continuously monitored by means of an automated metabolic measurement cart interfaced with an electrocardiograph. Statistical analysis revealed no significant differences (p greater than .05) between the mean values of the two test trials for six peak values. Reliability coefficients (p less than .01) were: oxygen uptake (0.98), heart rate (0.97), ventilation volume (0.96), respiratory exchange ratio (0.91), oxygen pulse (0.96), and ventilatory equivalent for oxygen (0.88). The investigators concluded that these six physiological responses in subjects with SCI undergoing WE are highly reliable, and that these variables can be used in the objective prescription, monitoring, and evaluation of exercise rehabilitation programs for individuals with SCI.

Adult↗
PubMed1990

Two nuclear proteins bind to the major positive element of the apolipoprotein B gene promoter.

The promoter of the apolipoprotein B-encoding gene (apoB) contains a number of regulatory elements, which together produce a high level of expression that is restricted to two tissues: liver and intestine. In this paper we have used the gel retardation and methylation interference assays to identify two nuclear proteins, LIT1 and LIT2, which bind to the major positive element (MPE) of the apoB promoter. LIT1 is large protein, estimated to be approx. 200 kDa by gel filtration, which binds to the apoB promoter between positions of -79 and -65 bp in relation to the transcription start point. Its binding site is identical to the region responsible for cell-specific transcriptional activation. However, whereas the MPE has no influence on expression from a heterologous promoter in the non-apoB-expressing HeLa cells, these cells still contain a DNA-binding activity indistinguishable from LIT1. LIT2 binds to the apoB promoter immediately downstream from the LIT1 site. It is present in nuclear extracts from the apoB-expressing cell lines of hepatic (HepG2) and intestinal (CaCo-2) origin, but absent from HeLa cells. CCAAT/enhancer binding protein (C/EBP), expressed in bacteria, binds to the LIT2 site and produces a methylation interference pattern indistinguishable from that of LIT2. That C/EBP binds to and activates the apoB promoter in vivo, is shown by the increased chloramphenicol acetyltransferase activity observed when HepG2 cells, transfected with apoB-promoter-cat constructs, are cotransfected with a plasmid expressing c/ebp; an effect that depends on the presence in the apoB promoter of the LIT2 site.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins B↗
PubMed1990

Quantitative analysis of the glucocorticoid receptor-DNA interaction at the mouse mammary tumor virus glucocorticoid response element.

Purified glucocorticoid receptor (GR) from rat liver was used for a quantitative analysis of the protein-DNA interaction at specific GR-binding segments within the 5'-long terminal repeat of the mouse mammary tumor virus. A truncated receptor was generated and used to demonstrate formation of heterodimeric GR, which furthermore was shown to be in rapid equilibrium with receptor-monomer. The relative affinity for GR binding to specific GR sites versus random calf thymus DNA was approximately 2 x 10(3). At equilibrium a free GR concentration of 3 x 10(-10) M was required for half-maximal saturation of the two functionally important DNA sites within the mouse mammary tumor virus 5'-long terminal repeat. Although these two DNA segments act synergistically in mediating hormonal response, we did not detect cooperative GR binding to these regions in vitro. However, GR bound cooperatively within the downstream binding region. Similarly, GR was unable to facilitate factor binding to a neighboring nuclear factor 1 site, another essential element in the promoter. In contrast, nuclear factor 1 binding was inhibited slightly by GR.

Animals↗
PubMed1990

Altered behaviour in adult mice exposed to a single low dose of DDT and its fatty acid conjugate as neonates.

DDT, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)-ethane is one of the best-known insecticides which produces neurotoxic syndrome in mammals. DDT is also a world-wide environmental contaminant which is still used in several countries. We have previously reported on pronounced retention of DDT in the neonatal mouse brain. We have also observed that DDT and a DDT metabolite, DDOH, conjugated to palmitic acid (DDOH-PA), which have been found in DDT-treated female rats, affect the muscarinic cholinergic receptors in the brain of the neonatal mouse. We now report that neonatal exposure to a single low oral dose of DDT and DDOH-PA (1.4 mumol/kg b.wt.) also can lead to a permanent hyperactive condition in the mice as adults.

Animals↗