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Biomedical subjects

P Eriksson

Publications and source records attributed to P Eriksson.

At least 181 records · Page 10Linked to original sources
PubMed1990

Effects of two pyrethroids, bioallethrin and deltamethrin, on subpopulations of muscarinic and nicotinic receptors in the neonatal mouse brain.

Ten-day-old NMRI mice were given deltamethrin, bioallethrin, or the vehicle once daily for 7 days. The doses used were as follows: deltamethrin, 0.71 and 1.2 mg/kg body wt; bioallethrin, 0.72 and 72 mg/kg body wt; and 20% fat emulsion vehicle, 10 ml/kg body wt. The mice were killed 24 hr after the last administration, and crude synaptosomal fractions (P2) were prepared from the cerebral cortex and hippocampus. The densities of the muscarinic and nicotinic receptors were assayed by measuring the amounts of quinuclidinyl benzilate ([3H]QNB) and [3H]nicotine, respectively, specifically bound in the P2 fraction. The proportions of high- and low-affinity binding sites of the muscarinic receptors were assayed in a displacement study using [3H]QNB/carbachol. The two types of pyrethroids affected the cholinergic system in the neonatal mouse brain in two different ways. At the lower dose, which did not cause any neurotoxic symptoms, both pyrethroid types affected the muscarinic receptors in the cerebral cortex. Here deltamethrin caused an increase and decrease in the percentage of high- and low-affinity binding sites, respectively, whereas the reverse was observed after bioallethrin treatment. Deltamethrin treatment also caused an increase in the density of nicotinic receptors in the cerebral cortex. The higher doses revealed typical symptoms of pyrethroid poisoning, such as choreoathetosis and tremor for deltamethrin and bioallethrin, respectively. The symptoms declined gradually during each successive day of administration and had disappeared by Day 4. At this dose deltamethrin affected the muscarinic receptors in the hippocampus and the nicotinic receptors in the cerebral cortex, whereas bioallethrin had no apparent effect. This study further supports that the cholinergic system under rapid development in the neonatal mouse is sensitive to xenobiotics.

Allethrins↗
PubMed1990

Protein-protein contacts in the glucocorticoid receptor homodimer influence its DNA binding properties.

We have investigated the influence of the N-terminal domain of the 94-kDa glucocorticoid receptor on the DNA:receptor interaction. An alpha-chymotrypsin-induced 39-kDa receptor fragment, containing the hormone and DNA binding domains, binds DNA with a reduced specificity compared to the intact 94-kDa receptor. Various footprinting assays did not reveal any qualitative differences when comparing the DNA contact points made by the two different receptor entities. Like the intact receptor, the 39-kDa receptor fragment binds as a dimer to DNA. Glutaraldehyde cross-linking demonstrated a difference in the protein:protein contacts of the two homodimers. Furthermore, the dimeric 94-kDa receptor did not recognize a half-DNA site, while the dissociated 94-kDa receptor dimer and the dimeric 39-kDa receptor fragment allowed binding to such a site. These results suggest that the loss of the N-terminal domain of the receptor affects the steric arrangement and/or rigidity of the two DNA binding domains of the receptor homodimer, resulting in a decreased DNA binding specificity of the 39-kDa receptor fragment.

Animals↗
PubMed1990

Neonatal exposure to DDT and its fatty acid conjugate: effects on cholinergic and behavioural variables in the adult mouse.

We have recently observed that DDT and a DDT metabolite, DDOH, conjugated to a fatty acid, palmitic acid, DDOH-PA, affects muscarinic cholinergic receptors (MAChR) in the neonatal mouse brain when given to suckling mice during rapid brain growth. This early exposure of the neonatal mouse also affects the behaviour of the animals as adults. When DDT and DDOH-PA was given as a single low oral dose of 1.4 mumol/kg body weight, DDT (0.5 mg), DDOH-PA (0.7 mg) and a 20% fat emulsion vehicle (10 ml) per kg body weight to 10-day-old NMRI mice, behavioural tests at adult age of four months, indicated disruption of a simple, non-associative learning process, i.e. habituation, in both DDT and DDOH-PA treated mice. There was also a significant increase in the potassium evoked release of ACh from slices of cerebral cortex and a tendency towards a decrease in the density of MAChR in mice receiving DDT. These effects in the adult mice could not be correlated to the concentration of DDT in the adult brain since DDT one month after its administration to the 10-day-old mouse no longer is present in the brain.

Animals↗
PubMed1989

The purified activated glucocorticoid receptor is a homodimer.

The structure of purified preparations of activated (DNA-binding) glucocorticoid receptor (GR) was analyzed in the presence or absence of DNA. A 35-base pair DNA fragment harboring a strong GR-binding site from the mouse mammary tumor virus promoter (-189/-166) was used for stoichiometric analysis of the GR.DNA complex. Glycerol gradient centrifugation was utilized in order to separate the 6 S GR.DNA complex from the 4 S GR and the 3 S DNA fragment. Synthetic glucocorticoid [3H]triamcinolone acetonide bound to GR and 32P-5'-end-labeled DNA fragment were used as probes for quantitation of each component. Such experiments demonstrated that two hormone molecules (two 87.5-kDa GR peptides) are associated with each cognate DNA site. Quantitative DNase I footprinting confirmed this result. The formation of the GR.DNA complex was ligand-dependent, but once formed the complex remained stable after ligand dissociation. Incubation of GR with 0.01-0.1% (w/v) glutaraldehyde resulted in a shift in its sedimentation rate from 4 to 6 S. Gel filtration chromatography of glutaraldehyde-treated GR resulted in a complex of slightly larger size than the gamma-globulin standard (158 kDa). Gel filtration of GR without glutaraldehyde treatment gave the identical result. This suggests that a GR multimer, probably a homodimer, is stable during gel filtration chromatography but needs to be stabilized by glutaraldehyde cross-linking or DNA during glycerol gradient centrifugation. We conclude that the activated GR exists as a homodimer when unbound as well as when bound to DNA.

Animals↗
PubMed1989

Reassessment of valve area determinations in mitral stenosis by the pressure half-time method: impact of left ventricular stiffness and peak diastolic pressure difference.

Estimation of the orifice area is of major importance in the timing of valve dilation or surgery in patients with mitral stenosis. Determination of the area has traditionally been accomplished at cardiac catheterization by the Gorlin equation. The valve area can also be estimated noninvasively with Doppler echocardiographic measurements of the pressure half-time, which is inversely proportional to the area. This method has gained widespread acceptance, but its accuracy has recently been questioned and factors other than reduction of orifice area appear to modify the pressure half-time. In the present study, the influence of left ventricular stiffness (defined as diastolic pressure rise per milliliter of mitral flow) and peak atrioventricular pressure difference on the pressure half-time was examined both in a hydraulic model and by review of data from 35 patients with mitral stenosis. Left ventricular stiffness less than 0.13 mm Hg/ml was considered normal. In the model study, the orifice area correlated only moderately with inverted pressure half-time (1/PHT) (r = 0.67). By multiple linear regression, inverted pressure half-time was shown to be dependent on valve area, chamber stiffness and peak pressure difference (R = 0.89), area and stiffness being most important (R = 0.85). In the clinical study, an increased ventricular stiffness was found in 22 of the 35 patients. The pressure half-time method overestimated the Gorlin-derived area by an average of 72% in these patients compared with only 10% in 13 patients with normal stiffness (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Changes in CSF and brain soluble proteins following vigabatrin treatment in rats.

1. Following the discovery of vacuoles in the white matter of the brain of small animals treated with vigabatrin (GVG) it was decided to investigate possible reasons for the occurrence of these vacuoles and to explore the possibility of finding CSF markers which could be applicable for monitoring toxicity in humans. 2. An animal model was developed to study the changes of protein synthesis and to assay soluble brain proteins by isoelectric focusing and two-dimensional electrophoretic techniques. 3. Five groups of rats were treated either with 300 mg kg-1 day-1 GVG, 50 mg kg-1 GVG every other day, 300 mg kg-1 day-1 sodium valproate, 100 mg kg-1 day-1 sodium valproate or sham treated. 4. All animals were given the drug in a liquid full nutrient diet. The dietary intake of the different groups was adjusted to the group which showed the smallest dietary intake, to compensate for possible differences between groups due to nutritional factors. 5. The rats on 300 mg kg-1 day-1 GVG had a 30% reduction of body weight and a 6% reduction of their brain weight, compared with the lower GVG dose group, the two valproate groups and the sham treated group. 6. The synthesis of soluble proteins in the cerebral cortex, hippocampus and cerebellum was decreased in rats given GVG at 300 mg kg-1 day-1 and was increased in rats given valproate at 300 mg kg-1 day-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminocaproates↗
PubMed1989

Complete occlusion of the left main coronary artery: clinical and angiographic observations in five cases.

Involvement of the left main coronary artery is observed in approximately 5 to 8% of patients with coronary artery lesions detected by coronary angiography, but occlusion of the left main artery is a very infrequent finding. Out of approximately 4000 patients undergoing coronary angiography, four men and one woman, 37 to 60 years old, showed total occlusion of this vessel. Four of them had angina pectoris and three had had a myocardial infarction. All five showed deep ST depression in V 2(or 3)-6 during bicycle exercise testing. Apart from the left main artery occlusion, all had significant obstructive lesions in other coronary vessels, including the right coronary artery or its major branches. There was collateral circulation from the right coronary artery in all patients. Left ventricular function was well preserved in three patients and markedly impaired in two. Four patients underwent bypass surgery and they have been followed for 10 to 28 months. Three are free of angina and one has only minimal angina. One patient refused surgery and he continued to have severe angina despite intense medical treatment. He died suddenly after 30 months follow-up. In patients with complete occlusion of the left main coronary artery, development of adequate collateral flow seems important in preserving left ventricular function, but collaterals are usually insufficient to prevent angina. Moreover, associated obstructive lesions in other coronary arteries constitute a potential threat to the collateral circulation. Effective symptomatic relief is obtained by coronary bypass grafting, and revascularization may also improve prognosis in this subset of patients with coronary heart disease.

Adult↗
PubMed1989

Doppler echocardiographic assessment of the valve area in patients with atrioventricular valve stenosis by application of the continuity equation.

The orifice area was non-invasively assessed in 19 patients with mitral or mitral and tricuspid stenosis by combined cross-sectional and Doppler echocardiography. Stroke volume was calculated as the product of aortic or pulmonic cross-sectional area and the time velocity integral of the flow across that valve, and the stenotic valve area was obtained as the stroke volume divided by the time velocity integral of the stenotic valve. In addition, the mitral valve area was estimated by the pressure half-time method of Hatle et al. The non-invasive determinations were compared with those calculated by the Gorlin formula at cardiac catheterization. The valve area obtained by combined cross-sectional and Doppler echocardiography showed a close correlation with the Gorlin area, r = 0.90, SEE = 0.13 cm2, n = 20. In contrast, the valve area estimated by the pressure half-time method showed only a moderate correlation with the Gorlin area, r = 0.68, SEE = 0.38 cm2, n = 18, and estimates by this method tended to significantly overestimate the Gorlin area. In conclusion, non-invasive valve area determinations based on combined cross-sectional and Doppler echocardiography can be used to accurately quantify the severity of the lesion in patients with atrioventricular valve stenosis, while determinations by the pressure half-time method may show errors of a magnitude that limits its clinical applicability.

Aged↗
PubMed1989

Glucocorticoid receptor binding to a specific DNA sequence is required for hormone-dependent repression of pro-opiomelanocortin gene transcription.

Glucocorticoids rapidly and specifically inhibit transcription of the pro-opiomelanocortin (POMC) gene in the anterior pituitary, thus offering a model for studying negative control of transcription in mammals. We have defined an element within the rat POMC gene 5'-flanking region that is required for glucocorticoid inhibition of POMC gene transcription in POMC-expressing pituitary tumor cells (AtT-20). This element contains an in vitro binding site for purified glucocorticoid receptor. Site-directed mutagenesis revealed that binding of the receptor to this site located at position base pair -63 is essential for glucocorticoid repression of transcription. Although related to the well-defined glucocorticoid response element (GRE) found in glucocorticoid-inducible genes, the DNA sequence of the POMC negative glucocorticoid response element (nGRE) differs significantly from the GRE consensus; this sequence divergence may result in different receptor-DNA interactions and may account at least in part for the opposite transcriptional properties of these elements. Hormone-dependent repression of POMC gene transcription may be due to binding of the receptor over a positive regulatory element of the promoter. Thus, repression may result from mutually exclusive binding of two DNA-binding proteins to overlapping DNA sequences.

Animals↗
PubMed1988

Effects of 3,3',4,4'-tetrachlorobiphenyl in the brain of the neonatal mouse.

To study the retention of TCB in the brain of the immature mouse and its effects on the muscarinic cholinergic receptors in the cerebral cortex and hippocampus, [14C]TCB and TCB were administered to 10-day-old mice as a single peroral dose of 1.5 MBq/kg body wt and 0.41 mg or 41 mg/kg body wt, respectively. The mice were killed 24 h or 7 days after treatment. The amount of radioactivity in the whole brain decreased by 78% between 24 h and 7 days after administration. The density of muscarinic receptors was measured using the muscarinic antagonist [3H]QNB. A significant decrease (16%) in specific [3H]QNB binding was observed in the hippocampus 7 days after treatment. Despite the relatively rapid elimination of TCB from the immature mouse brain, a single low dose of TCB given during the period of rapid development of the cholinergic system appeared to affect the muscarinic cholinergic receptors in the immature mice.

Administration, Oral↗
PubMed1988

Non-invasive estimation of pulmonary capillary wedge pressure at rest and during exercise by electrocardiography, phonocardiography and Doppler echocardiography.

Non-invasive estimation of the mean pulmonary capillary wedge pressure was accomplished by simultaneous electrocardiographic, phonocardiographic and continuous wave Doppler echocardiographic recordings. The interval from the onset of the QRS complex to the Doppler determined mitral valve closure (Q-MC) and the interval from the phonocardiographic aortic component of the second heart sound to the Doppler determined mitral valve opening (A2-MO) were measured. The non-invasive registrations were carried out simultaneously with direct measurements of the wedge pressure. In an initial group of 22 patients, a significant correlation was observed between the intervals alone and the wedge pressure, r = 0.60, SEE = +/- 6.9 mmHg, p less than 0.01, for the Q-MC interval and r = -0.70, SEE = 6.2 mmHg, p less than 0.001 for the A2-MO interval. A closer correlation was observed between the ratio Q-MC/A2-MO and the measured wedge pressure, r = 0.93, SEE = +/- 3.1 mmHg, p less than 0.001. The linear regression equation, PCW = 19.5 (Q-MC/A2-MO) + 3.0 (mmHg), was applied prospectively to a second group of 23 patients. Again the relationship between estimated and measured wedge pressure was highly significant, r = 0.90, SEE = +/- 3.1 mmHg, p less than 0.001. Twenty-two patients were also studied during an exercise test, and acceptable non-invasive recordings were obtained in 19 of them. The change in estimated wedge pressure during activity related closely to the change in actual wedge pressure, r = 0.80, SEE = +/- 5.7 mmHg, p less than 0.001. A simplified equation suitable for routine clinical practice, PCW = 24 (Q-MC/A2-MO) (mmHg), yielded almost equally accurate estimates of the wedge pressure over a wide range of pressures. The simplicity and reasonable accuracy of Doppler-assisted estimation of the wedge pressure makes it useful in the evaluation and follow-up of patients with suspected cardiac disorders. The method may assist in evaluating the effects of diagnostic or therapeutic procedures, since it is sufficiently sensitive to detect acute directional changes in wedge pressure.

Adult↗
PubMed1988

Aerobic power during maximal exercise in untrained and well-trained persons with quadriplegia and paraplegia.

The aerobic power during maximal exercise was studied in 58 males with traumatic spinal cord lesions from C4 to L4 (25 well-trained "world-class athletes" and 33 untrained). For comparison we tested five well arm-trained and five arm-untrained able-bodied subjects. During maximal wheelchair exercise the aerobic power (VO2 peak), pulmonary ventilation and blood lactate concentration was higher in subjects with lower levels of spinal cord injury. At each injury level above C6-C7, nearly all trained subjects reached higher VO2 peaks than untrained subjects with the corresponding level of lesion. The mean values for trained paraplegic persons were 2.16 +/- 0.38 l x min-1, corresponding to 33.6 +/- 6.7 ml x kg-1 x min-1. The peak heart rate was lower in the quadriplegic than in the paraplegic group with no or only small difference between trained and untrained subjects at the same level of spinal cord injury. Spinal cord lesions with pareses reduce the total active skeletal muscle mass. This can cause physical inactivity, medical complications and social isolation. As a consequence, cardiovascular disorders as cause of death is higher in this group compared to the general population. Therefore, one aim of rehabilitation is to increase the individual's performance in daily life activities. It has been shown that the normal daily life activities of quadri- and paraplegic individuals with no additional physical training are not intense enough to maintain a satisfactory level of physical fitness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗