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Biomedical subjects

K Magnusson

Publications and source records attributed to K Magnusson.

At least 37 records · Page 2Linked to original sources

Evidence for regulatory mechanisms maintaining testosterone-dependent AVP concentrations in terminal regions.

The dose and time relationships of testosterone treatment on arginine-vasopressin (AVP) concentrations of steroid-dependent vasopressinergic extrahypothalamic neurons were studied in the castrated male rat. The rate of AVP increase and the extent and limits of accumulation of AVP in the terminal regions were explored. Testosterone propionate (TP) treatment (0.25, 0.50, and 1.00 mg/kg SC given three times a week) started 15 weeks after castration. The periods of treatment lasted for 20, 40, and 80 days. AVP concentrations in the lateral septum (LS) and the lateral habenula (LH), determined by radioimmunoassay, increased dose and time dependently. A significant effect was achieved by 0.25 mg/kg and a maximum level obtained by 0.50 mg/kg after a 40-day period of treatment. The maximum concentration reached corresponded to the level of the intact animal. Increasing the dose or period of treatment did not raise the AVP concentration above that particular level. The data suggest regulatory mechanisms that maintain the AVP concentration in the terminal regions at a precastrational level.

Animals↗

Strain, age and sex differences in the release of vasopressin from the pituitary: a study in the spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rat.

The basal and depolarization-induced arginine-vasopressin (AVP) release from intact pituitaries of SHR and WKY rats was studied in vitro in a perfusion chamber. Differences associated to strain, sex and two age periods (pre-adult: 25-30 days of age; adult: 60-70 days of age) were assessed. The results show an enhanced AVP release in the adult male as well as female SHR compared to the WKY rat. The stimulated AVP release was also significantly higher in the preadult male SHR and indicated in preadult females SHR. No differences associated to strain in basal AVP release were detected at the age interval 25-30 days. The response to muscimol was increased in preadult female and male SHR rats compared to the WKY animals. It is concluded that the augmented depolarization-induced AVP release and sensitivity to muscimol in the SHR is not related to sex, and no apparent change in this pattern was associated to the transition between the juvenile and adult condition.

Age Factors↗

Rosin components identified in diapers.

As part of the investigation of sources of exposure to rosin allergens, disposable diapers (napkins) common on the Swedish market were analyzed, using gas chromatography, to detect the main rosin compounds. Rosin components were detected in all diapers, the highest amounts in those from the 2 major producers. In these diapers, more rosin was found in the top layer, which is in close contact with the skin than in the fluff. Despite the possibly minimal risk of induction of sensitization to rosin allergens in diapers, there is a real risk of elicitation of dermatitis in sensitive individuals, especially since penetration is enhanced by occlusion and irritation. Such material is not only used for infant diapers, but also for adult incontinence products and feminine hygiene products.

Abietanes↗

Percutaneous absorption of organic solvents during intermittent exposure in guinea pigs.

Skin absorption under intermittent exposure of guinea pigs to n-butanol, toluene, 1,1,1-trichloroethane was studied. Groups of guinea pigs were exposed to test organic solvents for 1 min at 30-min intervals during 4 h, in all 8 exposures. Skin absorption of solvent was assessed by following the concentration of solvent in the blood. This intermittent exposure was compared to continuous exposure over 4 h. Absorption of toluene and 1,1,1-trichloroethane was low, but a considerable amount of butanol was absorbed through the skin on intermittent exposure. A typical serrated absorption profile was seen for butanol that was less pronounced for toluene and 1,1,1-trichloroethane. The absorption of butanol was highest at the end of the exposure period. The differences in absorption profiles may be due to the differences in vapour pressure in the solvents in association with the animal method used. The amount absorbed varied inversely with vapour pressure. Hair stubble may act as a trap for solvents with low vapour pressure. Adequate ventilation reduces unoccluded skin absorption of volatile organic solvents.

1-Butanol↗

Influence of an anti-oxidant on the formation of allergenic compounds during auto-oxidation of d-limonene.

Butylated hydroxytoluene (BHT), a common anti-oxidant, was added to different samples of d-limonene. The decrease in concentration of d-limonene and the formation of oxidation products were compared between the samples and with samples without anti-oxidant using gas chromatography. The aim of the study was to investigate how long d-limonene to which BHT was added could be handled when air-exposed at room temperature, without formation of oxidation products which according to previous studies increase the risk of skin sensitization. In experiments trying to mimic the handling of limonene products at workplaces the addition of BHT prevented auto-oxidation for periods depending on the purity of the products and on the room temperature. Cold and dark storage of d-limonene in closed vessels prevented auto-oxidation for 1 year without addition of anti-oxidant.

Air Pollutants↗

Biodegradation of 4-nonylphenol in seawater and sediment.

Biodegradation of 14C-labelled nonylphenol at the concentration 11 microg litre (-1) in seawater has been estimated by collection and quantification of the formed labelled carbon dioxide. Initially degradation was very slow but when the microorganisms had become adapted, after four weeks at 11 degrees C, the degradation rate increased rapidly and after 58 days about 50% of 14C from NP was found in the CO2 fraction. In the presence of sediment the initial degradation rate was high and did not increase after longer incubation. Lack of oxygen reduced the degradation rate by half in the presence of sediment.

Journal Article↗

Validation of automated sleep stage and apnoea analysis in suspected obstructive sleep apnoea.

Full-night polysomnography is necessary for the diagnosis of obstructive sleep apnoea (OSA). However, analysis of the sleep stages and apnoeas is time-consuming. Computer systems for automated analysis have, thus, been developed to alleviate this task. We investigated 27 consecutive patients referred to our sleep laboratory with suspected OSA. The analysis of sleep stages and apnoeas was performed by visual scoring, according to Rechtschaffen and Kales, and by commercially available automated analysis device. The mean difference between visual scoring and automated analysis was -1, 111, -140, -3, 1 and 27 min, for sleep stages awake, I, II, III, IV and rapid eye movement (REM) respectively. For the apnoea index, the automated analysis rated a lower figure (mean difference 7.h-1, 95% confidence interval 2-12.h-1). The diagnosis of OSA was performed with a sensitivity of 85% and a specificity of 93% by automated analysis. Comparison of two independent handscores showed good agreement, with a mean difference of 6, 4, 3, -7, 1 and -1 min, for sleep stages awake, I, II, III, IV and REM, respectively. In conclusion, the automated analysis underestimates stage I sleep and the apnoea index. Visual scoring is advisable for control of the results. Automated analysis should only be used by those who are able to perform a visual analysis.

Aged↗

Rosin allergy: identification of a dehydroabietic acid peroxide with allergenic properties.

A peroxide of dehydroabietic acid was isolated from rosin using flash chromatography and preparative HPLC. It was identified by 1H-NMR and MS. In animal experiments, this peroxide cross-reacted with a previously identified allergen in rosin, 15-hydroperoxyabietic acid (15-HPA), despite differences in molecular weight and unsaturation. Both substances are able to react via a radical mechanism generating structurally similar molecules. In patch testing of patients, no reactions were observed to the peroxide. Low skin penetration of the peroxide could be the explanation for this. The peroxide seems of little clinical importance. The observed cross-reactivity is an indication of antigen generation via a radical mechanism. Only a few compounds that react with radical mechanisms to form antigens are described in the literature.

Abietanes↗

Air oxidation of d-limonene (the citrus solvent) creates potent allergens.

Products containing as much as 95% of d-limonene are used for, e.g., degreasing metal before industrial painting and for cleaning assemblies. Experimental studies on the sensitizing potential of limonene show diverging results. In a previous study, we found that the sensitizing potential of d-limonene increased with prolonged air exposure. The aim of this study was to make further chemical analyses, to identify compounds formed by air exposure of d-limonene and to study their allergenic potential. d-limonene was found to be a sensitizer after prolonged exposure to air according to 2 Freund's complete adjuvant test (FCAT) experiments and 1 guinea pig maximization test (GPMT) study. No significant response was obtained to d-limonene not air exposed, even if the animals were sensitized to oxidized d-limonene. 5 main oxidation products of d-limonene were identified. (R)-(-)-carvone and a mixture of cis and trans isomers of (+)-limonene oxide were found to be potent sensitizers, while no significant reactions were obtained in the animals induced with a mixture of cis and trans isomers of (-)-carveol. It can be concluded that air oxidation of d-limonene is essential for its sensitizing potential, and that potent allergens are created.

Air Pollutants↗

Protein synthesis in skeletal muscle during starvation and refeeding: comparison of data from intact muscle and muscle biopsy material.

The intact extensor digitorum longus (EDL) preparation in rat is a well-documented model for assessing protein synthesis in skeletal muscle. Human muscle biopsy material has also been used, but the extent to which biopsy material is representative for evaluation of muscle protein synthesis has not been established. Therefore, the aim of this study was to compare protein synthesis in intact muscle and in muscle biopsy material simultaneously in rats. The animals (70 g) were divided into three groups: fed (n = 22), starved for 36 hours (n = 22), and refed for 24 hours (n = 19). Protein synthesis and RNA content were measured in each group. Protein synthesis was determined as the incorporation of 14-C-phenylalanine into muscle protein in the intact EDL muscle from one leg and in a muscle biopsy from the contralateral EDL muscle. The incorporation of 14-C-phenylalanine was linear over time in both preparations, but was consistently lower in the muscle biopsy compared with the intact muscle. The relative change in incorporation, in % of that obtained in the fed state, showed a decrease in incorporation after 36 hours of starvation, in both intact muscle and in muscle biopsy material, 33% +/- 10% and 42% +/- 6%, respectively. After 24 hours of refeeding, an overshoot in protein synthesis was seen, to 136% +/- 6% in the intact muscle and to 133% +/- 6% in the muscle biopsy, as compared with the fed state. The RNA content decreased during the starvation period from 21.6 +/- 0.7 to 14.5 +/- 0.4 mg RNA/g protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Extracellular levels of quinolinic acid are moderately increased in rat neostriatum following severe insulin-induced hypoglycaemia.

Extracellular concentrations of the brain metabolite quinolinic acid, an endogenous excitotoxin, were monitored by microdialysis in rat neostriatum and hippocampus/cortex during and following a 30-min period of insulin-induced hypoglycaemia. During hypoglycaemia-induced isoelectricity, extracellular levels of quinolinic acid in the striatum (basal value, 1.1 +/- 0.3 pmol per 30-microliters fraction) were elevated 1.7 times as compared to the control period. Thirty to ninety minutes following hypoglycaemia a significant increase in extracellular quinolinic acid to 2.2 times basal level was noted. After 2 h recovery, the beginning of neuronal necrosis was observed in the dorsolateral striatum. Implantation of the dialysis probe did not influence the extent of neuronal damage. No changes in extracellular quinolinic acid levels were observed in the hippocampus/cortex. The data indicate that following a severe hypoglycaemic insult vulnerable striatal cells are exposed to hyperphysiological extracellular quinolinic acid concentrations over an extended period of time. Considering the pronounced susceptibility of rat striatal neurons to the toxin, the small but prolonged elevation in the extracellular levels of quinolinic acid could be of significance for the development of delayed neuronal death in hypoglycaemia.

Animals↗

Impairment of protein ubiquitination may cause delayed neuronal death.

The hippocampus is a brain structure specifically vulnerable to short periods of transient cerebral ischemia, and which displays delayed neuronal necrosis. Protein ubiquitination is a posttranslational modification of proteins and an important factor in heat shock response and a regulator of ATP-dependent protein degradation. Using affinity purified antibodies against ubiquitin and ubiquitin-protein conjugates we have found that the ubiquitin immunoreactivity (UIR), normally present in all neurons of the hippocampus, disappears in the early recirculation period following cerebral ischemia from all hippocampal cells except the interneurons. Later UIR reappears in the different hippocampal regions over a 72 h period in the following order: granule cells-CA3 pyramidal cells-CA2 pyramidal cells. This is the inverse order of sensitivity of these cells to ischemia. The UIR never recovers in the CA1 pyramidal neurons where a 95% neuronal necrosis is seen following three days of recovery. We propose that the loss of UIR in the pyramidal neurons in the CA1 region signifies a persistent impairment of protein ubiquitination, and thus a change in the turnover of structural and regulatory proteins, which could be an essential part of the mechanism of slow neuronal death following cerebral ischemia.

Animals↗

Lethal and sublethal toxicity of 4-nonylphenol to the common mussel (Mytilus edulis L.).

The toxicity of nonylphenol to the common mussel (Mytilus edulis L.) has been determined in both semistatic and continuous flow test systems. The LC50 values obtained were for 96 h, 30 mg litre(-1); 360 h, 0.5 mg litre(-1); and 850 h, 0.14 mg litre(-1). Sublethal effects, manifested as decreased byssus strength and change of scope for growth, were obtained at a concentration as low as 0.056 mg litre(-1). Fertilization and early developmental success were not affected at the highest concentration tested (0.2 mg litre(-1)).

Journal Article↗

Genetic and biochemical characterization of Bacillus subtilis mutants defective in expression and function of cytochrome b-558.

Bacillus subtilis succinate dehydrogenase is bound to the cytoplasmic membrane by cytochrome b-558, a 23-kDa transmembrane protein which also functions as electron acceptor to the dehydrogenase. The structural gene for the apocytochrome, sdhC, has previously been cloned and sequenced. In this work the structure and translation of cytochrome b-558 was studied in different sdhC mutants. Mutant cytochrome was analyzed both in B. subtilis and after amplification in Escherichia coli. It is concluded that amino acid substitutions in the C-terminal half of the cytochrome can prevent the binding of succinate dehydrogenase without affecting membrane binding of the cytochrome protein or heme ligation. Mutagenesis of His-113 excludes this residue as an axial heme ligand. A base-pair exchange of G to A in the ribosome-binding sequence of sdhC was found to reduce cytochrome b-558 translation about tenfold in B. subtilis, whereas the mutation had no effect on translation in E. coli. Translation of the two succinate dehydrogenase genes from the sdhCAB polycistronic transcript does not seem to be coupled to translation of sdhC. Less than 10% of the wild-type amount of membrane-bound succinate dehydrogenase in B. subtilis still allows growth on non-fermentable substrate, but makes the dehydrogenase a limiting enzyme in the tricarboxylic acid cycle and leads to succinate accumulation.

Bacillus subtilis↗

Protein synthesis in skeletal muscle of rats following starvation and refeeding.

Determination of protein synthesis in individual tissues is important to understand the changes in protein metabolism during catabolic states. Three methods based on different underlying assumptions were compared in assessing muscle protein synthesis during nutritional manipulation. Rats were nonstarved, starved for 1 or 3 days, or refed for 2 days after 3 days of starvation. The extensor digitorum longus (EDL) muscles from the two hindlegs were used for analysis. In one EDL muscle the concentration and size distribution of ribosomes as well as the incorporation of [14C]leucine into protein in a cell-free system were determined. The other EDL muscle was incubated as such and the incorporation of [14C]phenylalanine into protein was measured. The total ribosome concentration per milligram of DNA decreased to 65% on the third day of starvation and remained low after refeeding. The amount of polyribosomes in the percentage of total ribosomes fell to 90% on the first day of starvation, regained the initial level on the third day, and reached 110% upon refeeding. During refeeding amino acid incorporation into protein in a cell-free system decreased to 40% and that in intact muscle to 64% of the prestarvation level. Upon refeeding, the activity increased to or above the original values. The use of several different techniques in parallel to assess protein synthesis in skeletal muscle is recommended since it gives information about the factors involved in regulation of the translational process in intact mammalian tissues.

Animals↗

Identification of the promoter of the Bacillus subtilis sdh operon.

The Bacillus subtilis sdhCAB operon contains the structural genes for the three subunits of the membrane bound succinate dehydrogenase complex. An sdh-specific transcript of about 3,450 nucleotides was detected in vegetative bacteria. S1 nuclease mapping experiments showed that the sdh operon is transcribed from a sigma-43 promoter; the transcript starts at a guanosine residue 90 base pairs upstream from the first gene of the operon, sdhC. No sdh transcript was found in B. subtilis carrying the sdh-115 mutation, which decreases expression of the sdh operon by more than 99%. The sdh-115 mutation is a G-to-A transition in the -35 region of the sigma-43 promoter. The sdh operon is sensitive to glucose repression. When the sdh promoter region was used to drive transcription of the cat-86 gene this gene also became glucose repressed.

Bacillus subtilis↗

Bacillus subtilis mutant succinate dehydrogenase lacking covalently bound flavin: identification of the primary defect and studies on the iron-sulfur clusters in mutated and wild-type enzyme.

Succinate dehydrogenase consists of two protein subunits and contains one FAD and three iron-sulfur clusters. The flavin is covalently bound to a histidine in the larger, Fp, subunit. The reduction oxidation midpoint potentials of the clusters designated S-1, S-2, and S-3 in Bacillus subtilis wild-type membrane-bound enzyme were determined as +80, -240, and -25 mV, respectively. Magnetic spin interactions between clusters S-1 and S-2 and between S-1 and S-3 were detected by using EPR spectroscopy. The point mutations of four B. subtilis mutants with defective Fp subunits were mapped. The gene of the mutant specifically lacking covalently bound flavin in the enzyme was cloned. The mutation was determined from the DNA sequence as a glycine to aspartate substitution at a conserved site seven residues downstream from the histidine that binds the flavin in wild-type enzyme. The redox midpoint potential of the iron-sulfur clusters and the magnetic spin interactions in mutated succinate dehydrogenases were indistinguishable from the those of the wild type. This shows that flavin has no role in the measured magnetic spin interactions or in the structure and stability of the iron-sulfur clusters. It is concluded from sequence and mutant studies that conserved amino acid residues around the histidyl-FAD are important for FAD binding; however, amino acids located more than 100 residues downstream from the histidyl in the Fp subunit can also effect flavinylation.

Bacillus subtilis↗