[Mechanical ventilation at home: Multidisciplinary care is crucial for optimal treatment].
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Biomedical subjects
Publications and source records attributed to A Nilsson.
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The effect of phosphorylation on the functional activity of eukaryotic elongation factor 2 (eEF-2) was studied using a purified phosphorylated factor. The modified factor was unable to stimulate protein synthesis in an eEF-2-dependent rabbit reticulocyte lysate. The functional alteration was further analyzed by measuring the effects of phosphorylation on the ability of the factor to catalyse the ribosome-dependent hydrolysis of GTP. Kinetic analysis showed that both phosphorylated and unmodified factor was able to hydrolyse GTP with approximately the same maximum rate, indicating that the rate of nucleotide exchange was not impaired by the modification. However, the phosphorylated factor showed a marked reduction in the second-order rate constant, suggesting that the phosphorylation interfered with ribosome.eEF-2 complex formation by reducing the affinity of eEF-2 for the ribosome. This assumption was confirmed by direct measurements of the dissociation constants for the ribosomal complexes containing unmodified and phosphorylated eEF-2.
The NAD-dependent glycerol-3-phosphate dehydrogenase (EC 1.1.1.8) of the salt-tolerant yeast Debaryomyces hansenii was purified by poly(ethylene glycol) precipitation and a combination of chromatographic procedures. The enzyme existed in two forms with different ionic characters and specific activity. On SDS-polyacrylamide gel electrophoresis, both forms yielded one predominant band with an apparent molecular weight of 42,000. The specific activity of the enzyme was dependent on the concentration of the enzyme and on the ionic strength of the dissolving medium. All ions tested stimulated the enzyme activity in the ionic strength range 0-100 mM, with glutamate yielding the highest activity. Above these concentrations, the dehydrogenase showed high tolerance for glutamate in concentrations up to 0.9 M, whereas malate, sulfate and chloride were inhibitory. Enzyme activity showed little sensitivity to the type of cation present and was only slightly affected by 5 M glycerol. The true Km values for the substrates were 6.6 microM for NADH, 130 microM for dihydroxyacetone phosphate, 0.3 mM for NAD and 1.2 mM for glycerol-3-phosphate, and the enzyme showed specificity for these four substrates only. It is proposed that the enzyme functions in cellular osmoregulation by providing glycerol 3-phosphate for the biosynthesis of glycerol, the main compatible solute in D. hansenii, and that the enzyme is well adapted to function in yeast cells exposed to osmotic stress.
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This study was designed to investigate whether growth hormone (GH) influences the expression of its own receptor in chondrocytes. To investigate this possibility GH-receptor mRNA was measured in cultured rat epiphyseal chondrocytes in the absence or presence of GH under various experimental conditions. Chondrocytes were isolated enzymatically from epiphyseal growth plates of the proximal tibia of 20-day-old male rats and cultured in monolayer in Ham's F-12 medium supplemented with 10% calf serum and 1% of a serum substitute. The cells were seeded at various densities (100,000-1,000,000 cells per flask) and cultured for 14 days. Subsequently, the calf serum-containing medium and the cells cultured for various periods of time (0-24 h) before total nucleic acid preparation. GH-receptor mRNA was measured with a solution hybridization technique using [35S]UTP-labeled RNA growth hormone receptor cloned from rat liver cDNA. Human GH (hGH; 50 ng/ml) increased GH-receptor mRNA after 3 h and maximal levels were seen 12 h after GH addition. This effect of hGH was time and dose dependent with a significant effect of hGH at a concentration of 0.5 ng/ml and a maximal effect at 50 ng/ml. The hGH-stimulated increase of GH-receptor mRNA was completely blocked by actinomycin-C1 (1.0-0.1 micrograms/ml), while cycloheximide (10 micrograms/ml) only slightly counteracted the hGH effect. Rat and human GH were equally potent, and ovine prolactin was effective at 500 ng/ml but not 5 and 50 ng/ml. A high dose of insulin-like growth factor-I (IGF-I; 1 microgram/ml) caused a small stimulatory effect and addition of 10% calf serum caused a marked increase in GH-receptor mRNA. The level of GH receptor mRNA after 14 days of culture was inversely proportional to the cell density at the start of culture. These results show that GH specifically regulates mRNA levels for its own receptor in rat epiphyseal chondrocytes by interacting with somatogenic binding sites. These findings also suggest a transcription-dependent regulatory system between the GH-receptor and the GH-receptor gene.
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Mesenteric duct chylomicrons labelled with [3H]arachidonic (20:4) and [14C]linoleic (18:2) acid were injected intravenously into essential fatty acid-deficient (EFAD) and control rats. The rats were killed after 5, 10, 20 and 240 min, and serum and different organs were analysed for radioactivity of different lipid classes. 3H and 14C in the triacylglycerol (TG) and phosphatidylethanolamine (PE) fractions were cleared from blood faster in the EFAD than in the control rats. The incorporation of [14C]18:2 into liver and heart phospholipids was increased compared to control rats at all time intervals, the increase in the incorporation of [3H]20:4 being less pronounced. Furthermore, the total incorporation of [14C]18:2 was increased in the heart of the EFAD group. The increased incorporation into phosphatidylcholine (PC) and particularly into PE was observed already at 5-20 min, whereas a marked increase in the 14C radioactivity of cardiolipin occurred between 20 and 240 min. The 3H and 14C radioactivity per g white adipose tissue was lower in the EFAD group than in the controls. After 5-20 min there were no differences between the groups in the lipid radioactivity of the stomach and the small and the large intestine. In the upper small intestine, the 3H radioactivity in both groups and the 14C radioactivity in the EFAD group increased markedly between 20 and 240 min. The study demonstrates an increased plasma clearance and an efficient hepatic uptake and initial incorporation into PC and PE of chylomicron [14C]18:2 and [3H]20:4 in EFAD rats. In these rats a marked selective transfer of [14C]18:2 to cardiolipin from other tissue lipids occurred with time. In addition, the study demonstrates a preferential transfer of injected [3H]20:4, and in EFAD rats also of [14C]18:2, into lipids of the upper small intestine, possibly by secretion of [3H]20:4 and [14C]18:2 in bile phospholipids.
Fish oil chylomicrons, obtained from mesenteric duct chyle of rats fed [3H]20:5 and [14C]20:4 or [3H]20:5 and [14C]18:2 in a fish oil emulsion, were incubated with human pancreatic lipase-colipase, human carboxyl ester lipase (CEL) and human duodenal contents. With duodenal contents, the triacylglycerols labelled with [3H]20:5 and [14C]20:4 were rapidly converted to free fatty acids (FFA) and monoacylglycerols. Also during incubation with lipase-colipase the [3H]- and [14C]triacylglycerols disappeared completely and at equal rates, but in this case much [3H]20:5 and [14C]20:4 accumulated in diacylglycerols. When CEL was also added, the rate of disappearance of [3H]- and [14C]triacylglycerols increased and the radioactivity of diacylglycerols decreased markedly. During incubation of chylomicrons labelled with [3H]20:5 and [14C]18:2 with lipase-colipase, the rates of hydrolysis of [3H]- and [14C]triacylglycerols were similar, but more [3H]20:5 than [14C]18:2 accumulated in diacylglycerols. The accumulation of [3H]diacylglycerol was reduced by adding CEL. Also when fatty acids were analyzed by gas chromatography, 20:5 was enriched in remaining triacylglycerol and in diacylglycerol after incubation with lipase-colipase alone. The data thus indicate that both lipase-colipase and CEL participate in the hydrolysis of 20:5 and 20:4 ester bonds of dietary triacylglycerol.
All visits to or by the district nurses in Gothenburg, Sweden, were registered during one week (daytime Monday to Friday). Altogether 5,250 visits were registered. 77 per cent of all visits concerned subjects 65 years of age or older and 54 per cent subjects 75 years of age or older. It was more common for a woman to visit or be visited by a district nurse than for a man. Of the visits 70 per cent were made by the nurses (59 per cent to the homes of the patients and 11 per cent to homes for the aged), while 30 per cent of all visits were made by the patients to the district nurse's office. Very few visits concerned foreigners living in Sweden. Visits to or by old people were slightly more time-consuming than those to or by younger patients. When planning resources for visits to or by the district nurses it seems that age is by far the most important factor to take into consideration.
C 1300 neuroblastoma cells were cultured and used to study the effect of sodium dependent taurine transport on the membrane potential. Measuring net accumulation of taurine and the depolarization caused by externally applied taurine, we found both processes become active at an external concentration of taurine of 1 mM or more. Net accumulation had Km of 13 mM and a Vmax of 126 nmol x mg of protein-1 x min-1. The taurine induced depolarization of the neuroblastoma cell was parallelled by a 25 per cent decrease in its membrane impedance. The transport of taurine, the depolarization caused by taurine and the effect of taurine on the membrane impedance, all, had a similar dependence on the external sodium concentration. Our results on the depolarizing cotransport between taurine and sodium at the neuronal membrane, may illustrate an additional mechanism for the control of the electrical activity of neuronal cells.
Lipoprotein lipase (LPL) activities of postheparin plasma, heart, lungs, and adipose tissue, and salt-resistant lipase (hepatic lipase, SRL) activities of postheparin plasma, liver, and adrenals were examined in essential fatty acid deficient (EFAD) rats and in age-matched controls. The LPL activity of heart was higher in the deficient than in the control rats, but did not differ in the other tissues. The SRL activity of postheparin plasma was twofold higher, and that of liver and adrenals approximately 50% higher in the group with EFA deficiency. It is suggested that SRL exhibits an adaptive up-regulation in EFA deficiency. This up-regulation may be linked to a role for the enzyme in the transport of polyenoic fatty acids.
Regional cerebral blood flow (rCBF) measurements and clinical ratings were performed on 17 schizophrenic patients and a subgroup of 10 medication-free patients before and after treatment. While clinically exacerbated patients had normal blood flow, patients in remission showed a redistribution of flow with lower values in frontal areas. Anteroposterior ratios correlated with the degree of behavioral disturbances, suggesting that the level of frontal lobe activity in schizophrenia may be a function of the patient's clinical state at the time of study.
We have measured plasma concentrations of local anaesthetics, and the substance fraction of methaemoglobin (MetHb), in infants less than 3 months of age, after application of a lignocaine-prilocaine cream (EMLA). A total of EMLA 2 g was applied over four different skin areas, totalling 16 cm2, for 4 h before anaesthesia for a minor surgical procedure. Sampling was carried out before and 4, 8 and 12 h after application. Maximum MetHb values (median = 2.24%) were obtained usually at 8 h and were significantly (P less than 0.001) higher than before application (median 1.32%). The plasma concentrations of local anaesthetics were low (maximum values: prilocaine 78 ng ml-1, lignocaine 412 ng ml-1). The activity of erythrocyte MetHb reductase (cytochrome b5 reductase) was analysed. Data from a previously studied group of infants aged 3-12 months were included also. Enzyme activity did not reach adult levels until after the age of 3 months. It showed a good inverse correlation with the maximum MetHb values after application of EMLA. Although the MetHb concentrations in the infants younger than 3 months were small, the enzyme capacity may be overloaded when EMLA is administered at the same time as other MetHb-inducing agents. It is concluded that the use of EMLA should be restricted in this age group.
Human jejunal tissue obtained by peroral biopsy was cultured in control medium and in medium containing 100 mmol l-1 ethanol. Subsequently, the incorporation and metabolism of [3H]-arachidonic and [14C]-linoleic acid were evaluated. Of the two fatty acids a significantly higher amount of [3H]-arachidonic acid was incorporated into phospholipids and more [14C]-linoleic acid was incorporated into triacylglycerols. This preferential distribution of the labelled fatty acids was not affected by ethanol, but when ethanol was present in the tissue culture medium, there was a significant decrease in the incorporation of both fatty acids into tissue phospholipids. The study thus shows that ethanol in moderate concentrations can affect human jejunal absorption and metabolism of polyenoic fatty acids, contributing to a decrease in the amount of eicosanoid precursors available in jejunal tissue.
Midazolam, like other benzodiazepine agonists, reduces the autonomic and hormonal responses to emotional or surgical stress. This can be seen as a reduction in catecholamine levels after benzodiazepine treatment. The endocrine response with a reduction in cortisol values is mediated by a decrease in ACTH. The adrenal glands are immediately responsive to exogenous ACTH administration as well as to spontaneous recovery from the benzodiazepine action. Flumazenil given alone does not affect the response to emotional stress, neither does it cause any cardiovascular changes. Following benzodiazepine treatment, flumazenil given in a titrated fashion reverses the inhibitory effects of the agonists.
Eleven patients with major affective disorder (DSM-III) were investigated after a mean of 6.7 years on lithium prophylaxis and reinvestigated 7 years later, at which time they had discontinued lithium for a mean 2.3 years. Outcome was assessed by the Comprehensive Psychopathological Rating Scale, by relapse frequencies, by need for psychotropic medication and for inpatient treatment. The study period was associated with an increase in the rated score for depression, as previously observed also in lithium discontinuers. Although the relapse frequencies remained largely unchanged, a significantly increased number of inpatient treatment days indicated considerably more severe episodes after the discontinuation of lithium. Long periods without lithium were associated with higher doses of neuroleptic drugs.
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Exposure to elemental mercury (Hg) vapour results in an accumulation of Hg in the pituitary, the thyroid, and the testis. In this study, basal serum concentrations of pituitary hormones (thyrotrophin (TSH), prolactin (PRL), follicle stimulating hormone (FSH), and luteinising hormone (LH] or their response after administration of thyrotrophin and gonadotrophin releasing hormones did not differ between 11 male workers (mean urinary Hg (U Hg) concentration 26 nmol/mmol creatinine) and nine male dentists (U Hg concentration 1.3 nmol/mmol creatinine) exposed to elemental Hg vapour when compared with matched referent groups (U Hg concentration 0.6 and 0.4 nmol/mmol creatinine). Thus there was no evidence of an effect of Hg on the pituitary. Neither was there any association between exposure to Hg and serum concentrations of free thyroid hormones (S FT3, S FT4), testosterone, or cortisol. Increased plasma concentrations of selenium (Se) were associated with increased basal serum concentrations of TSH, decreased concentrations of basal serum cortisol, and decreased release of FSH.