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Biomedical subjects

A Nilsson

Publications and source records attributed to A Nilsson.

At least 397 records · Page 22Linked to original sources

Retinol and retinyl esters in patients with alcoholic liver disease.

Liver retinoid levels and the retinyl esters were examined in liver biopsy specimens from 70 patients with alcoholic and nonalcoholic liver diseases. There was a wide variation in the liver retinoid levels. The liver retinoid level was statistically significantly lower in 15 patients with alcoholic liver disease and a depressed Normotest (NT) value of less than 65% compared with patients with alcoholic liver disease and a normal NT value of greater than 65% (P less than 0.01). The mean serum retinol level in patients with alcoholic cirrhosis was 0.68 +/- 0.38 mumol/l compared with 1.99 +/- 1.14 mumol/l in patients with alcoholic fatty liver (P less than 0.03). The relative amount of retinyl oleate was increased in the alcoholic fatty liver compared with the nonalcoholic fatty liver (P less than 0.001).

Adult↗

Caesium-137 in Perch in Swedish Lakes after Chernobyl-present situation, relationships and trends.

The Chernobyl accident, and the general acidification of Swedish water systems, form the base for this project. The aims of the work have been to present results on the linkage between the concentration of Cs-137 in fish, lake load of Cs and lake characteristics, to give a preliminary prognosis on the recovery, and to put the results within a wider framework of environmental hazard analysis. A broad set of data on limnology, morphometry and drainage area conditions from 41 lakes were collected during 1986 and 1987. Cs-137 was determined in 1 + perch (Cs-pe, 1-year-old perch), water, material collected by sediment traps and from surficial sediments. The main results are as follows. The average value of Cs-pe for all lakes has dropped from 9800 Bq kg(-1) (wet) to 5040 between the 2 years. Generally, the decrease is between 5 and 90%. We have tested if any factor(s) could be specifically linked to this decrease-no such factors have been found. The concentrations of Cs in sediment traps have, on average, decreased by 80%. Very high correlations exist between Cs-pe and the caesium load as determined from the sediment traps. Between 1 and 10% (mean 3.9%) of the initial fall-out deposition to the drainage area was transported from land to water during June to August 1986. The variation in initial fall-out deposition explains 65-69% of the variability in Cs-pe; the degree of explanation (= coefficient of determination, r2) increases to about 85% if one also takes into account the lake water hardness and totP. A map showing with lakes likely to have 1 + perch with higher mean Cs-concentrations than 1500 Bq kg(-1) wet is presented. Between 4000 and 7000 lakes in Sweden appear to have Cs-pe higher than 1500 Bq kg(-1) wet, figures which emphasize the serious impact of the Chernobyl accident on the environmental conditions in Sweden.

Journal Article↗

Cell-density-dependent release of hepatic lipase from cultured rat hepatocytes.

Cultured rat hepatocytes release the enzyme hepatic lipase. In this study we investigated the effect of cell density on this metabolic function under a variety of experimental conditions. The release of hepatic lipase from cultured rat hepatocytes exhibits a cell-density dependence, the secretion per mg cell protein being increased with increasing cell density. When cell density dependence was taken into consideration no significant effect of insulin on the release of hepatic lipase from cultured hepatocytes was observed, whereas glucagon suppressed the release. Glucose stimulating the release of the enzyme, especially in cultures with high cell density.

Animals↗

Changes in peroxisomes and mitochondria in liver of ethionine exposed rats: a biochemical and morphological investigation.

Administration of ethionine resulted in a dose- and time-dependent enhancement of the activities of peroxisomal beta-oxidation, carnitine palmitoyltransferase and omega-oxidation, especially the 12-hydroxylation of lauric acid. The mitochondrial and, especially, the microsomal palmitoyl-CoA hydrolase activities were increased, whereas the peroxisomal and cytosolic activities were decreased. Ethionine administration decreased the catalase and urate oxidase activities in both a dose- and time-related manner. The liver cells and the volume fraction of cytoplasma decreased 40% in ethionine-exposed animals, whereas the average nuclei volume fraction increased approximately 50%. The volume fraction and the total number of mitochondria increased 1.5-fold after ethionine exposure and an accumulation of lipid in large droplets of the hepatocytes was observed. No proliferation of peroxisomes was observed after treatment; the volume fraction and the number of peroxisomes decreased. However, the size of peroxisomes in livers of ethionine-exposed rats tended to be greater than controls; a 1.5-fold increase in average size was observed. As there was no induction of the protein content of the bifunctional enoyl-CoA hydratase, an enzyme involved in peroxisomal beta-oxidation, it is considered that ethionine selectively stimulates the peroxisomal beta-oxidation due to increased peroxisome surface area rather than evoked a peroxisome proliferation capacity. Increased peroxisomal beta-oxidation was also observed in the kidney of ethionine-exposed rats at a dose of 750 mg/day/kg body weight. At that dose the amount of reduced glutathione (GSH) was significantly increased in kidney. The amount of GSH and the level of peroxisomal beta-oxidation were significantly increased in liver at an ethionine dose of 100 mg/day/kg body weight. These responses in liver were evident within 2 days of ethionine exposure and then leveled off whereas a significant increase in GSH and peroxisomal beta-oxidation in kidney was observed within 12 days. Whether the acute H2O2-generating peroxisomal oxidation of long-chain fatty acids in the liver may also make this organ susceptible to the long-term effects of low-dose ethionine and be an important step in the chain of events which eventually results in tumour development should be considered.

Acid Phosphatase↗

Lipolysis of polyenoic fatty acid esters of human chylomicrons by lipoprotein lipase.

Human chylomicrons, obtained from chylous pleural fluid of a patient with mesothelioma, were incubated with bovine milk lipoprotein lipase. No difference in the release of different C16-C18 fatty acids as unesterified fatty acids, or in their appearance in diacylglycerols, was observed. The rate of lipolysis of arachidonic (20:4), and eicosapentaenoic (20:5) acid ester bonds of chylomicron triacylglycerols was slower, and a larger proportion of these fatty acids accumulated in mono- and diacylglycerols. The hydrolysis pattern for docosahexaenoic acid (22:6) was intermediary between that of the C16-C18 fatty acids and that of 20:4 and 20:5. The data suggest that the presence of a double bond at position 5 in the eicosanoid precursors may be important for the rate of lipolysis. The relative resistance of the 20:4- and 20:5- esters of chylomicrons to lipoprotein lipase may be important for the tissue distribution of these fatty acids.

Arachidonic Acid↗

Factors associated with discontinuation of long-term lithium treatment.

Sixty-four outpatients with major affective disorder according to DSM-III and on continuous lithium treatment for an average duration of 7.8 years were first investigated in 1980 and then followed for 7 years. The predictive value of patients' attitudes to their lithium, the prognostic influence of psychiatric status, side effects, and anamnestic and laboratory data including lithium parameters were studied. At the end of the 7-year follow-up, 61% of the patients were still on lithium maintenance treatment, 25% had discontinued lithium for clinical reasons, and 14% of the patients had died. Side effects of lithium were the major clinical reason for discontinuing treatment, while attitudes towards medication were of minor importance. Approximately one fourth of the patients who discontinued lithium were differentiated from those who continued treatment by showing a high frequency of the neurologic side effects incoordination, paresthesia, and disturbed sensibility in addition to having more severe tremor. In yet another fourth of those who discontinued for clinical reasons, lithium was stopped by the treating psychiatrist as maximal urine osmolality values were considered to be too low. These patients did not show any signs of clinically significant impairment of renal functions. Their psychiatric status was excellent in terms of extremely low CPRS scores. The patients who died during the follow-up period were differentiated from those who continued treatment by a much higher frequency of alcohol and drug abuse prior to the initiation of lithium therapy. The total number of side effects and the number of severe side effects were significantly larger than in continuers on lithium. The most common causes of death were cardiovascular disease and suicide. In no case was the cause of death attributed to lithium therapy.

Adult↗

Psychopathology during long-term lithium treatment of patients with major affective disorders. A prospective study.

Thirty-seven patients with major affective disorders according to DSM-III and on continuous lithium treatment were followed during a 7-year period. Outcome was assessed by use of the Comprehensive Psychopathological Rating Scale and by the need for additional psychotropic medication and for hospital and outpatient care. Anamnestic variables and patient's attitudes to their lithium medication were also included in the analysis of outcome, as were laboratory data, including lithium parameters. An increase in psychopathology was demonstrated in a significant number of patients and was attributed mainly to an increase in the depressive symptoms, with a significant increase in the rated scores for fatiguability, pessimistic thoughts, reduced sleep, and inner tension. Suicidal thoughts were common, but no suicide attempts were made. A significant number of patients complained of failing memory, but no significant progression was demonstrated during the 7-year study period. The increase in the depressive symptoms was closely correlated with the number of hospital admissions for depressive recurrence and with the number of days in hospital. The following factors showed a significant relationship with the increase in depressive symptoms: serum lithium levels, large increase in the elimination half-life of lithium, low level of social functioning, low TSH values, and need of concomitant administration of antidepressants and benzodiazepines.

Adult↗

Growth hormone regulates the level of insulin-like growth factor-I mRNA in rat skeletal muscle.

Levels of mRNA for the insulin-like growth factor-I (IGF-I) in rat heart and skeletal muscle and its dependence on GH were investigated using a solution hybridization assay. Levels of IGF-I mRNA decreased following hypophysectomy, and replacement therapy with human GH (hGH) normalized heart and skeletal muscle levels. The stimulatory effect of hGH was dose-dependent, the lowest effective dose being 100 micrograms. A significant increase of IGF-I mRNA was observed 60 min after s.c. administration of 100 micrograms hGH and the maximum increase was apparent 6-12 h after hGH injection. Administration of 200 micrograms IGF-I or 11 micrograms insulin did not significantly change levels of IGF-I mRNA. The results show that GH regulates the level of IGF-I mRNA in rat heart and skeletal muscle and give further support to the hypothesis that locally produced IGF-I might be a local mediator for the direct stimulatory effect of GH on the growth and development of heart and skeletal muscle.

Animals↗

Demonstration of growth hormone receptors in cultured rat epiphyseal chondrocytes by specific binding of growth hormone and immunohistochemistry.

Growth hormone has been reported to exert direct effects on rat and rabbit epiphyseal chondrocytes in vitro, indicating that GH interacts with specific receptors on these cells. To investigate this possibility, binding of GH to cultured rat epiphyseal chondrocytes was studied under various experimental conditions. Chondrocytes were isolated enzymatically from epiphyseal growth plates of the proximal tibia of 20-day-old male rats and were 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 (25,000-200,000 cells/well) and cultured for 5-16 days. Twenty-four hours before binding experiments, the medium containing calf serum was changed for one containing serum obtained from hypophysectomized rats, in order to avoid binding of GH present in the calf serum. Binding was studied by incubating 125I-labelled human GH (hGH) with the cells in the presence or absence of various concentrations of unlabelled hGH, bovine GH (bGH), rat GH (rGH) and ovine prolactin (oPRL). Specific binding could be demonstrated in cells cultured for 5-16 days. Binding was dependent upon time and temperature, and maximal binding was obtained by incubating the labelled hormone for 4-6 h at 24 degrees C. An increase in binding was noted between 7 and 12 days in culture. In cells cultured for 12 days, addition of unlabelled hGH, bGH or rGH caused a dose-dependent displacement of 125I-labelled hGH, whereas oPRL was ineffective. Scatchard analysis resulted in a linear plot, and the number of binding sites/cell was approximately 5700, with a dissociation constant of 0.46 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Radiostrontium-induced oncogenesis and the role of immunosuppression. I. Influence of 90Sr dose, adult thymectomy and antilymphocyteglobulin treatment on the development of neoplastic and preneoplastic lesions in the skeleton of CBA mice.

Ionizing irradiation by incorporated strontium-90 exerts two major effects: it induces tumours (mainly osteosarcomas and lymphoreticular tumours) and depresses the immune system. The interrelation between these functions, i.e. the significance of decreased immunological responsiveness in the oncogenic process, remains unclear. The influence of the 90Sr dose and the role of immune modulation on the tumour yield, were investigated in young adult CBA mice. The animals were exposed to different single doses of 90Sr and, in addition, some groups were subjected to long-term unspecific immune suppression by adult thymectomy (ATx) and/or prolonged antilymphocyteglobulin (ALG) treatment. The present paper (part I) reports on the effects of the treatments on bone tumour responses as reflected by incidence, multiplicity, latency time, histologic characteristics and growth behaviour. The histogenesis of osteosarcomas, as evidenced morphologically by preneoplastic and early neoplastic growth, is illustrated and discussed. The results demonstrate a positive dose-response relationship for osteosarcomas, in which the relative incidences of the various osteosarcoma subtypes were differentially affected. Thus, well-differentiated tumours were gradually replaced by less differentiated types as the dose decreased. A correlation was also observed between the incidence of osteosarcomas and that of assumed preneoplastic lesions in the same bones and sites. Immune suppression by ATx and/or ALG did not distinctly alter the neoplastic or preneoplastic responses at any dose-level of 90Sr.

Animals↗

Plasma apolipoprotein A-I levels and bile lipid secretion during thoracic duct drainage in the rat.

A large part of the circulating apolipoprotein A-I (apoA-I) is produced by the intestine. Yet the plasma levels of apoA-I are retained or even increased in rats with thoracic duct drainage (Johansson, B. and Nilsson, A, (1981) FEBS Lett. 130, 305-308 and Franzén, J. et al. (1987) Biochim. Biophys. Acta 918, 11-15). In this study we examined the effects of biliary drainage and of combined biliary and lymphatic drainage on the plasma apoA-I levels, and also the effects of lymphatic drainage on the output of biliary lipids in the rat. 63 h of biliary drainage caused a 40% decrease of the serum apoA-I concentration. In contrast the concentration in rats with combined thoracic duct and biliary drainage was 153% of that in control rats. The biliary secretion of bile acids, phosphatidylcholine and cholesterol declined to a lower level in rats with combined thoracic duct and biliary drainage, but increased at the later time intervals to the same levels as in rats with bile fistulas only. Intravenous chyle infusion 3-36 h after commencing the biliary drainage did not prevent the decrease in biliary lipid output. The study thus provided no evidence that the reduced hepatic inflow of apoB-containing lipoproteins during biliary drainage is of importance for the reduced biliary lipid output. The loss of all the chyle lipoproteins leads, however, to an even more pronounced decrease in the biliary lipid secretion. The drainage of all the chyle constituents also leads to an increased apoA-I synthesis that more than compensates for the apoA-I loss in chyle, whereas biliary drainage only lowers the plasma apoA-I levels.

Animals↗

On the mechanism of induction of the enzyme systems for peroxisomal beta-oxidation of fatty acids in rat liver by diets rich in partially hydrogenated fish oil.

In this paper, we describe the early biochemical changes in liver cells that occur in rats fed a semisynthetic diet containing 20% (w/w) partially hydrogenated fish oil. Within hours the level of ornithine decarboxylase (ODC) increased, peaked at about 24 h (11-fold increase) and returned to subnormal levels within 48 h. The diet evoked a similar rapid increase in the cellular level of mRNA for the bifunctional enzyme of peroxisomal beta-oxidation (enoyl-CoA hydratase: beta-hydroxyacyl-CoA dehydrogenase (HD)) (12-fold), followed by increases in the specific content of HD protein (3-fold) and the capacity for beta-oxidation in peroxisomes (5.3-fold). The cellular level of long-chain acyl-CoA increased 2.1-fold. By contrast, no significant changes were observed in the specific activities of ornithine decarboxylase, peroxisomal beta-oxidation activity and microsomal omega-hydroxylation as well as the level of long-chain acyl-CoA in livers of rats fed (1 week) diets containing 20% (w/w) soybean oil with added 3 or 6% (w/w) of either elaidic acid (18:1(11) (trans)), brassidic acid (22:1(13) (trans)) or erucic acid (22:1(13) (cis)). Expression of normal levels of mRNA for the bifunctional enzyme was also found. Morphometric analyses revealed no proliferation of peroxisomes in these fatty acid-supplemented diets, in contrast to that observed with the partially hydrogenated fish oil diet. These results are consistent with the proposal (Flatmark, T., Christiansen, E.N. and Kryvi, H. (1983) Biochim. Biohys. Acta 753, 460-466) that components in dietary oils, different from C22:1 cis and trans fatty acids, are responsible for the pleiotropic responses evoked in target cells. Thus, the pattern of response induced by partially hydrogenated fish oil mimics those induced by xenobiotic compounds collectively termed peroxisome proliferators.

3-Hydroxyacyl CoA Dehydrogenases↗

Rapid stimulation of liver palmitoyl-CoA synthetase, carnitine palmitoyltransferase and glycerophosphate acyltransferase compared to peroxisomal beta-oxidation and palmitoyl-CoA hydrolase in rats fed high-fat diets.

Key enzymes involved in oxidation and esterification of long-chain fatty acids were investigated in male rats fed different types and amounts of oil in their diet. A diet with 20% (w/w) fish oil, partially hydrogenated fish oil (PHFO) and partially hydrogenated soybean oil (PHSO) was shown to stimulate the mitochondrial and microsomal palmitoyl-CoA synthetase activity (EC 6.2.1.3) compared to soybean oil-fed animals after 1 week of feeding. Rapeseed oil had no effect. Partially hydrogenated oils in the diet resulted in significantly higher levels of mitochondrial glycerophosphate acyltransferase compared to unhydrogenated oils in the diet. Rats fed 20% (w/w) rapeseed oil had a decreased activity of this mitochondrial enzyme, whereas the microsomal glycerophosphate acyltransferase activity was stimulated to a comparable extent with 20% (w/w) rapeseed oil, fish oil or PHFO in the diet. Increasing the amount of PHFO (from 5 to 25% (w/w)) in the diet for 3 days led to increased mitochondrial and microsomal palmitoyl-CoA synthetase and microsomal glycerophosphate acyltransferase activities with 5% of this oil in the diet. The mitochondrial glycerophosphate acyltransferase was only marginally affected by increasing the oil dose. Administration of 20% (w/w) PHFO increased rapidly the mitochondrial and microsomal palmitoyl-CoA synthetase, carnitine palmitoyltransferase and microsomal glycerophosphate acyltransferase activities almost to their maximum value within 36 h. In contrast, the glycerophosphate acyltransferase and palmitoyl-CoA hydrolase (EC 3.1.2.2) activities of the mitochondrial fraction and the peroxisomal beta-oxidation reached their maximum activities after administration of the dietary oil for 6.5 days. This sequence of enzyme changes (a) is in accordance with the proposal that an increased cellular level of long-chain acyl-CoA species act as metabolic messages for induction of peroxisomal beta-oxidation and palmitoyl-CoA hydrolase, i.e., these enzymes are regulated by a substrate-induced mechanism, and (b) indicates that, with PHFO, a greater part of the activated fatty acids are directed from triacylglycerol esterification and hydrolysis towards oxidation in the mitochondria. It is also conceivable that the mitochondrial beta-oxidation is proceeding before the enhancement of peroxisomal beta-oxidation.

Acyltransferases↗