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Biomedical subjects

M Karlsson

Publications and source records attributed to M Karlsson.

At least 235 records · Page 13Linked to original sources
PubMed1985

Adipocyte precursor cells in obese and nonobese humans.

Adipose precursors isolated from the stromal-vascular fraction of omental and subcutaneous adipose tissue, from defined hyperplastic obese and nonobese human adults were cultured in order to measure and compare replication rates. After multiplication to confluence these cells were also cultured in an enriched viscous suspension medium to optimize the expression of these cells to adipocytes, allowing an estimation of the number of cells having the ability to express an adipocyte phenotype. No difference in replication rate was seen between obese and nonobese donors or when adipocyte precursors from different depots were compared. When cells were allowed to develop fully in the enriched medium, approximately 6.5% of the original inoculated cell population exhibited an adipocyte morphology. Thus, these results suggest that environmental rather than genetic factors may be responsible for the hyperplasia seen in certain massively obese humans. Furthermore, the results indicate that fat-free cells found within the stromal-vascular fraction of adipose tissue have the ability to develop into adipocytes. However, it is suggested that the relatively low yield in obtaining fully differentiated fat cells under these conditions may be due to the heterogeneity of adipose related cells within the original stromal-vascular fraction from which these cultures were initially derived.

Adipose Tissue↗
PubMed1985

Alterations in intracellular deoxyribonucleotide levels of mutationally altered ribonucleotide reductases in Escherichia coli.

Four recombinant plasmid clones (pPS305, pPS308, pPS317, and pPS319) coding for Escherichia coli ribonucleotide reductase have been characterized in vivo and in vitro. Each clone carried a different missense mutation affecting the B1 subunit. Measurements were made of deoxyribonucleoside triphosphate pools. Cells carrying the wild-type plasmid, pPS2, overproduced ribonucleotide reductase 10 to 20 times. As a consequence of this elevated enzyme level, the deoxyribonucleotide pools were approximately three times higher. All four mutant clones showed disturbed deoxyribonucleotide pools. The in vitro studies involved chromatography on affinity media, measurements of enzyme activity and allosteric regulation with a variety of substrates and effector molecules, and direct photoaffinity labeling in the presence of dTTP. Clones pPS305 and pPS308 were shown to code for catalytically defective enzymes, whereas clones pPS317 and pPS319 were shown to code for allosterically altered enzymes. The characterized missense mutations can thus be localized to areas involved in regulation of the substrate specificity or to the active site of protein B1. The alteration of the deoxyribonucleotide pools found in cells containing the allosterically defective clones pPS317 and pPS319 clearly demonstrated in vivo significance for the allosteric control of protein B1 in E. coli cells.

Affinity Labels↗
PubMed1985

Dietary and species influence on potential of plasma to stimulate differentiation and lipid accumulation in cultured adipocyte precursors.

Sera and plasma from different species and from rats of various dietary statuses were compared with regard to effects on proliferation, glycerophosphate dehydrogenase (GPDH) activity, and lipid-filing of rat adipocyte precursors converting to adipocytes in primary cell culture. All of the tested sera and plasma samples were comparably supportive of cell multiplication, but their effects on elevation of GPDH activity (a key event in adipocyte differentiation) and lipid-filling varied greatly. Plasma supported a much greater increase in GPDH activity than serum, while serum from cats supported a much lower increase than serum from humans, calves, goats, or rats. Dietary status of rats did not affect the potential of plasma to support GPDH activity, but did affect plasma support of lipid-filing. A higher than normal degree of lipid-filling was promoted by plasma from rats fed a high-fat, high-sugar diet, while a lower than normal degree was promoted by plasma from fasted rats. Lipid-filling was also found to vary in response to changes in content of very low density lipoprotein (VLDL) in human plasma. This suggests that the influence of diet on the potential of plasma to promote adipocyte lipid-filling may be mediated by the effect of diet on plasma VLDL. The absence of a diet-dependent effect of plasma either on multiplication of adipocyte precursors or on degree of elevation of GPDH activity leaves unresolved the mechanism by which diet affects adipocyte production in animals.

Adipose Tissue↗
PubMed1984

Crystallization and preliminary crystallographic data of ribonucleotide reductase protein B2 from Escherichia coli.

The B2 subunit of ribonucleotide reductase from Escherichia coli has been crystallized from ammonium sulfate solutions at pH 6.0. Crystals grew as orthorhombic plates with cell dimensions a = 58 A, b = 73 A, and c = 205 A. The asymmetric unit probably contains one B2 dimer of molecular weight 2 X 43,000. The packing of molecules in the crystals is compatible with an elongated shape of the dimer. The crystals diffract to 2.5 A and are suitable for structural work.

Escherichia coli↗
PubMed1982

Transamination and other metabolic pathways of 3,4-dihydroxyphenylpyruvic acid in rats when simultaneously administered with L-dopa.

In the rat, 3,4-dihydroxyphenylpyruvic acid (DHPPA) was shown to be transaminated to L-dopa when administered orally concomitantly with L-[3H]dopa. As much as 40% of the serum L-dopa and brain dopamine was shown to be formed via transamination. Moreover, it was shown that DHPPA also caused a so-called L-dopa-sparing effect, i.e. more administered L-dopa reached the circulation and consequently more dopamine reached its target than after administration of L-dopa alone. This effect might be due to an inhibition of the deamination of L-[3H]dopa, since in this case the equilibrium of the transamination reaction will be forced into the L-dopa-forming direction. After administration of [14C]DHPPA alone and together with L-dopa, no differences in the absorption and distribution of radioactivity were found.

Animals↗
PubMed1980

Role of drugs in traffic accidents.

Serum samples from 201 drivers who presented at emergency departments within six hours after being injured in a road accident and 325 control drivers selected randomly at petrol stations were screened for drugs by combined thin-layer and gas chromatography. Blood alcohol concentrations were also measured, and a questionnaire on the subjects' state of health and use of drugs administered. At interview 30 patients (15%) and 44 controls (13%) said that they had taken drugs in the previous 24 hours. Four patients (2%) and six controls (2%) said that they had taken psychotropic drugs, but serum analysis detected psychotropic drugs in 10 patients (5%) and eight controls (2.5%). Diazepam was found in 16 of the 18 subjects in whom psychotropic drugs were detected. Alcohol was detected in 30 patients (15%) and three controls (1%). Drug use appeared to be somewhat lower in Finland than in other Western countries, and illness to be a more important traffic hazard than drugs in general. Interview was not a reliable method of establishing whether drivers had taken psychotropic drugs. Taking diazepam may increase the risk of being involved in a traffic accident, but alcohol was the most powerful risk factor.

Accidents, Traffic↗
PubMed1980

Liver function in some common rheumatic disorders.

Liver function was studied primarily by determination of serum gamma glutamyl transferase and alkaline phosphatase. In subsamples of patients the investigation was extended by determination of serum amino-transferases, isoenzyme analysis of alkaline phosphatase, 99mtechnetium scintigraphy, and liver biopsy. In 183 in-patients with rheumatoid arthritis, the serum gamma glutamyl transferase level was elevated in 47% and serum alkaline phosphatase (of liver origin) in 24%. A concomitant increase in serum aminotransferases was found in 15% of patients with elevated gamma glutamyl transferase level. A closely similar pattern was found in 45 patients with non-rheumatoid arthritis (ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and undefined arthritis), and in 5 patients with polymyalgia rheumatica. In 23 patients with non-rheumatic inflammation (pneumonia), liver dysfunction was common, though the pattern of serum enzyme changes was different. In rheumatoid arthritis, liver scanning showed irregular or low uptake, but biopsy only indicated reactive hepatitis. Hepatotoxicity could not be traced to any single drug or combination of drugs given. On the contrary, chloroquine appeared to reduce serum gamma glutamyl transferase, and corticosteroids had a similar effect on serum alkaline phosphatase. In patients not treated with corticosteroids, both serum gamma glutamyl transferase and alkaline phosphatase were weakly to moderately correlated with laboratory indices of disease activity (ESR and serum orosomucoid). The frequently occurring isolated increase of serum gamma glutamyl transferase and/or serum alkaline phosphatase in arthritis may be an unspecific reaction to inflammation.

Alanine Transaminase↗
PubMed1980

Differentiation and function of rat adipocyte precursor cells in primary culture.

Precursor cells to adipocytes were purified from the epididymal fat pads of small rats and studied in primary culture. A culture system in which substrate and cofactors were not rate-limiting for complete adipocyte conversion was used by utilizing an agarose feeding-layer. Detachment of cells from the culture dish was prevented by addition of a viscous layer of culture medium, containing methyl cellulose. This system allowed quantitation and definite characterization of formed adipocytes, defined as cells accumulating a lipid droplet >20 micro m in diameter. The cells could be subcultured but then gradually lost their adipocyte conversion ability. Age of the donor depressed the adipocyte conversion which, however, never seemed to stop completely. Prostaglandin E(1) and F(2alpha) had no definite effect in the physiological concentration range while indomethachin possibly had a weak inhibitory effect. Insulin, heparin, and isobutylmethylxanthine increased adipocyte formation. Development of characteristic adipocyte functions with time was examined. Lipoprotein lipase activity was very low in the isolated precursor cells before culture, but developed in culture at confluence and was a thousand-fold higher within a few days. At this peak lipoprotein lipase activity was 50-fold higher than in mature adipocytes from the same donor animal. Triglyceride synthesis from glucose peaked in parallel but never reached the value of mature adipocytes and very little fatty acid was synthesized. Hormone-sensitive glycerol release developed at confluence and reached the level of activity of mature adipocytes. This study and previous work have indicated a role for the cyclase system in the development of adipocytes from precursor cells. Dibutyrylcyclic AMP caused an enhancement of lipoprotein lipase activity and adipocyte conversion. In suspension media, the nucleotide caused inhibition. These results are compatible with an effect of the nucleotide, not directly on lipoprotein lipase and cell determination, but via events taking place at confluence associated with cell to cell interactions. In comparison with previously described cells from an established cell line which undergo adipose conversion (3T3 cells), the cells described in the present work, like adipocytes, showed more metabolic activity in pathways for fatty acid incorporation from exogenous lipid sources (lipoprotein lipase activity) than from de novo synthesis. Furthermore, host-factors could be followed such as in the age- and site-dependence of adipocyte formation. Physiological stimuli such as insulin, lipid substrate, and heparin had effects on adipocyte formation. It was therefore concluded that this cell preparation has a potential of yielding information of physiological significance in studies of the regulation of adipocyte multiplication.-Björntorp, P., M. Karlsson, P. Pettersson, and G. Sypniewska. Differentiation and function of rat adipocyte precursor cells in primary culture.

Adipose Tissue↗
PubMed1980

Effects of refeeding on adipocyte metabolism in the rat.

Glucose metabolism in fat cells from fasted-refed rats and ad-libitum-fed controls were studied in the postabsorptive state. Two types of experiments were performed. First, each rat donated one epididymal fat pad and the metabolic results were expressed in relation to the number and size of fat cells of these tissues. Second, the other epididymal fat pad in the rats in each experimental group was pooled for experiments in duplicate where liberated fat cells were separated in fat-cell size classes, which enabled comparisons of metabolic activities at the same fat-cell size. Glucose incorporation into carbon dioxide and triglyceride glycerol and fatty acids were about equally elevated in absolute terms in the refed rats. In relative terms the increase was much more pronounced in carbon dioxide and fatty acids because these activities were very low in control rats. These results confirm previous results showing elevated metabolism after fasting-refeeding, and also demonstrate that this is an adaptation of fat-cell metabolism rather than a consequence of a higher cellular density of adipose tissue after fasting-refeeding with smaller fat cells. Adaptations of metabolism after fasting-refeeding might be of potential importance for elucidation of the cause of the rapid relapse after weight decrease of obese subjects with diminished fat-cell size.

Adipose Tissue↗
PubMed1979

Quantitation of different cells in the epididymal fat pad of the rat.

To determine the number of adipocytes and cells developing into adipocytes (preadipocytes) in the epididymal fat pad of normal Sprague-Dawley rats, two methods were developed. Liberation of all cells from the tissue was obtained by a combination of lytic enzymes and mechanical treatment with only a limited loss of cell integrity; with large tissue masses, an initial perfusion was necessary. These cells were cultured in medium 199 supplemented with serum, glucose, insulin, a triglyceride emulsion, and methyl cellulose to form a culture medium with high viscosity in which it has been shown that the cells do no multiply. In this medium some of the cells developed into adipocytes and could be recognized and counted. The results show that there are about twice as many preadipocytes as mature adipocytes in the smallest rats examined (about 50 g). With increasing weight and age the mature adipocytes increased while the number of preadipocytes seemed to be constant up to a weight of about 150 g, after which they continuously diminished and could not be found in rats weighing more than 300 g. Here the number of mature fat cells had reached a constant level. These results are consistent with the formation of new preadipocytes up to a rat weight of about 150 g. In normal rats these cells successively fill up with triglyceride and disappear at a body weight of about 300 g when they have been transformed into mature adipocytes. The results are also consistent with the concept that no new adipocytes are formed spontaneously in the adult Sprague-Dawley rat. It was shown, however, that in media without methyl cellulose, isobutylmethylxanthine probably could induce the formation of new adipocytes in the cells isolated from all rats, including the heaviest (oldest). This finding shows that the potential of cells to develop into adipocytes also seems to exist in the adult rat under certain circumstances.

Adipose Tissue↗
PubMed1978

Isolation and characterization of cells from rat adipose tissue developing into adipocytes.

To identify cells developing into adipocytes by accumulation of triglyceride, rat epididymal fat pad cells from small rats were exposed to (3)H-labeled chylomicron fatty acids in vivo and then liberated with collagenase. Tissue remnants were removed by filtration and mature fat cells by flotation. Aggregating cells were then removed by filtration through a 25- micro m nylon screen. Further purification of cells labeled in vivo was obtained by removing floating cells from those adhering to the bottom of a culture dish. The adhering cells multiplied to a confluent monolayer when cultured in Medium 199 containing serum, glucose, insulin, and a triglyceride emulsion. The cells then gradually enlarged due to granulation of the cytoplasm by a lipid-staining material. After about 2 weeks these granules had coalesced forming mature adipocytes of typical signet-ring appearance. Free adipocytes could then be recovered from the cultures by collagenase treatment. After about 2 weeks of culture these cells had the same size (about 30 micro m) as adipocytes recovered in the original collagenase preparation of the rat epididymal fat pad. They contained triglyceride lipase activity and incorporated glucose into triglycerides to the same extent as cells developed in vivo but had higher lipoprotein lipase activity. In vitro, heparin in a low concentration, prostaglandin E(1), isobutylmethylxanthine, and cholera toxin markedly promoted the development of these cells into adipocytes. This could be shown to occur almost completely indicating that this fraction of cells was homogeneous and consisted of cells with the capacity to form adipocytes. The duplication time was about 2 days and did not change with subculturing. Preadipocytes could be obtained by density gradient centrifugation, isolating triglyceride-containing cells either directly from the pad or after 3 days in culture. All of these cells developed into adipocytes as described above but did not multiply as readily. It was concluded that cells from the epididymal fat pad from small rats can be isolated in a homogenous fraction that develops in culture into cells of identical morphology and function as adipocytes formed in vivo. The differentiation of these cells into adipocytes may be manipulated in vitro.

Adipose Tissue↗
PubMed1978

[Ambroxol, studies of biotransformation in man and determination in biological samples (author's transl)].

15 mg trans-4-[2-amino-3,5-dibromo-benzyl)-amino]-cyclohexanol-hydrochloride (ambroxol, NA 872) was administered i.v. and orally to healthy volunteers. The metabolic pattern in urine and plasma was similar for both routes of administration. Biotransformation reactions are straightforward, yielding two major products of phage I reactions identified as 6,8-dibromo-3-(trans-4-hydroxycyclohexyl)-1,2,3,4-tetrahydro-quinazoline and 3,5-dibromo-anthranilic acid. These metabolites as well as the parent compound are also converted to conjugates, predominantly glucuronides. Quantification of unlabelled ambroxol in biological fluids is achieved by radiochemical derivatisation with 14C-labelled formaldehyde in imitation of the biotransformation.

Administration, Oral↗
PubMed1977

Prevalence of drugs among drivers arrested for drinking and driving in Finland.

A combined thin layer and gas chromatography system was developed for qualitative and quantitative analysis of drugs in biological samples after extraction with heptane-isoamyl alcohol. Both acidic and basic extraction procedures were used. Special methods were used for the extraction and detection of salicylates, isoniazid, and morphine. Particular attention was given to the detection of psychostimulants; though these drugs have seldom been found in drinking drivers in Finland they are commonly found in Sweden. Two percent of all suspected drinking drivers were also suspected of concommitant drug use, which led to primary sampling of urine. Of 100 such drivers, 24 had blood alcohol levels (BALs) which were negative and 18 of that 24 had drugs in their sample. Seventy-six of the 100 had positive BALs and 25 of the 76 had drugs in their samples. Of the randomly chosen 100 suspected drinking drivers, 5 had drugs in their samples, and 4 of these 5 had positive BALs. The benzodiazeomes were the most commonly detected drugs. No stimulants were found in our subjects.

Adult↗
PubMed1977

Low-resistance skin points that may coincide with acupuncture loci.

Electrical resistance of skin was studied with the aid of a specially designed meter that compared the resistance per surface area of small skin points with that of the surrounding skin. In a systematic study of the hands, face and ears in five subjects low-resistance skin points were repeatedly found in characteristic loci, comparable in different individuals and symmetric about the body midline. The low-resistance skin points had diametres of 1.5 +/- 0.5 mm and their borders were abrupt. On the dry skin resistance values were around 10 kilo-ohms at the center of the points but around 3 mega-ohms in the surrounding skin. Voltages could also be recorded at these points, but they proved to be result of electrode polarization reflected at these points because of their low electrical resistance. The distribution of the low points in the hands, face and ears resembled that of classical acupuncture points.

Action Potentials↗