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Biomedical subjects

A Andersson

Publications and source records attributed to A Andersson.

At least 91 records · Page 5Linked to original sources

Blood-group-related carbohydrates are expressed in organotypic cultures of human skin and oral mucosa.

Cellular maturation and migration are usually associated with changes in cell-surface carbohydrates, but the relationship between these changes and cell behaviour is at present largely unknown. To investigate whether an organotypic culture system can be used as an in vitro model to study the function of cell-surface carbohydrates, we established organotypic cultures of skin and buccal mucosa. In these cultures, keratinocytes are grown at the air-liquid interface on a supporting matrix consisting of homologous fibroblasts embedded in a collagen type I gel. We examined the expression of blood-group-related carbohydrate structures, including Lewis x, sialylated Lewis x, Lewis y, Lewis a, and Lewis b, on the surface of epithelial cells in the cultures. We compared the results with the expression of more well-established markers, including cytokeratins, integrins, bullous pemphigoid antigen and laminin, in the same cultures. The organotypic skin and oral mucosa cultures showed a histological differentiation pattern analogous to that of normal skin and buccal mucosa, and a tissue-specific expression of carbohydrate structures and cytokeratins. However, both types of organotypic cultures also expressed markers which are normally seen during wound healing, including Lewis y, cytokeratin 16, and cytokeratin 19. We conclude that the organotypic cultures of oral mucosa and skin are suitable models for future studies of the function of cell-surface carbohydrates, although the expression of wound healing markers has to be taken into consideration.

Adult↗

Glucose metabolism in vitro of cultured and transplanted mouse pancreatic islets microencapsulated by means of a high-voltage electrostatic field.

The aim of this study was to assess the function of mouse pancreatic islets microencapsulated using a high-voltage electrostatic field. Islets were microencapsulated in alginate/poly-L-lysine/alginate (APA) capsules and maintained in tissue culture. Rates of glucose oxidation and insulin release were then assessed. Glucose metabolism was also measured in microencapsulated islets retrieved after transplantation to normal syngeneic mice. The high-voltage electrostatic system made possible the production of uniformly sized microcapsules, which were smaller than those produced by co-axial air-jet systems. Nonencapsulated islets were used as controls. Empty microcapsules or islet-containing microcapsules were transplanted intraperitoneally and retrieved after 2 weeks for assessment of foreign-body reactions and glucose oxidation rates. After 1 day and 2 weeks in tissue culture, both control islets and microencapsulated islets increased their rates of glucose oxidation and insulin release 7- to 10-fold in response to an increase in glucose concentration from 1.7 to 16.7 mmol/l. Both empty and islet-containing microcapsules, retrieved 2 weeks after transplantation, showed high rates of glucose oxidation at both low and high glucose concentrations, suggesting overgrowth with metabolically active fibroblasts. Morphological studies indicated a marked foreign-body reaction on the surface of all transplanted microcapsules. The islets in cultured microcapsules had a normal histological appearance, whereas the islets within transplanted microcapsules showed a range of morphological appearances, from intact islets to cell debris. In conclusion, this study shows that mouse pancreatic islets survive and remain functionally competent for at least 2 weeks in vitro after microencapsulation in APA capsules generated in an electrostatic field. However, a foreign-body reaction with cellular growth on the capsular surface was present after intraperitoneal syngeneic transplantation.

Animals↗

Minimally invasive treatment of infection staghorn stones with shock wave lithotripsy and chemolysis.

We report the results in 118 patients with infection staghorn stones treated with an anaesthesia-free minimally invasive method that combined repeated shock-wave lithotripsy (SWL) sessions (unmodified Dornier HM3 lithotripter) and percutaneous chemolysis with Renacidin. The stone-free rate was 60%. In 27 consecutive patients with infection staghorn stones representative of patients with this stone type in the population, a stone-free rate of 77% was recorded. The latter figure is comparable with results reported for open surgery, percutaneous surgery and sandwich therapy, and superior to that recorded with SWL alone. During the study period, no patient referred to us with an infection staghorn stone was treated with percutaneous, ureteroscopic or open surgery, and all treatments were carried out without regional or general anaesthesia. The described treatment concept had a very low complication rate, but required a fairly long hospital stay, with a mean of 32 days (range: 5-82). The long period necessary for completing the treatment in the most complicated cases might render the procedure less attractive as a standard method, but it is nevertheless an excellent option in high-risk patients and in all those patients in whom other procedures are impossible.

Citrates↗

Galanin modulates 5-hydroxytryptamine functions. Focus on galanin and galanin fragment/5-hydroxytryptamine1A receptor interactions in the brain.

The reciprocal interactions between galanin and 5-HT1A receptors in the rat brain are presented. Galanin and its NH2-terminal fragments antagonize 5-HT1A receptor-mediated transmission at the postjunctional level, whereas galanin receptor activation mimics the inhibitory action of 5-HT1A receptor activation at the soma-dendritic level, leading to reductions of 5-HT metabolism and release. These interactions have been shown in both receptor binding studies and functional studies. In view of the present findings, galanin antagonists may represent a new type of anti-depressant drug, based on the 5-HT hypothesis of depression, by enhancing 5-HT release and postjunctional 5-HT1A-mediated transmission. Moreover, following intracerebroventricular injection galanin was found to be internalized in a population of hippocampal nerve cells mainly representing GABA, somatostatin, and/or NPY-immunoreactive nerve cells. The relevance of these findings is discussed in relation to the concept of volume transmission.

Animals↗

Higher export rate of homocysteine in a human endothelial cell line than in other human cell lines.

Even mild hyperhomocysteinemia is associated with premature vascular disease. Despite the growing evidence that plasma homocysteine is a cardiovascular risk factor, the mechanism behind the vascular injuries is still unknown. Information about the metabolism of homocysteine is, therefore, essential for an understanding of its role in atherogenesis. In the present study we have, therefore, investigated the export mechanism of homocysteine. In HeLa cell lines the release of homocysteine was found to be a continuous process, which was increased in the presence of copper ions. High cell density led to a lowered release of homocysteine, probably due to a more extensive metabolism of the intracellular homocysteine. It was also found that HeLa cells were able to take up extracellularly released homocysteine and use it in the cellular metabolism. The ratio between intracellular homocysteine and the total amount of homocysteine is a measure of the ability of the cell to export the intracellularly produced homocysteine. The ratio also reflects the reuse of extracellular homocysteine. Under basal conditions, endothelial cells exported most of the intracellularly produced homocysteine and exhibited a very low concentration of homocysteine intracellularly, low reusage of exported homocysteine and consequently a low ratio in comparison with HeLa and hepatoma cell lines. After addition of homocysteine, all cell lines exhibited similar ratios. Thus, the intracellular homocysteine concentration in endothelial cells is more influenced by the extracellular concentration of homocysteine than is the intracellular concentration in HeLa and hepatoma cells. It may be speculated that this phenomenon could be associated with an increased sensitivity of endothelial cells to homocysteine and explain the association between hyperhomocysteinemia and vascular disease.

Biological Transport↗

Early IFN-gamma production and innate immunity during Listeria monocytogenes infection in the absence of NK cells.

NK cells are believed to play a mandatory role during the early phases of Listeria monocytogenes infection by producing IFN-gamma, which is required for the activation of macrophage effector functions. Mice deficient in the common cytokine receptor gamma-chain (gamma(c)-/-), which completely lack NK cells, were used to examine whether NK cells were essential for resistance to Listeria infection in vivo. Surprisingly, infected gamma(c)-/- mice showed normal innate immunity and macrophage responses against sublethal Listeria infection 2 days postinfection. At this time point, gamma(c)-/- mice showed increased blood IFN-gamma levels compared with those in noninfected controls, demonstrating an NK-independent source of IFN-gamma, which explains early resistance. Listeria-infected gamma(c)-/- x recombinase-activating gene-2-/- double-deficient mice were unable to produce IFN-gamma and were highly susceptible to L. monocytogenes. Since T cells, but not B cells, are major IFN-gamma producers, and gamma(c)-/- T cells were found to be efficient IFN-gamma producers in vitro, we conclude from these results that T cells functionally replace NK cells for the early IFN-gamma production that is necessary for activating the innate immune system following infection with L. monocytogenes. This novel observation in listeriosis underscores how the adaptive immune response can maintain and influence innate immunity.

Animals↗

Existence of striatal nerve cells coexpressing CCK(B) and D2 receptor mRNAs.

Co-localization of CCK(B) and D2 receptor mRNAs was analysed in adjacent sections of nucleus caudate putamen of the rat by means of in situ hybridization. A distinct subpopulation of D2 mRNA containing striatal nerve cells (in the order of 10%) was shown to co-express CCK(B) and D2 receptor mRNAs. All the CCK(B) receptor mRNA-positive nerve cells were co-localized with D2 receptor mRNA. These results give one morphological substrate to the previously demonstrated CCK(B)/D2 receptor interactions in the striatum.

Animals↗

Alterations of thiol metabolism in human cell lines induced by low amounts of copper, mercury or cadmium ions.

Ions of metals such as mercury, cadmium and copper are known to exhibit a high affinity for thiol groups and may therefore severely disturb many metabolic functions in the cell. The aim of the present study was to identify the most sensitive changes of thiol metabolism induced by the addition of low concentrations of metal ions in order to elucidate the mechanisms of metal-toxicity. The effects on thiol metabolism by copper ions seemed to differ from that of mercury and cadmium ions. Copper ions exhibited mainly two effects that were different from those of mercury and cadmium ions. They lowered the reduced fractions of thiols and increased the release of homocysteine into the medium, whereas mercury and cadmium ions mainly influenced the metabolism of glutathione by increasing its synthesis. Even 0.1 micromol/l of copper ions increased the release of homocysteine in HeLa cell lines. An increased cellular concentration of glutathione and an increased release of glutathione into the medium were observed after addition of mercury and cadmium ions at a concentration of 1 micromol/l, which is just above the toxicity limit in human blood. The different cell lines varied in some respects in their response to the addition of metal ions. Cadmium ions had no effect on thiol metabolism in endothelial cell lines, and copper ions did not significantly increase the release of homocysteine into the medium in hepatoma cell lines. Furthermore, the metabolism of thiols during basal conditions (without the addition of metal ions) differed somewhat in the three cell lines investigated. One example is the low amount of extracellular glutathione in hepatoma cell lines, which probably was due to its rapid degradation to cysteinylglycine by gamma-glutamyl-transpeptidase.

Cadmium↗

Protein binding of homocysteine and other thiols in HeLa cell cultures after addition of homocysteine and copper ions.

Homocysteine can be viewed as the first risk factor for atherosclerosis, believed to exert its effects through a mechanism involving oxidative damage. Oxygen radicals are known to interact with a variety of macromolecules leading to lipid peroxidation, DNA strand breakage and a variety of changes in proteins, including thiol oxidation. The present study deals with the protein-binding of homocysteine, cysteine and glutathione in a human cell line culture exposed to homocysteine and copper ions in order to elucidate the possible role of homocysteine in cell injury and atherogenesis. It is shown that homocysteine has the highest tendency of the thiols investigated to create disulfide bonds with proteins. The interaction with the protein cysteine thiol groups, which are involved in the function of many enzymes, structural proteins and receptors might disturb many metabolic functions in the cell. This finding might therefore be one reason for the cell-damaging effects of homocysteine. Addition of reduced homocysteine to cell cultures decreased the intra- and extracellular proportions of protein-bound thiols except that of intracellular glutathione. In agreement with the pro-oxidative effects of copper ions, the findings in the present study showed an increase of the protein-bound fractions of all thiols after the addition of copper ions. Another finding is that increased (in the presence of 100 mumol/l of copper ions) or decreased (in the presence of 100-2000 mumol/l of homocysteine) proportions of protein-bound fractions of the thiols in these short-term experiments did not seriously affect the cells since the cell growth was unchanged.

Copper↗

The adhesion of Bacillus cereus spores to epithelial cells might be an additional virulence mechanism.

Four out of ten Bacillus cereus strains produced spores able to adhere to monolayers of Caco-2 cells (human epithelial cells). One of these strains has been involved in an outbreak of food poisoning where the symptoms were more severe and persisted for longer than a normal B. cereus food poisoning. The hydrophobicity of the spores is a contributing factor for the adhesion to occur. The spores are able to germinate in an environment similar to that of the small intestine and then the vegetative cells can produce the enterotoxin directly at the target place. A concentrated and active form of the enterotoxin will be taken up by the epithelial cells in the small intestine. Spore adhesion could be an important virulence factor for some B. cereus strains.

Animals↗

A TCR alpha chain transgene induces maturation of CD4- CD8- alpha beta+ T cells from gamma delta T cell precursors.

The proportion of CD4- CD8- double-negative (DN) alpha beta T cells is increased both in the thymus and in peripheral lymphoid organs of TCR alpha chain-transgenic mice. In this report we have characterized this T cell population to elucidate its relationship to alpha beta and gamma delta T cells. We show that the transgenic DN cells are phenotypically similar to gamma delta T cells but distinct from DN NK T cells. The precursors of DN cells have neither rearranged endogenous TCR alpha genes nor been negatively selected by the MIsa antigen, suggesting that they originate from a differentiation stage before the onset of TCR alpha chain rearrangements and CD4/CD8 gene expression. Neither in-frame V delta D delta J delta nor V gamma J gamma rearrangements are over-represented in this population. However, since peripheral gamma delta T cells with functional TCR beta gene rearrangements have been depleted in the transgenics, we propose that the transgenic DN population, at least partially, originates from the precursors of those cells. The present data lend support to the view that maturation signals to gamma delta lineage-committed precursors can be delivered via TCR alpha beta heterodimers.

Animals↗

Histology corresponding to mildly dyskaryotic smears--a study of 190 laser cone biopsied patients.

OBJECTIVES: The aim of the study was to evaluate the histological outcome of laser ring biopsies in patients with one or more smears showing cytological mild dyskaryosis where punch biopsies were not performed. The possibilities of predicting histological findings of CIN 2 and CIN 3 were analyzed. METHODS: The study comprised 190 laser ring biopsied patients with mildly dyskaryotic smears. Eighty-five patients were excluded from the initial 275 because of up- and downgrading of smears. Conization specimens and smears were reviewed by an experienced histopathologist and two experienced cytotechnicians. The histological findings were correlated to smear findings. RESULTS: Histologically, CIN 2 was found in 60 and CIN 3 in 45 patients (31 and 24%, respectively). The incidence of histological CIN 3 was higher in those with two or more mildly dyskaryotic smears and in those dyskaryotic smears lacking koilocytic change. Mildly dyskaryotic smears without endocervical cells indicated higher incidence of histological CIN 3. The fact that 36 of 96 CIN 2 and 3 lesions (38%) involved only 3 mm or less of the mucosa might be one important explanation for the absence of representative cells in the corresponding smears. CONCLUSIONS: Our study has shown that a mildly dyskaryotic smear is a strong indicator of CIN 2-3 histologically, especially in those cases without koilocytic cells and in those with repeatedly abnormal smears. The importance of inadequate sampling is indicated by higher incidence of histological CIN 3 in those with less than optimal smears. These findings are some of the factors to be taken into account when planning treatment strategies for this group of patients.

Adult↗

Training induced changes in the fatty acid composition of skeletal muscle lipids. Functional aspects.

Insulin sensitivity relates to the fatty acid composition of the skeletal muscle phospholipids and the intramuscular triglyceride content. The fatty acid composition of the phospholipids--but not of the triglycerides--in the muscles are influenced by regular physical activity of low-moderate intensity. An increased degree of unsaturation of the cell membranes after training may hypothetically contribute to the improvement of insulin sensitivity. Different ways of reducing the supply of lipids in the muscles may possibly cause similar changes of the fatty acid composition of the cell membranes. Further studies are needed to explore the relationships between changes of the skeletal muscle lipid composition during physical activity, the interaction with dietary fat intake, and changes of insulin sensitivity and development of related metabolic disorders.

Animals↗

Comprehensive 1-year cost analysis of open antireflux surgery in Nordic countries. Nordic GORD Study Group. Gastro-oesophageal reflux disease.

BACKGROUND: Antireflux surgery is a highly effective treatment option in patients with severe gastro-oesophageal reflux disease. However, because of the increasing pressure of cost containment within health care, cost aspects must also be added to the decision-making process. METHODS: The aim of this analysis was to assess the total cost of open antireflux surgery during the first year after operation in 178 patients with chronic reflux, who were recruited into a controlled, prospective clinical trial. The study was carried out in 17 hospitals in the Nordic countries. RESULTS: The cost of the operation represented more than 90 per cent of the direct medical costs which amounted to approximately US $5700. For a patient in the work force the indirect cost, i.e. loss of production, represented 47 per cent of the total cost, which was about US $10800. CONCLUSION: The total cost profile of open antireflux surgery has now been established prospectively and can form a basis for future comparisons.

Adolescent↗

Outcome of open antireflux surgery as assessed in a Nordic multicentre prospective clinical trial. Nordic GORD-Study Group.

OBJECTIVE: To evaluate the outcome of antireflux surgery in various hospitals in Scandinavian countries. DESIGN: Partly randomised controlled study, and partly open study. SETTING: Hospitals throughout Norway, Sweden, Denmark and Finland. SUBJECTS: 310 patients with chronic reflux disease and oesophagitis who were initially entered into a randomised controlled study of omeprazole and antireflux surgery. INTERVENTIONS: Total fundic wrap, partial fundoplication, or omeprazole. MAIN OUTCOME MEASURES: Control of symptoms at one year. RESULTS: 154 patients who had their symptoms of reflux completely controlled with omeprazole were initially randomised to have an open operation but 10 refused, leaving 144 for analysis. 34 patients who had only a partial response were also offered operation; 120/178 (68%) had a total fundic wrap, and 53 (30%) partial fundoplication. 6 patients had postoperative complications that required reoperation and 123 made a completely uneventful recovery. Reflux was controlled in most patients, and only 10 (6%) required further treatment with omeprazole. The outcome in those patients who only responded partially to omeprazole was similar to that in patients who had a complete response. CONCLUSION: The outcome of antireflux surgery throughout Norway, Sweden, Denmark, and Finland is good.

Adolescent↗

Use of multiple competitors for quantification of human immunodeficiency virus type 1 RNA in plasma.

Quantification of human immunodeficiency virus type 1 (HIV-1) RNA in plasma has rapidly become an important tool in basic HIV research and in the clinical care of infected individuals. Here, a quantitative HIV assay based on competitive reverse transcription-PCR with multiple competitors was developed. Four RNA competitors containing identical PCR primer binding sequences as the viral HIV-1 RNA target were constructed. One of the PCR primers was fluorescently labeled, which facilitated discrimination between the viral RNA and competitor amplicons by fragment analysis with conventional automated sequencers. The coamplification of known amounts of the RNA competitors provided the means to establish internal calibration curves for the individual reactions resulting in exclusion of tube-to-tube variations. Calibration curves were created from the peak areas, which were proportional to the starting amount of each competitor. The fluorescence detection format was expanded to provide a dynamic range of more than 5 log units. This quantitative assay allowed for reproducible analysis of samples containing as few as 40 viral copies of HIV-1 RNA per reaction. The within- and between-run coefficients of variation were <24% (range, 10 to 24) and <36% (range, 27 to 36), respectively. The high reproducibility (standard deviation, <0.13 log) of the overall procedure for quantification of HIV-1 RNA in plasma, including sample preparation, amplification, and detection variations, allowed reliable detection of a 0.5-log change in RNA viral load. The assay could be a useful tool for monitoring HIV-1 disease progression and antiviral treatment and can easily be adapted to the quantification of other pathogens.

Binding, Competitive↗

Effects of physical exercise on phospholipid fatty acid composition in skeletal muscle.

The effects of low-intensity exercise on the fatty acid composition in skeletal muscle and in serum were studied in 19 sedentary, middle-aged Swedish men. During a 10-wk period, all subjects were given a standardized diet with an identical fat composition. After 4 wk on this diet, they were randomly allocated to a daily exercise program (55% peak oxygen uptake) or to continue to live a sedentary life for the remaining 6 wk. Aerobic capacity (submaximal bicycle test) and peripheral insulin sensitivity (hyperinsulinemic euglycemic clamp) improved with training, whereas the body weight as well as the body composition (underwater weighing and bioimpedance) were unchanged. The proportions of palmitic acid (16:0) and linoleic acid [18:2(n-6)] and the sum of n-6 fatty acids [18:2(n-6), 20:3(n-6), 20:4(n-6)] were decreased in skeletal muscle phospholipids, whereas the proportion of oleic acid [18:1(n-9)] was increased, by training. The fatty acid profile in skeletal muscle triglycerides remained unchanged. We conclude that regular low-intensity exercise influences the fatty acid composition of the phospholipids in skeletal muscle, which hypothetically may contribute to changes of the skeletal muscle membrane fluidity and influence the peripheral insulin sensitivity.

Adult↗