Search PubMed⌕ Search

Biomedical subjects

K Andersson

Publications and source records attributed to K Andersson.

At least 73 records · Page 4Linked to original sources
PubMed1999

Fumonisin B1-induced DNA damage in rat liver and spleen: effects of pretreatment with coenzyme Q10, L-carnitine, alpha-tocopherol and selenium.

Active oxygen radical species are reported to cause organ damage. This study was designed to determine whether oxidative stress contributed to the initiation or progression of hepatic and splenic cell DNA damage induced by fumonisin B1 (FB1) in rats. Another aim was to investigate the protective effects of the antioxidants coenzyme Q10 (CoQ10), L-carnitine, vitamin E (alpha-tocopherol) and selenium against DNA damage in the liver and spleen of rats treated with FB1. Fasted rats were injected intravenously with a single dose of fumonisin B1 at 1.55 mg kg-1 body wt. into the tail vein. Treatment with FB1 led to splenic and hepatic DNA fragmentation in 85% of the test animals. DNA fragmentation was investigated as a critical event in toxic cell death by testing total Ca2+ in liver. FB1 administration caused total Ca2+ in liver to increase within 4 h (204% of control). Measurement of liver enzyme activities showed an increase in aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT). FB1 also markedly decreased splenic and hepatic glutathione (GSH) levels. Pretreatment with CoQ10 (30 mg CoQ10 kg-1 diet) together with L-carnitine (2.8 mg carnitine kg-1 diet), alpha-tocopherol (30 IU vitamin E kg-1 diet) and selenium (1 mg selenium as sodium selenite kg-1 diet), decreased DNA damage and the activities of Ca2+, ASAT and ALAT in the liver. On the other hand, the level of GSH was slightly increased. The CoQ10 alone did not significantly protect against toxic cell death and glutathione depletion caused by FB1. Oxidative damage caused by FB1 may be one of the underlining mechanisms of FB1-induced cell injury and DNA damage.

Animals↗
PubMed1999

Hypoxia induces differential changes of dopamine metabolism in mature and immature mesencephalic and diencephalic cell cultures.

Perinatal hypoxia is known as a high risk factor for the development of long-lasting abnormalities in dopaminergic system. The early developmental alterations of dopamine (DA) metabolism induced by hypoxia could contribute to these abnormalities. To understand the hypoxia-induced changes of intra- and extracellular dopamine levels and its main metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in immature dopaminergic neurons, we compared these changes in rat mesencephalic and diencephalic cell cultures on day in vitro (DIV) 2 (immature cells), DIV 8 and DIV 13 (mature cells). Cell cultures were exposed to an oxygen-free gas mixture in a Billups chamber for 2-4 hours. Mature cell cultures responded to hypoxia with an increase of DA levels in the cells and in the medium during the first 45 min (by an average of 57 and 114% respectively). Thereafter, DA levels decreased, and returned to the baseline within the next 30 min. The cellular DA levels continued to decrease up to 15% of the baseline during 255 min hypoxia whereas the extracellular DA content stabilized at the prehypoxic levels. Immature cell cultures (DIV 2) in contrast to mature ones, were unable to maintain normal extracellular DA levels during hypoxia and showed a decrease of the cellular and extracellular levels to 50% of the prehypoxic levels. DOPAC and HVA changes mimick, however, at a lower level, the pattern of DA changes during the exposure to hypoxia. In principle, in the diencephalic cell culture similar effects of hypoxia exposure on the investigated parameters were found (studied during 0-120 min). The present study demonstrates that mature and immature dopaminergic cells differ in the regulation of the extra- and intracellular DA levels during hypoxia. In immature cells the low synthetic capacity of tyrosine hydroxylase and the deficient capacities of the transport and storage processes result in decreased extracellular DA levels. This could be an important factor for the long-term modulation of the expression of tyrosine hydroxylase and subsequent long-term behavioral and/or neurological abnormalities induced by perinatal hypoxia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1999

Hypoxia during early developmental period induces long-term changes in the dopamine content and release in a mesencephalic cell culture.

The present study was conducted to elucidate the long-term effects of exposure to hypoxia of dopaminergic neurons during the early developmental period. Primary mesencephalic cell cultures prepared from fetal rats and containing 0.5-2% of dopaminergic neurons were exposed to hypoxia between in vitro days 1 and 6, the putative critical developmental period. Changes in the content, release and uptake of dopamine were found to depend on the degree of hypoxia and on the duration of exposure. Following moderate hypoxia (7 h, 5% O2) on two consecutive days between in vitro days 1 and 3, the cultures showed a small increase in the dopamine levels, by 16%. After severe hypoxia (0% O2/95% N2 for 24 h), during the same time window, the cellular dopamine content was elevated by 100%. Moreover, severe hypoxia produced long-lasting modulations of the dopaminergic system. On in vitro day 14, cells exhibited increased levels of 3,4-dihydroxyphenylacetic acid and homovanillic acid (by 34% and 55%, respectively), and elevations of both the spontaneous and potassium-stimulated dopamine release by 70%. The dopamine transport and metabolism of cells exposed to hypoxia between in vitro days 4 and 6 remained unchanged with regard to long-term effects. The present study provides strong evidence for the induction of long-term changes in dopaminergic cells due to hypoxia during the critical developmental period in mesencephalic culture. The developmental period capable of inducing long-lasting changes in dopamine metabolism is restricted to in vitro days 1-3.

Animals↗
PubMed1999

Dexamethasone differentially regulates cytokine transcription and translation in macrophages responding to bacteria or okadaic acid.

Many microorganisms and microbial products induce expression of pro-inflammatory cytokines such as interleukin-1 (IL-1alpha/beta) and tumour necrosis factor-alpha (TNF-alpha) in macrophages, primarily by transcriptional activation. We show here, by using mouse macrophages in primary culture, that pre-treatment with dexamethasone inhibits bacteria-induced IL-1beta expression as mRNA and cellular pro-IL-1beta in parallel, consistent with an effect primarily on transcriptional activation. In contrast, the expression of TNF-alpha mRNA was only partly inhibited despite virtually complete inhibition of TNF-alpha protein formation. Furthermore, the selective induction of primarily cell-associated 26,000 M, pro-TNF-alpha by the protein phosphatase inhibitor okadaic acid also was partly inhibited at the mRNA level by dexamethasone, whereas additional translational inhibition appeared to be lacking. This latter finding is reminiscent of earlier findings regarding signalling to activation of cytosolic phospholipase A2, which is sensitive to dexamethasone when elicited by bacteria, but not when elicited by okadaic acid. The present results raise the possibility that the inhibitory effect of dexamethasone on TNF-alpha translation, but not on transcriptional activation, is mediated by one or more okadaic acid-sensitive protein phosphatases.

Animals↗
PubMed1999

A nitric oxide-mediated mechanism regulates lipolysis in human adipose tissue in vivo.

1. Possible nitric oxide (NO)-mediated effects on lipolysis were investigated in vivo in human subcutaneous adipose tissue using microdialysis, as well as in vitro on isolated fat cells of non-obese, healthy volunteers. NO donors were added to the ingoing dialysate solvents. 2. Changes in lipolysis and local blood flow were investigated by measuring glycerol levels and ethanol ratios, respectively, in the microdialysates. 3. It was shown that the NO synthase inhibitor, N(G)-monomethyl L-arginine (L-NMMA), but not the biologically inactive enantiomer N(G)-monomethyl D-arginine (D-NMMA), increased glycerol levels in the microdialysates without causing a change of local blood flow. In addition, L-NMMA increased glycerol levels in the microdialysate when local blood flow was stimulated with hydralazine. 4. Nitric oxide gas as well as the NO donor, nitroglycerine, reduced glycerol release from isolated adipocytes in vitro. 5. Expression of inducible nitric oxide synthase (iNOS) in human adipose tissue was shown by Western blot analysis. Biologically active NOS was demonstrated by measuring total enzymatic activity. 6. In conclusion, the data demonstrate that inhibition of NO release in subcutaneous adipose tissue results in an increased lipolysis in vivo. These effects, which were also observed in vitro, are independent of local blood flow changes. Furthermore, the demonstration of enzymatic NOS activity and the expression of inducible nitric oxide synthase (iNOS) in adipose tissue indicate that locally synthesized NO may play a role in the physiological control of lipolysis in human adipose tissue.

Adipose Tissue↗
PubMed1999

Localization of the Yersinia PTPase to focal complexes is an important virulence mechanism.

The protein tyrosine phosphatase YopH, produced by the pathogen Yersinia pseudotuberculosis, is an essential virulence determinant involved in antiphagocytosis. Upon infection, YopH is translocated into the target cell, where it recognizes focal complexes. Genetic analysis revealed that YopH harbours a region that is responsible for specific localization of this PTPase to focal complexes in HeLa cells and professional phagocytes. This region is a prerequisite for blocking an immediate-early Yersinia-induced signal within target cells. The region is also essential for antiphagocytosis and virulence, illustrating the biological significance of localization of YopH to focal complexes during Yersinia infection. These results also indicate that focal complexes play a role in the general phagocytic process.

Animals↗
PubMed1999

Repertoire shift occurs during the memory maintenance phase of the immune responses and is not affinity-driven.

We have examined the immunoglobulin variable gene usage and antibody affinities during the memory maintenance phase of the immune response to the hapten phenyl-oxazolone. Hapten-specific hybridomas representing the memory population were generated 4-6 months postimmunization. The V-gene expression of these hybridomas was determined by reverse transcriptase-polymerase chain reaction screening and antibody affinities were estimated by biointeraction analysis (BIA) using the BIAcore biosensor. Our results show that the V-gene repertoire has already been shifted during the memory maintenance phase of the immune response, i.e. prior to a second antigenic challenge, and did not entail any advantages in terms of antigen-binding capacities. Our results concur with the view that antibody affinities are modulated mainly through differences in dissociation rates rather than in association rates, and the implications of this with respect to affinity maturation is discussed.

Animals↗
PubMed1999

Transvaginal ultrasonography and endometrial histology in peri- and postmenopausal women on hormone replacement therapy.

OBJECTIVE: To determine the association between endometrial thickness and endometrial histology in a large sample of women using HRT. DESIGN: Results from three multi-centre studies were combined. PARTICIPANTS: Five hundred and sixty-four climacteric women were treated with either sequential, continuous combined or long-cycle therapy. MAIN OUTCOME MEASURES: The women underwent 717 examinations with both transvaginal ultrasonography and histological examination of the endometrium. Endometrial thickness was measured and associated with the histological findings. RESULTS: Eight cases of endometrial hyperplasia were diagnosed. All the hyperplasias were simple without atypia. Two cases had an endometrial thickness < 4 mm and two a thickness > 8 mm. The > 4 mm threshold for abnormal endometrium had a sensitivity of 75%, a specificity of 47%, a positive predictive value of 2% and a negative predictive value of 99%. CONCLUSION: No association could be found between the endometrial thickness measured by transvaginal ultrasonography and endometrial pathology. In six out of eight women with simple hyperplasia the endometrium measured > 4 mm.

Administration, Cutaneous↗
PubMed1999

Yersinia pseudotuberculosis-induced calcium signaling in neutrophils is blocked by the virulence effector YopH.

Pathogenic species of the genus Yersinia evade the bactericidal functions of phagocytes. This evasion is mediated through their virulence effectors, Yops, which act within target cells. In this study we investigated the effect of Yersinia pseudotuberculosis on Ca2+ signaling in polymorphonuclear neutrophils. The intracellular free calcium concentration in single adherent human neutrophils was monitored during bacterial infection and, in parallel, the encounter between the bacteria and cells was observed. When a plasmid-cured strain was used for infection, adherence of a single bacterium to the cellular surface induced a beta1 integrin-dependent transient increase in the intracellular concentration of free calcium. This was, however, not seen with Yop-expressing wild-type bacteria, which adhered to the cell surface without generating any Ca2+ signal. Importantly, the overall Ca2+ homeostasis was not affected by the wild-type strain; the Ca2+ signal mediated by the G-protein-coupled formyl-methionyl-leucyl-phenylalanine receptor was still functioning. Hence, the blocking effect was restricted to certain receptors and their signaling pathways. The use of different Yop mutant strains revealed that the protein tyrosine phosphatase YopH was responsible for the inhibition. This virulence determinant has previously been implicated in very rapid Yersinia-mediated effects on target cells as the key effector in the blockage of phagocytic uptake. The present finding, that Y. pseudotuberculosis, via YopH, specifically inhibits a self-induced immediate-early Ca2+ signal in neutrophils, offers more-detailed information concerning the effectiveness of this virulence effector and implies an effect on Ca2+-dependent, downstream signals.

Bacterial Adhesion↗
PubMed1999

alpha1-adrenoceptors and bladder function.

OBJECTIVE: To discuss the role of alpha-adrenoceptors (alpha-ARs) in the control of lower urinary tract function with special emphasis on their importance in the pathologically changed bladder. METHODS: Evaluation of published information. RESULTS: The functional role of the alpha-ARs in the normal detrusor muscle has not been established. Changes in the function of these alpha-ARs may occur in e.g., bladder outflow obstruction, bladder overactivity, and 'neurogenic' bladders. The filling (irritative) symptoms in patients with benign prostatic hyperplasia and outflow obstruction, which are relieved by alpha-AR antagonist treatment, have been associated with bladder dysfunction produced by the obstruction. There is evidence for involvement of alpha-ARs in the spinal control of both the sympathetic, somatic (filling) and parasympathetic (voiding) efferent activity to the lower urinary tract. The beneficial effects of alpha-AR antagonists on filling symptoms, which can be obtained even in the absence of outflow obstruction, give support for the involvement of extravesical, possibly spinal, alpha-ARs in their pathogenesis. CONCLUSIONS: A more complete understanding of the role of alpha-ARs in the control of the normal or functionally changed bladder should be helpful in the development of drugs for treatment of lower urinary tract disorders.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1998

Photoperiodic effects on pubertal maturation of spermatogenesis, pituitary responsiveness to exogenous GnRH, and expression of boar taint in crossbred boars.

Forty-eight weaned, winter-born crossbred males (average age of 42 days) were exposed to either a natural photoperiod (January-June at 60 degrees N, Control) or one of two artificial photoperiods (1400 lx) in light-sealed rooms. The Spring/Summer group was exposed to an artificial photoperiod simulating conditions from the vernal equinox (mid-March) to August at 60 degrees N and the Autumn/Winter group to a photoperiod, simulating conditions from the autumnal equinox (mid-September) to February at 60 degrees N. Plasma samples were collected biweekly until the pigs were slaughtered, after reaching 115 kg, and analysed for testosterone, estrone sulfate, thyroxine and prolactin. Additionally, three animals per treatment (n = 9) were injected with gonadotropin-releasing hormone (GnRH) and plasma samples were collected every 15 min and analysed for luteinizing hormone and testosterone. Boar taint, carcass composition and reproductive traits were measured at slaughter. Live-weight gain from start to slaughter was lower among the Control animals compared with the Autumn/Winter and Spring/Summer animals. There was a peak in plasma testosterone in both the Spring/Summer and Autumn/Winter groups at 71 days of age, whereas plasma testosterone in the Control group remained at prepubertal levels. At 113 and 127 days of age, the Control group had somewhat higher testosterone levels than the Spring/Summer group, but at 141 days of age and on the day before slaughter, the Autumn/Winter group had a higher mean plasma testosterone concentration. There were no differences between treatments in the endocrine response to the GnRH challenge. Bulbourethral gland weight at slaughter was lower in the Spring/Summer group than in the Autumn/Winter group. The percentage of proximal cytoplasmic droplets was higher in the Spring/Summer group than in both the Control and Autumn/Winter groups. Spermatogenesis at the time of slaughter was clearly more mature in animals in the Autumn/Winter group than in those in the Spring/Summer and Control groups. Fat androstenone was lower in the Spring/Summer group than in the Control group. In the sensory evaluation, the Spring/Summer group had less boar taint than the Autumn/Winter group. Artificial short days with moderate initial changes in photoperiod, stimulated spermatogenesis compared with long days, in accordance with the pattern seen in European Wild Boars (Sus scrofa). Boar taint was also affected with higher scores in the Autumn/Winter group than in the Spring/Summer group, although this was not clearly indicated by the traditional measurements of boar taint-fat contents of androstenone and skatole.

Animals↗
PubMed1998

Quantitation of dopamine D2 receptor mRNA in a mesencephalic cell culture using a nonradioactive competitive reverse transcription polymerase chain reaction method.

Studies on gene expression during differentiation and maturation processes have to cope with determinations of extremely low steady state levels of specific mRNA. Using the experimental model of dopamine D2 receptor (D2R) expression in a primary mesencephalic cell culture we worked out a quantitative reverse transcription polymerase chain reaction method which allows to analyze and quantify mRNA levels of cells present in a few wells of the culture. The method uses an internal cRNA standard which shares both primer binding sites and PCR product length with the target sequence. The amplicons are quantitated in microplates by hybridization with immobilized capture probes that allow for the distinction of internal standard and target sequences followed by the chemiluminescent detection of hybridized DNA. Applying this method the levels of D2 receptor mRNA of the mesencephalic cell culture on day in vitro 1 amounted to about 250 fg/microgram RNA and increased to about 1200 fg/microgram RNA on day in vitro 13-15.

Animals↗
PubMed1998

Influence of artificial light regimens on sexual maturation and boar taint in entire male pigs.

To determine if artificial light regimens could influence sexual maturation and boar-taint factors in entire male pigs, 48 weaned, winter-born crossbred males (52-64 days old) were exposed to either a natural photoperiod (January-June, 60 degrees N, Control, n= 16) or to one of two artificial photoperiods (1400 1x) in light-sealed rooms. We exposed the Spring group to an increasing artificial photoperiod (January - June, 60 degrees N, n=16) and the Autumn group to a decreasing one (July-December, 60 degrees N, n = 16). Plasma samples were collected bi-weekly until the pigs were slaughtered, after reaching 115 kg. Boar taint, carcass composition and reproductive traits were measured at slaughter. Plasma testosterone increased earlier in the Autumn group than in the Control and Spring groups, but the difference was only transient. Estrone sulfate concentrations remained low in the Autumn group, whereas they increased in the Control and Spring groups, indicating a lack of synchrony between testicular androgen and estrogen production in the Autumn group. In the beginning of the study, when the Autumn group was subjected to long days, plasma prolactin was higher in the Autumn group than in the Spring group, but the relation was reversed 14 weeks later when the spring group was exposed to long days. Weight of reproductive organs (epididymidal weight and the total weight of the testes, epididymides and the bulbourethral glands relative to carcass weight) were lower in the Autumn and Spring groups than in the Control group. The Spring and Autumn groups had lower concentrations of skatole in fat compared with the Control group, whereas no clear difference was detected between groups in concentrations of androsterone in fat or in the sensory evaluation of boar taint. Estimated lean meat percentage was lower among animals in both the Autumn and Spring groups compared with the Control group. This study shows that photoperiod can influence male pubertal development and boar-taint factors in the domestic pig.

Adipose Tissue↗
PubMed1998

Mice with an inactivated joining chain locus have perturbed IgM secretion.

A mouse with an inactivated joining chain locus was produced by gene targeting in embryonic stem cells by deleting the first exon. Heterozygote (J+/-) and homozygote (J-/-) offspring from these mice showed normal total serum immunoglobulin levels and a normal peripheral B cell compartment when compared to wild-type littermates. The distribution of serum immunoglobulin isotypes in serum was different; IgA levels were elevated while IgM levels were reduced in J-/- mice as compared to wild-type mice. High molecular weight serum IgM was reduced in J+/- and J-/- mice and instead found in oligomeric form of undefined structure. Furthermore, serum IgM from J+/- and J-/- mice showed a reduced ability to activate complement. The number of splenic and bone marrow IgM plaque-forming cells were reduced in unimmunized J+/- as well as in J-/- mice. Furthermore, the number of plaque-forming cells was reduced in B cells from both J+/- and J-/- mice after stimulation with lipopolysaccharide in vitro. The perturbation of IgM production in J-/- mice appears to affect a late stage of differentiation, because cells with intracellular IgM were readily detected both in vivo and in vitro. Finally, after immunization with T-dependent or T-independent antigens the IgM component of the immune response was reduced in J-/- mice while only a marginal reduction of the IgG response was detected.

Animals↗