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Biomedical subjects

L Nilsson

Publications and source records attributed to L Nilsson.

At least 109 records · Page 6Linked to original sources
PubMed1998

Effects of alpha-trinositol on peripheral circulation in diabetic patients with critical limb ischaemia. A pilot study using laser Doppler fluxmetry, transcutaneous oxygen tension measurements and dynamic capillaroscopy.

OBJECTIVES: To evaluate whether alpha-trinositol may have an effect on the microcirculation in patients with diabetes mellitus and critical ischaemia. MATERIAL AND METHODS: Ten patients with previously known diabetes mellitus and with critical limb ischaemia were given alpha-trinositol during a 24 h infusion, resulting in a total dose of 2400 mg. Microcirculation was evaluated by means of laser doppler fluxmetry (LDF), transcutaneous oxygen tension (tcPO2) and dynamic capillaroscopy (CBV). RESULTS: Plasma concentration of alpha-trinositol reached a steady state level after 1 h following the start of the administration. There were no detectable changes in blood pressure or heart rate. Laser Doppler flux increased from 41% to 57.5% and tcPO2 changed from 116 to 91 s in "half time recovery" after occlusion. Capillary blood flow showed an increase in resting velocity from 0.1 to 0.5 mm/s at 24 h. CONCLUSIONS: The infusion of alpha-trinositol did not cause any changes in the haemodynamics in general, but resulted in changes in LDF(rest value), tcO2(half-time recovery) and CBV(rest flow) during or following the infusion suggesting improved microcirculation.

Aged↗
PubMed1998

Results of gonadotrophin stimulation with the option to convert cycles to in vitro fertilization in cases of multifollicular development.

BACKGROUND: To avoid a high cancellation rate and/or a high multiple pregnancy rate due to multifollicular development in gonadotrophin stimulated cycles, such cycles were converted in the same cycle to in vitro fertilization/embryo transfer (IVF/ET). The results from a four year period using this strategy are summarized. PATIENTS AND METHODS: Seventy-three anovulatory women (seven WHO group I, 66 WHO group II) were studied during this period. In a majority of the cycles a GnRH-analogue was used for down-regulation according to a long protocol, followed by stimulation with FSH and/or hMG. RESULTS: Out of 154 WHO group II gonadotrophin stimulation cycles intended for ovulation induction, 25 cycles were converted to IVF. The pregnancy and delivery rates in the IVF-converted cycles were 50% and 41%, respectively, and 31% and 22% when gonadotrophin stimulation was followed by intercourse. The cancellation rate, including both ovulation induction and IVF cycles, was 15% and the multiple pregnancy rate was 30%, mainly twins. Lean women achieved better outcome than obese women. In WHO group I only 12 cycles were performed. One cycle was converted to IVF resulting in delivery and one cycle was cancelled. The pregnancy- and delivery rates were both 50% when gonadotrophin stimulation was followed by intercourse. CONCLUSION: It is concluded that the option to convert a gonadotrophin stimulation cycle to IVF in the same cycle, in cases of multifollicular development, seemed to be a good alternative. The conversion results in a low cancellation rate and a low incidence of high order multiple pregnancies. Patients should be informed of this opportunity before entering ovulation stimulation.

Adult↗
PubMed1998

Distinct T-cell subtypes induced with whole cell and acellular pertussis vaccines in children.

Recent clinical trials have demonstrated that new generation acellular pertussis vaccines can confer protection against whooping cough. However, the mechanism of protective immunity against Bordetella pertussis infection induced by vaccination remains to be defined. We have examined cellular immune responses in children immunized with a range of acellular and whole cell pertussis vaccines. Immunization of children with a potent whole-cell vaccine induced B. pertussis-specific T cells that secreted interferon-gamma (IFN-gamma), but not interleukin-5 (IL-5). In contrast, T cells from children immunized with acellular pertussis vaccines secreted IFN-gamma and/or IL-5 following stimulation with B. pertussis antigens in vitro. These observations suggest that protective immunity conferred by whole-cell vaccines, like natural immunity, is mediated by type 1 T cells, whereas the mechanism of immune protection generated with acellular vaccines may be more heterogeneous, involving T cells that secreted type 1 and type 2 cytokines.

Antigens, Bacterial↗
PubMed1998

Assessment of myocardial glutamate requirements early after coronary artery bypass surgery.

Glutamate is an important substrate for the intermediary metabolism of the heart, particularly in association with ischemia. Early after coronary artery bypass surgery (CABG) myocardial uptake of glutamate seems to be limited by substrate availability (arterial levels). However, glutamate is not an innocuous substrate. As arterial levels of glutamate are important both for myocardial uptake and adverse effects, an attempt was made to determine a minimum dose of glutamate sufficient to supply the needs of the heart after CABG. Ten patients received and infusion of 220-240 ml of 0.1 M L-glutamic acid solution at varying rates during two 30-min periods, starting 2 h after uncomplicated elective CABG. Intravenous glutamate infusion caused a dose-dependent linear increase in arterial glutamate and an increased myocardial uptake of glutamate. However, myocardial uptake of glutamate correlated with arterial levels only at lower infusion rates. Although maximal peak uptake in individual patients (6.6 +/- 1.1 mumol/min) occurred at an average increase of arterial whole blood glutamate of 172 +/- 34 mumol/L, the greatest impact on myocardial glutamate uptake was achieved by increasing arterial whole blood glutamate by less than 100 mumol/L. This implies that an infusion rate of 30-40 mg glutamate/kg BW/h could suffice to achieve a maximal or near maximal myocardial glutamate uptake in most patients after CABG. The adequacy of this dosage remains to be confirmed in high-risk patients.

Aged↗
PubMed1998

Structural and dynamic effects of point mutations in the recognition helix of the glucocorticoid receptor DNA-binding domain.

We have studied the wild type and two variants of the glucocorticoid receptor DNA-binding domain (GRDBD): in one variant the three residues (the 'P-box' in GRDBD) that are essential for the discrimination between GREH and EREH are mutated to those in the estrogen receptor DBD (GRDBDega) and the other variant is a point mutation of one P-box residue, Ser459Gly (GRDBDggv). Molecular dynamics simulations (0.5-0.7 ns) have been performed on the GRDBDs, free in solution as well as in complex with the half-site response elements of the glucocorticoid (GREH) and estrogen (EREH) receptors. The residues which are central when forming the protein dimer interface in GRE-(GRDBD)2 (the 'D-box') were found to have different conformations in the different GRDBD-DNA complexes. This is consistent with experimental results showing that the cooperativity of dimeric GRDBD binding to DNA strongly depends on both the response element and the P-box residues. In our simulations the structures of GREH-GRDBDgsv (i.e. wild-type) and GREH-GRDBDggv were more similar to each other than to the respective GRDBDs bound to EREH. This is due to a thymine methyl group which is present in the major groove of the GREH and prevents the first zinc coordinating subdomain in GRDBD to approach GREH, but which is absent in EREH. Thus, EREH-GRDBD is able to respond more to the Ser459Gly mutation than GREH-GRDBD.

Amino Acid Sequence↗
PubMed1998

Postmortem changes in blood concentrations of phenytoin and carbamazepine: an experimental study.

Observations of low postmortem blood concentrations of antiepileptic drugs in cases of sudden unexpected death in epilepsy (SUDEP) have led to the assumption that noncompliance may play a role in SUDEP. However, the reliability of postmortem drug levels has been questioned. The purpose of this study was to analyze possible postmortem changes in blood concentrations of carbamazepine (CBZ) and phenytoin (PHT). New Zealand white rabbits were fed with PHT or CBZ until assumed steady state. A blood sample was then drawn for determination of serum and whole blood concentrations of CBZ and PHT, after which the rabbits were killed and stored at 6 degrees C. A further blood sample for drug analysis was obtained 72 hours after death. Antemortem serum concentrations of CBZ were not significantly different from whole blood concentration 72 hours after death. In contrast, antemortem whole blood concentrations of PHT were only 65% of the corresponding serum concentrations, and postmortem PHT blood levels were even lower, being 35% of antemortem serum concentrations. In conclusion, blood concentrations of CBZ seem to be stable during 72 hours after death under these experimental conditions. However, postmortem PHT concentrations should be interpreted with caution and low postmortem concentrations do not necessarily imply a poor compliance.

Animals↗
PubMed1998

Pertussis IgE and atopic disease.

BACKGROUND: Pertussis toxin (PT) stimulates IgE production in animals, and pertussis vaccination and whooping cough may have similar effects in man. METHODS: We analyzed IgE responses to PT (PT-IgE) in sera from children primarily immunized with three doses of either an acellular 2- or 5-component vaccine, or a whole-cell (Wc) pertussis vaccine, and in children after whooping cough. The study comprised 50 children with both atopic disease and positive skin prick test, 99 nonatopic controls, and 40 children with verified pertussis. RESULTS: Immunoglobulin E antibodies against PT were demonstrated in 19% and 24% of sera from vaccinated children at 7 and 12 months, respectively, and in 9% at 2.5 years. At 7 months, PT-IgE was more common after vaccination with acellular (24%) than with the Wc vaccine (3%, P = 0.02). PT-IgE was also more common (P = 0.001) after vaccination in children classified as atopic (36%) than in the control group (10%). Thirty percent of the children with pertussis had PT-IgE, more often so in atopic than nonatopic children (P = 0.02). CONCLUSIONS: Transient production of PT-IgE seems to be common after primary pertussis immunization with acellular vaccines, and after whooping cough, particularly in atopic subjects.

Double-Blind Method↗
PubMed1998

Very-low-density lipoprotein response element in the promoter region of the human plasminogen activator inhibitor-1 gene implicated in the impaired fibrinolysis of hypertriglyceridemia.

Hypertriglyceridemia and impaired fibrinolytic function are linked to coronary heart disease and other atherothrombotic disorders. Triglyceride-rich lipoproteins may attenuate fibrinolysis by increasing the plasma levels of plasminogen activator inhibitor-1 (PAI-1). Furthermore, a common 4/5 guanosine (4G/5G) polymorphism in the promoter region of the PAI-1 gene has been indicated to influence plasma PAI-1 activity and to be involved in an allele-specific response to triglycerides. Herein we show by transfection assays that VLDLs induce transcription of the human PAI-1 promoter in endothelial cells. A VLDL response element (VLDLRE) is located to residues -672 to -657 in the promoter region by electromobility shift assay, methylation interference, and DNase I footprinting, and its activity is shown to be influenced by the common 4G/5G polymorphism located adjacent to and upstream of the binding site of a VLDL-inducible transcription factor. These findings may provide a molecular explanation to the link between VLDL and PAI-1 activity elevation in plasma and to the interaction between the 4G/5G polymorphism and plasma triglycerides.

Base Sequence↗
PubMed1998

Unsaturated fatty acids increase plasminogen activator inhibitor-1 expression in endothelial cells.

In vivo studies have demonstrated a strong positive correlation between plasma very low density lipoprotein (VLDL) triglyceride and plasma plasminogen activator inhibitor-1 (PAI-1) activity levels. Furthermore, VLDL has been shown to induce PAI-1 secretion from cultured endothelial cells. In contrast, no or variable effects on PAI-1 secretion have been reported for native low density lipoprotein. It could be speculated that fatty acids derived from VLDL triglycerides are the actual mediators, resulting in an enhanced secretion of PAI-1. In the present study, we have analyzed the effects of both saturated and unsaturated fatty acids on PAI-1 expression and secretion by endothelial cells. Addition of 0 to 50 micromol/L of either palmitic acid or stearic acid had no effect on PAI-1 secretion from human umbilical vein endothelial cells or EA. hy926 cells. In contrast, addition of oleic acid, linoleic acid, linolenic acid, and eicosapentaenoic acid resulted in a significant increase in PAI-1 secretion from both cell types. Northern blot analysis of PAI-1 mRNA levels was in agreement with these findings. Transfection experiments demonstrated that addition of linolenic acid and eicosapentaenoic acid significantly increased PAI-1 transcription. The fatty acid response region was localized to a previously described VLDL-inducible region of the PAI-1 promoter. Electromobility shift assays demonstrated that unsaturated fatty acids induced the same complex as did VLDL, whereas saturated fatty acids had no effect. Furthermore, it was demonstrated that the activation procedure did not involve fatty acid oxidation to any significant extent. In conclusion, the present study demonstrates that unsaturated fatty acids increase PAI-1 transcription and secretion by endothelial cells in vitro. The effect appears to be mediated by a previously described VLDL-inducible transcription factor.

Cells, Cultured↗
PubMed1998

Caenorhabditis elegans lin-25: cellular focus, protein expression and requirement for sur-2 during induction of vulval fates.

Induction of vulval fates in the C. elegans hermaphrodite is mediated by a signal transduction pathway involving Ras and MAP kinase. Previous genetic analysis has suggested that two potential targets of this pathway in the vulva precursor cells are two novel proteins, LIN-25 and SUR-2. In this report, we describe further studies of lin-25. The results of a genetic mosaic analysis together with those of experiments in which lin-25 was expressed under the control of an heterologous promoter suggest that the major focus of lin-25 during vulva induction is the vulva precursor cells themselves. We have generated antisera to LIN-25 and used these to analyse the pattern of protein expression. LIN-25 is present in all six precursor cells prior to and during vulva induction but later becomes restricted to cells of the vulval lineages. Mutations in genes in the Ras/MAP kinase pathway do not affect the pattern of expression but the accumulation of LIN-25 is reduced in the absence of sur-2. Overexpression of LIN-25 does not rescue sur-2 mutant defects suggesting that LIN-25 and SUR-2 may function together. LIN-25 is also expressed in the lateral hypodermis. Overexpression of LIN-25 disrupts lateral hypodermal cell fusion, suggesting that lin-25 may play a role in regulating cell fusions in C. elegans.

Animals↗
PubMed1997

Inhibition of Listeria monocytogenes on cold-smoked salmon by nisin and carbon dioxide atmosphere.

The bacteriostatic and bacteriocidal effect of nisin in combination with carbon dioxide, NaCl and low temperature on the survival of Listeria monocytogenes was investigated in in vitro model studies and in trials with cold-smoked salmon. Addition of nisin caused various degrees of inhibition and sometimes death of L. monocytogenes in model experiments performed at 10 degrees C. The antilisterial effect of nisin was improved in the presence of 100% CO2 and increasing NaCl concentrations (0.5 to 5.0% w/v). Minimal bactericidal concentrations (MBC) of nisin varied from 30 to more than 500 IU/ml. The most pronounced effect of nisin was found when 10(2) cfu/ml was grown in media with 5.0% NaCl and incubated in CO2 atmosphere (MBC = 30 IU/ml). The bactericidal effect of nisin was reduced in air and vacuum, and did not increase systematically with increasing NaCl concentrations. In general, nisin concentration < or = 50 IU/ml resulted in the survival and growth of L. monocytogenes in all combinations with other preservatives (NaCl, CO2). Addition of nisin (500 or 1000 IU/g) to cold-smoked salmon inoculated with L. monocytogenes and stored at 5 degrees C delayed, but did not prevent growth of L. monocytogenes in vacuum-packs. Numbers of L. monocytogenes increased to 10(8) cfu/g in vacuum packed cold-smoked salmon in 8 days, whereas CO2 packing of cold-smoked salmon resulted in an 8-day lag phase of L. monocytogenes, with numbers eventually reaching 10(6) cfu/g in 27 days. Addition of nisin to CO2 packed cold-smoked salmon resulted in a 1 to 2 log reduction of L. monocytogenes followed by a lag phase of 8 and 20 days in salmon with 500 and 1000 IU nisin/g, respectively. The levels of L. monocytogenes remained below 10(3) cfu/g during 27 days of storage at both concentrations of nisin.

Animals↗
PubMed1997

Coexistence of somatostatin receptor subtypes in the human neuroblastoma cell line LA-N-2.

Five distinct human somatostatin receptor subtypes have recently been cloned and characterized. Previous studies have suggested that these receptor subtypes might display coexistent localization, based on in situ hybridization or immunoblockage experiments. Here we provide evidence for coexistence of somatostatin receptor subtypes 2 and 5 in the human neuroblastoma cell line LA-N-2, using a combined approach with RT-PCR and receptor binding studies with somatostatin analogues. Somatostatin receptor subtypes simultaneously localized to a single cell might serve distinct functions in terms of targeting to different intraneuronal compartments or subtype specificity against so far unidentified somatostatin-related peptides.

Aged↗
PubMed1997

Is there a need for antithrombin III substitution early after burn injury?

The changes in antithrombin III (AT-III) levels in the blood and restitution in coagulation parameters between patients receiving and not receiving AT-III substitution were examined early after burn injury. The study was divided into two parts with a total of 14 consecutive patients (per cent total body surface area (TBSA) > or = 20 per cent). The first six patients were given AT-III substitution when AT-III levels fell below 50 per cent. The second part examined the restitution of the coagulation parameters when the patients (n = 8) obtained AT-III substitution only at extremely low values of AT-III. The decline in AT-III observed occurred in parallel to the permeability changes and the haemodilution normally seen secondarily to the initial fluid rescucitation. The observed changes in the coagulation parameters were modest and no hepatic dysfunction was noted. In addition, no differences of the restitution in these coagulation parameters were noted between the substituted and non-substituted groups. These results suggest that changes in AT-III early after burn injury depend mainly on factors other than an ongoing disseminated coagulation process. Probable causes are increased capillary leak and haemodilution. Our results suggest that substitution of AT-III in the early postburn period, on the assumption that low levels alone indicate ongoing coagulation, is not warranted.

Adolescent↗
PubMed1997

Effects of heparin-coating of cardiopulmonary bypass circuits on leukocytes during simulated extracorporeal circulation.

Heparin-coated circuits used during extracorporeal circulation reduce many postoperative complications occurring after heart surgery. Such complications are partly related to leukocyte activation with subsequent release of active substances, e.g. oxygen free radicals, myeloperoxidase and lactoferrin. This experiment was performed to elucidate a possible influence of heparin-coating on leukocytes. A 2-h-long simulated extracorporeal circulation was performed on two groups of five extracorporeal circulation circuits, primed with heparinized, fresh whole human blood and Ringer's solution. Heparin-coated circuits (HC group) were compared with uncoated circuits (NC group). Oxygen free radical production was estimated by determination of malonyldialdehyde in plasma and erythrocyte suspension. Granulocyte activation was measured in terms of myeloperoxidase and lactoferrin release. Time-related changes in leukocyte subset counts were analysed. Heparin-coating diminished myeloperoxidase and lactoferrin release. There were significant inter-group differences after 90 and 120 min of extracorporeal circulation for myeloperoxidase (101 (12) microg/l and 107(12) microg/l in the HC group versus 154(20) microg/l and 174(23) microg/l in the NC group), and after 120 min of extracorporeal circulation for lactoferrin (78(5) microg/l in the HC group versus 212(49) microg/l in the NC group). No significant changes of MDA concentration were observed in plasma or erythrocytes; however, a tendency towards lower MDA levels was seen after 90 and 120 min of extracorporeal circulation in the NC group. Neutrophil, monocyte and eosinophil numbers decreased significantly in the NC group but were unchanged in the HC group, as were lymphocyte counts. Heparin-coated extracorporeal circulation circuits significantly reduce granulocyte activation and better preserve the number of circulating neutrophils, eosinophils and monocytes, but do not change oxygen free radical production during simulated extracorporeal circulation.

Anticoagulants↗
PubMed1997

Bordetella pertussis respiratory infection in children is associated with preferential activation of type 1 T helper cells.

The mechanism of protective immunity against Bordetella pertussis generated following recovery from whooping cough in childhood has not yet been elucidated. Studies with a murine respiratory infection model have indicated that cellular immunity, mediated by Th1 cells, plays a role in the clearance of a primary infection with B. pertussis and in protection against subsequent challenge. In the present study, the induction of B. pertussis-specific Th cell subsets in children was examined. Peripheral blood mononuclear cells from B. pertussis-infected or convalescent children proliferated and secreted cytokines following antigen stimulation in vitro. In contrast, responses were weak or undetectable in the majority of children who had not been infected or vaccinated. In all cases, responding T cells produced interferon-gamma but low or undetectable interleukin-5. The findings suggest that Th1 cells may play a role in protective immunity generated following infection with B. pertussis in children.

Aging↗
PubMed1997

Recombinant human follicle stimulating hormone (r-hFSH; Gonal-F) versus highly purified urinary FSH (Metrodin HP): results of a randomized comparative study in women undergoing assisted reproductive techniques.

A prospective, randomized, comparative, assessor-blind study was carried out in two centres to compare the efficacy and safety of recombinant human follicle stimulating hormone (r-hFSH; Gonal-F) versus highly purified urinary FSH (u-hFSH HP; Metrodin HP), both administered s.c. in women undergoing ovarian stimulation for in-vitro fertilization including intracytoplasmic sperm injection (ICSI). A total of 235 patients started a long gonadotrophin-releasing hormone agonist protocol: 119 received r-hFSH and 114 received u-hFSH HP (150 IU/day) for the first 6 days. Two patients were excluded from the study because they mistakenly received the incorrect treatment combination. Human chorionic gonadotrophin (HCG; 10000 IU, s.c.) was administered once there was at least one follicle 18 mm in diameter and two others > or = 16 mm. In all, 119 (100%) and 102 (89%) of the patients respectively in the r-hFSH and u-hFSH HP groups achieved the criteria for HCG. The mean numbers (+/- SD) of oocytes recovered (the primary endpoint) were 12.2 +/- 5.5 and 7.6 +/- 4.4 in the r-hFSH and u-hFSH HP groups respectively (P < 0.0001). However, the number of FSH treatment days (11.0 +/- 1.6 versus 13.5 +/- 3.7) and the number of 75 IU ampoules (21.9 +/- 5.1 versus 31.9 +/- 13.4) used were significantly less (P < 0.0001) in the r-hFSH group than in the u-hFSH HP group. In patients treated using ICSI (63 patients in each group), no difference in oocyte maturation was observed. The mean numbers of embryos obtained were 8.1 +/- 4.2 and 4.7 +/- 3.5 (P < 0.0001), in favour of the r-hFSH group. In the majority of patients (96 and 99% respectively) only one or two embryos were replaced (mean 2.0 +/- 0.2 and 1.9 +/- 0.1 respectively) in the r-hFSH and u-hFSH HP groups. The clinical pregnancy rates per started cycle and per embryo transfer were 45 and 36%, and 48 and 47%, respectively in the r-hFSH and u-hFSH HP groups (not significant). There were six (5.1%) and two (1.7%) cases of ovarian hyperstimulation syndrome respectively. In conclusion, it was found that r-hFSH was more effective than u-hFSH at inducing multiple follicular development. However, the high rate of low ovarian response in the u-hFSH group compared with our general experience was unexpected. The availability of a gonadotrophin with less inter-batch variation would be beneficial for clinicians. r-hFSH seems to fulfil such a requirement.

Adolescent↗