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Biomedical subjects

L Nilsson

Publications and source records attributed to L Nilsson.

At least 91 records · Page 5Linked to original sources

Is allergy prevention realistic and beneficial?

Allergic diseases among children have shown a marked increase during the last two or three decades, despite increased awareness of possible preventive measures. Preventive efforts have focused on new-borns and infants with a biparental history of allergy as they are at particularly high risk of developing allergic disease (40-60%). No good intervention studies have been performed in the general population, only in high-risk families. Unfortunately, so far known risk factors can only explain a small part of the recent increase in allergic diseases. The most important recommendation for everyone is not to smoke during pregnancy and when living/working with young children. Breast milk is the best for every baby, even from an immunologic aspect. Humidity problems should be reduced in homes, day-care centres and schools. It is probably wise not to keep furred pets indoors in homes when babies have a family history of allergy. However, the effect of such advice should be assessed, including the acceptability, compliance, costs and effectiveness. There is no doubt that we should go on with preventive measures both in babies at high risk of allergy and also in the general population. At the same time, research should try to find even more efficient ways to reduce the current "allergy epidemic".

Adolescent↗

Atopic eczema: how to tackle the most common atopic symptom.

The disease management of atopic eczema includes topical and systemic treatments as well as the control of allergic and non-allergic trigger factors. The basis for topical treatment is the regular use of emollients. In addition, anti-inflammatory treatment with -- preferably mild -- topical steroids is the treatment of choice. At least-one third of the children with atopic eczema during the first years suffer from clinically relevant food allergy requiring elimination diets for at least one or two years. The most common cause of superinfection is Staphylococcus aureus. Recent data suggests that it may induce purulent superinfection as well as enhance the inflammatory process by superantigen mediated T-cell activation. Also, a number of alternative treatment strategies have been investigated during the last decade: the use of gamma-linoleic acid has been shown to be of limited benefit, while studies on interferon-gamma and on high-dose intravenous gamma-globulin are still anecdotal. The long-term effectiveness of disease management in atopic eczema depends largely on the understanding of the disease process as well as on the compliance of the parents. Thus, coping with the problem will be easier if the patient or the parents have been educated in understanding the pathogenesis, the role of trigger factors, the possibilities of prevention and the different treatment strategies.

Adult↗

Linopirdine (DUP 996): cholinergic treatment of older adults using successive and non-successive tests.

The purpose of this study was to examine whether cholinergic treatment of age-associated memory impairment with Linopirdine (DUP 996), a derivate of phenylindoline, affects explicit memory, implicit memory, and primary memory. We also assessed cognitive decision making in a reaction time test. Explicit memory was assessed by face recognition, word recall and a word recognition test, being part of a successive test paradigm. Implicit memory was assessed by primed word fragment completion in the same successive test paradigm. Primary memory was studied by means of digit recall. Thirty-eight elderly subjects fulfilled the criteria for memory impairment. Four groups of subjects were given 10, 20 or 30 mg of DUP 996 or placebo during 4 weeks. A double-blind procedure was applied. No significant treatment effects for recognition memory and priming were obtained in the successive test paradigm. Analysis of dependence/independence between tests did not show any clear pattern of treatment effects. The other explicit memory tests and the reaction time test showed no effect with DUP 996. Because of the range of the different tests used here, the result and the general evidence in other investigations of the cholinergic depletion among aged people, the conclusion is that DUP 996 does not improve memory performance either in explicit, implicit or primary tests.

Age Factors↗

Effects of native, triglyceride-enriched, and oxidatively modified LDL on plasminogen activator inhibitor-1 expression in human endothelial cells.

Whereas VLDL has consistently been shown to induce a concentration-dependent increase in the expression of plasminogen activator inhibitor-1 (PAI-1) in human umbilical vein endothelial cells (HUVECs) and liver cells, variable effects have been reported for native and oxidatively modified LDL. In the present study, activation of PAI-1 protein and mRNA expression by native LDL (nLDL), UV-oxidized LDL (uvLDL), and triglyceride (TG)-enriched LDL was studied in HUVECs by using different incubation times and a wide range of lipoprotein concentrations. No significant increase of PAI-1 protein expression was observed after 4 hours of incubation with nLDL or uvLDL. However, PAI-1 protein secretion from HUVECs was markedly enhanced after 18 hours of incubation with uvLDL (200% increase at 10 microg/mL). Stimulation of PAI-1 protein expression in HUVECs by nLDL was seen, however, after increasing the TG content of the LDL particle. LDL enriched in phospholipid had no effect on PAI-1 secretion. PAI-1 mRNA levels on northern blot increased in parallel with the activation of PAI-1 protein expression by native and modified forms of LDL. Low concentrations of TG-enriched LDL (10 microg/mL) and higher concentrations of nLDL and uvLDL (100 microg/mL) were found to increase the binding of a VLDL-inducible transcription factor to the PAI-1 promoter. These results indicate that the TG content of the LDL particle influences PAI-1 expression in endothelial cells. Low concentrations of uvLDL enhanced PAI-1 protein and mRNA expression in the HUVECs after an 18-hour incubation but did not influence the VLDL-inducible transcription factor. This suggests that low levels of oxidized LDL increase PAI-1 expression by a different mechanism than VLDL and TG-enriched LDL.

Cells, Cultured↗

Effects of fibrate compounds on expression of plasminogen activator inhibitor-1 by cultured endothelial cells.

The consistent positive correlation between triglyceride and plasminogen activator inhibitor-1 (PAI-1) levels in plasma and the fact that very low density lipoprotein (VLDL) induces secretion of PAI-1 from cultured human umbilical vein endothelial cells (HUVECs) and human hepatoblastoma cells have raised the question of whether fibrate treatment, the main effect of which is a profound lowering of plasma concentrations of VLDL, might improve fibrinolytic function by reducing the plasma levels of PAI-1. However, the findings of controlled clinical trials using various fibrate compounds have been discrepant. ECs express PAI-1 under normal conditions in humans. We therefore examined the effects of several fibrate compounds on PAI-1 expression and secretion by cultured HUVECs and the HUVEC-derived cell line EA.hy926. All fibrate compounds examined had significant effects on PAI-1 gene transcription in the EA.hy926 cells. Low concentrations of clofibric acid and bezafibrate increased PAI-1 transcription and secretion, whereas Wy-14643 increased PAI-1 synthesis in a dose-dependent way. In contrast, both fenofibric acid and gemfibrozil markedly decreased PAI-1 transcription and secretion from HUVECs and EA.hy926 cells. Thus, stimulation of the transcriptional activity of the PAI-1 gene by some fibrates is linked to increased secretion of PAI-1 protein by the cells, whereas the opposite effects occur with other fibrate compounds. Whether the different effects on PAI-1 transcription and secretion by ECs in vitro also reflect differences in treatment effects on the regulation of plasma PAI-1 activity in vivo will have to be determined in larger-scale, controlled clinical trials.

Bezafibrate↗

Predictors of subjective quality of life in schizophrenic patients living in the community. A Nordic multicentre study.

As part of a Nordic multi-centre study investigating the life and care situation of community samples of schizophrenic patients the aim of the present part of the study was to examine the relationship between global subjective quality of life and objective life conditions, clinical characteristics including psychopathology and number of needs for care, subjective factors such as satisfaction with different life domains, social network, and self-esteem. A sample of 418 persons with schizophrenia from 10 sites was used. The results of a final multiple regression analysis, explaining 52.3% of the variance, showed that five subjective factors were significantly associated with global subjective quality of life, together with one objective indicator, to have a close friend. No clinical characteristics were associated with global subjective quality of life. The largest part of the variance was explained by satisfaction with health, 36.3% of the variance, and self-esteem, 7.3% of the variance. It is concluded that the actual relationship between objective life conditions and subjectively experienced quality of life still remains unclear. Furthermore, it seems obvious that personality related factors such as self-esteem, mastery and sense of autonomy also play a role in the appraisal of subjective quality of life, which implies that factors like these are important to consider in clinical and social interventions for patients with schizophrenia in order to improve quality of life for these persons.

Adult↗

Growth control of Listeria monocytogenes on cold-smoked salmon using a competitive lactic acid bacteria flora.

A Lactobacillus sake strain LKE5 and four strains of Carnobacterium piscicola were evaluated as biopreservation cultures to control the growth of Listeria monocytogenes on vacuum-packed, cold-smoked salmon stored at 5 degrees C. All five strains were antilisterial as live cultures in an agar diffusion assay. Cell-free supernatants of two strains of C. piscicola and L. sake LKE5 were also antilisterial because of the production of bacteriocins. The presence of high cell numbers of strains of C. piscicola had no influence on the sensory quality of cold-smoked salmon stored at 5 degrees C, but L. sake LKE5 caused strong sulfurous off-flavors and was rejected as a culture for biopreservation of cold-smoked salmon. A bacteriocin-producing strain of C. piscicola (A9b) initially caused a 7-day lag phase of L. monocytogenes, followed by a reduction in numbers of L. monocytogenes from 10(3) CFU/ml to below 10 CFU/ml after 32 days of incubation, coinciding with the detection of antilisterial compounds. The presence of a nonbacteriocin-producing strain of C. piscicola (A10a) prevented the growth of L. monocytogenes during the 32-day incubation. The growth of L. monocytogenes was strongly repressed on cold-smoked salmon in the presence of C. piscicola A9b and A 10a, respectively. The initial cell numbers of L. monocytogenes that were found on Oxford plates incubated at 25 degrees C reached low maximum cell counts of 10(4) and 2 x 10(3) after 14 and 20 days of storage in mixed culture with C. piscicola A9b and A10a.

Animals↗

VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: involvement of the VLDL receptor.

The potential role of the very low density lipoprotein (VLDL) receptor in mediating VLDL-induced plasminogen activator inhibitor-1 (PAI-1) expression was studied in vitro. Cultured endothelial cells incubated with VLDL showed an increased secretion of PAI-1. This response to VLDL could be completely prevented by the receptor-associated protein (RAP) and partially blocked by rabbit polyclonal anti-VLDL receptor IgG. Furthermore, Chinese hamster ovary (CHO) control cells and cells overexpressing the VLDL receptor were transiently transfected with a PAI-1 promoter-reporter construct and incubated with VLDL. The PAI-1 promoter activity in response to VLDL was significantly higher in the VLDL receptor overexpressing cells compared to the control cells. Addition of RAP completely blocked the VLDL-activated PAI-1 transcription. Electromobility shift assay was performed to investigate whether the enhanced PAI-1 promoter activity seen in the VLDL receptor overexpressing cells in response to VLDL involved induction of the previously described VLDL-inducible factor(s) binding to the -675 to -653 region of the PAI-1 promoter. We found that the binding of the VLDL-inducible factor in VLDL receptor overexpressing cells was markedly enhanced by addition of VLDL as compared to control cells where no increased binding could be seen in response to VLDL. In summary, these results indicate that the VLDL receptor is a strong candidate for mediating VLDL effects on PAI-1 synthesis and secretion in cells expressing this receptor.

Animals↗

APC-resistance is a risk factor for postoperative thromboembolism in elective replacement of the hip or knee--a prospective study.

Postoperative venous thromboembolic complications are commonly seen after total replacement of the hip or knee. Recently, an inherited defect with resistance to the anticoagulant activity of activated protein C (APC-resistance) has been detected. APC-resistance seems to be a common risk factor, especially in Sweden, and it increases the propensity for venous thrombosis. This study assesses the prevalence of APC-resistance in a general population and its clinical significance for patients undergoing surgery associated with a high risk of thromboembolic complications. In a prospective cohort study, we analysed for APC-resistance in 645 consecutive patients before elective replacement of the hip or knee at 3 hospitals in southern Sweden. Thromboprophylaxis with LMWH-heparin was given to all patients throughout the hospitalisation period. We recorded events of clinical thromboembolism for 3 months postoperatively. Venography, ultrasonography or pulmonary scintigraphy was requested by the clinicians according to the existing routines, i.e. only patients with symptoms of thromboembolism were examined. A thromboembolic complication was registered in 20 (3.1%) patients. Fifty per cent of the venous thrombi had a proximal location. Only 0.3% of the patients had verified pulmonary embolism. APC-resistance was found in 14.1% of the patients, of whom 9.9% had experienced postoperative thromboembolism compared with 2.0% of the patients without APC-resistance (p<0.0007). We conclude that APC-resistance is a frequent risk factor for symptomatic postoperative deep venous thrombosis with an estimated relative risk of 5.0 (95% confidence interval: from 1.9 to 12.9) in elective replacement of the hip or knee.

Activated Protein C Resistance↗

Identification of coagulase-positive staphylococci isolated from bovine milk.

A total of 414 coagulase-positive staphylococcal strains obtained at the mastitis laboratory, National Veterinary Institute, Uppsala, Sweden, were studied. One hundred and seventy seven strains were used for a frequency study. Ninety-seven per cent were identified as Staphylococcus aureus, 2% as Staphylococcus intermedius and 1% as Staphylococcus hyicus. Two hundred and thirty seven strains with atypical hemolysis reactions on bovine blood agar were randomly selected, with the aim to increase the number of S. intermedius and S. hyicus strains available for testing. Eight different characteristics, including physiological, enzymatical and biochemical properties, were used to identify the coagulase-positive Staphylococcus species. The results of this study suggest that the following tests should be included for correct identification of the 3 different species of coagulase-positive staphylococci: P agar supplemented with acriflavin, beta-galactosidase and hemolytic reaction on chocolate agar. These 3 tests are simple and quick to perform and enable accurate for easy differentiation of the 3 coagulase-positive Staphylococcus species.

Acriflavine↗

Interaction of human SRY protein with DNA: a molecular dynamics study.

Molecular dynamics simulations have been conducted to study the interaction of human sex-determining region Y (hSRY) protein with DNA. For this purpose, simulations of the hSRY high mobility group (HMG) domain (hSRY-HMG) with and without its DNA target site, a DNA octamer, and the DNA octamer alone have been carried out, employing the NMR solution structure of hSRY-HMG-DNA complex as a starting model. Analyses of the simulation results demonstrated that the interaction between hSRY and DNA was hydrophobic, just a few hydrogen bonds and only one water molecule as hydrogen-bonding bridge were observed at the protein-DNA interface. These two hydrophobic cores in the hSRY-HMG domain were the physical basis of hSRY-HMG-DNA specific interaction. They not only maintained the stability of the complex, but also primarily caused the DNA deformation. The salt bridges formed between the positive-charged residues of hSRY and phosphate groups of DNA made the phosphate electroneutral, which was advantageous for the deformation of DNA and the formation of a stable complex. We predicted the structure of hSRY-HMG domain in the free state and found that both hSRY and DNA changed their conformations to achieve greater complementarity of geometries and properties during the binding process; that is, the protein increased the angle between its long and short arms to accommodate the DNA, and the DNA became bent severely to adapt to the protein, although the conformational change of DNA was more severe than that of the hSRY-HMG domain. The sequence specificity and the role of residue Met9 are also discussed.

Amino Acid Sequence↗

[Paresis of the superior oblique eye muscle].

Congenital or acquired palsy of the superior oblique eye muscle presents a clinical picture which is consistent and recognizable. The diagnosis is based upon two clinical findings: hypertropia of the affected eye with a greater than normal vertical deviation in adduction, and an increase of the hypertropia when tilting the head towards the affected side (positive Bielschowsky test). In the majority of cases the dominant feature of the clinical picture is overreaction of the ipsilateral inferior oblique. We have retrospectively examined 22 patients with superior oblique palsy who underwent surgery. Median follow-up time was three months. 20 (91%) of the patients were operated primarily by performing a recession of the ipsilateral inferior oblique muscle. Additional surgery had to be performed on five patients. The final postoperative examination showed the result to be a success in 19 (86%) of the patients, judged on relief of symptoms and objective measurements. We conclude that in the majority of cases surgical treatment of superior oblique palsy by recession of the ipsilateral inferior oblique gives good results.

Adolescent↗

The essential role of inflammation and induced gene expression in the pathogenic pathway of Alzheimer's disease.

Alzheimer's disease is among the most common diseases of advanced age affecting almost one out of ten individuals who survive beyond the age of 65 years, and an another 10% for each additional decade of the life-span. The prognosis of the disease is an inexorable decline of mental functions leading to complete dependence on caretakers in the late stages of the disease. Alzheimer's disease will become a steadily increasing financial health-care problem in the industrialized world with the increasing longevity and ageing of the population. To-date there are no effective therapeutics. However, during the last years promising findings suggest that anti-inflammatory treatment strategies might be efficient. Here, we will review the experimental and epidemiological findings which support the idea that inflammatory mechanisms play an important role in Alzheimer's disease pathogenesis. The review of the experimental findings will be focussed on the amyloid-associated proteins, alpha1-antichymotrypsin and apolipoprotein E, as well as the major cytokines. In addition, the epidemiological studies on non-steroidal anti-inflammatory drugs and traumatic head injury will be summarized. We hypothesize a pathogenic model for Alzheimer's disease in which the expression of amyloid-associated proteins/pathological chaperones, induced by inflammatory cytokines, plays an essential role in accelerating the disease progress, and suggest potential targets for drug discovery based on such a model.

Aged↗

Postnatal growth and health in children born after cryopreservation as embryos.

BACKGROUND: There is uncertainty about the health of children born from in-vitro fertilisation (IVF) with cryopreserved embryos. We investigated the postnatal growth and health (up to 18 months) of these children compared with those born after standard IVF with fresh embryos and those from spontaneous pregnancies. METHODS: 255 children from cryopreserved embryos were matched by maternal age, parity, single or twin pregnancy, and date of delivery with 255 children born after IVF with fresh embryos, and 252 children from spontaneous pregnancies. The main endpoint was growth; secondary endpoints were the prevalence of chronic illness, major malformations, cumulative incidence of common diseases, and development during the first 18 months. Growth was assessed by comparison with standard Swedish growth charts and by standard deviation scores. FINDINGS: Growth features were similar for both singletons and twins in the three groups. There were 6 (2.4%) of 255, 9 (3.5%) of 255, and 8 (3.2%) of 252 major malformations in the cryopreserved group, standard IVF, and spontaneous groups, respectively (p=0.6 between the cryopreserved and standard IVF group). The prevalence of chronic diseases did not differ between the three groups, with 18.0%, 15.3%, and 16.7% of children with a chronic illness in the cryopreserved group, standard IVF, and spontaneous groups, respectively. INTERPRETATION: The cryopreservation process does not adversely affect the growth and health of children during infancy and early childhood. Minor handicaps, behavioural disturbances, learning difficulties, and dysfunction of attention and perception cannot be ruled out at this age.

Body Height↗

A randomized controlled trial of the effect of pertussis vaccines on atopic disease.

BACKGROUND: Pertussis vaccination in infancy has been suggested to increase the risk for development of asthma and allergy. OBJECTIVE: To assess sensitization rates and development of atopic diseases in a prospective randomized controlled trial of pertussis vaccine. PATIENTS AND METHODS: A total of 669 children were randomized to 1 of 4 vaccine groups (2-component acellular pertussis, 5-component acellular pertussis, whole-cell pertussis vaccines, and placebo [diphtheria and tetanus toxoids]). Diphtheria and tetanus toxoids were also given to the children in the pertussis vaccine groups. The children were evaluated by means of questionnaires at age 2 months, 7 months, and 2 1/2 years; skin prick tests at age 7 months and 2 1/2 years; and blinded clinical investigation at age 2 1/2 years. The families were contacted at regular intervals to assess possible adverse effects after the vaccinations and symptoms of whooping cough. RESULTS: The cumulative incidence of atopic diseases was 30% and incidence rates were similar in the 4 groups after adjusting for family history. Exposure to environmental tobacco smoke and home dampness did not confound these results. The frequency of adverse effects did not differ appreciably between atopic and nonatopic children, with the exception that a nodule at the vaccination site was more frequent after whole-cell pertussis vaccination in the nonatopic children. Among 47 children with proven pertussis, atopic disease appeared in 19 (40%). Of these 47 children, 9 (19%) developed asthma, as compared with 58 (9%) noninfected children (P=.03). CONCLUSIONS: We found no support for a drastic increase in allergic manifestations after pertussis vaccination. There was a positive association between whooping cough and asthma by 2 1/2 years of age. There seems to be little reason to withhold pertussis vaccination from infants, irrespective of family history of allergy.

Asthma↗

Solvent influence on base stacking.

In this paper we present a detailed analysis of the base-stacking phenomenon in different solvents, using nanosecond molecular dynamics simulations. The investigation focuses on deoxyribo- and ribodinucleoside monophosphates in aqueous and organic solutions. Organic solvents with a low dielectric constant, such as chloroform, and solvents with intermediate dielectric constants, such as dimethyl sulfoxide and methanol, were analyzed. This was also done for water, which is highly polar and has a high dielectric constant. Structural parameters such as the sugar puckering and the base-versus-base orientations, as well as the energetics of the solute-solvent interactions, were examined in the different solvents. The obtained data demonstrate that base stacking is favored in the high dielectric aqueous solution, followed by methanol and dimethyl sulfoxide with intermediate dielectric constants, and chloroform, with a low dielectric constant.

Calorimetry↗

Catch-up primary vaccination with acellular pertussis vaccines in 3-4-year-old children--reactogenicity and serological response.

In order to evaluate the optimum number of doses for catch-up primary vaccination against pertussis, 248 Swedish children 3-4 years of age were randomized to receive either two or three doses of a three-component or a five-component acellular pertussis vaccine. Adverse reactions were mild, but increased with increasing number of doses, especially in a subgroup of 17 children with serological signs of earlier pertussis. There were no clinically significant differences between the two vaccines. Antibody levels against pertussis were higher after two doses in this age group than after three doses in infancy. A primary vaccination program for older children can use two instead of three doses.

Antibodies, Viral↗