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Biomedical subjects

O Bäck

Publications and source records attributed to O Bäck.

At least 19 recordsLinked to original sources
PubMed2003

IgE-reactivity to seven Malassezia species.

BACKGROUND: Malassezia yeasts play a role in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS). The revised genus Malassezia includes several species which all are natural habitants of the human skin. In this study, we evaluated the presence of immunoglobulin E (IgE) antibodies to different Malassezia spp. in AEDS patients to allow optimization of the characterization of the IgE antibody profile of IgE-associated AEDS. METHODS: Ninety-six adult patients, with a clinical diagnosis of AEDS, were included in the study. Seventeen of the patients had IgE antibodies to M. sympodialis, ATCC 42132 (m70 ImmunoCAP, Pharmacia, Diagnostic AB, Uppsala, Sweden). The IgE antibodies to seven Malassezia spp. were measured and inhibition immunoblotting was performed to investigate whether M. sympodialis contains all the allergen components present in the other Malassezia spp. RESULTS: Twenty per cent of 79 AEDS patients with a negative m70 ImmunoCAP test had IgE antibodies to at least one of the other six Malassezia spp. tested. Our inhibition studies indicated that Malassezia spp. to a great extent, share allergenic determinants. However, Malassezia species also contained species-specific allergens. CONCLUSION: The use of only one species of Malassezia is not sufficient to detect all patients IgE sensitized to Malassezia. To obtain an optimal allergen preparation both common allergenic components as well as species-specific allergens have to be considered.

Adolescent↗
PubMed2003

Atopy patch test reactions to Malassezia allergens differentiate subgroups of atopic dermatitis patients.

BACKGROUND: The yeast Malassezia is considered to be one of the factors that can contribute to atopic dermatitis (AD). OBJECTIVES: To investigate the reactivity to Malassezia allergens, measured as specific serum IgE, positive skin prick test and positive atopy patch test (APT), in adult patients with AD. METHODS: In total, 132 adult patients with AD, 14 with seborrhoeic dermatitis (SD) and 33 healthy controls were investigated for their reactions to M. sympodialis extract and three recombinant Malassezia allergens (rMal s 1, rMal s 5 and rMal s 6). RESULTS: Sixty-seven per cent of the AD patients, but only one of the SD patients and none of the healthy controls, showed a positive reaction to at least one of the Malassezia allergens (extract and/or recombinant allergens) in at least one of the tests. The levels of M. sympodialis-specific IgE in serum correlated with the total serum IgE levels. Elevated serum levels of M. sympodialis-specific IgE were found in 55% and positive APT reactions in 41% of the AD patients with head and neck dermatitis. A relatively high proportion of patients without head and neck dermatitis and patients with low total serum IgE levels had a positive APT for M. sympodialis, despite lower proportions of individuals with M. sympodialis-specific IgE among these groups of patients. CONCLUSIONS: These results support that Malassezia can play a role in eliciting and maintaining eczema in patients with AD. The addition of an APT to the test battery used in this study reveals a previously overlooked impact of Malassezia hypersensitivity in certain subgroups of AD patients.

Adolescent↗
PubMed2001

Systemic ketoconazole for yeast allergic patients with atopic dermatitis.

BACKGROUND: Adult patients with atopic dermatitis (AD), especially with the head-neck distribution, are often sensitized to the lipophilic yeast Malassezia furfur/Pityrosporum orbiculare, which is considered to contribute to the pathogenesis of the dermatitis. OBJECTIVE: Evaluation of the efficacy of oral ketoconazole on immunological and clinical parameters in yeast allergic adult patients with AD. STUDY DESIGN: Randomized double-blind placebo-controlled study. SUBJECTS: Twenty-nine patients with specific IgE antibodies to M. furfur/P. orbiculare and with elevated serum IgE participated in the investigation. Fifteen subjects were treated with 200 mg ketoconazole daily and 14 received placebo for 3 months. Betamethasone cream was allowed as supplementary therapy and the consumption was registered. The clinical score (SCORAD), total serum IgE and specific IgE antibodies to M. furfur/P. orbiculare, Candida albicans and Dermatophagoides pteronyssinus were monitored at the starting point and by the end of the first and third month. RESULTS: In the actively treated group the levels of specific IgE to M. furfur/P. orbiculare and C. albicans as well as total serum IgE decreased significantly. Sensitization to D. pteronyssinus was not influenced. The clinical score decreased in both groups, and the improvement was correlated to the consumption of topical steroids in the control group but not in the ketoconazole group.

Adult↗
PubMed1997

Elevated serum levels of soluble CD30 in patients with atopic dermatitis (AD).

The immunopathology of AD is still unclear, but evidence for an immune response polarized towards Th2 activity has been provided. The CD30 molecule belongs to the tumour necrosis factor (TNF) receptor family and is expressed on activated T cells with a sustained expression in Th2 cells. This molecule also exists in a soluble form (sCD30). Elevated serum levels of sCD30 have been found in patients with Hodgkin's disease, chronic hepatitis B infection and HIV infection. Studies were undertaken to compare the serum levels of sCD30 in patients with AD (n=49) and healthy non-atopic controls (n=94). The presence of sCD30 was analysed with ELISA. A significantly higher concentration of sCD30 was noted in AD patients, median sCD30 level 29 U/ml (range 1-708 U/ml), compared with healthy non-atopic controls (P<0.001), where the median level was 11 U/ml with a range of 1-1042 U/ml. No correlation was found between sCD30 levels and total serum IgE, or between the AD patients' SCORAD values and concentration of sCD30. sCD30 levels were also analysed in 20 AD patients, which during ketoconazole treatment had improved their clinical scores and reduced their serum IgE and eosinophil cationic protein levels. However, no significant decrease in sCD30 levels was noted after treatment. The results show that patients with AD have elevated levels of sCD30, but without correlation to total serum IgE or disease activity.

Adolescent↗
PubMed1996

IL-1 beta activation in human epidermis.

IL-1 beta is produced as an inactive 31-kDa precursor processed to active 18-kDa IL-1 beta by proteolytic cleavage, catalyzed by the highly specific IL-1-converting enzyme (ICE). In vitro activation of IL-1 beta can also be obtained by other proteases. Human keratinocytes express IL-1 beta, but not active ICE. The role played by IL-1 beta produced by keratinocytes has therefore been unclear. We asked whether normal human plantar stratum corneum contains biologically active IL-1 beta and, if so, by which mechanism this IL-1 beta is activated. Crude extracts and partially purified preparations from which IL-1 alpha had been removed were used. Biologic IL-1 activity was measured as the ability to induce expression of E-selectin in HUVEC. The crude extract contained IL-1-like activity that could be partially abolished with Abs to IL-1 alpha or IL-1 beta and totally inhibited with a mixture of the two Abs. IL-1 activity in the partially purified preparation was totally inhibited by Abs to IL-1 beta. The specific IL-1 beta activity in the two preparations was 60 to 85% of the sp. act. of recombinant human IL-1 beta. IL-1 beta from plantar stratum corneum had a slightly higher molecular mass than recombinant mature IL-1 beta. Its isoelectric point was approximately 6.1 compared with 6.9 for rIL-1 beta. We conclude that human plantar stratum corneum contains biologically active IL-1 beta that has been activated by an alternative mechanism that does not involve ICE. This is, to our knowledge, the first report of an alternative mechanism of IL-1 beta activation occurring in vivo.

Amino Acid Sequence↗
PubMed1995

Binding of tissue plasminogen activator to endothelial cells. The effect on functional properties. Localization of a ligand in the B-chain of tPA.

The binding of 125I-labelled tissue plasminogen activator (tPA), the tPA A- or B-chain to endothelial cells (EC) were studied in suspensions of cultured human umbilical vein EC (HUVEC) or immortalized microvascular EC (HMEC). By determinations of the concentration-dependent binding it was shown that both the A-chain and the B-chain, which were isolated after partial reduction of two-chain tPA, contain ligands for binding to EC. The affinity for the B-chain was much higher than for the A-chain according to Scatchard analysis (Kd 24 and 515 nM, respectively), whereas the number of binding sites was higher for the A-chain than for the B-chain (Bmax 8 x 10(5) and 1.2 x 10(5), respectively). There were no cross interactions between the A- and B-chains and their binding sites. The binding of tPA to EC induced an almost 100-fold increase of the activation rate when compared to the same amount of enzyme in free solution, which in contrast to the fibrin-induced stimulation was not inhibited by antibodies against fibrin. The enzymatic activity of the B-chain was much less affected by the association to the cells. Both tPA and the tPA B-chain were largely protected against inhibition by an excess plasminogen activator type-1 (PAI-1) when bound to EC, whereas the same amount of free tPA was totally inactivated. The competition studies strongly indicated that an N-terminal segment in the B-chain, AKHRRSPGER, may be the ligand part of the B-chain. It is interesting to note that this polypeptide segment also participates in a binding site for PAI-1, necessary for effective inhibition. This implies a possible competition between PAI-1 and a tPA-receptor for binding of tPA. High molecular weight urokinase had no quenching effect on the binding of the B-chain to EC.

Amino Acid Sequence↗
PubMed1995

Ketoconazole in atopic dermatitis: therapeutic response is correlated with decrease in serum IgE.

The prevalence of specific IgE antibodies to the yeasts Pityrosporum orbiculare and Candida albicans was investigated in adult patients with atopic dermatitis (AD) or with seborrhoeic dermatitis and in healthy controls by means of the radioallergosorbent test (RAST). Of 63 AD patients, 28 (44%) had IgE antibodies to P. orbiculare and 21 (33%) to C. albicans. This is highly significant, since no antibodies were found in sera from other patients or controls. With the intention to treat, 20 patients with AD and a positive RAST to P. orbiculare were given ketoconazole 200 mg daily for 2 months and 200 mg twice weekly for further 3 months. The clinical scores improved during treatment with a reduction in the levels of specific IgE to P. orbiculare and total serum IgE. However, there were no correlations between clinical score and serum levels of P. orbiculare-specific IgE. C. albicans-specific IgE, on the other hand, correlated both with clinical score and with total serum IgE.

Adolescent↗
PubMed1995

Retinoids and fibrinolysis.

Vitamin A and its analogues have been reported to increase the release of tissue plasminogen activator in vitro. The aim of the present study was to reevaluate these findings and to investigate whether retinoids in doses used in dermatological therapy could enhance the release of endothelial fibrinolytic factors. Our results showed that endothelial cells incubated in vitro with retinoic acid increased the release of tissue plasminogen activator to the supernatant without concomitant secretion of plasminogen activator inhibitor-1. In patients treated with isotretinoin or etretinate these findings were confirmed, showing enhanced baseline tissue plasminogen activator concentrations in plasma in association with unchanged levels of plasminogen activator inhibitor-1 and von Willebrand factor. These findings are consistent with chronically augmented tissue plasminogen activator secretion without evidence of endothelial cell damage and may be of importance for the interpretation of the safety of lon-term therapy with regard to retinoid-induced hyperlipemia and the development of cardiovascular disease.

Adolescent↗
PubMed1993

Decreased peripheral glucocorticoid sensitivity in Alzheimer's disease.

Both peripheral and central glucocorticoid sensitivity was examined in patients with Alzheimer's disease (AD; n = 13), glucocorticoid-treated patients (n = 8), healthy elderly controls (n = 10) and young controls (n = 9). We performed glucocorticoid receptor-mediated skin vasoconstrictor responses to clobetasol and low-dose dexamethasone suppression tests. Patients with AD showed skin blanching at a significantly higher clobetasol concentration than did healthy elderly controls (p = 0.002). There was no difference in skin blanching between patients with AD and patients treated with corticosteroids. Patients with AD had significantly higher post-dexamethasone serum cortisol levels than healthy elderly (p = 0.01). No association was found between skin blanching and dexamethasone suppressibility. Thus patients with AD have apparently independent reductions in both central nervous system and peripheral glucocorticoid sensitivity. These results predict an increase in glucocorticoid secretion in some patients, which might accelerate neuronal degeneration in the absence of features of overexposure to glucocorticoids in peripheral tissues.

Adult↗
PubMed1992

Binding of tissue plasminogen activator to human endothelial cells. Importance of the B-chain as a ligand.

The aim of the present study was to investigate the binding of tissue plasminogen activator (tPA) to cultured endothelial cells and to characterize binding structures present in the cultures. Studies on the binding of 125I-tPA to cultured endothelial cells from human umbilical-cord veins (HUVEC) indicated that the number of sites for specific binding of tPA is 8 x 10(5) per cell. Treatment with an excess of antibodies against plasminogen-activator inhibitor type 1 (PAI-1) caused an 80% decrease in the binding, leaving about 1.6 x 10(5) unoccupied binding sites per cell, which appeared to be different from PAI-1. About 1.9 x 10(5) binding sites/cell for tPA were found on the surface of HUVEC that had been detached from the matrix. This indicates that only minor amounts of PAI-1 occur on the surface of the cells. In addition, immunocytochemical analysis showed that PAI-1 antigen is present almost exclusively in the cytoplasm but was not observed on the surface of the cells, whereas tPA antigen is abundant on the plasma membrane of tPA-treated cells as well as intracellularly. Competition studies using unlabelled compounds showed that native tPA and tPA B-chain (the proteinase domain), as well as the inactive derivatives, B-chain inactivated with D-Phe-Pro-Arg-chloromethane and tPA-PAI-1 complex, caused a considerable quenching of the binding of 125I-tPA to HUVEC, whereas the isolated A-chain had no demonstrable effect. Two components (apparent molecular masses 38 kDa and 56 kDa) reacting with tPA but lacking PAI-1 antigen determinants were identified. Thus the data suggest that tPA binds to HUVEC by two principally different mechanisms. One is mediated by PAI-1, which binds and inactivates tPA with a functional active site. The other binding is achieved by components which react with sites on the activator molecule other than structures of the A-chain or the active site.

Cell Membrane↗
PubMed1992

In-vivo administration of interleukin 1 both enhances and suppresses contact sensitivity in the mouse.

The in-vivo effects of systemic administration of recombinant human interleukin 1 beta (rIL-1 beta) were studied in the mouse contact-sensitivity model. rIL-1 beta in a single dose of 20 micrograms injected intraperitoneally 72-48 h before or 2-24 h after sensitization suppressed contact sensitivity. Given before challenge rIL-1 beta modulated the response in a biphasic way with an enhancement at 48 h and a suppression at 2 h before challenge. Only microgram doses of rIL-1 beta could enhance the contact sensitivity at 48 h, while microgram doses of rIL-1 beta at 2 h before challenge suppressed and nanogram doses enhanced the response. Treatment with indomethacin could only abrogate the effects of nanogram doses of rIL-1 beta. Measurements of the thickness of unchallenged control ears revealed that rIL-1 beta by itself could cause a small but significant increase in thickness depending on the dose and the time of administration.

Animals↗
PubMed1990

Plasma levels of endothelial-derived haemostatic factors in autoimmune thrombocytopenia and haemolytic anaemia.

The endothelial cell-synthesized haemostatic factors tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI) and von Willebrand factor (vWF) were assayed in a cross-sectional study of patients with immune thrombocytopenia (ITP) (n = 12) and autoimmune haemolytic anaemia (AIHA) (n = 3), and compared with a simultaneously selected contrast group of other hospitalized patients with obscure blood cytopenia at the time of sampling. All three factors were grossly elevated in both the study group and the contrast group. In the autoimmune patient group, the three haemostatic variables were significantly correlated with orosomucoid levels, demonstrating the acute-phase nature of the increased levels of vWF, tPA and PAI. These findings support the view that haemostatic factors of the vessel wall are implicated in the pathophysiology of a wide spectrum of diseases.

Adult↗
PubMed1990

Interleukin-1 decreases the number of Ia+ epidermal dendritic cells but increases their expression of Ia antigen.

It is generally accepted that ETAF/IL-1 is produced in epidermis by both keratinocytes and Langerhans' cells. We have studied the density and morphology of Ia+ epidermal dendritic cells in mice after systemic or intracutaneous injection of recombinant IL-1 beta. We found that rIL-1 beta decreased the density of Ia+ dendritic cells in the time period 2-7 days after rIL-1 beta administration. However, the remaining dendritic cells were enlarged and more arborized with increased expression of Ia antigen 1-4 days after injection of rIL-1 beta. The implication of the results is that ETAF/IL-1 modulates the function of Langerhans' cells through autocrine and paracrine regulation.

Animals↗
PubMed1989

Systemic interleukin I administration suppresses arachidonic acid-induced ear oedema in the mouse.

Recombinant human interleukin 1 beta (IL-1 beta), given intraperitoneally to mice as a single injection, significantly suppressed the development of arachidonic acid (AA)-induced ear oedema. This effect was noted 2 h after administration and for at least 5 days afterwards. IL-1 beta was effective in the dose range of 250 ng-20 micrograms/mouse. Injection of IL-1 beta per se resulted in erythema of the ears, and thus, IL-1 beta has the capacity not only to induce and augment but also to suppress inflammatory responses. Indomethacin administered as subcutaneously-implanted pellets did not influence the IL-1 beta induced-ear erythema, but suppressed to some extent the effect of IL-1 beta on the AA-induced ear oedema.

Animals↗
PubMed1988

Decreased peripheral beta-adrenergic reactivity in asthmatics treated with oral beta 2-agonists.

Peripheral beta-adrenoceptor reactivity, measured as the dermal erythematous reaction to iontophoretically administered isoprenaline was studied in 41 asthmatics, 13 patients with allergic rhinoconjunctivitis and 21 healthy control subjects. The response of intact superficial dermal blood vessels to isoprenaline, which has previously been demonstrated to be beta 2-adrenoceptor mediated, was reduced in asthmatics treated with high dose, oral, slow-release beta 2-agonists compared to healthy controls. The response in asthmatics not treated with oral beta 2-agonists and in patients with allergic rhinoconjunctivitis did not differ from controls. Thus, the peripheral beta 2-adrenergic reactivity of intact human superficial blood vessels is affected by oral, slow-release beta 2-agonists.

Administration, Inhalation↗
PubMed1988

Iontophoretic study of skin vessel reactivity in atopic dermatitis and its correlation to serum IgE levels.

Skin vessel reactivity was studied by means of an iontophoretic technique in 19 adult patients with atopic dermatitis. Fifteen patients were available for reinvestigation some 6 months later in winter. Compared with a control group, we found a significantly increased sensitivity in summer of dermal skin vessels toward the alpha 1-agonist phenylephrine. Patients with elevated serum IgE levels seemed to be more sensitive to phenylephrine. However, the difference was not significant. Isoproterenol, the beta-adrenoceptor agonist, induced blanching (as opposed to erythema) in 7 of 19 (37%) atopic dermatitis patients in summer and in 9 of 15 (60%) in winter compared with 1 of 36 in the control groups. This blanching was antagonized by the alpha-blocker phentolamine. From the results we concluded that there may be an increased alpha-adrenoceptor reactivity and/or a decreased beta-adrenoceptor reactivity in atopic dermatitis patients, which might be a primary defect.

Adult↗
PubMed1988

Increased peripheral alpha-adrenoceptor response in allergic asthmatics.

The peripheral alpha-adrenoceptor reactivity, measured as dermal blanching response to iontophoretically administered phenylephrine, was studied in 28 allergic asthmatics, 13 patients with allergic rhinoconjunctivitis and 21 healthy controls. The blanching response, which has previously been demonstrated to be mediated via alpha 1-adrenoceptors, was found to be significantly increased in allergic asthmatics compared with controls. It is suggested that there is an increased peripheral alpha-adrenoceptor reactivity in allergic asthma.

Adolescent↗