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The present study was designed to discriminate and analyze the presence of direct PMN chemotaxis and leucocyte-induced PMN chemotaxis in filter assay systems of PMN chemotaxis, namely the Wilkinson chamber and the Boyden chamber, which yield a more quantified information on leucocyte chemotaxis than filming of vital cells. The PMN chemotaxis was reduced by approximately 30–35 μm after incubation with vinblastine, 0.01, 0.10 and 1.00 μg/ml respectively, as measured by the leading front method in the Wilkinson chamber. This figure was thought to represent the contribution of the leucocyte-induced antitubulin-sensitive PMN chemotaxis to the casein-induced PMN chemotaxis under the experimental conditions prevailing. The remaining 60 μm antitubulin-insensitive PMN migration into the filter probably represented a combination of direct PMN chemotaxis and stimulated PMN random motility. Since the above-mentioned vinblastine inhibition of PMN chemotaxis was recorded in the absence of serum, complement factors included, the vinblastine-inhibited PMN chemotaxis was thought to be due to the release of a leucocyte-derived cytotaxin. The significance of incubation time and chemotactic parameters was further analyzed in the presence of serum in Boyden chambers, in the intercompartmental filters by means of PMN distribution curves and on the bottom filter by cell numbers. The antitubulin inhibition of PMN chemotaxis was evident in the intercompartmental filter during the initial period of incubation and later by cell counts on the bottom filter. These observations suggested that the antitubulin inhibition of PMN chemotaxis was due to antitubulin inhibition of the direction-finding in a minor proportion of fast-moving PMNs.

The active metabolite of vitamin D, 1,25-(OH)2D3, has immunomodulatory properties in addition to its more established action on bone and calcium metabolism. Recently vitamin D has been proposed as one of several environmental factors responsible for the increase in atopic diseases during the last decades. The objective of this study was to determine whether the estimated dose of dietary vitamin D3 during the first year of life is associated with atopic diseases up to the age of 6 years. In a prospective birth cohort study 123 six-year-old children were investigated for the cumulative incidence of atopic dermatitis, allergic rhinitis or asthma by means of a postal questionnaire. Their vitamin D3 intake during infancy was recorded in a previous study and the relationship between lower or higher vitamin D3 intake and atopic illness later in childhood was assessed. Atopic manifestations were more prevalent in the group with higher intake of vitamin D3. Although small, this study supports previous investigations suggesting a role of vitamin D intake during infancy in the development of atopic allergy later in childhood. If these findings are confirmed in prospective controlled clinical trials, prevention through modified vitamin D3 supplementation in infancy could be discussed to reduce the burden of atopic illnesses.

Background Vitamin D, a common food additive, has been shown to prevent the induction of experimental autoimmune diseases in mice. A possible immune deviation from T H 1 to T H 2 responses has been postulated. Although there is no doubt about the beneficial effects of vitamin D, its role in allergy has not been investigated. Objective To define the role of vitamin D in modulating the development of a T H 2-mediated disease, we used a murine model of pulmonary eosinophilic inflammation. Methods Five-week-old mice were primed on day 0 with ovalbumin intraperitoneally. Then they were nasally challenged with ovalbumin on days 7, 8, 9, and 10, and on day 11, samples were studied. Some mice received subcutaneous injections of vitamin D every second day as follows: days −3, −1, 1, 3, 5, 7, and 9. The control groups received PBS on the same days. Results Early treatment with vitamin D augmented allergen-induced T-cell proliferation along with T H 2 cytokine (IL-4 and IL-13) and IgE production. Surprisingly, the local inflammatory response in bronchoalveolar lavage fluid and lung tissue was significantly ameliorated with impaired recruitment of eosinophils and inferior levels of IL-5. These findings were attributed to late treatment with vitamin D after establishment of an early immune response. Conclusion We suggest that excess supplementation of vitamin D could influence the development of a sustained T H 2 response, leading to an increasing prevalence of allergy, whereas vitamin D might hold promising beneficial effects in airway eosinophilia.

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.

There have been contradictory reports on the shift in the T-cell cytokine expression pattern of peripheral blood mononuclear cells from patients with atopic dermatitis (AD); more specifically the interleukin (IL)-4 and interferon (IFN)-gamma profiles. The aim of this study was to shed further light on this contradiction by measuring the intracellular cytokines IL-4 and IFN-gamma by flow cytometry on unseparated whole blood to obtain results that, as accurately as possible, reflect the situation in circulating cells in vivo. The patient group including 64 patients with AD was compared with 18 nonatopic healthy adults. The results showed that the percentage of CD4+ T cells expressing IFN-gamma was significantly decreased (P < or = 0.001), as well as the percentage expressing IL-4 (P < 0.05) in AD patients compared with healthy controls. Furthermore, in supernatants from whole blood samples stimulated with phorbol 12-myristate 13-acetate and ionomycin, production of IFN-gamma was significantly decreased, while IL-4 production remained unchanged in AD patients compared with healthy controls. We also investigated if there was a relationship between serum IgE level and Phadiatop, a screening test for atopy, vs. the levels of IL-4 and IFN-gamma, but found no correlation with either. However, there was a significant correlation between disease severity and the level of total IgE (r = 0.67, P < 0.05). In conclusion, our results support the evidence for a decreased ability of peripheral CD4+ T cells to produce IFN-gamma among AD patients.

IgE reactivity to the opportunistic yeast Malassezia furfur can be found in patients with atopic dermatitis (AD). We have previously cloned and expressed 6 recombinant allergens (rMal f 1, rMal f 5-9) from M. furfur. In the present study, we used ImmunoCAP to investigate whether these rMal f allergens can be useful in the diagnosis of M. furfur-associated AD compared with the M. furfur extract. A total of 156 adult patients with a clinical diagnosis of AD participated in the study. Sixty-four percent had increased total serum IgE levels, 79% had specific IgE antibodies to common inhalant allergens and 47% had IgE antibodies to M. furfur extract. IgE antibodies to any of the rMal f allergens were detected among 86 (55%) of the patients, 14 (16%) of whom did not react to the M. furfur extract. Any individual rMal f allergen detected between 32% and 89% of the patients ImmunoCAP-positive to the M. furfur extract, with the highest sensitivity for rMal f 9. Therefore, a couple of individual rMal f allergens can improve the diagnosis of M. furfur-associated IgE allergies in patients with AD.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. The pathogenesis of AD involves skin barrier defects and dysregulation of innate and adaptive immunity. Some environmental factors such as stress, infections, and allergens are associated with aggravation of AD. The aim of the study was to investigate the relationship between skin barrier function, skin colonization of Staphylococcus aureus, and sensitization to antigens of skin-associated microorganisms in adult patients with AD.Thirty adult patients with AD and 10 controls were recruited. Eczema severity was assessed, and transepidermal water loss (TEWL) was measured. Bacterial samples were taken from the skin using a swab technique for qualitative identification of S. aureus and a contact agar disc method for quantitative assessment. Immunological analyses of specific IgE to staphylococcal enterotoxins and yeasts as well as total serum IgE levels, were performed.TEWL was significantly higher among S. aureus-positive patients in comparison to S. aureus-negative patients with AD (P0.05). TEWL increased with increasing bacterial load (P = 0.018). In the group of patients sensitized to all three of the investigated skin-associated microorganisms (S. aureus, Malassezia, and Candida), an increased TEWL was observed, in comparison to patients sensitized to none, or one or two (P = 0.026).In adult patients with AD, a disrupted skin barrier promotes skin colonization by microbes, such as S. aureus. Heavy microbial colonization may facilitate skin penetration of microbial antigens leading to subsequent IgE sensitization. These results illustrate the importance of skin-associated microbial colonization and sensitization to microbial-derived allergens in eczema pathogenesis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Environmental and genetic factors, as well as microbial products from yeasts and bacteria, play a role in triggering the disease. A cohort of 619 adult patients with AD was screened for severity of AD, sensitization to Malassezia sympodialis, Candida albicans, Staphylococcus aureus enterotoxins and Dermatophagoides pteronyssinus. Serum levels of interleukin (IL)-18 were measured. Immunoglobulin E (IgE) sensitization to the combination of both yeast and mite antigens was found to be associated with more severe disease and higher levels of total IgE. AD patients with IgE sensitization to several microbial antigens had more severe disease than those with no IgE sensitization to microbial antigens. Sera from patients with IgE-associated AD showed higher levels of IL-18. Skin-associated microorganisms are exogenous factors triggering IgE-response and severity of AD. These findings are clinically important, and sensitization to these organisms should be assessed and considered in treatment strategies.

Summary We have previously shown that the catalytic domain of tissue plasminogen activator (t-PA), the B-chain, binds specifically to hydrophobic components on the endothelial cell (EC) surface. The binding is mediated by amino acids within the sequence, AKHRRSPGER (B 20–29 ). The complex imparts a strong fibrinolytic potential to the EC surface, which is not inhibited by plasminogen activator inhibitor 1 (PAI-1). Here we characterize membrane proteins from EC that interact with the binding peptide and have hydrophobic properties. Specific labelling of cell surface components with affinity for the t-PA B-chain was performed using B-chain derivatized with the heterobifunctional and cleavable cross-linked SASD labelled with 125 I. Analysis of the cell extract by SDS/PAGE before and after reduction demonstrated the presence of a complex between the B-chain and a membrane protein of about 56 kDa. Radiolabelled proteins from the surface of EC were affinity purified on B 19–30 -Sepharose. The adsorbed proteins were eluted with lysine and the peptide B 20–29 . The hydrophobic fraction from the peptide eluate contained one main component with a molecular mass 56 kDa, which was absent in the hydrophilic fraction. In addition, four minor components were observed. Only traces of radiolabelled proteins were found in the hydrophobic fraction of the lysine eluate. Complexes between 125 I-t-PA and hydrophobic proteins from EC obtained by affinity chromatography on B 19–30 -Sepharose were crosslinked with disuccinylsuberate (DSS). Two radioactive complexes were identified after electroblotting to a PVDF membrane, one major component with a molecular mass of about 120 kDa and one minor 200 kDa complex. The 120 kDa compound had a significant activator activity before and after treatment with an excess of PAI-1. This is in contrast to free t-PA, which completely loses its activity in the presence of PAI-1. This indicates that t-PA (about 65 kDa) can form complexes with membrane components from EC with an approximate molecular mass of 55 kDa.

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 immortali ...

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.

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.

The prevalence of anti-endothelial cell antibodies (AECA) of IgA, IgG and IgM classes was studied by means of enzyme-linked immunosorbent assays (ELISA) in 466 patients with autoimmune/inflammatory disorders. The reference limits in the ELISAs for the AECA were determined from a random population sample of 249 subjects. The frequency of AECA was highest in patients with SLE (n = 42), 14.6% mainly of IgG class, and the presence of AECA correlated with disease activity in these patients. In the RA patient group (n = 200), 9.5% had AECA, mostly of IgA type. We found no association between the presence of AECA and extra-articular manifestations of RA or survival rate. In patients with undefined connective tissue disease (n = 57), ankylosing spondylitis (n = 109), and psoriatic arthritis (n = 58), the frequency of AECA corresponded to that of the random population sample. In a cohort of samples sent to the laboratory for determination of anti-nuclear antibodies (ANA) there was a correlation between the presence of ANA and AECA. Our findings indicate that RA patients are characterized by IgA class AECA, whereas SLE patients have IgG class AECA also correlating to disease activity.

Background Vitamin A may have some influence on the immune system, but the role in allergy modulation is still unclear. Objective To clarify whether high levels of retinoic acid (RA) affects allergic response in vivo, we used a murine experimental model of airway allergic disease. Methods Ovalbumin (OVA)-immunization/OVA-challenge (OVA/OVA) and house dust mite (HDM)-immunization/HDM-challenge (HDM/HDM) experimental murine models of allergic airway disease, using C57Bl.10/Q groups of mice (n = 10) treated subcutaneously with different concentrations of all-trans RA (0, 50, 500 and 2,500 ug) every 2-days were used to assess the allergic immune response. Results Levels of total and specific-IgE in sera were increased in all groups of RA treated OVA/OVA and HDM/HDM mice. Percentage and total amount of recruited eosinophil in airways by bronchoalveolar lavage fluid (BALF) were significantly enhanced in groups treated with 50, 500 and 2,500 ug of RA compared to non-treated mice. However, the group of mice treated with 2,500 ug had less eosinophil recruitment than the other two groups (50 and 500 ug). In parallel, levels of IL-5 and total IgE in BALF were also significantly diminished in the group treated with 2,500 ug compared to the other 2 groups (50 and 500 ug). Finally, total lung resistance was decreased in group treated with 2,500 ug compared to non-treated mice. Conclusion Our results suggest that retinoic acid directly enhances allergic response in vivo, but in higher doses may produce of immune suppression.

Background: The physiological requirement for vitamin D in infants and young children is not known. The current Nordic recommendation is a daily intake of 10 µg or 400 IU. In Sweden a daily supplement with vitamins A and D (AD-drops) is recommended from 6 weeks to 6 years of age, but compliance has been questioned, particularly after the first 2 years of life. Objective: To estimate the total dietary intake of vitamin D and the contribution from AD-drops to the total daily intake during the second half of infancy. Design: A postal survey on food intake with emphasis on vitamin D, including the recommended AD supplements at 5, 7 and 10 months of age, was answered by parents of 174 infants. Results: The average total intake of vitamin D was estimated at 11-15 µg day-1. AD-drops accounted for 76,64 and 53% of the total daily intake of vitamin D at 5, 7 and 10 months of age, respectively. Infant formula, milk cereal drink and commercial infant porridge were the most important food sources of vitamin D in these age groups. Conclusions: During the second half of infancy, when food is becoming successively more diversified, the average daily vitamin D intake was above the recommended daily intake of 10 µg for that age group. Vitamin D supplement accounted for more than half of the daily intake in all age groups studied. Without the recommended supplement the average vitamin D intake would have been below the level considered to lead to a risk of developing rickets in the youngest age group of the healthy, term infants. Keywords: allergy; infancy; retrospective; questionnaire; vitamin D

Cultures for Malassezia yeasts were taken from both normal-looking skin and lesional skin in 124 patients with atopic dermatitis, 16 patients with seborrhoeic dermatitis and from normal skin of 31 healthy controls. Positive Malassezia growth was found in fewer patients with atopic dermatitis (56%) than in patients with seborrhoeic dermatitis (88%) or in healthy controls (84%, p

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.

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.

A new, Swedish case with Tay or IBIDS syndrome is presented. The boy had growth and mental retardation, congenital ichthyosis and brittle hair. He was the only child in an uncle–niece marriage. The boy suffered recurrent infections and died at the age of 3 years from pneumonia. Clinical data on 15 cases are presented from a study of the literature.

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.

The immunosuppressive effect of purified human pregnancy zone protein (PZP) was studied in an experimental animal model for contact sensitivity to picryl chloride.

In a previous study, polymorphonuclear (PMN) leukocyte chemotaxis in vitro was inhibited by therapeutic concentrations of griseofulvin. In the present investigation, PMN migration in a casein gradient was studied in a cell suspension containing serum collected before and after a therapeutic peroral single-dose of griseofulvin. The PMN migration in vitro was not influenced significantly by the presence of griseofulvin-containing serum. It is suggested that peroral griseofulvin treatment has negligible effect on PMN chemotaxis in vitro.

The effect of rifampicin on contact sensitivity to DNCB (1-chloro-2,4-dinitrobenzene) was studied in outbred guinea pigs. The administration of rifampicin in a dose of 30 mg/kg body weight prior to and during the sensitization procedure suppressed the development of skin hypersensitivity. When sensitized animals were given rifampicin for 2 weeks prior to and during the epicutaneous test no suppression was demonstrated. Following rifampicin treatment there was a significant reduction of the weight of both the thymus and the spleen. We think that our findings are due to a rifampicin-mediated inhibition of lymphoid cell proliferation.

Fifty-one patients, thirty-nine women and twelve men, with Pityrosporum folliculitis are described. This investigation clearly demonstrates that Pityrosporum folliculitis is a real entity. The diagnosis is based primarily on the clinical picture, direct microscopy, histopathology, and the effect of antimycotic treatment. The typical patient is a woman of 30 years with itching follicular papules and pustules localized to the upper trunk or upper arms. Direct microscopy reveals round yeast cells and sometimes even hyphae. In biopsy specimens, abundant round budding yeast cells and occasionally hyphae are seen in a dilated follicle. Yeast growth is obtained only on lipid-enriched media. Twenty-five patients were treated with selenium sulfide shampoo, twelve with 50% propylene glycol in water, and ten with topical econazole cream with good results. Cure or marked improvement was seen after 3 to 4 weeks, but symptoms and lesions recurred if treatment was not continued intermittently. Predisposing factors such as occlusion and greasy skin are probably important, and future studies should focus on fungal hypersensitivity, quantitative variations in the number of Pityrosporum orbiculare, lipid composition of the skin, and extended epidemiologic data.

Werner's syndrome is often regarded as a segmental progeroid syndrome. It has been suggested that free radical damage involving oxygen contributes to aging. Furthermore, lymphocytes from Werner's syndrome patients show in vitro increased chromosome breakage and are protected by exogenous superoxide dismutase and catalase. We prepared erythrocytes and lymphocytes from three patients with Werner's syndrome and determined four important enzymes protecting against oxygen toxicity; CuZn superoxide dismutase, Mn superoxide dismutase, catalase and glutathione peroxidase. All enzymic activities were found to be normal.

In patients with Pityrosporum folliculitis the mean serum antibody titer against Pityrosporum orbiculare was significantly higher than in healthy control subjects (p less than 0.01). The mean number of P. orbiculare organisms per square centimeter cultured from normal-looking skin in patients was not significantly higher than the number cultured from normal-looking skin in control subjects. Results of prick tests against P. orbiculare extract were negative or weak, indicating that patients with Pityrosporum folliculitis had no type I hypersensitivity against P. orbiculare. Immunohistochemical staining of skin lesions showed perivascular dermal cell infiltrates near the hair follicles dominated by anti-Leu 3a-reactive T lymphocytes. Human lymphocyte antigens with the DR locus, but not those with the DQ locus, on keratinocytes were observed in one case.

Granular deposits of IgA in radioactively labeled thin slices of papillary dermis from 4-mm punch biopsies of clinically normal skin from patients with dermatitis herpetiformis were solubilized with sodium dodecyl sulfate (SDS) or peptic digestion at pH 4.5. Solubilized IgA-like material was isolated by immunoprecipitation and analyzed by electrophoresis in one and two dimensions in polyacrylamide gels containing SDS followed by autoradiography. SDS extracts contained IgA-like components corresponding to monomers, dimers, as well as higher polymers of IgA. A fraction of the SDS-soluble material behaved like IgA upon immunoprecipitation but could not be deaggregated to alpha- and light chains by reduction and alkylation, suggesting that it was present as irreversible aggregates with itself or with other proteins. Peptic digestion at pH 4.5 released fragments which were precipitated by antibodies to human alpha-chains and had molecular weights similar to the proteolytic fragments corresponding to F(ab)2 and Fab formed by peptic digestion of human monomeric IgA under the same conditions.

In preparations of papillary dermis taken from clinically normal skin of patients with dermatitis herpetiformis (DH), the disappearance of granular IgA deposits induced by peptic digestion was partial at pH 4.5 and total at pH 4.1, as visualized by immunofluorescence microscopy. In a model system in which human monomeric IgA was digested by pepsin using a pepsin-IgA ratio of 100:0.3, an IgA concentration of 3 lambda g/ml and a pH range of 5.1-4.1, the degradation of IgA molecules did not appear to proceed beyond the formation of fragments corresponding to F (ab)'. When supernatants after peptic digestion of papillary dermis at pH 4.1 were analysed by sodium-dodecylsulphate (SDS)-polyacrylamide gel electrophoresis after reduction and alkylation followed by electrophoretic transfer to nitrocellulose membranes and subsequent immunochemical detection, IgA-like material corresponding to the alpha-chain part of F (ab)' fragments was found in preparations from DH patients but not in those from controls.

Reserpine treatment in doses of 1.0 and 5.0 mg/kg body weight, given 6 h before antigen challenge significantly suppresses the contact sensitivity reaction to picryl chloride in sensitized mice. The suppression involves both the edema formation, measured as ear swelling, and the accumulation of inflammatory cells at the test site. This is probably mediated through inhibition of the release of vasoactive amines from local mast cells.

Several previous studies have demonstrated a chemotactic factor for white blood cells in extracts from psoriatic scales. In the present work, the question was studied whether chemotaxis is a primary or a secondary event in the development of a psoriatic lesion. The migration-stimulating properties of polymorphonuclear leukocytes of different extracts were determined by means of a modified Boyden technique. Aqueous extracts of psoriatic scales were good stimulators of migration of both autologous and homologous leukocytes. Uninvolved skin adjacent to psoriatic plaques (perilesional skin) has previously been shown to differ from control skin in various respects. Extracts of such perilesional skin of psoriatic patients did not have migration-stimulating properties. This result indicates that chemotaxis is a secondary event in the pathogenesis of psoriasis.

The contact activation and fibrinolytic systems were assessed in 5 patients with hereditary angioedema (HAE). Reductions in F XII levels and increase in kallikrein-like activity in some patients indicated activation of the contact (intrinsic) system of coagulation. A great increase in plasmin-α2-antiplasmin complex in all subjects indicated that in this disease, there is a constantly ongoing fibrinolysis. Since C1-inhibitor, the deficient protein in HAE, is a poor inhibitor of the well-known extrinsic (tissue-type) plasminogen activator, but the major inhibitor of the contact activation system and a related in vitro phenomenon termed intrinsic fibrinolysis, our data show that this fibrinolytic system is also sometimes operating efficiently in vivo . Furthermore, the known clinical data on HAE are compatible with a role of intrinsic fibrinolysis in the pathophysiology of this disease.

A technique has been devised to isolate the thin papillary part of the dermis from punch biopsies. Papillary dermis has been treated with various proteolytic enzymes in order to release or solubilize the granular IgA deposits from the papillary dermis of patients with dermatitis herpetiformis. Incubation of the thin skin preparations with pepsin caused a disappearance of the specific fluorescence with antibodies to human IgA. After peptic digestion small amounts of IgA could be detected in the supernatants. There was some evidence that this amount was larger for preparations from patients with dermatitis herpetiformis than from controls. Corresponding procedures with trypsin, collagenase, or elastase had no detectable effect on the IgA deposits. The experiments with elastase seemed to give support for previous reports on association between the granular IgA deposits and the microfibrils of elastic fibers.

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.

The efficacy of oral acyclovir in a twice-daily treatment regime was demonstrated in an open long-term study in 8 patients with frequently relapsing genital herpes type II infections. The treatment was well tolerated and no side effects were noted during the medication period of 6–21 months. No signs of decreased sensitivity for acyclovir appeared.

Iontophoresis was used to evaluate the peripheral reactivity of phenylephrine (alpha 1-agonist), isoproterenol (beta-agonist) and metacholine (cholinergic agonist) in patients with Alzheimer's disease (AD). The cutaneous responses--erythema and blanching--were visually recorded. Healthy personnel, medical students and patients with various dermatoses served as controls. A reduced response towards the adrenergic agonists was seen in AD. The reduced sensitivity was highly significant for the beta-agonist isoproterenol (p less than 0.001), in contradistinction the metacholine response did not differ between AD and age-matched controls. Furthermore, increasing age did not seem to significantly influence the cutaneous responses in mentally healthy controls. Thus, a reduced peripheral adrenergic reactivity was observed in the patients suffering from AD.