Ara h 8, a Bet v 1-homologous allergen from peanut, is a major allergen in patients with combined birch pollen and peanut allergy

BACKGROUND: We recently described patients with soybean allergy mainly mediated by cross-reactivity to birch pollen allergens. A majority of those patients were reported to have peanut allergy. OBJECTIVE: We sought to study the occurrence of peanut allergy in patients allergic to birch pollen and characterized the Bet v 1-homologous peanut allergen Ara h 8. METHODS: Recombinant Ara h 8 was cloned with degenerated primers and expressed in Escherichia coli. Nine Swiss and 11 Dutch patients with peanut and birch pollen allergy and a positive double-blind, placebo-controlled food challenge result to peanut were investigated for IgE reactivity to birch pollen and purified peanut allergens and cross-reactivity between birch and peanut. Ara h 8 stability against digestion and roasting was assessed by means of RAST inhibition. The IgE cross-linking potency of Ara h 8 was tested on the basis of basophil histamine release. RESULTS: During double-blind, placebo-controlled food challenge, all patients experienced symptoms in the oral cavity, progressing to more severe symptoms in 40% of patients. CAP-FEIA detected recombinant (r) Ara h 8-specific IgE in 85%. IgE binding to Ara h 8 was inhibited by Bet v 1 in peanut extract immunoblotting and in RAST inhibition. In EAST inhibition recombinant rAra h 8 inhibited IgE binding to peanut in 4 of 7 tested patient sera. Antipeanut response was dominated by Ara h 8 in 12 of 17 tested patients. Furthermore, our results demonstrate a low stability of Ara h 8 to roasting and no stability to gastric digestion. Basophil histamine release with rAra h 8 was more than 20% in 5 of 7 tested sera. CONCLUSIONS: Peanut allergy might be mediated in a subgroup of our patients by means of cross-reaction of Bet v 1 with the homologous peanut allergen Ara h 8.     

Immunopathogenesis of Sjögren's syndrome

Sjögren's syndrome (SS) is an autoimmune disease characterized by the sicca symptoms of dry eyes and dry mouth. Glandular dysfunction is thought to arise from destruction associated with lymphocytic infiltration. The degree of glandular destruction, however, does not correlate with the severity of sicca symptoms, suggesting that other mechanisms are involved, including abnormalities in parasympathetic neurotransmission. Autoantibodies against the muscarinic acetylcholine receptor have been implicated in this process, but multiple other autoantibodies have been found. Cytokines elaborated in the inflammatory lesions also appear to be involved and dysregulation of apoptosis are also involved in the pathogenesis of SS. A new two-stage model of SS has been proposed. First, there is a lymphocyte-independent phase during which inappropriate apoptosis results in the generation of apoptotic autoantigens which then attract lymphocytes. Subsequently, in the second lymphocyte-dependent phase, an immune attack causes further cell death and salivary dysfunction. Although the disease generally takes a rather stable and benign course, patients with SS have a significant risk of developing B cell lymphoma.     

Proteomics reveals a global phenotypic shift of NK cells in HCV patients treated with direct-acting antivirals

Chronic hepatitis C virus (HCV) infections compromise natural killer (NK)-cell immunity. Direct-acting antivirals (DAA) effectively eliminate HCV, but the long-term effects on NK cells in cured patients are debated. We conducted a proteomic study on CD56⁺ NK cells of chronic HCV-infected patients before and 1 year after DAA therapy. Donor-variation was observed in NK-cell proteomes of HCV-infected patients, with 46 dysregulated proteins restored after DAA therapy. However, 30% of the CD56⁺ NK-cell proteome remained altered 1 year post-therapy, indicating a phenotypic shift with low donor-variation. NK cells from virus-negative cured patients exhibited global regulation of RNA-processing and pathways related to “stimuli response”, “chemokine signaling”, and “cytotoxicity regulation”. Proteomics identified downregulation of vesicle transport components (CD107a, COPI/II complexes) and altered receptor expression profiles, indicating an inhibited NK-cell phenotype. Yet, activated NK cells from HCV patients before and after therapy effectively upregulated IFN-γ and recruited CD107a. Conversely, reduced surface expression levels of Tim-3 and 2B4 were observed before and after therapy. In conclusion, this study reveals long-term effects on the CD56⁺ NK-cell compartment in convalescent HCV patients 1 year after therapy, with limited abundance of vesicle transport complexes and surface receptors, associated with a responsive NK-cell phenotype.     

Diagnosis and treatment of risk factors in Germany and the UK

Objective

To estimate the impact of different systems of family practitioners’ payment on process of care: fee-for-service vs. capitation.

Design

Cross sectional international survey using cardiovascular prevention as an indicator of the quality of care.

Setting

Family physicians’ practices in Germany (fee-for-service) and the UK (capitation).

Subjects

778 patients attending for consultation regardless of morbidity or risk factor status.

Main outcome measures

Intervals since last consultation, since last BP-measurement, prevalence of known hypertension.

Results

There is a higher overall level of activity under FFS, but under capitation FPs seem to concentrate their efforts on the more severely ill or at risk. This would explain that under different systems of remuneraton the quality of care (outcome) is usually similar.

Conclusions

In areas of uncertainty FFS seems to stimulate activity or intervention, whereas under capitation FPs are rather reluctant to engage in procedures or interventions that are not sufficiently evaluated. Under prepaid remuneration FPs adjust in a way that the quality of care does not suffer.     

Parasite communities of the Salzhaff (Northwest Mecklenburg, Baltic Sea). I. Structure and dynamics of communities of littoral fish, especially small-sized fish

The parasites of ten fish species, including four Gobiidae, three Gasterosteidae, two Syngnathidae, and one Zoarcidae from the Salzhaff region, Northwest Mecklenburg, Baltic Sea, were investigated in 1995 and 1996. As many as 36 parasite species, represented by diverse groups of helminths and protozoans as well as annelids and copepods, are found during 4 seasons in these hosts. By far the most abundant group is represented by digeneans, comprising 15 species, followed by 7 cestodans and 6 nematodes. With regard to component communities, 8 host-parasite combinations are core and secondary species with more than 40% prevalence in which generalists such as the digeneans Podocotyle atomon and Cryptocotyle concavum (in 3 hosts). C. lingua, Diplostomum spathaceum, and Acanthostomum balthicum, and the nematode Hysterothylacium are involved. Also, specialists such as Aphalloides timmi in Pomatoschistus microps as well as Magnibursatus caudofilamentosa and Thersitina gasterostei in Gasterosteus aculeatus attain high levels of prevalence. A comparison of different investigations reveals greater prevalence of allogenic and autogenic parasite species with 3 host cycles in the Rerik-Riff (free Baltic) and higher levels of prevalence of autogenic parasite species with 1 or 2 host cycles in the entire Salzhaff. The component communities of gobies from Dahmeshöved, Lübeck Bight, attain generally lower degrees of prevalence than those of the Salzhaff region. The infracommunities consist mostly of 1–3 parasite species per host specimen; this value is surpassed on occasion in P. microps (maximum 7 species) and in G. aculeatus (maximum 9 species, which may compete for 5 microhabitats in a host specimen). In this context the theory of empty niches propagated by some parasitologists is critically discussed and substituted by the assumption of variable niche widths. The seasonality of the more abundant parasites is either unclear – as in the case of C. concavum– or evident – as in the case of P. atomon, which prevail in early spring and summer, or A. timmi, which dominate in late summer, as do M. caudofilamentosa, which is absent in spring. The main causes of the infestation of fish hosts may be their ages and the availability of parasites due to the presence of intermediate hosts.     

Intensity dependence of auditory evoked potentials (AEPs) as biological marker for cerebral serotonin levels: effects of tryptophan depletion in healthy subjects

Rationale: The intensity dependence of the auditory evoked potentials (AEP) has been suggested to be a specific biological marker of central serotonergic activity. Objective: While previous studies used circumstantial evidence to support this hypothesis, we manipulated (decreased) cerebral levels of serotonin directly by using tryptophan depletion. Methods: Twelve healthy young subjects were investigated using placebo and two different amino acid mixtures in a double blind cross over design on three different occasions. AEPs recorded during tryptophan depletion were analyzed by dipole analysis and regional sources using methods published in the literature. Results: For none of the mixtures a significant effect of tryptophan depletion was found. There was a trend towards reduced intensity dependency after tryptophan depletion, especially in the right hemisphere. This reduction correlated with the amount of reduced tryptophan in plasma. Conclusions: The results indicate, in contrast to earlier indirect studies, that the intensity dependence of AEPs is not a specific marker of central serotonergic activity. Received: 8 March 1999 / Final version: 25 May 1999     

The influence of penetrating keratoplasty and cyclosporin A therapy on MHC class II (Ia)-positive cells in the rat iris and choroid

Background: The presence of Ia-positive cells (MHC class II equivalent) has been previously reported in the iris and choroid of various species. They have been reported to have both round and dendritic morphologies; the latter may represent classic dendritic cells, potent antigen-presenting cells (APCs). It is possible that the dendritic-like cells play a important role in (auto)immune processes of uveal and other ocular tissues. Using the flat or whole mount technique, the distribution of Ia-positive cells in the rat iris and choroid was investigated following penetrating Keratoplasty (PKP) and following treatment with cyclosporin A (CsA). Methods: Lewis (LW) rats received corneal buttons from Lewis-Brown Norway (LW-BN) donors and were randomly assigned to the following groups: (i) operated, untreated (n=24); (ii) operated, CsA-treated (10 mg/kg i.m.;n=22). Controls were groups (iii) normal LW rats (n=13); (iv) unopcrated, CsA-treated (16 days' treatment;n=8); (v) anterior perforation of the anterior chamber (n=3); (vi) eight corneal sutures only (n=4); (vii) syngeneic operated (LW to LW;n=4). Animals of groups (i) and (ii) were killed on the 5th, 9th and 13th postoperative days and on appearance of the corneal rejection (group i, day 13; group ii, day 16). Both eyes were enucleated, immediately fixed, and iris-choroid flat mounts were examined for Ia-positive cells using APAAP immunohistochemistry. Results: In the normal Lewis rat iris, scattered Ia-positive cells of both nondendritic and dendritic morphology were observed. CsA treatment in the unoperated rat did not result in a significant decrease in the percentage of dendritic cells in the iris or choroid. Anterior chamber perforation, the placement of sutures in the cornea and syngeneic PKP resulted in a moderate increase in iris Ia-positive cells. Allogeneic transplantation resulted in a large increase in both types of Ia-positive cells, particularly on day 13 with corneal rejection. In group ii, an initial decrease in Ia-positive cells until day 13 was observed; upon rejection (day 16), the histological picture was similar to that of untreated animals. Alterations in the operated choroid were also apparent following CsA treatment. Conclusion: Corneal transplantation in the Lewis rat results in an increase in Ia-positive cells in the iris; CsA therapy can delay but not prevent this reaction. Changes in choroidal Ia-positive cells following PKP were not apparent, their numbers being affected only by CsA treatment following grafting.     

Continent Cutaneous Urinary Diversion Using The Full-Thickness Bowel Flap Tube as Continence Mechanism: A Simplified Tunneling Technique

Purpose

We present a time and labor saving embedding technique for a full-thickness bowel flap tube used as a continent outlet.

Materials and Methods

In 17 patients the bowel flap tube was extramurally embedded instead of being submucosally tunneled. The reservoir was attached to the abdominal wall to reinforce the continence mechanism and prevent the tunnel from opening.

Results

All 17 patients are completely continent and 14 of 16 evacuate urine easily with a 14F catheter. Due to recurrent stomal stenosis 1 patient with severe diabetes has undergone incontinent diversion.

Conclusions

Our described tunneling procedure for the full-thickness bowel flap tube is easy to perform and provides excellent continence.