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Biomedical subjects

J Fäh

Publications and source records attributed to J Fäh.

11 recordsLinked to original sources

Asthma, rhinitis and dermatitis triggered by fungal infection: therapeutic effects of terbinafine.

We report 2 atopic patients suffering from tinea unguium caused by Trichophyton rubrum. In addition, both patients had symptoms of allergies: one had perennial rhinoconjunctivitis and bronchial asthma, the other had chronic dermatitis of the face and neck. In both cases, their allergy symptoms improved dramatically during oral therapy with the antifungal agent terbinafine (250 mg/day) and relapsed after its discontinuation.

Administration, Oral↗

Safety and efficacy of specific immunotherapy with standardized allergenic extracts adsorbed on aluminium hydroxide.

Specific immunotherapy (SIT) with standardized allergenic extracts is the only specific treatment of allergic patients. In order to evaluate the safety, side effects, and efficacy of SIT with standardized extracts adsorbed to aluminium hydroxide manufactured by Stallergènes S.A., a prospective multicenter open study was performed in Switzerland. Fifteen patients suffering from seasonal or perennial rhinoconjunctivitis with or without asthma were included in the trial and received a total of 442 injections with standardized mix of grass pollens (n = 8) or house dust mites (n = 7) over one year. Low incidence of local reactions was noted (7%). Subcutaneous nodules (granuloma) following injections were not recorded. Only a few systemic reactions (one mild rhinitis, one mild asthma attack, one worsening of eczema) were recorded. No anaphylactic reactions requiring adrenaline were recorded. No admission to the hospital was required. Global appreciation of the physicians and the patients after the first year of treatment showed a good efficacy of SIT: Only two patients (13%) did not improve. A worsening of the symptoms was not observed. In order to assess the efficacy, skin reactivity and conjunctival reactivity to allergen challenge were compared before and after one year of treatment as well as immunologic parameters (such as specific IgE, specific IgG4) in blood samples. A significant decrease in skin reactivity (p = .001) and in conjunctival reactivity (p = .01) was observed. Specific IgE level decreased for both types of allergens but to a significantly greater extent for grass pollen allergen (p = .03). Specific IgG4 level increased significantly for grass (p = 0.01) and for mites (p = 0.04). Specific immunotherapy appears to be a valuable tool in the efficient management of the allergic respiratory diseases.

Adult↗

IgE antibodies specific for carbohydrates in a patient allergic to gum arabic (Acacia senegal).

The present study deals with the detailed investigation of the IgE antibody response of a gum arabic-allergic patient. The patient showed multiple serologic and skin test sensitizations to a range of pollen, other inhalants and foods, and bee venom, and to the recombinant allergens Bet v 1 and Bet v 2. Moreover, the patient's serum reacted strongly to gum-arabic extract. The NaIO4-treated and thus deglycosylated extract showed no binding to IgE. In contrast, removal of the protein backbone by basic hydrolysis did not deplete the IgE reactivity. Therefore, it is concluded that the gum arabic-specific IgE antibodies of this patient were mainly directed against the carbohydrate fraction of this material. In IgE-inhibition assays, cross-reactions occurred in the range of 60% between gum arabic and known immunogenic N-glycans containing alpha1-3-linked fucose. Since the inhibition graphs were not parallel and the inhibition was not complete with heterologue antigens, the cross-reacting epitopes of gum arabic appeared to be different from the latter well-known cross-reactive carbohydrate determinants (CCD). Inhibition may have been caused by a partial immunologic identity of the investigated carbohydrate moieties. A strong IgE response to the fucose-containing glycan from bromelain was measured in a glycan ELISA that utilizes purified glycopeptides at the solid phase. This response, which may explain the multiple sensitizations without clinical significance diagnosed in the patient, could originate from inhalation of pollen, which is known to contain similar glycans, or from occupational sensitization during work as a baker and confectioner. Since the gum-arabic protein showed only very weak participation in the IgE reactivity, the clinical symptoms of the patient caused by gum arabic may be attributed to carbohydrate epitopes. Due to the repetitive polysaccharide sequence of gum arabic, several epitopes for the cross-linking of IgE should exist.

Allergens↗

[Unusual Koebner phenomenon in psoriasis caused by varicella and UVB].

An isomorphic response is defined as a nonspecific skin stimulus eliciting a disease-specific skin reaction. We report on the development of the Koebner phenomenon in a 32 year old patient with psoriasis after skin testing with UVB at a dose above 0.055 J/cm2. In addition we describe a 28 years old patient who developed new psoriatic plaques in the areas affected by the virus after a varicella infection.

Adult↗

Human sunlight-induced basal-cell-carcinoma-associated dendritic cells are deficient in T cell co-stimulatory molecules and are impaired as antigen-presenting cells.

Immune surveillance of skin cancer involves the stimulation of effector T cells by tumor-derived antigens and antigen-presenting cells (APCs). An effective APC must not only display processed antigen in the context of MHC molecules but also express co-stimulatory molecules that are required to fully activate T cells. One of the most common cutaneous neoplasms is basal cell carcinoma. To investigate expression of the co-stimulatory molecules CD80 (B7-1) and CD86 (B7-2) on tumor-associated dendritic cells (TADCs), cryosections from basal cell carcinomas were immunostained. In basal cell carcinomas, only 1 to 2% of intratumor and 5 to 10% of peritumor APCs expressed CD80 or CD86. In contrast, biopsies of immunological/inflammatory dermatoses revealed that 38 to 73% of APCs expressed CD80 and CD86. To further evaluate their phenotype and function, TADCs were isolated from tissue samples of basal cell carcinomas; they were non-adherent to plastic, displayed a typical dendritic morphology, and expressed high levels of major histocompatibility class II molecules on their surface. When TADCs were compared with dendritic cells from blood for presentation of superantigens (staphylococcal enterotoxins A and B) to resting autologous T cells, TADCs were consistently weaker stimulators of T cell proliferation than blood dendritic cells. When analyzed by flow cytometry, TADCs expressed high levels of HLA-DR, but only 5 to 10% co-expressed CD80 or CD86. A 3-day culture in granulocyte/macrophage colony-stimulating factor-containing medium partially reconstituted the TADC expression of CD80 and CD86 as well as their immunostimulatory capacity. Thus, in this common skin cancer, although there are prominent collections of HLA-DR-positive APCs in and around tumor cells, the TADCs are deficient in important co-stimulatory molecules as well as being weak stimulators of T cell proliferation. The paucity of co-stimulatory molecule expression and functional activity of TADCs may explain why the local T lymphocytic infiltrate fails to become fully activated to eradicate adjacent tumor cells. From a clinical perspective, these findings suggest a novel immunotherapeutic strategy targeting T cell co-stimulatory molecules on professional APCs in cutaneous oncology.

Antigen-Presenting Cells↗

Anaphylactic reaction to lychee fruit: evidence for sensitization to profilin.

BACKGROUND AND OBJECTIVE: Due to the increasing popularity of exotic fruits in the Western diet, allergologists are confronted with allergic reactions to substances in these plants. The present report describes an anaphylactic reaction after the consumption of lychee fruit (Litchi sinensis). The atopic patient also suffers from rhinoconjunctivitis due to a sensitization against pollen of the Compositae family, as well as from dyspnoea after eating sunflower seeds. Our goals were to determine crossreactivity between antibodies against lychee fruit and other plants and to characterize the allergen. METHODS AND RESULTS: Specific IgE against lychee fruits were detected by an EAST assay. The allergen was characterized by immunoblot, immunoblot inhibition and EAST inhibition assays. Broad crossreactivity between lychee fruit and other plants was found and profilin identified as the protein responsible for the patient's complex allergy syndrome. CONCLUSION: Lychee fruit contains a significant amount of profilin. Consumption of this exotic fruit can cause severe anaphylactic reactions in patients being sensitized against the plant pan-allergen profilin.

Adult↗

Expression of MxA protein in inflammatory dermatoses.

The human MxA protein can be detected in the cytoplasm of IFN-alpha/beta-treated cells, whereas other cytokines, including IFN-gamma, are poor inducers. Because IFN-alpha/beta is predominantly synthesized in response to viral infections, MxA protein should be detectable in virally infected tissue. Biopsy specimens (n = 64) of 12 different dermatoses were therefore screened with an MxA-specific monoclonal antibody on formalin-fixed, paraffin-embedded and microwave-treated tissue sections. As expected, high amounts of MxA protein were found in acute viral skin lesions (chickenpox, Herpes zoster, and Herpes labialis). In addition, MxA protein was also detected in some inflammatory skin lesions of unknown etiology (lupus erythematosus, lichen planus, Schoenlein-Hennoch's anaphylactoid purpura and psoriasis). MxA protein was not found in non-viral infections (bacterial, mycotic, and parasitic) and was also not detectable in various other dermatoses (eczema, scleroderma, urticaria, granulomatous and bullous disorders). MxA staining proved a reliable, sensitive histochemical viral marker for infectious dermatoses. The positive results in non-infectious inflammatory dermatoses might implicate viral involvement or activation of the IFN system by thus far unknown mechanisms.

Antibodies, Monoclonal↗

Eruptive hamartomatous clear-cell acanthomas.

This is a report on a 38-year-old female, suffering from over 100 solid papules arising on her legs, arms and trunk during the past 10 years. The histology shows the typical feature of clear-cell acanthoma (CCA). Extensive investigations did not reveal any extracutaneous abnormalities. This case is exceptional because of the high number of hamartomatous CCA which exceeds the maximal number of about 20 seen in multiple CCA so far and therefore is referred to as eruptive hamartomatous CCA.

Adult↗

Interferon-regulated Mx genes are not responsive to interleukin-1, tumor necrosis factor, and other cytokines.

Accumulation of Mx gene products in cells of patients and experimental animals has been recognized as a useful marker for detecting minute quantities of biologically active interferon (IFN). Goetschy et al. (J. Goetschy, H. Zeller, J. Content, and M. A. Horisberger, J. Virol. 63:2616-2622, 1989) reported that not only IFNs but also interleukin-1 (IL-1) and tumor necrosis factor (TNF) were potent inducers of the human Mx genes. However, we observed no Mx induction in cultured human fibroblasts or in human peripheral blood mononuclear cells treated with various concentrations of IL-1 alpha or TNF-alpha. Mx induction was found in the spleens of mice treated with TNF-alpha or IL-1 alpha, but this effect could be neutralized with antibodies to murine IFN-alpha/beta. Of the other cytokines that we tested (IL-2, IL-6, and granulocyte-macrophage colony-stimulating factor), only IL-2 induced the Mx genes in peripheral blood mononuclear cells, but antibodies to human IFN-beta efficiently neutralized this effect. Our results thus indicate that IFNs are the only cytokines with intrinsic Mx-inducing activity.

Animals↗

cDNA structures and regulation of two interferon-induced human Mx proteins.

Human cells treated with interferon synthesize two proteins that exhibit high homology to murine Mx1 protein, which has previously been identified as the mediator of interferon-induced cellular resistance of mouse cells against influenza viruses. Using murine Mx1 cDNA as a hybridization probe, we have isolated cDNA clones originating from two distinct human Mx genes, designated MxA and MxB. In human fibroblasts, expression of MxA and MxB is strongly induced by alpha interferon (IFN-alpha), IFN-beta, Newcastle disease virus, and, to a much lesser extent, IFN-gamma, MxA and MxB proteins have molecular masses of 76 and 73 kilodaltons, respectively, and their sequences are 63% identical. A comparison of human and mouse Mx proteins revealed that human MxA and mouse Mx2 are the most closely related proteins, showing 77% sequence identity. Near their amino termini, human and mouse Mx proteins contain a block of 53 identical amino acids and additional regions of very high sequence similarity. These conserved sequences are also present in a double-stranded RNA-inducible fish gene, which suggests that they may constitute a functionally important domain of Mx proteins. In contrast to mouse Mx1 protein, which accumulates in the nuclei of IFN-treated mouse cells, the two human Mx proteins both accumulate in the cytoplasm of IFN-treated cells.

Amino Acid Sequence↗

A family of interferon-induced Mx-related mRNAs encodes cytoplasmic and nuclear proteins in rat cells.

Mouse Mx protein, an interferon (IFN)-induced nuclear protein, confers selective resistance to influenza virus. We show here that, as with influenza virus-resistant Mx+ mouse embryo cells, influenza virus mRNA accumulation and protein synthesis are strongly inhibited in rat embryo cells treated with IFN-alpha/beta. IFN-alpha/beta induced in rat cells the synthesis of Mx-related mRNAs migrating on Northern (RNA) gels as two bands of about 3.5 and 2.5 kilobases which directed the synthesis of three electrophoretically distinct proteins called rat Mx proteins 1, 2, and 3. The three rat proteins were antigenically related to the mouse Mx protein but differed in molecular weight and intracellular location. Rat Mx protein 1 was found predominantly in the nucleus and, on the basis of several criteria, resembled the nuclear mouse Mx protein. It was induced by IFN-alpha/beta in all 28 inbred rat strains tested. Rat Mx proteins 2 and 3 differed from protein 1 at the carboxy terminus and were predominantly cytoplasmic like the human Mx homolog. Sequence data of partial cDNA clones indicate that three Mx-related genes, rather than one, exist in the rat.

Animals↗