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Biomedical subjects

K H Schulz

Publications and source records attributed to K H Schulz.

At least 19 recordsLinked to original sources

Detection of IgE antibodies specific for 1-phenyl-2,3-dimethyl-3-pyrazoline-5-one by RAST: a serological diagnostic method for sensitivity to pyrazoline drugs.

Certain adverse reactions to pyrazoline drugs resemble IgE-mediated hypersensitivity. However, convincing evidence of antigen-antibody interactions is not fully demonstrated. In this study, IgE antibodies specific for 1-phenyl-2,3-dimethyl-3-pyrazoline-5-one have been found in 17 out of 19 serum samples from individuals sensitive to pyrazoline drugs with 4-aminoantipyrine discs by Radio Allergo Sorbent Test (RAST). In contrast, we have not found any positive results from 10 normal donors without sensitivity to pyrazoline drugs after ingestion of metamizol 500 mg/day for 14 days. Therefore, our results provide further evidence in favor of an IgE-dependent mechanism in patients suffering from sensitivity to pyrazoline drugs. The determination of specific IgE antibodies could be used as a serodiagnostics method.

Adult

The presence of specific IgE to salicyloyl and O-methylsalicyloyl in aspirin-sensitive patients.

Certain adverse reactions to aspirin (ASA), nonsteroidal anti-inflammatory drugs (NSAIDs) and pyrazoline derivatives resemble IgE-mediated hypersensitivity. However, convincing evidence of antigen-antibody interactions or of the inhibition of the cyclooxygenase pathway of arachidonic acid metabolism leading to an increase in the generation of leukotrienes (LTs) and a decrease in the generation of prostaglandins (PGs) was not fully demonstrated. In this study, two types of specific IgE antibodies have been found in 27 serum samples from 28 ASA-sensitive patients with salicyloyl-discs and O-methylsalicyloyl-discs by Radio Allergo Sorbent Tests (RAST). The positive rates were 96.4% and 71.4%, respectively. In contrast, no positive results could be found in 10 normal donors without ASA sensitivity after ingestion of ASA 500 mg/day for 14 days. Further investigation of the chemical structure of epitopes was done by cross inhibition studies. Our results are an increasing evidence in favour of an IgE-dependent mechanism in patients suffering from ASA sensitivity. Hopefully, the determination of specific IgE antibodies will be a safe diagnostic method of ASA sensitivity in vitro.

Adult

Structure of 2-methoxy-6-nonyl-1,4-benzoquinone, C16H24O3, a synthetic contact allergen related to the naturally occurring primin.

C16H24O3, Mr = 264.36, triclinic, P1, alpha = 4.167 (1), b = 9.658 (1), c = 19.093 (1) A, alpha = 89.66 (1), beta = 87.27 (1), gamma = 79.07 (1) degrees, V = 753.65 (1) A3, Z = 2, D chi = 1.165 Mg m-3, lambda(Cu K alpha) = 1.5418 A, mu = 0.595 mm-1, F(000) = 288, T = 295 K, R is 0.047 for 1682 observed unique reflections. The angle between the quinone ring plane and the mean plane defined by the aliphatic nonyl chain atoms is 17.4 (3) degrees. The average Csp3--Csp3 bond distance and corresponding angle of the side chain are 1.522 (3) A and 113.2 (2) degrees. The average dimensions of the quinone ring are C--C 1.485 (3), C = C 1.337 (3), C = O 1.209 (3) A, C--C--C 118.4 (2), C = C--C 120.8 (2), O = C--C 120.8 (2) degrees. Neighboring molecules form dimers across centres of symmetry which are linked by C--H...O hydrogen bonds, with H(3)...O(4i) 2.42 (4), C(3)...O(4i) 3.29 (2) A, and angle C(3)--H(3)...O(4i) 164 (3) degrees. The dimers are held together by van der Waals forces between the nonyl side chains, and by C(16)--H...O(2ii) hydrogen bonds, with H(163)...O(2ii) 2.56 (4), C(16)...O(2ii) 3.357 (3) A, and angle C(16)--H(163)...O(2ii) 140 (3) degrees [(i) -x, 1 -y, -z; (ii) -1 -x, 1-y, -z].

Allergens

[Papaverin--effective in therapy of pruritus of atopic dermatitis?].

Patients suffering from atopic dermatitis show increased phosphodiesterase activity in leucocytes. As a result, the level of intracellular c-AMP is reduced, which can produce a number of metabolic dysfunctions: We found strong evidence that an enhanced release of several inflammation mediators can favor itching, which in turn promotes the development of eczema, since it induces reflectory scratching. In order to solve the question whether papaverine as a phosphodiesterase inhibitor might offer a new approach in the systemic therapy of itching, we performed a placebo-controlled study on 51 patients with atopic dermatitis, who were orally treated with papaverin-HCl over 8 weeks. However, we did not observe any improvement of itching or eczema during treatment. Some other recently developed phosphodiesterase inhibitors are discussed.

Administration, Oral

A differentiated approach to testing skin sensitization. Proposal for a new test guideline skin sensitization.

The present EEC and OECD Guidelines for testing skin sensitization have been reviewed in light of scientific evidence demonstrating that those methods which use Freund's Complete Adjuvant (FCA) are likely to be more accurate in predicting a probable skin-sensitizing effect of a new substance in humans than those methods not employing Freund's Complete Adjuvant. In this new test guideline, therefore, the primary testing of a substance should be carried out using one of the recommended Adjuvant methods. In special cases a non-adjuvant method may be performed in addition. Not all of the seven methods in the EEC Guideline or eight methods in the OECD Guideline have been included, but in a proposal for an updated test protocol two Adjuvant tests (Maximization test by Magnusson and Kligman and Optimization test by Maurer), and two non-Adjuvant tests (Open Epicutaneous test by Klecak and Buehler test) are suggested. The criteria for selecting these methods are based on the fact that they are well validated and widely used on a broad basis by the scientific community. Furthermore, it is considered appropriate to permit the use of a lower number of animals than presently recommended for the testing of skin sensitization. This is also in agreement with aspects of animal welfare.

Animals

Structure of 6-dodecyl-2-methoxy-1,4-benzoquinone, a new synthetic contact allergen.

C19H30O3, Mr = 306.45, triclinic, P-1, a = 5.453 (1), b = 5.608 (1), c = 30.129 (2) A, alpha = 85.85 (1), beta = 88.66 (1), gamma = 83.02 (1) degree, V = 912.0 (1) A3, Z = 2, Dx = 1.116 Mg m-3, Cu K alpha radiation, lambda = 1.5418 A, mu = 0.548 mm-1, F(000) = 336, T = 296 K, R is 0.040 for 2489 observed unique reflections. The aliphatic side chain is slightly rotated from the quinone ring. The angle between the quinone-ring plane and the mean dodecyl-chain plane is 20.8 (2) degrees. The average Csp3-Csp3 bond lengths and corresponding angles of the side chain are 1.515 (5) A and 113.8 (3) degrees. The average dimensions of the quinone ring are C-C 1.477 (4), C = C 1.337 (4), C = O 1.222 (3) A, C-C-C 118.9 (3), C = C-C 120.6 (3), O = C-C 120.6 (3)degrees. Neighbouring molecules form dimers by C-H...O interactions across centres of symmetry [C(3)...O(3) 3.413 (2) A]. The dimers are linked together via methyl H and carbonyl O along [100] [C(19)...O(3) 3.338 (3) A]; O(3) is a bifurcated acceptor.

Allergens

Activated Fc alpha T cells in Crohn's disease are involved in regulation of IgA.

Activated peripheral T cells (APT) of patients with Crohn's disease (CD) have been analysed for the expression of IgA-Fc receptors and for competence of IgA regulation. It was found that within the subset of APT an increased number of cells express binding sites for IgA (IgA-Fc), that was not found in other diseases with elevated numbers of APT. Moreover the number of IgA-Fc receptor expressing T cells was found to be increased in the inflamed mucosa too. Cocultures with autologous B cells revealed that isolated IgA-Fc receptor bearing T cells of patients with CD suppress IgA secretion. These data support the hypothesis that APT are involved in the immunopathogenesis of CD.

Antibodies, Monoclonal

Induction of contact dermatitis in guinea pigs by quaternary ammonium compounds: the mechanism of antigen formation.

Eight quaternary ammonium compounds were tested for their ability to induce contact dermatitis in guinea pigs by using a modified Freund's complete adjuvant test together with the guinea pig maximization test. Only two quaternary ammonium salts of the eight tested could be designated as strong allergens. These two active substances were shown to be capable of stable association with membrane lipids in forming immunogenic complexes. This surface complexation phenomenon was confirmed by using a spin-labeled quaternary ammonium salt which competed for binding sites at the surface of epidermal cells in vivo. Electron spin resonance was used to demonstrate that stable "ion-pairs" are formed between binding sites and the two allergenic preservatives. Furthermore, information was obtained on the kinetics of immunogenic complex formation as well as on the position and orientation of the quaternary ammonium ion at the cell surface.

Allergens

["Malabsorptive" dermatitis herpetiformis. A study with particular regard to biopsy findings of the small intestine (author's transl)].

21 patients (6 females and 15 males) with Dermatitis herpetiformis have been studied with special considerations of the small intestinal biopsy-findings. During this investigation the patient's mean age was 45 years (20-68) and the mean age at onset was 38 years (17-64). In 5 patients (23.8%) total villous atrophy (group I) and in 4 patients (19.0%) a severe partial or subtotal villous trophy (group II) was found on small intestinal biopsy. The sprue-like changes were patchy lesions. Histocompatibility-antigens of type HLA-AL were found in 38.1% and of type HLA-B8 in 47.6%. After 20 years of the disease one patient died of a malignant lymphoma of the intestine (immunoblastic sarcoma). In all patients the number of interepithelial lymphocytes in the small bowel mucose was significantly increased, as it was in those patients with a normal villous pattern (group III). In a quantitative analysis of specifically labeled (peroxidase-anti-perosidase complex) IgG-, IgA- and IgM-cells in the intestinal mucosa it was found that the number of all three plasma cell classes are increased significantly (P less than 0.01).

Adult

The sensitizing capacity of naturally occurring quinones. Experimental studies in guinea pigs. II. Benzoquinones.

Experimental studies on the sensitizing capacity of naturally occurring benzoquinones, isolated from plants and woods have been carried out in guinea pigs of the Pirbright white strain. Seven compounds were available: primin, three dalbergiones, mansonia quinone (mansonone A), 2,6-dimethoxybenzoquinone and rapanone. With five of these substances (primin, mansonone A, three dalbergiones) guinea pigs could be sensitized. Primin, the allergen of Primula obconica Hance (primrose) proved to be the most effective one of all quinones tested in this and the preceding studies. As a similar but weaker sensitizer R-3, 4-dimethoxydalbergione from Machaerium scleroxylon Tul. (Pao ferro, Caviuna vermelha) could be identified. The results obtained with mansonone A, a sesquiterpenoid quinone from Mansonia altissima A. Chev. demonstrate that even naturally occurring orthoquinones are capable of inducing contact allergy. Allergic cross reactions could be obtained between all chemically related mansonones A-F. The results are in good accordance with the view that the sensitizing capacity of naturally occurring quinones depends on the fundamental quinoid structure and the length, position and configuration of the aliphatic side-chain.

Animals

[Immunofluorescence test in the diagnosis of mushroom worker's lung (author's transl)].

Growing and harvesting a new edible mushroom (Pleurotus florida mushroom--oyster mushroom) liberates a high amount of spores the inhalation of which causes symptoms similar to those of "farmer's lung". The Ouchterlony test detects precipitins against antigens of the spore membrane only in cases with high serum antibody levels, i.e. only one in eight sufferers from the disease had a positive antibody test. Because of this, indirect immunofluorescence was used as a more sensitive method for serum antibody detection: all mushroom workers with clinical symptoms were found to have precipitating antibodies. The test is, therefore, superior to the Ouchterlony one, is simpler and saves time. Furthermore, the immunoglobulin class can easily be obtained at the same time.

Alveolitis, Extrinsic Allergic

Occupational allergic contact dermatitis due to leatherleaf fern Arachniodes adiantiformis (Forst) Tindale.

Leatherleaf fern has been imported from the United States, Honduras and Puerto Rico to the Federal Republic of Germany since 1966 and cultivated in Germany since 1970/71. It is slowly displacing the floral arrangements with asparagus used until now as filler and background material. This change is due primarily to its better keeping quality. Continuous contact with the leatherleaf fern induced an allergic contact dermatitis of the palms and fingers in a female florist. Patch tests with the leaf revealed the allergic origin of the dermatitis. Five fractions of a chromatographically separated extract of the fern were tested on sensitized guinea-pigs and on the patient. Only the first fraction gave a positive patch test response. By further separation colourless crystals of the contact allergen could be obtained. Elucidation of the structure is in progress. The sensitizer could only be detected during sporogenesis of the fern, that means when sporecapsules are present on the surface of the leaves.

Adult

[Polyvalent contact allergy in a florist].

A female florist, who ran a flowershop from 1954 to 1966 had to quit her job because of her known contact allergy due to chrysanthemums and primrose. Though in the meantime 12 years had passed she suffered occasionally from redness of the pharynx and stomachache after ingestion of tea prepared from yarrow and camomile. Cleaning off her garden from weeds and frequently followed by swelling of her face and pruritus. After epicutaneous testing she developed positive reactions to chrysanthemum as well as cross reactions to sunflower, arnica, camomile, yarrow, tansy, mugwort and frullania (this lichen does not occur in the Northern part of Germany). Patch test with primin revealed the persistence of the highgrade hypersensitivity to Primula.

Adult