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Biomedical subjects

K Thestrup-Pedersen

Publications and source records attributed to K Thestrup-Pedersen.

At least 91 records · Page 5Linked to original sources

[A study of skin and mucosal irritation and incidence of allergy among office staff exposed to self-copying paper].

At a public office with a staff of 129, twenty people work for short periods with large amounts of self-copying paper. A controlled study has shown a significantly higher incidence of pruritus and nasal congestion amongst staff exposed to large amounts of self-copying paper or its components, no drying of the skin after working with the paper and no increased degree of irritation of the skin were found in the study group at dermatological examination. No differences were found between the study group and the control group with respect to allergy or skin status or working conditions apart from the contact with self-copying paper. The study confirms that contact with fresh self-copying paper may result in pruritus and skin irritation, but allergy to the paper or microcapsule contents could not be demonstrated in this study.

Adult↗

Expression of monocyte chemotactic and activating factor (MCAF) in skin related cells. A comparative study.

A significant proportion of the infiltrating cells in several inflammatory skin diseases, including psoriasis and allergic contact dermatitis, are monocytes. Additionally, it is known that the cytokine monocyte chemotactic and activating factor (MCAF) can be produced by several cell types present in the skin, suggesting a significant role for MCAF in the accumulation of monocytes during immunological and inflammatory skin reactions. We have recently developed a precise method for quantification of the amount of a specific mRNA species in a given sample and have used this technique to compare specific MCAF mRNA amounts in cultures of human keratinocytes, dermal fibroblasts, endothelial cells, and monocytes, after stimulation with interleukin 1 alpha (IL-1 alpha) for 6 h. Endothelial cells produced very high, monocytes and fibroblasts intermediate, and keratinocytes low amounts of MCAF mRNA. We have also performed time course studies of MCAF mRNA levels in the four cell types. Our findings suggest that the regulation of MCAF mRNA expression in these cells parallels the regulation of the lymphocyte and neutrophil chemotactic factor interleukin 8.

Cells, Cultured↗

Basophil histamine release induced by anti-IgE and concanavalin A. Relation to the total plasma IgE content.

The plant lectin concanavalin A (Con A) has been shown to induce basophil histamine release by an IgE-receptor-dependent process resembling that of anti-IgE-antibodies. In this study, the concentration-response for basophil histamine release from washed blood cells was analyzed in a population of blood samples from adults with a total plasma IgE content ranging from < 5 kU/l to > 18,000 kU/l (n = 108), as well as 148 cord blood samples. The concentration-response-curves for anti-IgE in all adult blood samples were similar, despite the large variation in total plasma IgE--only the cord blood samples showed a decreased sensitivity. In contrast, the optimal concentration of Con A was inversely related to plasma IgE, and this relation was most pronounced in the adult blood samples. It is proposed that IgE-receptor-mediated histamine release may be dependent not only on the number of stimulatory, dimeric cross-links formed between IgE-receptors, but also on the molecular structure of the cross-linking agent.

Adult↗

The efficacy of a moisturizer (Locobase) among cleaners and kitchen assistants during everyday exposure to water and detergents.

Workers exposed to various irritants are widely advised to use moisturizers. To evaluate the efficacy of a moisturizer (Locobase), we studied 111 cleaners and kitchen workers during everyday exposure to water and detergents. All took part in a standardized interview. After randomization, 1/2 the workers (n = 56) used Locobase during a period of 2 weeks (period L), followed by a period without any emollient (period C), or vice versa (n = 55). Clinical assessment and measurements of the skin surface temperature, electrical capacitance and transepidermal water loss (TEWL) were performed on the fingers, hands and arms on entry to the study, after 2 weeks and 4 weeks, or at drop out. The final evaluation showed that 70 (63%) were able to complete the study; 23 (21%) completed period L, but withdrew from period C after a mean of 6 days because of progressive dryness of the skin and eczema; and 12 (11%) were excluded because they used topical corticosteroids or emollients. The remaining 6 (5%) participants were lost to follow-up. Clinically, we observed a significant increase in dryness (p < 0.001) during periods of no treatment (period C), and normalization of the skin texture during use of Locobase. Clinical observations were confirmed by statistically significant differences (p < 0.001) in the electrical capacitance (epidermal hydration), which decreased during period C and increased to pre-study values during period L. No significant differences were found in skin temperatures and TEWL rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

ETH615, a synthetic inhibitor of leukotriene biosynthesis and function, also inhibits the production of and biological responses towards interleukin-8.

ETH615 (4-(2-quinolylmethoxy)-N-(3-fluorobenzyl-phenyl-amino-methyl -4- benzoic-acid), a synthetic inhibitor of leukotriene B4 production and activities, was tested for its effect on the production of and biological responses towards human interleukin-8. We found that ETH615 inhibits lipopolysaccharide-induced (LPS-induced) expression of interleukin-8 messenger-RNA (mRNA) and interleukin-8 production in human peripheral blood mononuclear cells. We also observed that ETH615 completely inhibited interleukin-8 as well as leukotriene B4 directed chemotaxis of human neutrophils in a dose-dependent manner. A moderate effect on fMLP-directed neutrophil chemotaxis was observed. Further, no significant effect on either interleukin-8, leukotriene B4 or fMLP-directed T-cell migration was observed. These results further support the concept of a cytokine-leukotriene regulatory circuit and encourage the establishment of clinical trials testing the effect of ETH615 on inflammatory skin diseases, which are characterized by high levels of interleukin-8 and leukotriene B4 in lesional skin.

Anti-Inflammatory Agents, Non-Steroidal↗

The polymerase chain reaction and dermatology. A new technique with important implications for the study of skin inflammation and for diagnostic tests of dermatological disorders.

The polymerase chain reaction is a powerful and versatile tool for the analysis of nucleic acids. Through a reaction imitating in vivo DNA replication, a defined fragment of DNA is repeatedly replicated by a DNA polymerase in an exponential manner. Such selective amplification of a sequence of interest has created new possibilities in molecular biology and related sciences. The basic principle and some of its variations and applications for both qualitative and quantitative analyses of potential interest to dermatologists are described.

Dermatitis↗

[UV cured acrylates--potent contact allergens in the occupational environment].

Allergic contact dermatitis is still an important disease in occupational medicine. Acrylic compounds are known to be potent contact sensitizers causing allergic eczema after occupational exposure. To illustrate the problem and the need for preventive arrangements the authors present an unusual clustering of allergic contact dermatitis in three technicians who produced hearing aids using ultraviolet cured akrylate compounds. All three technicians developed eczema on their fingers few months after introduction of the new acrylate compounds in the production. Skin patch testing with the products confirmed that sensitization.

Adult↗

Phenotypic determination of T-lymphocytes responding to chemotactic stimulation from fMLP, IL-8, human IL-10, and epidermal lymphocyte chemotactic factor.

Human T lymphocytes were collected after they had migrated towards N-formyl-methionyl-leukylphenylalanine (fMLP), rIL-8, human IL-10 (hIL-10), and epidermal lymphocyte chemotactic factor (ELCF). They were stained for determination of their phenotype by FACS analysis using anti-CD4, -CD8, -CD18, -CD45R0 and OPD4 antibodies. Human IL-10 increased the percentage of CD8+ T lymphocytes in the migrating cell population by 152% compared with cells migrating towards the medium and decreased the number of CD4+ T lymphocytes by 79%. ELCF increased the number of CD4+ T lymphocytes by 18%, and the number of CD45R0+ T lymphocytes by 52%, while the number of CD8+ T lymphocytes was decreased by 20%. rIL-8 increased the number of CD4+ T lymphocytes and decreased the CD8+ T lymphocytes. The distribution of the different subpopulations of T lymphocytes was not changed significantly by fMLP. The observed changes in the phenotypes did not occur when incubating T lymphocytes with the chemotaxins. Our observations demonstrate that individual chemotactic factors will attract specific subsets of T lymphocytes. They may help to explain the predominance of memory T lymphocytes (CD4R0+, CD4+) in allergic contact dermatitis and certain other skin diseases. They also confirm the results of a recent study, that showed hIL-10 to be selectively chemotactic for CD8+ T lymphocytes.

Antigens, CD↗

Human T lymphocytes and T-cell lines as target cells for lymphocyte chemotaxis.

We have observed that freshly isolated T lymphocytes from healthy donors give a chemotactic response to complement C5a in 26 of 55 individuals and to epidermal lymphocyte chemotactic factor in 15 of 23 donors using 51chromium-labelled lymphocytes in a double-filter Boyden chamber system. The reason for a lack of demonstrable chemotaxis among some cell populations is unknown, but it makes donor selection important when studying lymphocyte chemotaxis. In order to obtain a standardized screening assay for T lymphocyte chemotactic activity, we investigated a number of T-cell lines or T-cell-related cell lines such as HuT78, Jurkat, MOLT4, K562 and 1301. We observed that HuT78, K562 and Jurkat showed chemotactic responses to a variety of mediators, whereas 1301 showed chemotaxis only towards C5a, and MOLT4 was completely negative. The HuT78 cell line, which is derived from a patient with Sézary's syndrome, exhibited the highest chemotactic capacity similar to freshly isolated T lymphocytes. The only difference was its chemotactic response towards stimulation with recombinant interleukin-1 alpha and beta, which did not induce chemotaxis in human peripheral blood T lymphocytes in the Boyden chamber assay. We conclude that HuT78 can be used in screening various inflammatory mediators for their potential T lymphocyte chemotactic properties.

Biological Assay↗

Hyperosmolarity selectively enhances IgE-receptor-mediated histamine release from human basophils.

Increased osmotic pressure has been reported to cause non-cytotoxic histamine release (HR) from human basophils, as well as a potentiation of HR induced by anti-IgE. In this study, the effects of hyperosmolar Na-K-acetate (300-600 mOsm/kg H2O) on HR was studied in washed human blood cells from newborns, adult volunteers and patients with severe atopic dermatitis. These three patient groups represented 3 very distinct populations with respect to total plasma IgE content, medians were less than 0.2 IU/ml, 20.5 IU/ml and 2508 IU/ml; respectively. Increasing osmolarity to 500 mOsm/kg H2O caused little HR in the absence of other stimuli, whereas at 600 mOsm/kg H2O a significant increase in spontaneous HR was seen. The HR induced by anti-IgE and Concanavalin A, acting through the IgE-receptor, was increased approximately twofold at 500 mOsm/kg H2O. Responses were highly correlated to results at 300 mOsm/kg H2O. The use of 600 mOsm/kg H2O buffers caused a further increase in most, but not all blood samples. The potentiation of IgE-receptor-mediated HR when using hyperosmolar media was clearly independent of plasma IgE contents, and did not change the concentration-response to anti-IgE. In contrast, HR induced by the IgE-receptor-independent stimuli, Formyl-met-leu-phe and calcium ionophore A 23187, were not enhanced at all by increased osmotic pressure. We conclude, that hyperosomolar media selectively enhance IgE-receptor-mediated HR. The use of hyperosmolar media may therefore be beneficial in a diagnostic application of washed blood HR assays used in allergy diagnosis.

Acetates↗

Establishment of two continuous T-cell strains from a single plaque of a patient with mycosis fungoides.

From a plaque biopsy of a patient with mycosis fungoides, two different continuous cell lines were established by including both IL-2 and IL-4 in the culture medium. Both continuous cell lines appeared with characteristic chromosome markers after approximately 40 cell population doublings. The initial karyotype recognized in T cells from the skin biopsy was 46,XY and the karyotypes of the continuous cell strains were 46,XY, -18, + i(18q) and another with multiple chromosome aberrations as described in Sezary T-cell leukemia. Phenotyping with monoclonal antibodies and T-cell receptor analysis indicates that the latter cell strain represents a minority of T-cells in the plaque. Due to its many chromosomal aberrations it probably represents the malignant cell, which may be a central cell in the immune stimulation taking place in the skin.

Aged↗

The effect of second-line antirheumatic drugs on interleukin-8 mRNA synthesis and protein secretion in human endothelial cells.

Interactions between interleukin 8 (IL-8) and endothelial cells play an important role in the emigration of mononuclear cells from the blood into areas of inflammation. We examined the ability of specific second-line antirheumatic drugs to regulate (IL-8) gene expression and protein secretion in interleukin 1 (IL-1) stimulated human umbilical vein endothelial cells and peripheral blood mononuclear cells. The drugs sodium aurothiomalate, D-penicillamine and sulphasalazine were all able to modulate IL-8 mRNA synthesis in and protein secretion from endothelial cells. A bimodal effect was observed: at low concentrations IL-8 was suppressed, whereas higher concentrations resulted in an increased IL-8 production. In endothelial cells, treatment with hydrocortisone led to a linear suppression of IL-8 production in concentrations ranging from 0.5 micrograms/ml up to 500 micrograms/ml. Sulphapyridine, auranofin, hydroxychloroquine and methotrexate, had no effect on IL-8 secretion in endothelial cells. By contrast, 5-aminosalicylic acid induced a threefold increase in the IL-8 release. In peripheral blood mononuclear cells it was only possible to suppress the IL-8 production by hydrocortisone treatment. These results indicate that suppression of IL-8 production in endothelial cells could be an important factor in the mode of action for a number of second-line antirheumatic drugs.

Anti-Inflammatory Agents↗

Use of the polymerase chain reaction in quantification of interleukin 8 mRNA in minute epidermal samples.

Quantitative studies of cytokine gene expression in vivo are necessary in order to properly describe the cytokine network and to elucidate its role in skin inflammation. Ideally, one should be able to follow cytokine gene expression in epidermal, dermal, and blood compartments. However, such studies are limited by small amounts of available material. Here we report a polymerase chain reaction (PCR) cDNA amplification protocol useful for quantification of specific mRNAs in small skin samples. We found that analysis of dilution series of each sample permitted establishment of quantitative PCR amplification conditions using only picogram to nanogram amounts of total RNA. Cytokine mRNA amounts could then be measured relative to an internal standard species, co-reverse transcribed, and co-amplified with the cytokine species as a measure of cDNA input. Large numbers of samples can be screened rapidly with initial short dilution series identifying cytokine-positive samples and the correct dilution range for each, followed by closer analysis in this range. Epidermal samples obtained through curettage of a small skin area, 2-mm dermal biopsies from the scraped sites, and a few blood drops from the biopsy sites all yielded sufficient RNA for analysis by this protocol. Any mRNA of known sequence can be studied. We analyzed interleukin 8 mRNA levels in more than a hundred epidermal samples from patients and normal test persons and found a variation over several orders of magnitude that seemed to follow the degree of inflammation of the skin.

Base Sequence↗

PUVA treatment of vitiligo: a retrospective study of 59 patients.

We have performed a retrospective study of 59 patients with vitiligo who received PUVA therapy from 1972 to 1986. Sixteen patients had generalized vitiligo and 43 vitiligo in four locations (focal vitiligo). In both groups there were repigmentation in 44% of the patients. Half of the repigmented patients had improved more than 50%. None developed hypertrichosis, actinic keratosis, lentigines, or skin cancer within the observation period. Regardless of the results of PUVA therapy half of the patients thought PUVA was an acceptable therapy.

Adult↗