Biomedical subjects

K Thestrup-Pedersen

Publications and source records attributed to K Thestrup-Pedersen.

At least 73 records · Page 4Linked to original sources

PubMed1995

Cetirizine inhibits the in vitro and ex vivo chemotactic response of T lymphocytes and monocytes.

We have studied the effect of a nonsedating antihistamine, cetirizine dihydrochloride, on the in vitro chemotaxis of leukocytes from human peripheral blood. We observed that 0.25 microgram/ml of cetirizine dihydrochloride in vitro significantly inhibited the chemotaxis of monocytes toward N-formyl-methionyl-leucyl-phenylalanine and leukotriene B4. Higher concentrations of cetirizine, 1.0 and 2.5 micrograms/ml, completely inhibited monocyte chemotaxis without affecting cell viability. T-lymphocyte migration was also significantly depressed but not abolished. Pyrilamine (mepyramine) was not inhibitory in equimolar concentrations. According to these in vitro observations, we extended our studies to measure monocyte and T-lymphocyte chemotaxis in an open study, where four healthy volunteers and six patients with atopic dermatitis took 10 and 20 mg/day cetirizine 3 days. We observed a reduction in ex vivo monocyte and T-lymphocyte chemotaxis toward N-formyl-methionyl-leucyl-phenylalanine and leukotriene B4 without a reduction of the blood cell count. The results were confirmed in an ensuing double-blind, placebo-controlled study of 16 healthy subjects and 14 adult patients with atopic dermatitis, where ex vivo monocyte chemotaxis was reduced or abolished during cetirizine therapy. Serum levels of the two eosinophil-derived granule proteins, eosinophilcationic protein P and eosinophil protein X, were not changed during the treatment period of 7 days. The results show that cetirizine dihydrochloride has an inhibitory effect on monocytes and T lymphocytes in vitro and ex vivo. Our findings support the clinical observations that cetirizine dihydrochloride has an antiinflammatory effect besides its H1-blocking activity.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1995

Cutaneous barrier function after cold exposure in hairless mice: a model to demonstrate how cold interferes with barrier homeostasis among workers in the fish-processing industry.

Dry skin and eczema only seldomly occur in workers in the Danish fish-processing industry (FPI) during work, when their fingers and palms have a low skin surface temperature, low transepidermal water loss (TEWL), and a high capacitance. However, shortly after work, when the skin temperature has become normal, TEWL levels increase to above normal, and capacitance decreases to below normal, followed by the development of dry skin or chapping, which subsequently revert to normal over a period of hours. These observations suggest that workers in the FPI may have a defect in skin barrier function, which is, however, masked by a low skin temperature, resulting in misleadingly low TEWL levels during work. To test this hypothesis, we disrupted the permeability barrier in hairless mice with topical acetone, and exposed the treated skin to ice for 3.5 h. Although TEWL rates immediately after cold exposure were low, suggesting normal barrier recovery, TEWL increased to levels slightly above pre-cold exposure levels (i.e. levels just after the barrier was disrupted with acetone) when the skin temperature reverted to normal (> or = 15 min). The changes in TEWL were paralleled by equivalent changes in percutaneous penetration of the electron-dense tracer lanthanum nitrate. This indicates that cold masks a defective barrier, and inhibits barrier repair. After a few hours at ambient temperatures, normal barrier recovery was observed. Electron microscopy revealed empty or partially empty lamellar bodies during the first 30 min post-cold exposure. After 1 h the majority of nascent LBs displayed normal morphology. Moreover, histochemical studies showed a delayed reappearance of stratum corneum intercellular lipids following cold exposure. These results demonstrate that cold exposure prevents barrier recovery after acetone disruption, and provide an explanation for the occupational dermatosis observed in the fish-processing industry and related occupations.

Acetone↗

PubMed1995

T lymphocyte chemotaxis and skin diseases.

Recent advances in our understanding of the mechanisms of T lymphocyte motility and chemotaxis, particularly in aspects of lymphocyte-endothelial adhesion, transendothelial cell migration, and T-lymphocyte response to chemotactic gradients have contributed to our knowledge of how T lymphocytes accumulate during the initiation, the development and the control of inflammatory skin responses. In this review, we will summarize the present situation of studies on T lymphocyte adhesion and chemotaxis. The 3 major steps in T lymphocyte chemotaxis, e.g., recognition of extracellular chemotactic gradients, transduction into appropriate intracellular signals, and generation of motion, will be outlined. Skin-homing T lymphocytes, chemokines and other chemoattractants will also be discussed in relation to skin diseases.

Animals↗

PubMed1995

Chemotaxis of human osteoblasts. Effects of osteotropic growth factors.

The in vitro chemotactic response of human osteoblasts was investigated towards the following growth factors: TGF-beta, PDGFs, FGFs and IGFs. Human osteoblasts grown from trabecular bone after enzymatic digestion were studied. TGF-beta stimulated the migration of human osteoblasts in a dose-dependent manner with a four-fold increase in migrated cells at 100 pg/ml, which was the optimum concentration. PDGF-BB also stimulated migration four-fold in a dose-dependent manner with a maximum response at 10 ng/ml. PDGF-AA, IGF-I and IGF-II stimulated migration two-fold at 100 ng/ml. The results show that TGF-beta and PDGF-BB are important regulators of human osteoblast migration, but other growth factors IGF-I, IGF-II and PDGF-AA may also stimulate osteoblast migration. Our results additionally suggest that TGF-beta and PDGF-BB may participate in the recruitment of osteoblasts during bone remodeling since both TGF-beta and PDGF-BB are found in bone matrix and could be released during osteoclastic bone resorption. They furthermore support a possible use of TGF-beta and PDGF-BB in growth factor-induced osteogenesis.

Cells, Cultured↗

PubMed1995

[Cytokines and skin diseases].

Many skin diseases such as eczema and psoriasis are characterised by a chronic inflammatory skin condition. In this respect they resemble other chronic diseases such as rheumatoid arthritis, bronchial asthma, ulcerous colitis and Crohn's disease. A persistent accumulation, predominantly of T-lymphocytes constitutes the central pathophysiological feature of such diseases. The past 15-20 years have witnessed the characterisation of an extensive series of peptides known as cytokines. These are soluble, relatively low molecular weight peptides which at low concentrations mediate regulation of cellular receptors, new phenotype expression, secretion and migration. Many cytokines have been found to be present in conjunction with skin diseases, and it is suggested that they are involved in the development of inflammation.

CD4-Positive T-Lymphocytes↗

PubMed1994

In vitro genetically aberrant T-cell clones with continuous growth are associated with atopic dermatitis.

Atopic dermatitis is a disease with a genetic predisposition affecting the immune system, with T lymphocytes participating in the immune dysregulation. Most in vitro T lymphocyte studies of atopic dermatitis have focused on antigen-specific T-cell clones. However, antigen-non-specific regulatory T lymphocytes may also take part in the pathway leading to antigen-specific clonal T-lymphocyte proliferation. T lymphocytes from skin biopsy specimens from three patients with severe atopic dermatitis were cultured in the presence of IL-2 and IL-4, but without antigen added. Initially, proliferation was oligo- or polyclonal, but in all cases overgrowth by T cells with clonal chromosomal aberrations was subsequently observed. These abnormal T-cell clones demonstrated continuous growth and complete or partial phenotypic loss of the T-cell antigen receptor complex. In summary, these findings suggest that a subset of aberrant skin-homing T lymphocytes is associated with atopic dermatitis.

Adult↗

PubMed1994

Genotraumatic T cells and cutaneous T-cell lymphoma. A causal relationship?

Mycosis fungoides, or cutaneous T-cell lymphoma (CTCL), is a T-cell mediated chronic inflammatory skin disease, which can occasionally progress with a variable time course to a fatal lymphoma or to a leukaemic form called Sézary's syndrome. Extensive research into CTCL has not yet elucidated the primary pathophysiological mechanisms. Immunohistological studies are so far less helpful than expected in establishing early diagnosis and prognosis of the disease. The proposition that an exogenous virus is the cause of CTCL has not been substantiated. Karyotypic analysis of lymphocytes from the skin and blood of patients with CTCL have shown the existence of several genetically aberrant T-cell clones in the same patient. These changes are discussed as potential primary events for the development of CTCL. The hypothesis is put forward that the development of genotraumatic T lymphocytes is involved in the progression of the disease.

Clone Cells↗

PubMed1994

Lysophosphatidylcholine: a chemoattractant to human T lymphocytes.

Various cell stimuli act through activation of phospholipase A2 resulting in the release of arachidonic acid, the precursor of eicosanoids, from the sn-2 position of cell membrane phospholipids. A byproduct of phospholipase A2 activity is the lysophospholipids which have been found to potentiate T-lymphocyte activation. The purpose of the present study was to determine whether the various lysophospholipids modulate the migration of peripheral normal human T lymphocytes in vitro. It was found that lysophosphatidylcholine (lysoPC) induced T-lymphocyte migration in the concentration range 10(-7) to 10(-4) M with a maximum at 10(-6) M (mean chemotactic index, 2.06). The migration was due to chemotaxis rather than chemokinesis. In contrast, lysophosphatidylethanolamine (lysoPE) and lysophosphatidylinositol (lysoPI) did not exhibit chemotactic properties towards T lymphocytes. Further studies showed that the length of the fatty acids in the sn-1 position as well as the presence of double bonds modulated the chemotactic ability. The lysoPC compound with the highest chemotactic activity was lysoPC;1-palmitoyl (C = 16:0). The results demonstrated that lysoPC, a phospholipase A2-generated hydrolysis product of phosphatidylcholine, induced T-lymphocyte chemotaxis in vitro. Because phosphatidylcholine is the major phospholipid in the epidermis, the activation of phospholipase A2 may result in the release of lysoPC in concentrations capable of inducing migration of T lymphocytes into the epidermis.

Chemotactic Factors↗

PubMed1994

Interleukin-8 secretion and 15-lipoxygenase activity in rheumatoid arthritis: in vitro anti-inflammatory effects by interleukin-4 and interleukin-10, but not by interleukin-1 receptor antagonist protein.

We have examined the ability of interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-1 receptor antagonist protein (IL-1ra) to regulate spontaneous interleukin-8 (IL-8) production in cultured SF mononuclear cells (SFMC) from RA. Furthermore, we examined whether IL-4, IL-10, or IL-1ra could influence the production of the arachidonic acid products leukotriene B4 (LTB4), 12-hydroxy-eicosatetraenoic acid (12-HETE) and 15-hydroxy-eicosatetraenoic acid (15-HETE). IL-4 induced a maximal suppression of 75% in the IL-8 secretion in SFMC from 10.0 ng/ml down to 2.5 ng/ml after 24 h and from 17.2 ng/ml to 4.2 ng/ml after 72 h of culture. IL-10 induced a 55% inhibition of the IL-8 secretion at 24 h and a 40% inhibition at 72 h. IL-1ra did not change the spontaneous IL-8 secretion from rheumatoid SFMC. We also examined, whether addition of IL-4, IL-10 or IL-1ra was able to modulate formation of the arachidonic acid products LTB4, 12-HETE and 15-HETE in cultured SF cells, stimulated with the calcium ionophore A23187. 15-HETE was not detected in untreated cultures, nor in IL-10 or IL-1ra treated cultures. IL-4, however, stimulated the formation of the anti-inflammatory mediator; 15-HETE (23 ng/10(6) cells). These results suggest that IL-4 or IL-10, could have beneficial anti-inflammatory effects in RA.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1994

Estimates of nuclear volume in plaque and tumor-stage mycosis fungoides. A new prognostic indicator.

It is well documented that mycosis fungoides (MF), a cutaneous T-cell lymphoma, has a variable clinical course. Unbiased stereological estimates of three-dimensional volume-weighted mean nuclear size (nucl vV) of mycosis cells were obtained in a retrospective study of 18 patients with a total of 34 biopsies of cutaneous plaque and tumor-stage MF. The value of nucl vV in the first sampled biopsy, as well as the average and highest values, were determined in biopsies from each patient. The patients were divided into two groups, either above or below the group median. There was a strong positive correlation between shorter survival and an average value of nucl vV > 104 microns 3 or a highest value of nucl vV > 126 microns 3 (2p = 0.002 and 0.003, respectively). A nucl vV > 91.6 microns 3 in the first biopsy was also suggestive of a shorter survival (2p = 0.07). There was no clear pattern of nucl vV evolution in the patients with multiple biopsies, but the impact of various therapeutic regimens cannot be assessed. Certain estimates of nucl vV appear to be good prognostic indicators in plaque and tumor-stage MF, but further study of a larger series of patients is needed to corroborate these results and assess the impact of differing therapeutic regimes.

Adult↗

PubMed1994

Interferon therapy for atopic dermatitis reduces basophil histamine release, but does not reduce serum IgE or eosinophilic proteins.

Nine adult patients suffering from severe atopic dermatitis (AD) and increased total serum IgE were treated with recombinant human interferon-alpha 2A (Roferon-AR; IFN-alpha-2A) 3 x 10(6) units daily for 21 d to study the effect upon serum IgE, basophil histamine release (HR), eosinophil-derived proteins in serum, and clinical symptoms. The skin disease was so severe that all patients needed topical treatment with glucocorticosteroid cream. Changes were not observed in total serum IgE or in eosinophil-derived proteins, the latter being increased in six of nine patients. A significant reduction in basophil HR was found in six of nine patients after anti-IgE and concanavalin A (Con A) stimulation, but not after A23187 stimulation. The clinical skin score was reduced in eight of nine patients at the end of therapy, but disease activity returned to pretreatment levels within 3 weeks despite continued topical treatment. rIFN-alpha-2A was well tolerated with few clinical side-effects, and all patients completed the study. The short-term therapy using IFN-alpha-2A neither brought a sustained clinical remission nor reduced total serum IgE or eosinophil-derived proteins. However, a significant reduction in IgE-receptor-mediated basophil HR was observed in six of nine patients.

Adolescent↗

PubMed1994

Changes in cellular immune function after immune specific guided imagery and relaxation in high and low hypnotizable healthy subjects.

This article presents the results of two investigations, each measuring cellular immune function on 3 investigation days 1 week apart in 15 high and 15 low hypnotizable healthy subjects randomly selected for three groups: (1) a guided imagery group receiving instructions to enhance cellular immune function: (2) a relaxation group which did not receive instructions regarding the immune system, and (3) a control group. Study 1 investigated changes in monocyte chemotaxis (MC) and lymphocyte proliferative response (LPR) to three mitogens, while natural killer cell activity (NKCA) was measured in study 2. The results show similar patterns of brief decreases in LPR and NKCA immediately after intervention on all investigation days in both the imagery and relaxation groups. Increases in MC were found in both intervention groups on day 1. On a follow-up investigation day in study 2, a brief stress task yielded a slight increase in NKCA. In study 2, the control group showed decreases in NKCA similar to those observed in the two intervention groups. In general there were no significant changes in preintervention immune function throughout the investigation period. When comparing the effects in high and low hypnotizable subjects, we found that high hypnotizables showed greater decreases in LPR and NKCA than low hypnotizables. There are several inconsistencies between the results of the limited number of investigations studying the effects of guided imagery and relaxation on immune function. These differences may in part be explained by differences in methodology, time intervals between blood sampling, and subject characteristics such as age, health status and hypnotizability. The inconsistent results make it premature to make inferences about possible benefits of the application of these techniques in the treatment of immune related diseases, and further investigations are needed.

Adolescent↗

PubMed1994

Nickel patch test reactivity and the menstrual cycle.

Premenstrual exacerbation of allergic contact dermatitis and varying allergic patch test responses have been reported at different points of the period. Using a dilution series of nickel sulphate, we studied the variation in patch test reactivity in nickel allergic women in relation to the menstrual cycle. Twenty women with regular periods were tested on day 7-10 and on day 20-24. Ten nickel patch tests with different concentrations were applied using the TRUE test assay, and the threshold concentration of nickel sulphate eliciting an erythematous reaction was determined. Half of the women were tested first on day 7-10 and the other half first on day 20-24. There was no difference in the degree of patch test reactivity, when the results from day 7-10 and day 20-24 were compared (p > 0.4). However, when we compared the patch test results from the first and second test procedure, we found an increased nickel sensitivity at the second patch test (0.02 < p < 0.05), suggesting a booster effect from the first patch test procedure. In conclusion, we could not demonstrate an increased sensitivity to nickel sulphate patch tests premenstrually in 20 nickel allergic women, but we found that elicitation of positive patch tests led to an increased skin reactivity towards the same allergen, when the patients were retested weeks later.

Adolescent↗

PubMed1994

Toxic epidermal necrolysis and erythema multiforme following therapy with terbinafine.

We report two cases with severe skin reactions following oral terbinafine (Lamisil) therapy. The first case was a 49-year-old woman with onychomycosis of the toe nails. She had suffered from diabetes for 3 years, but it was well controlled on insulin. Five days after start of terbinafine 250 mg once daily she developed erythema. The treatment was continued for 2 days, but the skin eruption progressed, and a clinical diagnosis of toxic epidermal necrolysis was confirmed histologically. The second case was a 51-year-old woman with dermatomycosis on the right foot. She developed a papular eruption in the second week after taking terbinafine 250 mg once daily. Despite this eruption she continued treatment for 6 days. Generalized erythema multiforme developed in the following days. Terbinafine is a recently introduced efficacious fungicidal drug. This is the first report of toxic epidermal necrolysis following terbinafine.

Administration, Oral↗

PubMed1994

Long-term topical nitrogen mustard treatment does not induce pulmonary fibrosis in MF patients.

Eleven patients with mycosis fungoides had X-ray examinations of their lungs before, during and after topical treatment with mechlorethamine. The mean number of treatments was 163, ranging from 28 to 300 treatments within a period of 1 to 13 years (mean 7.8 years). Each exposure to the skin of mechlorethamine was between 20 and 40 mg giving a cumulative dosage in the range from 1.120 mg to a maximum of 12.000 mg. We looked for potential lung damage from mechlorethamine vapours, such as fibrosis of the lungs, but found none. Thus, we conclude that topical treatment with mechlorethamine of patients with mycosis fungoides is not only an effective treatment, but also a safe therapy.

Administration, Cutaneous↗

PubMed1994

Cytogenetic findings in cell lines from cutaneous T-cell lymphoma.

Cytogenetic analysis of some patients with CTCL demonstrates the presence of more than one cytogenetically aberrant clone in a given patient. These findings lead us to suggest that CTCL is defined by a family of "genotraumatic" T cells. A genotraumatic T cell, unlike a normal T lymphocyte, is defined by its ability to develop clonal, cytogenetically visible chromosome aberrations. Based on this hypothesis, an investigation was performed in detail of cell lines from the plaques and blood of a patient with MF. Several genotraumatic T cells could be demonstrated. Of particular interest was the establishment of two continuous T-cell lines from a single plaque. Both genotraumatic T-cell lines were genetically unstable, and multiple and complex chromosome aberrations could be demonstrated in both cell lines, suggesting that two potentially malignant T-cell clones exist in a single plaque. It is proposed that CTCL is defined by a family of genotraumatic T cells and is thus, in principle, oligoclonal or polyclonal. All genotraumatic T cells may be considered cancer prone because of their ability to develop clonal chromosomal aberrations. A genotraumatic T cell is per se not malignant, but owing to its genetic instability, it may develop into a tumor cell. This could explain how an apparent benign disorder, CTCL, occasionally may progress into malignant lymphoma.

Chromosome Aberrations↗

PubMed1993

Human IL-10 is a chemoattractant for CD8+ T lymphocytes and an inhibitor of IL-8-induced CD4+ T lymphocyte migration.

Human IL-10 (hIL-10) is a newly described cytokine that was originally identified as a cytokine synthesis inhibitory factor regulating the production of several pro-inflammatory cytokines such as IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF-alpha, and IFN-gamma. Additionally, hIL-10 also inhibits the macrophage-dependent proliferative response of CD4+ T lymphocytes to Ag stimulation, and it down-regulates the constitutive class II MHC expression on human monocytes. We report hIL-10 to be a potent and specific chemotaxin for human T lymphocytes with optimum activity in the range between 10 and 100 U/ml. Checkerboard analysis shows the activity to be chemotactic and not chemokinetic. The chemotactic activity is directed toward CD8+ T lymphocytes and not towards CD(4+)-enriched cells. Also, hIL-10 lacks chemotactic activity toward human monocytes or neutrophil granulocytes. Further, we found that hIL-10 inhibits the chemotactic response of CD4+, but not CD8+, T cells toward IL-8. Because hIL-10 can be produced by several cells including CD4+ T cells of the Th2 type, our results suggest that hIL-10 participates in a complex regulatory circuit between CD4+ and CD8+ T cells with implications for the control of lymphocyte-mediated inflammatory responses.

CD4-Positive T-Lymphocytes↗

PubMed1993

[Fulminant acne].

We describe a case of a 16-year old boy, who presented with sudden onset of an extreme pustular reaction in seborrhoeic areas of the skin with accompanying general malaise such as fever and arthralgia. This picture is one of fulminant acne, which is a rare disease, for which reason diagnosis may be delayed. Permanent scarring of the skin is inevitable, but scarring may be reduced if early treatment with 13 cis-retinoid is started.

Acne Vulgaris↗