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Biomedical subjects

L Kemeny

Publications and source records attributed to L Kemeny.

14 recordsLinked to original sources

Endogenous phospholipid metabolite containing topical product inhibits ultraviolet light-induced inflammation and DNA damage in human skin.

BACKGROUND: N-palmitoylethanolamine (PEA) and organic osmolytes are endogenous components of the human epidermis and are generated from phospholipids in the stratum granulosum. PEA has been shown to exert potent antioxidant and anti-inflammatory activities. The endogenous organic osmolytes such as betaine and sarcosine control skin humidity, but have also been shown to inhibit ultraviolet (UV) light-induced oxidative stress in keratinocytes. OBJECTIVES: To investigate the effect of a PEA- and organic osmolyte-containing topical product (Physiogel AI) on the development of UV light-induced erythema, thymine dimer formation and p53 tumor suppressor gene activation, as well as intercellular adhesion molecule 1 (ICAM-1) and Ki67 expression in normal human skin. METHODS: The UV-induced erythema was measured by a spectrofluorometric method. Thymine dimers, p53, ICAM-1 and Ki67 were detected in skin biopsies using immunohistochemistry. RESULTS: Physiogel AI cream significantly inhibited the development of UV light-induced erythema and thymine dimer formation in normal human skin, but did not alter the number of Ki67+ proliferating keratinocytes and the expression of p53 and ICAM-1. CONCLUSIONS: Our results suggest that PEA and organic osmolytes might represent a new generation of compounds which suppress UV-induced photodamage.

Administration, Cutaneous↗

Repeated epicutaneous exposures to ovalbumin progressively induce atopic dermatitis-like skin lesions in mice.

BACKGROUND: Atopic dermatitis (AD) is a chronic skin disease in which environmental factors play a great role. A widely used murine model for AD has provided a useful tool to study the disease. OBJECTIVE: The purpose of this study is to investigate kinetically the induction of this AD model and the processes involved in the development of AD due to extrinsic allergen exposures. METHODS: BALB/c mice were epicutaneously exposed to ovalbumin (OVA) for 3 weeks; each week was separated by a 2-week resting period. Mice were killed after each exposure week. Skin biopsies and blood were obtained for histological study, RNA isolation and antibody analysis. RESULTS: There was a progressive and significant thickening of the epidermis and dermis in OVA-exposed mice. Significantly increased dermal cell infiltration of eosinophils, mast cells and total inflammatory cells, including CD3 and CD4 cells, was found after each OVA exposure week. Total IgE, IgG2a and OVA-specific IgE were significantly increased after the second and third exposure week, while OVA-specific IgG2a was significantly induced after the third exposure week. Gradual and/or significant increases in mRNA expression of IL-1beta, TNF-alpha, IL-4, IL-10, IL-13, IFN-gamma and IL-12p35 were found after each exposure week. Chemokines and their receptors involved in both T-helper type 1 (Th1)- and Th2-type cell recruitment (CCL1, CCL8, CCL11, CCL24, CXCL9, CXCL10, CCR1, CCR3, CCR5, CCR8 and CXCR3) were up-regulated significantly at different time-points. CONCLUSION: This study provides an insight into the dynamic nature and time-dependent transition of skin inflammation and systemic immune responses in a murine AD model induced by repeated epicutaneous exposures to OVA.

Allergens↗

Current state and perspectives of dendritic cell vaccination in cancer immunotherapy.

Recent progress in the approach towards immunotherapy of cancer consists in molecular definition of tumor antigens, new tools for phenotypical and functional characterization of tumor-specific effector cells and clinical use of novel adjuvants for optimal stimulation of a cancer-specific immune response such as dendritic cells. In spite of these advances and immunological as well as clinical responses in selected patients, mechanisms involved in dendritic-cell-based cancer immunotherapy are still poorly understood. Therefore, a standardized study design and small pilot trials are needed to explore open scientific questions in future clinical trials. This review focuses on the different parameters of dendritic cell biology relevant to cancer immunotherapy and on innovative approaches to hopefully enhance the efficacy of dendritic cell vaccination.

Animals↗

Budesonide, but not tacrolimus, affects the immune functions of normal human keratinocytes.

Topical immunosuppressant therapy is widely used in the treatment of inflammatory skin diseases such as psoriasis and atopic dermatitis. Besides its beneficial therapeutic effects, application of topical anti-inflammatory drugs may render the epidermis more vulnerable to invading pathogens by suppressing innate immune responses in keratinocytes, such as cytokine production and Toll-like receptor (TLR) expression. In order to evaluate and compare the immunosuppressive effects of different immunosuppressant drugs on keratinocytes, we treated lipopolysaccharide (LPS)-stimulated and -unstimulated normal human keratinocytes with the synthetic corticosteroid budesonide and the macrolide tacrolimus. The expressions of the pattern recognition receptors (PRRs) TLR2 and TLR4 were measured by quantitative RT-PCR, pro-inflammatory cytokines IL-1alpha, IL-8 and TNF-alpha were monitored by quantitative RT-PCR and by ELISA, and alterations in TLR2 protein level were measured by flow cytometry. Budesonide had a suppressive effect on both constitutive and LPS-induced IL-8 gene expression. The amount of TNF-alpha mRNA was diminished in unstimulated keratinocytes, while TLR2 mRNA expression was markedly enhanced both in unstimulated and LPS-treated cells after incubation with budesonide. This increase in TLR2 mRNA expression was also detectable at the protein level in LPS-stimulated cells. Tacrolimus had no effect on any of the examined genes. Budesonide, but not tacrolimus, significantly inhibited the NF-kappaB-dependent luciferase reporter activity in HaCaT cells after induction with LPS or TNF-alpha. Although tacrolimus and budesonide are both effective treatments in some inflammatory skin diseases, the data provided here imply differences in local therapeutic and adverse effects of these two topical immunosuppressants.

Anti-Inflammatory Agents↗

Review of the potential photo-cocarcinogenicity of topical calcineurin inhibitors: position statement of the European Dermatology Forum.

Topical Calcineurin Inhibitors (TCIs) used for the treatment of atopic eczema modify the immune regulatory function of the skin and may have the potential to enhance immunosuppressive ultraviolet (UV) effects. Current recommendations on UV protection in eczema patients treated with PCIs are inconsistent and have given rise to uncertainty and anxiety in patients. Therefore, the European Dermatology Forum (EDF) developed a position statement which reviews critically the available data with regard to the problem, especially analysing and commenting the limitations of rodent models for the human situation. There is no conclusive evidence from rodent trials to indicate that long-term application of TCIs is photococarcinogenic. There is a need for further studies to investigate the validity of mouse models as well as long-term cohort studies in patients using TCIs. Available data suggest that long-term application of TCIs is safe, that there is no evidence of increased skin cancer risk and that it is ethical to treat patients with TCIs when indicated.

Administration, Topical↗

FK506 in the treatment of inflammatory skin disease: promises and perspectives.

The immunosuppressive macrolide drug FK506 is currently gaining increasing importance in dermatopharmacology. Here, Gunter Michel and colleagues summarize the current state of research into the molecular mechanisms responsible for the functional modulation of cell types other than T cells, particularly epidermal cells, by this drug.

Animals↗

Alpha-melanocyte stimulating hormone induces collagenase/matrix metalloproteinase-1 in human dermal fibroblasts.

Recent reports have suggested that alpha-melanocyte stimulating hormone (alpha-MSH) plays an important role in untraviolet (UV) irradiation mediated skin changes including pigmentation, inflammation and connective tissue damage. alpha-MSH synthesis has been found to be induced in human keratinocytes following UV irradiation. In order to test the hypothesis whether UV induced alpha-MSH - via a paracrine loop - regulates the synthesis and the activity of collagenase/MMP-1, we studied the effects of alpha-MSH on the expression of MMP-1 and its tissue inhibitor of matrix metalloproteinases (TIMP-1). Confluent human dermal fibroblast cultures from foreskin biopsies of healthy human donors were treated with 10(-5)M, 10(-8)M and 10(-11)M alpha-MSH for 30 min. As determined by Northern blot analysis 10(-5)M and 10(-8)M alpha-MSH dose- and time-dependently induced steady state levels of MMP-1 mRNA up to 9-fold compared to untreated controls. TIMP-1 mRNA steady state levels were also slightly induced, however, the increased MMP-1/TIMP-1 ratio when normalized to beta-actin reflected an unbalanced synthesis. MMP-1 protein expression was studied with an immunofluorescence technique using a monoclonal antibody against MMP-1. After alpha-MSH treatment an increased number of fibroblasts revealed an intense perinuclear staining pattern compared to the less intense staining of control fibroblasts. The overall collagenolytic activity of supernatants from alpha-MSH treated fibroblasts was increased by 35%. Our data support the view that UV induced alpha-MSH - by the stimulation of collagenase/MMP-1 - may contribute to the loss of interstitial collagen related to cutaneous photoaging.

Cell Extracts↗

[Psoriasis arthropathica].

BACKGROUND: Five to seven percent of patients with psoriasis suffer additionally from accompanying arthritis. AIM OF THE STUDY: In this article, we review the current knowledge on clinical, diagnostic and therapeutic aspects of the disease. PATIENTS AND RESULTS: Data are presented on the treatment of six patients with the immunosuppressant ciclosporin. Therapeutic results with this drug are superior to agents traditionally used for management of psoriatic arthritis. CONCLUSION: The therapeutic options have been enlarged by the introduction of new immunosuppressive drugs, particularly ciclosporin.

Adolescent↗

Fitness promotion for adolescent girls: the impact and effectiveness of promotional material which emphasizes the slim ideal.

This study looks at techniques for promoting fitness participation among adolescent girls, in particular those which emphasize the "slim ideal." Various promotional posters were designed which systematically used different models (slim, average, and overweight) and different messages (slimness, activity, and health). The relative effectiveness of these posters was tested using a probability sample of 627 female high school students. The slim model was found to be the most effective poster, while slimness was the least effective of the messages. Demographic and self- and body-image factors had relatively little effect on the ratings of the posters. Focus group interviews conducted with the student sample indicated that they were concerned about their body weight, and that they associated slimness with fitness. However, the slimness message was not thought to encourage participation in fitness because overt emphasis on body image may lead to self-consciousness and fear of social rejection. The idea that participation would lead to a slim physique was also thought to be unrealistic. The students were more critical of the slimness message than of the slim model in the posters. Overall, the data indicate that promoting fitness through messages relating fitness to slimness is not an effective approach with adolescent girls. The use of very slim models in promotional material may be effective, but this approach may not be desirable because it reinforces the dominant cultural stereotype of the "ideal" slim female form.

Adolescent↗

Isolation of herpesvirus from equine leukocytes: comparison with equine rhinopneumonitis virus.

An agent which possessed the properties of herpesviruses was isolated from the leukocytes of 71 out of 80 (88.7%) apparently normal Iowa horses. It was ether- and heat-sensitive, DNA type, and produced type-A intranuclear inclusion bodies in cell cultures. Electron micrographs revealed a virion of typical herpesvirus structure. Leukocyte isolate virus could be differentiated from equine rhinopneumonitis virus (ERV) by serum neutralization, by growth differences in rabbit kidney cells, and by fluorescent antibody staining. Specific neutralizing antibody against this agent was found in a pooled serum sample from normal horses and in the serums of herpesvirus carrier horses. Serum from a mare inhibited growth of both ERV and leukocyte viral isolates. Normal sheep, calf, and rabbit serum did not neutralize either virus.

Animals↗