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Biomedical subjects

Thomas A Luger

Publications and source records attributed to Thomas A Luger.

At least 37 records · Page 2Linked to original sources
PubMed2005

[Sunprotection: possibilities and limitations].

Protection against ultraviolet (UV) irradiation prevents from the development of acute skin damage such as erythema formation and chronic skin changes such as premature skin ageing. Especially those sunscreens with higher sun protection factors do not only protect against solar dermatitis but also inhibit UV-induced immunosuppression by blocking the release of immunosuppressive mediators from UV-exposed epidermis. In particular, the protection against UV-induced immunosuppression by sunscreens is supposed to reduce the development of UV-induced skin cancer. Besides immunosuppression UV-irradiation is also able to induce "UV signature" mutations within UV-exposed DNA. Topical application of DNA repair enzymes induces nucleotide excision repair and corrections of DNA damages. Thereby, the risk to develop UV-induced skin malignancies is markedly reduced. Accordingly, future perspectives in the development of sunscreens include DNA repair enzymes or factors, which can induce the endogenous cellular DNA repair system. Until these developments come to practice reasonable sun protection according to the skin complexion is of primary importance.

Clinical Trials as Topic↗
PubMed2005

Pathway management in ambulatory wound care: defining local standards for quality improvement and interprofessional care.

Growing health care costs and changes in health care delivery, such as the adoption of the diagnosis-related groups, have tremendously affected treatment patterns all over the world. Pathway management is suitable to be responsive to the growing operating requirements and to manage effective and efficient medical care in hospitals. Pathways standardise clinical processes for patients with a similar diagnosis, procedure or symptom thereby optimising the quality of treatment and patient satisfaction. They are utilised by a multidisciplinary team with a primary focus on quality and coordination of care. Considering the key strategies of pathway management, an interprofessional team containing physicians and nurses developed and implemented a clinical pathway for ambulatory treatment of chronic wounds. A precise medical protocol was created to standardise routine procedures, to improve the treatment outcome and to provide an integrated documentation that enhances interprofessional collaboration. We designed a modular concept of four different sheets which provide pre-defined standards: (a) medical admission, (b) findings and history, (c) topic and systemic treatment and (d) evaluation of outcome criteria. Variances must be merely written down in detail. After 1 year in clinical practice, we state that the use of a clinical pathway for chronic wound management is an effective method of improving clinical processes and patient outcomes.

Ambulatory Care↗
PubMed2005

Proteinase-activated receptors: transducers of proteinase-mediated signaling in inflammation and immune response.

Serine proteinases such as thrombin, mast cell tryptase, trypsin, or cathepsin G, for example, are highly active mediators with diverse biological activities. So far, proteinases have been considered to act primarily as degradative enzymes in the extracellular space. However, their biological actions in tissues and cells suggest important roles as a part of the body's hormonal communication system during inflammation and immune response. These effects can be attributed to the activation of a new subfamily of G protein-coupled receptors, termed proteinase-activated receptors (PARs). Four members of the PAR family have been cloned so far. Thus, certain proteinases act as signaling molecules that specifically regulate cells by activating PARs. After stimulation, PARs couple to various G proteins and activate signal transduction pathways resulting in the rapid transcription of genes that are involved in inflammation. For example, PARs are widely expressed by cells involved in immune responses and inflammation, regulate endothelial-leukocyte interactions, and modulate the secretion of inflammatory mediators or neuropeptides. Together, the PAR family necessitates a paradigm shift in thinking about hormone action, to include proteinases as key modulators of biological function. Novel compounds that can modulate PAR function may be potent candidates for the treatment of inflammatory or immune diseases.

Amino Acid Sequence↗
PubMed2005

[Introduction of quality management with the EFQM Self-Assessment method. Implementation and experience in a university department of dermatology].

In the near future, the German legislative and health insurance agencies will increasingly demand proof of quality in hospital health care. The role of quality management in hospitals is emphasized by the introduction of per-case payment (DRG) in Germany. The implementation of internal quality management at an early stage sets the course of a systematic and continuous quality improvement process, with the goal to increase performance and results by efficient utilization of resources. The decision for or against one or another quality management model appears to be difficult, since the possible impacts of the quality management system can hardly be foreseen. As this article shows, the Self-Assessment method of the European Foundation for Quality Management (EFQM) provides a valuable and efficient tool to introduce quality management in a hospital environment. The Self-Assessment method enables a systematic survey of levels of performance and outcome of the hospital. Furthermore, it provides an appropriate basis to identify areas of strengths and weaknesses. A high degree of motivation of the personnel is fostered by the creation of a local guidance circle, a coordinating group, and several Self-Assessment teams. However, formulation and deployment of improvement actions are necessary for the long-term implementation of quality management. The application of Self-Assessment in quality management appears a suitable tool to promote excellence.

Dermatology↗
PubMed2004

alpha-Melanocyte-stimulating hormone protects from ultraviolet radiation-induced apoptosis and DNA damage.

Ultraviolet radiation is a well established epidemiologic risk factor for malignant melanoma. This observation has been linked to the relative resistance of normal melanocytes to ultraviolet B (UVB) radiation-induced apoptosis, which consequently leads to accumulation of UVB radiation-induced DNA lesions in melanocytes. Therefore, identification of physiologic factors regulating UVB radiation-induced apoptosis and DNA damage of melanocytes is of utmost biological importance. We show that the neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) blocks UVB radiation-induced apoptosis of normal human melanocytes in vitro. The anti-apoptotic activity of alpha-MSH is not mediated by filtering or by induction of melanin synthesis in melanocytes. alpha-MSH neither leads to changes in the cell cycle distribution nor induces alterations in the expression of the apoptosis-related proteins Bcl(2), Bcl(x), Bax, p53, CD95 (Fas/APO-1), and CD95L (FasL). In contrast, alpha-MSH markedly reduces the formation of UVB radiation-induced DNA damage as demonstrated by reduced amounts of cyclobutane pyrimidine dimers, ultimately leading to reduced apoptosis. The reduction of UV radiation-induced DNA damage by alpha-MSH appears to be related to induction of nucleotide excision repair, because UV radiation-mediated apoptosis was not blocked by alpha-MSH in nucleotide excision repair-deficient fibroblasts. These data, for the first time, demonstrate regulation of UVB radiation-induced apoptosis of human melanocytes by a neuropeptide that is physiologically expressed within the epidermis. Apart from its ability to induce photoprotective melanin synthesis, alpha-MSH appears to exert the capacity to reduce UV radiation-induced DNA damage and, thus, may act as a potent protection factor against the harmful effects of UV radiation on the genomic stability of epidermal cells.

Apoptosis↗
PubMed2004

Cutaneous allergic contact dermatitis responses are diminished in mice deficient in neurokinin 1 receptors and augmented by neurokinin 2 receptor blockage.

Sensory neuropeptides such as neurokinin A (NKA) or particularly substance P (SP) by neurokinin receptor (NK-R) activation modulate skin and immune cells functions during neurogenic inflammation. In this study, we examined the relative importance of SP/NK-1Rs or NKA/NK-2Rs in a murine model for allergic contact dermatitis (ACD) and tested if the functional absence of NK-Rs will impair inflammatory response in vivo. Mice lacking NK-1Rs (C57BL/6J-NK-1R-/-) displayed a significantly reduced ACD inflammatory ear swelling response to dinitrofluorobenzene (DNFB) with histological less edema and 50% fewer infiltrating leukocytes compared with the ACD response in wild-type (+/+) animals. In NK-1R+/+ mice, transient NK-1R inhibition impaired ACD sensitization. In vitro haptenized bone marrow-derived dendritic cells from NK-1R+/+ mice matured in the presence of an NK-1R antagonist displayed a reduced capability to induce T cell proliferation in vitro and ACD after adoptive transfer into naïve wild-type mice in vivo. By contrast, NK-2R inhibition significantly enhanced the ACD response in NK-1R null or in wild-type mice, whereas epicutaneous application of NK-2R agonists diminished the ACD inflammation. In conclusion, NK-1R and SP are required for antigen sensitization and a full inflammatory response to cutaneous allergens and NKA and the NK-2R mediate a contrasting anti-inflammatory role in ACD. Thus, SP, NKA, NK-1R, and NK-2R have important but differential roles in the regulation of cutaneous inflammatory responses.

Animals↗
PubMed2004

L-FABP is exclusively expressed in alveolar macrophages within the myeloid lineage: evidence for a PPARalpha-independent expression.

Peroxisome proliferator-activated receptors (PPARs) play a role in inflammation and, in particular, PPARgamma is involved in monocyte/macrophage differentiation. Members of the fatty acid-binding protein (FABP) family have been reported to function as transactivators for PPARs. Therefore, the expression of PPARs and FABPs in the myeloid lineage was investigated by real-time PCR and immunofluorescence analysis. We found adipocyte-, epidermal-, and heart-type FABP to be ubiquitously expressed within the myeloid lineage. In contrast, liver-type FABP was exclusively detected in murine alveolar macrophages (AM), confirmed on protein level by double fluorescence analysis. The PPAR subtypes also showed a temporally and spatially regulated expression pattern in myeloid cells: the beta-subtype was expressed in bone marrow, peritoneal, and alveolar macrophages, whereas it was not detected in dendritic cells (DCs). The gamma1-isoform was present in all cells, however, at different levels, whereas the gamma2-isoform was expressed in alveolar macrophages and dendritic cells. A low level PPARalpha mRNA could be detected in peritoneal macrophages and immature dendritic cells but not in mature dendritic cells and bone marrow macrophages. Interestingly, PPARalpha mRNA was also absent in the alveolar macrophages although liver-type FABP was expressed, indicating that gene expression of liver-type FABP was independent of PPARalpha. Since liver-type FABP is known as transactivator of PPARgamma the simultaneous expression of both proteins may have general implications for the activation of PPARgamma in alveolar macrophages.

Animals↗
PubMed2004

Solar-simulated ultraviolet radiation-induced upregulation of the melanocortin-1 receptor, proopiomelanocortin, and alpha-melanocyte-stimulating hormone in human epidermis in vivo.

Ultraviolet light is one of the most crucial environmental factors with regard to its capacity to induce skin cancer, premature aging of the skin, and immunosuppression. Although ultraviolet directly affects the function of epidermal cells, many of these effects are mediated by induction of cytokines, growth factors, and neuropeptides, such as alpha-melanocyte-stimulating hormone. Recently, in addition to its well-known pigmentation inducing activity, a strong anti-inflammatory as well as an immunomodulatory potential of alpha-melanocyte-stimulating hormone has been recognized. The aim of this study was to determine, whether ultraviolet irradiation affects the expression of both alpha-melanocyte-stimulating hormone and the melanocortin-1 receptor in human epidermis in vivo. The volar aspects of the forearms were exposed to twice the minimal erythema dose of solar-simulating radiation. Three, 6, and 24 h after irradiation, the proopiomelanocortin and interleukin-10 mRNA levels in suction blister induced epidermal sheets were considerably upregulated as detected by semiquantitative reverse transcription-polymerase chain reaction. Furthermore, alpha-melanocyte-stimulating hormone and interleukin-10 protein levels in blister fluids were significantly increased 24 h after ultraviolet irradiation, an effect that could be abolished by application of the broad-spectrum sunscreen Anthélios XL prior to ultraviolet (solar-simulating radiation) exposure. In addition, enhanced melanocortin-1 receptor mRNA and receptor protein expression upon solar-simulating radiation was ascertained by reverse transcription-polymerase chain reaction and immunohistochemistry of the epidermal sheets, respectively. Proopiomelanocortin-derived neuropeptides, such as alpha-melanocyte-stimulating hormone may therefore play an important part in modulating ultraviolet-induced inflammation.

Adolescent↗
PubMed2004

[DRGs in dermatology: results of the DRG evaluation project of the German Society of Dermatology (DDG)].

SUMMARY BACKGROUND: The implementation of a DRG system in Germany--voluntarily since January 1st, 2003, and obligatory after January 1 st, 2004--has led to uncertainty, particularly in the hospitals. There are fears that current well-accepted German diagnostic and therapeutic services may not be properly financed by the new system. In response, the German Dermatologic Society (DDG) in cooperation with the DRG Research Group of the University Hospital Muenster and the German Medical Association carried out a DRG evaluation project in order to investigate the medical and economic homogeneity of the case groups. PATIENTS AND METHODS: 19,403 dermatological cases from 19 hospitals--ten university hospitals and nine non-university hospitals-were collected over a period of four months and then evaluated with regard to their performance, length of stay and cost homogeneity. RESULTS: The data provided the background needed to indicate suspected potential deficiencies for mapping dermatology cases within the German DRG system. Based on the data 10 modifications were formulated and submitted to the InEK by the deadline of March 31st, 2003. CONCLUSIONS: The results of the DRG Evaluation Project show that the G-DRG-Variant Version 1.0 does not offer the necessary possibilities of differentiation to map the broad spectrum of various dermatology services in Germany.

Cost-Benefit Analysis↗
PubMed2004

[G-DRG Version 2004: changes in view of dermatology].

In the year 2004 the obligatory introduction of the new hospital funding system based on a Diagnosis Related Groups (DRG) system will become reality for all German hospitals. After all fundamental items of the new G-DRG version were made generally known, the possible consequences had to be considered. The first mandatory German case-based lump sum catalogue differs importantly from the previous payment models and requires intensive study. Economic considerations will increasingly play a role in the daily routine of hospitals and influence treatment patterns. Therefore, comprehensive knowledge of basic principles of G-DRG is essential. In the following aspects of the reimbursement system with special relevance to dermatology are reviewed in detail. Additionally, the revised classification system versions OPS-301 SGB V and ICD-10-GM 2004 and the German coding standards version 2004 must be appropriately applied for dermatologic purposes.

Dermatology↗
PubMed2004

Expression of SOCS-1, suppressor of cytokine signalling-1, in human melanoma.

Cytokine resistance is a well-established feature of melanoma cell progression and represents also a major obstacle in immunotherapy of patients with metastatic melanoma. To check whether suppressors of cytokine signalling (SOCS) play a role in cytokine resistance and tumor progression of melanoma, we investigated the expression and regulation of SOCS-1, an established negative regulator of interleukin-6 (IL-6) and interferon (IFN) signalling. In vitro SOCS-1 transcripts were detectable by RT-PCR in 8 out of 8 human melanoma cell lines derived from different tumor stages. Normal human melanocytes also expressed SOCS-1 mRNA in the presence or absence of artificial growth factors. Both IL-6 and alpha-IFN induced rapid and transient SOCS-1 mRNA expression in WM35 and WM9 melanoma cells. At the protein level, SOCS-1 was undetectable in normal human melanocytes whereas uniformly expressed in all tested melanoma cell lines. The aberrant SOCS-1 protein expression in melanoma cells was recapitalized in situ as shown by immunohistochemical analysis. SOCS-1 immunoreactivity was closely related to tumor invasion (Clark level), tumor thickness according to Breslow, and stage of the disease. In contrast, melanocytes in normal skin or melanocytic nevi lacked SOCS-1 protein expression. Our findings show that melanoma cells express a member of the SOCS family, SOCS-1, in vitro and in situ. SOCS-1 is a progression marker of human melanoma and may downregulate biological responses by endogenous and/or therapeutically administered cytokines.

Antineoplastic Agents↗
PubMed2004

Expression of vanilloid receptor subtype 1 in cutaneous sensory nerve fibers, mast cells, and epithelial cells of appendage structures.

The vanilloid receptor subtype 1 (VR1)/(TRPV1), binding capsaicin, is a non-selective cation channel that recently has been shown in human keratinocytes in vitro and in vivo. However, a description of VR1 localization in other cutaneous compartments in particular cutaneous nerve fibers is still lacking. We therefore investigated VR1 immunoreactivity as well as mRNA and protein expression in a series (n = 26) of normal (n = 7), diseased (n = 13) [prurigo nodularis (PN) (n = 10), generalized pruritus (n = 1), and mastocytosis (n = 2)], and capsaicin-treated human skin (n = 6). VR1 immunoreactivity could be observed in cutaneous sensory nerve fibers, mast cells, epidermal keratinocytes, dermal blood vessels, the inner root sheet and the infundibulum of hair follicles, differentiated sebocytes, sweat gland ducts, and the secretory portion of eccrine sweat glands. Upon reverse transcriptase-polymerase chain reaction and Western blot analysis, VR1 was detected in mast cells and keratinocytes from human skin. In pruritic skin of PN, VR1 expression was highly increased in epidermal keratinocytes and nerve fibers, which was normalized after capsaicin application. During capsaicin therapy, a reduction of neuropeptides (substance P, calcitonin gene-related peptide) was observed. After cessation of capsaicin therapy, neuropeptides re-accumulated in skin nerves. In conclusion, VR1 is widely distributed in the skin, suggesting a major role for this receptor, e.g. in nociception and neurogenic inflammation.

Adolescent↗
PubMed2004

Melanocortins in fibroblast biology--current update and future perspective for dermatology.

The skin is a target organ and source for proopiomelanocortin (POMC)-derived peptides, such as alpha-melanocyte-stimulating hormone (alpha-MSH), which acts by binding to melanocortin receptors (MC-Rs). Recent progress in our understanding of the cutaneous POMC system has demonstrated that human dermal fibroblasts (HDFs) are a novel target for alpha-MSH. MC-1R is expressed by HDFs in vitro and in situ. MC-1R expression is also detectable in human connective tissue sheath fibroblasts (CTSFs) and in dermal papilla cells (DPCs) of the hair follicle, the latter concomitantly expressing MC-1R and MC-4R in vitro and in situ. Both HDFs and DPCs are capable of generating POMC-derived peptides, although cell-specific differences exist in the expression of prohormone convertases and the amounts of POMC-derived peptides generated. Functional studies have shown that alpha-MSH exerts anti-inflammatory actions in human fibroblastic skin cells by suppressing interleukin-1 (IL-1)-induced IL-8 production, activation of the transcription factor activator protein-1 (AP-1) and induction of intercellular adhesion molecule-1 by interferon-alpha. In addition, alpha-MSH antagonizes the effect of transforming growth factor-beta1 (TGF-beta1) on collagen synthesis in HDFs in vitro and exerts antifibrogenic activity in a mouse model of cutaneous fibrosis. These findings indicate that fibroblastic cells participate in the cutaneous POMC system in which alpha-MSH appears to act as a modulator of inflammatory and fibrogenic responses. The biological activities of alpha-MSH in fibroblastic cells of the skin point towards novel clues in our understanding of the pathophysiology of fibrotic skin disorders and inflammatory diseases of the hair follicle and, finally, suggest innovative therapeutic options for the treatment of these conditions.

Animals↗
PubMed2004

Neutral endopeptidase and angiotensin-converting enzyme -- key enzymes terminating the action of neuroendocrine mediators.

Zinc-metalloproteases, such as neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE), effectively control the bioavailability of peptide mediators released from sensory nerves, immune and skin cells during the cutaneous response to endogenous or exogenous noxious stimuli. Functional inactivation of NEP or ACE by transient inhibition or permanent genomic deletion results in a relative abundance of substance P (SP) and bradykinin (BK); this augments murine allergic contact dermatitis (ACD) by affecting ACD sensitization and elicitation, which involves neurokinin 1 receptors (NK1), BK receptors (B2) and an intact cutaneous sensory nervous system. Present evidence suggests that increased SP via NK(1) is capable of boosting important functions of SP- and NK1-expressing dendritic cells (DCs) and T cells (TCs) in an auto- or paracrine manner, which promotes ACD antigen sensitization. Moreover, skin inflammation or wounding in vivo, as well as treatment of epidermal and dermal cells by UV light and inflammatory mediators in vitro, regulates NEP and ACE expression and activity. Likewise, NEP and ACE are capable of processing neuroendocrine hormones, such as adrenocorticotropin and alpha-melanocyte-stimulating hormone. Thus, present data indicate that ACE and NEP, via proteolytic cleavage of peptide mediators and growth factors, represent important control factors for the inflammatory response in skin disorders such as psoriasis or allergic inflammation, but may also be capable of affecting pigmentation, cell survival, wound healing and tissue regeneration.

Animals↗