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Meinhard Schiller

Publications and source records attributed to Meinhard Schiller.

10 recordsLinked to original sources
PubMed2006

Dermatomyositis associated with malignant melanoma--a marker of poor prognosis?

BACKGROUND: Dermatomyositis (DM) is an inflammatory connective tissue disorder well recognized as a paraneoplastic syndrome in adults. OBJECTIVE: The objective of this study was to assess the prognosis of DM associated with malignant melanoma (MM). PATIENTS AND METHODS: We systematically searched databases (PubMed, MEDLINE, and WEB OF SCIENCE) for articles reporting the concurrence of DM and MM. For the literature study, time of onset of DM in relation to diagnosis of MM (before, concomitant with, or after), stage of MM after restaging (according to the American Joint Committee on Cancer [AJCC] guidelines, 2001), and survival time after diagnosis of DM were recorded. Survival time studies and univariate statistical analyses were performed. Furthermore, we present our own clinical case of a patient with DM concomitantly occurring with regional lymph node metastasis of MM. RESULTS: In 5 cases DM occurred before, in 6 cases concomitantly with, and in 6 cases after progression of MM. Univariate analysis identified the AJCC stage of MM as a significant prognostic factor. Gender, age, and the time interval between onset of DM and progression of melanoma were unrelated. The 1-year actuarial survival rate was 0% for patients with DM when occurring with MM at stage IV and 60% when occurring with MM at stage III (P < .05). The estimated mean survival time was 6.6 months for patients with MM stage IV and 57 months for stage III. LIMITATIONS: The conclusions from this study are limited by the relatively small number of articles that reported the association of MM and DM. CONCLUSION: DM occurring in patients with MM at stage IV is connected with an extremely poor prognosis, whereas the few reported patients with DM and MM at stage III, including our case, have a prognosis similar to stage III patients without DM.

Adult↗
PubMed2006

Immune response modifiers--mode of action.

The innate immune system governs the interconnecting pathways of microbial recognition, inflammation, microbial clearance, and cell death. A family of evolutionarily conserved receptors, known as the Toll-like receptors (TLRs), is crucial in early host defense against invading pathogens. Upon TLR stimulation, nuclear factor-kappaB activation and the interferon (IFN)-regulatory factor 3 pathway initiate production of pro-inflammatory cytokines, such as interleukin-1 and tumor necrosis factor-alpha, and production of type I IFNs (IFN-alpha and IFN-beta), respectively. The innate immunity thereby offers diverse targets for highly selective therapeutics, such as small molecular synthetic compounds that modify innate immune responses. The notion that activation of the innate immune system is a prerequisite for the induction of acquired immunity raised interest in these immune response modifiers as potential therapeutics for viral infections and various tumors. A scenario of dermal events following skin cancer treatment with imiquimod presumably comprises (i) an initial low amount of pro-inflammatory cytokine secretion by macrophages and dermal dendritic cells (DCs), thereby (ii) attracting an increasing number type I IFN-producing plasmacytoid DCs (pDCs) from the blood; (iii) Langerhans cells migrate into draining lymph nodes, leading to an increased presentation of tumor antigen in the draining lymph node, and (iv) consequently an increased generation of tumor-specific T cells and finally (v) an accumulation of tumoricidal effector cells in the treated skin area. The induction of predominately T helper (Th)1-type cytokine profiles by TLR agonists such as imiquimod might have further benefits by shifting the dominant Th2-type response in atopic diseases such as asthma and atopic dermatitis to a more potent Th1 response.

Adjuvants, Immunologic↗
PubMed2005

[G-dRG version 2005: relevant aspects for dermatology].

One year after the obligatory implementation of a new hospital funding system based on Diagnosis Related Groups (DRG) the third version of a German DRG-system has been published. It differs significantly from the previous version. Modifications in the classification system and the introduction of further procedure-based payments contribute to a better depiction of specialized clinical services. A number of acknowledged problems which caused great discussion in 2004 have been solved, yielding a more appropriate mapping of clinical services. The algorithms of the major diagnostic categories have been modified and complications, comorbidities and/or multiple procedures will be considered more precisely in selecting a group. However, some inconsistencies concerning highly specialized medical procedures and special features of impatient dermatological care remain. Nevertheless, a great improvement over the previous versions is apparent. The crucial aspects of the G-DRG version 2005 and the accompanying rules and regulations of payment are reviewed in detail with special relevance to dermatology.

Algorithms↗
PubMed2004

TGF-beta-induced SMAD signaling and gene regulation: consequences for extracellular matrix remodeling and wound healing.

Members of the transforming growth factor-beta (TGF-beta) superfamily are pleiotropic cytokines that have the ability to regulate numerous cell functions, including proliferation, differentiation, apoptosis, epithelial-mesenchymal transition, and production of extracellular matrix, allowing them to play an important role during embryonic development and for maintenance of tissue homeostasis. Three TGF-beta isoforms have been identified in mammals. They propagate their signal via a signal transduction network involving receptor serine/threonine kinases at the cell surface and their substrates, the SMAD proteins. Upon phosphorylation and oligomerization, the latter move into the nucleus to regulate transcription of target genes. This review will summarize recent advances in the understanding of the mechanisms underlying SMAD modulation of extracellular matrix gene expression in the context of wound healing and tissue fibrosis.

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↗
PubMed2003

Cyclic adenosine 3',5'-monophosphate-elevating agents inhibit transforming growth factor-beta-induced SMAD3/4-dependent transcription via a protein kinase A-dependent mechanism.

Transforming growth factor-beta (TGF-beta) plays complex roles in carcinogenesis, as it may exert both tumor suppressor and pro-oncogenic activities depending on the stage of the tumor. SMAD proteins transduce signals from the TGF-beta receptors to regulate the transcription of specific target genes. Crosstalks with other signaling pathways may contribute to the specificity of TGF-beta effects. In this report, we have investigated the effects of cyclic adenosine 3',5'-monophosphate (cAMP), a key second messenger in the cellular response to various hormones, on SMAD-dependent signaling in human HaCaT keratinocytes. Using either an artificial SMAD3/4-dependent reporter construct or the natural TGF-beta target, plasminogen activator inhibitor-1, we show that membrane-permeable dibutyryl cAMP, and other intracellular cAMP-elevating agents such as the phosphodiesterase inhibitor isobutyl-methylxanthine, the adenylate cyclase activator forskolin, or exogenous prostaglandin E2 (PGE2), interfere with TGF-beta-induced SMAD-specific gene transactivation. Inhibition of protein kinase A (PKA), the main downstream effector of cAMP, with H-89, suppressed cAMP-dependent repression of SMAD-driven gene expression. Inversely, coexpression of either an active PKA catalytic subunit or that of the cAMP response element (CRE)-binding protein (CREB) blocked SMAD-driven gene transactivation. cAMP-elevating agents did not inhibit nuclear translocation and DNA binding of SMAD3/4 complexes, but abolished the interactions of SMAD3 with the transcription coactivators CREB-binding protein (CBP) and p300 in a PKA-dependent manner. These results suggest that suppression of TGF-beta/SMAD signaling and resulting gene transactivation by cAMP-inducing agents occurs via PKA-dependent, CREB-mediated, disruption of SMAD-CBP/p300 complexes.

Cell Nucleus↗
PubMed2003

Collagen metabolism is a novel target of the neuropeptide alpha-melanocyte-stimulating hormone.

Suppression of collagen synthesis is a major therapeutic goal in the treatment of fibrotic disorders. We show here that alpha-melanocyte-stimulating hormone (alpha-MSH), a neuropeptide well known for its pigment-inducing capacity, modulates collagen synthesis and deposition. Alpha-MSH in vitro suppresses the synthesis of collagen types I, III, and V and down-regulates the secretion of procollagen type I C-terminal peptide (PICP) in human dermal fibroblasts treated with the fibrogenic cytokine transforming growth factor-beta1 (TGF-beta1). Alpha-MSH did not interfere with TGF-beta1 signaling, because TGF-beta1-induced expression of collagen mRNA was not affected, implying a posttranscriptional mechanism. Human dermal fibroblasts in vitro express a high affinity binding site for MSH, which was identified by reverse transcription PCR and immunofluorescence analysis as the melanocortin-1 receptor (MC-1R). Immunohistochemical studies on normal adult human skin confirmed MC-1R expression in distinct dermal fibroblastic cells. The MC-1R on fibroblasts appears to be functionally relevant because alpha-MSH increased the amount of intracellular cAMP, and coincubation with a synthetic peptide corresponding to the human Agouti signaling protein abrogated the inhibition of TGF-beta1-induced PICP secretion by alpha-MSH. To assess the in vivo relevance of these findings, a mouse model was used in which dermal fibrosis was induced by repetitive intracutaneous injections with TGF-beta1. The inductive activity of TGF-beta1 on collagen deposition and the number of dermal cells immunoreactive for vimentin and alpha-smooth muscle actin was significantly suppressed by injection of alpha-MSH. Melanocortins such as alpha-MSH may therefore represent a novel class of modulators with potential usefulness for the treatment of fibrotic disorders.

Actins↗
PubMed2003

Significant risk of a second melanoma in patients with a history of melanoma but no further predisposing factors.

It is a well-accepted fact that melanoma patients are prone to develop further melanomas. In a cohort of 535 melanoma patients, we determined the incidence of second melanomas, as well as risk factors known to be associated with melanoma development. A retrospective analysis of patients regularly consulting our melanoma care unit revealed second or even further melanomas in 5.6% (n = 30). When compared to the overall population, melanoma patients have at least a 30-fold increased risk for the development of a second melanoma. Twenty of these 30 patients revealed none of the known predisposing conditions for multiple melanomas.

Female↗
PubMed2002

Evidence for expression of melanocortin-1 receptor in human sebocytes in vitro and in situ.

Many lines of evidence indicate that the activity of sebaceous glands can be modulated by neuropeptides. Direct evidence in man, however, is still missing. We show that SZ95 sebocytes, an immortalized human sebaceous gland cell line, express receptors for alpha-melanocyte-stimulating hormone. Reverse transcription polymerase chain reaction with primers against the five melanocortin receptors and immunofluorescence studies using an antibody directed against a peptide corresponding to the amino acids 2-18 of the human melanocortin-1 receptor disclosed specific transcripts and immunoreactivity for melanocortin-1 receptor in these cells. Melanocortin-1 receptor expression was confirmed in sebocytes of normal human skin by immunohistochemistry. In contrast, no immunostaining for the melanocortin-5 receptor could be detected in sebocytes in situ, in accordance with the lack of specific transcripts for this melanocortin receptor in SZ95 sebocytes. As cytokines play an important role in the recruitment of inflammatory cells in acne and related disorders and alpha-melanocyte-stimulating hormone exerts immunomodulatory effects in many other cell types, we investigated the effect of alpha-melanocyte-stimulating hormone on interleukin-8 secretion by SZ95 sebocytes. Treatment with interleukin-1beta resulted in a marked increase in interleukin-8 release that was partially blocked by coincubation with alpha-melanocyte-stimulating hormone in a dose-dependent manner. Taken together, we show here that the melanocortin-1 receptor is expressed in vitro and in situ in human sebocytes. By modulating interleukin-8 secretion, alpha-melanocyte-stimulating hormone may act as a modulator of inflammatory responses in the pilosebaceous unit.

Cell Membrane↗