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Joachim Dissemond

Publications and source records attributed to Joachim Dissemond.

32 records · Page 2Linked to original sources
PubMed2005

[Methicillin-resistant Staphylococcus aureus (MRSA) in chronic wounds: therapeutic options and perspectives].

The contamination of chronic wounds with Methicillin-resistant Staphylococcus aureus (MRSA) represents a world-wide increasing problem. Although it is still unclear whether bacterial contamination is a relevant factor for delayed wound-healing, verification of MRSA contamination has significant logistic consequences for the medical institution as well as for the patient. In particular, if MRSA contamination progresses towards a systemic infection, options for antibiotic therapy are greatly limited. In this article, we discuss current therapeutic standards and potential alternatives for eradication of MRSA. There is evident need for effective, novel approaches for elimination of MRSA from chronic wounds that avoid the development of bacterial resistance; otherwise therapeutic alternatives for antibacterial treatment of chronic wounds will become more limited.

Chronic Disease↗
PubMed2004

Overexpression of phospholipid-hydroperoxide glutathione peroxidase in human dermal fibroblasts abrogates UVA irradiation-induced expression of interstitial collagenase/matrix metalloproteinase-1 by suppression of phosphatidylcholine hydroperoxide-mediated NFkappaB activation and interleukin-6 release.

Phospholipid-hydroperoxide glutathione peroxidase (PHGPx) exhibits high specific activity in reducing phosphatidylcholine hydroperoxides (PCOOHs) and thus may play a central role in protecting the skin against UV irradiation-triggered detrimental long term effects like cancer formation and premature skin aging. Here we addressed the role of PHGPx in the protection against UV irradiation-induced expression of matrix metalloproteinase-1 (MMP-1). For this purpose, we created human dermal fibroblast cell lines overexpressing human PHGPx. Overexpression led to a significant increase in PHGPx activity. In contrast to a maximal 4.5-fold induction of specific MMP-1 mRNA levels in vector-transfected cells at 24 h after UVA irradiation, no MMP-1 induction occurred at any studied time point after UVA treatment of PHGPx-overexpressing fibroblasts. As interleukin-6 (IL-6) was earlier shown to mediate the UVA induction of MMP-1, we studied whether PHGPx overexpression might interfere with the NFkappaB-mediated IL-6 induction and downstream signaling. Using transient transfections of IL-6 promoter constructs containing NFkappaB binding sites, we observed a high induction of the reporter gene luciferase in vector-transfected control cells and a significantly lower induction in PHGPx-overexpressing fibroblasts following UVA irradiation. Consistently both UVA irradiation and treatment of fibroblasts with PCOOHs led to phosphorylation and nuclear translocation of the p65 subunit, whereas cells overexpressing PHGPx exhibited impaired NFkappaB activation, p65 phosphorylation, and nuclear translocation. In line with this, the PHGPx-overexpressing fibroblasts showed a reduced constitutive and UVA irradiation-induced IL-6 release. After incubating PHGPx-overexpressing cells with PCOOHs a reduced induction of IL-6 was observed. This together with the suppression of UVA irradiation-induced IL-6 release in the presence of Trolox, a chain breaker of PCOOH-initiated lipid peroxidation, indicates that UVA irradiation-induced PCOOHs and subsequent lipid peroxides initiate the NFkappaB-mediated induction of IL-6, which mediates the induction of MMP-1. Our finding is particularly relevant in light of the already available small molecule mimetics of PHGPx.

Active Transport, Cell Nucleus↗
PubMed2004

Differential downregulation of endoplasmic reticulum-residing chaperones calnexin and calreticulin in human metastatic melanoma.

Characterization of the molecular basis of tumor recognition by T cells has shown that major histocompatibility complex (MHC) class I molecules play a crucial role in presenting antigenic peptide epitopes to cytotoxic T lymphocytes. MHC class Ia downregulation has been repeatedly described on melanoma cells and is thought to be involved in the failure of the immune system to control tumor progression. Proper assembly of MHC class I molecules is dependent on several cofactors, e.g. the chaperones calnexin and calreticulin residing in the endoplasmic reticulum. Alterations in the expression of these chaperones may have important implications for MHC class I assembly, peptide loading, and presentation on the tumor cell surface and thus may contribute to the immune escape phenotype of tumor cells. In the present study, we compared melanoma lesions representing different stages of tumor progression with regard to the expression of calnexin and calreticulin in tumor cells by means of immunohistochemistry. Metastatic melanoma lesions exhibited significant downregulation of calnexin as compared to primary melanoma lesions. In contrast, chaperone calreticulin was expressed in melanoma cells of primary as well as of metastatic lesions. Our data suggest that chaperone-downregulation, particularly calnexin-downregulation, may contribute to the metastatic phenotype of melanoma cells in vivo. Consistently, conserved chaperone expression in metastatic melanoma lesions may be a useful criterion for selection of patients for treatment with T cell-based immunotherapies.

Calnexin↗
PubMed2004

[Thromboangiitis obliterans: an overview].

Thromboangiitis obliterans is a vascular disease characterized by a segmental, non-atherosclerotic inflammation of the small and medium-sized arteries and veins. The vascular changes are mainly found on the distal extremities. Involvement of visceral organs is rare. Affected patients are mostly young male smokers, who develop ulcers and gangrene of the toes and fingers as a result of the vascular ischaemia. Diagnosis is made using characteristic clinical criteria as well as pathological findings in arteriography and histopathology. Although the exact underlying causes of Buerger's disease are still unknown, the disease is strongly associated with tobacco smoking. Although most investigators speculate about an autoimmune mechanism, no causative antigens have yet been discovered. The only definite form of therapy is the discontinuation of tobacco use. On the basis of smoking cessation, further therapies (e.g. administration of prostacyclin analoga) are possible. The mortality rate for patients with Buerger's disease is not higher than that for the rest of the adult population, but patients often require minor and major limb amputation due to ulcerations.

Female↗
PubMed2004

[Options for debridement in the therapy of chronic wounds].

Debridement is defined as the removal of non-vital tissue from wounds. In chronic wounds, debridement means the elimination of necrosis as well as the clearing away of wound dressings, foreign bodies, and other non-vital substances. Sufficient debridement represents one basic prerequisite for a non-delayed wound-healing process. In addition to treating the causal factors for delayed wound healing, debridement should be the first step in an adequate phase-adapted wound-bed preparation for chronic wounds. This report aims to review the different options available in the execution of debridement in chronic wounds. The following therapeutic measures are available for the debridement of chronic wounds: surgery, maggot therapy, laser, ultrasound, hydrotherapy, wet-to-dry method, autolysis, proteolytic enzymes, osmotic or chemical debridement. There is no single correct debridement for all patients! Patients are individuals and therefore different methods of debridement may make sense. Which therapeutic option is chosen is determined by multiple factors. Moreover, depending on the wound milieu, the successive application of different methods can be useful.

Chronic Disease↗
PubMed2004

[Syphilis with HIV coinfection].

In recent years a rising incidence of syphilis has been observed, especially in the population of homosexual men. Because of altered sexual behavior in terms of increased promiscuity paralleled by decreased use of condoms and the fact that a syphilis infection increases the susceptibility to HIV coinfection, the incidence of HIV is also rising once again in this population. In patients with HIV coinfection, the course of syphilis is often atypical or dramatic. Stage-specific features suggesting coinfection include prolonged primary ulcers persisting well into the secondary stage, numerous atypical cutaneous findings in the second stage and a rapid progression from stage to stage. The diagnosis of syphilis may be more difficult because of false positive or false negative serological findings in patients with HIV coinfection. Whether or not the CNS is more often involved is this patient group has not been established by prospective studies and remains controversial. However, WHO and CDC recommendations include evaluation of the CSF in HIV-infected patients with either late syphilis or when the time course is unknown period. There is worldwide agreement on the therapy of syphilis in patients with HIV coinfection. Patients with early syphilis should be treated with 2.4 benzathine penicillin i.m. once or twice; patients with late syphilis, twice or three times. Patients presenting with clinical or serological signs of neurosyphilis require 18-24 million IU penicillin i.v. daily for at least 2 weeks.

Female↗
PubMed2004

Oral lichen planus: an overview.

Lichen planus (LP) is a chronic inflammatory muco-cutaneous disease. Since disorders of NK-cell functional activity could be observed in patients with LP, it is considered to be an autoimmune disease. The pathogenesis of LP is complex and not completely understood. The involvement of mucous membranes is frequently seen, usually asymptomatic, but occasionally complicated by extensive painful erosions, causing a considerable loss of quality of life. Patients with symptomatic oral lichen planus (OLP) often require intensive therapy to reduce the signs and symptoms of this painful and disabling inflammatory disease. OLP is considered to be a precancerous lesion for the development of squamous cell carcinomas. OLP is highly resistant to topical treatment and tends to pursue a chronic course with little tendency to spontaneous resolution. Until now meta-analysis provided little evidence for the superiority of the assessed interventions over placebo for palliation of symptomatic OLP.

Diagnosis, Differential↗
PubMed2004

C-KIT expression in primary cutaneous T-cell lymphomas.

BACKGROUND: Mutations of the stem cell factor receptor C-KIT play a major pathogenetic role in the development of different malignant diseases like human mastocytosis, myeloproliferative disorders, gastrointestinal stromal tumors, acute myelogenous leukemia, and sinonasal lymphomas. Furthermore, the expression of C-KIT has been described in Hodgkin's disease and nodal CD30+ anaplastic large cell lymphomas (ALCLs). As it is possible to inhibit C-KIT by innovative kinase inhibitors like STI571, it may be an attractive target for new therapeutical approaches. Therefore, we screened more than 50 different types of cutaneous T-cell lymphomas (TCLs) for the presence of C-KIT. Immunohistochemical stainings were performed on paraffin-embedded tissue sections using a polyclonal rabbit anti-human C-KIT antibody. Naphtol-ASD-chloroacetate esterase (NASDCE)-control stainings were performed on every positive sample to distinguish C-KIT-positive lymphoma cells from C-KIT-positive mast cells. RESULTS: We found weak expression of C-KIT in seven of 18 patients with primary cutaneous CD30+ ALCL, two of eight patients with primary cutaneous pleomorphic TCL, six of 18 patients suffering from mycosis fungoides, and three of five patients with Sezary's syndrome. Generally, only a very small population of the lymphoma cells expressed C-KIT. This finding indicates a difference to the systemic variant of CD30+ ALCL. The potential use of C-KIT targeting new therapeutical approaches is therefore discussed critically, because C-KIT expression is very rare in all investigated types of primary cutaneous lymphoma.

Adult↗
PubMed2003

Association of TAP1 downregulation in human primary melanoma lesions with lack of spontaneous regression.

Spontaneous regression of primary melanoma lesions is regarded as the result of the recognition of melanoma-associated antigen (MAA)-derived peptides by cytotoxic T-lymphocytes and destruction of melanoma cells. The transporter associated with antigen processing (TAP1/2) is likely to play a crucial role in this process since it loads antigen peptides onto MHC class I molecules. To determine the impact of TAP defects on the spontaneous regression of melanoma lesions, we have compared the expression of TAP1 and TAP2 in 39 primary melanoma lesions exhibiting clinical and histological signs of tumour regression and in 35 primary melanoma lesions without regression phenomena. TAP1 expression was significantly associated with regression of melanoma lesions, since the staining pattern with anti-TAP1 antibody was positive in 38 of the 39 lesions exhibiting regression phenomena and in only 24 of the 35 lesions without histopathological signs of tumour regression. In the latter group, six lesions were stained with a heterogeneous pattern and five with a negative pattern. Furthermore, in lesions with a heterogeneous staining pattern, a clear association was found between TAP1 expression in melanoma cells and the presence of tumour-infiltrating lymphocytes. These results suggest that TAP1 plays an important role in the MAA-specific cytotoxic T-lymphocyte response, which has been suggested to underlie the spontaneous regression of primary melanoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Immunoproteasome subunits LMP2 and LMP7 downregulation in primary malignant melanoma lesions: association with lack of spontaneous regression.

Recently, expression of the immunoproteasome subunits low molecular protein (LMP) 2 or LMP7 was shown to reduce the presentation of certain major histocompatibility complex (MHC) class I-restricted tumour peptide epitopes in renal cell carcinoma and melanoma cells. This may provide the tumour cells with an immune escape mechanism. To test the relevance of this hypothesis, we have taken advantage of the fact that spontaneous regression of human primary melanoma is thought to be the result of a successful peptide-specific cellular immune response in vivo. Immunohistochemical staining with anti-LMP2 and anti-LMP7 xenoantibodies showed a significantly higher expression of these immunoproteasome subunits in primary melanoma lesions exhibiting histological signs of tumour regression than in primary melanoma lesions without regression phenomena. In spontaneously regressing melanoma lesions, LMP2 and LMP7 expression was significantly associated with the presence of tumour-infiltrating lymphocytes. Our results are compatible with the possibility that the expression of the immunoproteasome subunits LMP2 and LMP7 rather than their downregulation in melanoma cells is associated with the presence of a successful anti-melanoma immune response.

Cysteine Endopeptidases↗
PubMedDate not supplied

Tirilazad amelioriates extracellular effects of photooxidative stress by sealing the membrane of UVA irradiated human dermal fibroblasts.

The evaluation of antioxidant medication might provide further tools to protect the skin against the detrimental effects of photooxidative stress. In this context we have previously shown that the lazaroid tirilazad protects fibroblasts effectively against lipid peroxidation (LPO). Now we investigated whether and how tirilazad also influences two typical stress responses after UVA exposure, i.e. IL-6 and collagenase (MMP-1) release. Fibroblasts pre-incubated with tirilazad at a concentration of 30 microM show significantly less IL-6 in the extracellular medium after UVA exposure. Correspondingly, pre-incubation with tirilazad also significantly diminishes the extracellular MMP-1 protein concentration 24h post-irradiation. These effects observed are due to a membrane stabilisation, as tirilazad neither diminishes IL-6 mRNA production nor intracellular IL-6/MMP-1 protein levels after UVA exposure and thus most likely acts by sealing off the cell, delaying the typical leakage of IL-6 and MMP-1.

Antioxidants↗