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Harald Gollnick

Publications and source records attributed to Harald Gollnick.

48 records · Page 3Linked to original sources
PubMed2003

The defect of the perforin granule system in cytotoxic T lymphocytes of atopic patients--are perforin reduction and hyperreleasability of clinical relevance?

Perforin-containing lytic granules are secretory lysosomes of cytotoxic lymphocytes. They act as a negative regulator of activated T cells, control immunoglobulin production, contribute to the regulation of the TH1/TH2 balance, and occupy a central role in anti-viral defense mechanisms. This review focuses on recent evidence for a fundamental defect in the lymphocytic perforin system of atopic patients, namely perforin reduction and the hyperreleasability of perforin granules. These findings are set in relation to the immune imbalance in atopy, which is characterized by a weakly restrained proliferation of allergen-specific T and B cells, a predominance of Ttype-2 cytokines, and an increased susceptibility to cutaneous infections. In the context of the wellknown defect of secretory lysosomes in mast cells and keratinocytes of atopic patients, the possibility of a cell type-independent major pathological factor in atopy is discussed: pan-cellular reduction and hyperreleasability of secretory lysosomes.

Animals↗
PubMed2003

Routine flow cytometric immuno-staining of T-cell perforin is preserved using diethylene glycol for erythrocyte-lysis but lost by the use of ammonium chloride.

The system of perforin-containing lytic granules of cytotoxic lymphocytes plays an important role in the immune defense machinery. Investigating the capacity and efficacy of this system in and ex vivo is helpful to understand immune responses and their modulation by therapeutic interventions. With regard to its pathophysiological function, we recently demonstrated a substantial increase of perforin-positive CD8+ T cells in the peripheral blood of patients with acute exacerbated psoriasis and severe generalized drug reactions, and, in marked contrast, a highly significant perforin-depletion and a perforin-hyperreleasability in atopic dermatitis (AD). To streamline the perforin staining procedure, isolation of peripheral blood mononuclear cells (PBMC) by Ficoll density centrifugation was to be replaced by lysis of erythrocytes. Ammonium chloride lysis, however, reduced the perforin content of CD8+ T cells substantially (up to 75-100%) as compared with Ficoll isolation of PMC. Incubation of cells in concanamycin A, a selective inhibitor of H+-ATPases, resulted in a similar loss of perforin staining pointing to the critical influence of lysosomal pH. Using diethylene glycol-mediated erythrocyte lysis, perforin was well preserved to be readily detectable by immuno flow cytometry. Representative examples of the application of this optimized perforin staining procedure as well as accumulated data are given for various dermatological disorders (psoriasis, atopic dermatitis, cutaneous drug reactions, graft-versus-host disease (GVHD) with strong involvement of the cytotoxic T-cell population. Our findings may help to explain recent conflicting reports about a widely varying range of the portion of perforin-positive cells in healthy individuals as a reflection of such artificial methodological influences.

Adenosine Triphosphatases↗
PubMed2003

Transdermal penetration of topical drugs used in the treatment of acne.

Acne vulgaris is a very common skin disease. Most patients present with mild to moderate acne comedonica or papulopustulosa grade I-II. The first-line treatment for these cases is generally via the topical route, whereas systemic medication is indicated when higher severity grades with small nodes or scarring occur. There are several topical agents available that affect at least one of the main pathogenetic factors responsible for the development of acne: hyperseborrhoea, hyperkeratosis, microbial colonisation and inflammatory and immunological reactions. Topical retinoids have a comedolytic and anticomedogenic activity, and some of them have anti-inflammatory potency. Azelaic acid and benzoyl peroxide have a moderate to strong antibacterial effect without inducing bacterial resistance, which is becoming a significant problem with the increasing use of topical antibacterials. Topical antiandrogens may soon be available for the treatment of the pathogenetic factor hyperseborrhoea. The transdermal penetration and the resulting systemic bioavailability of the various topical agents has not been widely considered. Apart from the retinoids, which can be associated with the risk of embryotoxicity/teratogenicity, and clindamycin, which might cause pseudomembranous colitis, information on the systemic pharmacokinetics of other topical agents is not readily available. There is still no consensus on the safe use of topical retinoids in pregnancy, and the occurrence of pseudomembranous colitis after the topical use of clindamycin does not appear to be of clinical relevance. In general, topical anti-acne agents are well tolerated and, as would be expected from their limited transdermal uptake, other significant safety concerns have not so far arisen.

Acne Vulgaris↗
PubMed2003

Current concepts of the pathogenesis of acne: implications for drug treatment.

The pathogenesis of acne is complex, with strong evidence supporting the involvement of sebaceous hyperplasia, follicular hyperkeratinisation, bacterial hypercolonisation, as well as immune reactions and inflammation. High sebum concentrations and follicular hyperkeratinisation lead to a change of the follicular milieu with consecutive proliferation of bacteria, chiefly Propionibacterium acnes. This leads to further increased production of the pro-inflammatory cytokines interleukin-1alpha and tumour necrosis factor alpha by T cells and keratinocytes, leading to proliferation of both cell types. Follicular keratinocytes fail to differentiate by apoptosis and produce hypergranulosis similar to the impermeable skin outer layer, resulting in the formation of microcomedones. Further inflammatory responses lead to the development of increasing degrees of severity in inflammatory forms of acne. Retinoids aid the differentiation and reduce the hyperproliferation of keratinocytes, and can inhibit the migration of leucocytes. Combination therapy using retinoids plus benzoyl peroxide or antibacterials can treat existing acne lesions faster than the individual agents alone and can also prevent the development of new lesions. The new retinoids (e.g. adapalene) have not only the typical potent comedolytic activity but also anti-inflammatory effects. When added to antibacterial therapy, topical retinoids demonstrate faster and significantly greater reduction of inflammatory acne lesions and comedones than antibacterials alone.

Acne Vulgaris↗
PubMed2003

[Sentinel lymph node biopsy in melanoma patients: methods, indications, and clinical significance].

The incidence of melanoma in Lithuania has doubled over the last decade. Sentinel lymph node biopsy, currently becoming a standard method in the US and Europe, is a minimal invasive and highly sensitive surgical procedure. It can be used for the detection of melanoma micrometastasis in regional lymph nodes in cases when non-invasive methods fail to reveal them. Both disease-free survival and disease-specific survival were significantly better for patients with a negative sentinel lymph node biopsy. A. Breslow thickness, W. H. Clark level, and ulceration of the melanoma were strong predictors, but not as strong as the histological status of the sentinel lymph node. The procedure for sentinel lymph node biopsy is nowadays standardized, including preoperative dynamic lymphoscintigraphy combined with intraoperative gamma probe guidance and blue-dye injection. The aim of this article is to present an update of the sentinel lymph node biopsy method and the prognostic significance of this procedure on the basis of more than 400 sentinel lymph node biopsy's carried out at the Department of Dermatology of the Otto-von-Guericke University, Magdeburg since 1997 and the results of recently published studies in the literature.

Humans↗
PubMed2003

[Scabies triggering Darier's disease].

An increased incidence of scabies has been noted in many countries. Difficulties may arise when unrecognized infestations trigger or aggravate other dermatological disorders. We present an instructive case of Darier's disease, which did not respond to appropriate therapy regimens due to constant triggering by an undetected underlying scabies infestation. In this case, a 44-year-old Italian man presented with typical symptoms of Darier's disease. In addition, the patient reported massive pruritus, which is rather uncommon in this disorder. The disease proved recalcitrant to established treatment regimens resulting in excessive treatment costs. We confirmed the diagnosis of Darier's disease by histopathological analysis, and, in addition, detected arthropod fragments in the upper epidermis. Systemic ivermectin and topical allethrin followed by acitretin and PUVA-bath therapy resulted in rapid improvement of the debilitating pruritus as well as alleviation of the symptoms of Darier's disease.

Administration, Topical↗
PubMed2002

Imiquimod, a topical immune response modifier, in the treatment of cutaneous metastases of malignant melanoma.

BACKGROUND: Imiquimod 5% cream (Aldara, a novel topical immune response modifier, has been approved for the topical treatment of anogenital HPV-induced warts. In addition, several studies have demonstrated antitumoral activity in solar keratoses, superficial basal cell carcinomas and Bowen's disease. AIM: Given the convincing therapeutic results of imiquimod when used for treating selected types of epithelial skin cancer, we became interested to study imiquimod as an adjuvant for treating cutaneous metastases of malignant melanoma. METHODS: Three patients with multiple, i.e. more than 15, cutaneous in-transit metastases of malignant melanoma in unilateral localization on the leg were treated topically with imiquimod 5% cream. RESULTS: Twice daily application under occlusive conditions for a period of 21-28 weeks resulted in >90% regression of cutaneous metastases in 2 patients. The third patient showed marked response only when topical imiquimod was intermittently supplemented by intralesional interleukin (IL)-2 for 2 weeks. Unwanted side effects were mild in all patients. CONCLUSION: Overall, imiquimod as a single agent or in combination with intralesional IL-2 may be a promising immunomodulatory compound for the adjuvant topical treatment of patients with multiple cutaneous metastases of malignant melanoma.

Adjuvants, Immunologic↗
PubMedDate not supplied

Update in retinoid therapy of acne.

The pathogenesis of acne, the most common skin disease, is complex and multifactorial. Clinical experience has demonstrated that parallel targeting of various pathogenetic factors, achieved either by mono- or combination therapy with appropriate drugs, represents the most effective approach to treating acne. Topical retinoids have been shown to expulse mature comedones, reduce microcomedone formation, and exert immunomodulatory effects. They have broad anti-acne activity without the risk of inducing bacterial resistance, which justifies their use as first-line treatment in most types of noninflammatory and inflammatory acne and makes them uniquely suitable as long-term medication to maintain remission after cessation of initial combination therapy. Systemic isotretinoin as a monotherapeutic agent strongly affects all four major pathogenetic factors and has been, in the hand of experienced dermatologists, a potent and safe agent for the treatment of severe and recalcitrant acne forms for more that 20 years. However, patient counseling, careful monitoring, and evaluation and management of adverse events are necessary. The use of isotretinoin has experienced a drawback now that its indication has been lowered from a first-line to a second-line medication.

Acne Vulgaris↗
PubMedDate not supplied

Photoprotection of UV-irradiated human skin: an antioxidative combination of vitamins E and C, carotenoids, selenium and proanthocyanidins.

Endogenous antioxidants are decreased in skin and blood during UV exposure. Combined supplementation of beta-carotene, alpha-tocopherol and ascorbic acid in addition to topical sunscreens may help to lower the risk of sunburning. Acute UV erythema with sunburn reaction are the most important factors in conjunction with the cumulative life-long UV dose for inducing skin damage resulting in photoageing and precancerous and cancerous lesions. Therefore, a clinical, randomized, double-blind, parallel group, placebo-controlled study was conducted in healthy young female volunteers (skin type II) investigating the preventive, photoprotective effect of supplementation with Seresis, an antioxidative combination containing both lipid and water-soluble compounds: carotenoids (beta-carotene and lycopene), vitamins C and E, selenium and proanthocyanidins. In this study, the oral administration of Seresis appeared to be well tolerated. The preparation contains antioxidant compounds in quantities occurring at physiological levels and can therefore be used safely over a long period of time. Despite the fact that the assessment of the light sensitivity (minimal erythemal dose, chromametry) of the skin did not show any statistically significant differences between the Seresis and the placebo group, a clear statistical trend, however, could be demonstrated, i.e. Seresis was able to slow down the time of the development and grade of UVB-induced erythema. The primary efficacy parameter matrix metalloproteinases 1 (MMP-1) between treatment and placebo group following UV irradiation showed a significant difference (p < 0.05), which occurred due to the fact that after a 2-week UV irradiation, MMP-1 slightly increased (p < 0.03) in the placebo group and decreased (p < 0.044) in the treated group. The MMP-9 changes showed a clear tendency of decrease in the Seresis group (p < 1.393) and increase (p < 0.048) in the placebo group. These data emphasise that supplementation with Seresis decreases the UV-induced expression of MMP-1 and 9, which might be important in photoprotective processes. From our data, we thus finally draw the conclusion that by the combination of antioxidants, such as in the formulation of Seresis, a selective protection of the skin against irradiation can be achieved. This might be important for future recommendations for immediate suppression of the early phase of UV-induced erythema, that means pharmacological prevention of sunburn reaction as well as subsequent chronic skin damage.

Adolescent↗
PubMedDate not supplied

Recurrence rate of superficial basal cell carcinoma following successful treatment with imiquimod 5% cream: interim 2-year results from an ongoing 5-year follow-up study in Europe.

Imiquimod is an immune response modifier that acts through Toll-like receptor 7 to induce innate and cell-mediated immune responses. This ongoing phase III, open-label study conducted in Europe is evaluating the long-term (5 year) clinical efficacy and safety of imiquimod 5% cream applied once daily 5 times per week (5 x/week) for 6 weeks for the treatment of superficial basal cell carcinoma (sBCC). A total of 182 subjects were enrolled. The initial sBCC clearance rate was 90% (12-week post treatment), whereas the proportion of subjects who were clinically clear at 2 years (current time point) was estimated to be 79.4%. Local skin/application site reactions were the most frequently reported safety findings. Initial efficacy rates of imiquimod applied 5 x/week for 6 weeks demonstrate its clinical utility as an alternative approach to the treatment of sBCC. The recurrence rate seen to date supports ongoing follow up of subjects treated with imiquimod.

Adjuvants, Immunologic↗
PubMedDate not supplied

Profiling lymphocyte subpopulations in peripheral blood under efalizumab treatment of psoriasis by multi epitope ligand cartography (MELC) robot microscopy.

CD11a-blocking efalizumab has recently been approved as a systemic treatment of moderate to severe chronic plaque psoriasis. When treating 6 psoriasis patients with efalizumab over 12 weeks in the present study, we observed an overall good tolerability and 5 treatment responders characterized by a decrease of PASI from 21.3 +/- 5.4 to 3.9 +/- 0.6. The accompanying significant increase of peripheral blood lymphocytes from 1.9 +/- 0.7 to 4.3 +/- 1.0 x 10(9)/L (p < 0.05) was analyzed by multi epitope ligand cartography (MELC) robot microscopy. Thereby a high-dimension simultaneous multiplex immunophenotyping was pursued using 39 fluorophore-labeled antibodies including labeled efalizumab and 3 other affinity reagents such as lectins. Due to efalizumab treatment there was a substantial decrease of the cellular expression of CD11a (detected by mab clone 25.3.1) and efalizumab binding sites (EfaBSs). This was paralleled by an increase of the number of EfaBS- and EfaBS+ lymphocytes by a factor of 2.4x and 2.2x, respectively. The latter effect was mainly derived from a subpopulation showing a low degree of EfaBS expression. Efalizumab treatment led furthermore to an increase of the numbers of CD3+, CD4+, CD8+, CD44+, CD45+, CD45R0+, CD45 RA+, CD52+, CD58+, CD247+, HLA-DR+ and Sambucus nigra lectin-reactive lymphocytes (by factors from 2.0 to 3.3x). In terms of a combinatorial molecular phenotype we identified a CD3+/CD4+/CD44+/CD52+ lymphocyte subpopulation which accumulated most predominantly from 0.824 +/- 0.270 x 10(9)/L up to 1.616 +/- 0.152 x 10(9)/L under efalizumab treatment (p < 0.01). Thus, the current study extends the knowledge of efalizumab-dependent perturbations of recirculating blood lymphocyte subpopulations in psoriasis patients.

Adult↗