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Harald Gollnick

Publications and source records attributed to Harald Gollnick.

At least 19 recordsLinked to original sources
PubMed2006

Analyzing proteome topology and function by automated multidimensional fluorescence microscopy.

Temporal and spatial regulation of proteins contributes to function. We describe a multidimensional microscopic robot technology for high-throughput protein colocalization studies that runs cycles of fluorescence tagging, imaging and bleaching in situ. This technology combines three advances: a fluorescence technique capable of mapping hundreds of different proteins in one tissue section or cell sample; a method selecting the most prominent combinatorial molecular patterns by representing the data as binary vectors; and a system for imaging the distribution of these protein clusters in a so-called toponome map. By analyzing many cell and tissue types, we show that this approach reveals rules of hierarchical protein network organization, in which the frequency distribution of different protein clusters obeys Zipf's law, and state-specific lead proteins appear to control protein network topology and function. The technology may facilitate the development of diagnostics and targeted therapies.

Dermatitis, Atopic↗
PubMed2006

Inhibitors of dipeptidyl peptidase IV and aminopeptidase N target major pathogenetic steps in acne initiation.

Acne is a chronic disease hallmarked by sebaceous hyperplasia, follicular hyperkeratosis, and inflammation. Parallel targeting of these factors is required to treat acne effectively. Inhibitors of dipeptidyl peptidase IV (DP IV) and aminopeptidase N (APN) show strong anti-inflammatory effects on immune cells and therapeutic efficacy in autoimmune disorders. Our investigation focused on the expression and functional relevance of these ectopeptidases in three cell types which exhibit an altered phenotype in early acne lesions. We showed for the first time expression of DP IV and APN on human sebocytes. In the SZ95 sebocyte cell line, the DP IV inhibitors Lys[Z(NO2)]-thiazolidide and Lys[Z(NO2)]-pyrrolidide and the APN inhibitors actinonin and bestatin suppressed proliferation, enhanced terminal differentiation, and slightly decreased total neutral lipid production. The anti-inflammatory and differentiation-restoring cytokine IL-1 receptor antagonist was significantly upregulated in SZ95 sebocytes and the HaCaT keratinocyte cell line in the presence of inhibitors. Furthermore, the inhibitors suppressed proliferation and IL-2 production of Propionibacterium acnes-stimulated T cells ex vivo and enhanced the expression of the immunosuppressive cytokine transforming growth factor-beta1. Our data provide first evidence for a functional role of DP IV and APN in the sebaceous gland apparatus and for their inhibitors, used alone or in combination, as completely new substances possibly affecting acne pathogenesis in a therapeutic manner.

Acne Vulgaris↗
PubMed2006

UVA1 radiation (340-400 nm) interferes with the perforin-granule system of CD8hi+ cytotoxic T lymphocytes in vitro.

UVA1-irradiation was introduced as an innovative and effective phototherapy of atopic dermatitis (AD) and other skin diseases. In AD, a defect of a central apoptosis inducing effector system involved in immunoregulation and immune defense, i.e., the system of perforin-granules in cytotoxic T lymphocytes (CTL), was recently reported: perforin-reduction and perforin-hyperreleasability. We now investigated UVA1-effects on the perforin-granule system in vitro. Peripheral blood CTLs were exposed in vitro to 10-100 J/cm2 UVA1 (340-400 nm), and to 30-150 mJ/cm2 UVB (280-315 nm) as a control. A time-dependent perforin-granule release was induced by phorbol 12-myristate 13-acetate (PMA) and ionomycin. This release was inhibited dose-dependently by UVA1, but not by UVB. An UVA1-dose dependent pattern of sensitive (80%) and insensitive (20%) individuals was found. The kinetics of perforin release in AD-CTLs, i.e. hyperreleasability, was normalized by 50 J/cm2 UVA1 in vitro. Sodium azide as a quencher of reactive oxygen species prevented the UVA1-mediated inhibition of perforin-granule release. Our data demonstrate for the first time a dose- and wavelength-dependent UVA1-effect in vitro on a major effector system of cytotoxic lymphocytes, the system of perforin-granules. This might contribute to the further understanding of immunomodulatory UVA1-effects in vivo.

CD8-Positive T-Lymphocytes↗
PubMed2006

A comparison of oral methylprednisolone plus azathioprine or mycophenolate mofetil for the treatment of pemphigus.

OBJECTIVE: To investigate the safety and efficacy of oral methylprednisolone combined with azathioprine sodium or mycophenolate mofetil for the treatment of pemphigus. DESIGN: A prospective, multicenter, randomized, nonblinded clinical trial to compare 2 parallel groups of patients with pemphigus (pemphigus vulgaris and pemphigus foliaceus) treated with oral methylprednisolone plus azathioprine or oral methylprednisolone plus mycophenolate mofetil. Settings Thirteen departments of dermatology in Germany. Patients We included patients with pemphigus vulgaris (n = 33) or pemphigus foliaceus (n = 7) evidenced by clinical lesions suggestive of pemphigus, intraepidermal blistering on histological analysis of skin biopsy specimens, intercellular deposition of IgG within the epidermis, and immunoblot analysis findings for antidesmoglein 3 and/or antidesmoglein 1 autoantibodies. MAIN OUTCOME MEASURES: The cumulative total methylprednisolone doses and rate of remission. Secondary outcome measures were safety profiles and duration of remission. RESULTS: In 13 (72%) of 18 patients with pemphigus receiving oral methylprednisolone and azathioprine, complete remission was achieved after a mean +/- SD of 74 +/- 127 days compared with 20 (95%) of 21 patients receiving oral methylprednisolone and mycophenolate mofetil in whom complete remission occurred after a mean +/- SD of 91 +/- 113 days. The total median cumulative methylprednisolone dose used was 8916 mg (SD, +/-29 844 mg) in the azathioprine group compared with 9334 mg (SD, +/-13 280 mg) in the mycophenolate group. In 6 (33%) of 18 patients treated with azathioprine, grade 3 or 4 adverse effects were documented in contrast to 4 (19%) of 21 patients who received mycophenolate mofetil. Conclusion Mycophenolate mofetil and azathioprine demonstrate similar efficacy, corticosteroid-sparing effects, and safety profiles as adjuvants during treatment of pemphigus vulgaris and pemphigus foliaceus.

Administration, Oral↗
PubMed2006

"Bak (and Bax) to the future"--of primary melanoma prognosis?

Bcl-2 proteins either block or activate the "intrinsic" mitochondrial apoptosis pathway. Loss of expression of proapoptotic Bcl-2 proteins, namely Bax and Bak, in primary melanomas is associated with a worse long-term prognosis. Consequently, inactivation of mitochondrial signaling pathways of apoptosis may not only be a prerequisite for melanoma progression but may also hamper therapeutic efforts with chemotherapeutic drugs.

Apoptosis↗
PubMed2006

Long-term survival benefit after adjuvant treatment of cutaneous melanoma with dacarbazine and low dose natural interferon alpha: A controlled, randomised multicentre trial.

In a prospective, controlled, randomised, multicentre study 252 patients with totally resected cutaneous melanoma (248 in stage II-III and 4 in stage IV) were either treated with two doses of dacarbazine (DTIC) followed by a 6-month treatment with 3 MU thrice weekly of highly purified natural interferon-alpha (n = 128; arm A) or received no adjuvant treatment (n = 124; arm B). Treatment was well tolerated. After a median follow-up of 8.5 years ITT analysis showed that the difference in survival was statistically significant with respect to melanoma-related deaths (HR = 0.65, CI = 0.46-0.97, p = 0.022) and close to significance with respect to overall survival (HR 0.71, CI 0.49-1.00, p = 0.052). The risk reduction of melanoma-associated death, calculated by Cox proportional hazards modelling, after adjusting for identified predictive variables, was almost 50% (p = 0.002). The overall efficacy of the treatment appeared to be mainly attributable to effects observed in patients with deep and/or metastasizing tumours (HR 0.60, CI 0.40-0.90, p = 0.013).

Adult↗
PubMed2006

[Current situation of dermatologic surgery in Germany].

BACKGROUND: Dermatologic surgery has become an increasingly important issue in dermatology in recent years. At present, no current epidemiologic or care-related data on cutaneous surgery procedures in dermatology are available. METHODS: To determine the extent of cutaneous surgery procedures in dermatological hospitals, a national survey was performed. Both the procedure codes for 2004 based on the OPS-classification and the DRG figures grouped to the major diagnostic category 09 of G-DRG version 2004 were considered in detail. Methods of descriptive statistics were applied. RESULTS: The submitted data reveal that the contributing hospitals provided 164487 cutaneous surgery procedures in the investigation period. The vast majority is represented by extensive procedures and plastic-reconstructive operations, as opposed to less complex surgeries such as simple excisions. Analysis of DRG assignment indicates that surgical procedures account for 44.2% of inpatient cases. CONCLUSIONS: The present survey demonstrates that in Germany cutaneous surgery procedures are widely performed by dermatological hospitals and dermatologists. The increasing incidence of melanoma and nonmelanoma skin cancer including precursor lesions will increase the need for dermatologists to perform cutaneous surgery in the future.

Dermatology↗
PubMed2005

The prevalence of common acquired melanocytic nevi and the relationship with skin type characteristics and sun exposure among children in Lithuania.

OBJECTIVE: To evaluate the prevalence of common acquired melanocytic nevi and its relationship with pigmentary characteristics and severe sunburns in children. DESIGN: Cross-sectional study. SETTING: Kaunas city, Lithuania (latitude of 55 degrees 55 minutes). PATIENTS: A random sample of 484 children aged 1 to 2 years, 4 to 5 years, and 9 to 10 years and adolescents aged 14 to 15 years. INTERVENTIONS: A questionnaire that provided information about the history of sunbathing and skin type. MAIN OUTCOME MEASURES: Atypical melanocytic nevi were defined according to the clinical criteria of the ABCDE rule. RESULTS: The median number of all common acquired melanocytic nevi was 12 in boys and 11 in girls; the median number of melanocytic nevi 2 mm or larger in boys and girls was 4. Twenty-seven percent of children experienced severe sunburns more than once. After adjustment for age and sex, it was found that children who had severe sunburns in summer and skin type I had a higher density of all melanocytic nevi and melanocytic nevi 2 mm or larger. The prevalence of atypical melanocytic nevi was 7% in all children and was age dependent (age 4-5 years, 1%; 9-10 years, 4%; 14-15 years, 16%). Three percent of children had congenital melanocytic nevi. CONCLUSIONS: The total number of common acquired melanocytic nevi in children increased with age. There was a positive association between severe sunburns, the tendency of the skin to burn, and the number of all melanocytic nevi and nevi 2 mm or larger.

Adolescent↗
PubMed2005

Treatment of scalp angiosarcoma by controlled perfusion of A. carotis externa with pegylated liposomal doxorubicin and intralesional application of pegylated interferon alfa.

BACKGROUND: Angiosarcoma of the scalp is a rare but highly aggressive malignant tumor that differentiates toward vascular endothelial cells and shows a tendency for diffuse, often clinically occult spread. OBSERVATIONS: A 65-year-old Caucasian man presented with multiple erythematous skin lesions at the right scalp hemisphere and a prominent forehead edema that had developed during a period of 2 months. The clinical diagnosis of angiosarcoma was confirmed by histopathology. Because of the advanced local progression of the tumor and the unilateral localization on the right side of the scalp, we initiated an intra-arterial chemotherapy using pegylated liposomal doxorubicin (Caelyx) (8 mg/cycle every 4 weeks by an A. carotis externa port system). In addition, the patient received pegylated interferon alfa (50 microg/wk) by a percutaneous intralesional injection route. After 2 months, the tumor showed a marked regression; after 4 months, only one nodule located at the margins of the area perfused by the A. carotis externa persisted but regressed after focal irradiation. At 30 months after diagnosis, the patient shows no recurrence of tumor growth. CONCLUSIONS: In combination with intralesional interferon alfa, intra-arterial doxorubicin may be a promising innovative therapeutic option for localized scalp angiosarcoma, a hitherto poorly manageable and aggressive malignant tumor.

Aged↗
PubMed2005

Expression of gp130 in tumors and inflammatory disorders of the skin: formal proof of its identity as CD146 (MUC18, Mel-CAM).

Two antibodies, BT14 and L101, detect a tumor-associated cell surface glycoprotein (gp130) whose properties in normal and diseased skin were assessed, and whose molecular identity was determined in this study. In normal skin, gp130 was constitutively expressed on dermal blood vessels and epidermal appendages, but not in interfollicular epidermis. Marked induction was detected within benign and malignant tumors of various origins including viral warts, basal cell carcinomas, squamous cell carcinomas, metastatic melanomas, and cutaneous T cell lymphomas. In vitro studies confirmed the general upregulation of gp130 expression in malignantly transformed cells. Surprisingly, gp130 was also induced in inflammatory skin diseases including psoriasis and allergic contact dermatitis. Halting proliferation of transformed keratinocytes through cytostatic drugs or increasing the Ca2+ concentration in the medium resulted in increased gp130 expression. In addition, overexpression of Bcl-2 led to upregulation of gp130. When the protein was purified and analyzed by peptide mass fingerprinting, we could demonstrate that it is MUC18 (Mel-CAM, CD146). Sequential immunoprecipitations and western blot analyses confirmed the identity of the antigen. Thus, both expression pattern and regulation characteristics of the now-known glycoprotein gp130 extended beyond previously published data regarding MUC18, thus shedding some new light on a supposedly well-known antigen.

Antigens, CD↗