Wolf Nürnberg

Expression of interleukin‐8 detected by in situ hybridization correlates with worse prognosis in primary cutaneous melanoma

Previous in vitro studies have demonstrated that endogenously produced human interleukin‐8 (IL‐8) can act as an important growth factor for human melanoma cells in vitro. The present study, has investigated whether IL‐8 mRNA expression in primary melanomas may be of prognostic relevance with regard to melanoma progression and metastatic spread. In order to evaluate the clinical significance of IL‐8 mRNA expression of melanoma cells in vivo, 59 melanocytic tissue specimens (37 primary melanomas and 22 melanocytic naevi) were studied using a semiquantitative in situ hybridization technique. Significant mRNA expression of IL‐8 was found in 59 per cent (22/37) of melanomas. In 19 per cent (7/37) of the malignant melanomas, additional hybridization signals were noted within keratinocytes of the overlying epidermis. In contrast, paralesional normal‐appearing epidermis and melanocytes in non‐malignant lesions (melanocytic naevi) showed no IL‐8 mRNA. Analysis of the relationship between IL‐8 expression and clinico‐histopathological features showed a significant association between IL‐8 mRNA expression and the histological melanoma subtype (IL‐8 mRNA: 14/19 in superficial spreading melanoma versus 4/12 in nodular melanoma, p< 0·05). Furthermore, IL‐8 expression in primary tumours could be correlated with the patients clinical course, with time to progression being significantly reduced in primary tumours expressing IL‐8 in either the tumour cells or keratinocytes of the overlying epidermis. These results demonstrate for the first time that IL‐8 expression, as detected by in situ hybridization in primary tumours, may serve as a significant prognostic factor for tumour progression in human malignant melanoma. Copyright

Interferon treatment of patients with chronic urticaria and mastocytosis

REFERENCES 1. Maycock RL, Bertrand P, Merrison CEo Manifestations of sarcoidosis: analysisof 145 patients with a review of nineseries selected from the literature. Am J Moo 1963;36:67-89. 2. Von Lichtenberg F. Infectious diseases: fungal, protozoal, and helminthic diseases and sarcoidosis. In: Robbins SL, Cotran RS, Kumar V, eds.Pathologicbasisofdisease.Philadelphia: WB Saunders, 1984:390-2. 3. Mitchell ON, Scadding JG, Heard BE, et al. Sarcoidosis: histopathology and clinical diagnosis. J Clin Pathol 1977; 30:395-408. Journal of the American Academy of Dermatology March 1994

Distribution and potential biologic function of the thrombin receptor PAR-1 on human keratinocytes

Abstract Thrombin has recently been shown not only to exert procoagulant activities, but also to induce mitogenic responses of different cell types involved in wound healing via binding to and cleavage of the thrombin receptor. In order to further explore these aspects of thrombin function, human keratinocytes (HaCaT cell line) were examined for their potential mitogenic responsiveness to thrombin and for the dependency of this process on the expression of the high-affinity thrombin receptor. Quiescent keratinocytes were stimulated in the mitogenic assay with ·-thrombin and ¶the thrombin receptor activating peptides TRAP 42–55 (SFLLRNPNDKYEPY) and TRAP 42–46 (SFLLR). A strong induction of cell proliferation was noted with ·-thrombin, TRAP 42–55 and TRAP 42–46 , but not with the “scrambled” peptide (FSLLR). These findings confirm that keratinocytes express the thrombin receptor and that the sequence of the first two amino acids of the generated neo-N-terminus are important for the activation of the receptor. Using cDNA fragments of the 5′ coding sequence of the receptor, Northern blot analysis confirmed that HaCaT keratinocytes express the thrombin receptor. Expression of the receptor was also detected on normal human keratinocytes by immunohistochemistry and in situ hybridization. These data demonstrate the expression and biologic function of the human thrombin receptor on human keratinocytes, suggesting that thrombin, among other mediators, plays an important part in the orchestration of epidermal growth and repair processes.

Glucocorticoid-induced modulation of cytokine secretion from normal and leukemic human myelomonocytic cells.

Since glucocorticoid effects on inflammatory processes may be mediated via modulation of cytokine release, different types of myelomonocytic cells were stimulated in vitro with lipopolysaccharide (50 ng/ml) or phorbol myristate acetate (25 ng/ml) plus the ionophore A23187, 2 x 10(-7) M, and release of interleukin (IL)-1 beta, IL-8 and tumor necrosis factor (TNF)-alpha was measured after 24 h by ELISA. Peripheral blood mononuclear cells from two allergic and two normal human donors released similarly large quantities of IL-8 and lower amounts of IL-1 beta and TNF-alpha. This also held for myelomonocytic cell lines, with THP-1 cells being most active, followed by U-937 and HL-60 cells. All potent glucocorticoids studied caused a dose-dependent inhibition of cytokine release from donor cells, being most marked for IL-1 beta and lowest for IL-8. Inhibition of cytokine release was also noted with U-937 cells, with clear differences in potency between the glucocorticoids, whereas release was enhanced in all experiments with THP-1 cells. These results were confirmed with Northern blot analysis. Modulating effects of glucocorticoids on cytokine release are thus complex, and are particularly dependent on the cell type studied.

Erfolgreiche Behandlung des chronisch diskoiden Lupus erythematodes mittels Argon-Laser

ZusammenfassungWir berichten über eine Patientin mit chronisch diskoidem Lupus erythematodes (CDLE), bei der wir erstmals den Argon-Laser zur Lokaltherapie einsetzten. Die Patientin litt unter langjährigen Hautveränderungen, die sich nicht oder nur geringfügig durch etablierte Behandlungsstrategien beeinflussen ließen. Nach Anwendung des Argon-Lasers kam es im Bereich der therapierten Läsionen zu einer vollständigen und dauerhaften Abheilung. Histologische und immunhistologische Befunde sprechen dafür, daß gefäßmediierte Effekte des Argon-Lasers für die beobachtete Wirkung bei LE-bedingten diskoiden Läsionen von Bedeutung sind. Im Rahmen dieser Fallbeschreibungen wird erstmals die Wirksamkeit des Argon-Lasers bei der Behandlung von therapieresistenten diskoiden Hautläsionen beim Lupus erythematodes gezeigt.SummaryWe report on a patient with chronic discoid lupus erythematosus who was treated with argon-laser. The patient suffered from long-standing lesions and had been pretreated with various drugs, with no or slight improvement. After a few argon-laser applications, the treated skin lesions improved dramatically while the untreated lesional skin showed continuous disease activity. Histological and immunohistological investigations of biopsies from treated and untreated lesional skin suggest that endothelial mechanisms play a role in the generation and maintenance of discoid lesions in lupus erythematosus. This is the first reported case of successful treatment of chronic discoid skin lesions of a lupus erythematosus patient with argon-laser.