PubMed Health⌕ Search

Biomedical subjects

H H Wolff

Publications and source records attributed to H H Wolff.

At least 55 records · Page 3Linked to original sources

[The Malignant Melanoma Central Register of the German Society of Dermatology 1983-1993. Epidemiologic developments and current therapeutic management of malignant melanoma of the skin].

The Central Malignant Melanoma Registry of the German Dermatological Society was founded in 1983 and has meanwhile developed into a major continuously updated multicentre project. Up to June 1994, 19,250 reports of cutaneous melanoma had been received, from 41 departments of dermatology in the former Federal Republic of Germany, from 14 departments in the former German Democratic Republic, from 2 departments in Austria, and from 1 department in Switzerland. Analysis of the data revealed some epidemiological trends over time during the years 1983 to 1993. (1) During the last 10 years the percentage of male patients has steadily increased, from an average of 38% in the year 1983 to 46% in 1993. (2) Early diagnosis of malignant melanoma improved during the period of time investigated. The percentage of diagnoses of primary tumour alone increased between 1983 and 1993. The mean tumour thickness (Breslow) decreased in the West Germany from 1.8 mm to 1.3 mm and in East Germany from 2.5 mm to 1.7 mm. The proportion of nodular melanoma decreased correspondingly from 29% to 14% in the former Federal Republic of Germany and from 40.6% to 22.6% in the former Germany Democratic Republic. During the years 1990 and 1993, 64% of melanoma patients with the primary tumour alone were operated on in two consecutive sessions in the former Federal Republic of Germany and 34.2% of those in the former Germany Democratic Republic. During this period 73.7% of all melanoma patients were operated on under local anaesthesia. In recent years surgical operations were more often performed in two consecutive sessions, mostly under local anaesthesia and with decreasing safety margins, in keeping with the decrease in tumour thickness. The present analysis shows that the Central Malignant Melanoma Registry is an important instrument for investigating trends in clinical epidemiology and treatment of malignant melanoma in the German-speaking countries.

Adult↗

Collagen synthesis in (sun-) aged human skin and in fibroblasts derived from sun-exposed and sun-protected body sites.

Endogenous and sun-induced aging of the skin cause distinct morphological alterations. In this study, we have analysed the ratio of collagen III to collagen III plus I in extracts of sun-exposed (face) and sun-protected (abdomen) aged skin, as well as in collagens synthesized by fibroblasts during in vitro culture derived from actinically damaged and sun-protected skin of other subjects (face, medial aspect of the upper arm vs. abdomen, lateral aspect of the forearm). Furthermore, the amount and extent of post-translational modifications of newly synthesized collagens were determined. Chronic sun exposure of the skin does not have an impact on the quantity of collagenous proteins newly synthesized in cell culture. The proportion of collagen III in pepsin extracts of sun-damaged skin is increased relative to sun-protected skin. However, fibroblasts derived from sun-exposed skin synthesize a lower proportion of collagen III than cells from sun-protected skin. The hydroxylation of lysyl residues in newly synthesized alpha 2(I) and alpha 1(III) collagen chains is reduced by UV irradiation, whereas hydroxylation of lysyl residues in alpha 1(I) chains and of prolyl residues in alpha 1(I), alpha 2(I) and alpha 1(III) chains is unaffected by UV irradiation. These data provide circumstantial evidence to indicate that collagen synthesis is influenced independently by endogenous and sun-induced aging.

Aged↗

UV-irradiated melanocytic nevi simulating melanoma in situ.

A causative role of UV light in the development of melanocytic neoplasms has often been suggested. In order to investigate the short-term effects of UV light on melanocytic nevi, the morphological and immunohistochemical changes in nevi after a single UV irradiation are studied in 12 nevi from 10 patients and compared with the nonirradiated part of the same nevus. After irradiation more melanocytes above the dermal-epidermal junction are observed in seven nevi, simulating a melanoma in situ in three nevi. Moreover, a marked increase in the expression of HMB-45 is found after irradiation in all investigated nevi, indicating an activation of the melanocytes and active melanosome formation. The metabolic activity correlates with the ultrastructural findings, which show a large cytoplasm, hypertrophic Golgi apparatus, abundant mitochondria, and an increased number of melanosomes of different stages. One week after irradiation, no increase in the proliferative activity of the melanocytes is found. The morphological and immunohistochemical changes after one low dose of UV irradiation should be considered in the differential diagnosis of pigmented skin lesions. The UV-irradiated nevus should be added to the list of so-called simulators of malignant melanoma.

Adolescent↗

Ultraviolet irradiation induces acute changes in melanocytic nevi.

Ultraviolet (UV) light represents one of the factors that might play a role in the initiation and promotion of malignant transformation of human melanocytes. To determine the short-term effects of UV irradiation on melanocytic nevi in vivo, we investigated one half of symmetric melanocytic nevi after a single UV exposure with double the patient's minimal erythema dose. This half was compared with the nonirradiated, shielded half of the same nevus. The different parts were examined histologically for differences and immunohistochemically for the presence of HMB-45 antigen and proliferating cell nuclear antigen. The features were assessed quantitatively by image analysis. One week after the single UV irradiation, we observed a significant increase of suprabasally located melanocytes and a markedly enhanced expression of HMB-45, whereas proliferative activity of the cells was unchanged. In nevi that were excised 2 or 3 weeks after irradiation, no significant differences were observed between the irradiated and the nonirradiated part. The results indicate that a single UV irradiation may induce transient melanocytic activation with morphologic and histologic changes. Although these data do not formally assess resemblance to melanoma, these changes may be similar to those of melanoma in situ.

Adolescent↗

Analysis of the age-related composition of human skin collagen and collagens synthesized by fibroblast culture.

Age-related differences in the composition and the post-translational modifications of human skin collagens were examined in the present study. The data were compared with results of collagen synthesis from in vivo-aged fibroblasts in culture. Skin extracts and newly synthesized collagen from fibroblast cultures derived from both old and young donor groups showed the same ratio of collagen III to collagen I. Furthermore, no difference was noted in the degree of prolyl and lysyl hydroxylation of collagen I and collagen III Young and old fibroblasts synthesized a similar quantity of collagen in vitro. The data suggest that fibroblasts maintain a uniform level of collagen production, composition and modification independent of the age of the donor.

Adult↗

Control function of protein kinase C isozymes on leukotriene generation from human basophils?

Arachidonic acid metabolites generated from activated basophils and/or mast cells mediate different types of cutaneous inflammatory reactions. To clarify the mechanisms of leukotriene C4 (LTC4) production from human basophils, cells were purified from the peripheral blood by negative selection with immunobeads. The protein kinase C (PKC) activators 12-O-tetradecanoyl-phorbol-13-acetate, phorbol-12,13-dibutyrate and phorbol-12,13-didecanoate did not induce a significant LTC4 generation from human basophils in vitro, indicating that phorbol-ester-sensitive PKC isozymes are not involved in the mechanisms of arachidonic acid metabolism in these cells. However, selective PKC inhibitors (Ro 31-7549, ilmofosine, GF109203X, and calphostin C) potentiated the IgE-mediated LTC4 production in a dose-dependent fashion. We therefore suggest that PKC isozymes which are influenced by these inhibitors modulate the degree of LTC4 release after stimulation with anti-IgE antibodies.

Basophils↗

Functional comparison of different histamine-containing IgE-receptor positive cells.

The present study was performed to investigate the histamine-releasing activity of non-immunological stimuli on cultured mast cell lines in comparison to isolated skin mast cells and basophils as human therapeutic target cells. The ionophore A23187 induced a dose dependent histamine release from all cell populations (enzymatically isolated human skin mast cells, human peripheral basophils and rat basophilic leukemia cells, RBL-1 and RBL-2H3). The lectin concanavalin A and the tripeptide formyl-methionyl-leucyl-phenylalanine activated only basophils, while the neural mediator substance P and compound 48/80 were active only in experiments with skin mast cells. Activators of protein kinase C (different phorbol esters and the non-phorbol mezerein) induced direct histamine release only from basophils. The data provide further evidence for heterogeneity of mast cells and indicate different signal transduction mechanisms following non-immunological activation.

Animals↗

Direct effects of second-generation H1-receptor antagonists on the activation of human basophils.

The present study was performed to investigate the putative suppressive effects of H1-receptor antagonists (HRA) of the second generation (astemizole (AS), cetirizine (CT), loratadine (LO), oxatomide (OX) and terfenadine (TF)) on the mediator release from human basophils activated by two classical stimuli. Anti-IgE-mediated histamine release was inhibited in a dose-dependent fashion by TF (maximum inhibitory value: 33.8 +/- 7.6%, 100 microM, n = 7), whereas the other HRA exhibited weaker activity. The anti-IgE-induced LTC4 production was strongly suppressed by TF, LO and OX (92.4 +/- 6.3%, 90.8 +/- 6.0% and 88.5 +/- 5.6%, 100 microM, n = 4-5), while AS was less active (56.4 +/- 4.1%, 100 microM, n = 5). Histamine release induced by incubation with grass pollen antigen (0.01%) was inhibited by TF (40.7 +/- 4.1%, 50 microM, n = 4), but the other HRA showed only low activity. The present findings suggest that some HRA might exhibit direct inhibitory effects on activation of IgE-receptor bearing cells.

Basophils↗

Immunohistochemical studies with skin mast cells.

Using different histochemical and immunohistochemical methods we demonstrate that isolated skin mast cells used for different pharmacological and biochemical studies exhibit the same staining pattern compared to skin mast cells in situ. Surface structures and enzyme content of the cells appear not to be influenced by the isolation technique. We also observed no differences in the staining pattern of mast cells in neurofibroma, a cutaneous disorder characterized by an increase of mast cell numbers.

Chymases↗

Investigations with the selective PKC inhibitor chelerythrine on human basophils.

Modulation of protein kinase C (PKC) activity in basophils (B) can influence IgE-mediated histamine release (HR). The present study investigated the effects of chelerythrine, which inhibits isolated PKC (IC50 0.7 microM), on different activation pathways in B. Fc epsilon RI-mediated HR was strongly inhibited by chelerythrine (86.5 +/- 5.4%, 5 microM, n = 11). TPA-induced mediator release was also suppressed: 77.1 +/- 8.5% inhibition (7.5 microM). HR due to non-immunological stimuli (A23187, FMLP) was strongly inhibited by chelerythrine. Previously, other selective PKC-inhibitors have been shown to potentiate IgE-mediated HR from B suggesting a negative modulatory role of PKC, whereas non-specific inhibitors such as staurosporine inhibited HR. Chelerythrine might therefore be less selective for PKC. This may be indicated by the fact that chelerythrine inhibits PKC at its catalytic domain, which is homologous with other protein kinases.

Alkaloids↗

[Position and recommendations of the Malignant Melanoma Committee of the German Society of Dermatology on diagnosis, treatment and after-care of malignant melanoma of the skin. Status 1993/94].

The Melanoma Committee of the German Dermatological Society has prepared this position paper on prognostic factors, classification and clinical staging of cutaneous malignant melanoma and has recommended guidelines for diagnosis, treatment and follow-up. The aim is to achieve a consensus procedure for dealing with this tumour.

Aftercare↗

Investigations on plasma levels of mast cell mediators in acute atopic dermatitis.

Skin mast cells have been proposed to be involved in the pathogenesis of acute and chronic phases of atopic dermatitis (AD). The aim of the present study was to investigate the significance of different mast cell mediators during acute exacerbation of this frequent skin disease. Plasma levels from 19 patients with AD were screened for elevation of the mast cell-specific protease tryptase, the biogene amine histamine, and the arachidonic acid metabolite prostaglandin D2. None of the patients showed elevated plasma levels of these three mediators, whereas the mean serum IgE level was strongly elevated. We conclude that the investigated mediators are either only active on the cutaneous level or that other mediators are responsible for the development of the acute eczematous and pruritic skin reactions. Alternatively, the assays could have been insufficiently sensitive since some studies have demonstrated increased plasma histamine levels, e.g. after food challenge of such patients.

Acute Disease↗

Surfactant-induced skin irritation and skin repair. Evaluation of the acute human irritation model by noninvasive techniques.

BACKGROUND: Although the induction of irritant dermatitis by surfactants has been extensively studied in recent years, our understanding of the repair phase of irritant dermatitis is limited. OBJECTIVE: We investigated qualitative and quantitative differences in surfactant-induced irritant skin reactions from short-term exposure to three structurally different surfactants. METHODS: Sodium lauryl sulfate (SLS), dodecyl trimethyl ammonium bromide (DTAB), and potassium soap were the model irritants. Surfactant solutions (0.5%) were applied for 24 hours to the volar aspect of the forearm of 11 volunteers. Irritant reactions were assessed until complete healing was indicated by visual assessment and by various aspects of skin function, that is, transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum that is, transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum corneum hydration (electrical capacitance). RESULTS: SLS and DTAB induced similar degrees of erythema, whereas SLS induced significantly higher TEWL increase. Although both erythema and TEWL were highest 1 hour after exposure to surfactants, skin dryness was a symptom with delayed onset, justifying the long observation period in this study. Minimum hydration values were measured as late as 7 days after surfactant exposure. Dryness was significantly more pronounced in areas exposed to SLS than in areas exposed to DTAB. Complete repair of the irritant reaction induced by either SLS or DTAB was achieved 17 days after surfactant exposure. Stratum corneum hydration was the last feature to return to baseline values. Potassium soap did not significantly influence any skin function. CONCLUSION: We emphasize the importance of extended periods needed before a patient with irritant contact dermatitis can be reexposed to irritant substances. The evaluation of the irritation potential of diverse surfactants depended significantly on the feature (erythema vs hydration and TEWL) measured.

Adult↗

Surfactant-induced skin irritation and skin repair: evaluation of a cumulative human irritation model by noninvasive techniques.

BACKGROUND: Although surfactant-induced acute irritant dermatitis has been extensively studied, our understanding about the induction and repair of the clinically more relevant chronic form is limited. OBJECTIVE: Our purpose was to investigate qualitative and quantitative differences in surfactant-induced irritant skin reactions from cumulative exposure to structurally unrelated surfactants and to compare the maximal irritant responses from this model with corresponding reactions noted in a previously reported acute irritation model. METHODS: Sodium lauryl sulfate (SLS), dodecyl trimethyl ammonium bromide (DTAB), and potassium soap were the model irritants. Surfactant solutions (7.5%) were applied for 20 minutes daily (for 8 consecutive days excluding the weekend) to the volar aspect of the forearm of 11 volunteers. Irritant reactions were repeatedly assessed until complete healing was indicated by visual assessment and by measurements of transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum corneum hydration (electrical capacitance). Maximum irritant responses were compared with corresponding reactions from an acute irritation model. RESULTS: TEWL was increased by SLS and DTAB to the same extent, but erythema was significantly higher in DTAB-treated skin. Skin dryness, as demonstrated by decreased capacitance values and increased scores for scaling and fissuring, was significantly more pronounced than in an acute irritation model for SLS and DTAB, although no difference was detected between the two surfactants. Potassium soap led to a slight increase in TEWL, whereas the remaining features were not significantly changed. CONCLUSION: This chronic irritation model appears to represent the clinical situation of irritant contact dermatitis with pronounced skin dryness more closely than the acute irritation model. The present study confirms that an extended time is needed for complete healing of irritant skin reactions. We also demonstrated that the evaluation of the irritation potential of diverse surfactants depended significantly on the feature evaluated (erythema vs electrical capacitance and TEWL), on the mode of application (acute vs cumulative), and, in the cumulative model, on the point of observation.

Adult↗