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Biomedical subjects

K Wolff

Publications and source records attributed to K Wolff.

At least 235 records · Page 13Linked to original sources
PubMed1987

Skin tumors in the European PUVA Study. Eight-year follow-up of 1,643 patients treated with PUVA for psoriasis.

In the continuation of the European PUVA Study, 1,643 patients of the original cohort of 3,175 patients enrolled in this prospective study were reevaluated for skin tumors after an average observation period of 96 months. Thirty-six patients with a total of seventy-one tumors (forty squamous cell carcinomas, twenty-three basal cell carcinomas) were observed. In contrast to the U.S. sixteen-center study, we were unable to demonstrate a clinically relevant increase in the risk of tumors induced by psoralens with ultraviolet A (PUVA), and we also failed to show a clear relationship between PUVA exposure and tumor development. Almost all patients with tumors had been exposed to various carcinogens before the initiation of PUVA. No tumors were detected in patients without such prior treatment, although 10% of the patients had received more than 3,000 joules/cm2 total cumulative phototoxic PUVA dose during the observation period. The discrepancy between the results of the U.S. study and our findings may partly be explained by a variety of factors such as a different treatment approach, a different attitude toward sun exposure, and the overall lower incidence of skin cancer in the European population.

Basal Cell Carcinoma↗
PubMed1986

Interleukin 2 receptors on cultured murine epidermal Langerhans cells.

Rat monoclonal antibodies 3C7 and 7D4 detect two distinct functional regions of the murine interleukin 2 (IL 2) receptor. When studying the emergence kinetics of IL 2 receptors in mixed epidermal cell (EC)-lymphocyte cultures by using 3C7 and 7D4 in an indirect immunofluorescence assay, we regularly encountered a distinctive membrane fluorescence not only on lymphocytes, but also on a subpopulation of cells exhibiting a dendritic morphology. Reasoning that these 3C7/7D4-reactive dendritic cells might represent a subpopulation of epidermal dendritic cells, we studied mouse EC for the presence of 3C7/7D4- reactive cells. Although 3C7/7D4 reactivity was never detected on freshly isolated EC or on epidermal sheets, a small number of 3C7/7D4+ cells was encountered after 24 to 48 hr of culture. These cells exhibited a dendritic shape, expressed Ia antigens, lacked Thy-1 antigens, and displayed the ultrastructural features of Langerhans cells (LC) with the notable exception of Birbeck granules. Although after 24 hr, only 20% of Ia+ EC were 3C7/7D4+, the vast majority of LC displayed 3C7/7D4 binding sites after 4 to 5 days of culture. Preincubation of cultured LC-enriched EC with recombinant human IL 2 prevented subsequent 3C7-but not 7D4-binding to these cells. Western blot analysis of 7D4-reactive material of detergent extracts from LC-enriched EC revealed three bands in the same m.w. range as reported for CTLL cells. These results demonstrate that cultured LC express IL 2 receptors and may bear important implications for a better understanding of growth regulation, differentiation, and immunologic functions of LC.

Animals↗
PubMed1986

Polymorphous light eruption: action spectrum and photoprotection.

Polymorphous light eruption is a common seasonal photodermatosis with a typical history and clinical picture. In the interval, when no lesions are present, the diagnosis relies on artificial reproduction of polymorphous light eruption by phototesting. Photochemotherapy (psoralens with ultraviolet A [PUVA]) is currently an effective preventive treatment. One hundred sixty-seven patients with either a history of polymorphous light eruption or manifest disease entered our study. Of 142 patients tested, 49% developed typical lesions of polymorphous light eruption at the test sites. In 56% the action spectrum was found to be in the ultraviolet A range, in 17% in the ultraviolet B range, and in 26% in both ranges. A total of 122 patients received preventive treatment with PUVA. Of these, fifty-one returned for follow-up. Of the patients who were followed up, 64% reported total protection during outdoor activities in the summer, 26% reported partial protection, and 10% were not protected. Failure to improve was unrelated to the action spectrum. The action spectrum and the incidence of positive results on phototests in our patient population differed from those reported by others. It is possible that differences in the test protocols and in the light sources used may account for this discrepancy. There is clearly a need for a standardized test procedure. However, the majority of patients benefit from PUVA pretreatment regardless of their action spectrum.

Adolescent↗
PubMed1986

Nonmelanoma skin tumors in long-term photochemotherapy treatment of psoriasis. An 8-year follow-up study.

Two hundred ninety-seven long-term photochemotherapy (PUVA)-treated patients from an original cohort of 418 subjects reported in 1980 were reevaluated in a second follow-up in order to determine the risk of tumor development under long-term PUVA. Within an observation period of up to 8 years (mean, 63.1 months) six patients with squamous cell carcinomas and three with basal cell carcinomas were observed. Eight of the nine tumor patients had been exposed to potential carcinogens such as arsenic and/or ionizing radiation prior to PUVA treatment. Five with squamous cell carcinomas were skin type I or II; in four of the six patients with squamous cell carcinomas the tumors were located on unexposed skin areas. The mean cumulative ultraviolet A (UVA) dose in three of the six squamous cell carcinoma patients was three times as high as that in the group of nontumor patients. The other three squamous cell carcinoma patients had lower mean doses than nontumor patients, as did the three patients with basal cell carcinomas. Although the cumulative UVA dose may eventually turn out to be relevant for PUVA carcinogenesis, our present data do not sufficiently substantiate a correlation between cumulative UVA dose and squamous cell carcinoma formation in PUVA-treated patients. This report confirms that previous exposure to carcinogens appears to be the most important factor for nonmelanoma skin tumor formation in long-term PUVA patients.

Adult↗
PubMed1986

Leu-3/T4 expression on epidermal Langerhans cells in normal and diseased skin.

Recent evidence exists that the expression of the Leu-3/T4 antigen is not restricted to thymus-derived lymphocytes but can also be detected on mononuclear phagocytes and epidermal Langerhans cells (LC). When searching for the presence of Leu-3/T4 antigen-bearing cells in tissue sections of a variety of inflammatory and neoplastic skin disorders, we observed quantitative and qualitative differences in the intensity of anti-Leu-3a labeling of epidermal dendritic cells. Reasoning that Leu-3/T4 expression by these cells might be a dynamic event, we compared the anti-Leu-3a LC staining pattern in clinically normal-appearing skin (CNAS) with the expression of this antigen on epidermal dendritic cells in a variety of skin disorders. For this purpose, 4-microns cryostat sections were exposed to the monoclonal anti-Leu-3a reagent and antibody binding was visualized by a sensitive 4-step immunoperoxidase technique. Within CNAS, Leu-3a+ dendritic epidermal cells were visualized at the threshold of detectability. Immunoelectron microscopic studies confirmed the LC nature of these cells. In sharp contrast to CNAS, strong and prominent anti-Leu-3a LC labeling was almost invariably encountered in biopsy specimens from patients with cutaneous T-cell lymphoma and various inflammatory conditions but not in proliferative disorders of resident skin cells. Whereas in CNAS the density of T6+ epidermal dendritic cells greatly exceeded that of anti-Leu-3a-reactive dendritic cells, these differences were less pronounced in diseased skin. Our results: confirm earlier observations that epidermal LC may bear Leu-3/T4 antigens; and in addition, suggest that the degree of Leu-3/T4 expression is regulated by signals from inflammatory cells. The induction of class II alloantigen receptors on class II alloantigen-bearing LC may represent an important regulation mechanism of antigen-presenting cell function.

Adolescent↗
PubMed1986

Immediate pigment darkening phenomenon. A reevaluation of its mechanisms.

Proposed mechanisms of immediate pigment darkening (IPD) are controversial. They include photooxidation of "premelanin," changes in the distribution pattern of microfilaments and microtubules, movement of melanosomes to melanocyte dendrites, increased transfer of melanosomes to keratinocytes, and changes in the melanosome distribution pattern in keratinocytes. We investigated the following aspects of IPD: production of IPD by UVA under physiologic and nonphysiologic conditions in fullthickness skin and epidermal sheets; reversibility of IPD in vitro after in vivo and in vitro production; blocking of IPD by disruption of the microfibrillar or microtubular system in vitro; alterations of the cytoskeleton of melanocytes; the melanosome distribution pattern in melanocytes and keratinocytes. The results were as follows: IPD could be elicited in vitro in full-thickness skin and in epidermal sheets. Its production was temperature independent (0 degrees-37 degrees C) and was not inhibited by repeated freezing and thawing, or by formalin fixation. IPD was reversible in vitro under tissue culture conditions but only in viable skin. IPD could not be blocked by substances that disrupt the microfibrillar or microtubular system (cytochalasin B, colcemid, vincristine). As shown with a monoclonal antivimentin antibody, IPD-producing UVA doses did not induce changes in the cytoskeleton of melanocytes. No changes in number and distribution pattern of melanosomes were observed electron-microscopically and by morphometric analysis of EM micrographs. Production of IPD does not depend on the structural and functional integrity of the melanocyte cytoskeletal apparatus and is not confined to viable skin, whereas its reversibility is. The fact that no increased melanosome transfer occurs may explain the lack of a UV protective action.

Cytochalasin B↗
PubMed1986

Morphological changes in peripheral blood cells and skin in amiodarone-treated patients.

Amiodarone, used in the treatment of cardiac arrhythmia, may lead to severe discolouration of sun-exposed skin. The lysosomal storage of a lipid-like material has been shown to be the morphological substrate for this cutaneous hyperpigmentation. Examination of peripheral white blood cells of amiodarone-treated patients disclosed identical lysosomal structures indicating that amiodarone treatment leads to a more generalized lysosomal storage of lipids and of amiodarone and its metabolites.

Amiodarone↗
PubMed1986

Late metastases of cutaneous malignant melanoma.

Although late recurrence of cutaneous malignant melanoma (CMM) is a known clinical phenomenon, only 12 adequately documented cases exist in the literature. We describe two female patients with CMM who developed melanoma metastases 18 years after radical excision of their primary tumours and presumed cure. Increasing numbers of reports of cases of delayed metastases of CMM might have implications for management and follow up of melanoma patients.

Adult↗
PubMed1985

Sulfone treatment of granuloma annulare.

Although spontaneous remission of granuloma annulare is not uncommon, most cases are chronic and resistant to a variety of therapeutic modalities. In our study we confirm the beneficial effect of dapsone treatment in patients with localized or generalized granuloma annulare. The results indicate that dapsone is a useful drug to control or at least to improve skin lesions in the majority of patients.

Adult↗
PubMed1985

Expression of the Ly-5 alloantigenic system on epidermal cells.

The expression of Ly-5 alloantigens is confined to hemopoietic cell types and is therefore considered a valuable indicator for the bone marrow derivation of a given cell. The further finding that different hemopoietic cell lineages express different molecular forms of the Ly-5 alloantigens prompted us to investigate (1) whether murine epidermal cells or subpopulations thereof express Ly-5 specificities and if so, (2) whether the expression of particular molecular configurations of Ly-5 antigens would allow us to gain a clue about the derivation of certain epidermal cell populations. When epidermal sheets from BALB/c, C57Bl/6, and C3H/He mice, were exposed to monoclonal anti Ly-5.1 antibody in an indirect immunofluorescence technique, a system of evenly distributed, dendritic cells was visualized. Allelic exclusion of the Ly-5 system was demonstrated by replacing anti-Ly-5.1 antibody by anti-Ly-5.2 reagent and by using epidermal sheets from SJL/J mice. Studies on epidermal cell (EC) suspensions revealed that about 1.6-5.2% of C3H/He EC were Ly-5-reactive and that approximately equal numbers of Ly-5-positive cells bore either Thy-1 or Ia antigens. Electron microscopic studies disclosed two morphologically different Ly-5-positive cell populations, i.e., cells of the Langerhans cell lineage and a recently defined cell system, whose most prominent feature is the expression of the Thy-1 antigen. We have termed these cells dendritic Thy-1+EC (dTHY-1+EC). In order to define the molecular configurations of the Ly-5 alloantigens, EC and spleen cells were internally labeled and--after immunoprecipitation of cell-membrane detergent extracts with anti-Ly-5.1--were analyzed on sodium dodecyl sulfate-polyacrylamide gels. Spleen cells yielded 3 bands with a molecular weight of 180,000, 195,000, and 215,000, respectively, as is characteristic for T lymphocytes, non-T/non-B cells, and B lymphocytes. In contrast, a single 195,000-200,000 dalton band was found in precipitates of both untreated and Langerhans cell-depleted (anti-Ia+C) EC. These data demonstrate the existence and active biosynthesis of the Ly-5 alloantigenic system on certain EC populations, i.e., Langerhans cells and dThy-1+EC, and therefore imply that both cell types originate from a bone marrow-derived precursor. The expression of the same molecular configuration of Ly-5 alloantigens on both LC and dThy-1+EC suggest that these two cell populations do not belong either to the T-cell or to the B-cell lineage and imply an ontogenetic relationship between dThy-1+EC and Ia-positive EC.

Animals↗
PubMed1985

Morphological and phenotypical characterization of bone marrow-derived dendritic Thy-1-positive epidermal cells of the mouse.

Increasing evidence exists that the spectrum of dendritic cells within the epidermis is more complex than previously thought. In addition to Langerhans cells, Merkel cells, and melanocytes, the murine epidermis contains a dendritic cell population whose most prominent phenotypic feature is the Thy-1 antigen. These cells are now generally referred to as dendritic Thy-1+ epidermal cells (dThy-1+EC). The ultrastructural features of these cells do not resemble those of other resident epidermal cells (EC). In particular, their cytoplasm contains abundant intermediate-sized filaments of the vimentin type as well as membrane-limited organelles with a central granular core. The bone marrow derivation of dThy-1+EC is now well established: dThy-1+EC carry Ly-5 determinants whose expression is restricted to cells of the hemopoietic differentiation pathway, and studies using Thy-1-disparate radiation bone marrow chimeras have revealed the presence of donor-type Thy-1+ cells within the epidermis; by immunoelectron microscopy, these cells represent dThy-1+EC. dThy-1+EC repopulate the epidermis at a slower rate than Langerhans cells as evidenced by a direct comparison of the repopulation kinetics of both cell systems in radiation bone marrow chimeras, and by experiments studying the emergence of either Ia+- or dThy-1+EC in an epidermis which had been previously depleted of either Langerhans cells (glucocorticosteroids) or of dThy-1+EC (PUVA). The phenotypical features of dThy-1+EC differ from those of thymus-derived lymphocytes, B cells, dendritic cells, and mononuclear phagocytes. The surface marker repertoire of dThy-1+EC (Thy-1, Ly-5, asialo-GM1) resembles certain members of the rather heterogeneous natural killer (NK) cell system but functional studies are needed to ascertain this contention.

Animals↗
PubMed1985

Inhibition of DNA synthesis of melanoma cells by azelaic acid.

Azelaic acid was successfully used in the clinical treatment of 7 cases of lentigo maligna in that remission of the lesions was observed in all our patients. In order to elucidate mechanism(s) of the beneficial clinical effects, we studied the effect of azelaic acid on cultured melanoma cells. Cell numbers recovered from melanoma cell cultures grown for several days in the presence of 10 mM azelaic acid were 50-70% less than those recovered from control cultures or from cultures containing 10 mM adipic acid. This reduction of cell numbers was not due to a simple cytotoxic or cytolytic effect of azelaic acid but rather due to a dose-dependent inhibition of DNA synthesis. Interestingly, nontoxic concentrations of azelaic acid, which significantly reduced DNA synthesis of cultured melanoma cells, had no overt effect on the protein synthesis of these cells. It is conceivable that inhibition of DNA synthesis is one of the mechanisms by which azelaic acid prevents growth and proliferation of abnormal melanocytes.

Administration, Topical↗