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Biomedical subjects

H Pehamberger

Publications and source records attributed to H Pehamberger.

At least 109 records · Page 6Linked to original sources
PubMed1987

Comparison of the effects of three different treatment regimens of recombinant interferons (r-IFN alpha, r-IFN gamma, and r-IFN alpha + cimetidine) in disseminated malignant melanoma.

A total of 30 patients with progressively growing visceral and/or cutaneous malignant melanoma metastases were entered in a prospective phase II trial comparing three different therapeutic regimens of recombinant interferons (r-IFN). The first group of 12 patients received r-IFN alpha A 9-36 IU/day i.m. on 5 consecutive days/week. A second group of 11 patients was treated with r-IFN alpha A and oral cimetidine, 1000 mg/day. The third group of 7 patients had i.v. infusions of r-IFN gamma 0.25-0.5 mg/m2 on 3 days/week. Of the 12 r-IFN alpha A-treated patients, 1 responded (complete response, CR), 5 patients exhibited no change (NC), 3 patients had progressive disease (PD), and 3 patients could not be evaluated after therapy. In the group treated with r-IFN alpha A plus cimetidine 3 patients responded (1 CR, 2 partial responses) and 3 exhibited NC. The remaining patients showed PD. Treatment responses were found exclusively in patients with cutaneous and/or lymph node metastases. In contrast, none of the r-IFN gamma-treated patients responded to therapy. Known IFN side effects of varying degrees, sometimes severe, were observed in all patients. Despite the small numbers of patients treated, our preliminary data indicate that r-IFN alpha A therapy seems (1) to be of some therapeutic value in the treatment of cutaneous melanoma metastases, (2) to be superior to r-IFN gamma therapy, and (3) that overall response rates improve with the addition of oral cimetidine to r-IFN alpha A treatment.

Cimetidine↗
PubMed1987

In vivo epiluminescence microscopy of pigmented skin lesions. I. Pattern analysis of pigmented skin lesions.

The importance of recognizing early melanoma is generally accepted. Because not all pigmented skin lesions can be diagnosed correctly by their clinical appearance, additional criteria are required for the clinical diagnosis of such lesions. In vivo epiluminescence microscopy provides for a more detailed inspection of the surface of pigmented skin lesions, and, by using the oil immersion technic, which renders the epidermis translucent, opens a new dimension of skin morphology by including the dermoepidermal junction into the macroscopic evaluation of a lesion. In an epiluminescence microscopy study of more than 3000 pigmented skin lesions we have defined morphologic criteria that are not readily apparent to the naked eye but that are detected easily by epiluminescence microscopy and represent relatively reliable markers of benign and malignant pigmented skin lesions. These features include specific patterns, colors, and intensities of pigmentation, as well as the configuration, regularity, and other characteristics of both the margin and the surface of pigmented skin lesions. Pattern analysis of these features permits a distinction between different types of pigmented skin lesions and, in particular, between benign and malignant growth patterns. Epiluminescence microscopy is thus a valuable addition to the diagnostic armamentarium of pigmented skin lesions at a clinical level.

Basal Cell Carcinoma↗
PubMed1987

In vivo epiluminescence microscopy of pigmented skin lesions. II. Diagnosis of small pigmented skin lesions and early detection of malignant melanoma.

Pattern analysis by epiluminescence microscopy of pigmented skin lesions was tested in a study of 318 small pigmented skin lesions that were diagnostically equivocal when examined with the naked eye. An improvement of clinical diagnosis was achieved by epiluminescence microscopy for practically all lesions, both benign and malignant, and was equally impressive for melanocytic and nonmelanocytic lesions. Improvement in diagnostic accuracy was as follows: for small nodular melanomas, from 50% to 70%; for superficial spreading melanoma in situ, from 46% to 80%; for invasive superficial spreading melanoma, from 64% to 90%; and for early lentigo maligna and lentigo maligna melanoma, from 67% to 88%. Conversely, the diagnosis of pigmented Spitz nevi improved from 46% to 93% and of pigmented basal cell carcinomas from 60% to 90%, which appears equally important because most of these lesions had clinically been considered to represent melanomas. The use of epiluminescence microscopy also resulted in considerable improvement in the diagnosis of dysplastic nevi, which was particularly helpful in making therapeutic decisions. Epiluminescence microscopy greatly expands the diagnostic armamentarium available for pigmented skin lesions at a clinical level and thus increases the chances of detecting or ruling out melanoma in its earliest stages.

Basal Cell Carcinoma↗
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↗
PubMed1986

[Oral leukoedema--sequela of an artifact].

A 23-year-old white female with a history of psychological instability presented with burning, adhesive, white plaques of the buccal mucosa. She had been unsuccessfully treated for 1.5 years with topical retinoids as well as topical and systemic corticosteroids. The differential diagnoses included leukoplakia, cheek biting and lichen planus. Clinical and histopathological examinations suggested the diagnosis of severe oral leukoedema. Careful history and clandestine surveillance of the patient finally revealed the lesions to be due to a caustic (over-the-counter product for the treatment of corns), which the patient regularly applied to her buccal mucosa.

Adult↗
PubMed1986

[Secondary cutaneous mycoses caused by Alternaria species].

Analysis of 2 of our own cases of cutaneous alternariosis (CA) and 31 reported cases showed this mycosis to be nosologically heterogeneous. CA may present as an endogenous, multilocular form or as an exogenous, usually localized form. In the endogenous form of CA (11 cases), infection most probably occurs via the lung by inhalation. The highly dermatotropic organisms spread hematogenically to the skin where they cause the typical verruciform or granulomatous lesions. In the exogenous form (8 cases), the organisms are inoculated at the site of a trauma ("traumatogenic CA"). In both forms, the underlying pathogenic disorders are of a non-mycotic nature, and hypercorticism plays the most important role. In the third form ("dermatopathic CA", 14 cases), Alternaria alternata secondarily colonizes, in a non-parasitic fashion, in preexisting lesions, which are predominantly steroid-treated eczema of the face. This form represents nosoparasitism of A. alternata rather than genuine mycosis. With regard to the pathogenesis of alternariosis, the predisposing factors mentioned are more important than the relatively weak pathogenicity of the organisms. Elimination of the predisposing factors usually cures the disease. If this fails, surgical excision of the lesions is required since an effective systemic anti-mycotic drug for CA is not yet available.

Adolescent↗
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

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↗
PubMed1985

Epidermal cells as accessory cells in the generation of allo-reactive and hapten-specific cytotoxic T lymphocyte (CTL) responses.

The capacity of epidermal cells (EC) to stimulate T cell activation is a Langerhans cell (LC)-dependent phenomenon. In all in vitro assays probed, LC subserve antigen-presenting cell functions in that they display surface-bound foreign or altered-self structures and thereby activate T cell responses. In contrast, attempts to demonstrate accessory cell (ACC) function of LC-containing EC have yielded negative results, i.e., EC lacking foreign cell surface antigens were not able to restore cytotoxic T lymphocyte (CTL) responses in Ia+ adherent cell-depleted cultures. Reasoning that the ACC function of EC might be critically linked to cluster formation between LC and other cell types involved, we tested the ACC function of EC under experimental conditions that allow a close physical contact between the cell types involved (round-bottomed microtiter plates and brief centrifugation of culture plates). By using these modifications, the failure of highly purified B6 T cells to develop alloreactive CTL activity when stimulated with either highly purified, mitomycin C-treated C3H or B6CF1 T cells was restored by the addition of B6 EC. The CTL thus generated produced significant lysis of Con-A-stimulated C3H or BALB/c, but not B6, spleen cell targets. In a similar fashion, TNP- or FITC-specific CTL were generated when (in a syngeneic system) mitomycin C-treated TNP- or FITC-modified stimulator T cells and responder T cells were co-cultured in the presence, but not in the absence, of unmodified EC. The capacity of EC to restore CTL activity in a culture system depleted of Ia-bearing cells was not dependent upon their H-2 type, but was critically linked to the presence of Ia-bearing LC. We therefore conclude that LC-containing EC can subserve the ACC function in the generation of H-2-restricted CTL, provided that culture conditions are chosen that allow a close physical contact between the cell types involved.

Animals↗
PubMed1984

Dysplastic nevus syndrome with multiple primary amelanotic melanomas in oculocutaneous albinism.

Melanomas are rare in albinos, although the incidence of solar radiation-induced skin tumors is extremely high because of the absence of photoprotective melanin. This report describes a 40-year-old white woman with tyrosinase-negative oculocutaneous albinism who developed four primary amelanotic melanomas--three of the superficial spreading and one of the nodular type-and, in addition, displayed nevi that exhibited histologically the characteristic features of dysplastic nevi. The concomitant occurrence of multiple primary melanomas and several dysplastic nevi classifies the patient's condition as "dysplastic nevus syndrome," which to our knowledge has not been described in albinism so far.

Adult↗
PubMed1984

Epidermal Langerhans cells can function as stimulatory cells but not as accessory cells in CTL induction.

In this study, we determined whether Langerhans cells (LC) can function as both stimulatory and accessory cells (ACC) in alloreactive and syngeneic modified CTL induction in vitro. LC exhibited potent Ia+ stimulatory function, comparable to spleen cells, in both allo-CTL induction and in TNP-modified CTL induction assays. In contrast to spleen cells, however, when LC were syngeneic to the responders in an Ia+-adherent cell-depleted CTL culture, they could not restore the CTL responses. This was due, in part, to the suppression of CTL induction, presumably via secretion of prostaglandin E by epidermal cells (EC), because addition of indomethacin reversed the suppression. Even in the presence of indomethacin, however, LC were unable to exhibit ACC function. Finally, we tested the possibility that both Ia+ and Ia- cells were required to fulfill ACC functions. However, when spleen cells treated with anti-Ia antibody and complement and EC and indomethacin were added to an Ia+-adherent cell-depleted CTL culture, there was no significant restoration of the CTL response. Thus, LC can clearly act as Ia+ stimulatory cells in CTL induction but cannot serve as ACC in CTL induction, whereas Ia+ spleen cells may subserve both functions. These data suggest a functional heterogeneity of Ia+ antigen-presenting cells in spleen and in epidermis.

Animals↗
PubMed1983

Epidermal cell-induced generation of cytotoxic T-lymphocyte responses against alloantigens or TNP-modified syngeneic cells: requirement for Ia-positive Langerhans cells.

The role of epidermal cells (EC) in the activation of T-cell proliferation is well established. In this study we asked whether EC can provide a stimulus resulting in the generation of genetically restricted T-cell cytotoxicity. For this purpose, C57Bl/6 or C3H/He highly purified, accessory cell-depleted responder splenic T lymphocytes, were stimulated in 5-day cell-mediated cytotoxicity cultures with mitomycin C-treated allogeneic or trinitrophenyl (TNP)-modified syngeneic EC, or, for control purposes, with unfractionated spleen cells (SC). Untreated and complement (C')-treated EC induced strong cytotoxic T lymphocyte (CTL) activity in highly purified allogeneic T cells and, in analogy, TNP-modified EC led to the generation of TNP-self CTL, as tested in 4-h 51Cr release assays against allogeneic or TNP-modified syngeneic EC or SC targets. These cytotoxic responses were comparable in magnitude to those seen with allogeneic or TNP-modified syngeneic SC stimulators. In contrast, alloreactive or TNP-self CTL responses were not generated when stimulating EC were depleted of Langerhans cells by pretreatment with anti-Ia monoclonal antibodies plus C' or, for control purposes, when highly purified T-cell stimulators were used. These results demonstrate that EC induce the generation of alloreactive and TNP-self CTL in the absence of Ia-positive splenic accessory cells and that Ia-bearing Langerhans cell are required for this process to occur.

Animals↗
PubMed1982

Langerhans cell-containing epidermal cells are not cytotoxic in antibody-dependent- and mitogen-induced-cellular cytotoxicity.

Langerhans cells (LC) constitute a small (2-6%) subpopulation of mammalian epidermal cells (EC) and are the only EC that bear Fc-IgG receptors and that share several other cell-surface characteristics and functional capabilities with cells of the monocyte-macrophage series. Since Fc-IgG receptor-positive macrophages are potent effector cells in antibody-dependent cellular cytotoxicity (ADCC), we determined whether LC-containing EC populations are also able to mediate ADCC. In the ADCC assay employed, BALB/c LC-containing EC at different effector/target cell ratios consistently failed to lyse bovine red blood cell (BRBC) targets which were either trinitrophenyl(TNP)-modified or not modified and reacted with an appropriate antibody: a purified rabbit IgG anti-BRBC, or a mouse or rabbit anti-TNP antiserum. In addition, LC-containing EC did not mediate mitogen-induced cellular cytotoxicity using purified phytohemagglutinin. BALB/c spleen cells, used as a positive control, gave substantial specific release in all experiments performed.

Animals↗
PubMed1982

Induction of cell-mediated cytotoxic self responses by epidermal cells modified with a haptenic sulphydryl reagent.

Murine epidermal cells (EC) act as stimulator cells in the generation of allogeneic cytotoxic T lymphocytes (CTL) in cell-mediated lympholysis (CML) and are suitable targets for allogeneic and hapten-self CTL. To analyse the role of EC in the generation of and recognition by anti-self CTL, syngeneic hapten-modified murine EC were used as in vivo and in vitro stimulating populations and as target cells in a hapten-self CML system. Epidermal cells were modified with the sulphydryl-reactive haptenic reagent N-iodoacetyl-N'-(5-sulphonic-1-naphthyl)ethylenediamine (I-AED). C3H.SW (H-2b) AED-self CTL responses were generated by stimulation with syngeneic AED-modified EC and were readily demonstrated when tested on syngeneic hapten-modified EC. These CML responses were hapten-specific and H-2 restricted. No substantial difference was detected in the ability of AED-modified EC and spleen cells (SC) to stimulate the generation of secondary AED-self CTL. Cold target inhibition experiments with hapten-modified EC and SC blockers did not reveal tissue-specific recognition of hapten-modified EC or SC targets by AED-self CTL. These findings demonstrate that hapten-modified EC, when used for priming in vivo and subsequently for in vitro sensitization, can induce hapten-specific self CTL that are reactive against syngeneic hapten-modified EC.

Animals↗