Lytic susceptibility of target cells to cytotoxic T cells is determined by their constitutive major histocompatibility complex class I antigen expression and cytokine-induced activation status.

Cytotoxic T-cell lines (TCL) were raised in vitro using stimulator cells with a defined major histocompatibility complex (MHC) mismatch and tested in a cytotoxic chromium-release assay against haemopoietic and non-haemopoietic target cells from the original stimulator. Monoclonal antibody (mAb)-blocking experiments and simultaneous determination of MHC class I, class II, lymphocyte function-associated antigen-1 (LFA-1) and intracellular adhesion molecule-1 (ICAM-1) density by quantitative radioimmunometric methods and flow cytometry on target cells demonstrated that lysis was restricted by MHC class I and dependent upon the constitutive MHC class I antigen expression. Measurements showed a high constitutive expression of class I MHC antigens on peripheral blood mononuclear cells (PBMC), but a low one on keratinocytes (K). Also, PBMC were more susceptible to lysis by TCL than K. Interferon-gamma (IFN-gamma) treatment of K resulted in increased MHC class I antigen expression and enhanced lytic susceptibility to TCL. IFN-alpha and tumour necrosis factor-alpha (TNF-alpha) treatment, which did not modulate MHC class I antigen expression on K, did not influence the amount of K lysis either. None of the cytokines tested in this analysis, however, increased the expression of MHC class I, class II, ICAM-1 and LFA-1 on PBMC. Only IFN-gamma pretreatment showed a minimal, statistically significant increase in MHC class I antigen expression. In spite of the minimal effect of IFN-gamma and no effect of IFN-alpha on class I MHC expression, pretreatment of target cells with both cytokines considerably increased their lytic susceptibility. The mechanism of cytokine-induced enhanced lytic susceptibility to TCL was not explained by increased MHC class I, LFA-1 or ICAM-1 expression, since no correlation was found between surface expression of these molecules and lytic susceptibility to TCL. These data demonstrate that: (1) the constitutive density of MHC class I antigens determines the extent of TCL lysis; (2) IFN-gamma, and not IFN-alpha or TNF-alpha controls the amount of K target cell lysis by increasing their MHC class I antigen expression; and (3) IFN-gamma and IFN-alpha control the amount of PBMC target cell lysis by a mechanism independent of MHC class I, ICAM-1 or LFA-1 expression.

Clinical study with recombinant interferon gamma versus interferon alpha-2c in patients with condylomata acuminata.

A multi-centre, randomized, open-label trial was conducted to evaluate the safety and efficacy of recombinant interferon (rIFN) alpha-2c versus rIFN gamma in patients with recurrent or persistent condylomata acuminata (CA). Thirty-three such patients were treated either with 6 micrograms rIFN alpha-2c or with 0.1 mg rIFN gamma (both equivalent to 2 x 10E6 IU), single dose, subcutaneously 3 times a week for 6 weeks. In case of no complete clearance at week 10, a second course of treatment with the other type of rIFN was given. There was no significant difference in the complete clearance proportions at week 10 between the two treatment groups (3/16 vs 6/17). No relapses occurred in these patients during the 16 weeks' follow-up. Further clearances during the follow-up resulted in a total complete clearance proportion of 14/33 at the end of study. The treatment was well tolerated. Repeated interferon therapy has its place in treating persistent or recurrent condylomas.

Long-term adjuvant therapy of high-risk malignant melanoma with interferon alpha 2b.

Fifty-three high-risk melanoma patients in stage I and 15 patients in stage II were treated after standard surgical intervention with adjuvant therapy with recombinant interferon alpha-2b (rIFN alpha 2b) therapy for a total period of 20 months. Concomitant patients (stage I, n = 82; stage II, n = 33) with identical stages and prognostic factors without adjuvant therapy were used to evaluate the efficacy of rIFN alpha 2b therapy. No difference in 5-year relapse incidence and overall survival rates could be detected. However, it appears that patients of both stage I and stage II benefit from long-term adjuvant rIFN alpha 2b therapy, because during the treatment period (20 months), the incidence of relapses was lower in comparison to controls. After stopping treatment the incidence of relapse is equal in treated and control groups. According to the results of our study, we suggest using continuous low-dose rIFN alpha 2b therapy for adjuvant treatment of malignant melanoma.

MRI evaluation of pigmented skin tumors. Preliminary study.

Magnetic resonance imaging (MRI) was performed in 16 patients with pigmented skin lesions, seven with nodular melanomas, two with superficial spreading melanomas, two with subcutaneous melanoma metastases, and five with different benign pigmented nodular skin lesions. The results of MRI were compared with the histologic diagnoses. Signal intensities of the lesions were compared with subcutaneous fat, revealing a lower signal intensity of all lesions on T1-weighted images. Intensity measurements showed a significant (P less than .01) difference between benign and malignant lesions on T2-weighted images.

[Polyvinylpyrrolidone iodine--its significance in dermatology]. / Polyvinylpyrrolidon-Jod (PVP-Jod)--seine Bedeutung für die Dermatologie.

In an open comparative study, 40 patients suffering from pyoderma, combustion (1st and 2nd degrees), leg ulcer, or inflammatory white atrophy were treated with a topical preparation containing either polyvinyl pyrrolidone iodine or neomycin. Both preparations were well-tolerated. There was no local hypersensibility. With regard to the therapeutic effect, we did not observe any differences between the two groups of patients. We discuss the properties, modes of action, and contraindications, as well as the possible systemic influences of topically applied PVP iodine.

[Sonography of benign skin tumors]. / Sonographie bei benignen Hauttumoren.

Evaluation of 62 pigmented skin tumors of unknown pathology showed that benign and malignant tumors can easily be separated. Benign skin tumors have many internal echoes whereas malignant melanomas show an almost echo-free structure. Superficial spreading melanomas (SSM) and very flat benign tumors were both recorded as thin echogenic layers. It is not possible to differentiate them by US. Real time US is a simple non stressful, reproducible procedure that should be established as a routine diagnostic tool in dermatology.

Polymorphous light eruption: experimental reproduction of skin lesions by whole-body UVA irradiation.

Fifty patients suffering from polymorphous light eruption (PLE), selected by criteria pointing to UVA sensitivity, were phototested with 2 different polychromatic UVA sources for reproduction of skin lesions. To simulate natural conditions, the patients were whole-body irradiated for up to 5 consecutive days. In 64% of the patients successful reproduction of PLE lesions was obtained by 1 to 4 irradiations. The total dosage ranged from 20 to 280 J/cm2, and the total exposure times from 10 to 60 min. Our results suggest that irradiation of the whole body in UVA-sensitive PLE patients does not provide more convincing test results than phototesting of small previously involved skin sites, as has been done by other groups.

[Immunoscintigraphy with a technetium 99m-labeled monoclonal antibody in patients with melanoma]. / Immunszintigraphie mit einem Technetium-99-m-markierten monoklonalen Antikörper bei Patienten mit Melanom.

In 24 patients with malignant melanoma the clinical feasibility of immunoscintigraphy (ISC) with a Tc99m-labeled F(ab)2 fragment of an anti-melanoma monoclonal antibody was evaluated. This antibody (225.28S) recognizes a human high molecular weight melanoma associated antigen with restricted tissue distribution, which is expressed on melanoma cells in about 90%. The results of ISC were related with the clinical stage of the patients and the level of invasion of the primary tumor (Clark level). Results of ISC indicate the possibility that patients with the highest Clark level have a higher incidence of false negative scintigrams than those with lower levels of invasion of the primary tumor. In 3 out of 5 patients with Clark level 5 false negative scintigrams were found, whereas in 14 patients with lower Clark levels ISC was true positive, however, the number of metastases was underestimated. 14 of 18 patients with clinical stage II-IIIb had positive scans visualizing 27 of 59 metastases. Thus overall sensitivity was 77% and regional sensitivity 46%. Scintigraphically lesions in lymph-nodes, liver and skin were frequently detected, whereas ISC was less sensitive for lung, bone and brain metastases. No false positive findings were observed by ISC (specificity 100%). Relating the sensitivity and specificity of ISC to the prevalance of disease post-test likelihoods for a normal and an abnormal test result were calculated. Post-test likelihood for the disease with an abnormal scintigraphic finding is 100%. However, with a disease prevalance of 75%, according to our patients, the predicitive value of a normal test result is 60%, thus the post-test likelihood for the disease remains rather high (40%).(ABSTRACT TRUNCATED AT 250 WORDS)

[Diagnostic value of ultrasound in malignant melanoma]. / Der diagnostische Stellenwert des Ultraschalls beim malignen Melanom.

High-resolution real-time sonography enables visualisation of the morphology of the cutis and of cutaneous tumours. Evaluation of 26 malignant melanomas showed that there is a high degree of correlation between the sonographically measured values of maximal tumour thickness with those determined postoperatively by histometry. As malignant melanomas have very few internal echos, they can be easily differentiated from benign tumours. High-resolution sonography is thus the only diagnostic imaging method which helps to evaluate preoperatively malignant melanomas.

Parenteral interferon-alpha treatment of psoriasis.

12 patients suffering from psoriasis were given recombinant interferon (IFN)-alpha-2c at a daily dosage of 2.5 X 10(6) or 5 X 10(6) IU for up to 4 weeks by the intramuscular route. One patient showed complete regression and remained free of lesions after 12 months of follow-up. Three patients were judged as partial remission with stop of scale formation and flattening of skin lesions. No beneficial effect was seen in 8 patients. Side effects due to IFN-alpha application, such as fever, headache, malaise, and chills disappeared with subsequent treatments. Our findings suggest a possible positive effect of IFN-alpha in psoriasis.

Treatment of polymorphous light eruption with nicotinamide: a pilot study.

In a pilot study, 42 patients suffering from polymorphous light eruption (PLE) were treated with oral nicotinamide, 3 g daily, for 2 weeks. Twenty-five patients remained free from lesions despite extensive sun exposure. We suggest that an abnormality in tryptophan metabolism is important in the aetiology of PLE, and that nicotinamide administration partially corrects this.