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Biomedical subjects

E G Jung

Publications and source records attributed to E G Jung.

At least 19 recordsLinked to original sources

Distribution of Merkel cells in acute UVB erythema.

Merkel cells (MC) were identified immunohistochemically using antibodies specific for cytokeratin (CK) 20 within human epidermis 12 to 72 h after exposure to UVB (4 MED). 12 h after exposure all MC were normally localized within the epidermal basal layer. However, 24 h after exposure 4% of the MC were detected suprabasally, the remaining 96% still being situated in the basal layer. Surprisingly, at 48 h and 72 h more than 50% had lost contact with the basal membrane. The MC of hair follicles did not show any obvious changes. These results argue, in the context of acute epidermal UV damage, for an abnormal turnover in dermatitis.

Acute Disease

Dysplastic nevus syndrome: intrafamilial identification of carriers by cytogenetics.

Seven members of a family with dysplastic nevus syndrome (DNS) were examined clinically; skin biopsies of unaffected skin from 6 were taken. Biopsy-derived cultivated fibroblasts were examined by cytogenetic methods, i.e. by measuring the spontaneous and the UVB- and UVC-driven increase in sister chromatid exchange (SCE). A male patient with malignant melanoma, his son and his nephew, both with multiple dysplastic nevi, showed a distinctive elevation of UV-induced SCE, whereas the other, unaffected members of the family showed normal values. These results give evidence that in siblings with DNS the affected members can be identified not only on clinicopathological grounds but also by UV-induced elevated SCE at the cytogenetic level.

Adult

De Sanctis-Caccione syndrome: xeroderma pigmentosum with oligophrenia, short stature and neurologic disorders.

A 6 year-old boy with de Sanctis-Cacchione syndrome is reported. This syndrome is characterized by the triad xeroderma pigmentosum (XP), mental deficiency and neurological disturbances. The patient's cells were assigned to genetic complementation group A by use of the cell fusion technique. DNA repair capacity as measured by unscheduled DNA synthesis (UDS) was drastically reduced to 7.5%, compared with 100% of the controls. The rate of sister chromatid exchange (SCE), an indicator of the hypermutability in XP, was clearly elevated after ultraviolet radiation of skin fibroblasts of the patient.

Child

Clinical symptoms and DNA repair characteristics of xeroderma pigmentosum patients from Germany.

Sixty-one xeroderma pigmentosum (XP) patients living in the Federal Republic of Germany were investigated. Clinical symptoms were correlated with DNA repair parameters measured in fibroblasts grown from skin biopsies. Classification according to the international complementation groups revealed that of the 61 patients 3 belonged to group A, 26 to group C, 16 to group D, 3 to group E, and 2 to group F; 11 were of the XP variant type. A striking clinical aspect was the frequency of histogenetically different skin tumors varying from one XP complementation group to the other: squamous and basal cell carcinomas predominated in XP group C; lentigo maligna melanomas were most frequent in group D; basal cell carcinomas occurred preferentially in group E and XP variants. Three DNA repair parameters were determined for 46 fibroblast strains: colony-forming ability (D0); DNA repair synthesis (G0); and DNA-incising capacity (E0). Dose-response experiments with up to 13 dose levels were performed throughout to achieve sufficient experimental accuracy. DNA-damaging treatments included UV light, the "UV-like" carcinogen N-acetoxy-2-acetylaminofluorene, and the alkylating carcinogens methyl methanesulfonate and N-methyl-N-nitrosourea. Comparison of clinical signs and repair data was made on the basis of D0, G0, and E0 values of both individual cell strains and weighted means of XP complementation groups. Despite considerable clinical and biochemical heterogeneity within complementation groups distinctive features emerged. In general, D0, G0, and E0 values of all XP strains investigated, including XP variants, were found to be reduced upon treatment with UV light or N-acetoxy-2-acetylaminofluorene. After treatment with UV light or N-acetoxy-2-acetylaminofluorene, cell strains in which DNA-incising capacity was reduced also showed a similar reduction in both colony-forming ability and DNA repair synthesis. Consequently, the weighted mean D0, G0, and E0 values of XP complementation groups and XP variants correlated with each other. Furthermore, the onset of both early dermatological symptoms of XP and tumor growth correlated with the extent of DNA repair defects. Of 45 XP fibroblast strains checked for colony-forming ability after treatment with methyl methanesulfonate only 3 cell strains from group D were found to be more sensitive than normal controls, suggesting that overall repair in XP strains was equal to that in controls. Weighted means of DNA repair synthesis of XP complementation groups, however, showed reductions hinting at impaired excision of distinct alkylated bases.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetoxyacetylaminofluorene

Fibroblasts derived from patients with dysplastic nevus syndrome are not more sensitive towards 254-nm and 312-nm ultraviolet light than fibroblasts from normal donors.

DNA repair capacity of 18 fibroblast strains from patients with dysplastic nevus syndrome, 5 of them with malignant melanoma, was investigated and their colony-forming ability (D0) after UV exposure was determined as a measurement of this. Seventeen fibroblast strains from normal donors served as controls. The dose/response experiments included up to 11 dose levels and two UV wavelength ranges: UV-C (using a low-pressure mercury lamp emitting predominantly 254-nm light) and UV-B (artificial "sunlamp" radiation centering around 312-nm light). The exponential segments of the dose/response curves were analysed by linear regression and the negative reciprocals of the regression coefficients, D0, were calculated for each cell strain and each wavelength range. When comparing D0 values of individual cell strains from patients with and without melanomas with the mean value for all normal donors, only 4 out of 18 showed increased sensitivity towards UV-B. This difference, however, was not statistically significant. On the contrary, weighted-mean D0 values for fibroblast strains from patients with and without melanoma were found to be slightly but significantly higher than those for normal donors (significance level: 5%), indicating that cell strains from these patients were less sensitive to UV light (UV-C and UV-B) of both wavelength. This result, which on the basis of current literature data is somewhat unexpected, holds true within the limits of experimental accuracy of +/- 12%.

DNA Repair

Malignant melanoma in southern Germany: different predictive value of risk factors for melanoma subtypes.

The presented case-control study with 204 melanoma patients and 200 control persons assesses the significance of melanoma risk factors for an ethnically homogeneous population from a geographically small region. In a multivariate analysis of the data the total number of benign naevi proved to be the most predictive parameter with a relative risk (RR) of 14.9 (total number of naevi higher than 50). The constitutional factors red hair colour and skin type 1 were less predictive with an RR of 2.9 and 4.9, respectively. Occupational and recreational sun exposure were of ancillary importance (RR 1.8 and 2.1). The assessment of the risk for the subtypes of melanoma however showed a clear difference in the predictive value of the mentioned risk factors. The risk of developing superficial spreading melanoma is nearly exclusively defined by the number of benign naevi (RR 24.8), red hair colour was of subordinate importance (RR 4.2), whereas the risk of lentigo maligna melanoma is dependent on skin type 1 (RR 12.9) and sun exposure (RR 3.4).

Case-Control Studies

Presence of Merkel cells in sun-exposed and not sun-exposed skin: a quantitative study.

Merkel cells (MCs), the neuroendocrine cells of the skin cannot be identified with certainty using conventional light microscopic staining methods. Using immunoperoxidase microscopy with antibodies specific for cytokeratin 18, which has been established as a marker protein of MCs, we have evaluated the numbers of MCs per mm2 skin in normal and sun-damaged upper arm skin. The sun-exposed skin contained twice as many MCs as the not sun exposed skin. Further quantification of MC density at various body sites (trunk, leg) showed a rather variable but often unexpectedly high MC density. The possible role of MC in development of actinic elastosis is discussed.

Adolescent

Phototoxic erythema following PUVA treatment: independence of complement.

The effect of PUVA treatment on normal human serum (NHS), on isolated PMN, or on C3-deficient guinea pigs and congenic (C3-competent) control animals was tested. At a concentration of 0.1 or 1 mM/l 8-MOP and UVA doses of 5-30 J/cm2, PUVA failed to induce any detectable C3-cleavage in NHS. Furthermore, when the complement (C) activation in NHS had been induced before or after PUVA treatment by various methods. PUVA did not modulate the extent of C3-cleavage. PUVA did not affect the viability of isolated PMN, nor did it induce a release of LDH or elastase. No differences between C3-deficient and C-competent guinea pig skin exposed to PUVA were observed in erythema or histologic responses. Immunohistologic examination of specimens from normal guinea pigs revealed C3b and C3d deposits on necrotic keratinocytes, findings restricted to the PUVA-treated areas. Necrosis of keratinocytes was present in skin specimens of C3-deficient animals from PUVA-treated sites to a similar extent. However, deposits of C3-related antigens were completely absent there. From these observations, we suggest that the induction of phototoxic erythema following PUVA treatment is independent of complement.

Animals

[Risk factors for the development of malignant melanoma in West Germany. Results of a multicenter-case control study].

In this multicenter case-control study (1,079 melanoma patients, 778 control persons), the significance of the well-known risk factors for the development of malignant melanoma (MM) was assessed for a German population. The multifactorial analysis of the data confirmed the total number of melanocytic nevi (MCN) as the most robust indicator for an increased melanoma risk. For persons with more than 50 MCN the relative risk was 4.8 times as high as for persons with fewer than 10 MCN. Hair color was found to be another valuable indicator. In persons with red hair the risk of MM was 4.7 that in individuals with black hair. Remarkably fair persons with skin type 1 (always sunburn, never tanning) had two times the risk of that in persons with skin type 4 (never sunburn, always tanning). The habit sun bathing for recreation showed no influence on the development of melanoma. A 2.7 x increased melanoma-risk was detected in persons with occupational sun exposure and out of doors work.

Case-Control Studies