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Biomedical subjects

G Frentz

Publications and source records attributed to G Frentz.

At least 37 records · Page 2Linked to original sources

On circadian rhythms in human epidermal cell proliferation.

The ascertainment of consistent diurnal variations in human epidermal cell proliferation may have important implications for the treatment of many skin diseases. For the evaluation of diurnal rhythms in the growth of human epidermis, skin biopsies were taken every 4th hour for 48 h from each of two persons under synchronized living conditions. The epidermal cell proliferation was assessed by the fraction of cells in S and in G2-M phase as determined by measurements of the DNA content in the individual cells in single-cell suspensions. The existence of diurnally consistent body functions in the test persons was verified by monitoring the excretion of cortisol by urine. The fraction of cells in G2-M phase indicated circadian rhythmicity for the first 32 h of the test period. No regular variation according to time of day could be established in the fraction of cells in S-phase.

Adult↗

HLA-DP antigens in patients with alopecia areata.

The distribution of HLA-DP antigens were studied in 41 patients with alopecia areata (AA) and 188 ethnically matched controls. An increase of DR4 and possibly DR5 in 24 of these patients has previously been reported. HLA-DP typing for DPw1 through w6 and the local specificity, CDP HEI, was performed using the primed lymphocyte typing (PLT) technique. The frequencies of DPw4 were 92.9% in AA patients and 71.3% in controls (relative risk, RR = 5.1, p = 0.0019 and p less than 0.03 when corrected). DPw1 was decreased to 4.9% in patients compared to 14.9% in controls, but the difference was not statistically significant. The frequency of DR4 was 48.8% compared to 31.9% in controls (RR = 2.0) whereas the frequency of DR5 did not differ from that in controls. DPw4 was not associated (in linkage disequilibrium) with DR4 or DR5 in patients or controls. Thus, in AA the association with DP and DR are independent of each other. However, individuals with both the DPw4 and DR4 alleles are at increased risk for AA, indicating that synergism between DP and DR gene products may play a role in the genetic susceptibility to AA.

Alopecia Areata↗

Intralesional interferon-alpha 2b treatment of basal cell carcinoma.

Ten patients with histologically proven basal cell carcinoma were treated with sublesional injections of interferon-alpha 2 b (Introna), 1.5 x 10(6) units per injection, three times per week for 3 weeks. Six of the treated lesions cleared completely without further therapy. These lesions measured less than 19 x 19 mm. There was no relapse during an observation period of up to 21 months. Non-healing tumours were large (greater than 20 x 20 mm) and two of them were of nodular type. Side effects were negligible, if present at all. Introna seems to offer a valuable alternative treatment for selected cases of basal cell carcinoma, when excision or X-ray therapy cannot be performed.

Adult↗

Grenz ray-induced nonmelanoma skin cancer.

In 28 patients, nonmelanoma skin cancers developed in areas previously exposed to grenz rays. In 17 patients who did not have psoriasis, no other relevant carcinogenic exposure could be incriminated. Women were more often affected than men. Most of the tumors were basal cell cancers, and most of the patients had multiple tumors. No threshold dose could be established. The distribution of the latency time among patients without psoriasis was strictly normal (median 18 years). These observations suggest that usual therapeutic doses of grenz rays, as a single agent, are capable of causing skin cancer, but only in those persons who are abnormally sensitive to x-rays.

Basal Cell Carcinoma↗

Non melanoma skin cancer of the scalp. On the etiology.

In order to evaluate the relative significance of previous grenz-ray treatment for human non melanoma skin carcinogenesis, the files were studied of all patients treated for non melanoma skin cancer of the scalp (n = 82, male/female ratio 1.1) at the Department of Dermatology, the Finsen Institute, from 1976 to 1985. Fourteen patients, with a male/female ratio of 3.7, were treated for squamous cell cancer (SCC). Sixty-five patients, with a male/female ratio of 0.9, were treated for basal cell cancer (BCC). Twelve patients (15%, 11 with BCCs, 1 SCC), of which eight with psoriasis, were previously treated with grenz rays on the scalp, and two of them had not been exposed to additional skin carcinogens. Comparably, malignant conversion in sebaceous and verrucous nevi accounted for 9 cases or 11%. Characteristically, scalp cancers associated with previous grenz-ray treatment were BCCs, the male/female ratio were less than 0.1 and two-thirds occurred in patients with multiple skin cancer. That grenz-ray related scalp cancers more often develop in females than in males was further confirmed by comparison to the sex distribution among patients treated on the scalp with grenz rays in the years 1950, 1960 and 1970 (p less than 0.01). (Accepted August 10, 1988.)

Adult↗

Increased number of circulating suppressor T-lymphocytes in sun-induced multiple skin cancers.

The distribution of peripheral lymphocyte subsets was studied in fifteen patients with multiple nonmelanoma skin cancers, selected according to history of ultraviolet (UV) or X-ray exposure. The skin cancer was associated with previous heavy exposure to UV light in seven patients, and past exposure to x-rays in eight patients. In the UV group, the helper T-lymphocytes/suppressor T-lymphocytes (Th/Ts) ratio was abnormally low (P less than 0.01) compared with the ratios of the x-ray and control groups. The low Th/Ts ratio was associated with an absolute increase in the number of Ts. This suggests that heavy sun exposure may cause a permanent increase in the number of Ts in certain persons. These extra T-lymphocytes may in turn prevent immune rejection of transformed keratinocytes.

Adult↗

Normal sister chromatid exchange in lymphocytes from patients with multiple epidermal cancer?

Exposure to toxins in the environment and due to personal habits, e.g., tobacco smoking, may increase the rate of spontaneous sister chromatid exchange (SCE). The SCE in lymphocytes from a group of 31 patients with multiple epidermal cancer, who in the past had been exposed to various skin carcinogens, as a whole exceeded that of a control group--matched by sex, age, and smoking habits--but the difference was not statistically significant (p = 0.08). The individual SCE in these patients was also statistically independent of the nature of the carcinogenic exposure. We were unable to detect correlations between the SCE and UVC-radiation induced DNA synthesis, UVC-radiation tolerance, or rate of X-ray damage repair. This suggests that the molecular mechanisms involved in SCE induction and in repair of radiation damage are basically independent.

Adult↗

The nevoid basal cell carcinoma syndrome: sensitivity to ultraviolet and x-ray irradiation.

Demographic studies in patients with skin cancer have demonstrated the importance of exposure to ultraviolet and x-ray irradiation. This paper describes in vitro studies in peripheral lymphocytes from three patients with the nevoid basal cell carcinoma syndrome. Particular stress was placed on the following factors: (1) the distribution of the lymphocyte subsets, (2) the frequency of spontaneous sister chromatid exchange, (3) the effect of ultraviolet C (UVC) (254 nm) on deoxyribonucleic acid (DNA) synthesis, (4) the effect of UVC on the phytohemagglutinin-stimulated lymphocyte proliferation, and (5) the capacity to repair x-ray-induced DNA damage. Our data indicate that the distribution of the peripheral lymphocytes was normal, while the frequency of spontaneous sister chromatid exchange was high. The capacity of the lymphocytes to repair x-ray-induced DNA damage was low in all three patients. In two patients the UVC-induced DNA synthesis was reduced, while an increased UVC-induced inhibition of lymphocyte proliferation was observed. These cellular responses in vitro to ultraviolet and x-ray irradiation correspond to the clinical features of the nevoid basal cell carcinoma syndrome. A clearly defective in vitro cellular response to x-ray irradiation, reflecting the clinically evident x-ray sensitivity in the nevoid basal cell carcinoma syndrome, has not been reported previously.

Adult↗

Immunohistochemical localization of urokinase- and tissue-type plasminogen activators in psoriatic skin.

Biopsies of involved and uninvolved skin from psoriatic patients and of normal skin were stained immunocytochemically with monoclonal antibodies against urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activator using a multilayer peroxidase technique. Epidermis from psoriatic lesions showed focal staining for u-PA in and between the basal keratinocytes in the suprapapillary epidermal areas, while t-PA was found in the superficial keratinizing cells, including both stratum spinosum and the parakeratotic layer. No staining of keratinocytes was observed in uninvolved and normal skin. The specificity of the staining was supported by the finding that 3 different monoclonal antibodies and polyclonal antibodies against each of the plasminogen activators gave identical staining, while monoclonal antibodies of irrelevant specificity gave no staining. The present findings suggest abnormalities in the regulation of both types of plasminogen activators in psoriatic epidermis.

Antibodies↗

DNA flow cytometry of human epidermal tumours. Intra- and intertumour variability in ploidy and proliferative characteristics.

Tumour ploidy and proliferative characteristics can be estimated by flow cytometric measurements of the nuclear DNA content. This study considers the question whether human epidermal tumours are intrinsically homogeneous with regard to these properties, i.e. whether a single biopsy analysed by flow cytometry is representative of the entire tumour. Analyses of multiple biopsies from ten human epidermal tumours--two kerato-acanthomas (KA), two basal cell carcinomas (BCC), two basosquamous carcinomas (BSC), one Bowen's disease (BO) and three squamous cell carcinomas (SCC)--indicated that both ploidy and proliferation characteristics were reproducible and specific for the peripheries of the different tumours regardless of the histopathologic diagnosis. The tumour centres, however, may deviate considerably from the corresponding periphery. None of the ten tumour peripheries contained more than one cell clone, but six of the ten clones were aneuploid. Both the BO and the KA's were hypodiploid, while one SCC, one BSC and one BCC were hyperdiploid as assessed in their peripheries. The remaining BSC was diploid in its periphery, while both a hypodiploid and a hypotetraploid cell clone were found in the corresponding centre.

Aneuploidy↗

A method for flow cytometric cell cycle analysis of normal and psoriatic human epidermis based on a detergent/citric acid technique for suspension of nuclei.

A new method is described for flow cytometric cell cycle analysis of normal and psoriatic human epidermis, based on non-enzymatic tissue disaggregation. The epidermis was isolated by treatment with acetic acid and stored by freezing. After thawing, the epidermis was disintegrated into a nuclear suspension by 3 steps: incubation with dithiotreitol, whirling in a buffer (pH 7.4) with the non-ionic detergent Nonidet P40, EGTA, RNase and spermine, and whirling after addition of citric acid to a final concentration of 1% (pH 2.4). The suspension was stained with propidium iodide and filtered before flow cytometry. The yield of suspended nuclei was approximately 70% of the original number of cells in the tissue. The detergent/citric acid method was found to be preferable to an ultrasonication method previously used on human epidermis. All cell cycle and cell maturation stages were represented in the detergent/citric acid suspension, in contrast to the selection of immature G1, S and G2 stages with enzymatic methods. In the analysis of psoriatic epidermis inadequately matured (parakeratotic) cells were present in the suspension and had to be discriminated by gating on light scattering intensity, as they were not susceptible to lysis and did not stain properly. The fraction of S phase nuclei was on average 1.9% in normal and 7.7% in psoriatic epidermis, thus confirming the results of other investigators using enzymes. The presence of mitotic figures in the suspension was demonstrated by flow sorting. In this way the mitotic fraction was estimated to 0.06% in normal and 0.22% in psoriatic epidermis, confirming histological data of other investigators.

Biopsy↗