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Biomedical subjects

W Brenner

Publications and source records attributed to W Brenner.

At least 19 recordsLinked to original sources

UV-induced unscheduled DNA synthesis in human skin: dose response, correlation with erythema, time course and split dose exposure in vivo.

Unscheduled DNA synthesis (UDS) has been shown to be saturated above a threshold dose of UV-C in human fibroblasts in vitro. We have investigated by autoradiography whether a similar saturation occurs in human skin in vivo with UV-B and whether this phenomenon correlates with the erythemal response. In addition, we determined the time course of UDS at 24 h after exposure and the effect of dual exposures separated by 24 h. The dose-response curve was established by exposure to 1/16, 1/8, 1/4, 1/2, 1, 2, 3, 4 and 6 MEDs UV-B. For the time-course study, areas exposed to 1/2 and 2 MEDs were biopsied after 1, 3, 6, 12 and 24 h. Autoradiography was performed in vitro. The dose-response curve showed a significant increase in UDS from 1/16 to 1 minimal erythema dose (MED), whereas no significant difference was observed between 1 MED and the higher UV-B doses tested. The 24 h time sequence revealed a gradual decrease in UDS activity. The 1/2 MED curve declined more rapidly and reached the zero-level between 12 h and 24 h, whereas about 50% of the initial UDS value was still retained 24 h after 2 MEDs. The dual-dose study revealed that a second hit of fractions of the MED resulted in lower levels of UDS than induced by these fractions alone in previously untreated areas. UDS increases with the erythemal dose between 1/16 and 1 MED. It reaches a plateau after 1 MED and cannot be increased by doses up to 6 MEDs, suggesting a saturation of excision repair in vivo. Time course studies support such a saturation phenomenon. The failure to increase significantly UDS by a second irradiation 24 h after the first exposure needs further clarification. Since persistence of DNA lesions may lead to an accumulation after repeated exposures, additional mechanisms other than excision repair may protect human skin by error-free removal of possibly mutagenic sites. Photoreactivation may be important in this respect.

Adult

[Dowling-Degos disease: unsuccessful therapeutic trial with retinoids].

A patient with the typical features of Dowling-Degos disease (reticulate pigmented anomaly of the flexures) is described; the clinical picture and differential diagnosis are discussed. Systemic retinoids were used for treatment, but no essential improvement could be observed.

Administration, Topical

Severe preeclampsia with persistent postpartum hemolysis and thrombocytopenia treated by plasmapheresis.

A case of severe preeclampsia in which hemolysis and rapid platelet consumption persisted after delivery, but in which the blood urea nitrogen and serum glutamic oxaloacetic acid transaminase levels returned to normal is presented. Antiplatelet aggregating medications and exchange plasmapheresis with fresh frozen plasma were begun on the eighth postpartum day, but the hemolysis and rapid platelet consumption did not begin to improve until the 12th postpartum day. The use of plasmapheresis in highly selected cases of severe preeclampsia with hemolysis and thrombocytopenia that do not resolve after delivery is discussed.

Adult

Toxemia in a patient with none of the standard signs and symptoms of preeclampsia.

A case of gravida presenting with upper abdominal pain, an elevated serum glutamic oxaloacetic transaminase level, and thrombocytopenia, all of which resolved promptly after delivery, and with none of the standard signs and symptoms needed for the diagnosis of preeclampsia is presented. The issues of how this case relates to preeclampsia, nomenclature, differential diagnosis, and management are discussed.

Abdomen

[Photoprotection by psoralen-UVA therapy: experimental and clinical results (author's transl)].

Studies on minimum erythema doses, histological investigations and quantitative determination of DNA repair synthesis of epidermal cells revealed that a tan induced by the oral administration of 8-methoxy-psoralen (8-MOP) and subsequent UVA irradiation gives protection from the erythemogenic effects of sunlight, diminishes UVA-induced cellular injury in the epidermis and, possibly, also shields DNA from incident UV radiation. In a study of 14 patients with severe polymorphous light dermatosis the 8-MOP-UVA induced tan proved to be a clinically effective sunscreen. The uncontrolled use of this method for UV protection of normal individual is, however, not recommended.

DNA Repair

[HLA B13, B17, B37 and Cw6 in psoriasis vulgaris: relationship to age of onset (author's transl)].

The frequency of HLA B13, B17, B37 and Cw6 was investigated in 77 patients with psoriasis vulgaris (57 patients with an onset of the disease between 10 and 20 years of age and 20 patients with an onset between 35 and 45 years). A highly significant increase in the frequency of the four HLA antigens tested was found. The highest relative risk was calculated for Cw6 (RR = 8.28). Furthermore, a significant positive association was observed between the presence of Cw6 and an early onset of psoriasis vulgaris.

Adolescent

Decreased DNA repair activity in sunburn cells. A possible pathogenetic factor of the epidermal sunburn reaction.

The pathogenesis of the formation of sunburn cells is unknown. Based on autoradiographic methods the unscheduled DNA repair synthesis of UV-induced thymin dimers was investigated in vivo in sunburn cells and in irradiated but histologically normal stratum spinosum cells. The results show a significant lower number of sparsly labeled cells in the sunburn cell-population (13.2 +/- 2.5; mean) when compared to the population of normal stratum spinosum cells (57.8 +/- 7.5; mean). These data indicate that the population of those epidermal cells, which become manifest as sunburn cells 24 h after UV exposure exhibit a reduced DNA repair of UV induced thymine dimers immediately after UV irradiation. Nuclear factors thus seem to play at least some role in the origin of sunburn cells.

DNA Repair

Kinetics of epidermal Langerhans cells.

Langerhans cells are considered to play an important role in the initiation of the immune response. This study was performed in order to analyze the kinetics of the Langerhans cell population under different experimental conditions. Using tritiated thymidine, the number of labeled Langerhans cells (demonstrated by the Leucinaminopeptidase reaction), and of labeled basal keratinocytes was investigated by autoradiography in guinea pig skin in vivo, before and 2, 5 and 8 days after stripping and before and 2, 5 and 8 days after initiation of repeated topical exposures to a 0.25% solution of dinitrochlorobenzene (DNCB). In addition the total number of Langerhans cells per mm2 was determined before and after DNCB treatment of epidermal guinea pig sheet preparations using the ATPase reaction. A total of more than 100,000 cell as of basal keratinocytes was stimulated significantly (by statistical analysis), both by stripping and by application of DNCB. After stripping, however, the increase of the Langerhans cell turnover was found to be secondary to the turnover of basal keratinocytes, whereas after DNCB application the increase in the proliferative activity of Langerhans cells appeared as the primary event in epidermal cellular kinetics.

Animals

PUVA suppresses the proliferative stimulus produced by stripping on hairless mice.

Hairless mice were fed with 8-methoxypsoralen by gastric tube and exposed to UVA light to produce threshold phototoxic reactions. 3H-thymidine autoradiography revealed no significant difference of the epidermal labelling index as compared to that of nonirradiated animals (4.8 vs 6.2). Single PUVA exposures performed 2,8,14 and 24 hr after tape stripping lead to suppression of a wave of synchronized DNA synthesis present in nonirradiated control animals. These data demonstrate different reactions of stripped and unstripped epidermis to PUVA exposures and offer indirect evidence for the suppression of DNA synthesis in hyperproliferative skin disorders by PUVA in vivo.

Animals

5-Methoxypsoralen (Bergapten) in photochemotherapy of psoriasis.

5-Methoxypsoralen (5-MOP, Bergapten) was evaluated as a potential photosensitizing drug in oral photochemotherapy of psoriasis. Treatment results indicate that (1) 5-MOP is as effective as, and in high doses more effective than, 8-methoxypsoralen in clearing psoriatic lesions; (2) therapeutic doses of 5-MOP do not lead to erythema; the acute side-effects of 8-MOP PUVA therapy--erythema, blistering, pruritus--are thus avoided; (3) even high doses of 5-MOP are not followed by nausea. 5-MOP PUVA therapy thus represents a real alternative to 8-MOP PUVA, its advantages over 8-MOP PUVA being greater safety and patient acceptance.

Drug Administration Schedule

Coincidence of vitiligo, alopecia areata, onychodystrophy, localized scleroderma and lichen planus.

The unique coincidence of five dermatological disorders, which occurred in a 39-year-old patient, is discussed. The clinical and laboratory examination did not reveal a common underlying cause. It is hoped this report will stimulate the recognition of other cases and thus aid in determining whether the coincidence of these disorders is a true association of diseases with a common underlying factor or a rare abnormality.

Adult

Serum uric acid levels in untreated and PUVA-treated patients with psoriasis.

Elevated uric acid serum levels are a frequent finding in psoriasis and, despite some reports to the contrary, it is generally believed that an association does exist between hyperuricemia and psoriasis. It seems a convincing idea that the rapid epidermal turnover in psoriasis might lead to an increased purine breakdown and may thus influence the uric acid serum levels. Consequently, a relationship might well be expected between hyperuricemia and the extent of psoriatic skin involvement. The present study was undertaken in order to prove or disprove such an assumption and to investigate the influence of oral photochemotherapy on the serum uric acid levels in psoriatic subjects.

Furocoumarins

[Diagnosis of lupus erythematosus].

For the exact classification of lupus erythematosus, morphological criteria alone (clinical picture, histopathology, immunopathology from involved skin, immunoelectron microscopy) are not sufficient. It is the aim of this paper to discuss briefly the known criteria for the diagnosis of systemic lupus erythematosus with particular reference to the interpretation of more recent deagnostic methods (determination of certain antinuclear antibodies; lupus band test; C1q-binding assay.

Antibodies, Antinuclear

[Ataxia telangiectasia (Louis-Bar syndrome)].

Ataxia telangiectasia (Louis-Bar syndrome) represents a disease of childhood, characterized by diffuse telangiectasia of the skin and the conjunctivae and cerebellar ataxia. Patients are frequently predisposed for infections due to disturbances of the cellular and humoral immunity. This paper discusses the syndrome referring to an own observation of ataxia telangiectasia and literature of the past.

Ataxia Telangiectasia

Kwashiorkor-like zinc deficiency syndrome in anorexia nervosa.

This report deals with a 26-year-old white woman exhibiting signs of both Kwashiorkor (marasmus, pallor, hypopigmentation of hair and hepatomegaly) and acrodermatitis enteropathica (eczematous dermatitis predominantly on acral areas). Clinical and laboratory examinations excluded malabsorption syndrome and glucagonoma syndrome and revealed hypoproteinemia and marked zinc deficiency. Psychiatric examination disclosed anorexia nervosa. Substitution therapy led to rapid clearing of the skin lesions.

Adult

Photoprotective effect of a psoralen-UVA-induced tan.

To determine whether a tan produced by 8-MOP and UVA protects from subsequent solar light irradiation, volunteers were irradiated with unfiltered Xenon arc light before and 10 days after a 1 week's course of four 8-MOP-UVA treatments. Evaluation of the minimal erythema doses and of histological changes before and after 8-MOP-UVA treatment revealed that the 8-MOP-UVA induced tan protected against the erythemogenic and cell damaging effects of Xenon arc light. Unscheduled repair DNA synthesis, used as a measure for UVB-induced DNA damage and repair, was also investigated in skin irradiated with the Xenon arc before and after 8-MOP-UVA induced tanning. Both the number of grains per sparse labeled cell and the number of sparse labeled cells per 1000 cells, were found to be significantly lower in tanned skin; taking decreased unschedules repair DNA synthesis as a measure for decreased DNA-damage, these findings also demonstrate a photoprotective effect of the 8--MOP-UVA induced tan.

DNA Repair