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Biomedical subjects

W Brenner

Publications and source records attributed to W Brenner.

At least 91 records · Page 5Linked to original sources
PubMed1981

3H-thymidine autoradiography of guinea pig cornea and skin after exposure to solar simulating radiation.

In vitro autoradiography with tritiated thymidine was performed in guinea pig cornea and guinea pig skin after in vitro exposure to solar simulating radiation (UVB). UVA-irradiated and unirradiated specimens served as controls. Sparsely labelled nuclei, indicating the unscheduled thymine dimer repair DNA-synthesis (dark repair), were observed immediately after UVB exposure in the epidermis and upper dermis of the skin and in all cellular compartments of the cornea. Control samples did not exhibit dark repair. The ratio of sparsely labelled cells was similar in the epidermis and in the corneal epithelium, but was significantly higher in the corneal stroma and highest in the endothelium.

Animals↗
PubMed1981

Unscheduled DNA synthesis in normal human skin after single and combined doses of UV-A, UV-B and UV-A with methoxsalen (PUVA).

The aim of this study was to measure unscheduled DNA synthesis (UDS) by autoradiography in normal human skin (I) after high dose UV-A, (2) after low dose UV-A applied before or after erythemogenic doses of UV-B, (3) after high dose PUVA and (4) after therapeutic doses of PUVA applied before and after erythemogenic doses of UV-B. Single high dose UV-A exposure induced roughly 60% of the amount of UDS induced by equally erythemogenic doses of UV-B. Single low dose UV-A exposure did not induce UDS, nor did it significantly alter the amount of UV-B induced UDS when combined with UV-B exposure. Single high dose PUVA did not lead to UDS and had no influence on UV-B induced UDS when combined with UV-B exposure. Our findings indicate: (I) erythemogenic doses of UV-A induce a considerable DNA excision repair; (2) low dose UV-A neither augments UV-B induced DNA repair nor does it inhibit the repair process; (3) no UDS was shown to occur after eight high or therapeutic doses of PUVA. This was unexpected since psoralen-DNA monoadducts have been shown to be repairable by a mechanism similar to excision repair of pyrimidine dimers. It is therefore assumed that PUVA as performed for therapeutic purposes either preferentially induced interstrand crosslinks not repairable via the classical repair mechanism or the repair of monoadducts was below resolution in this study; (4) therapeutic PUVA doses apparently do not interfere with excision repair of UV-B induced DNA lesions.

Adult↗
PubMed1981

Uptake of amino acids by brain microvessels isolated from rats after portacaval anastomosis.

The uptake of amino acids by microvessels isolated from brains of rats was studied. Previous studies have demonstrated alterations in blood-brain amino acid transport after portacaval shunt in rats. In order to elucidate whether such changes in the blood-brain barrier were located in the microvessels, brain microvessels were isolated from both rats with portacaval shunt and controls. Brain microvessels from rats 2 weeks after shunt operations took up significantly greater amounts of 14C-labeled neutral amino acids, but not of glutamic acid, lysine, or alpha-methylaminoisobutyric acid than microvessels from sham-operated controls. Measurement of uptake kinetics showed a higher Vmax for phenylalanine and leucine uptake and a lower Vmax for lysine uptake in microvessels from shunted rats compared with control, whereas the respective Km's of uptake were similar in both preparations. The results suggest that changes in brain microvessel transport activity account for altered brain neutral amino acid concentrations after portacaval shunt and that such changes can be studied in vitro in isolated microvessels.

Amino Acids↗
PubMed1980

Plasma amino acid analysis in the differential diagnosis of jaundice.

Distinguishing between obstructive (surgical) and hepatocellular (medical) jaundice is sometimes impossible using the relatively simple diagnostic means of history, physical examination and liver function tests. In an attempt to reduce the number of jaundiced patients in need of complex and expensive diagnostic procedures, we investigated the use of the plasma amino acid pattern in the diagnosis of jaundice. Jaundiced rats with galactosamine-induced hepatitis and seven patients with acute onset hepatitis presented a plasma amino acid pattern in which most all amino acid levels were elevated except for arginine in the rat and branched chain amino acids in the patients. Rats jaundiced due to common bile duct ligation and seven patients with obstructive jaundice proved at surgery exhibited a near-normal amino acid pattern. These experimental and clinical data demonstrate very clear qualitative and quantitative differences in plasma amino acid patterns of hepatocellular and obstructive jaundice, with the latter exhibiting an almost-normal pattern. We suggest the use of the plasma amino acid pattern as a useful adjunct in the differential diagnosis of medical and surgical jaundice.

Adult↗
PubMed1980

Long-term photochemotherapy: histopathological and immunofluorescence observations in 243 patients.

Skin biopsies of 243 patients treated with photochemotherapy (PUVA) for 1--4 years were examined histologically. Two hundred and six patients were examined retrospectively after total cumulative UV-A doses of 579 . 6 +/- 598 . 0 J/cm2 (mean +/- s.d.). An eosinophilic homogenization and a reduction of elastic fibres at the dermo--epidermal junction, and an increase of dermal macrophages were found as possible abnormalities. However, except for the increase of melanophages there was no statistically significant correlation between the incidence of these changes, the total UV-A dose applied and the skin type of the patients. Neither were such correlations found in thirty-seven patients biopsies twice after 394 . 8 +/- 267 . 6 J/cm2 and 808 . 5 +/- 458 . 9 J/cm2 (mean +/- s.d.), respectively. Studies with direct immunofluorescence techniques revealed no immunoglobulin deposits in PUVA treated skin in fifty-six patients after 469 . 2 +/- 370 . 2 J/cm2; antinuclear antibodies were observed in 4 . 6% of 129 patients after 169 J/cm2 (mean); in 11% of fifty-three patients reexamined after 381 J/cm2 (mean) and in 13 . 6% of twenty-two patients reexamined a second time after 643 J/cm2 (mean). Thirteen out of a total of 572 patients developed a peculiar mottling of skin in areas previously overdosed by PUVA. Subepidermal homogenization and reduction of elastic fibres were found in 45% of the patients, indicating that these changes indeed are a consequence of PUVA. Nuclear and cellular irregularities were found in 45% of the biopsies and 63% showed a disturbed epidermal architecture, but no carcinomas were observed. PUVA-induced mottling was reversible in 31%, partially reversible in 15%, but continued to be present in 54%.

Adult↗
PubMed1980

Ultrastructural and immunological findings in Graves' disease with pretibial myxedema.

This is a report on a 67-year-old female patient with Graves' disease and extensive pretibial myxedema. Linear IgM deposits were observed in the basement membrane zone by direct immunofluorescence. These deposits were found, by immunoelectron microscopy, to be haphazardly distributed in the uppermost dermis without any correlation to preexisting structures. An amorphous material that coated not only the surface of fibroblasts and collagen bundles but was also present within the dilated endoplasmic reticulum of the fibroblasts was the predominating pathological finding at the ultrastructural level. Mast cells were morphologically normal. These results support previous in vivo and recent in vitro findings indicating that the fibroblast plays a major role in the pathogenesis of pretibial myxedema.

Aged↗
PubMed1980

Autosensitization to DNA.

The spontaneous occurrence of widespread ecchymoses in a patient not exhibiting coagulopathy leads to a spectrum of differential diagnoses including amyloidosis, anaphylactoid purpura, pseudoxanthoma elasticum, Ehlers-Danlos syndrome, autoerythrocyte sensitization and autosensitization to DNA (11). This paper reports on a patient exhibiting the characteristic clinical findings and skin reactivity indicative of DNA autosensitization. The syndrome will be discussed briefly with particular reference to the differential diagnosis to autoerythrocyte sensitization.

Autoimmune Diseases↗
PubMed1979

[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↗
PubMed1979

[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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗