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Biomedical subjects

N J Lowe

Publications and source records attributed to N J Lowe.

At least 145 records · Page 8Linked to original sources

Ultraviolet light and epidermal polyamines.

Numerous studies have indicated that the activities of the polyamine biosynthetic enzymes, ornithine decarboxylase (ODC) and S-adenosyl methionine decarboxylase (SAM.D) are increased in hyperplastic and neoplastic growth. The levels of the polyamines themselves, putrescine, spermidine, and spermine are also often altered in these situations. Epidermal ODC activity is greatly elevated in response to tumor promoting chemicals and also in response to irradiation with short-wave length and mid-wave length ultraviolet. In addition, the levels of the epidermal polyamines change after mid-wavelength ultraviolet irradiation, leading to elevation of putrescine and spermidine, but depression of the spermine level. The spermidine to spermine ratio was significantly elevated after chronic ultraviolet irradiation. Preliminary studies on human skin also shows that mid-wavelength ultraviolet light is capable of inducing ODC. Different pharmacological agents have been found to significantly inhibit the ultraviolet induction of epidermal ODC. Topical corticosteroids and indomethacin significantly inhibit ultraviolet induced opidermal ODC. In addition, retinoic acid inhibited the ultraviolet induction of this enzyme in some experimental situations. Long-wave length ultraviolet alone produced no significant induction of ODC, however, certain phototoxic drugs (8-methoxypsoralen and anthracene) in combination with long-wave length ultraviolet did induce epidermal ODC. It is possible that further studies of changing epidermal polyamine metabolism in response to ultraviolet and tumor promoting agents, may lead to a greater understanding of cutaneous carcinogenesis.

Adenosylmethionine Decarboxylase↗

Mutagenicity of urine from psoriatic patients undergoing treatment with coal tar and ultraviolet light.

The possible percutaneous absorption of the mutagens from patients receiving crude coal tar (CCT) and ultraviolet light was investigated. Urine samples were collected from nonsmoking volunteers, smoking, and nonsmoking psoriatic patients. Patients were treated with 1% CCT U.S.P. or 1 to 10% CCT in petrolatum in the evening. The following morning, patients received coal tar baths and then ultraviolet light (mainly 290-320 nm, UVB). Nonpolar organics in urine samples were extracted by adsorption onto XAD-2 resin and the extracted organics assayed in the Ames Salmonella/Microsome test. TA98 was the most sensitive bacterial strain to detect mutagenicity. Except for smoking psoriatic patients, the addition of liver homogenate was necessary to see mutagenicity. No increase in the number of revertants was observed when B-glucuronidase was added to the assay. Of 14 patients studied 12 had at least one mutagenic urine sample. Typical values for nonsmoking psoriatics treated with CCT ranged from 42 to 496 his +/20 ml of urine after the subtraction of spontaneous his + counts (26 +/- 6). Two nonsmoking normal volunteers were found to excrete mutagenic urines. Smoking psoriatic patients ranged from 213 to 1,100 his +/20 ml urine. This study demonstrates the percutaneous absorption of mutagens from CCT and indicates that its effects may not be limited to the skin.

Absorption↗

Psoriasiform dermatosis in a rhesus monkey.

We describe a dermatosis in a rhesus monkey (Macaca mulatta) that has the characteristic features of the human skin disease, psoriasis vulgaris. The monkey was affected by chronic erythematous, scaling plaques that occurred on the scalp, face, dorsal back, the extensor aspects of the limbs and the palms and soles. Subungual hyperkeratosis was present. Skin biopsies of the affected skin showed a regular acanthosis with reduction of granular cell layer, parakeratosis and supra papillary thinning of the epidermis. Foci of inflammatory cells were seen in the upper epidermis. The dermal changes were tortuous capillary loops and benign inflammatory infiltrate, particularly in the papillary dermis, all of which are features of the human skin disease psoriasis vulgaris. The presence of a nutritional deficiency syndrome was excluded and there was no evidence of any systemic disease.

Animals↗

Topical drug effects on normal and proliferating epidermal cell models.

The effects of 28 different antiproliferative agents applied topically to normal and hyperproliferative hairless mouse skin were studied. Epidermal cell hyperproliferation was induced by an essential fatty acid-deficient diet or by irradiation with short-wavelength ultraviolet (UV) energy. Epidermal DNA synthesis was measured by hydroxyapatite column chromatography. We compared the effects of these drugs used on normal and hyperproliferative hairless mouse skin with clinical responses in patients with psoriasis treated using the same topical preparations. For most of the drugs tested, the normal and essential fatty acid-deficient mouse model effects showed a good correlation with clinical responses seen in treated patients with psoriasis. The short-wavelength UV energy-treated mouse model effects showed a poorer clinical correlation, perhaps partially caused by wide variations in DNA synthetic rates encountered in the epidermis in this model.

Animals↗

Evaluation of sunscreen protection by measurement of epidermal DNA synthesis.

Different sunscreens were tested to determine their protection of epidermis from ultraviolet light effects. Ultraviolet light-induced changes in hairless mouse epidermal DNA synthesis were used for measurement of sunscreen protection. Visual assessment of erythema and edema was also performed. This initial study has evaluated sunscreens containing para-aminobenzoic acid (PABA) as the principle sunscreen chemical. These experiments were conducted using fluorescent sunlamp tubes and hydroxylapatite extraction of epidermal DNA. The ultraviolet light exposure was measured using a recording radiometer. The results showed that the sunscreens tested were able to partially prevent ultraviolet light induced changes in epidermal DNA synthesis. It may be possible to use this assay as one of the initial evaluations of potential ultraviolet light protectants.

4-Aminobenzoic Acid↗

Antiinflammatory drug effects on ultraviolet light-induced epidermal ornithine decarboxylase and DNA synthesis.

Ornithine decarboxylase which forms putrescine by the decarboxyalation of ornithine, is the first and probably the rate-limiting enzyme in the biosynthesis of the other polyamines, spermidine and spermine. Epidermal ornithine decarboxylase activity is greatly elevated in response to tumor promoting agents and ultraviolet light. The purpose of this paper is to report modification of ultraviolet-induced epidermal ornithine decarboxylase activity by antiinflammatory agents. Topical triamcinolone acetonide and indomethacin were found to significantly inhibit the UV-B induction of epidermal ornithine decarboxylase in hairless mice when applied following ultraviolet light irradiation. The corticosteroid also showed inhibition of ultraviolet light increased epidermal DNA synthesis. Indomethacin failed to show any inhibition of DNA synthesis. It is suggested that these assays may be used to study drugs that may modulate some ultraviolet light effects on the epidermis.

Animals↗

A report of two patients with lichen aureus.

Two patients with lichen aureus are described. The clinical and histologic features of our patients were compared with previously reported cases of lichen aureus in an effort to classify this entity properly among the pigmented purpuric dermatoses. We regard lichen aureus as a distinct entity. Although this disorder has been described principally in adult patients it began at the age of 14 years in one of our patients.

Adult↗

Percutaneous absorption in experimental epidermal disease.

Little is known about the absorption of topical drugs in epidermal disease associated with epidermal proliferation and altered keratinization. An abnormal hairless mouse epidermis was produced by three different methods: ultraviolet light irradiation, topical vitamin A acid and topical acetic acid. An increased epidermal thickness resulted and the in vitro percutaneous absorption of 0.1% (4-14C) hydrocortisone was found to be increased when compared with normal hairless mouse epidermis. This is evidence for defective skin barrier function in experimental epidermal disease.

Animals↗

Proliferative epidermis of essential fatty acid deficient mice has reduced cyclic AMP content.

We have simultaneously measured epidermal DNA synthesis, epidermal thickness and cyclic nucleotide levels in essential fatty acid (EFA) deficient hairless mice skin. In vitro epidermal DNA synthesis and epidermal thickness were significantly increased in EFA deficient epidermis. Cyclic AMP levels were significantly reduced when expressed using three different data bases. Cyclic GMP levels were increased using two data bases but these increases were not statistically significant; Cyclic AMP/cyclic GMP ratios were significantly decreased in the EFA deficient skin. The results provide evidence that cyclic nucleotide levels are altered in an animal model of benign epidermal proliferation.

Animals↗

Staphylococcal scalded skin syndrome in an adult with Hodgkin's disease.

An elderly man with Hodgkin's disease who was receiving multiple drug chemotherapy became septic and a wide spread bullous eruption developed. Intraepidermal cleavage on skin biopsy supported a diagnosis of the staphylococcal scalded skin syndrome (SSSS) type of toxic epidermal necrolysis. Blood cultures confirmed a staphylococcal septicemia. Occurrence of this syndrome in an adult is unusual. A review of the literature on SSSS indicates an increased mortality when adults are compared with children with this syndrome.

Aged↗

Photochemotherapy for mycosis fungoides: a clinical and histological study.

Nine patients with stages 2 or 3 mycosis fungoides (MF) and one with Sézary's syndrome were treated with oral methoxsalen and long-wave ultraviolet light. Previous therapy had either failed or achieved only partial control. Satisfactory clinical control was achieved in all but one case. Histological improvement was seen in all cases, but complete clearance of lymphoid infiltrate was noted mainly in epidermal and papillary dermal infiltrates. Lower dermal infiltrate remained largely unchanged. The case of Sézary's syndrome was inadequately controlled with systemic prednisone and cyclophosphamide, but addition of photochemotherapy improved the erythema and pruritus. This shows that photochemotherapy may have a place in MF treatment both alone and perhaps in conjunction with other treatments. An early relapse occurred on stopping photochemotherapy in four cases, but one patient has had three months' full remission.

Adult↗

Burn unit management of toxic epidermal necrolysis.

Toxic epidermal necrolysis is the name given to a group of dermatologic disorders characterized by a separation of epidermis and dermis with a subsequent skin slough. The denuded areas have the appearance of a second-degree burn. The complications of infection, negative nitrogen balance, severe pain, and emotional instability are identical to those seen in the patient with major burns. There are difficulties in patient management and advantages in burn unit care. As with the major burn, care of the patient with skin loss from toxic epidermal necrolysis is extremely complex, requiring the expertise of a burn team along with that of the dermatologist.

Adult↗

Linoleic acid effects on epidermal DNA synthesis and cutaneous prostaglandin levels in essential fatty acid deficiency.

An essential fatty acid (EFA) deficient state has been induced in hairless mice. The epidermal changes included hyperkeratosis, hypergranulosis and acanthosis. Epidermal DNA synthesis was increased 3-fold compared with normal diet mice. Prostaglandin E (PGE) and prostaglandin F (PGF) levels, measured by radioimmunoassay, were much reduced in the EFA deficient mice skin. 10% Linoleic acid applied topically for 2 weeks corrected the gross and histological skin abnormalities and reduced epidermal DNA synthesis to normal values. The levels of PGE and PGF were only partially corrected. Linoleic acid applied to normal diet mice increased skin levels of PGE and PGF compared with the control vehicle treated normal diet mice. These results provide further evidence for the importance of essential fatty acids in the control of epidermal proliferation and differentiation. The importance of PGE and PGF in controlling epidermal DNA synthesis in EFA deficiency is less clear.

Animals↗

Percutaneous absorption in experimental epidermal proliferation.

Essential fatty acid deficiency (EFAD) results in epidermal hyperproliferation with acanthosis and hyperkeratosis. The EFAD hairless mouse has been used to study the percutaneous absorption of a 0.1% solution of 4-(14)C-hydrocortisone. In vitro absorption was increased significantly through EFAD compared with normal hairless mouse skin. This is further evidence for a defective skin barrier function in epidermal hyperproliferation.

Animals↗