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Biomedical subjects

J Lauharanta

Publications and source records attributed to J Lauharanta.

At least 55 records · Page 3Linked to original sources

A semiquantitative light and electron microscopic analysis of histopathologic changes in photochemotherapy-induced freckles.

Photochemotherapy(PUVA)-induced freckles were found in 25 patients (41%) who had received more than 1,000 J/cm2 of PUVA. The patients had been treated with PUVA for more than 2 years, with more than 150 exposures before PUVA lentigines appeared on the thighs, the upper arm, the mid-lower arm, the waist, and the buttocks. The histopathology of these freckles was analyzed by light and electron microscopy. Light microscopy showed an increased amount of pigment and melanophages and increased numbers and size of melanocytes. The keratinocytes often displayed atypical features such as enlarged nuclei, giant size, or fibrillar degeneration. Homogenization of the papillary dermis was observed in 11 patients. The activation of melanocytes was confirmed electron microscopically, and pathological features such as large amounts of lipid droplets and lysosome-melanosome complexes within the melanocytes were seen. The Langerhans cells were mostly normal, whereas the keratinocytes showed cytolytic changes, fibrillar degeneration, and vacuolization. A close follow-up of patients with prolonged PUVA treatment is recommended.

Epidermis↗

Lymphocytes and Langerhans cells in patch tests. An immunohistochemical and electron microscopic study.

The distribution of immunocompetent cells was analysed in allergic (nickel) and irritant (dithranol) patch tests using conventional transmission electron microscopy and labelling with monoclonal antibodies in an avidin-biotin immunoperoxidase study. The biopsies were taken 24 or 48 h after the allergen/irritant application. In allergic and irritant reactions, most inflammatory cells were OKT11 positive (pan T lymphocytes). The majority of these cells were also OKT4 positive (helper/inducer T lymphocytes), while the minority were OKT8 positive (suppressor/cytotoxic T lymphocytes). NK9 positive cells (natural killer cells) were observed in small numbers. The number of dendritic OKT6 and OKIal positive cells (Langerhans cells) in the epidermis was unaffected in allergic reactions. In irritant reactions, a normal number of OKT6 positive Langerhans cells was observed, while the number of OKIal positive cells had increased in the epidermis. Dithranol caused prominent fine structural changes in the mitochondria of the Langerhans cells, while the keratinocytes appeared largely unaffected. The present study indicates that allergic and irritant patch tests cannot be differentiated reliably using current immunohistopathological or electron microscopic techniques, in spite of the small differences observed.

Anthralin↗

Motretinide versus benzoyl peroxide in the treatment of acne vulgaris.

30 patients with acne vulgaris were treated topically with motretinide 0.1% vanishing cream or benzoyl peroxide 5% gel in an open study. Good results were obtained in both groups. Benzoyl peroxide caused local irritation in 73% of the patients, whereas motretinide was well tolerated except in 1 case. Motretinide is considered an alternative in the treatment of papulopustular acne in young adults.

Acne Vulgaris↗

New observations on the fine structure of lamellar ichthyosis and the effect of treatment with etretinate.

Light and electron microscopy were used to study specimens from four patients suffering from lamellar ichthyosis. Three of these patients had been treated with etretinate for 10 months. Biopsy specimens taken from the patients before treatment showed hyperkeratosis with focal parakeratosis, a thickened granular layer in which the cellular content of tonofibrils and keratohyalin was moderately diminished, and acanthosis with increased cellular activity. During treatment with etretinate there was moderate clinical improvement. The most conspicuous microscopic change was thinning of the cornified layer. The intercellular spaces of the epidermis showed increased amounts of fine and coarse granular substance. The number of keratinosomes was increased. Stimulation of Langerhans' cells was observed. Two new ultrastructural findings in lamellar ichthyosis were discovered. First, the marginal band of the cornified layer was absent in conventional glutaraldehyde-osmium tetroxide fixation. Second, the corneocytes contained electron-lucent crystals. The treatment with etretinate did not influence these structures. The mechanism of action of retinoids in lamellar ichthyosis is discussed.

Adult↗

Inhibition of DNA and protein synthesis in UV-irradiated mouse skin by 2-difluoromethylornithine, methylglyoxal bis(guanylhydrazone), and their combination.

Exposure of mouse skin to UVB irradiation greatly enhanced the biosynthesis and accumulation of putrescine and spermidine before or concomitantly with stimulation of epidermal macromolecular (DNA and protein) synthesis. Topical treatment of UV-exposed skin with 2 inhibitors of polyamine biosynthesis, 2-difluoromethylornithine (DFMO) and methylglyoxal bis(guanylhydrazone) (MGBG) prevented the enhanced epidermal accumulation of polyamines, especially spermidine, and also inhibited the incorporation of radioactive precursors into DNA and protein. When applied in combination, these 2 antimetabolites of polyamines produced an inhibition of macromolecular synthesis that was at least additive: [3H]thymidine incorporation decreased by 80% and [14C]leucine incorporation by 44% as compared with the UVB-irradiated control mice. A slight decrease in the ratio of [3H]histidine/[14C]leucine incorporation indicated that protein synthesis of the differentiating cell layers was also affected by the inhibitors. The effects of the combined DFMO and MGBG treatment were partially reversed by concomitant topical application of spermidine.

Animals↗

Ultrastructure of pityriasis rubra pilaris with observations during retinoid (etretinate) treatment.

The light and electron microscopic structure of pityriasis rubra pilaris (PRP) is described in five patients. Hyperkeratosis, hypergranulosis, keratotic plugs in the follicular openings, acanthosis and focal parakeratosis were observed. A moderate perivascular infiltrate was seen in the upper dermis. Electron microscopy revealed moderately activated keratinocytes, a decreased number of tonofilaments and desmosomes, enlarged intercellular spaces, parakeratosis with lipid-like vacuoles and a large number of keratinosomes. Lymphoid cells were present in the epidermis in moderate numbers. At the dermo-epidermal junction, the basal lamina was focally split, containing gaps. Etretinate therapy produced moderate to marked clinical improvement. The histological picture improved but the typical signs of PRP, including follicular plugging, persisted. Ultrastructurally the cellular activity and the amount of hyperkeratosis and parakeratosis decreased, while increases in keratinosomes, intercellular substance, microvilli and desmosomes were observed during treatment.

Adolescent↗

Efficacy of etretinate (Tigason) in clearing and prevention of relapse of palmoplantar pustulosis.

A total of 40 patients with palmoplantar pustulosis (PPP) were initially treated with oral etretinate (Tigason) in an open trail with a maximum treatment period of 16 weeks. Remission, with only slight residual changes in some cases, was achieved in 26 patients (65%) who were randomized to either a low dose of Tigason or placebo. In the Tigason group, 7 of 11 patients were still in remission afer 6 months while in the placebo group, remission persisted in 4 of the 10 patients who stayed in the study throughout the whole 6 months' period. Alopecia led to stopping the treatment in 6 patients and desquamation of the healthy skin in 2 patients. Other side-effects were only mild. As a conclusion, Tigason shows a beneficial effect in the majority of patients with PPP and is better than placebo in preventing relapse of the disease but intolerable side-effects restrict its use in many patients.

Adult↗

Persistent ashen-gray maculae and freckles induced by long-term PUVA treatment.

Persistent ashen-gray maculae 5-7 mm in diameter and freckles developed after prolonged PUVA therapy of psoriasis. Histopathology of maculae showed extensive collections of melanophages in the upper dermis. The melanocytes were strongly stimulated at the site of the freckles. The number of melanosomes, mitochondria, endoplasmic reticulum and dendrites were increased. Pathological features such as large amounts of lipid droplets and lysosome-melanosome complexes were also found within the melanocytes.

Humans↗

Arginase activity and polyamine biosynthesis in psoriasis.

Polyamine biosynthesis and arginase activity in psoriasis were studied using keratotome strips and suction blister roofs as specimens. In the uninvolved psoriatic skin a slight (1.3-fold; p less than 0.05) increase in the spermidine level was observed compared with control skin. There was also a 1.2-fold increase (p less than 0.05) in the spermidine/spermine molar ratio, which is considered to be an indicator of proliferation activity. No changes were noted in other polyamines or polyamine-synthesizing enzymes ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase (AMDC) in the uninvolved psoriatic skin vs. control skin. Neither was there any significant difference in the arginase activity. In psoriatic lesions the levels of all polyamines, as well as the activities of biosynthetic enzymes, were significantly (p less than 0.001) elevated. The putrescine level was elevated to 2.5-fold, spermidine to 2.7-fold and spermine to 1.4-fold. The enzyme activities expressed severalfold increases. The enhancement of arginase activity was less prominent than that of polyamine-synthesizing enzymes, but the increase from 271 +/- 88 to 354 +/- 126 mumol/g/h (1.3-fold) was statistically significant (p less than 0.001; paired t-test). The increase in arginase activity in suction blister roofs, which represents pure epidermis, was more pronounced than that in keratotome strips, i.e. about double. The results show thus that polyamine biosynthesis is significantly enhanced in psoriatic lesions, but there is only a slight difference between the uninvolved psoriatic skin and control skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Langerhans cell--mononuclear cell contacts are not specific for allergy in patch tests.

Langerhans cell-mononuclear cell contacts in the epidermis were analysed in minimum positive allergic and toxic patch tests after 6, 12, 24, 48, and 72 hours. No differences between allergic and toxic patch tests were observed in the appearance of Langerhans cells or in the number of Langerhans cell-mononuclear cell contacts. Thus, Langerhans cell-mononuclear cell contacts are not specific for contact allergic reactions, as has previously been suggested.

Allergens↗

Pharmacokinetics of 8-methoxypsoralen in serum and suction blister fluid.

Micronized 8-methoxypsoralen (8-MOP), with a smaller crystal size, produced significantly higher serum level profiles than nonmicronized 8-MOP. Furthermore, the absorption of the micronized drug was more rapid, resulting in peak serum levels within 1 h in 75% of the patients. Our blister fluid studies suggest, however, that reduction of the photosensitizer concentration is slower in skin than in serum. This implies that despite markedly reduced 8-MOP serum level after 2 h the skin remains sufficiently sensitized up to that point of time.

Blister↗