Biomedical subjects
A Oikarinen
Publications and source records attributed to A Oikarinen.
Application of topical corticosteroids.
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Prostaglandins in blister fluid after contact with an irritant and contact allergens.
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Collagen biosynthesis in systemic scleroderma: regulation of posttranslational modifications and synthesis of procollagen in cultured fibroblasts.
Activities of prolyl hydroxylase (PH), lysyl hydroxylase (LH), and the collagen glycosyltransferases and the extent of the posttranslational modification of lysine residues in newly synthesized collagen were studied in fibroblast cultures obtained from 9 scleroderma patients. The rate of procollagen synthesis had increased more than 3-fold in 3 scleroderma fibroblast lines, but had not changed to the same extent in the others, even though these did not differ from the "high-producers" histologically, clinically, or immunohistologically. The activities of PH and LH correlated significantly with the rate of procollagen synthesis in the same cell lines (p less than 0.001), but the glycosyltransferase activities were not elevated in the scleroderma fibroblasts. Further studies nevertheless indicated that the extent of the posttranslational modification of lysine residues had not significantly changed in the procollagen synthesized by any of the scleroderma fibroblasts investigated.
Prevention by zinc of rat lung collagen accumulation in carbon tetrachloride injury.
Orally administered zinc was studied as a protective antifibrotic agent with respect to experimentally caused lung collagen accumulation in rats. Intraperitoneally injected carbon tetrachloride induced a diffuse alveolar damage with interstitial pulmonary fibrosis, and the morphologic findings suggested a primary toxic effect on the lungs. The carbon tetrachloride induction increased significantly the lung to body weight ratio, lung total protein and collagen content, lung total prolyl hydroxylase and galactosylhydroxylysyl glucosyltransferase activities, and daily urinary hydroxyproline excretion. Treatment with 114 mg/L of zinc in the animals' drinking water inhibited the lung prolyl hydroxylase activity and prevented the increases in lung collagen content and urinary hydroxyproline excretion but did not normalize any of the other above parameters. Enhanced lung prolyl hydroxylase activity was noted when a ferrous ion excess was included in the assay in order to reverse the competitive inhibition of the enzyme activity by zinc. It is suggested that zinc has a direct and selective preventive effect on rat lung collagen accumulation by inhibiting procollagen proline hydroxylation.
Basement membrane components and keratin in the dominantly inherited form of cylindroma.
Specific antibodies against basement membrane associated, connective tissue components: type IV and V collagens, laminin, fibronectin and heparan sulphate proteoglycan were used to study the basement membrane-like structures in cylindroma lesions. All these components were immunohistochemically demonstrated as a band surrounding islands of epithelial cells and all except fibronectin also inside the islands. Antibodies to keratin filaments stained most of the cells inside the epithelial islands confirming the epithelial origin of the cells.
[Bullous diseases of the skin: basal membrane disorders?].
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Connective tissue alterations in skin exposed to natural and therapeutic UV-radiation.
Aging of human skin represents a complex situation where several factors contribute to the age-related changes. One of these factors relates to UV-radiation, but the exact mechanistic details are not well established. Several morphologic studies have indicated definite changes in the quantitative aspects of dermal connective tissue components, collagen and elastin. Also, recent biochemical studies have suggested that UV-irradiation can alter the metabolism of these proteins in the skin. This review summarizes the current state of knowledge of the effects of natural and therapeutic UV-radiation on dermal connective tissue, and further delineates additional research needs necessary for disclosure of the exact mechanistic details of the aging processes in human skin.
Modulation of glucocorticoid receptor activity by cyclic nucleotides and its implications on the regulation of human skin fibroblast growth and protein synthesis.
The modulation of glucocorticoid receptor activity by cyclic nucleotides was studied in cultured human skin fibroblasts. The receptors appeared to be activated in the presence of dibutyryl-cAMP and inactivated by dibutyryl-cGMP. Significantly, the cGMP content of the fibroblasts increased during cell growth, with a concomitant decrease in the glucocorticoid receptor activity, while when the cells reached early confluency the decrease in cGMP content was accompanied by an increase in cAMP and increased activity of the glucocorticoid receptors. In addition, cortisol induced (2'-5')oligoadenylate synthetase in these cells and raised the cellular (2'-5')oligoadenylate concentrations. This resulted in a decrease in both DNA and protein synthesis activity in the cells, a response which correlated with the (2'-5')oligoadenylate concentration. The combination of cortisol and dibutyryl-cAMP had a synergetic stimulatory effect on the (2'-5')oligoadenylate concentration and a synergetic inhibitory effect on protein synthesis. In conclusion, it is demonstrated here that cyclic nucleotides can modulate glucocorticoid receptor activity in cultured human skin fibroblasts, and thus these compounds may indirectly affect cellular metabolism by regulating the cellular responses to glucocorticoids.
Ichthyosis hystrix (Curth-Macklin). Light and electron microscopic studies performed before and after etretinate treatment.
Clinical and light and electron microscopic observations of a 16-year-old male patient suffering from ichthyosis hystrix (Curth-Macklin) are presented. The patient had no family history for this disease. The diagnosis was based on the distinct electron microscopic finding of continuous perinuclear tonofibril shells in the keratinocytes. About 10% of the keratinocytes were binucleate and one third contained conspicuous vacuoles. The steroid sulphatase activity in a skin biopsy was normal. Etretinate treatment proved beneficial during the first year of therapy. Later the treatment was less effective. The basic genetic defect persisted in the phenotype of the keratinocytes during etretinate therapy, but the exceedingly thick horny layer was considerably thinned.
Congenital fascial dystrophy--a noninflammatory disease of fascia: the stiff skin syndrome.
Our patient's disease was similar to the persons with stiff skin syndrome described by Esterly and McKusick (1). Stony-hard indurations of the skin and deeper tissue were generalized but most pronounced in the buttocks, thighs, and legs, with limitation of joint mobility and particularly extensive contractures in the lower limbs. The disease was noticed when the patient was 18 months old, and was nonprogressive within a follow-up period of 12 years. There was no visceral involvement except functional impairment of the lungs, probably due to thickened thoracic fascia. Biochemical, histologic, and electron microscopic studies of the skin and muscle were not remarkable. In skin fibroblasts, collagen synthesis was increased and was accompanied by elevated activity of the prolylhydroxylase and lysylhydroxylase, whereas the transferases were not altered. The fascia was considerably thickened, but contained no inflammatory infiltrates. The significant electron microscopic finding was the presence of amianthoid-like collagen fibers in the fascia.
Decrease in liver collagen accumulation in carbon tetrachloride-injured and normal growing rats upon administration of zinc.
Several attempts have been made to develop antifibrotic drugs for human use, but their success has been limited. The present data suggest that peroral zinc treatment has a direct and selective inhibitory effect on carbon tetrachloride-induced collagen accumulation in rat liver. Zinc did not normalize the carbon tetrachloride-induced increases in either liver relative weight, liver total protein content, fat accumulation, or the standard liver function tests, but it did efficiently inhibit liver collagen accumulation. It also reduced skin and liver collagen content and urinary hydroxyproline excretion in normal growing animals, indicating that the inhibition is not limited to the fibroproliferative inflammation associated with carbon tetrachloride injury. Neither inhibition of polysomal protein synthesis nor increased degradation of mature collagen fibers was found to play any major role in the effect of zinc. Instead, a plausible mechanism is inhibition of proline hydroxylation.
A local potent glucocorticosteroid decreases the induction of galactosylhydroxylysyl glucosyltransferase in suction blisters but has no effect on basement membrane structures.
The effects of local glucocorticosteroid treatment on collagen biosynthesis and basement membrane components were studied in suction blisters in human abdominal skin. Pretreatment with clobetasol-17-propionate, applied three times a day for 4 days, did not affect the activity of galactosylhydroxylysyl glucosyltransferase (GGT) in fresh blisters but post-blistering treatment for 3 days with the steroid markedly inhibited the increase of this enzyme activity during the initial phases of re-epithelialization. The GGT activity was over 50% lower in steroid-treated blisters compared with control values. Protein concentrations and blister fluid volumes were also significantly decreased in healing 3-day blisters after steroid treatment. These results suggest that local glucocorticosteroid decreases either the synthesis of GGT or its release from the tissue into the blister fluid. The treatment did not affect the blister histology nor the early process of re-epithelialization. Immunohistochemically, type IV and V collagens and laminin of the basement membrane zone were similarly located in blisters of steroid-treated and placebo-treated skin, suggesting that local glucocorticosteroid does not affect the integrity of the basement membrane.
Prostaglandins in contact urticaria induced by benzoic acid.
To study the role played by prostaglandins (PGs) in contact urticaria, concentrations of 13,14-dihydro-15-keto-PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane B2, the stable metabolites of PGF2 alpha, prostacycline and thromboxane A2 were measured by radio-immunoassay of the fluid taken from suction blisters in 11 patients. The blisters were raised on contact urticarial reactions induced by benzoic acid. The effect of peroral indomethacin on contact urticaria from benzoic acid was studied in a further 14 dermatological patients. The levels of these prostanoids in the blister fluid of urticarial skin did not differ from those derived from control blisters raised on apparently normal skin. Premedication with indomethacin, 50 mg t.i.d., completely prevented contact urticarial reactions to benzoic acid in all patients.
Types I and III collagens and the activities of prolyl hydroxylase and galactosylhydroxylysyl glucosyltransferase in skin lesions of tuberous sclerosis.
Collagen synthesis and the ratios of collagen types I and III were assayed from the skin lesions of five subjects with tuberous sclerosis. Collagen synthesis, measured by the activities of prolyl hydroxylase and galactosylhydroxylysyl glucosyltransferase, was clearly increased in three angiofibromas of these patients and in one soft tumour of the face, but it was unchanged in shagreen patches. The total collagen content was decreased in angiofibromas, indicating either increased turnover of collagen or an increased amount of cellular or other macromolecular elements in these lesions. The proportions of types I and III collagens, estimated by cyanogenbromide digestion and SDS-gel electrophoresis, were 80-90% and 10-20%, respectively, in all samples except two angiofibromas, in which the relative amount of type III collagen was increased. This may indicate that angiofibromas of tuberous sclerosis are heterogenous with respect to the collagen types they contain, and that there may be disturbed cell growth or collagen synthesis, with individual variation from case to case.
Basement membrane components and galactosylhydroxylysyl glucosyltransferase in suction blisters of human skin.
Basement membrane components and collagen biosynthesis were studied in suction blisters in human skin. The basement membrane components were characterized by immunofluorescence using specific antibodies to type IV collagen, laminin and fibronectin, and collagen biosynthesis was studied by assaying galactosylhydroxylysyl glucosylatransferase. In suction blisters, the separation of epidermis and dermis occurred above the lamina lucida, indicating that the basement membrane, composed of lamina lucida and lamina densa, forms a mechanically strong entity. During the regeneration phase of blisters, type Iv collagen and laminin were not observed in the old epidermal blister roof. This indicates that keratinocytes when separated from the underlying basement membrane or connective tissue do not synthesize laminin or type IV collagen. Galactosylhydroxylysyl glucosyltransferase activity could be demonstrated in blister fluid and was about the same as in serum when expressed on the basis of protein in fresh blisters. It increased by 2-3 fold during the repair of blisters, indicating that there was local production of this enzyme. Further studies revealed that pure epidermis contained galactosylyhdroxylysyl glucosyltransferase and hydroxyprolineand this suggests that epidermis may synthesize some collagen type which, according to these studies, is not type IV (basement memebrane) collagen.
Prostacyclin, thromboxane and prostaglandin F2 alpha in suction blister fluid of human skin: effect of systemic aspirin and local glucocorticosteroid treatment.
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Steroid sulphatase activity in the skin biopsies of various types of ichthyosis.
A simple method was developed for the determination of steroid sulphatase activity in a skin biopsy for routine use. In this method, 6 mg of minced tissue is incubated in 1 ml of Krebs-Ringer bicarbonate buffer with radioactive dehydroepiandrosterone sulphate (20,000 c.p.m., S.A. 1.1 Ci/mmol) for 4 h. After the incubation the liberated unconjugated dehydroepiandrosterone and its possible metabolites are separated from the conjugated compound by extraction with ethyl acetate-ethyl ether 10:90 (v/v). The organic phase is counted in a scintillation counter. The results are expressed as c.p.m. values per 6 mg tissue wet weight. Steroid sulphatase activity was measured in skin biopsies from nine control subjects and from thirteen patients with various types of ichthyosis. In the different groups studied, the ranges of the c.p.m. values were as follows: controls (n = 9) 377-1802; X-linked ichthyosis (n = 5) 140-214; ichthyosis vulgaris (n = 5) 607-1320; ichthyosiform erythroderma (n = 2) 2146-2214; lamellar ichthyosis (n = 1) 2185. The reagent blank varied from 180 to 259 c.p.m. In X-linked ichthyosis the c.p.m. values were always less than in the corresponding reagent blank, indicating that no enzyme activity was present in the tissue. In other types of ichthyosis, steroid sulphatase activity was normal. The method described is easy to accomplish in any clinical laboratory where scintillation counting is possible.