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Biomedical subjects

A Oikarinen

Publications and source records attributed to A Oikarinen.

At least 91 records · Page 5Linked to original sources
PubMed1992

Collagen synthesis in granuloma annulare.

Previous research has demonstrated active collagen synthesis in granuloma annulare (GA), a mainly degenerative disease of the skin. The present investigation is aimed to characterize details of the collagen synthesis and its regulation. Northern and in situ hybridization techniques and immunohistochemical methods are used to identify type I and type III collagen synthesis, regulation-associated polypeptides TGF-beta, Il-1 alpha, and Il-1 beta and an extracellular matrix protein tenascin, as well as lymphohistiocytic cells present in GA lesions. High mRNA levels of both pro-alpha 1 (I) and pro-alpha 1 (III) collagens were detected in GA lesions. In situ hybridization with cDNA probes revealed active fibroblasts with signals for both type I and III collagen mRNA around GA lesions. Some TGF-beta expression was found within the areas of inflammatory cells. Immunohistochemically, most of the mononuclear/lymphatic cells were CD3+ T cells. The helper/inducer phenotype (CD4+) was common among them, but there were no T-suppressor (CD8) cells. CD1+ cells were few in number, as were cells with activation or proliferation markers (CD26, CD30, and Ki67 antigens). Il-1 alpha- and Il-1 beta-positive lymphocytes/monocytes as well as interleukin-2 receptor containing cells were detected around the lesions, i.e., in the same areas as collagen-synthesizing fibroblasts. Another possible association with the regulation of collagen synthesis was the finding of an accumulation of tenascin, a growth-promoting extracellular matrix protein, in the surroundings of the GA lesions. We suggest that the firmly established and seemingly well-regulated type I and type III collagen synthesis presents a reparative phenomenon in the cutaneous lesions of GA.

Adult↗
PubMed1992

A new method to measure type I and III collagen synthesis in human skin in vivo: demonstration of decreased collagen synthesis after topical glucocorticoid treatment.

Collagen is synthesized as procollagen and large extra domains known as propeptides are cleaved off enzymatically. In the present study we have measured the carboxyterminal propeptide of type I collagen (PICP) and the aminoterminal propeptide of type III collagen (PIIINP) in blister fluids of human skin. High concentrations of PICP were found in the spontaneous blisters of patients with bullous pemphigoid, erysipelas, or erythema multiforme. Detectable amounts were also found in suction blisters induced on healthy skin. Because the concentrations in suction blisters were several times higher than in corresponding serum, most of PICP and PIIINP was derived from the underlying dermis. This method was used for assessing type I and type III collagen synthesis after topical glucocorticoid treatment. Clobetasol-17-propionate (CP) decreased the concentrations of PICP by 75% after 1 d of treatment, the maximum inhibition (92%) being found after 2 d treatment. PIIINP was also affected. Hydrocortisone and hydrocortisone-17-butyrate also decreased the concentrations of PICP and PIIINP, but less markedly than CP. Partial recovery was seen 3 d after stopping the treatment. Thus measurement of collagen type specific propeptides in suction blisters can be used as an estimate of collagen synthesis in vivo, avoiding both local anesthesia and skin biopsing. With radioimmunoassays for PICP and PIIINP a large number of samples can also be processed simultaneously.

Administration, Topical↗
PubMed1992

Systemic glucocorticoid treatment decreases serum concentrations of carboxyterminal propeptide of type I procollagen and aminoterminal propeptide of type III procollagen.

The effect of systemic glucocorticoid treatment on collagen synthesis in patients with various dermatoses was studied by measuring the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) in serum. Changes in the propeptide concentrations were compared with those of osteocalcin, which reflects osteoblastic activity, and tartrate resistant acid phosphatase (TRAP), which reflects osteoclastic activity. The treatment caused significant decreases in levels of PICP, PIIINP and osteocalcin of 38, 34 and 49%, respectively (P less than 0.001). For TRAP, both increases and decreases were seen. The effects on PICP and PIIINP were evident 2-4 days after the onset of steroid therapy. The decrease in PICP was dose-related (r = 0.470, P less than 0.005) but even relatively small doses (0.1 mg of prednisone/kg/1 day) caused a significant reduction in PICP. After cessation of treatment, the levels of PICP returned to the pretreatment level in 1 week. The present study demonstrates that systemic glucocorticoid therapy in humans suppresses the synthesis of type I and III collagens and also non-collagenous bone matrix proteins.

Acid Phosphatase↗
PubMed1992

Comparison of muscle-derived serum carbonic anhydrase III and myoglobin in dermatological patients: effects of isotretinoin treatment.

The serum levels of muscle-specific serum carbonic anhydrase III (S-CAIII) and myoglobin (S-Myo) were analyzed in various male dermatological patients of the same age. The mean levels of S-CAIII and S-Myo were essentially similar in patients with acne, psoriasis vulgaris, atopic eczema and tinea, suggesting that common dermatological diseases do not affect the serum levels of the muscle markers. Increased levels of S-CAIII, which is specific for skeletal muscle cells, were found in the acne patients who had been treated with isotretinoin. However, when S-CAIII and S-Myo were studied in 24 patients (16 males, 8 females) before and during isotretinoin treatment, no constant increases in these markers could be observed. When individual patients were followed for several months, transient increases or decreases could be observed. The changes in S-CAIII, or S-Myo, did not correlate with the dose of isotretinoin, nor with the duration of the treatment. The results suggest that systemic isotretinoin does not specifically affect skeletal or myocardial muscles. The increases in these markers observed in the course of dermatological diseases and isotretinoin treatment are obviously due to other factors, such as exercise.

Adolescent↗
PubMed1992

A study of bone formation in osteoma cutis employing biochemical, histochemical and in situ hybridization techniques.

A female presenting multiple osteoma cutis lesions without underlying endocrinological disturbance was studied. Histologically, lesions revealed true bone formation with multiple osteoblastic cells. This was confirmed by demonstrating high alkaline phosphatase activity and osteonectin expression in osteoma cutis lesions. Interestingly, tenascin and type III procollagen were in close association to bony lesions, indicating that these matrix proteins may be somehow involved in bone formation. In situ hybridization revealed fibroblastic cells around bony lesions, which actively deposited type I collagen and osteonectin. One of the activators of bone formation, TGF beta, was also present in some osteoblastic cells. The results thus indicate that in osteoma cutis, fibroblasts have the ability to differentiate into osteoblastic cells, which have some properties of osteoblasts, such as high alkaline phosphatase activity and a high expression of osteonectin.

Adult↗
PubMed1991

Comparison on collagen gene expression in the developing chick embryo tendon and heart. Tissue and development time-dependent action of dexamethasone.

Glucocorticoids modulate various cellular functions such as proliferation, energy metabolism and the synthesis of proteins. In the present study, the response of collagen genes to dexamethasone in different stages of chick embryo development was studied in tendon and heart using Northern blot analysis and specific cDNA probes. The changes in collagen gene expression were compared to alterations in two reference mRNAs: actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The levels of specific mRNAs measured per ribosomal RNA in tendon and heart varied markedly during normal development. In tendon the relative levels of alpha 1(I), alpha 2(I) and alpha 1(III) collagen mRNAs were highest between days 14-16 when also the synthesis of matrix proteins is most active. In heart the levels of these mRNAs peaked at day 12. In addition, qualitative differences were observed in the expression of actin genes between tendon and heart. Dexamethasone in high dose decreased collagen mRNA levels in tendons, while in heart a stimulatory effect was noted. Dexamethasone also decreased GAPDH mRNA levels in tendons. The alterations in gene expression after dexamethasone treatment in tendon and heart did not correlate with the level of specific glucocorticoid receptors, which varied markedly during the development of chick embryos. The cDNA for pro alpha 1(I) collagen hybridized to two transcripts corresponding to 6.2 and 5.1 kb in tendon and heart. During normal development of chick embryos the ratio of 6.2/5.1 kb mRNAs decreased markedly in heart, but no such change was observed in tendons. Dexamethasone, however, decreased the ratio of 6.2/5.1 kb transcripts in tendons. There was a significant correlation between the ratio 6.2/5.1 kb transcripts and total alpha 1(I) mRNA both in tendon and heart, suggesting that the 6.2 kb transcript may be associated with the rate of synthesis of type I collagen.

Actins↗
PubMed1991

New aspects of the mechanism of corticosteroid-induced dermal atrophy.

Glucocorticoids are effective for the treatment of various inflammatory skin diseases, but their long-term use may lead to serious side-effects such as osteoporosis and skin atrophy. The incidence of skin atrophy following application of potent corticosteroids is especially high among children and the elderly. During recent years the effects of glucocorticoids on connective tissue have been elucidated, and it is evident that skin atrophy is mostly due to a decrease in collagen synthesis. Since collagen is the most abundant protein in the skin, the inhibition of its synthesis leads to atrophy. This review discusses the molecular mechanisms of glucocorticosteroid-induced skin atrophy and therapeutic possibilities.

Aged↗
PubMed1991

Ultraviolet radiation in skin ageing and carcinogenesis: the role of retinoids for treatment and prevention.

The mechanisms of UV-induced ageing and carcinogenesis of the skin have been elucidated in animals and humans, and both UVB and UVA radiation have been shown to have deleterious effects on the skin. Thus the use of solaria which deliver mostly UVA radiation is not safe. There is also an increased risk of ageing when using therapeutic UV sources. UV radiation is beneficial in many cases of skin disorders such as psoriasis, atopic eczema, acne and pruritus. Nevertheless by careful patient selection and follow-up the risks of UV can be minimised when treating patients with artificial UV radiation. During recent years there has been intensive research into the development of agents which prevent harmful effects of radiation. The retinoids are particularly interesting as they enhance skin repair after UV damage, have an anticarcinogenic effect and are effective for treating precancerous lesions such as solar keratosis and as adjuvant therapy for skin cancers. Topical retinoids are already used for the treatment of actinic skin damage, and systemic retinoids are also used in certain groups of patients who have an increased risk of contracting skin cancers such as xeroderma pigmentosum.

Animals↗
PubMed1991

Collagen biosynthesis in lichen sclerosus et atrophicus studied by biochemical and in situ hybridization techniques.

Collagen was studied by biochemical and immunohistochemical techniques and by in situ hybridization in four patients with lichen sclerosus et atrophicus (LSA). The solubility of collagen in acetic acid and pepsin was increased in the lesional skin of the LSA patients when compared with their non-affected skin or samples from control subjects, indicating that a marked proportion of the collagen was newly synthesized. Collagen synthesis was slightly increased in fibroblasts derived from the lesional skin of the LSA patients. In situ hybridization with human sequence-specific cDNAs to type I procollagen demonstrated active fibroblasts in lesional skin of LSA patients, further confirming a high level of collagen synthesis in LSA. Remarkably, active fibroblasts were not associated with inflammatory cell infiltrates noted in LSA skin nor did they express transforming growth factor beta(TGF beta 1). Our results indicate that despite the degeneration of connective tissue, there is an active regeneration process in LSA with significant collagen synthesis.

Aged↗
PubMed1990

Dexamethasone-induced plasminogen activator inhibitor: characterization, purification, and preparation of monoclonal antibodies.

The effects of dexamethasone on protein synthesis were studied in human fibrosarcoma (HT-1080) cells. Dexamethasone induced a new protein of 46 kD which was rapidly secreted into the medium, while neither progesterone nor estradiol would induce the synthesis of this protein and only a small increase in its amount could be seen in the presence of testosterone. The 46 kD protein was partially purified by ammonium sulfate precipitation and gel filtration and mouse monoclonal antibodies to it were produced in mouse hybrid cells. Altogether 13 positive clones were found, of which six reacted only with native and seven reacted with the unreduced 46 kD protein in Western blotting. It was possible by using polyclonal antibodies to plasminogen activator inhibitor type I (PAI-1) and purified plasminogen activator inhibitor type I to confirm that the 46 kD protein purified and characterized here was PAI-1. In addition, the 46 kD protein clearly inhibited plasminogen activation, thus further confirming that protein isolated was an inhibitor of plasminogen activator. Since the induction of PAI-1 by dexamethasone was very extensive, it is possible that glucocorticoids regulate proteolysis and fibrinolysis in vivo by increasing the amount of the inhibitor of plasminogen activator and thus preventing the activation of plasminogen to plasmin. The reduction of activation of plasminogen to plasmin by glucocorticoid-induced inhibitor could be of great importance, e.g., in various blistering diseases, in metastases from malignant cells, and in the migration of inflammatory cells.

Antibodies, Monoclonal↗
PubMed1990

Effect of long-term PUVA treatment of psoriasis on the collagen and elastin gene expression and growth of skin fibroblasts in vitro.

The proliferation rate, collagen metabolism and collagen and elastin messenger-RNA levels were studied in fibroblasts derived from patients who had received many courses of either systemic 8-methoxypsoralen or topical trioxsalen PUVA treatment. The proliferation rate of fibroblasts as measured by the incorporation of 3H-thymidine or by cellular division was decreased in those obtained from patients who had PUVA treatment as compared with controls. Collagen synthesis was slightly increased in the cells from PUVA-treated patients, but the relative collagen synthesis and the ratio between types I and III collagen were unchanged. The levels of collagen and elastin mRNAs were increased in fibroblasts derived from the PUVA-treated patients. No significant differences in histology or immunochemistry could be found in the biopsies taken from topical and systemic PUVA-treated patients.

Adult↗
PubMed1989

Comparison of the effects of dexamethasone and 13-cis-retinoic acid on connective tissue biosynthesis in human skin fibroblasts.

The effects of glucocorticoids and retinoids on connective tissue biosynthesis were studied in cultured human skin fibroblasts (HSFs). More specifically attention was paid to the effects of dexamethasone and 13-cis-retinoic acid (RA) on total protein and collagen synthesis and on collagen and fibronectin mRNA levels. The results indicated that dexamethasone reduced the relative collagen synthesis and collagen mRNA levels in HSFs and increased the total incorporation of proline into proteins, the latter effect being due to increased activity in the intracellular proline pool. 13-cis-RA did not affect collagen synthesis at the concentration studied (10(-7) M) but it did reduce the corresponding mRNA levels. Simultaneous addition of both dexamethasone and 13-cis-RA or etretinate resulted in the largest decrease in type I and type III procollagen mRNA levels, indicating that retinoids do not oppose the effect of glucocorticoids on collagen synthesis in cultured HSFs. For comparison the effects of dexamethasone and 13-cis-RA on the mRNA levels of another extracellular matrix component, fibronectin, and of a constitutive enzyme, glyceraldehyde-3-phosphate dehydrogenase, were also studied. The results indicated, that dexamethasone treatment did not alter fibronectin mRNA levels in HSFs, while 13-cis-RA did so to a marked extent. Both dexamethasone and 13-cis-RA also reduced the mRNA level of glyceraldehyde-3-phosphate dehydrogenase, indicating that glucocorticoids and retinoids have both similar and different effects on gene expression in HSF.

Cell Line↗
PubMed1989

Comparison of the effects of retinoids and glucocorticosteroid on protein and type IV collagen synthesis in HT-1080 (human basement membrane forming fibrosarcoma) cells.

The effects of various retinoids and dexamethasone on protein and type IV collagen synthesis were studied in human basement membrane-forming fibrosarcoma (HT-1080) cells. Retinol, etretinate (Ro-10-9359), free acid of etretinate (Ro-10-1670) and 13-cis-retinoic acid (RA) in 10(-7) M concentrations slightly reduced total protein and type IV collagen synthesis in the HT-1080 cells, the largest decrease being found with Ro-10-1670 and 13-cis-RA. In contrast, dexamethasone markedly stimulated the incorporation of [14C]proline and the synthesis of [14C]hydroxyproline, an index of the synthesis of type IV collagen. Part of the increase noted in total protein synthesis and type IV collagen synthesis after dexamethasone was due to enhanced intracellular activity of proline. Retinoids did not markedly affect the specific activity of proline. The addition of 13-cis-RA with dexamethasone also increased total protein and type IV collagen synthesis, but to a lesser extent than did dexamethasone alone. 13-cis-RA did not affect the synthesis of fibronectin, a component of connective tissue matrix, while dexamethasone clearly increased the absolute and relative synthesis of fibronectin. Thus the results indicate that retinoids modulate the metabolism of HT-1080 cells, in a way which is separate from that of glucocorticoids. It is also possible that retinoids used in vivo in clinical practice may modulate the metabolism of the connective tissue matrix of basement membranes, i.e. type IV collagen.

Acitretin↗