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Biomedical subjects

A Oikarinen

Publications and source records attributed to A Oikarinen.

At least 109 records · Page 6Linked to original sources
PubMed1989

Biochemical and immunohistochemical comparison of collagen in granuloma annulare and skin sarcoidosis.

Collagen was studied by biochemical and immunohistochemical means in 5 patients with granuloma annulare (GA) and 3 with cutaneous sarcoidosis (SA). The solubility of collagen from the lesional skin in acetic acid was higher than that of collagen from unaffected skin from both patients and control subjects. Collagen concentration in the skin lesions, measured in terms of hydroxyproline content, was reduced in 3 patients with granuloma annulare and one with sarcoidosis, but the ratio of type III/I collagen was unchanged vis-à-vis non-affected skin. The collagen concentration in non-affected skin of both GA and SA-patients was also lower than in controls. The most typical immunohistochemical finding was the association of type III procollagen and fibronectin with granulomas in the lesional skin of both GA and SA cases. The activity of prolyl hydroxylase, a key enzyme in collagen biosynthesis, was markedly increased in the lesional skin, indicating that collagen synthesis in vivo was also increased. Surprisingly, collagen synthesis was not increased in cell culture studies. This could be due to cell selection as observed previously in scleroderma. Another possibility could be that various mediators released in vivo from inflammatory cells activate fibroblasts. However, when cells are subcultivated, this effect is not maintained. In conclusion, marked changes in collagen could be observed in granuloma annulare and skin sarcoidosis, reflecting increased turnover of collagen in vivo.

Adult↗
PubMed1989

Etretinate reduces connective tissue degeneration in lichen sclerosus et atrophicus.

Retinoids have effects on the metabolism of keratinization and on the metabolism of connective tissue. Recent results have indicated that they may be helpful for treating dermatological diseases which involve marked connective tissue changes such as scleroderma, keloids and actinic skin damage. In addition, retinoids have been shown to reduce the clinical and histological alterations occurring in vulvar lichen sclerosus. For these reasons, etretinate was tried in a patient with extensive lichen sclerosus et atrophicus (LSA). Clinical improvement was seen after three months' treatment, i.e. a decrease in pruritus and softening of the skin. The degenerated zone in the lesional skin was shown by histological analyses to have reduced markedly. The immunohistochemistry, with unaltered staining for type III procollagen and fibronectin, disclosed no signs of enhanced collagen synthesis. Thus the reparation mechanism remained obscure.

Connective Tissue↗
PubMed1989

13-cis retinoic acid and dexamethasone modulate the gene expression of epidermal growth factor receptor and fibroblast proteoglycan 40 core protein in human skin fibroblasts.

The effects of 13-cis retinoic acid (RA) and dexamethasone on the levels of epidermal growth factor (EGF) receptor and fibroblast derived proteoglycan core protein (PG40) mRNAs were studied in human skin fibroblasts. The EGF receptor is involved in the regulation of cellular proliferation and the synthesis of matrix proteins, and proteoglycan 40 is important for cell attachment and interaction with collagen and fibronectin. 13-cis-RA at a concentration of 10(-7) M markedly reduced the levels of the EGF receptor and PG40 mRNAs, the decreases being 33 and 56%, respectively. Dexamethasone reduced these mRNAs markedly less. Simultaneous treatment of the fibroblasts with 13-cis-RA and dexamethasone resulted in similar decreases in EGF receptor and PG40 mRNAs as with 13-cis-RA alone. Surprisingly, the proliferation rate of the fibroblasts was increased in the presence of dexamethasone under conditions similar to those which caused slight decrease in the EGF receptor mRNA levels. This indicates that glucocorticoids also affect the cellular growth by mechanisms which do not involve EGF receptors.

Aggrecans↗
PubMed1989

Increased non-enzymatic glycosylation and reduced solubility of skin collagen in insulin-dependent diabetic patients.

The solubility of skin collagen into acetic acid and by pepsin digestion and the degree of non-enzymatic glycosylation of collagen (ketoamine linkage) in these fractions was determined in skin specimens from 27 insulin-dependent diabetic subjects and from 17 age-matched controls. Glycosylation in acid soluble collagen specimen was significantly increased in the diabetics, 1.9 +/- 1.8 (SD)ng of hexose/micrograms of hydroxyproline in comparison to the controls. 0.9 +/- 0.8 ng of hexose/micrograms of hydroxyproline. No significant difference in this respect was noted in pepsin soluble collagen specimens. The solubility of collagen into acetic acid and by pepsin digestion were significantly reduced in the diabetics. No clear relationships between non-enzymatic glycosylation or collagen solubility and diabetic late complications (nephropathy, retinopathy or limited joint mobility) were noted. We suggest (a) that equilibrium levels of early glycosylation products are different in acid and pepsin soluble collagen specimens. (b) ketoamine linkage glycosylation products by themselves are not directly involved in diabetic late complications and (c) the solubility in acid and digestibility of collagen by pepsin may be an indicator, even though nonspecific, of increased amounts of advanced glycosylation end products.

Collagen↗
PubMed1989

A biochemical and immunohistochemical study of collagen in sun-exposed and protected skin.

UV radiation can induce definitive ultrastructural and biochemical alterations in the dermis of the human skin that are independent of the aging process. We present observations on the solubility of collagen and the ratio of type III/type I collagen in skin protected from the sun (abdomen/axilla) and exposed to the sun (neck/face) in 15 subjects, together with histological and immunohistochemical data on the same subjects. The solubility of collagen in acetic acid was similar for protected and exposed skin and solubility in the pepsin-digestable fraction was not significantly altered by chronic sun damage. This indicates that UV radiation does not affect synthesis or cross-link formation of the collagen chains of the human skin in vivo. Further studies indicated that the proportion of type III collagen in pepsin-soluble fraction was not increased in actinic damage. These findings were in line with immunohistochemical studies using antibodies to type III procollagen.

Aged↗
PubMed1988

Aminoterminal propeptide of type III procollagen in methotrexate-induced liver fibrosis and cirrhosis.

Twenty-four psoriatic patients on methotrexate were studied with liver biopsies and serum measurements of aminoterminal propeptide of type III procollagen (PIII NP). All but one of nine patients with serum levels of PIII NP above the normal range had liver fibrosis or cirrhosis and no normal liver biopsies were obtained in this group. In contrast, nine normal liver biopsies and two biopsies with minimal fibrosis were found among the 15 patients with normal serum levels of PIII NP. The study indicates that aminoterminal propeptide of type III procollagen can be utilized as a valuable non-invasive marker of fibrogenesis in the liver. This analysis is not specific for the liver, but it seems that the number of liver biopsies probably can be reduced in psoriatics on methotrexate who have normal levels of PIII NP.

Adult↗
PubMed1987

Dexamethasone modulates the metabolism of type IV collagen and fibronectin in human basement-membrane-forming fibrosarcoma (HT-1080) cells.

The effect of dexamethasone on the synthesis and degradation of type IV collagen was studied in human fibrosarcoma cells, HT-1080. A dexamethasone concentration as low as 0.1 microM markedly increased collagen synthesis in HT-1080 cells labelled with [14C]proline. The increase in type IV collagen synthesis was not specific, since total protein synthesis was also increased. Further studies indicated that part of the increase was due to an increase in the specific radioactivity of the intracellular proline pool, after dexamethasone treatment. In fact, with dexamethasone concentrations of 0.1-10 microM the relative collagen synthesis was decreased, indicating that synthesis of other protein was increased more than that of type IV collagen. This was also confirmed by measuring the relative amount of type IV collagen RNA by using recombinant plasmid cDNA specific for the human procollagen pro alpha l (IV) RNA. The results indicated that relative collagen synthesis and the relative amount of type IV collagen messenger RNA was decreased similarly, indicating that dexamethasone affected type IV collagen synthesis at the pre-translational level. The dexamethasone-induced effect on total protein and collagen synthesis was maximal after 12-24 h. Dexamethasone induced a marked accumulation of collagen into the cell layer, leading to diminished deposition of soluble collagen into the medium. Since bacterial-collagenase treatment of the cell layer drastically decreased the collagen content of the dexamethasone-treated cells, this indicates that dexamethasone caused an accumulation of collagen into the extracellular matrix of the cell layer. In contrast, the amount of fibronectin was markedly increased in the medium. Dexamethasone decreased the type IV collagen-degrading activity in HT-1080 cells. The HT-1080 cells contained glucocorticoid receptors, as demonstrated by two different methods: by a whole-cell binding assay and by using a cytosol-gel-filtration method. The number of specific binding sites was similar to that in human skin fibroblasts. In conclusion, glucocorticoids affect the metabolism of type IV collagen and fibronectin in HT-1080 cells, and, since these cells contain specific glucocorticoid receptors, the effects are apparently receptor-mediated.

Basement Membrane↗
PubMed1987

Scleredema and paraproteinemia. Enhanced collagen production and elevated type I procollagen messenger RNA level in fibroblasts grown from cultures from the fibrotic skin of a patient.

An edematous rash developed on the abdominal skin of a 76-year-old woman who had had diabetes mellitus for ten years. Some months later, the affected skin became thickened and indurated. Histopathologic examination revealed marked dermal fibrosis with excessive deposition of collagen. The patient also had IgA (k-type) paraproteinemia. Fibroblast cultures from the affected and unaffected skin were studied for collagen metabolism. Procollagen synthesis was elevated about sixfold on fibroblasts derived from the affected skin. A similar increase was detected in messenger RNA (mRNA) levels using a complementary DNA clone specific for human pro alpha 1(l) collagen mRNA. The elevated mRNA level could be the result of increased transcriptional activity of collagen genes or decreased degradation of collagen mRNAs. Our findings suggest that increased collagen deposition may account for the marked dermal fibrosis that we observed in this patient.

Aged↗
PubMed1987

Necrobiosis lipoidica: ultrastructural and biochemical demonstration of a collagen defect.

Ten patients with necrobiosis lipoidica lesions were studied. Five patients had diabetes mellitus. The age of the patients varied from 15 to 73 years and the duration of the skin lesions was from 2 to 20 years. Histologically, the lesions were characterized by degeneration of collagen and elastin. In some lesions elastin fibers could be seen in areas devoid of normal-looking collagen. Electron microscopy revealed loss of cross-striation of collagen fibrils and a marked variation in the diameter of individual collagen fibrils. The concentration of collagen, measured by assay of hydroxy-proline, a collagen-specific amino acid, was markedly decreased in the lesional skin, but the ratio of type I/III collagen was unchanged in the affected skin. Fibroblasts established from affected skin synthesized less collagen than cells derived from healthy-looking skin. The decreased collagen synthesis was due to a decreased amount of messenger RNA for type I procollagen, measured by hybridization with a specific human cDNA clone. The production of collagenase by these fibroblasts was not increased. Our results thus indicate that in necrobiosis lipoidica lesions, collagen fibrils are defective and the amount of collagen is reduced, probably due to decreased synthesis of collagen by affected fibroblasts.

Adolescent↗
PubMed1987

Modulation of collagen metabolism in cultured human skin fibroblasts by dexamethasone: correlation with glucocorticoid receptor density.

Connective tissue metabolism was studied in detail in three human skin fibroblast lines, demonstrating low, medium, or high levels of glucocorticoid receptor densities. In the cell lines with low and medium receptor density, dexamethasone, in the range of 10(-5)-10(-9) M, had no effect on collagen production, using short incubation time periods and high (20%) fetal calf serum concentration, while in the cells with highest receptor density, a slight stimulation of collagen synthesis was noted in the concentration range 10(-6)-10(-9) M. In the presence of low concentration (0.5%) of serum, dexamethasone markedly inhibited collagen production. The production of collagenase, assayed by degradation of 3H-labelled type I collagen substrate with a brief trypsin activation of the enzyme, was reduced in a dose dependent manner in all 3 cell lines, the inhibition with 10(-5) dexamethasone being up to 56% of the control. Similarly, the activity of an elastase-like neutral protease was decreased in the presence of dexamethasone. Thus the results indicate that glucocorticoids may have profound effects on the degradation of connective tissue components, while the effects on collagen synthesis may be more variable depending on the environmental milieu.

Collagen↗
PubMed1987

Glucocorticoid receptors in cultured human skin fibroblasts: evidence for down-regulation of receptor by glucocorticoid hormone.

In the present study, we have determined the specific glucocorticoid receptors in cultured human skin fibroblasts with [3H]dexamethasone as the ligand. The whole-cell assay was employed for determination of glucocorticoid receptor densities and binding affinities in fibroblast cultures established either from 16 healthy control subjects, from 4 patients with active progressive systemic sclerosis (PSS), from 3 patients with keloids and 3 patients with diabetes mellitus. The receptor densities in PSS, keloid, diabetes and control fibroblasts were in the same range, the values being 6.3 +/- 4.9, 7.7 +/- 3.6, 5.3 +/- 1.3 and 7.9 +/- 6.2 fmol/micrograms DNA (mean +/- SD), respectively. In further studies, the cells were incubated with 10(-7) M dexamethasone for 4 or 9 days before the receptors were assayed. The specific binding of [3H]dexamethasone in steroid treated cultures was 62 and 13% of that observed in controls, suggesting down-regulation. In contrast, incubation of fibroblasts with 10(-5) M all-trans-retinoic acid did not alter the binding of [3H]dexamethasone, suggesting lack of pharmacologic interference at the receptor level.

Cells, Cultured↗
PubMed1987

Developmental changes in the level of glucocorticoid receptors in chick-embryo tissues.

The concentrations of glucocorticoid receptors were assayed in various chick embryo tissues by a cytosol charcoal-dextran method using [3H]dexamethasone as ligand. The highest levels of receptors were found in muscle on developmental day 15-16. The order of maximum binding of dexamethasone in various tissues was muscle greater than heart greater than skin greater than tendon greater than kidney greater than cartilage greater than liver. However, marked variation in the level of receptors was found even in the same tissue during development of the chick-embryo. The highest levels of receptors were generally found on days 15-17. For example, in tendon the difference between the highest and lowest level of receptors was about 6-7 fold. Thus the results show that specific glucocorticoid receptors may be found in various tissues of developing chick-embryos.

Animals↗
PubMed1986

Regulation of serum testosterone in men with steroid sulfatase deficiency: response to human chorionic gonadotropin.

Human chorionic gonadotropin (hCG; 5000 IU) was administered to 6 control men and 6 patients with recessive x-linked ichthyosis (RXLI) with verified 3 beta-hydroxysteroid sulfate sulfatase (3 beta-HSS) deficiency in their skin biopsy samples. Concentrations of steroids and their sulfate conjugates were determined in peripheral serum specimens collected a day before and 4 days after hCG administration. Testosterone concentrations were identical in patients and controls. Baseline serum LH concentrations were also identical in the 2 groups showing that there were no major differences in the regulation of the hypothalamic-pituitary-gonadal axis. The significantly increased (31-82%) serum concentrations of sulfated pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone and 5-androstene-3 beta,17 beta-diol in patients compared with controls indicated that their circulating concentrations were regulated by 3 beta-HSS. This is in line with the fact that the baseline concentrations of the same unconjugated steroids were significantly lower (32-90%) in patients with RXLI, suggesting that a proportion of these circulating steroids were derived from the corresponding sulfated precursors. The response patterns and actual concentrations of testosterone, 17-hydroxyprogesterone and estradiol were similar in the patients and the controls after hCG. The decreased concentrations of testosterone sulfated at carbon 17 under baseline conditions and after hCG in patients with RXLI remains enigmatic. In conclusion, testosterone production and the response to hCG seem to be identical in patients with RXLI and controls despite the fact that significant differences were observed in the circulating concentrations of several unconjugated and sulfated testosterone precursors.

Adult↗
PubMed1986

Characterization of elastase-like enzymes in various blistering diseases.

Blister fluid samples were collected from suction induced control blisters and from spontaneous blisters from various blistering diseases for the measurement of elastase-like enzyme activities using synthetic succinyl-L-(alanyl)3-paranitroanilide (SAPNA) and alanyl paranitroanilide (ala-PNA) as the substrates. The blister fluids derived from bullous pemphigoid, pyoderma or epidermolysis bullosa dystroficans lesions contained higher levels of elastase-like enzyme activities than burn blisters or fresh suction blisters. The gel filtration studies using Sepharose CL-4B chromatography revealed two major peaks of SAPNA hydrolysing enzyme activity in burn blister and in bullous pemphigoid blister. The first peak eluted in void volume, and the second peak had an apparent molecular weight of 2.5 X 10(5) daltons. The results indicate that various proteinases are present in blisters fluids and that they may participate in the blister formation by degrading structural components of the basement membrane zone and the dermis.

Aniline Compounds↗
PubMed1986

Effects of retinoids on type IV collagenolytic activity in melanoma cells.

The effects of retinol, all-trans-retinoic acid, isotretinoin and etretinate on the activity of basement membrane collagen degrading enzyme was studied in melanoma cells. The results indicated that retinoids at concentrations of up to 10(-6) M did not significantly affect type IV collagenolytic activity in these cells in vitro. Since type IV collagenolytic enzyme may be involved in the metastatic potential of tumour cells, it appears that retinoids do not affect the metastatic potential of melanoma cells by affecting type IV collagenolytic activity.

Cells, Cultured↗