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Biomedical subjects

A Oikarinen

Publications and source records attributed to A Oikarinen.

At least 55 records · Page 3Linked to original sources

Effect of topical tretinoin on non-sun-exposed human skin connective tissue: induction of tenascin but no major effect on collagen metabolism.

The effects of topical tretinoin on collagen synthesis and degradation were studied in 29 volunteers. The subjects applied 0.1% tretinoin cream on their non-sun-exposed abdominal skin once a day for 1 week (n = 10) (experiment 1) or twice a day for 2 weeks (n = 8) (experiment 2) or once a day for 2 months (n = 11) (experiment 3). After the treatments, suction blisters were induced and amino-terminal propeptides of type I and III procollagens (PINP, PIIINP, respectively) (experiments 1 and 3) and carboxy-terminal propeptide of type I procollagen (PICP) (experiment 2) were assayed as an index of de novo collagen synthesis by radioimmunoassays. Matrix metalloproteases 2 (MMP-2) and 9 (MMP-9) were assayed by the zymography method in experiment 2. In experiment 3, histology, immunohistochemistry of type I and III procollagens, tenascin, mRNA levels of type I collagen alpha 1-chain [alpha 1 (I)], interstitial collagenase (MMP-1), MMP-2, MMP-9 by slot-blot analysis and the levels of alpha 1 (I) collagen mRNA by a quantitative polymerase chain reaction method were studied. The proportional area of elastic fibres visualized in Verhoeff-stained sections was analysed by computerized digital image analysis. The results indicated that treatment with topical tretinoin does not markedly induce de novo synthesis of collagen in vivo or affect matrix metalloproteases. In the immunohistochemical staining, tenascin was increased in the papillary dermis. As it has been suggested that tretinoin could counteract the atrophogenic effect of corticoids on the dermis, the effect of a combination of betamethasone-17-valerate (once a day) and tretinoin (once a day) on the propeptide levels was also studied. Betamethasone alone caused a 60% decrease in the concentrations of PINP and PIIINP, and a similar decrease was found after the combination treatment, indicating that topical tretinoin administered during short treatment periods does not counteract the inhibitory effect of a potent corticoid on collagen propeptides.

Abdomen↗

Application of machine vision to assess involved surface in patients with psoriasis.

An objective method is still lacking in the quantitative assessment of psoriasis severity. The purpose of this study was to examine whether computer image analysis (CIA) by a new colour segmentation method can be used as an objective method of estimating involved surface area in patients with psoriasis. Involved surface area in psoriasis was assessed from colour photographs covering the same areas as the psoriasis area and severity index (PASI) scores of 26 patients by human observers from different medical professional groups and by CIA. The reliability of CIA was tested with reference analysis by colouring manually the involved areas in the images with the aid of projected slides. The surface area estimates by the different methods were compared with each other and the resulting effects on the PASI score were assessed. The agreement between the reference analysis and the image analysis was high, especially on trunk areas, but the cylindrical shape of the limbs resulted in some difficulties in assessing involved skin area. The human eye estimates differed from the image analysis ones in almost one-third of the cases and mostly when psoriasis affected under 30% of the skin surface area. Both over- and underestimates emerged, but overestimates were more common. Error estimates had a significant effect on the PASI score. The CIA method seems to be reliable and practicable in estimating the actual surface of psoriasis. The method has the disadvantage of being time-consuming (photographing, processing of pictures) and technically demanding. Further development of this method should make it faster in the future.

Adult↗

Expression of the tissue metalloproteinase inhibitors TIMP-1 and TIMP-2 in malignant fibrous histiocytomas and dermatofibromas as studied by in situ hybridization and immunohistochemistry.

The expression of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) was studied in eight malignant fibrous histiocytomas (MFH) and in eight dermatofibromas (DF) using in situ hybridization methods (ISH). Immunohistochemical stainings were also performed using corresponding antibodies to TIMP-1 and TIMP-2. In ISH the neoplastic cells of MFHs showed a high level of expression for both TIMP-1 and TIMP-2 mRNAs. The cells usually expressed similarly both TIMPs, except for osteoclast-like giant cells, which showed a distinct signal for TIMP-2 but not for TIMP-1. A distinctly lower level of both TIMP-1 and TIMP-2 mRNAs was seen in DFs. Immunohistochemical stainings were concordant with the results obtained by ISH. The findings suggest that the behavior of MFHs and DFs is not directly or solely dependent on the quantity of type IV collagenase inhibitors. The increased TIMP synthesis in MFHs might represent a chaotic response of malignant cells to increased matrix degradation. Alternatively, it may reflect a deranged communication between type IV collagenases and TIMPs in malignant tissues.

Adult↗

Quantification of Pro alpha 1(I) collagen mRNA in skin biopsy specimens: levels of transcription in normal skin and in granuloma annulare.

The synthesis of type I collagen, the major component of the skin, is known to be modulated in aging and in various skin diseases and treatments. In vivo analysis of type I collagen expression, however, is difficult because of the low cell density of the dermis and the small amount of RNA obtainable from skin biopsy specimens. We present here a quantitative polymerase chain reaction method for the quantification of pro alpha 1(I) collagen mRNA in skin punch biopsy specimens. The targeted mRNA and a synthetic RNA as an internal standard were co-amplified together with the same primers. Collagen synthesis was found to decline after birth, so that the amount of pro alpha 1(I) collagen mRNA in the skin of 5- to 58-y-old donors was 17-37% of that in fetal skin. Slot-blot hybridization also indicated that the amount of pro alpha 1(I) collagen mRNA was much lower in adult skin than in fetal skin. In samples from lesional skin of two granuloma annulare patients, the number of pro alpha 1(I) mRNA molecules was increased 4- or 5-fold compared with values from nonlesional skin of the same patients. The method presented is a highly sensitive polymerase chain reaction application, requiring only very small amounts of total RNA.

Adult↗

Nonmelanoma skin cancer in northern Finland.

BACKGROUND AND OBJECTIVES: The incidence of nonmelanoma skin cancers is highest in those geographic areas where light-skinned people are exposed to large amounts of sunlight. The purpose of this study was to detect differences in nonmelanoma skin cancers diagnosed in Northern Finland compared to those from elsewhere. Another purpose was to estimate whether changes have occurred in clinical diagnosis, site distribution, and recurrence rate during the past 15 years. METHODS: The material included patients treated at Oulu University Hospital in Northern Finland (64.6 degrees N) during the years 1976-1977 and 1991-1992. Information was collected from files on 334 patients with 428 different, histologically verified skin cancers. RESULTS: In 1976-1977, the average age of men with basal cell carcinoma (BCC) was 61 years, whereas the women's average age was 66 years. In 1991-1992, the corresponding ages were 69 and 72 years. The site distribution did not show any obvious changes in the 15 years, but the differences between sexes had become more prominent. Men had more BCC on the ears and the trunk, whereas women had more BCC on the nose and the forehead. Most of the squamous cell carcinomas (SCC) were on the head and neck similar to BCC, but on the ears of men there occurred relatively more SCC than BCC. CONCLUSIONS: The clinical diagnosis of BCC was fairly easy to make, whereas that of SCC seemed to be very difficult clinically and was only correct in 10% of the cases. The markedly decreased recurrence rate of BCC between 1976 and 1992 probably occurred because of changes in treatment practices.

Aged↗

Effects of an inhaled steroid (budesonide) on skin collagen synthesis of asthma patients in vivo.

Skin atrophy has been observed after prolonged use of inhaled corticosteroids. We therefore studied the effect of inhaled budesonide and nedocromil in patients with asthma on concentrations of procollagen propeptides in suction blister fluid reflecting skin collagen synthesis in vivo. Both types I and III procollagen propeptide concentrations decreased significantly after 6 wk of either 1,600 micro g/day (n=10) or 400 micro g/day (n=9) of inhaled budesonide but not in control subjects using inhaled nedocromil 16 mg/day (n=9). The reduction in mean propeptide concentrations ranged from 39 to 63%; the effects of the two budesonide doses did not differ significantly. Thus, even a low dose of inhaled corticosteroid represses skin collagen synthesis within a relatively short period.

Administration, Inhalation↗

Effects of dexamethasone and cell proliferation on the expression of matrix metalloproteinases in human mucosal normal and malignant cells.

Matrix metalloproteinases (MMPs) have an important role in many biological processes, such as tumor metastasis, wound healing, and inflammation. The regulation of MMPs and their inhibitors is still not known in detail, and the aim of this study was to investigate the effects of dexamethasone on cultured oral benign and malignant cell lines. The expression of MMPs in culture was studied: in four gingival (GF) and one periodontal ligament (PLF) fibroblast cell lines; in six gingival keratinocyte (GK) cell lines; and in UNR (UNR-108, rat osteogenic sarcoma) and SCC (SCC-25, human tongue squamous cell carcinoma) cell lines. In the GFs, PLFs, and UNR cells, only MMP-2 (72 kDa gelatinase) was detected by gelatin zymography, while in most of the GK cell lines only MMP-9 (92 kDa gelatinase) was observed. In confluent SCC cultures, both MMP-2 and MMP-9 were found, while only MMP-2 was seen in rapidly growing SCC cells, demonstrating that cell proliferation influenced gelatinase expression in these cells, but not in the other cell lines studied. Dexamethasone at concentrations of 10(-5) mol/L and 10(-7) mol/L decreased the production of gelatinases in the GFs and PLFs, but not in the GKs, SCC, or UNR cells. The expression of mRNAs for matrix metalloproteinases (MMP-1 [interstitial collagenase] and MMP-2) and their inhibitors (TIMP-1 and TIMP-2) was also studied in the GFs by Northern hybridization. Dexamethasone markedly decreased the amount of MMP-2 mRNA in the GFs. The mRNA level of MMP-1 decreased even more in the same GFs. The mRNA levels for TIMP-1 and TIMP-2 were also decreased by dexamethasone in the GFs. Cell proliferation influenced the degree to which dexamethasone decreased these mRNA levels. The results indicate that glucocorticoids decrease the levels of MMPs and TIMPs in oral fibroblastic cells, whereas they do not appear to affect the production of gelatinases in either normal or malignant oral epithelial cell lines.

Cell Division↗

mRNA expressions of TIMP-1, -2, and -3 and 92-KD type IV collagenase in early human placenta and decidual membrane as studied by in situ hybridization.

Cytotrophoblasts of early placenta invade the decidual membrane, gestational endometrium, and spiral arteries during early pregnancy. Unlike tumor invasion, this physiological invasion is well controlled, although its molecular mechanisms are largely unknown. We have previously shown that cytotrophoblasts synthesize significant mRNAs for 72-KD Type IV collagenase, laminin, and Type IV collagen, proteins implicated in extracellular matrix turnover and migration. In this study we used in situ hybridization and immunohistochemistry to investigate the mRNA expression pattern of 92-KD Type IV collagenase and the matix metalloproteinase inhibitors TIMP-1, TIMP-2, and TIMP-3 in early human placenta and decidual membrane. mRNAs for 92-KD Type IV collagenase, TIMP-1, TIMP-2, and TIMP-3 were found in the cells of cytotrophoblastic columns, the endothelial and fibroblastic stromal cells of villi, and the large decidualized cells of decidual membrane. TIMP-1 expression was notably accentuated in the fibroblasts of fibrotic villi. In the decidual membrane, the signals for 92-KD Type IV collagenase and TIMP-1 mRNA were particularly strong around the glandular structures. The trophoblastic epithelium of villi and the epithelial cells of decidual glands showed a signal for 92-KD Type IV collagenase and TIMP-2, but not for TIMP-1 or TIMP-3. The coincidental expression of the proteolytic 92-KD Type IV collagenase and inhibitors TIMP-1, TIMP-2, and TIMP-3 generally in the same cells suggests that the activity of 92-KD Type IV collagenase, which is regulated by TIMPs, plays an important role in placental tissue organization and in the invasion of trophoblastic cells into the uterine wall.

Collagenases↗

Role of adhesion molecules in the development of pustular lesions in patients with pustulosis palmaris et plantaris.

The expression of adhesion molecules and the ligands on endothelial cells and infiltrating inflammatory cells in lesional skin specimens from patients with pustulosis palmaris et plantaris was studied. Intercellular adhesion molecule-1 and E-selectin were expressed on endothelial cells of microvessels in the papillary dermis. Intercellular adhesion molecule-1 was also expressed focally on keratinocytes in the epidermis of the lesional skin. On the other hand, lymphocyte function-associated antigen-1, Mac-1 and sialyl Lewis(x) were expressed on infiltrating inflammatory cells. Further, flow cytometric analysis demonstrated that circulating leukocytes in peripheral blood from patients with pustulosis palmaris et plantaris expressed the ligands of adhesion molecules. It is therefore suggested that the expression of adhesion molecules and the ligands on circulating leukocytes, endothelial cells, infiltrating inflammatory cells and keratinocytes might be closely related to the formation of pustular lesions in patients with pustulosis palmaris et plantaris.

Adult↗

Increased collagen propeptides in the skin of a scleredema patient but no change in re-epithelialisation rate.

Scleredema is a rare disease, affecting the skin connective tissue with increased amounts of collagen and glycosaminoglycans. In the present study, the collagen synthesis and re-epithelialisation rate were measured from a 64-year-old male patient, who rapidly developed extensive tightening of the skin, without any underlying disease. The skin was thickened at several sites when measured with ultrasound, and the histology revealed accumulation of glycosaminoglycans and collagen bundles. The collagen synthesis rate was measured from suction blisters induced on two different sites of the skin before the treatment and three times later up to 6 months after the treatment with a systemic steroid was started. The aminoterminal propeptide of type I collagen (PINP) was increased manifold in the affected skin when compared with the controls, indicating active collagen deposition in vivo. Systemic steroid medication with high doses (over 20 mg/d) decreased both the type I and the type III collagen propeptide levels. The time schedule of the decreases in the propeptides in the thickened, affected skin and in the clinically normal-looking skin varied, and especially in the thickened skin in the abdomen the decrease in PINP was noted only after 3 months of prednisolone therapy. When the prednisolone dose was only 10 mg daily, the propeptides were again up-regulated, perhaps reflecting the natural course of the disease. The re-epithelialisation rates at two different sites of the patient were similar to those in the controls, suggesting that even massive fibrosis with active deposition of collagen does not alter the basal rate of re-epithelialisation in the skin. In conclusion, collagen synthesis is markedly elevated in scleredema, leading to fibrosis of the skin. A recently developed method utilizing assays of collagen propeptides from suction blister fluid allows monitoring of the collagen synthesis and detection of changes in the collagen synthesis during the treatment of fibrotic disorders.

Abdomen↗

Recovery of human skin collagen synthesis after short-term topical corticosteroid treatment and comparison between young and old subjects.

In the present study, the recovery of the collagen synthesis rate after topical potent glucocorticoid treatment in the human skin in vivo was investigated. In the first experiment, two age groups were compared: young subjects with an age range of 21-26 years (mean 23), and old subjects, aged 55-70 years (mean 64). Twenty healthy male volunteers applied betamethasone-17-valerate to their abdominal skin for 3 days twice a day. Suction blisters were induced on the treated areas, and on the opposite side (healthy non-treated skin), of the abdominal skin on the day following the discontinuation of the treatment, and on the second and seventh day. In another experiment, suction blisters were induced after the treatment and 2 weeks later on the treated area and on healthy skin, in eight male volunteers. In both experiments, the aminoterminal propeptides of type I and III collagens (PINP and PIIINP, respectively) were measured radioimmunologically from the suction blister fluid. Corticosteroid treatment decreased the collagen synthesis in both age groups after a 3-day treatment period, and essentially no recovery in the collagen synthesis could be seen during a 1-week corticoid-free period. The inhibition and downregulation of collagen synthesis in the corticoid-treated skin was similar in both young and old subjects, up to 7 days after the treatment. During the 2-week corticoid-free period, collagen synthesis was recovered to about 50% of the level seen in the non-treated skin, indicating that collagen synthesis is not completely normalized in the human skin even during a 2-week corticoid-free period.

Administration, Topical↗

Influence of aging, localization, glucocorticoids and isotretinoin on matrix metalloproteases 2 (MMP-2) and 9 (MMP-9) in suction blister fluids.

The expression of two matrix metalloproteases (MMPs), 72 kDa gelatinase (MMP-2) and 92 kDa gelatinase (MMP-9), was studied in suction blister fluids and serum using a zymographic method. Both of the enzymes were detectable in blister fluid and serum, but their expression varied. The MMP-2 levels in serum were only about half of the levels in blister fluid, while the level of MMP-9 was about the same in both serum and blister fluid. The overall level of MMP-2 in serum was much lower than the level of MMP-9 which was possibly derived from inflammatory cells. In subjects aged from 20 to 86 years, no marked changes were seen in the serum or blister fluid gelatinases. Interestingly, body site affected the level of MMP-9. The lowest level was recorded in fluid from blisters on the lower leg, in which the level was only about 19% of the level in fluid from blisters on the abdomen. The levels of MMP-2 and MMP-9 were not decreased by pharmacological doses of systemic prednisone or isotretinoin, which indicates that systemic glucocorticoid or retinoid treatment does not affect the basal levels of MMP-2 and MMP-9.

Adult↗

A fibroblast cell line cultured from a hypertrophic scar displays selective downregulation of collagen gene expression: barely detectable messenger RNA levels of the pro alpha 1(III) chain of type III collagen.

The present study was designed to investigate the expression of type I, III and VI collagens by a fibroblast cell line initiated from a hypertrophic scar. The same tissue has previously been demonstrated to display markedly elevated expression of type I and III collagen mRNAs in vivo. Unexpectedly, slot-blot and Northern hybridizations revealed a barely detectable steady-state level of pro alpha 1(III) collagen chain mRNA in cultured hypertrophic scar fibroblasts. The levels of pro alpha 1(I) and alpha 2(VI) collagen chain mRNAs were essentially the same in fibroblasts cultured from hypertrophic scar and in fibroblasts cultured from normal skin. However, Northern blot analyses indicated that the ratio of 5.8 kb to 4.8 kb species of pro alpha 1(I) collagen mRNA was slightly reduced in fibroblasts originating from the hypertrophic scar compared to that in normal fibroblasts. When normal fibroblasts were incubated in conditioned medium from hypertrophic scar cultures, the expression of pro alpha 1(III) collagen chain mRNA decreased to a markedly lower level. Our studies suggest that collagen synthesis by fibroblasts in hypertrophic scars is stimulated by humoral factors which are active only in vivo. Furthermore, the results suggest that fibroblasts cultured from hypertrophic scar display a selective downregulation of different collagen genes and that this downregulation is exerted through an autocrine mechanism.

Adult↗

Increased collagen synthesis in psoriasis in vivo.

Psoriasis is an inflammatory skin disease of unknown a etiology which also involves changes in dermal elements. Previous in vitro studies have shown an increased collagen synthesis rate in cultured fibroblasts. In this study collagen synthesis was studied in vivo in the uninvolved skin of psoriatic patients using a newly developed method in which collagen propeptides were measured in suction blister fluid. Both type I and type III collagen synthesis rates, as measured in terms of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP), were increased about two-fold in uninvolved psoriatic skin as compared with controls, the mean level of PICP being 870 and 457 micrograms, respectively (P < 0.001), and of PIIINP being 294 and 124 micrograms, respectively (P < 0.01). The increased collagen synthesis rate was also confirmed by in situ hybridization using specific probes. Collagen mRNAs were found to be particularly abundant in psoriatic patients, who also demonstrated a high collagen synthesis rate when assayed by measuring collagen propeptides. The increased rate of collagen synthesis in the uninvolved psoriatic skin seemed not to be related to the severity of the disease or to various treatments such as UVB, PUVA, retinoids or cytostatic drugs, but seemed more likely to be due to the psoriasis itself. Interestingly, skin thickness was not increased in the patients with psoriasis, even though collagen synthesis was markedly elevated, perhaps suggesting that in psoriasis the turnover rate of collagen is enhanced.

Adult↗

Destruction of the epithelial anchoring system in lichen planus.

To find out whether the epithelial anchoring system shows any alterations in lichen planus, we examined the distribution of type VII collagen, alpha 6 beta 4 integrin, and kalinin in lesions of lichen planus. These molecules were chosen because they are structural components of anchoring fibrils, hemidesmosome-associated complexes, and anchoring filaments. The localization of type VII collagen in lichen planus was strikingly different from that in nonaffected mucosa or dermis or in other mucocutaneous lesions. In the normal mucosa, type VII collagen was localized only at the basement membrane zone. In lichen planus, type VII collagen was present not only in the basement membrane area but also in streaked patterns deep in the connective tissue. The hemidesmosome-associated complex, alpha 6 beta 4 integrin, was localized at the basal aspect of basal epithelial cells of nonaffected sites, but was diffuse and discontinuous in lichen planus lesions. Most of the basal keratinocytes, however, stained for this integrin. Kalinin staining was discontinuous in lichen planus lesions. Often, finger-like projections of kalinin staining were found protruding into the connective tissue stroma. Kalinin was localized at the basement membrane zone of the nonaffected tissue and other mucocutaneous lesions. These results indicate that in cutaneous and mucosal lichen planus, the epithelial anchoring system is disturbed.

Antigens, Surface↗

Expression of cytokeratins in regenerating human epidermis.

The expression of cytokeratin polypeptides in regenerating human epidermis was immunohistochemically examined during re-epithelization of suction blisters. The regenerating basal and suprabasal epidermis expressed keratin polypeptides K13, K14, K16 and K18, which are not present in normal suprabasal epidermis. On the contrary, K10, a normal constituent of terminally differentiated keratinocytes, was lacking from the epidermis until the ninth day of re-epithelization. The findings indicate changes similar to other hyperproliferative states (expression of K16), basal-like features (expression of K14), or properties reminiscent of fetal skin (K13 and K18) in the newly formed epidermis. Monoclonal antibodies for cytokeratins and a technique using suction blisters seemed to be a suitable methodology for the study of epidermal regeneration in normal skin. The technique may also have advantages in the investigation of keratin expression in diseased skin.

Adult↗

Topical mometasone furoate and betamethasone-17-valerate decrease collagen synthesis to a similar extent in human skin in vivo.

Topical corticosteroids are used extensively to treat inflammatory skin diseases. Long-term use, however, may be associated with adverse effects such as skin atrophy. New steroids have been developed with the objective of increasing efficacy and reducing the incidence of adverse effects. Mometasone furoate (MMF) is one of these new derivatives. The aim of our study was to compare the effects of MMF and betamethasone-17-valerate (BM-17-valerate) on collagen synthesis in human skin in vivo. Fifteen healthy male volunteers applied MMF, BM-17-valerate and vehicle for 1 week to different areas of abdominal skin. Suction blisters were raised on these areas, and a control site, and procollagen propeptide (PICP, PINP, PIIINP) levels in the suction blister fluid were measured by radioimmunoassay. Skin thickness was measured ultrasonically by Dermascan A at the end of the treatment period. The levels of the three propeptides in suction blister fluid were reduced to similar extent by MMF and BM-17-valerate. The 1-week treatment period had no detectable influence on skin thickness. We conclude that MMF and BM-17-valerate decrease collagen synthesis to the same extent in human skin in vivo.

Administration, Topical↗

The effect of topical oestradiol on skin collagen of postmenopausal women.

OBJECTIVE: To examine the effect of topical oestradiol on skin collagen and elastin. SUBJECTS: Twelve postmenopausal women, aged 52 to 76 years. INTERVENTIONS: Topical oestradiol treatment on the skin of lower abdomen and the vehicle only on the contralateral site; once a day for three months. MAIN OUTCOME MEASURES: The content of skin hydroxyproline; the levels of the carboxyterminal propeptide of human type I procollagen (PICP) and of the aminoterminal propeptide of human type III procollagen (PIIINP). The number and the quality of collagen and elastic microfibrils. RESULTS: The amount of hydroxyproline in the skin significantly (P = 0.012) increased from 11.8 to 16.3 micrograms (38%) during oestradiol treatment. After treatment, the PICP level in the blister fluid was significantly (P = 0.024) higher on the treated site than on the control site. Also the level of PIIINP increased, but the change was not statistically significant. Electron microscopy showed morphologic improvement of elastic and collagen fibres, while the number of oxytalan and elaunin fibres was unchanged in light microscopy. CONCLUSIONS: Topical oestradiol treatment increases the amount of skin collagen. The increase in the level of PICP and PIIINP in skin blister fluid indicates that oestradiol treatment stimulates collagen synthesis. Furthermore, our results show that topical ostradiol treatment has a greater influence on the amount than on the quality of skin collagen. On the contrary, in elastic tissue the oestradiol treatment will only result in morphologic improvement.

Administration, Topical↗