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Biomedical subjects

A Oikarinen

Publications and source records attributed to A Oikarinen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Increased prevalence of vitiligo, but no evidence of premature ageing, in the skin of patients with bp 3243 mutation in mitochondrial DNA in the mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome (MELAS).

The MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) belongs to the category of mitochondrial disorders. The most common molecular aetiology of the syndrome is a mutation at base pair (bp) 3243 in the mitochondrial genome (mtDNA). The phenotype is varied and, apart from central nervous system involvement, the patients with this mutation may present with neurosensory hearing loss, diabetes mellitus and cardiomyopathy. These phenotypes suggest that organs dependent on aerobic metabolism suffer most. We investigated the possible clinical and physiological manifestations of impaired energy metabolism in the skin of 28 patients with the bp 3243 mutation in mtDNA. Non-invasive sonography and laser Doppler flowmetry were used to measure skin thickness and the blood flow of the skin. Skin collagen synthesis was assayed from suction blister fluid. Evaporimetry was used to assess the re-epithelialization rate of suction blister wounds. Histochemistry and immunohistochemistry were used to evaluate the melanocytes and pigment in the skin. Vitiligo was found in three of the 28 patients (11%), which was markedly more than in the general population. Histological findings showed an absence of pigment, but an apparently normal distribution of melanocytes in the dermoepidermal junction. Seborrhoeic eczema and atopy were also somewhat more frequent. No features of premature ageing, such as a marked decrease in skin thickness, blood flow, collagen synthesis or re-epithelialization rate, were demonstrated.

Adult↗
PubMed1999

Delayed restoration of epidermal barrier function after suction blister injury in patients with diabetes mellitus.

AIMS: Diabetes mellitus is a risk factor for compromised wound healing. The present study examines the restoration of the epidermal barrier function using the suction blister wound model. METHODS: The healing process was evaluated over time by measuring water evaporation (WE) and blood flow (BF) in the wound area. Seventeen Type 1 diabetic males and 11 non-diabetic control males were studied. RESULTS: At the onset, the WE of diabetic patients was 116 +/- 11 g x m(-2) x h(-1) and that of controls 95 +/- 13 g x m(-2) x h(-1) (P < 0.001). On the second day, the WE of diabetic patients was 90 +/- 21 g x m(-2) x h(-1) and that of controls 60 +/- 24 g x m(-2) x h(-1) (P < 0.02). The most profound difference was encountered during the fourth day, when the WE of diabetic patients was 40 +/- 17 g x m(-2) x h(-1) and that of controls 14 +/- 8 g x m(-2) x h(-1) (P < 0.001). The value recorded on the fourth day was 37% of the onset value in diabetic patients and 16% in controls (P < 0.001). Eight days after wounding the values were close to that of normal skin in both diabetic and control subjects. At the onset, the BF was 93 +/- 20 (arbitrary units) in diabetic men and 112 +/- 18 in controls (P = 0.02). On the second, fourth and eighth day there was no significant differences. CONCLUSIONS: The results suggest that restoration of the epidermal barrier function is delayed in the patients with diabetes. There were also a trend toward an initially weaker inflammatory response.

Adult↗
PubMed1999

Accumulation of matrilysin (MMP-7) and macrophage metalloelastase (MMP-12) in actinic damage.

Photodamage is characterized by degradation of collagen and accumulation of abnormal elastin in the superficial dermis and several matrix metalloproteinases have previously been implicated in this process. Using immunohistochemistry and in situ hybridization, we have studied the localization of two elastolytic matrix metalloproteinases, matrilysin (matrix metalloproteinase-7) and human macrophage metalloelastase (matrix metalloproteinase-12) in solar damage. Human macrophage metalloelastase protein was detected in the superficial dermis in areas of elastotic material. Matrix metalloproteinase-7 was seen in the mid-dermis in regions with less damaged elastic fibers and morphologically better preserved collagen as well as in a band-like pattern below basal keratinocytes in eight of 18 solar elastosis. In samples taken from healthy volunteers 3 d after repeated ultraviolet A or ultraviolet B photoprovocation, occasional immunopositive cells for human macrophage metalloelastase (stromal) or matrix metalloproteinase-7 (sweat gland epithelium) were detected. In samples taken 1 d after ultraviolet B exposure, however, basal keratinocytes were matrix metalloproteinase-7 immunopositive, explaining the linear immunostaining below basal keratinocytes noted particularly in ultraviolet B treated 3 d specimens. Upregulation of metalloelastase was also demonstrated in the skin of hairless mice after repeated ultraviolet exposure. In normal skin, no staining for human macrophage metalloelastase or matrix metalloproteinase-7 was observed in association with elastin. The amount of immunoreactivity for the substrates of matrix metalloproteinase-7, versican, and tenascin, was clearly increased in solar elastosis and photoprovocated skin; versican but not tenascin was detected in the same areas as matrix metalloproteinase-7. Our results suggest that both matrix metalloproteinase-7 and -12 may contribute to remodeling of elastotic areas in sun-damaged skin.

Adult↗
PubMed1998

The short and long forms of type XVIII collagen show clear tissue specificities in their expression and location in basement membrane zones in humans.

Two N-terminal ends of human type XVIII collagen chains have recently been identified. The two chains have different signal peptides and variant N-terminal noncollagenous NC1 domains of 493 (NC1-493) and 303 (NC1-303) amino acid residues, respectively, but share 301 residues of their NC1 domains as well as the collagenous and C-terminal noncollagenous portions of the molecule. Antibodies were produced against the NC1 region common to both human alpha1(XVIII) chain variants and against NC1 sequences specific to the long variant and were used in combination with in situ hybridization to localize this collagen in a number of human tissues. They were also used for Western blotting, which resulted in detection of overlapping high-molecular weight bands above the 200-kd standard in a kidney extract. Heparin lyase II and heparin lyase III digestions of kidney and placenta extracts indicated that at least in these tissues, type XVIII collagen contains heparin sulfate glycosaminoglycan side chains. Type XVIII collagen was found to be a ubiquitous basement membrane component, occurring prominently at vascular and epithelial basement membranes throughout the body. Comparison of the expression of the NC1-493 and NC1-303 variants revealed marked differences. The short variant was found in most conventional basement membranes, including blood vessels and the various epithelial structures, and around muscular structures. The long variant was expressed very strongly in liver, where it was virtually the only variant in the liver sinusoids, and it occurred only in minor amounts elsewhere. Thus, the 192 N-terminal residues specific to the long variant apparently confer some functional property needed above all in the liver sinusoids, but also at certain other locations.

Antibodies↗
PubMed1998

Demonstration of increased levels of type I collagen mRNA using quantitative polymerase chain reaction in fibrotic and granulomatous skin diseases.

Collagen changes occur in localized scleroderma, scleredema and sarcoidosis. Previous biochemical, immunohistochemical and in situ hybridization studies have revealed increased collagen synthesis in these diseases. In the present study, we measured by pro alpha 1 (I) collagen and beta-actin mRNA levels in skin punch biopsy specimens from lesional and healthy skin using a quantitative polymerase chain reaction (PCR). In this method, the targeted mRNA and a synthetic RNA as a internal standard are co-amplified together with the same primers. The amount of pro alpha 1 (I) collagen mRNA in cutaneous sarcoidosis lesions was found to be increased about two- to threefold compared with the values obtained for the healthy skin of the same two patients. In lesional skin of three patients with localized scleroderma the number of pro alpha 1 (I) collagen molecules was increased about two-fold. The beta-actin mRNA values were at the same level in the affected and unaffected skin of all the patients studied. In conclusion, a marked increase in type I collagen gene expression was seen in localized scleroderma and scleredema, leading to fibrosis of the skin, and in a granulomatous skin disease, cutaneous sarcoidosis.

Actins↗
PubMed1998

The molecular basis of glucocorticoid-induced skin atrophy: topical glucocorticoid apparently decreases both collagen synthesis and the corresponding collagen mRNA level in human skin in vivo.

The effects of topical betamethasone-17-valerate on collagen propeptide levels, collagen mRNA level, lysyl oxidase mRNA and matrix metalloproteinase (MMP)-1 and MMP-2 mRNA levels were studied in human skin. Three days' treatment of healthy skin with topical betamethasone caused a 70-80% decrease in type I and III collagen propeptides in suction blister fluid. A similar decrease was found in type I collagen mRNA when assayed by either slot-blot hybridization or a quantitative polymerase chain reaction method, indicating that the decrease in collagen synthesis after topical glucocorticoid treatment is apparently due to a decrease in corresponding mRNA. mRNA of lysyl oxidase, which is an important enzyme catalysing the cross-linking of collagen chains, and collagen-degrading enzyme MMP-1 and MMP-2 mRNAs were not decreased in the same skin samples. This suggests that in vivo, glucocorticoids modulate variably the genes involved in collagen synthesis and degradation. Our study provides a solid molecular basis for glucocorticoid-induced dermal atrophy, which results from the decrease in functional collagen mRNA in the skin.

Administration, Topical↗
PubMed1998

Comparison of actual psoriasis surface area and the psoriasis area and severity index by the human eye and machine vision methods in following the treatment of psoriasis.

The lack of a quantitative method for assessing psoriasis severity poses a problem for quality control in dermatology. Quantitative estimation of involved surface area is important, as in the psoriasis area and severity index (PASI), but the reliability of many methods is poor. The purpose of this study was to assess the involved surface area of 15 psoriasis patients before and after different anti-psoriasis treatments using the human eye method and a computer image analysis (CIA) system based on colour segmentation. The human eye assessments were compared with the results of the CIA system and the resulting effects on the PASI score were also compared. The human eye estimates were higher than those obtained by the CIA method and, as a consequence, the values of the PASI by the human eye method were also higher than those by CIA. The human eye estimates differed most in cases where the PASI was under 15. The changes in the PASI by the human eye method before and after treatments differed significantly from those by CIA. The CIA system offers a possibility to quantify actual surface in patients with psoriasis, and will be an alternative for developing quality control when evaluating different treatment efficacies.

Acitretin↗
PubMed1998

Production of membrane-type matrix metalloproteinase-1 (MT-MMP-1) in early human placenta. A possible role in placental implantation?

The extracellular matrix proteolytic machinery is known to play a major role in trophoblast invasion, a process that shares similar features with the pathology of tumor invasion. In this study we investigated the expression of the recently described membrane-type matrix metalloproteinase-1 (MT-MMP-1; MMP-14) in early human placenta and decidual membrane to determine whether it might play a role in invasion. With in situ hybridization, the cytotrophoblasts of trophoblastic columns and the infiltrating intermediate trophoblasts in the decidual membrane were found to be the main producers of MT-MMP-1 mRNA. Gene expression was also seen in the villous double-layered trophoblastic epithelium and in the decidual cells of the decidual membrane. In endothelial and fibroblastic cells, however, the hybridization signal was either very weak or nonexistent. Immunohistochemical analysis and immunoelectron microscopy correlated well with the in situ hybridization findings. The most significant exception to this consisted of pericytes of spiral arteries, which appeared to lack MT-MMP-1 mRNA but showed intensive intracytoplasmic staining for the antigen. Our results show that MT-MMP-1 mRNA production is highly characteristic of intermediate trophoblasts, and MT-MMP-1 may have general importance in the tissue organization of early human placenta. We propose that MT-MMP-1 could be one of the key enzymes in the process of trophoblast invasion, acting alone or as a cell-surface activator of other proteinases.

Chorionic Villi↗
PubMed1998

Laminin-5 expression is independent of the injury and the microenvironment during reepithelialization of wounds.

We examined the expression of laminin-5 and its integrin receptors during reepithelialization of human wounds. We used suction blisters of skin as a model of keratinocyte migration on a basement membrane matrix and mucosal full-thickness wounds as a model in which keratinocytes migrate in a provisional matrix. An animal model, in which human epidermal keratinocytes were injected into the back of athymic mice, was used to follow the deposition of the basement membrane components. In 4-day-old blisters, about 20-50 cells at the leading edge of the migrating tongue showed cytoplasmic laminin-5 immunostaining. Laminin-5 mRNA was detected in 15-30 cells at the leading edge of the migrating epidermis. alpha3beta1 and alpha6beta4 integrins were found in membrane projections of the migrating basal cells and also in suprabasal cell layers, suggesting their combined role in binding laminin-5. In mucosal wounds, laminin-5 was the only basement membrane zone component that was deposited between the clot and the migrating keratinocytes. In the animal model, linear deposition of laminin-5 and alpha6beta4 integrin was already seen on Day 2, whereas the other basement membrane zone components were not yet organized. The results suggest that, regardless of the injury and the microenvironment, laminin-5 plays an essential role in the interaction between wound keratinocytes and the surrounding matrix.

Adult↗
PubMed1998

Effects of long-term inhaled corticosteroids on skin collagen synthesis and thickness in asthmatic patients.

There are only a few studies on the adverse effects of inhaled corticosteroids on the skin in asthmatic patients. Therefore, we evaluated the effect of inhaled corticosteroids on de novo collagen synthesis of skin and bone, skin thickness and the total amount of skin collagen. Twenty seven consecutive new asthmatic patients, on a moderate dose of budesonide or beclomethasone dipropionate, were invited to take part in this prospective study. Radioimmunological analyses of aminoterminal propeptides of type I and III procollagens (PINP, PIIINP, respectively) in suction blister fluid (SBF) of skin and in serum and carboxyterminal propeptide of type I procollagen (PICP) and cross-linked carbox terminal telopeptide of type I collagen (ICTP) in serum were performed at entry and after 3 and 6 months of inhaled corticosteroid treatment. Ultrasound measurements of skin thickness at two sites were performed at entry, at 3 and 6 months and after 1-2 yrs of inhaled corticosteroid treatment in 20 patients, six of whom had been prescribed one or more courses of oral corticosteroids. Skin hydroxyproline of punch biopsies was determined to measure the total amount of skin collagen (males, at entry and at 6 months). Skin thickness and the total amount of skin collagen on the abdomen were unchanged after 1-2 yrs of inhaled corticosteroid use. A slight decrease was observed in the upper arm skin thickness, especially in those subjects who had received inhaled plus oral corticosteroids. The procollagen propeptide concentrations (PINP, PIIINP) were markedly decreased in SBF at 3 months and remained at this level at 6 months. In serum, a slight decrease was seen in the PINP, PIIINP and ICTP concentrations at 3 and 6 months. In conclusion, inhaled corticosteroids decrease the collagen synthesis of skin and bone, but skin thickness and the total amount of collagen in skin are not changed markedly after 1-2 yrs of treatment.

Administration, Inhalation↗
PubMed1997

Systemic therapy with estrogen or estrogen with progestin has no effect on skin collagen in postmenopausal women.

OBJECTIVES: To investigate the effect of estrogen alone or combined with progestin on the amount and synthesis of skin collagen in postmenopausal women. METHODS: Forty-three early postmenopausal women were enrolled into this open, non-randomized parallel-groups study. Fifteen women received a continuous oral dose of 2 mg of 17 beta-estradiol and 1 mg of norethisterone acetate daily and 14 women an oral dose of 2 mg estradiol valerate daily. Fourteen subjects served as controls. The histology and type I and III procollagen immunohistochemistry of the skin, skin thickness, the amount of total collagen determined by a colorimetric method and the synthesis of type I and III collagens determined by analysing procollagen propeptides in the suction blister fluid were studied before the treatment and at 6 and 12 months. The proportional area of elastic fibers and the thickness of the epidermis were assessed from the sections obtained before the treatment and at 12 months, with computerized image analysis. RESULTS: Skin thickness, the amount and rate of collagen synthesis, the proportional area of elastic fibers and the thickness of the epidermis were not affected by either 17 beta-estradiol and 1 mg of norethisterone acetate or 2 mg of estradiol valerate. No histological or immunohistological changes were detected in the skin specimens during the 12-month treatment period compared to the baseline or to the skin specimens of the control group. CONCLUSIONS: A 1-year treatment with systemic estrogen alone or combined with progestin does not change the amount of collagen or the rate of collagen synthesis in postmenopausal women.

Administration, Oral↗
PubMed1997

A homozygous nonsense mutation and a combination of two mutations of the Wilson disease gene in patients with different lysyl oxidase activities in cultured fibroblasts.

Wilson disease is a rare autosomal recessive disease of copper metabolism. The gene for Wilson disease was characterized recently and has been predicted to encode a copper-transporting ATPase highly homologous to the protein encoded by the gene of Menkes disease. In this study, the genetic mutations of two Finnish patients with Wilson disease were investigated. One patient was homozygous for a novel nonsense mutation in exon 4, while the other was a compound heterozygote. Lysyl oxidase (EC 1.4.3.13) is an extracellular copper enzyme with deficient activity in Menkes disease. The levels of lysyl oxidase activity in cultured skin fibroblasts from these Wilson disease patients were also measured.

Adult↗
PubMed1997

Distribution and synthesis of type VII collagen in oral squamous cell carcinoma.

The distribution of the basement membrane anchoring fibril component type VII collagen was studied in oral squamous cell carcinoma by using in situ hybridization and immunohistochemical methods. The expression of type VII collagen in oral normal mucosa, lichen planus and epithelial dysplasias was also investigated. In squamous cell carcinomas, the signals for type VII collagen mRNA were located exclusively in malignant peripheral cells in tumour islands and in fibroblast-like cells among the stromal tissue. In normal buccal mucosa, type VII collagen mRNA expression was located in basal epithelial cells. In oral lichen planus and epithelial dysplasias, the signals for type VII collagen mRNA were also located in basal keratinocytes; however, the signal was especially strong in some epithelial cells. In oral squamous cell carcinomas, the linear immunohistochemical staining pattern of type VII collagen was noted surrounding partly squamous epithelial tumour cell islands, and a large number of tumour cells showed a cytoplasmic staining reaction using the type VII collagen antibody. Some fibroblast-like stromal cells also showed a positive immunostaining reaction. In conclusion, the results of this study indicate that a high synthesis level, but an impaired distribution of type VII collagen, are highly characteristic of squamous epithelial tumour cells.

Basement Membrane↗
PubMed1997

Effect of hydrocortisone, methylprednisolone aceponate and momethasone furoate on collagen synthesis in human skin in vivo.

BACKGROUND: Topical corticoids decrease de novo collagen synthesis in the human skin. OBJECTIVE: We studied the effect of three corticoids, hydrocortisone (HC), methylprednisolone aceponate (MPA) and momethasone furoate (MMF) on the de novo synthesis of type I and III collagens. METHODS: Fifteen healthy male volunteers treated four areas marked on their abdominal skin for 1 week. HC was applied twice a day, MPA and MMF once a day plus vehicle once a day and vehicle twice a day. After the treatment, suction blisters were induced on the treated areas, the suction blister fluid (SBF) was collected and procollagen propeptides of type I and III procollagens (PINP, PIIINP, respectively) were analyzed by radioimmunological assays. The protein concentration in SBF was determined by a colorimetric method. RESULTS: All the corticoids studied decreased the procollagen propeptide concentrations in SBF. HC decreased PINP concentration by 66%, MPA by 68% and MMF by 72%. HC decreased PIIINP by 62%, MPA by 68% and MMF by 72%. The protein concentration in SBF was decreased by 11-15% by these topical corticoids. CONCLUSION: HC decreases the concentration of procollagen propeptides in human skin in males to nearly the same extent as MPA and MMF.

Administration, Topical↗
PubMed1997

Isotretinoin, tetracycline and circulating hormones in acne.

Isotretinoin, used to treat severe acne, has been shown to induce hormonal changes, especially to reduce 5 alpha-reductase in the production of the tissue-derived dihydrotestosterone (DHT) metabolite 3 alpha-Adiol G. However, the effects of isotretinoin on other pituitary, adrenal or gonadal hormones have not been thoroughly elucidated. In the present study, isotretinoin administered at a dose of 0.5 mg/kg/day for 4 weeks caused no marked changes in the serum levels of pituitary, adrenal or gonadal hormones or 3 alpha-Adiol G in patients with severe papulopustulotic acne (n = 19). After 12 weeks of therapy, there was a decrease in the levels of the precursor androgens androstenedione, testosterone and 3 alpha-Adiol G in 6/9 patients. Acne improved after 4.5 months in all but 2 male patients, who had very low serum hormone binding globulins (SHBG) and a high free androgen index (FAI). Isotretinoin did not affect the elevated LH/FSH ratio in a patient with the polycystic ovarian syndrome (PCOS); nor did it change the high FAI or low SHBG in the male patients. For comparison, tetracycline had no effects on the serum hormonal levels of patients with mild acne (n = 19) after 7 days of treatment. This study confirms that the effects of isotretinoin on the serum hormone levels are small and unlikely to be of relevance for the resolution of acne or the suppression of sebum excretion.

Acne Vulgaris↗
PubMed1997

Altered distribution and synthesis of laminin-5 (kalinin) in oral lichen planus, epithelial dysplasias and squamous cell carcinomas.

Laminin-5 is a glycoprotein which mediates epithelial cell adhesion to the basement membrane. This study describes the distribution and synthesis of laminin-5 in oral lichen planus, epithelial dysplasias, squamous cell carcinomas and a lymph node metastasis using immunohistochemistry and in situ hybridization. In normal oral mucosa and lichen planus, immunoreaction to the laminin-5 was seen as a thin continuous, delicate line in the basement membrane region, although slight irregularities in the thickness and intensity of the immunoreaction could be detected in some cases with lichen planus. In epithelial dysplasias, the laminin-5 staining was discontinuous and more diffuse compared to lichen planus and normal mucosa. The immunoreaction was generally extracellular, although in some cases with lichen planus and epithelial dysplasia there were a few basal epithelial cells showing cytoplasmic staining. The invasive carcinomas and the lymph node metastasis showed a striking, intense cytoplasmic, staining of the carcinoma cells along the invasive border of the neoplastic islands and in individual infiltrating carcinoma cells. Using in situ hybridization, the laminin-5 gamma 2 chain mRNA expression could not be detected in normal oral mucosa whereas, in non-dysplastic lichen planus and, more strongly, in dysplasias, there was a clear increase in the expression of laminin-5 mRNA in the basal epithelial cells. The most intensive signal was detected in the invasive front of the oral squamous cell carcinomas and the lymph node metastasis. We conclude that, in oral squamous cell carcinoma, there is altered synthesis and secretion of laminin-5 mRNA and protein. It is also evident that in dysplastic lesions of oral epithelium the synthesis and distribution of laminin-5 is abnormal.

Carcinoma, Squamous Cell↗