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Biomedical subjects

J Peltonen

Publications and source records attributed to J Peltonen.

At least 19 recordsLinked to original sources

Immunohistological distribution of the tight junction components ZO-1 and occludin in regenerating human epidermis.

BACKGROUND: Molecular characterization of tight junction proteins during the past few years has provided novel methods for studying these specialized junctions. Tight junctions have recently been characterized in the granular cell layer of human epidermis, and the role of these junctions in the epidermal barrier is now being re-evaluated. OBJECTIVES: To investigate the expression of tight junction components during the re-epithelialization of suction blisters and the regeneration of the corneal layer after tape stripping. METHODS: Suction blisters were induced in eight healthy volunteers, and skin biopsies were taken 4 or 6 days afterwards. The restoration of epidermal barrier function was evaluated by measuring water evaporation (WE) from the wound area. Tape stripping was performed on three volunteers to remove the corneal layer. The tissues were immunolabelled using indirect immunofluorescence or the avidin-biotin method. RESULTS: Prior to the biopsies, WE from the blister wounds was markedly elevated in comparison with normal skin. In the epidermis surrounding the blister, occludin and ZO-1 were expressed in the granular cell layer only. In the hyperproliferative zone adjacent to the border of the blister, the expression of ZO-1 was redistributed into several spinous cell layers, while occludin expression was restricted to the upper epidermis. In the leading edge of migrating keratinocytes, both proteins were expressed exclusively in the most superficial layer of keratinocytes. Double labelling for ZO-1 and involucrin showed expression of both proteins in the same layers of hyperproliferative keratinocytes, while the expression patterns were clearly different in the migrating keratinocytes. CONCLUSIONS: Tight junctions of regenerating epidermis may provide a functional barrier prior to regeneration of the corneal layer.

Adult↗

Stability of leisure-time physical activity during adolescence--a longitudinal study among 16-, 17- and 18-year-old Finnish youth.

Participation in physical activity during childhood and adolescence is frequently mentioned as one factor likely to promote a more active lifestyle in adulthood with its health benefits. We studied the changes in leisure-time physical activity pattern and self-reported fitness during a three-year period in adolescence and investigated whether the type of sports has an effect on stability of physical activity at leisure. A questionnaire with identical physical activity items was sent to Finnish twins on their 16th and 17th birthdays and 6 months after the 18th birthday. A total of 1338 boys and 1596 girls responded to all three questionnaires, with response rates of 73.6% and 86.5%. The proportions of very active adolescents and adolescents with very good self-reported fitness seem to be alike at each age. Among girls, 23.7% to 27.7% reported being very active (4-5 times a week) and 13.7% to 15.1% considered their physical fitness to be very good at the ages of 16, 17 and 18. Among boys, the comparable percentages were 31.5% to 35.5% and 30.6% to 34.4%. However, the longitudinal three-year follow up showed substantial changes over time among individuals from one physical activity group to another. Only 19.1% of boys and 11.2% of girls were persistent exercisers (i.e., very active on all three years) and 15.6% of boys and 5.1% of girls were persistently fit (i.e., very good self-reported fitness on all three years). Stability of leisure-time physical activity was highest among those who participated in several different types of sports. Among boys the proportion of persistent exercisers was highest for those who participated in cross-country skiing, jogging and body-building (22.0-41.5%) and among girls for those who participated in ball games (11.9-28.6%). Those who participated in organised sports were more often persistent exercisers than those who did not (odds ratio = 13.2 for boys (CI 9.4-18.7) and 8.9 for girls (CI 6.4-12.5)). Also, those who participated in organised sports were more often persistently fit (odds ratio = 7.3 for boys (CI 5.2-10.2) and 10.4 for girls (CI 6.4-16.9). Adolescents are recommended to participate in and try different types of sports, and especially for girls ball games would appear to favour long-term maintenance of leisure-time physical activity.

Adolescent↗

Charcot arthropathy of the diabetic foot. Current concepts and review of 36 cases.

BACKGROUND AND AIMS: The incidence of diabetic Charcot neuroarthropathy has increased. The purpose here was to study the current diagnostics and treatment of the Charcot foot. MATERIALS AND METHODS: During a time period from 1994 to 2000, a total of 36 feet were diagnosed as cases of diabetic Charcot neuroarthropathies. A retrospective analysis of patient records and radiographs was undertaken. A review of the recent literature is presented. RESULTS: 29 cases were diagnosed in the dissolution stage, 2 in coalascence, and 5 in the resolution stage. The diagnostic delay averaged 29 weeks. Treatment with cast immobilisation ranged from 4 to 37 weeks (mean 11 weeks). A total of 14 surgical procedures were carried out on 10 patients: six exostectomies, four midfoot arthrodeses, one triple arthrodesis, one tibiocalcaneal arthrodesis and two below-knee amputations. A radiological fusion was achieved in two thirds of the attempted arthrodeses. CONCLUSIONS: A physician should always consider the Charcot neuroarthropathy when a diabetic patient has an inflamed foot. In the absence of fever, elevated CRP or ESR, infection is a highly unlikely diagnosis, and a Charcot process should primarily be considered. The initial treatment of an inflamed Charcot foot consists in sufficiently long non-weightbearing with a cast, which should start immediately after the diagnosis. The prerequisites of successful reconstructive surgery are correct timing, adequate fixation and a long postoperative non-weightbearing period. In the resolution stage most Charcot foot patients need custom-molded footwear.

Adult↗

Scoliosis in patients with diastrophic dysplasia: a new classification.

STUDY DESIGN: Scoliosis in patients with diastrophic dysplasia was analyzed. OBJECTIVES: To study the natural history of scoliosis and to classify the patients with different types of scoliosis. SUMMARY OF BACKGROUND DATA: Typical findings in diastrophic dysplasia are short-limbed short stature, multiple joint contractures, early degeneration of joints, and spinal deformities. The largest studies have reported scoliosis in 37% to 88% of the patients with this rare skeletal dysplasia. The natural history of the deformity is unknown. METHODS: Of the 130 unselected patients, 98 (75%) who were older than 16 years and/or had undergone surgery at the time of the last radiograph were included in the final analysis. These 98 patients included 37 males and 61 females. Their ages at the first radiograph ranged from newborn to 78 years (average, 21 years). The mean follow-up period was 20 years (range, 2-41 years) for 80 patients. Standard standing anteroposterior and lateral radiographs were taken. The degrees of scoliosis, kyphosis, and lordosis were measured according to the Cobb method. Classification of the scoliosis was based on the patient's age at onset of scoliosis, the rate of progression, the magnitude of the scoliosis at the end of growth, and the curve pattern. RESULTS: Of the 98 patients in this study, 86 (88%) had scoliosis. This difference was highly significant statistically (P < 0.001), as compared with the normal population. The frequency of scoliosis was 90% among females and 84% among males. Scoliosis can be divided further into three subtypes: early progressive (11 patients), idiopathic-like (41 patients), and mild nonprogressive (33 patients). One patient had a congenital scoliosis. CONCLUSIONS: Scoliosis is very common in patients with diastrophic dysplasia. The natural history of scoliosis varies from severe deformity with rapid progression to mild deformity without any progression. The authors suggest that the classification described in this report offers a tool for the predicting natural history of scoliosis in diastrophic dysplasia, and for adjusting the timing of surgery in individual patients.

Adolescent↗

Thoracic and lumbar spine in diastrophic dysplasia: a clinical and magnetic resonance imaging analysis.

STUDY DESIGN: Cross-sectional study to evaluate the thoracic and lumbar spine in patients with diastrophic dysplasia (DD). OBJECTIVES: To find the causative factors behind the spinal deformities and restricted mobility of the spine. SUMMARY OF BACKGROUND DATA: Typical findings in this skeletal dysplasia are short-limbed stature, multiple joint contractures, early degeneration of joints, and spinal deformities such as cervical kyphosis, scoliosis, and exaggerated lumbar lordosis. The pathogenic mechanism of scoliosis is unknown. METHODS: A physical examination was performed on 88 patients (55 females, 33 males) with an average age of 31 years (range, 3-56). Magnetic resonance (MR) images from T2 to S1 and radiographs were obtained. Degree of scoliosis was measured according to Cobb from standing radiographs. The anatomy of the medulla and the size of the spinal canal were assessed. The transverse dural tube area was measured from L2 to S1. Disc space, degeneration, and protrusions were evaluated. Vertebral abnormalities, if any, facet joint degeneration and the state of the spinal muscles were also assessed. RESULTS: Physical examination showed diminished mobility of the spine. Scoliosis was noted in 70 patients with an average of 42 degrees (range, 11-188 degrees ). The mean transverse area of the dural tube ranged from 94 mm(2) at L2-L3 to 57 mm(2) at L5-S1. The area was smaller at all levels compared with reference values (P < 0.001). One patient had severe thoracic and lumbar spinal stenosis. Five patients had compression of neural structures in the lumbar spinal canal in MR images, but had no clinical symptoms. All patients exhibited narrowed disc heights and a decrease in the signal intensity of discs on T2-weighted images. The prevalence of disc protrusions was low; three patients had a prolapse in the lumbar spine. Two patients displayed vertebral anomalies. All patients also had muscular atrophy and degenerative-like facet joint hypertrophy. The severity of these changes increased with age. CONCLUSIONS: Abnormal disc structure and rapid degeneration explain the diminished decreased mobility of the spine and may be a causative factor in the development of scoliosis. Muscular atrophy may be caused by reduced physical activity and rigid spinal deformities. The spinal canal is narrowed, but symptomatic lumbar spinal stenosis is uncommon.

Adolescent↗

Effect of sucrose on collagen metabolism in keloid, hypertrophic scar, and granulation tissue fibroblast cultures.

Sucrose has been used to treat wounds with excellent results and with minimal abnormal scarring. In this study the effects of sucrose on collagen metabolism in fibroblast culture was evaluated. Sucrose (5.5, 15, or 25 mM) was added to granulation tissue, hypertrophic scar, and keloid fibroblast cultures, mRNA levels and procollagen aminopropeptides for type I and III collagens in cell culture medium were studied. Sucrose decreased mRNA levels for pro alpha 1(I) and pro alpha 1(III) collagens in fibroblast cultures derived from hypertrophic scar and keloid. In normal granulation tissue fibroblast cultures, 5.5 mM sucrose increased mRNA levels for pro alpha 1(I) and pro alpha 1(III) collagen, and higher concentrations decreased them. The synthesis of type I collagen decreased dose-dependently in all cell strains, whereas the synthesis of type III collagen decreased only in granulation tissue fibroblasts. To conclude, in vitro high concentrations of sucrose down-regulate both collagen gene expression and synthesis in normal granulation tissue fibroblasts, whereas in fibroblasts derived from abnormal scar sucrose down-regulates only type I collagen gene expression and synthesis, changing the pattern of collagen metabolism toward normal.

Cicatrix, Hypertrophic↗

Differential effects of hexoses and sucrose, and platelet-derived growth factor isoforms on cyclooxygenase-1 and -2 mRNA expression in keloid, hypertrophic scar and granulation tissue fibroblasts.

Cyclooxygenase (COX) is the key enzyme in the formation of prostaglandins in inflammation. In the present study the effects of biomedically relevant hexose sugars (glucose, fructose, galactose, mannose) and sucrose disaccharide on the expression of COX-1 and COX-2 genes were evaluated in granulation tissue fibroblasts, hypertrophic scar fibroblasts and keloid fibroblasts. The effects of three isoforms (AA, AB and BB) of PDGF on COX gene expression in granulation tissue fibroblasts were also examined. All cell lines expressed COX-1 mRNA, whilst fibroblasts derived from abnormal scars did not express COX-2 mRNA. COX-1 mRNA expression was decreased by sugars in granulation tissue fibroblasts and increased in hypertrophic scar fibroblasts. No major changes were seen in keloid fibroblasts. On the other hand, COX-2 mRNA expression in granulation tissue fibroblasts was decreased dramatically in the presence of fructose, mannose and sucrose and moderately in the presence of galactose. All isoforms of PDGF increased COX-1 and COX-2 mRNA expression in granulation tissue fibroblasts, the most marked increases being elicited by PDGF-BB. All fibroblast cell lines studied expressed the COX-1 gene while the COX-2 gene was not expressed by abnormal scar-derived fibroblasts. Further, granulation tissue fibroblasts seemed to behave differently under the influence of sugars compared to hypertrophic scar fibroblasts whilst keloid fibroblasts seemed to be relatively unaffected by sugars. In addition, the PDGF-BB isoform is a potent inducer of COX-2 gene expression in wound fibroblasts. These findings may be relevant to the development of abnormal scars and indicate the need for further studies.

Cells, Cultured↗

Expression profiles of cell-cell and cell-matrix junction proteins in developing human epidermis.

The spatial distribution of a panel of cell junction proteins was studied in developing human epidermis by confocal laser scanning microscopy. The results demonstrated that many of the cell junction proteins were expressed in early two-layered embryonic epidermis, but their subcellular distribution displayed marked changes during development. Specifically, desmosomal proteins, desmoplakin, desmocollin and desmoglein, adherens junction components, E-cadherin, alpha-catenin and vinculin, and an actin-binding protein alpha-actinin were expressed as early as 8 weeks of estimated gestational age (EGA). Type IV collagen and beta1 and beta4 integrins were also present. At this early developmental stage, the epidermis is known to comprise two layers of cells, the basal layer and the peridermal layer. In addition to being present in cell-cell contacts, desmosomal antigens and E-cadherin were unexpectedly localized to the basal aspect of basal cells in samples at 8 weeks. On the other hand, talin, which in adult skin is localized to the dermal-epidermal junction, could not be detected until 12 weeks. These results suggest that the separation of cell membranes to the basal and apicolateral compartments does not occur before the maturation of the basement membrane zone. At 8 weeks EGA, gap junction antigen connexin 43 was expressed in scarce spots in cell-cell contacts of basal cells. In samples of 11-21 weeks EGA, the density of desmosomal and adherens junction markers as well as connexin 43 increased in cell-cell junctions, together with the appearance of the intermediate cell layer and beginning of stratification of the epidermis.

Actinin↗

Epidermal tight junctions: ZO-1 and occludin are expressed in mature, developing, and affected skin and in vitro differentiating keratinocytes.

This study demonstrates the presence of tight junction antigens in adult and developing human epidermis. Indirect immunofluorescence labeling and immunoelectron microscopy with antibodies to ZO-1 and occludin localized tight junction components ZO-1 and occludin to a narrow zone of the granular cells of adult epidermis. Double immunolabeling for tight junction components with adherens junction or desmosome proteins suggested that occludin is more specific for tight junctions than ZO-1, which may also be associated with adherens junctions. In developing skin, tight junctions interconnected the peridermal cells, and after the fetal stratification localized to the granular cell layer. Immunolabeling of psoriasis, lichen planus, and ichthyosis vulgaris, representing aberrant differentiation of the epidermis, showed that these conditions were associated with relocation of ZO-1 and occludin to the spinous cells. Cultures of epidermal keratinocytes, which offer a useful model for the formation of cellular contacts, revealed that tight junction components, ZO-1 and occludin, displayed a marked degree of colocalization relatively late during the process when the fusion zone had assumed a linear appearance. This suggests that the formation of adherens junctions and desmosomes precedes that of tight junctions. We speculate that the epidermal barrier, isolating the human body from the external environment, is in part formed by tight junctions of stratum granulosum.

Adult↗

The effects of sialic acid on the gene expression of fibrillar collagens: different changes in normal and fibrotic scar derived fibroblasts.

OBJECTIVE: To investigate the effect of free sialic acid on collagen gene expression in fibroblasts. DESIGN: Cell culture study. SETTING: University hospital, Finland. CELL LINES: Human granulation tissue fibroblasts, human hypertrophic scar fibroblasts and human keloid fibroblasts. INTERVENTIONS: Treatment of cell cultures with 3 microM, 30 microM and 300 microM N-acetyl-neuraminic acid. MAIN OUTCOME MEASURES: The measurement of steady state level of mRNA for type I and type III collagen. RESULTS: Fibroblast lines react dissimilarly under the influence of sialic acid. Granulation tissue fibroblasts showed decrease in the gene expression of type I and III collagen, while keloid fibroblasts contrastingly showed an increase. Hypertrophic scar derived fibroblasts showed no change. CONCLUSIONS: Sialic acids may decrease collagen gene expression in granulation tissue and that disturbed wound healing in diabetics and smokers may in part be due to direct effect of sialic acids on fibroblasts. Sialic acids may in part induce keloid formation.

Cells, Cultured↗

Effects of glucose on collagen mRNA levels and collagen secretion in EAhy 926 endothelial cell line.

Diabetes mellitus (DM) is a complex metabolic disease associated with increased accumulation of extracellular matrix by endothelial cells and contributing to vascular complications of long-standing diabetes. On the other hand, DM is also associated with decreased accumulation of extracellular matrix in granulation tissue, which is suggested to be a consequence of impaired angiogenesis. The role of hyperglycemia in these situations is not fully understood. We examined the effects of high glucose concentrations on the gene expression and secretion of various collagens in cultured EAhy 926 endothelial cells. EAhy 926 endothelial cells expressed alpha 1(I) collagen mRNA at a low level and small amount of the corresponding peptide was secreted from the cells; mRNA was not affected but peptide secretion was increased by elevated glucose concentration. mRNAs for type III and VI collagens were not detected in the endothelial cells Furthermore, high glucose concentration in long term had no morphological effects on cultured endothelial cells but increased the expression of type IV collagen, which could rather be beneficial for angiogenesis in a healing wound. Our results suggest that high glucose concentration per se may contribute to increased accumulation of extracellular matrix in blood vessels but probably is not responsible for decreased angiogenesis and granulation tissue formation in diabetic patients.

Cell Line↗

The effects of sialic acid on the gene expression of fibrillar collagens: different changes in normal and fibrotic scar derived fibroblasts.

OBJECTIVE: To investigate the effect of free sialic acid on collagen gene expression in fibroblasts. DESIGN: Cell culture study. SETTING: University hospital, Finland. CELL LINES: Human granulation tissue fibroblasts, human hypertrophic scar fibroblasts and human keloid fibroblasts. INTERVENTIONS: Treatment of cell cultures with 3 microM, 30 microM and 300 microM N-acetyl-neuraminic acid. MAIN OUTCOME MEASURES: The measurement of steady state level of mRNA for type I and type III collagen. RESULTS: Fibroblast lines react dissimilarly under the influence of sialic acid. Granulation tissue fibroblasts showed decrease in the gene expression of type I and III collagen, while keloid fibroblasts contrastingly showed an increase. Hypertrophic scar derived fibroblasts showed no change. CONCLUSIONS: Sialic acids may decrease collagen gene expression in granulation tissue and that disturbed wound healing in diabetics and smokers may in part be due to direct effect of sialic acids on fibroblasts. Sialic acids may in part induce keloid formation.

Cells, Cultured↗

Effects of glucose on collagen mRNA levels and collagen secretion in EAhy 926 endothelial cell line.

Diabetes mellitus (DM) is a complex metabolic disease associated with increased accumulation of extracellular matrix by endothelial cells and contributing to vascular complications of long-standing diabetes. On the other hand, DM is also associated with decreased accumulation of extracellular matrix in granulation tissue, which is suggested to be a consequence of impaired angiogenesis. The role of hyperglycemia in these situations is not fully understood. We examined the effects of high glucose concentrations on the gene expression and secretion of various collagens in cultured EAhy 926 endothelial cells. EAhy 926 endothelial cells expressed alpha1(I) collagen mRNA at a low level and small amount of the corresponding peptide was secreted from the cells; mRNA was not affected but peptide secretion was increased by elevated glucose concentration. mRNAs for type III and VI collagens were not detected in the endothelial cells. Furthermore, high glucose concentration in long term had no morphological effects on cultured endothelial cells but increased the expression of type IV collagen, which could rather be beneficial for angiogenesis in a healing wound. Our results suggest that high glucose concentration per se may contribute to increased accumulation of extracellular matrix in blood vessels but probably is not responsible for decreased angiogenesis and granulation tissue formation in diabetic patients.

Cell Line↗