| 11. |
- Karlsson, Teresa, et al.
(författare)
-
13-cis-retinoic acid competitively inhibits 3 alpha-hydroxysteroid oxidation by retinol dehydrogenase RoDH-4 : a mechanism for its anti-androgenic effects in sebaceous glands?
- 2003
-
Ingår i: Biochemical and Biophysical Research Communications - BBRC. - 0006-291X .- 1090-2104. ; 303:1, s. 273-278
-
Tidskriftsartikel (refereegranskat)abstract
- Retinol dehydrogenase-4 (RoDH-4) converts retinol and 13-cis-retinol to corresponding aldehydes in human liver and skin in the presence of NAD(+). RoDH-4 also converts 3 alpha-androstanediol and androsterone into dihydrotestosterone and androstanedione, which may stimulate sebum secretion. This oxidative 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) activity of RoDH-4 is competitively inhibited by retinol and 13-cis-retinol. Here, we further examine the substrate specificity of RoDH-4 and the inhibition of its 3 alpha-HSD activity by retinoids. Recombinant RoDH-4 oxidized 3,4-didehydroretinol-a major form of vitamin A in the skin-to its corresponding aldehyde. 13-cis-retinoic acid (isotretinoin), 3,4-didehydroretinoic acid, and 3,4-didehydroretinol, but not all-trans-retinoic acid or the synthetic retinoids acitretin and adapalene, were potent competitive inhibitors of the oxidative 3 alpha-HSD activity of RoDH-4, i.e., reduced the formation of dihydrotestosterone and androstandione in vitro. Extrapolated to the in vivo situation, this effect might explain the unique sebosuppressive effect of isotretinoin when treating acne.
|
|
| 12. |
- Arrelöv, Britt, 1953-
(författare)
-
Towards Understanding of Determinants of Physicians’ Sick-listing Practice and their Interrelations : A Population-based Epidemiological Study
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Physicians are supposed to act as sick-listing experts and they possess a role as gate-keepers to the social insurance system. Earlier studies have demonstrated variation between physicians and physician categories regarding sick-listing practice. In addition to the patient's disease and its severity, a number of other factors may be expected to influence sick-listing practice. Most earlier studies have focused on the patient's disease and his or her work place as cause for sickness absence.The aims of this study were to analyse variation of sick-listing practice between physician categories and the influence of physician characteristics on sick-listing practice, the influence of structure, organisation and remuneration of health care on physician sick-listing practice, the influence of local structural factors in the community, and the influence of a legislative change on physician sick-listing practice.The study was conducted as a cross-sectional epidemiological study of 57563 doctors’ certificates for sickness absence, received by 28 local social insurance offices in eight Swedish counties, during four months in 1995 and two months in 1996.Patient age, sex, and diagnostic group, issuing physician category, presence of a hospital in the municipality, municipality population size and county were all significantly and independently correlated to number of net days of sick-listing. Physician characteristics, such as age, sex and degree of specialisation were all associated with number of net days of sick-listing. Physicians working in general practice issued significantly shorter periods of sick-listing than the other physician categories. Reimbursement of general practice and participation in financial co-operation with social insurance were significantly correlated to length of sickness episode issued by general practitioners. A legislative change performed during the study period was associated with small effects in sick-listing practice.In conclusion, a number of factors other than disease and disease severity and other patient and physician linked factors were found to influence the variation of sick-listing practice. It appears that the closer the influencing factor was to the place were the decision was taken, i.e., the patient-physician consultation, the higher the impact on the decision appeared to be.
|
|
| 13. |
- Pienimaki, Juha-Pekka, et al.
(författare)
-
Epidermal growth factor activates hyaluronan synthase 2 in epidermal keratinocytes and increases pericellular and intracellular hyaluronan.
- 2001
-
Ingår i: Journal of Biological Chemistry. - : American Society of Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 276:23, s. 20428-20435
-
Tidskriftsartikel (refereegranskat)abstract
- Hyaluronan is an abundant and rapidly turned over matrix molecule between the vital cell layers of the epidermis. In this study, epidermal growth factor (EGF) induced a coat of hyaluronan and a 3-5-fold increase in its rate of synthesis in a rat epidermal keratinocyte cell line that has retained its ability for differentiation. EGF also increased hyaluronan in perinuclear vesicles, suggesting concurrent enhancement in its endocytosis. Cell-associated hyaluronan was most abundant in elongated cells that were stimulated to migrate by EGF, as determined in vitro in a wound healing assay. Large fluctuations in the pool size of UDP-N-acetylglucosamine, the metabolic precursor of hyaluronan, correlated with medium glucose concentrations but not with EGF. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed no increase in hyaluronan synthases 1 and 3 (Has1 and Has3), whereas Has2 mRNA increased 2-3-fold in less than 2 h following the introduction of EGF, as estimated by quantitative RT-PCR with a truncated Has2 mRNA internal standard. The average level of Has2 mRNA increased from approximately 6 copies/cell in cultures before change of fresh medium, up to approximately 54 copies/cell after 6 h in EGF-containing medium. A control medium with 10% serum caused a maximum level of approximately 21 copies/cell at 6 h. The change in the Has2 mRNA levels and the stimulation of hyaluronan synthesis followed a similar temporal pattern, reaching a maximum level at 6 h and declining toward 24 h, a finding in line with a predominantly Has2-dependent hyaluronan synthesis and its transcriptional regulation.
|
|
| 14. |
- Rilla, Kirsi, et al.
(författare)
-
Changed lamellipodial extension, adhesion plaques and migration in epidermal keratinocytes containing constitutively expressed sense and antisense hyaluronan synthase 2 (Has2) genes.
- 2002
-
Ingår i: Journal of Cell Science. - Cambridge : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 115, s. 3633-3643
-
Tidskriftsartikel (refereegranskat)abstract
- Hyaluronan is a major component of the epidermal extracellular matrix, is actively synthesized by keratinocytes and shows fast matrix turnover in the stratified epithelium. We probed the importance of hyaluronan synthesis in keratinocytes by establishing cell lines carrying the exogenous hyaluronan synthase 2 (Has2) gene in sense and antisense orientations to increase and decrease their hyaluronan synthesis, respectively. Compared with cell lines transfected with the vector only, most clones containing the Has2 sense gene migrated faster in an in vitro wounding assay, whereas Has2 antisense cells migrated more slowly. Has2 antisense clones showed delayed entry into the S phase of cell cycle following plating, smaller lamellipodia and less spreading on the substratum. The decrease of hyaluronan on the undersurface of Has2 antisense cells was associated with an increased area of adhesion plaques containing vinculin. Exogenous hyaluronan added to the keratinocyte cultures had a minor stimulatory effect on migration after wounding but did not restore the reduced migratory ability of Has2 antisense cells. Hyaluronan decasaccharides that displace receptor bound hyaluronan in keratinocytes, and Streptomyces hyaluronidase sufficient to remove most cell surface hyaluronan had little effect on cell migration. The results suggest that the dynamic synthesis of hyaluronan directed by Has2, rather than the abundance of pericellular hyaluronan, controls keratinocyte migration, a cell function vital for the repair of squamous epithelia following wounding.
|
|
| 15. |
- Rilla, Kirsi, et al.
(författare)
-
Hyaluronan synthase-2 (HAS-2) regulates migration of epidermal keratinocytes
- 2002
-
Ingår i: Hyaluronan, Vol 1: Chemical, Biochemical and Biological Aspects. - Great Britain : Woodhead Publishing Limited. - 1855735709 ; , s. 557-560
-
Konferensbidrag (refereegranskat)abstract
- Hyaluronan (HA) is a linear polysaccharide abundant in the extracellular space between epidermal keratinocytes. It is synthesized at the inner face of the plasma membrane by hyaluronan synthases (Has). We probed the importance of hyaluronan in keratinocytes by establishing cell lines carrying exogenous hyaluronan synthase 2 (Has2) gene(s) in sense and antisense orientations in order to increase and decrease their hyaluronan synthesis, respectively.The cell lines with the sense Has2 cDNA showed increased HA synthesis, while most cell lines with Has2 antisense cDNA contained less HA. Has2 antisense cells differed from control cell lines; they spread at a slower rate and retained a rounded morphology for a longer time. Further, during the first 24 hours after plating, proliferation was delayed in the antisense cell lines. In an in vitro wounding assay the antisense cells showed a significantly decreased migration rate as compared to controls. Cell lines with the Has2 sense cDNA were similar to the control cell lines in spreading and proliferation rates. However, they migrated faster than control cell lines.
|
|
| 16. |
- Tammi, Markku, et al.
(författare)
-
EGF regulates HAS-2 expression, controls epidermal thickness and stimulates keratinocyte migration
- 2002
-
Ingår i: Hyaluronan, Vol 1: Chemical, Biochemical and Biological Aspects. - Great Britain : Woodhead Publishing Limited. - 1855735709 ; , s. 561-570
-
Konferensbidrag (refereegranskat)abstract
- High concentrations of hyaluronan reside in the small space between the vital kertinocyte layers of human and animal epidermis and influence keratinocyte interactions, including growth, mobility and differentiation. We have previously found that the content of epidermal hyaluronan in human skin organ cultures is decreased and increased by cortisol and retinoic acid, and associated with enhanced and retarded terminal differentiation, respectively. To further substantiate this idea, we incubated epidermal keratinocytes with epidermal growth factor (EGF), and found a marked increase in hyaluronan synthesis which correlated with faster migration in an in vitro wounding assay of keratinocyte monolayers. EGF increased hyaluronan also in stratified, differentiated organotypic cultures, and increased the height of vital epidermis and reduced the thickness of the cornified layers, findings in line with an inhibition of terminal differentiation of keratinocytes. The stimulation of hyaluronan synthesis by EGF was due to upregulation of hyaluronan synthase 2 (HAS2) but not HAS1 or HAS3. A part of the EGF influence on the structure of epidermis, and on skin wound healing, is thus mediated through its control of HAS2 expression.
|
|
| 17. |
- Törrönen, Kari, et al.
(författare)
-
Hyaluronan stimulates keratinocyte migration and activates the transcription factor AP-1 in keratinocytes through the JNK pathway
- 2002
-
Ingår i: Hyaluronan, Vol 1: Chemical, Biochemical and Biological Aspects. - Great Britain : Woodhead Publishing Limited. - 1855735709 ; , s. 551-556
-
Konferensbidrag (refereegranskat)abstract
- Hyaluronan (HA) has been considered a passive extracellular matrix (ECM) polysaccharide, but recent studies have shown its importance in controlling many cell functions including motility, proliferation and adhesion, which imply signaling from ECM to cytosol. Hyaluronan is a major ECM component in stratified epithelia such as skin epidermis. We found that hyaluronan added to the growth medium of newly plated human skin keratinocytes increased cell migration in an in vitro wound-healing assay. Hyaluronan also increased the transcription factor AP-1, as determined by gel shift assays. The kinase signals that apperently led to the increased AP-1 level were associated with the activation of c-Jun, mainly via the JNK pathway as early as 10 min after the addition of hyaluronan, and with the minimum concentration of 10 ng/ml. ERK1 was also slightly activated, while p38 MAPkinase was not affected.
|
|
| 18. |
- Gruvberger, Birgitta, et al.
(författare)
-
Methyldibromoglutaronitrile
- 2003
-
Ingår i: Management of positive patch test reactions. - 3540443479 ; , s. 41-41
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 19. |
- Björkegren, Karin
(författare)
-
Studies on Vitamin B12 and Folate Deficiency Markers in the Elderly : A Population-based Study
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims of this study were to document the levels of cobalamin, folate, methylmalonic acid (MMA) and total homocysteine (tHcy) in serum and their relations to symptoms, clinical findings, and other factors in order to improve the possibilities of detecting early deficiency of vitamin B12 or folate, and to study the effects of cobalamin and folic acid treatment over a three-year period. The study population consisted of a 20% random sample of persons 70 years or older living in Älvkarleby in mid-Sweden. They were invited to a survey and 224 (88.4%) persons responded. Data were obtained by questionnaire, laboratory investigations and physical examination for the period 1993 – 1999. In a multivariate analysis performed at baseline, serum MMA and tHcy were significantly and independently correlated to age, serum cobalamin, and creatinine levels, and tHcy also to sex and serum folate. Neither serum cobalamin, folate, MMA nor tHcy had any significant correlation to haemoglobin or mean red cell volume. Almost half of the study population had signs of low tissue levels of vitamin B12 or folate. Among those who took multivitamin preparations, the proportion was much lower, 25%. Among traditional symptoms and clinical findings that have been linked to vitamin B12 or folate tissue deficiency, only changes in the tongue mucosa and mouth angle stomatitis were significantly associated with abnormal serum folate and tHcy levels. Traditional symptoms of vitamin deficiency may appear later in the course. 69 persons who had laboratory indications of early or overt tissue deficiency of vitamin B12 or folate and who had no ongoing vitamin treatment were given cobalamin for six months. Those whose MMA or tHcy levels did not normalise were given folic acid in addition to cobalamin. After further treatment for three months, all persons but one had normal levels. The laboratory effect still remained after three years of treatment. There was a tendency towards improvement of vibration sense, especially in the long nerve paths, and improvement of neurological symptoms and oral mucosa findings. Conclusion: A substantial proportion of elderly persons have laboratory signs of incipient tissue deficiency of vitamin B12 and folate. Treatment normalises lab parameters and some symptoms.
|
|
| 20. |
- Engvall, Karin, 1949-
(författare)
-
A Sociological Approach to Indoor Environment in Dwellings : Risk factors for Sick Building Syndrome (SBS) and Discomfort
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The principal aim was to study selected aspects of indoor environment in dwellings and their association with symptoms compatible with the sick building syndrome (SBS). A validated questionnaire was developed specifically for residential indoor investigations, using sociological principles and test procedures. The questionnaire was mailed to 14,243 multi-family dwellings in Stockholm, selected by stratified random sampling. Females, subjects with a history of atopy, those above 65 y, and those in new buildings reported more symptoms. Subjects owning their own dwelling had less symptoms. A multiple regression model was developed, to identify residential buildings with a higher than expected occurrence of SBS. In total, 28.5% reported at least one sign of building dampness in their home (condensation on windows, humidity in the bathroom, mouldy odour, water leakage). All indicators of dampness were related to symptoms, even when adjusting for demographic data, and other building characteristics (OR=2.9-6.0). Associations between symptoms and other building data was evaluated in older houses, built before 1961. Subjects in older buildings with a mechanical ventilation system had fewer symptoms. Heating by electric radiators, and wood heating was associated with an increase of most types of symptoms (OR=1.2-5.0). Multiple sealing measures (OR=1.3), and major reconstruction (OR=1.1-1.9), was associated with an increase of symptoms. The effect of seasonal adapted ventilation (SAV) was studied in a small experimental study. A 20% reduction of ventilation flow from 0.5-0.8 ac/h to 0.4-0.5 ACH during the heating season increased the perception of poor indoor air quality in the dwelling in general, and in the bedroom. In conclusion, low building age, and building dampness in the dwelling are associated with SBS. In older houses, mechanical ventilation is beneficial. The thesis did not support the view that energy saving measures in general is an important risk factor for SBS, but major reconstruction and multiple sealing measures can be risk factor for symptoms. Reducing the outdoor ventilation flow below the current Swedish ventilation standard (0.5 ACH) may increase the perception of impaired air quality.
|
|
