| 1. |
- 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.
|
|
| 2. |
- Nilsson, H-J., et al.
(författare)
-
Profound inhibition of chronic itch induced by stimulation of thin cutaneous nerve fibres
- 2004
-
Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Elsevier. - 0926-9959 .- 1468-3083. ; 18:1, s. 37-43
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite the fact that severe itch is common in many dermatological diseases, the therapeutic arsenal against itching is limited. From neurophysiological experiments, using a new technique termed cutaneous field stimulation, it is known that acute itch can be effectively relieved by stimulation of cutaneous nociceptors. METHODS: We tested the effects of cutaneous field stimulation (25 min, 16 electrodes, 4 Hz per electrode, up to 0.8 mA) on chronic itch due to atopic dermatitis. Transcutaneous electrical nerve stimulation (100 Hz, up to 26 mA) was used for comparison. In 27 patients, itch was measured just prior to, during and at regular intervals up to 12 h after either type of treatment. RESULTS: Both treatments augmented the itch sensation during ongoing stimulation, presumably reflecting an altered sensory processing in the somatosensory pathways of chronic itch patients. However, after cessation of cutaneous field stimulation, but not transcutaneous electrical nerve stimulation, the itch sensation was significantly depressed for up to 7 h. The peak inhibitory effect (about 25% of control) was reached between 1 and 5 h poststimulation. Neither treatment had any significant effect on alloknesis, as measured before and 10 min after stimulation. CONCLUSION: It is concluded that cutaneous field stimulation strongly depresses chronic itch, and is a potentially useful symptomatic treatment of itch.
|
|
| 3. |
- Björklund, Martin, 1961-
(författare)
-
Effects of repetitive work on proprioception and of stretching on sensory mechanisms : implications for work-related neuromuscular disorders
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims of the thesis were (i) to investigate the impact of repetitive low-intensity work exposure on proprioception and (ii) to examine effects of muscle stretching (especially sensory effects and effects on muscle nociception) and to relate its application to the prevention, alleviation and/or treatment of work-related neuromuscular disorders. The effects of low-intensity repetitive work on the shoulder proprioception were tested in healthy subjects. The effect of working time on the retention of subjective fatigue and their relation to changes in proprioception, and the immediate effect of stretching on shoulder proprioception were investigated. A new method to test the stretchability of the rectus femoris muscle was investigated for reliability and validity and used to assess the effects of a two-week stretching regimen on range of motion and on subjective stretch sensation. Finally, the interactions between innocuous muscle stretch and nociceptive chemical stimulation on discharge behavior of nociceptive dorsal horn neurons in the feline spinal cord were explored. The main findings were as follows: 1) The repetitive low-intensity work to fatigue diminished the shoulder proprioception; the working time as well as the retention of subjective fatigue were partly related to the extent of changed proprioception. 2) There was no effect of acute muscle stretching on the proprioception. 3) The new method for testing muscle stretchability proved valid and reliable. A two-week stretching regimen increased the tolerance to stretch torque, but the range of motion remained unchanged. 4) Half of the nociceptive dorsal horn neurons that responded to close arterial injections of bradykinin were modulated by muscle stretching applied directly after the injections. Altogether, the results give credence to the hypothesis of an involvement of sensory information distortion due to repetitive low-intensity work exposure in the development of work-related neuromuscular disorders. Increased tolerance to stretch torque may be an important mechanism in explaining improvements following stretch treatment. The spinal interactions between innocuous stretch and nociceptive muscle afferent inputs indicate a possible mechanism involved in stretching-induced pain alleviation.
|
|
| 4. |
- Blomberg, Stina, 1966-
(författare)
-
Autoantibodies and the Type I Interferon System in the Etiopathogenesis of Systemic Lupus Erythematosus
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In sera remitted for anti-nuclear antibody (ANA) analysis, the supplement of a sensitive anti-SSA/Ro ELISA to the conventional ANA screening by immunofluorescence (IF) revealed that one fourth of the individuals with IF-ANA negative, but SSA/Ro ELISA positive sera, had systemic lupus erythematosus (SLE) or cutaneous LE. Consequently, adding a sensitive anti-SSA/Ro ELISA to the ANA screening is valuable for the serological detection of ANA negative SLE/LE patients.SLE patients often have measurable interferon-alpha (IFN-α) levels in serum, and IFN-α treatment of patients with non-autoimmune diseases can induce SLE. Thus, the type I IFN system seems to be important in SLE and was therefore investigated. Initially, a decreased IFN-α producing capacity, due to a 70-fold reduction in the number of circulating natural IFN-α producing cells (NIPC), was noted in peripheral blood mononuclear cells (PBMC) from SLE patients. SLE-sera contained an endogenous IFN-α inducing factor (SLE-IIF), consisting of IgG and DNA in the form of small immune complexes (300-1000 kD). The SLE-IIF selectively activated NIPC and was more common in sera from patients with active disease compared to individuals with inactive disease. IFN-α producing cells could be detected by immunohistochemistry in both lesional and unaffected skin from SLE patients, and IFN-α gene transcription could be verified by in situ hybridisation in some of the skin biopsies. A reduced number of NIPC, detected by expression of the blood dendritic cell antigen (BDCA)-2, was noted among SLE-PBMC. The IFN-α production triggered by SLE-IIF in SLE-PBMC was inhibited by monoclonal antibodies (mAbs) to BDCA-2 and markedly decreased by anti-BDCA-4 mAbs. The observations in the present thesis may explain the ongoing IFN-α production in SLE patients, indicate an important role for the activated type I IFN system in the pathogenesis, and suggest that direct targeting of SLE-NIPC may constitute a new therapeutic principle in SLE.
|
|
| 5. |
- Båve, Ullvi
(författare)
-
Mechanisms of Interferon-α Induction in Systemic Lupus Erythematosus
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients with systemic lupus erythematosus (SLE) have an activated type I interferon (IFN) system with an ongoing IFN-α synthesis. This may be caused by circulating immune complexes, consisting of anti-DNA antibodies (Abs) and DNA, with IFN-α inducing capacity. Produced IFN-α may be crucial in the pathogenesis, because this cytokine can break tolerance and promote autoimmunity.In the present thesis, possible mechanisms of the IFN-α production in SLE were studied. To investigate whether IFN-α inducing material could be derived from apoptotic cells, IgG from SLE patients (SLE-IgG) were combined with apoptotic cells. This combination induced high IFN-α production in normal peripheral blood mononuclear cells (PBMC). The IFN-α induction was associated to presence of anti-RNP Abs, but not to anti-dsDNA Abs, indicating that two inducers could be active in SLE, one containing DNA and the other RNA.Apoptotic cells and SLE-IgG exclusively activated the natural interferon producing cells (NIPC) and the IFN-α response was enhanced by type I IFN and inhibited by IL-10 and TNF-α. The IFN-α induction was dependent on FcγRII, because blocking this receptor reduced IFN-α production and NIPC were found to express FcγRIIa.To further elucidate the role of different autoantibodies in the IFN-α induction, sera from patients with Sjögren´s syndrome (SS), containing autoantibodies to RNA binding proteins (SSA, SSB, RNP and/or Sm) were investigated. The combination of SS or SLE sera and apoptotic or necrotic cell material induced high IFN-α production in PBMC. RNA, but not DNA, was required for IFN-α induction, indicating that RNA and Abs to RNA-binding proteins form potent IFN-α inducing complexes.The findings in this thesis can explain central mechanisms for the activation of NIPC in SLE, and perhaps also other autoimmune diseases. This activation is mediated by interferogenic immune complexes, and modulating the NIPC activation may be a novel therapeutic approach in SLE.
|
|
| 6. |
- Dahmoun, Marju, 1954-
(författare)
-
Apoptosis, proliferation, and sex steroid receptors in endometrium and endometrial carcinoma
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis focuses on the involvement of apoptosis and proliferation in the mechanisms of menstruation and hormonal replacement therapy, HRT, as well as in the mechanisms of progesterone therapy in endometrial carcinoma. The aim of the first study was to investigate endometrium for 4 days before and for 2 days during menstruation. In the epithelium, rapid increase in the apoptotic index, decreasing expression of estrogen receptor α (ER) and progesterone receptor (PR), and minimal proliferation were observed prior to menstruation. In the stroma, an increase in the expression of ER and PR and proliferation was seen before the final decrease, and increased apoptosis was seen during menstruation. Thus, apoptosis is involved in the remodeling of the endometrium during menstruation. Postmenopausal endometrium showed unaffected homeostasis, i.e. unchanged ratio between apoptotic index and Ki-67 index during substitution therapy. ER expression was decreased both in the epithelium and stroma, while PR showed some increase in receptor expression. The unchanged homeostasis contributes to endometrial safety during combined continuous HRT. Unchanged apoptosis and increasing proliferation were observed with increasing tumor grade in 29 patients with endometrioid endometrial carcinoma, which may contribute to greater aggression as tumor grade increases. Decreased proliferation was observed after medroxy-progesterone at 20 mg per day particularly in the foci of maximal proliferation in G1 and G2 tumors. The expression of ER was unchanged, while PR was decreased in the foci of maximal expression for PR in G1 and G2 tumors. Since high proliferation and PR expression also coexisted in the same foci, evaluated in G1 and G2 tumors, the effect of progesterone could be facilitated in these tumor groups. High expression of sex steroid receptors was also a predicting factor for good response to progesterone (= decrease in proliferation), while the amount of stroma could not predict that effect.
|
|
| 7. |
- Ingberg, Claes-Mårten, 1956-
(författare)
-
Type 1 diabetes mellitus: Aspects of long-term complications and body composition
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Studies concerning social consequences, gastrointestinal and urinary tract symptoms were conducted in a population-based cohort comprising patients with long-standing type 1 diabetes and matched control persons. Three different questionnaires were sent by mail to diabetic patients and control persons. After a mean duration of 28.7±2.6 years, compared to the controls the diabetic patients showed an almost 10 times higher mortality, a lower employment rate and greater need for welfare benefits. These differences were mainly due to diabetic late complications. Education, housing conditions, life-style, civil state, alcohol and smoking habits were similar in the two groups. The prevalence of gastrointestinal symptoms was significantly higher in the diabetic patients than in the controls, and this was found to be attributable to the female diabetic patients. Female diabetic patients had been treated with antibiotics for urinary tract infections more often than controls, they experienced more social problems than controls in daily life because of urinary tract problems and used clamps to prevent wetting more often than did controls. Body composition and bone mineral density were evaluated in parts of the cohort with long-standing type 1 diabetes and control persons in another population-based cohort comprising diabetic females aged 16-19 years with type 1 diabetes since childhood and matched controls. Besides a tendency to reduced abdominal fat mass in diabetic males, no difference was observed in fat mass, muscle mass or bone mineral density between the patients with long-standing type 1 diabetes and controls. Significant correlations were found between insulin dosage and whole body fat mass in diabetic females and between serum cholesterol levels and abdominal fat mass in diabetic males. The female adolescents had a higher body mass index than the controls, and their overweight was shown to consist almost entirely of an increased fat mass. The distribution of fat, expressed as abdominal-to-leg ratio, correlated significantly to HbA1c and daily dosage of insulin. Bone mineral density did not differ between the groups. IGF I was significantly lower both in patients with long-standing type 1 diabetes and in the adolescent diabetic females compared with their matched controls.
|
|
| 8. |
- Nordström, Anna, 1973-
(författare)
-
Bone mass and physical activity
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abstract Weak and osteoporotic bones in old age are an increasing cause of mortality and painful physical impairment of the elderly, especially in the western world. Bone mineral accrual during childhood and adolescence is thought to play a vital role in preventing osteoporosis. Identifying and optimizing the factors influencing peak bone mass is thus important for the prevention of osteoporosis and related fractures. A main aim of this thesis was to investigate the potential effects of various types of weight-bearing physical activity on bone accretion in young males just out of puberty. The results from our subgroups of athletes consisting of badminton, ice hockey, and soccer players suggest that weight-bearing physical activity gives rise to regional specific bone response that is determined by the degree of impact of the activity in areas subject to mechanical loading (papers I–IV). In summary, the bone is sensitive to loading after puberty in males, and important bone mass gains can be achieved by proper amount and type of exercise. Another aim of this thesis was to studythe effect of detraining on weight-bearing and non-weight-bearing bone in a cohort of adolescent males who participated in ice hockey and soccer training. Our results indicate that exercise-induced bone mineral density benefits decline, predominantly in weight-bearing bones, after retirement from an active sports career (papers II–IV). High bone density stemming from physical loading might be at least partly preserved even by reduced physical activity at nonweight-bearing sites after about three years of reduced activity (III, IV). A final aim was to follow prospectively the development of BMD during years of reduced activity in former male athletes, and evaluate whether exercise during adolescence could be associated with fewer fractures in old age. We found fewer fragility fractures in a cohort of 400 former athletes compared to in 800 age-matched controls. Thus, high bone density stemming from previous weight-bearing physical activity may reduce the risk of sustaining fragility fractures in the elderly. Key words: physical activity, peak bone mineral density, males.
|
|
| 9. |
- Rehn, Börje, 1967-
(författare)
-
Musculoskeletal disorders and whole-body vibration exposure among professional drivers of all-terrain vehicles
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Musculoskeletal disorders are common among professional driver groups. Ergonomic risk factors at work are often suggested as causative, aggravating or preserving. The general aim with this thesis is to investigate the association between musculoskeletal disorders and physical exposure with special with special focus on whole-body vibration (WBV), among professional drivers of all-terrain vehicles (ATVs). Drivers of ATVs are expsosed to high magnitudes of WBV and shock. This thesis included drivers of forest machines, snowgroomers and snowmobiles. A cross-sectional study revealed that ATV drivers had an increased risk of musculoskeletal symptoms in the neck-shoulder and thoracic regions, even after adjusting for age, smoking habits and psychosocial stress. Prevalence rates were in the range of 1.5-2.9 (CI:1.2-5.2) compared to an age-matched group from the general population. No group of ATV drivers had a significantly increased risk of low back pain. Trend analysis showed no association between symptoms and exposure time. A clinical investigation of a subgroup found that it was for ATV drivers with neck pain to have assymetrical and focal neuropathies, pure or in mix with a nociceptive disorder, in the neck and upper extremities (47-79%), which was in contrast to referents with neck pain who had more nociceptive disorders (27% prevalence of neuropathy). Two studies measured characteristics of seated WBV exposure in forest machines (forwarders), snowgroomers and snowmobiles. The magnitudes of WBV in ATVs, measured and analyzed according to ISO 2631-1, were between 0.5-3.5 m/s2 (frequency weighted vector sum), which was considered high compared to limits suggested by the international standard ISO 2631-1 and the physical agent directive from the Euoropean Union (0.5 m/s2, rms). Drivers of ATVs were exposed to horizontally directed WBV and shocks. Non-neutral neck postures are ergonomic risk factors that occured infrequently and with short duration. The magnitude of seated WBV in forwarder vehicles varied substantiálly depending on model, terrain condition and driver. This may result in different conclusions regarding health risk assessments. The main conclusion from this thesis is that musculoskeletal symptoms and disorders in the neck and upper extremities, among drivers of ATVs, may be a result of long-time exposure to shock-type and horisozontally oriented seated WBV.
|
|
| 10. |
- Tenerz, Åke
(författare)
-
Diabetes mellitus and related glucometabolic disturbances in acute myocardial infarction : Diagnosis, prevalence and prognostic implications
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In patients with diabetes mellitus (DM), acute myocardial infarction (AMI) is a major cause of death. We have studied two populations with respect to the relationship between DM or related glucometabolic disturbances and AMI.In the first population, the prevalence of DM and the importance of the glycaemic state for the long-term prognosis in non-diabetic patients were investigated in patients with AMI admitted to the Coronary Care Unite at Västerås Central Hospital.In the second population, the prevalence of impaired glucose tolerance (IGT), DM and other metabolic abnormalities was investigated in patients with AMI and without known DM admitted to the Coronary Care Units at Västerås and Karolinska Hospital, Stockholm.21% of the patients with AMI had previously known DM and 4% had newly detected DM if diagnosis is based upon fasting blood glucose (F-BG). The glycemic state, measured as HbA1c, at a 5.5 years follow-up was a risk factor for re-infarction and/or death in non-diabetic patients after AMI.If an oral glucose tolerance test (OGTT) is performed, 40-45% of all patients with AMI have DM and in addition about 30% have IGT. Both an OGTT and a single post-challenge blood glucose value after 60 minutes performed at hospital discharge, were independent predictors of IGT or DM at follow-up. Insulin resistance, measured by homeostatic model assessment (HOMA-IR), decreased during hospital stay, with no further decrease from hospital discharge to follow-up.In summary, the studies in this dissertation have revealed an unexpectedly high prevalence of abnormal glucose tolerance in patients with AMI. The glycaemic state, reflected by HbA1c, in non-diabetic patients after AMI has an impact on the long-term prognosis. Consequently, in all patients with AMI, HbA1c and casual blood glucose should be measured at admission and, at least, F-BG at hospital discharge.
|
|
| 11. |
- Windahl, Torgny, 1948-
(författare)
-
Clinical aspect of laser treatment of lichen sclerosus and squamous cell carcinoma of the penis
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of these studies was to investigate the efficacy, complications and the long term results after laser treatment of lichen sclerosus et atrophicus and of squamous cell carcinoma of the penis.Patients and Methods: Paper I: In a prospective study from 1985-1991, 62 men with histologically verified lichen sclerosus et atrophicus were given carbon dioxide (CO2) laser treatment following the failure of local corticosteroid treatment. The study was subsequently updated at a median follow-up time of 14 years.Paper II-IV: Sixty-seven men aged 26 to 87 (mean 60 years) with newly diagnosed penile carcinoma were included in a prospective study. The patients were treated by a new combined laser method (CO2 and Nd:YAG) between 1986 and 2000. The median follow-up time was 42 months (range 12-186 months). All patients could be assessed for local recurrence, progression and survival at the end of 2001. Forty-six patients agreed to participate in face-to-face interviews addressing sexual activity, sexual function/dysfunction, satisfaction and cosmetic results.Results: Paper I: The laser treatment was successful in 47 patients (76%) with no local symptoms at a mean follow-up of 30 months. Fifty-three of the 62 men were alive when the update was carried out in February 2004, and we were able to get in contact with 50 of them. Forty of these patients (80%) had no local symptoms or visible lesion. We found concomitant squamous cell carcinoma of the penis in two patients and two further patients had died from anal cancer.Paper II-IV: Local recurrences appeared in 13 patients (19%) at a median follow up of 42 months, and 10 of these patients were successfully retreated with laser treatment. Two patients died from penile carcinoma. The disease-specific 5-years survival rate was 95%. Concomitant lichen sclerosus was found in 11 patients. All patients younger than 75 years reported that they were sexually active before the treatment, and 80% of them had resumed their sexual activity after the treatment. Ten patients (22%) reported decreased erectile function after the treatment, while 33 patients (72%) reported unaltered erectile function. The cosmetic result was regarded as satisfying or very satisfying in 78% of the patients.Conclusion: Carbon dioxide laser treatment is an efficient treatment for lichen sclerosus et atrophicus with excellent long-term results, and the side effects are few. One disadvantages of the treatment is a slow postoperative healing process. Combined CO2 and Nd:YAG laser treatment is effective for treatment of the primary tumour in patients with localized penile carcinoma. It can be safely carried out with good local tumour control and highly satisfactory results with respect to cosmetic aspects and sexual function.
|
|
| 12. |
- Isaksson, Marléne
(författare)
-
Clinical and experimental studies in corticosteroid contact allergy
- 2000
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Corticosteroids are anti-inflammatory and anti-proliferative substances that also can induce sensitization, mainly through skin contact. In a sensitized individual, it can be hard to disclose the contact allergy at patch testing because the anti-inflammatory effect may mask the allergic contact reaction. This is primarily seen when patch testing to potent corticosteroids is performed and the reading is done early, when the anti-inflammatory effect still prevails. In this thesis I present a hypothetical model, which can explain the different situations that emerge, when the anti-inflammatory effect influences the elicitation depending on the individual degree of hypersensitivity in a sensitized subject. Some patients allergic to the corticosteroid budesonide only reacted to very low concentrations of the sensitizer at early readings. When patch testing the corticosteroid triamcinolone acetonide, concentrations 1000 to 10,000 times lower than internationally recommended resulted in allergic reactions while the recommended concentration gave negative reactions. If testing with a corticosteroid at a high concentration results in a negative patch-test reaction, lowering the concentration may result in a positive patch-test reaction. Introducing another parameter into the model, the time factor, made it possible also to explain why negative patch test reactions are sometimes seen at early readings, while the tests may turn positive on late reading occasions. Therefore, not to miss contact allergy to corticosteroids, a reading after one week in addition to an early reading is advocated. The multi-centre study showed that 25% of the allergic reactions to corticosteroids would have been missed if a late reading had not been done. The edge reaction, consisting of a blank centre representing the whole area of the test unit and surrounded by an eczematous infiltrate, is seen in some corticosteroid allergic patients when potent corticosteroids are patch-tested. This phenomenon can also be explained by the same model. If an edge reaction appears, a late reading or testing with a lower concentration should be done. I also investigated the cross-reactivity pattern for the two diastereomers of budesonide, the R and S diastereomers, and found that results concurred with the theory that the R diastereomer cross-reacts with other substances from the group to which it belongs, group B, while the S diastereomer cross-reacts not only with other group B substances but also with some esters of group D. No inhibition of the patch test reactions was observed when patch testing the corticosteroid tixocortol pivalate and potentially cross-reacting substances at high concentrations. Aldehydes of corticosteroids are thought to be intermediates in the sensitization process. The aldehyde of hydrocortisone was therefore tested in subjects allergic to hydrocortisone. Patients reacting to hydrocortisone also reacted to the aldehyde, speaking in favour of the aldehyde being an intermediate in the sensitization. When trying to elucidate whether a corticosteroid mix, consisting of the three corticosteroids budesonide, tixocortol pivalate and hydrocortisone-17-butyrate (Hc-17-B) in petrolatum, could disclose corticosteroid allergy I found that 60% of the patients allergic to tixocortol pivalate were missed. Thus, in a corticosteroid mix containing budesonide and Hc-17-B, tixocortol pivalate should not be a part. Of the separate markers that were patch-tested simultaneously in petrolatum, budesonide 0.10% detected most allergic subjects, followed by budesonide 0.002% and tixocortol pivalate, both concentrations (1.0% and 0.10%) detecting the same number of patients. Hc-17-B at 1.0% detected more than 0.10%. Investigations on the stability of budesonide, tixocortol pivalate and Hc-17-B patch-test preparations in petrolatum disclosed that these were stable for at least one year in room temperature, refrigerated and frozen. Budesonide and tixocortol pivalate in ethanol showed the same stability. Hc-17-B 1.0% in ethanol was only stable frozen for one year and at room temperature for three months. In the study on local clinical relevance, the flare-up reactions in the budesonide-allergic individuals consisted not only of a severe deterioration of the Preferid® treated eczema but also toxicoderma-like eruptions with a conspicuous distribution. A correlation was found between contact allergy to budesonide and deterioration of the eczema treated with Preferid® cream containing budesonide. To study flare-up reactions at earlier budesonide test sites a systemic provocation with Pulmicort® Turbuhaler® (budesonide) via inhalation was performed in subjects allergic to budesonide but without asthma or other lung dysfunction. The study clearly showed that flare-up reactions were found after normal doses of budesonide. Therefore, a person hypersensitive to budesonide should not be given the drug as an inhalant. In the same study a new method in humans to test for cross-sensitivity was used. When budesonide was inhaled, a flare-up was noted where triamcinolone acetonide had been tested previously, indicating cross-reactivity between budesonide and triamcinolone acetonide.
|
|
| 13. |
- Pontén, Ann
(författare)
-
Contact Allergy to Epoxy Resins of the Bisphenol F-type
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Epoxy resins based on bisphenol A are well-known contact allergens and often cause occupational contact allergy. The most important allergen is the monomer diglycidyl ether of bisphenol A (DGEBA). Epoxy resins of the bisphenol F-type contain 3 isomers of the diglycidyl ether of bisphenol F; p,p'-DGEBF, o,p'-DGEBF, and o,o'-DGEBF, whereas epoxy resin(s) based on bisphenol A (DGEBA-R) contain virtually only 1 isomer of DGEBA. The allergenicity of DGEBA has been investigated earlier, but the DGEBF isomers have not previously been investigated as contact allergens. When an epoxy resin based on bisphenol F was inserted in the standard patch test series of our department, it was found that contact allergy to this type of epoxy resin was at least as common as contact allergy to DGEBA-R. A majority of the patients reacted to both types of epoxy resins. Both p,p'-DGEBF and o,p'-DGEBF were shown to be sensitizers in humans, while o,o'-DGEBF elicited surprisingly few reactions. p,p'-DGEBF was found to be a sensitizer and at least as strong as DGEBA. All 3 DGEBF isomers were found to be strong sensitizers in animal studies. It was also found that DGEBA, p,p'-DGEBF and o,p'-DGEBF cross-reacted with one another to a high degree, while o,o'-DGEBF did not. o,o'-DGEBF was assumed to be a sensitizer mainly in the absence of the other 3 substances. Humans are then generally not sensitized to o,o'-DGEBF, since it does not occur alone in the epoxy resins of the bisphenol F-type. For the individuals with contact allergy both to DGEBA-R and epoxy resins of the bisphenol F-type, concomitant sensitization as well as cross-sensitization might be the case. When contact allergy to epoxy resins of the bisphenol F-type is suspected, this type of epoxy resin should be patch tested, especially if the DGEBA-R patch test is negative. Depending on the clinical situation, the patch-test concentration recommended is 0.25-0.5%. Consecutive patch testing with epoxy resins of the bisphenol F-type at a concentration of 1.0% is not recommended due to the possibility of patch-test sensitization. It was found that the sensitivity of the thin-layer chromatography method was around 200 times more sensitive for DGEBA than for DGEBF isomers. In patients with contact allergy to DGEBA-R, the cause of allergic contact dermatitis might be an epoxy resin of the bisphenol F-type. The latter resins are most probably not detected by the TLC method developed for DGEBA-R. If the product is analyzed only with the TLC method, the relevance of the contact allergy to DGEBA-R might therefore remain unrecognized. In an industrial investigation among 603 workers exposed to epoxy resins 20.3% of the 325 patch-tested workers had occupational ACD. Approximately 15% of the workers with occupational ACD had contact allergy to DGEBA-R and 36% had contact allergy both to epoxy resins of the bisphenol F-type and DGEBA-R. Around 40% of the patch-tested workers were estimated to have skin disease either caused or aggravated by work. Although a well-known occupational contact allergen, a high frequency of contact allergy to DGEBA-R among exposed workers was found. Thorough instruction concerning protection, most importantly for new employees, as well as the development of production methods that minimize exposure, especially to DGEBA-R, are necessary measures for preventing occupational dermatoses among workers exposed to ERS in the manufacture of rotor blades for wind turbines.
|
|
| 14. |
- Sköldberg, Filip
(författare)
-
Studies of Autoantibodies in Systemic and Organ-Specific Autoimmune Disease
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease, whereas autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal disorder characterized by combinations of organ-specific autoimmune manifestations including hypoparathyroidism and intestinal dysfunction, and may serve as a model for organ-specific autoimmunity. Autoantibodies directed against proteins expressed in the affected tissues are found in both diseases. From a chondrocyte cDNA expression library, we identified the protein AHNAK as an autoantigen in SLE. Anti-AHNAK antibodies were found in 29.5% (18/61) of patients with SLE, 4.6% (5/109) of patients with rheumatoid arthritis, and 1.2% (2/172) of blood donors. Using a candidate approach, we analyzed the prevalence in APS1 and other organ-specific autoimmune diseases, of autoantibodies against the pyridoxal phosphate-dependent enzymes histidine decarboxylase (HDC) and cysteine sulfinic acid decarboxylase (CSAD), which are structurally closely related to known autoantigens. Anti-HDC and anti-CSAD reactivity was detected exclusively in APS1 patient sera. Anti-HDC antibodies were detected in 37.1% (36/97) of the APS1 sera, did not cross-react with aromatic L-amino acid decarboxylase, and were associated with intestinal dysfunction and loss of histamine-producing gastric enterochromaffin-like cells. In contrast, anti-CSAD reactivity was detected in 3.6% (3/83) of APS1 sera and cross-reacted with recombinant glutamic acid decarboxylase. From a parathyroid cDNA expression library, novel spliced transcripts of the CLLD4 gene on human chromosome 13q14, encoding 26 and 31 kDa isoforms recognized by autoantibodies in 3.4% (3/87) of APS1 patients, were identified and found to be preferentially expressed in lung and ovary. Both isoforms contain an N-terminal BTB/POZ domain, similarly to the TNF-alpha-regulated protein B12, localize both to the cytoplasm and nucleus in transfected COS cells, and form oligomers in vitro. The CLLD4 gene is located in a region frequently deleted in several forms of cancer, including lung and ovarian tumors. In conclusion, we have identified and partially characterized AHNAK and HDC as two common targets of autoantibodies in SLE and APS1, respectively. We have also identified CSAD and CLLD4 as two minor autoantigens in APS1, one of which is a novel protein with unknown function.
|
|
| 15. |
- Zimerson, Erik
(författare)
-
Contact allergens in p-tert-butylphenol-formaldehyde resin
- 2000
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- p-tert-Butylphenol-formaldehyde resin (PTBP-F-R) is used as a binder in many adhesive formulations and it consists of a complex mixture of substances, most of which are unknown. The resin has been reported to cause allergic contact dermatitis since the 1950s. The aim of the study was to investigate allergens in p-tert-butylphenol-formaldehyde resin (PTBP-F-R) and to isolate and identify sensitizers that are important factors for the development of hypersensitivity to PTBP-F-R in man. Chemical separation methods were used to isolate fractions and pure substances from the resin. These were patch tested in patients hypersensitive to PTBP-F-R. The sensitizing capacities and cross-reaction patterns of 11 isolated substances were investigated using the Guinea pig maximization test. In the present investigation 7 new allergens in PTBP-F-R were established and 1 more was strongly indicated. The allergens were found among monomers, dimers and trimers. Patch testing of formaldehyde and 4-tert-butyl-phenol, the raw materials for production of PTBP-F-R, indicated that these substances are not frequent allergens among patients hypersensitive to PTBP-F-R. 5-tert-Butyl-2-hydroxy-3-hydroxymethyl-benzaldehyde was considered to be an important allergen among the monomers. The dimers 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-3-hydroxymethyl-benzyloxymethyl)-6-hydroxymethyl-phenol and 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-benzyloxymethyl)-6-hydroxymethyl-phenol were considered main allergens in the resin. The investigated substances were quantitatively determined in 2 PTBP-F-Rs and shown to be present in concentrations varying between 0.01 and 1.7% w/w.
|
|
| 16. |
- Albinsson, Lars, 1944-
(författare)
-
A Palliative Approach to Dementia Care : Leadership and organisation, existential issues and family support
- 2002
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main purpose of this thesis was to apply the WHO and NHS palliative care approach to dementia care. Thirty-one staff-members in mid-Sweden (studies I and II) and 20 next-of- kin (study IV) were interviewed. In study III, 316 staff-members from dementia care and 121 staff-members from palliative cancer care responded to a questionnaire about family support. The interviews were tape-recorded and analysed with a qualitative phenomenographic (I and II) and a hermeneutic approach (IV). The questionnaires (III) were analysed using qualitative and quantitative content analysis.The staff-members stated almost unanimously that daily leadership was lacking, and consequently clear goal formulations and care planning were rare (I). Proper teamwork between the doctor and the staff who worked on a daily basis with the patients was absent (I). With respect to existential issues, education and staff discussions were lacking (II). The staff were at a loss concerning how to deal with these issues. Nevertheless, these issues are central to family-members who have to deal with an existential crisis (IV). Important questions emerged about obligation and guilt, faithfulness, responsibility, and paying back what you once received. Existential isolation could be identified e.g. in the reversal of roles experienced as "being a parent to your parent" and in the burden of "visiting a living dead person". There were no routines for bereavement visits. The type of support suggested for dementia family members is partly similar to support in palliative cancer care, but it also differs in other respects such as feelings of guilt because the early signs of the disease are misunderstood, the need for respite because of the long trajectory of dementia diseases, and the occurrence of anticipatory grief because in the late phase family members can no longer make any contact at all with the patient (III).A palliative approach can improve the quality of life for the dementia patient and for the family. It can be used as a basis for a clear goal formulation. Some of the suggestions listed in this thesis for improving the quality of care are more a reflection of the need for a change in attitudes rather than the need for substantial budget increases.
|
|
| 17. |
- 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.
|
|
| 18. |
- Lindgren, Torsten
(författare)
-
Cabin Air Quality in Commercial Aircraft : Exposure, Symptoms and Signs
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The objective of the dissertation was to study the cabin environment, and identify personal and environmental risk factors, associated with symptoms, and perception of cabin air quality. Another objective was to study if ban of smoking, and increased relative air humidity on intercontinental flights, could have a beneficial health effect. The studies were performed among Scandinavian cabin crew in one Airline Company. Office workers from the same company served as controls. Exposure differed between cruise and non-cruise conditions. Air humidity was very low during intercontinental flights (3-8%). Concentration of moulds, bacteria, formaldehyde, and ozone was low. Tobacco smoking increased respirable particles in the cabin air, from 3 to 49 mg/m3, and increased cotinine in urine. The ETS-exposure was highest in the aft part of the cabin. Symptoms and environmental complaints were more common among flight crew than office workers. We could identify personal factors of importance, and certain conditions that could be improved, to achieve a better cabin environment. There was an association between symptoms and environmental perceptions and work stress, lack of influence on working condition, and a history of atopy. After ban on smoking in aircraft, there was a decrease of ocular and general symptoms, and increased tear-film stability in aircrew. Air humidification reduced headache and ocular, nasal, and dermal dryness symptoms, increased tear-film stability, and increased nasal patency. Our result indicates that ETS and low air humidity are important environmental factors in aircraft, and that atopy, and work stress could be significant risk factors for symptoms and environmental perceptions.
|
|
| 19. |
- André, Malin, et al.
(författare)
-
The Use of CRP Tests in Patients with Respiratory Tract Infections in Primary Care in Sweden Can Be Questioned
- 2004
-
Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 36:3, s. 192-197
-
Tidskriftsartikel (refereegranskat)abstract
- A diagnosis-antibiotic prescribing study was performed in 5 counties in Sweden during 1 week in November in 2000 and 2002 respectively. As a part of the study, the use and results of C-reactive protein (CRP) tests in relation to duration of symptoms and antibiotic prescribing in 6778 patients assigned a diagnosis of respiratory tract infections were analysed. In almost half (42%) of the patients, a CRP test was performed. The majority of CRP tests (69%) were performed in patients assigned diagnosis upper respiratory tract infection, where the test is not recommended. Overall, there was a minor decrease in antibiotic prescribing when CRP was used (41%), in comparison to 44% of the patients where no CRP was performed (p<0.01). Patients assigned diagnoses implying a bacterial aetiology were prescribed antibiotics irrespective of result of CRP or length of symptoms before consultation. For patients assigned viral diagnoses, antibiotic prescribing increased with increasing duration of symptoms and increasing value of CRP. The use of CRP decreased antibiotic prescribing in patients assigned to viral diagnoses and with longstanding symptoms (p<0.001). However, 59% of the patients assigned viral diagnoses with CRP≥25 received antibiotics, which seems to indicate a misinterpretation of CRP and a non-optimal use of antibiotics.
|
|
| 20. |
- André, Malin, et al.
(författare)
-
Upper respiratory tract infections in general practice: diagnosis, antibiotic prescribing, duration of symptoms and use of diagnostic tests
- 2002
-
Ingår i: Scandinavian Journal of Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 0036-5548 .- 1651-1980. ; 34, s. 880-
-
Tidskriftsartikel (refereegranskat)abstract
- A diagnosis/antibiotic prescribing study was performed in 5 counties in Sweden for 1 week in November 2000. As part of this study, the characteristics and clinical management of patients with upper respiratory tract infections (n = 2899) in primary care were analyzed. Almost half of the patients were aged < 15 y and one-fifth of the patients consulted out of hours. Of all patients seeking primary care for upper respiratory tract infections, 56.0% were prescribed an antibiotic. Almost all patients who were given the diagnoses streptococcal tonsillitis, acute otitis media or acute sinusitis were prescribed antibiotics, compared to 10% of patients with common cold or acute pharyngitis. The most frequently prescribed antibiotic was penicillin V (79.2%) and this was even more pronounced out of hours, when the diagnoses otitis media and streptococcal tonsillitis were more frequently used. In patients with common cold and acute pharyngitis, the percentage who received antibiotics increased with increasing length of symptoms and increasing CRP levels. In patients with acute pharyngitis or streptococcal tonsillitis, antibiotics were prescribed less frequently provided streptococcal tests were performed. The management of patients with upper respiratory tract infections in general practice seems to be in good agreement with current Swedish guidelines. However, the study indicates some areas for improvement. The diagnosis of acute sinusitis seems to have been overestimated and used only to justify antibiotic treatment.
|
|
| 21. |
- 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.
|
|
| 22. |
- 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.
|
|
| 23. |
- 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.
|
|
| 24. |
- 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.
|
|
| 25. |
- 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.
|
|
| 26. |
- Jin, Yuesheng, et al.
(författare)
-
Clonal chromosome abnormalities in premalignant lesions of the skin.
- 2002
-
Ingår i: Cancer Genetics and Cytogenetics. - 0165-4608. ; 136:1, s. 48-52
-
Tidskriftsartikel (refereegranskat)abstract
- Two lesions, actinic keratosis (AK) and squamous cell carcinoma in situ (CIS), are believed to be precursors of squamous cell carcinoma (SCC) of the skin. These lesions can serve as an excellent model system for studying genetic changes associated with the inception of skin SCC. In the present study, five such lesions of the skin, three AKs and two AK+CIS, from three patients were short-term cultured and analyzed cytogenetically. One of the patients (case 3) had also an SCC in addition to three premalignant lesions. All lesions, but one, showed clonal karyotypic abnormalities. The recurrent changes identified were numerical, that is, +7 and +20. The structural rearrangements found in three AK were different, but it could be noted that the distal part of the long arm of chromosome 4 was involved in two AK and the SCC of case 3A. It was also interesting that chromosome 1 participated in structural rearrangements in three AK with band 1p31 being involved in two tumors. The karyotypic profile of these lesions is compared with that of skin SCC; it turns out that the general patterns are different in the sense that the SCC more often have complex karyotypes and display unbalanced aberrations involving the centromeric regions. Some karyotypic similarities between the SCC and their precursors are revealed. The fact that the structural rearrangements involving chromosomal band 3p13 and the centromeric region of chromosome 3 in AK are common features for many types of malignant tumors, including skin SCC, indicates that these changes are early genetic events associated with malignant transformation.
|
|
| 27. |
- Gruvberger, Birgitta, et al.
(författare)
-
Methyldibromoglutaronitrile
- 2003
-
Ingår i: Management of positive patch test reactions. - 3540443479 ; , s. 41-41
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 28. |
- Gånemo, Agneta, 1947-
(författare)
-
Hereditary ichthyosis : Causes, Skin Manifestations, Treatments and Quality of Life
- 2002
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hereditary ichthyosis is a collective name for many dry and scaly skin disorders ranging in frequency from common to very rare. The main groups are autosomal recessive lamellar ichthyosis, autosomal dominant epidermolytic hyperkeratosis and ichthyosis vulgaris, and x-linked recessive ichthyosis. Anhidrosis, ectropion and keratodermia are common symptoms, especially in lamellar ichthyosis, which is often caused by mutations in the transglutaminase 1 (TGM1) gene. The aim of this work was to study patients with different types of ichthyosis regarding (i) the patho-aetiology (TGM1 and electron microscopy [EM] analysis), (ii) skin signs and symptoms (clinical score and subjective measure of disease activity), (iii) quality of life (questionnaires DLQI, SF-36 and NHP and face-to-face interviews) and (iv) a search for new ways of topical treatment. Patients from Sweden and Estonia with autosomal recessive congenital ichthyosis (n=83) had a broader clinical spectrum than anticipated, but a majority carried TGM1 mutations. Based on DNA analysis and clinical examinations the patients were classified into three groups, which could be further subdivided after EM analysis. Our studies indicate that patients with ichthyosis have reduced quality of life as reflected by DLQI and by some domains of SF-36, by NHP and the interviews. All the interviewees reported that their skin disease had affected them negatively to varying degrees during their entire lives and that the most problematic period was childhood. All patients with ichthyosis use topical therapy. In a double-blind study creams containing either 5% urea or 20% propylene glycol were found inferior to a cream formulation containing lactic acid 5% and propylene glycol 20% both regarding clinical improvement and thinning of the skin barrier. Improved topical therapy may reduce the need of more toxic, oral drugs. Future studies should elucidate whether this increases the quality of life of ichthyosis patients, especially if combined with more detailed information about the aetiology and inheritance of the diseases.
|
|
| 29. |
- Karlsson, Teresa, et al.
(författare)
-
Immunofluorescence localization of nuclear retinoid receptors in psoriasis versus normal human skin
- 2004
-
Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 84:5, s. 363-369
-
Tidskriftsartikel (refereegranskat)abstract
- Psoriasis responds favourably to treatment with retinoids but the cellular pathways mediating these effects are poorly understood. Retinoids regulate keratinocyte proliferation and maturation via binding to nuclear retinoic acid receptors (mainly RARalpha and RARgamma) which form heterodimers with the 9-cis-RA receptor, RXRalpha. We have previously shown that mRNA expression of RARalpha and RXRalpha is down-regulated in psoriatic lesions as compared with non-lesional human skin. In the present study, we investigated the protein expression of RARalpha, RARgamma and RXRalpha in normal and psoriatic skin using indirect immunofluorescence analysis. Epidermal keratinocytes of normal and non-lesional psoriatic skin displayed similar nuclear localization of all three receptors; RARalpha was detected with decreasing intensity from basal to suprabasal layers, RARgamma showed the opposite trend, whereas RXRalpha was evenly expressed throughout the epidermis. In lesional psoriatic skin, however, all three receptor proteins showed a much higher staining intensity in the lower half of the epidermis; in particular, RARalpha immunoreactivity was low or even absent in the upper layers of epidermis. The results support the idea that psoriasis is associated with abnormal retinoid signalling in lesional epidermis.
|
|
| 30. |
- Aneblom, Gunilla
(författare)
-
The Emergency Contraceptive Pill – a Second Chance : Knowledge, Attitudes and Experiences Among Users and Providers
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to study knowledge, attitudes and experience of emergency contraceptive pills among women and providers. Both quantitative and qualitative methods were used. Focus-group interviews were conducted with teenage-girls (I) and with women who had purchased ECP without prescription (IV). Self-administered waiting-room questionnaires were administered to women presenting for induced abortion in three large hospitals (II, III), and after the deregulation of ECP, a postal questionnaire was sent to pharmacy staff and nurse-midwives in three counties in mid-Sweden (V). Overall, women showed high basic awareness of ECP although specific knowledge such as the level of effectiveness, time-frames and how the method works was lacking. Approval of the method was high and most women were positive to use the method if they needed. Contradictory views as to whether ECP undermines contraceptive behavior were expressed. As many as 43% of women requesting induced abortion had a history of one or more previous abortions. Among the abortion applicants, one out of five, 22%, had previously used ECP and 3% had used it to prevent the current pregnancy. Media and friends were the two most common sources of information on ECP. Half of the women, 52%, were positive to having ECP prescription-free. Those women who had purchased ECP in a pharmacy without prescription, appreciated this possibility, and the major benefits expressed were time saving aspects. No severe side-effects were reported. The women's experiences of interaction with pharmacy staff were both positive and negative. The importance of up-to-date information about ECP and the OTC-availability from the health care providers was emphasized. Both pharmacy staff and nurse-midwives had positive attitudes towards ECP and the OTC availability. Of pharmacy staff, 38% reported that they referred women to nurse-midwives/gynecologists for further counseling and follow-ups. The need for increased communication and collaboration between pharmacies and local family planning clinics was reported by both study groups with suggestions of regular meetings for information and discussions. The results suggest that ECP is still underused and that more factual information is needed before the method is becoming a known, accepted and integrated back-up method to the existing family planning repertoire. Longitudinal research to assess the long-term effects of ECP is needed.
|
|
| 31. |
- 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.
|
|
| 32. |
- 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.
|
|
| 33. |
- Bukachi, Frederick, 1960-
(författare)
-
Ventricular Long Axis Function: Amplitudes and Timings : Echocardiographic Studies in Health and Disease
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The ageing process not only increases the risk of coronary artery disease (CAD) but also complicates its diagnosis and treatment. It is therefore important to understand the newer concepts of cardiovascular ageing physiology as well as methods of predicting the outcomes of therapeutic options available for the elderly with severe CAD. Studies of atrioventricular (AV) ring or plane motion have attracted considerable interest in the last few years as a means of assessing ventricular and atrial function. As the displacement of AV rings towards the ventricular apex is a direct reflection of longitudinal fibre contraction, its measurement by echocardiography provides additional information regarding global and regional systolic and diastolic function. Left ventricular (LV) long axis amplitude of motion, referred to as mitral valve annular (MA) motion, is reduced in CAD and to some extent in the elderly as part of the normal ageing process. Objectives & Methods: The aim of the present study was two-fold. First, to investigate the relationship between the timing of MA motion and transmitral and pulmonary venous flow in healthy subjects, and to define the physiological significance of that relationship including its potential diagnostic utility. Second, to investigate the relationship between the clinical outcome and the behaviour of long axis function in patients with severe ischaemic LV dysfunction (SLVD) after percutaneous coronary angioplasty (PTCA). Transmitral early (E) and late (A) filling, and pulmonary venous flow reversal (Ar) were studied by Doppler echocardiography, while at the left lateral AV ring, the MA motion in early (Em) and late (Am) diastole were recorded by Doppler tissue imaging (DTI) and M-mode echocardiography. Results: Healthy subjects – In early diastole the onsets of LV filling (E) and relaxation (Em) were simultaneous, and peak Em preceded peak E by 26 msec in all age groups, constituting a time interval referred to as early diastolic temporal discordance (EDTD). Similarly, the onsets of Am, A and Ar were simultaneous at onset and began approximately 84 msec after the electrocardiographic P wave. Peak Am preceded peak A by 23 msec in the young and by 13 msec in the elderly, a time interval referred to as late diastolic temporal discordance (LDTD). Peak Ar, on the other hand, coincided with peak Am in all age groups. With increasing age and sequential prolongation of isovolumic relaxation time, the peaks of Am, Ar and A converged. This point of convergence is described as atrial mechanical alignment (AMA). Patients – MA total amplitude of motion, rates of shortening and lengthening were all reduced in patients with SLVD. At mid-term, 3-6 months after PTCA, there was improvement in all these variables. A pre-procedure long axis cut off value of ≥5 mm was associated with favourable symptomatic outcome. Overall angiographic success was 95.2%, and event-free survival was 78.4% at one month and declined steadily to 62.3% at one year with 2.5% mortality. Conclusions: EDTD, which reflects ventricular restoring forces (suction) is age independent while the narrowing of LDTD leading to AMA provides a novel method to identify healthy subjects at increased dependency on left atrial contraction for late diastolic filling. Peak atrial contraction (Am) coincides with peak Ar, thus the timing of regional atrial contraction by DTI can be used to estimate corresponding measurements of Ar, which is often difficult to image by transthoracic echocardiography. In patients with SLVD long axis total amplitude of at least 5 mm at the left MA suggests a significant potential for segmental function recovery after PTCA. Keywords: Echocardiography, Doppler tissue imaging, ageing, coronary disease, left ventricular dysfunction, atrial contraction, electromechanical function, coronary angioplasty.
|
|
| 34. |
- Bäckman, Ulrika, 1971-
(författare)
-
Treatment of Experimental Neuroblastoma with Angiogenic Inhibitors
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neuroblastoma is a childhood cancer that originates from neuroblasts in the peripheral nervous system. Neuroblastoma show considerable heterogeneity with respect to location, responsiveness to treatment and prognosis. Since current therapy involves drugs with risk of serious side effects in the growing child, there is a clinical need for more effective and less toxic treatment strategies.Angiogenesis, the formation of new blood vessels, is critical for tumor progression. Specific inhibition of tumor-induced angiogenesis should restrict growth of most solid tumors and thereby provide a new treatment strategy. The aim of this study was to investigate the effects of angiogenic inhibition in experimental neuroblastoma in mice.We found that experimental neuroblastomas expressed the perhaps most potent angiogenic growth factor, VEGF-A, and that plasma VEGF-A levels correlated with tumor size. SU5416, a novel antagonist of VEGFR-1 and 2, reduced angiogenesis and tumor growth in our model. We also investigated the properties of SU11657, a new, orally available, synthetic small molecule multi-targeted tyrosine kinase inhibitor. SU11657, at a well-tolerated dose, was more potent than SU5416 in reducing tumor growth rate and angiogenesis, even in MYCN-amplified tumors. Chemotherapeutics can also inhibit angiogenesis, when administrated daily in a non-toxic dose. CHS 828, a new chemotherapeutic, given orally, alone induced complete neuroblastoma regression in 44 % of the animals. Furthermore, the bisphosphonate zoledronic acid, developed to reduce bone resorption, showed anti-tumor activity in our model. Zoledronic acid was more potent than the angiogenic inhibitor TNP-470. Thus bisphosphonates may have other beneficial properties in patients with cancer apart from preventing bone resorption.In conclusion, SU5416, SU11657, CHS 828, and zoledronic acid represent new drugs with potent anti-tumor effects. Angiogenic inhibition as single therapy or in combination with chemotherapeutics may be beneficial in the treatment of rapidly growing and highly vascularized solid tumors of childhood such as neuroblastoma.
|
|
| 35. |
- Chen, Hongjiang, 1965-
(författare)
-
Studies on Cell Injury Induced by Hypoxia-Reoxygenation and Oxidized Low Density Lipoprotein : With Special Reference to the Protectiove Effect of Mixed Tocopherols, Omega-3 Fatty Acids and Transforming Growth Factor-beta1
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hypoxia-reoxygenation (H-R) injury is an important clinical phenomenon in patients with coronary artery disease (CAD). Endothelial injury is a critical step in the initiation and progression of atherosclerosis. Therefore, endothelial and cardiomyocyte protection has been considered an effective step in prevention and treatment of CAD.To investigate the cardioprotective effect of tocopherols, omega-3 fatty acid [eicosapentaenoic acid (EPA)] and transforming growth factor-β1 (TGF-β1) during H-R, calcium tolerant myocytes isolated from adult rats were cultured and subjected to hypoxia for 24 hrs followed by reoxygenation of 3 hrs. All strategies, including tocopherol preparations, EPA and TGF-β1, showed attenuation of H-R-induced myocyte injury indicated by reduction of lactate dehydrogenase (LDH) release. Both a-tocopherol and a mixed- tocopherols (α-, γ-, and δ-) decreased the effects of H-R on iNOS expression and SOD activity in cultured myocytes. The mixed-tocopherols was more potent than a-tocopherol alone. EPA inhibited H-R-induced lipid peroxidation, MMP-1 expression and p38MAPK phosphorylation. TGF-β1 blocked the increase in iNOS and PKB phosphorylation as well as the decrease in eNOS expression in cultured myocytes exposed to H-R. To further investigate the protective effect of omega-3 fatty acids [docosahexaenoic acid (DHA) and EPA] and TGF-β1, the cultured endothelial cells were exposed to oxidant injury mediated by oxidized low-density lipoprotein (ox-LDL). Ox-LDL markedly reduced TGF-β1 release, increased the expression of TGF-β1 receptors, upregulated the expression of adhesion molecules, P-selectin and ICAM-1, enhanced the adhesion of monocytes to endothelial cells, and decreased protein kinase B (PKB) activation. Both DHA and EPA blocked these effects of ox-LDL on endothelial cells. Exogenous recombinant TGF-β1 also ameliorated ox-LDL-induced expression of adhesion molecules and monocytes adhesion, which were blocked by antibodies to the TGF-β1 type 2, but not to the type 3 receptor.These observations provide mechanistic insights into H-R and oxidant injury and tissue protection by three different strategies.
|
|
| 36. |
- Dunder, Kristina, 1961-
(författare)
-
Clinical Manifestations of Coronary Heart Disease and the Metabolic Syndrome : A Population-based Study in Middle-aged Men in Uppsala
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During the past decades the knowledge concerning risk factors and pathophysiology of coronary heart disease (CHD) has substantially increased. However, despite identification of important risk factors CHD remains the leading cause of death in the western world.The metabolic syndrome is a cluster of metabolic disorders such as hypertension, hypertriglyceridemia, low HDL-cholesterol, and glucose intolerance associated with an increased risk of cardiovascular morbidity and mortality.The studies in this thesis are epidemiological in their character, and examine the relationships between different aspects of CHD and the metabolic syndrome in a population-based study of middle-aged men (ULSAM).The findings indicated that serum lipids were important risk factors for the development of both angina pectoris demanding revascularisation and acute myocardial infarction (MI). Proinsulin and blood pressure were independent predictors of MI only, suggesting these factors to be involved in thrombosis and plaque rupture. It was also found that antihypertensive treatment with beta-blockers and thiazide diuretics resulted in increased fasting blood glucose concentrations in subjects with an insulin resistant state with elevated proinsulin concentrations. Both proinsulin concentrations and increase in fasting blood glucose were associated with increased risk of developing future MI. The finding of a new Q/QS-pattern on the resting ECG, regardless of history of MI, was associated with impaired insulin secretion and was an independent predictor of total and cardiovascular mortality. A risk prediction score for MI including proinsulin and the ratio between apolipoprotein B and apolipoprotein A1 was developed in middle-aged men. This score was predictive for future fatal and nonfatal MI, and proved to be at least as good as the Framingham and the PROCAM scores, being based on traditional risk factors.In summary these studies provide further knowledge about the associations between CHD and the metabolic syndrome and the possible importance of new markers of cardiovascular risk such as proinsulin and the apolipoproteins.
|
|
| 37. |
- Erlandsson, Anna, 1973-
(författare)
-
Neural Stem Cell Differentiation and Migration
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neural stem cells are the precursors of neurons, astrocytes and oligodendrocytes. During neural development, the division of stem cells takes place close to the lumen of the neural tube, after which they migrate to their final positions within the central nervous system (CNS). Soluble factors, including growth factors, regulate neural stem cell proliferation, survival, migration and differentiation towards specific cell lineages.This thesis describes the function of platelet-derived growth factor (PDGF) and stem cell factor (SCF) in neural stem cell regulation. PDGF was previously suggested to stimulate neuronal differentiation, but the mechanisms were not defined. This study shows that PDGF is a mitogen and a survival factor that expands a pool of immature cells from neural stem cells. The PDGF-treated cells can be stained by neuronal markers, but need further stimuli to continue their maturation. They can become either neurons or glia depending on the secondary instructive cues. Moreover, neural stem cells produce PDGF. Inhibition of this endogenous PDGF negatively affects the cell number in stem cell cultures. We find that SCF stimulates migration and supports the survival of neural stem cells, but that it has no effect on their proliferation or differentiation into neurons and glia. Intracellular signaling downstream from the receptors for PDGF and SCF includes activation of extracellular signal-regulated kinase (ERK). This investigation shows that active ERK is not needed for the differentiation of stem cells into neurons, at least not during early stages.Neural stem cells have a future potential in the treatment of CNS disorders. To be able to use neural stem cells clinically we need to understand how their proliferation, differentiation, survival and migration are controlled. The results presented in this thesis increase our knowledge of how neural stem cells are regulated by growth factors.
|
|
| 38. |
- Hedberg, Ylva, 1975-
(författare)
-
Cell Cycle Regulation in Human Renal Cell Carcinoma
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- ABSTRACTCell cycle regulation in human renal cell carcinomaYlva Hedberg, Departments of Medical Biosciences, Pathology, and Surgical andPerioperative Sciences, Urology Andrology, Umeå University, SwedenDeregulated growth control is a hallmark of neoplasia potentially caused by aberrant expression of cell cycle regulatory proteins. The importance of such aberrations in human renal cell carcinoma (RCC) has not been fully clarified. Therefore, the protein expressions of several G1/S regulatory proteins in human RCC were evaluated and their relation to clinico-pathological data was examined.Western blotting and immunohistochemistry were used to detect the proteinexpression of cyclin D1, D3, and E in 80 RCCs. Most tumors expressed higher levels of cyclin D1 (75%) and cyclin E (65%) compared to corresponding normal kidney cortex. In contrast, only 16 % of the tumors had high levels of cyclin D3. In conventional RCCs, low levels of cyclin D1 were associated with large tumor size, aneuploidy and a poor outcome for the patients. High expression of cyclin D3 and Ewere associated with aneuploidy, high proliferation, high TNM-stage, and high nuclear grade. Cyclin E was positively correlated to cyclin D3 but inversely associated with cyclin D1. Cyclin D3 and E were not associated with survival. The majority of RCCs had normal p27 levels, determined by immunohistochemistry, whereas the few tumors with low p27 levels were associated with large tumor size and poor survival.In order to confirm and extend our initial studies, a tissue microarray consisting of 218 RCCs was constructed and cyclin D1, D3, E, p27 were detected by immunohistochemistry. The tissue microarray results were validated by comparing the array data with western analyzes. Due to the large number of tumors analyzed we could evaluate potential differences in expression patterns of cell cycle regulators between conventional, papillary, and chromophobe RCCs. Interestingly, the protein expression differed between RCC types, showing that the conventional tumors generally had high cyclin D1 expression. In contrast, papillary and chromophobe RCCs had high cyclin E expression. Downregulation of p27 was found mostly in chromophobe RCCs. The retinoblastoma protein (pRb) was detected in all RCCs. Phosphorylation of pRb, detected by western blotting or immunohistochemistry and phospho-specific antibodies, was observed in approximately 50% of the tumors. The cdk-inhibitor p16 was not overexpressed suggesting that pRb was functional in the majority of RCCs.In summary, abnormal expression of G1-cyclins and the CDK-inhibitor p27 was common in RCC whereas the main G1/S-substrate, pRb, seemed to be functional. The aberrations further differed between the separate RCC subtypes and were linked to clinical behavior.
|
|
| 39. |
- Hedin, Hanne, 1948-
(författare)
-
External Fixation of Femoral Fractures in Children : Clinical, radiological and functional outcome and cost analysis
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to evaluate the outcome when treating children for displaced femoral fractures with external fixation.In a consecutive and prospective study during the period 1993-2000, 96 children aged 3-15 years with 98 displaced femoral fractures were treated with external fixation and early mobilisation. The mean age was 8.1 years, the mean hospital stay was 8.7 days and the mean treatment time was 61 days. All fractures healed. Minor complications included pin tract infections (18%), clinical insignificant malunions, heterotopic ossification and two re-reductions. Major complications (6%) included two re-fractures after significant trauma and three plastic deformations after premature fixator removal leading to an osteotomy.Radiological evaluation was performed up to one year for the whole group and for a subgroup up to two years. The evaluation showed that malunions were few and prone to remodelling almost completely. Although the fractures were fixated without shortening, as recommended earlier, the overgrowth was far less than expected.Isokinetic muscle strength was measured in both hamstrings and quadriceps in 31 of the patients and compared with 31 matched children without previous injury to the legs. Early mobilisation seems to prevent residual muscle weakness previously shown after treatment with traction or cast for femoral fractures in children.A cost analysis was performed, comparing three different treatment modalities of femoral shaft fractures: traction in hospital, traction in hospital/at home and external fixation. The analysis included both total medical costs and costs for the care provider. The most important factors were days spent at the hospital and the sick leave for the care provider. Treatment that can minimise these factors will contribute strongly to a lowering of health care costs.Conclusion: External fixation of displaced femoral fractures in children can be used as standard treatment in children aged 3-15 years. The treatment provides satisfactory results with a low rate of major complications. Early mobilisation seems to prevent residual muscle weakness. The treatment reduce the number of days in hospital and the number of days of sick leave for the care provider and contributes strongly to lowering health care costs.
|
|
| 40. |
- Henriques, Thomas, 1957-
(författare)
-
Biomechanical and Clinical Aspects on Fixation Techniques in the Cervical Spine
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present work is analyzing the general biomechanical aspects of fixation techniques in the upper and lower cervical spine along with clinical implications.The in vitro biomechanical properties of five different posterior atlanto-axial fixation techniques are compared. They provided for either a one, two or three-point fixation between atlas and axes. A new device, the C1 claw was biomechanically tested, which allow for fixation without the need for a structural bone graft. The three-point reconstructions indicated superior biomechanical properties compared to all others.The new C1 claw device was clinically evaluated in a series of 26 patients treated with a posterior C1-C2 fusion. There were no clinical or radiological failures in the series, Twenty-one patients out of twenty-three with any length of follow up either showed a solidly healed fusion or a healed fracture. Distractive flexion (DF) injuries in the lower cervical spine treated with anterior plate alone were analyzed with respect to healing rate and complications in a consecutive series of 36 patients. Results indicated that DF injury stage 1 and 2 according to Allen and Ferguson healed without complication, whereas DF injuries stage 3 had a high frequency of failure, needing an additional posterior fixation. The in vitro biomechanical properties of four different fixation techniques for a distractive flexion injury stage 3 were analyzed. The result indicated that anterior plate alone for fixation of a DF injury stage 3 is insufficient supporting the clinical finding in the previous study.Adjacent level motion was analyzed following a one segment fusion in the lower cervical spine. Motion was found to increase in adjacent levels possibly contributing to accelerated degeneration.
|
|
| 41. |
- Holmberg, Sara, 1967-
(författare)
-
Musculoskeletal Disorders among Farmers and Referents, with Special Reference to Occurence, Health Care Utilization and Etiological Factors : A Population-based Study
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objectives. To study the prevalence of musculoskeletal symptoms among farmers as compared to rural referents and to evaluate the effects of physical work exposures, psychosocial factors, lifestyle and comorbidity.Material and methods. A cross-sectional population-based survey of 1013 farmers and 769 matched referents was performed. Data on various symptoms, consultations and sick leave and information on primary health care and hospital admissions were obtained along with information on physical workload, psychosocial factors and lifestyle. Results. The farmers reported higher lifetime prevalence of symptoms from hands and forearms, low back and hips as compared to the referents. However, the farmers did not seek medical advice more often than the referents, and they reported significantly fewer sick leaves. After adjustment for the influence of physical work exposure, farmers still had a excess rate of low back pain (LBP) and hip symptoms as compared with the referents, while a lower rate of neck-shoulder symptoms was revealed. Several of the psychosocial variables were associated with LBP but the difference in LBP prevalence between farmers and referents could only be explained to some extent. LBP was associated with musculoskeletal symptoms other than LBP and with chest discomfort, dyspepsia, symptoms from mucous membranes, skin problems, work-related fever attacks, and primary care for digestive disorders. Presence of both respiratory and digestive disorders doubled the LBP prevalence.Conclusions. Symptoms from hips and low back were more frequent among farmers than among referents, but farmers did not seek more health care and reported fewer sick leaves than referents. Physical work exposure and psychosocial factors did not explain the differences in low back and hip symptoms between the two groups. Significant associations between LBP and digestive and respiratory disorders might indicate that these disorders may have etiological factors in common.
|
|
| 42. |
- Holmqvist, Kristina, 1972-
(författare)
-
The Role of Shb in Angiogenesis, FGF and VEGF Signalling in Endothelial Cells
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Angiogenesis is defined as the formation of new capillary blood vessels from pre-existing ones. This process involves several steps including: migration, proliferation and differentiation of endothelial cells into blood vessels. Angiogenesis is initiated by binding of specific growth factors, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), to their cell surface receptors. Shb is a ubiquitously expressed adaptor protein with the ability to bind several tyrosine kinase receptors. My aim has been to identify the role of Shb in FGF- and VEGF-signalling in endothelial cells. Shb was found to be phosphorylated in a Src-dependent manner upon both FGF- and VEGF-stimulation. This was confirmed using fibroblasts overexpressing temperature sensitive v-Src. Furthermore, Shb-induced cell spreading on collagen of immortalised brain endothelial (IBE) cells was also Src-dependent. FGF stimulation led to a direct association between Shb and FAK, which was mediated by the phosphotyrosine binding domain of Shb. IBE cells overexpressing wild-type or R522K Shb (inactive SH2 domain) displayed increased FAK activation on collagen.The SH2-domain of Shb was found to bind to tyrosine 1175 in the VEGFR-2 in a phosphotyrosine dependent manner using PAE cells expressing VEGFR-2. Furthermore, by use of siRNA, Shb knock-down experiments revealed that Shb regulates FAK activity, cellular migration and stress fiber formation in response to VEGF stimulation of VEGFR-2. In summary, Shb binds to both FGFR-1 and VEGFR-2 and regulates the activity of FAK and thereby stress fiber formation and cellular migration, which are necessary for formation of new blood vessels. IBE cells with an inactive SH2 domain of Shb displayed disorganised formation of tubular structures in the tube formation assay, while overexpression of wild-type Shb led to accelerated tubular morphogenesis.Taken together, my data show that the adaptor protein Shb plays an important role in the process angiogenesis, in response to angiogenic tyrosine kinase receptors, by interacting with FAK and regulating spreading, stress fiber formation and cellular migration.
|
|
| 43. |
- James, Stefan
(författare)
-
Coagulation, Inflammation and Myocardial Dysfunction in Unstable Coronary Artery Disease and the Influence of Glycoprotein IIb/IIIa Inhibition and Low Molecular Weight Heparin
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hjärt-kärl sjukdom är den vanligaste dödsorsaken i västvärlden. Samtidigt som antalet patienter med hjärtinfarkt har minskat, har antalet patienter med instabil kranskärlsjukdom d.v.s. svår kärlkramp ökat påtagligt. Diagnosen är nu den vanligaste orsaken till vård på hjärtinfarktavdelningar i Sverige. Modern behandling av instabil kranskärlssjukdom består av en kombination av läkemedel för att minska blodproppsbildning och avlasta hjärtarbetet samt, i de flesta fall, s.k. ballongvidning eller operation av hjärtats kranskärl. Trots stora behandlingsframsteg är risken för hjärtinfarkt och död hög, såväl på kort som lång sikt. Det finns därför ett stort behov av ytterligare förbättrad behandling utan att samtidigt erhålla oacceptabelt hög risk för allvarliga biverkningar. För att erbjuda en effektiv behandling till patienter med hög risk och samtidigt undvika dyr och potentiellt riskfylld behandling till patienter med låg risk behövs också bättre instrument för tidig riskbedömning. Syftet med avhandlingen var att undersöka en stor grupp patienter med instabil kranskärlssjukdom avseende säkerhet och effektivitet av en behandlingskombination av två moderna blodproppshämmande läkemedel, dalteparin och abciximab (ca 1000 patienter). Syftet var också att studera hur denna behandling påverkar system för inflammation och koagulation (ca 400 patienter). Dessutom ville vi värdera hur blodnivåer av markörer för inflammation, hjärtmuskelskada och nedsatt hjärtfunktion kan förutsäga risken för framtida komplikationer (ca 7000 patienter). Tillägg av abciximab till dalteparin minskade inte risken för dödsfall eller hjärtinfarkt inom trettio dagar. Däremot ökade antalet blödningskomplikationer. Totala antalet blödningar var emellertid relativt lågt och behandlingen syntes vara lika säker som kombinationen av abciximab och det internationellt mycket använda blodproppshämmande medlet heparin. Trots den kraftfulla behandlingskombinationen skedde en samtidig aktivering av system för såväl inflammation som koagulation. Detta kan vara en orsak till den observerade avsaknaden av behandlingseffekt av abciximab. Att hindra denna aktivering skulle samtidigt kunna innebära möjligheter för nya behandlingsstrategier. Förhöjda nivåer av markörer för hjärtmuskelskada (troponin T), inflammation (CRP), nedsatt hjärtfunktion (proBNP) eller nedsatt njurfunktion (kreatininclearance) ökade risken för dödlig utgång både på kort och lång sikt, oberoende av andra riskfaktorer. En kombination av två av dessa markörer gav den högsta risken för dödlig utgång. Således dog endast 0.3 % av patienter med låga nivåer av proBNP och normal njurfunktion inom ett år, jämfört med 25.7 % av patienter med höga nivåer av proBNP och nedsatt njurfunktion. Förhöjda nivåer av troponin T eller nedsatt kreatininclearance (men inte av CRP eller proBNP) ökade dessutom risken för hjärtinfarkt. Resultaten i avhandlingsarbetet har givit kliniskt tillämpbar kunskap om hur kärlkrampspatienter med hög respektive låg risk kan selekteras tidigt efter inkomst till sjukhus och ny kunskap om behandlingseffekt av abciximab och dalteparin. Resultaten har redovisats på internationella kongresser och i högt rankade medicinska tidskrifter och har citerats i europeiska och amerikanska ”guidelines” för behandling av instabil kranskärlssjukdom.
|
|
| 44. |
- Johnell, Matilda, 1961-
(författare)
-
Monocytes, Tissue Factor and Heparin-coated Surfaces : Clinical and Experimental Studies
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiopulmonary bypass (CPB) is associated with inflammatory response and activation of coagulation. Heparin coating of the CPB circuit is shown to improve the biocompatibility of the surface. The biological effects of a new heparin surface, the Corline Heparin Surface (CHS), prepared according to a new principle, have been studied. The CHS used during coronary artery bypass grafting with CPB in sixty patients prevented adhesion of cells to the extracorporeal device. The activation of inflammation, coagulation, and fibrinolysis was significantly reduced by the use of CHS. Both a reduced and an increased dose of systemic heparin in combination with the heparin-coated surface resulted in more activation of inflammation and coagulation. Photoelectron spectroscopy studies of the molecular structure of the CHS demonstrated that a single layer of the heparin surface, equivalent to what was used in the in vivo studies, did not completely cover the substrate surface. Additional layer of immobilized heparin has resulted in a complete coverage. We examined the biological effects, i.e. activation of inflammation and coagulation, by CHS in one and two layers in an in vitro-study. The data from this study clearly demonstrated that a uniform surface coating of the CHS results in only minor activation of coagulation, inflammation and cell activation. Monocytes do not normally express tissue factor (TF), initiator of the coagulation in vivo, but can be induced upon adhesion to artificial surfaces. TF is receptor for coagulation factor VIIa (FVIIa) and binding subsequently leads to formation of thrombin. Other biological effects beyond coagulation, as inflammation and angiogenesis, has recently been associated with the formation of TF·FVIIa. The TF∙FVIIa signal transduction induced an increased sensitivity to PDGF-BB-stimulated migration and an increased production of IL-8 and TNF-α in monocytes. These could be important mechanisms for continued recruitment of cells to sites of inflammation.
|
|
| 45. |
- Khan, Tanweera Shaheena
(författare)
-
New Diagnostic and Therapeutic Approaches in Adrenocortical Cancer
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Adrenocortical cancer (ACC) is a rare disease that is often difficult to diagnose, and therefore often presents at an advanced stage. Various cytotoxic treatments have been tried with little success. Evaluation of new diagnostic methods and improvement of medical therapies are therefore crucial.The diagnostic potential of 11C-metomidate positron emission tomography (PET) was evaluated in eleven ACC patients. PET visualized all viable tumors with high tracer uptake, including two lesions that CT failed to detect. Necrotic or fibrotic tumors were PET negative. Medication with adrenal steroid inhibitors and chemotherapy may decrease the tracer uptake.We performed a phase-II study with streptozocin and o,p’-DDD (SO) combination therapy in 40 ACC patients. The SO therapy was found to have impact on the disease-free interval (P = 0.02) as well as on survival (P = 0.01) in patients who received adjuvant therapy after curative resection. Complete or partial response was obtained in 36.4% of patients with measurable disease.The efficacy and tolerability of combination therapy with vincristine, cisplatin, teniposide, and cyclophosphamide (OPEC) were evaluated in eleven patients with advanced ACC after failure of SO therapy. The median survival was 21 months from the start of treatment. A partial response was achieved in two patients. Adverse events were mainly restricted to grade 1-2 toxicities, and grade 3 toxicities were observed in only two cycles.We tested 21 ACC tumors to analyze the expression of receptor tyrosine kinases and 15 ACC for mutation analysis of c-Kit exon 11, which can be targeted by antagonists such as imatinib. All ACCs expressed one or more kinases: c-Kit in 19 ACC and phospho-c-Kit in three while 14 ACCs expressed PDGFR-beta, suggesting the potential usefulness of tyrosine kinase inhibitors. No c-Kit mutations were detected in exon 11. Further evaluation of other mutations targeted by this drug may be needed.
|
|
| 46. |
- Larsson, Tobias Erik Martin, 1976-
(författare)
-
The Role of Fibroblast Growth Factor 23 in Phosphate Homeostasis
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The regulation of serum phosphate (Pi) concentrations is a complex process and our current models are far from complete. Due to major advancements in biotechnology and the development of more powerful research tools, recent advances in the field of genetics has led to the identification of several candidates for the long sought-after phosphatonin(s), or Pi regulating hormones. One of these candidates is fibroblast growth factor 23 (FGF-23) and this thesis is based upon studies of the role of FGF-23 in Pi homeostasis. We demonstrate that FGF-23 is a secreted protein which is highly expressed in tumors giving rise to oncogenic hypophosphatemic osteomalacia (OOM). Furthermore, we have developed a two-site enzyme-linked immunosorbent assay for the detection of circulating FGF-23 and established that FGF-23 is present in the circulation of healthy individuals. Also, FGF-23 serum levels are elevated in patients with disturbances in Pi homeostasis such as OOM, X-linked hypophosphatemic rickets (XLH) and chronic kidney disease and are likely to play an important role in the pathogenesis of these disorders. A transgenic mouse model that express human FGF-23 under the control of the α1(I) collagen promoter exhibit similar clinical and biochemical characteristics as do patients with OOM, XLH and autosomal dominant hypophosphatemic rickets indicating that FGF-23 is an important determinant of Pi homeostasis, vitamin D metabolism and bone mineralization.
|
|
| 47. |
- Lindberg, Anne, 1957-
(författare)
-
Chronic obstructive pulmonary disease (COPD) : prevalence, incidence, decline in lung function and risk factors
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Obstructive Lung Disease in Northern Sweden (OLIN) Studies started in 1985 as an epidemiological project with the aim to detect preventable risk factors for obstructive lung diseases and allergy. In recent years there has been a focus also on obstructive sleep apnoea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD) besides asthma and allergy. The aim of this thesis was to estimate the prevalence and incidence of COPD, risk factors for COPD, and decline in lung function in relation to COPD.The OLIN cohort I (cI) was recruited in 1985/86 and consisted of all 6610 subjects born 1919-20, 1934-35 and 1949-50 in eight geographical areas of Norrbotten. A postal questionnaire survey was performed in 1985/86, 1992 and in 1996. All subjects reporting respiratory symptoms at the questionnaire in 1985/86 were invited to examination in 1986, 1996 and 2002-03. A random sample of 1500 subjects from the participants at the 1996 postal questionnaire survey was invited to examination in 1996 and 2003. The participation rate has been high, ≥85%. The OLIN cohort III (cIII) was recruited in 1992, a postal questionnaire was sent to a random sample of 5681 subjects aged 20-69 years. In 1994/95 a random sample of 970 subjects were invited to examination of whom 666 participated.The prevalence of COPD in the general population sample (cIII) in ages <45 was 4.1%, 11.6%, 9.1%, and 5.1% according to the criteria of BTS1 , ERS2 , GOLD3 , and ATS4 respectively. The corresponding figures in ages ≥45 were 9.7%, 15.4%, 17.1%, and 16.5% respectively. In the age-stratified general population sample (>45 y, cI), the prevalence was 8.1% and 14.3% according to the BTS and GOLD criteria. The prevalence was strongly associated with higher age and smoking but not gender. The prevalence among smokers 76-77 years old was 45% and 50% (BTS and GOLD criteria). A majority of subjects with COPD had respiratory symptoms (in prevalent BTS 94%), most commonly cough and sputum production. Nearly a half of the subjects with COPD had contacted health care due to respiratory complaints other than common colds, but only a minority reported a physician diagnosis relevant for COPD (16% of prevalent COPD according to BTS in cIII, 31% in cI). The 10-year cumulative incidence of COPD (1986-1996) was estimated at 8.2% (BTS) and 13.5% (GOLD) in the symptomatics of cI, associated with higher age and smoking but not gender. Persistent smoking, male gender and reported chronic productive cough were associated with a faster decline in FEV1. Among incident cases of COPD a large proportion (23% of incident BTS) had a rapid decline in FEV1, >90 ml/year, corresponding to a decrease of 28 percent-units of normal value during ten years.The 7-year cumulative incidence of COPD in the random sample of cI (1996-2003) was estimated at 4.9% and 11.0% (NICE guidelines5 and GOLD) and associated with smoking but not gender. The incidence according to GOLD, but not NICE, was associated with increasing age. In multi-variate analysis most respiratory symptoms were markers of increased risk for developing COPD.In conclusion, the prevalence and the incidence of COPD were associated with age and smoking and affected by the use of different spirometric criteria. Respiratory symptoms marked an increased risk for developing COPD. A high proportion of subjects developing COPD had a rapid decline in lung function. Further, there was a substantial underdiagnosis of COPD.1 British Thoracic Society: FEV1/VC<0.70 & FEV1<80%predicted (pred), 2 European Respiratory Society: FEV1/VC<88%pred in men, <89%pred in women, 3 Global initiative for Chronic Obstructive Lung Disease:FEV1/FVC<0.70, 4 American Thoracic Society: FEV1/FVC<0.75 + symptoms or physician diagnosis, 5 The British National Institute for Clinical Excellence: FEV1/FVC<0.70 & FEV1<80%pred.
|
|
| 48. |
- Liu, Meilin
(författare)
-
Effects of Antioxidant and Lipid Lowering Treatment on Risk Factors for Cardiovascular Disease : With special reference to Mixed Tocopherols and Stable Fish Oil
- 2002
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Vitamin E in food, polyunsaturated fatty acids (PUFAs) and lipid lowering treatment with statins have been found to decrease the risk for cardiovascular disease (CVD) and cardiac death. However, clinical trials revealed no beneficial effect of intake of alpha-tocopherol alone. Absence of tocopherols other than alpha-tocopherol in the clinical studies may account for the conflicting results. The aim of the present investigation was to study the effects and potential mechanisms of mixed tocopherols and lipid lowering treatment with stable fish oil and/or simvastatin on risk factors for cardiovascular disease and potential mechanisms behind the effects.Mixed tocopherols were found to have more potent effects on inhibition of lipid peroxidation and prevention of loss of PUFAs in erythrocytes, than alpha-tocopherol alone. Mixed tocopherols but not alpha-tocopherol prevented ADP-induced platelet aggregation. Effects of mixed tocopherols were associated with increased NO release, ecNOS activation and increased SOD protein levels in platelets. Supplementation with tocopherols increased ecNOS activation, and SOD protein level, and decreased PKC activation in platelets and leukocytes. Mixed tocopherols were more potent than alpha-tocopherol alone in modulating NO release and increasing ecNOS activation.Supplementation with stable fish oil reduced triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL) and increased high density lipoprotein cholesterol (HDL), and simvastatin reduced TC, LDL and the LDL/HDL ratio in subjects with hyperlipidemia. The combination of stable fish oil and simvastatin further reduced TC, LDL, the LDL/HDL ratio and TG, showing that simvastatin therapy with addition of stable fish oil may be more beneficial in lowering plasma lipoproteins than simvastatin or fish oil alone. A small daily intake of stable fish oil in bread increased n-3 PUFAs and HDL, and decreased TG and malondialdehyde in plasma in subjects with hyperlipidemia.
|
|
| 49. |
- Mattsson, Göran, 1967-
(författare)
-
Experimental Studies on the Vasculature of Endogenous and Transplanted Islets of Langerhans
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The blood vessels of the pancreatic islets are of crucial importance for oxygen and metabolite supply as well as dispersal of secreted hormones. In addition to this, endothelial cells have an important role in the revascularization process after islet transplantation. Previous studies have reported signs of poor engraftment of transplanted islets, presumably due to impaired revascularization. The aims of this thesis were to investigate the revascularization process of transplanted islets and to examine the role of islet endothelial cells. In this context, the lectin Bandeiraea simplicifolia was found to stain endothelium of both endogenous and transplanted pancreatic islets. By using this lectin we investigated the vascular density of both endogenous and islets transplanted syngeneically beneath the renal capsule, into the spleen or intraportally into the liver of normoglycemic C57BL/6 mice. One month post-transplantation, a time point when the grafts are assumed to be completely revascularized, the vascular density was decreased at all three implantation sites when compared to endogenous islets. Furthermore, most of the blood vessels were located in the graft connective tissue stroma. Similar results were obtained when islet transplant vascular density was determined six months post-transplantation and in cured diabetic animals after one month. In order to evaluate the function of intraportally transplanted islets, we developed a method to retrieve such islets. We treated the implantation organ (liver) first enzymatically (collagenase) and then mechanically, thereafter we could re-isolate the transplanted islets for further in vitro studies. The retrieved islets had a decreased insulin relase, insulin content and glucose oxidation rate when compared to non-transplanted control islets. To understand the role of islet endothelium in the revascularization of transplanted islets we performed angiogenesis GEArray studies on islet endothelial cells, from non-cultured, cultured and transplanted islets. We found that the islet endothelium expressed mRNA for both inhibitors and inducers of angiogenesis, and that this expression differed with time. The functional consequences of this remain to be determined. In summary, the results presented above provide a useful platform for future studies of the morphology and function of islet endothelial cells, especially with a view for elucidating changes induced by islet transplantation.
|
|
| 50. |
- Melin, Roland
(författare)
-
On life satisfaction and vocational rehabilitation outcome in Sweden
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation has two parts. Firstly, satisfaction with life as a whole and with 10 life domains (using an instrument termed LiSat-11 with 6-graded scales) is described in a nationally representative sample aged 18-64 years (n: 2,533) and is related to some socio-demographic circumstances. Secondly, vocationally disabled people (n: 109) at an employability institute are prospectively followed in order to determine their life satisfaction and to identify early predictors of vocational rehabilitation outcome.Main results: Gender independently, 70 % of the national sample were satisfied with life as a whole (were happy). The ten domains formed a 4-factor pattern: ”Closeness, Health, Spare time, Provision”. Seven domains were sizeable predictors of overall life satisfaction. In a complex manner socio-demographics were predictive of (gross levels) all LiSat-11 items. Main predictors were perceived health, immigrant status and educational level. Generally, the vocational rehabilitees had low LiSat-11 levels except for the closeness items. They had relatively poor background resources (low “sense of coherence“ level) for successful coping. Whereas a positive rehabilitation outcome was accompanied by increases in several LiSat-11 aspects, only satisfaction with the vocational situation was clearly responsive. Three early predictors of outcome were identified: belief in vocational return, educational level and sense of coherence. In summary: Besides providing reference values for the LiSat-11 instrument, this dissertation demonstrates that different socio-demographic factors influence different areas of concern (domains) in 18- to 64-year-old Swedes. In turn, satisfaction derived from different areas heavily influences level of overall life satisfaction. Moreover, the vocational rehabilitees generally seemed to be predisposed to being poor copers, possibly a major background of low levels of many LiSat-11 aspects. The identified set of predictors of the outcome of vocational rehabilitation emphasizes a need for focusing on psycho-social aspects within vocational rehabilitation.
|
|
