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Träfflista för sökning "L4X0:0345 0082 ;srt2:(1995-1999);srt2:(1999)"

Sökning: L4X0:0345 0082 > (1995-1999) > (1999)

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31.
  • Vergis, Anil, 1961- (författare)
  • Sagittal plane knee translation in healthy and ACL deficient subjects : a methodological study in vivo with clinical implications
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This study on human subjects, comprises of four cross sectional and one prospective cohort study. The general purpose of this work was to develop a technique for measuring in vivo, sagittal anterior-posterior translatory motions in the knee joint using a computerized electrogoniometer (CA-4000, OS Inc., Hayward CA, USA). Healthy human subjects served as controls while patients with arthroscopically confirmed unilateral ACL deficiency served as the experimental group.The measurements were repeatable, accurate and valid. In all groups, as a consistent pattern, the tibia maintained an anterior position in relation to the femur during the load bearing phases and a posterior rosition in the non load bearing phases of step ascents and descents. Contraction of the gastro-soleus grour of muscles, before the lift off phase of ascent, resulted in an anterior positiOn of the tibia in relation to femur which was anterior to the posterior limit of static laxity testing. Step heights between 15 to 23 cm did not influence the amount of tibial translation.During step ascent the amount of femoral roll-forward per degree extension was significantly smaller in the ACL deficient knees than the contralateral noninjured or healthy control knees.ACL deficiency resulted in a larger than normal static space (125% to 257%) in the injured knees. It also resulted in an anterior shift of the tibia-femoral resting position of the injured knees.The amount of the static laxity space the ACL deficient knee utilised during stair climbing varied, depending upon the knee flexion angle. Nearer to extension it was 90% and near to mid flexion (50°--{50°) it was 42% of the maximal static laxity space. In the conservatively treated ACL deficient group, the contralateral healthy knees showed 28% increase in the static AP laxity at follow up when compared to the index measurement and the control knees.In the ACL reconstructed group, the increased static AP laxity and anterior shift of the tibia-femoral resting position in the reconstructed knees persisted at a minimum follow up of 21 months. Over the same period of time, the contralateral healthy knee also showed an anterior shift in the tibia-femoral resting position. The force at the anterior inflection point in static laxity testing, which was similar at index examination in both knees, diminished by 20% in the reconstructed knees at follow up.The ACL plays an important role in optimally positioning the tibia-femoral articulation and maintaining the position during quadriceps and gastro-soleus muscle contraction.
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32.
  • Wigren, Jane, 1967- (författare)
  • Identification of natural activators of the nuclear receptor peroxisome proliferator-activated receptor : relevance to the pathogenesis of atherosclerosis
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Polyunsaturated fatty acids induce peroxisome proliferation. This phenomenon is mediated by the ligand-dependent transcription factor peroxisome proliferator-activated receptor (PPAR). This thesis is an investigation on the role of eicosanoids and oxidized products of linoleic acid for the activation of PPARs. Special emphasis was given to the subtype PPAR/gamma/ in the context of atherosclerosis.It had earlier been shown that arachidonic acid induces peroxisome proliferation in Morris Hepatoma 7800C1 cells. We investigated whether this effect could be attributed to a cytochrome P-450IVA product of arachidonic acid, 20-hydroxy-arachidonic acid. Arachidonic acid, but not 20-hydroxy-arachidonic acid induced lauryl-CoA oxidase activity. The effect of arachidonic acid was potentiated by all-trans retinoic acid, consistent with the notion that PPAR/RXR heterodimers mediate the effect.Several reports in the litterature were suggestive of an important role of peroxisomes in eicosanoid metabolism. However, nobody had isolated pure peroxisomes and investigated their eicosanoid metabolizing ability. We therefore investigated the ability of peroxisomes to metabolize the eicosanoid 12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(S)-HETE). Incubation of tritium-labeled 12(S)-HETE with isolated peroxisomes from rat liver or kidney peroxisomes demonstrated that more than 90 % of the diethyl ether extractable radioactivity was due to a single metabolite, identified as 8-hydroxy-6, 8, 12-octadecatrienoic acid (8-OH-16:3). This compound was apparently formed by two rounds of ß-oxidation. The data for the first time provided conclusive evidence for a role of peroxisomes in HETE metabolism.The second half of the thesis deals with the identification of natural PPAR/gamma/ ligands in LDL from atherosclerotic patients and in activated macrophages. Analyses of the endogenous content of selected monohydroxy fatty acids in LDL isolated from a group of patients diagnosed with intermittent claudication, showed the presence of 9- and 13-HODE, 5-, 12-, and 15-HETE. These compounds activated PPAR/gamma/ in macrophages and preferentially recruited the coactivator protein CBP to PPAR/gamma/RXR/alpha/ heterodimers. 15-deoxy-/DELTA/12,14-Prostaglandin J2 (15-deoxy-/DELTA/12,14-PGJ2) was identified as a PGD2 metabolite in macrophage cultures (see below). It induced the interaction of PPAR/gamma/RXR/alpha/ heterodimers with both CBP and SRC-1. This observation suggests that different PPAR/gamma/ ligands may induce different effects through a single kind of receptor by differential recruitment of coactivators.Although PGD2, is not a PPAR/gamma/ ligand, it induces PPAR/gamma/-mediated effects in IFN-/gamma/-stimulated RAW 264.7 macrophages, suggesting that the effects required metabolism. We therefore investigated PGD2 metabolism in macrophage cultures, and determined the capacity of these metabolites to activate PPAR/gamma/. Two novel (/DELTA/12-PGD2, 15-deoxy-/DELTA/12,14-PGD2) and two previously known PPAR/gamma/ activators (/DELTA/12-PGJ2 and 15-deoxy-/DELTA/12,14-PGJ2) were identified by mass spectrometry. The structural difference between the novel products and the previously recognized PPAR/gamma/ agonists , /DELTA/12-PGJ2 and 15-deoxy-/DELTA/12,14-PGJ2, is that they contain a 9/alpha/-hydroxy group and lack a /DELTA/9,10 double bond. Two novel PPAR/gamma/ activators were formed in equal or greater amounts and were more potent activators of PPAR/gamma/ in macrophages.
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33.
  • Yngve, Smedberg (författare)
  • On the reporting of dental health, time for dental care, and the treatment panorama : Methodological studies of measuring and analysing dental care outcomes within a Swedish Public Dental Service organization
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The thesis included five methodological studies and one caries epidemiological investigation, the general aim being to study how to measure and report dental health, time for dental care, treatment panorama, and dental care outcomes, within a Public Dental Service organization. The specific aims were to monitor dental clinic activities using a time study method, to apply time study results of a dental health-related patient group system for the 3-19 year age groups, and to compare time study results with corresponding results from computerized systems used for reporting dental care. Other specific aims were to compare longitudinal caries index data results between cohort and cross-sectional samples, to analyse caries index for extreme caries groups among adolescents leaving organized dental care, and — using time series methods — to analyse dental health development of the 15-19 year age groups. Results from the time studies portrayed the dental clinic as a working unit, showed that reported values can represent dental care only for intervention procedures, and indicated that clinic patterns were not adapted to the health situation of the patient groups. Longitudinal cohort attempts gave different values from those of the cross-sectional year classes, which should be the primary focus when presenting caries index mean values in dental health reviews. Caries freegroups from 15 to 19 years of age seem to be stable in their caries development in about 60%-80% of cases; while the 20% groups with the highest index values accounted for about 80% of all approximal lesions. In times of major economic adjustment, dental health for adolescents in Göteborg was an example of sustainable dental health development. A model system for monitoring, analysing, and reporting dental health and dental care outcomes within a dental care-giving organization calls for several conditions, for example, a dental healthrelated patient group system, and a rationale for the choice of dental team models. These areas could be gathered into a system where contemporary socio-economic factors and dental research results interact with performed dental care, and also with different methods for reporting and evaluating dental health, dental care costs, and the demand for dental care competence.
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34.
  • Zhuang, Shi-Mei, 1965- (författare)
  • Molecular genetic alterations in chemically-induced lymphomas
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Lymphoma is one of the most common malignancies in humans. Its incidence has increased rapidly in the past 30 years. However, the molecular mechanisms underlying the development of lymphomas are largely unknown.Environmental carcinogens play an important role in tumorigenesis. 1,3-butadiene (BD) and 2~,3-dideoxycytidine (ddC) are two carcinogens to which humans are exposed. Cancer bioassays in mice have revealed that both BD and ddC induce high frequencies of lymphomas. The present study provides a genetic dissection of these chemically-induced lymphomas, with a focus on identification of potential turner suppressor loci and genetic alterations in genes involved in the pRb, p53 and Ras/Raf pathways. These pathways are important in the control of cell proliferation.Approximately 87% of BD-induced and 75% of ddC-induced lymphomas show allelic losses or mutations in genes examined. Similar frequencies for inactivation of the p53 pathway were observed in BD- and ddC-induced tumors, whereas disruption of the pRb pathway is more common in ddC-induced lymphomas. On the other hand, BD-induced tumors display more frequent activation of the Ras/Raf pathway. These data indicate the genotoxicity of both ddC and BD, and also confirm the carcinogenicity of these chemicals at a molecular level.This study also reveals that different genetic alterations occur in distinct stages of the development of BD-induced lymphomas. Ras mutations were detected in tumors derived from mice exposed to BD for only 26 weeks or at a rather low concentration (20 ppm), suggesting that ras mutations may occur early in tumor formation. In contrast, all six tumors with aberrations of p53 occurred in the high dose (625 ppm), continuous long-term exposure group, and these tumors appear to have a more aggressive phenotype, indicating that inactivation of p53 may be a late event, associated with progression of BD-induced lymphomas. Furthermore, two or more genetic alterations were found in 67% of tumors from the 625 ppm dose group and in only 46% of lymphomas derived from mice exposed to s312 ppm of BD. In addition, more than five genetic aberrations occurred only in the 625 ppm dose group. These results support the contention that there is a dose-dependent increase of genetic alterations in BD-induced tumors.The mutational pattern resulting from carcinogen-exposure has been observed in both human and animal turners. In the present study, the specific K-ras codon 13 CGC mutation and allelic loss of the Rafl locus on chromosome 6 were detected only in BD-induced lymphomas, while frequent allelic loss of the telomeric region of chromosome 2 was observed only in ddC-induced tumors, suggesting an agent-specific effect.The genome-wide screen of allelic losses revealed that multiple potential tumor suppressor genes contribute to the development of BD- and ddC-induced lymphomas. Moreover, most of the identified regions with frequent allelic losses carry unknown tumor suppressor genes, whose isolation and identification are of great interest for further investigation.
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35.
  • Ziedén, Bo (författare)
  • LDL Oxidation Susceptibility and Its Relation To Antioxidants and Fatty Acids : A Clinical and Experimental Study
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Atherosclerosis is an arterial disease characterized by lipid deposits in the artery wall. These lipid deposits partly consist of oxidatively modified low density lipoprotein (LDL). Several lines of evidence indicate a role of oxidized LDL in atherogenesis. The susceptibility of human circulating LDL towards oxidation was therefore considered to be of interest.The LDL oxidation susceptibility was followed spectrophotometrically after addition of copper and was expressed as LDL lag time. We also investigated the plasma concentrations of oxidized cholesterol, lipophilic antioxidative vitamins and fatty acids to get a better understanding of the mechanisms governing LDL oxidation.We compared 50-54 year old men from Vilnius, Lithuania who have a four fold higher coronary heart disease (CHD) mortality compared to men from Link6ping, Sweden. Plasma or LDL cholesterol, blood pressure and smoking could not account for this difference. We found a significantly shorter Jag time in Vilnius men, higher serum concentrations of 7-ß hydroxycholesterol, lower concentrations of y-tocopherol, ß-carotene and lycopene and also higher amount of easily oxidized highly unsaturated fatty acids, such as eicosapentaenioc acid ( EPA). Important determinants of the LDL lag time were found to be EPA (negative), a-tocopherol (positive), but also LDL cholesterol and plasma triglyceride concentrations were associated with a shorter LDL lag time.The effect of ω-3 fatty acid compared to corn oil supplementation was investigated in patients with severe hypertriglyceridernia. Plasma triglyceride concentrations decreased by 48% in the ω-3 group. In both groups the LDL lag time shortened after 12 weeks of supplementation.In vitro addition of the antihypertensive drug captopril to LDL was investigated. Captopril prolonged the LDL lag time, decreased other oxidation products such as thiobarbituric acid reactive substances (TBARS) and lipid peroxides in a dose dependent manner.These studies show that the LDL oxidation susceptibility differs between two groups of healthy men from two populations with a marked difference in CHD mortality. Supplementation with ω-3 fatty acids shortened the LDL lag time. LDL oxidation susceptibility is related to low serum concentrations of lipophilic antioxidative vitamins and high content of long chain highly unsaturated fatty acids.
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