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Sökning: L4X0:0345 0082 > (1995-1999) > (1998)

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  • Vasar, Marie (författare)
  • Allergic diseases and bronchial hyperreactivity in Estonian children in relation to environmental influences
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>This thesis is based on the cross-sectional and prospective study of Estonian children. The aim of this thesis was to assess the prevalence of allergic diseases and respiratory symptoms in Estonian schoolchildren and in young children, to study environmental risk factors for allergic diseases and repiratory symptoms. The cross-sectional study was a part of an epidemiological study in Northeastern part of Europe of the same age group and using standardised methodology in order to allow meaningful comparisons between the countries. The Estonian study was extended to include more extensive assessment of lung function to assess bronchial hyperreactivity (BHR) in Estonian schoolchildren.</p><p>1580 schoolchildren from Tallinn and Tartu participated in a cross-sectional study which included parental questionnaires, skin-prick tests, serial peak-flow measurements, methacholine provocation and exercise challenge tests.</p><p>Among 10-12 year-old schoolchildren the prevalence of asthma was lower than in children of similar age in Sweden (2.9% vs 8.1% ). In contrast to the low prevalence of atopic diseases, the frequent respiratory infections were more common among the Estonian schoolchildren than in Sweden. Respiratory symptoms and allergic disorders in Tall inn, compared to Tartu showed a similar tendency as the urban-rural gradient in Sundsvall, Sweden. These findings suggest an influence of air pollutants and other adjuvant factors, as related to urbanisation in both countries. Atopic heredity, current dampness and maternal smoking were significant risk factors for the respiratory symptoms in Estonia. The prevalence of BHR to methacholine was 19% in Tall inn and 32% in Tartu (p&lt;O.OOI). Positive exercise challenge tests were recorded in 6% of the children living in Tallinn and in 18% in Tartu (p&lt;O.OOl). In contrast to the results of studies in Western Europe, most children with BHR were not atopic. BHR was apparently more related to other environmental factors, as paternal smoking, use of gas stoves, but also other lifestyle factors could be related, what were not examined. In onr study methacholine challenge and peak-flow rate variability were related to asthma. There was a poor correlation between the different methods to assess BHR, however.</p><p>In prospective study 298 healthy, consecutively born newborn babies werefollowed from birth up to 2 years of age. Skin-prick tests with fresh food allergens and inhaled allergens were carried out at 6, 12, and 24 months of age. Symptoms of allergy were searched by employing questionnaires at 3, 6, 9, 12 and 24 months of age.</p><p>The prevalence of allergic diseases .increased from 8% at 6 months to 17% at 24 months. The cumulative incidence of allergy was 25%, and atopic dermatitis was the main manifestation of atopy with a peak prevalence of 15% at 2 years of life. Asthma was present in 4 children and allergic rhinoconjunctivitis in 2 children at 2 years. The results of our prospective study showed that prevalence of allergy among Estonian young children was not as low as would be expected. This could possibly indicate that 'western lifestyle' has already affected the infant population born in 1993/94.</p>
  • Vitak, Bedrich (författare)
  • Interval cancers, positive predictive value for malignance and other early quality indicators in mammographic screening for breast cancer
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>The study was designed to evaluate early quality indicators in screening for breast cancer. lt comprised, (i) investigations of compliance, recall, referral, cancer detection, and interval cancer rates in the Östergötland screening programme of women aged 40-74 years; (ii) evaluation of the three-stage diagnostic procedure for pre-operative assessment of women with suspicious mammographic findings; (iii) comprehensive analysis of all invasive interval cancers detected; and (iv) investigation into how to reduce the number of interval cancers without a concomitant increase in false positives.</p><p>The attendance rates were 85.5% at the initial screen and 81.3% at subsequent screens. The referral rates for further examination at subsequent screens were roughly half of th'lt at the initial screen. The cancer detection rates were 6.4/1000 at the initial and 2.6/1000 at subsequent screens. The positive predictive value for malignancy at surgery was 96% for ages 50-74 years. Apart from the tumour grade (not analysed) the diagnostic outcome tallied with the quality targets stipulated by Tabár et al.</p><p>The study confirmed the less favourable prognosis for interval cancer patients and cancers in non-attenders compared to screen-detected patients, but the mode of detection was not an independent predictor of metastatic capacity (hazard rate ratio [RR] of distant recurrence /adjusted for other variables/ RR=1.39, 95%confidence interval [95%CI] 0.78-2.46 for interval cancers; and RR=1.6, 95%CI 0.76-3.36 for non-attenders). The higher metastatic potential in these tumours could be explained by the differences in tumour characteristics at the time of diagnosis.</p><p>The incidence risk of interval cancer was 0.46/1000 for tumours detected within 1 year of the latest screen, and 1.2/1000 for tumours detected within 2 years of the latest screen. Despite the lower age-specific breast cancer incidence in women aged 40-49 years, these women ran roughly the same risk of interval cancer after a negative screen as did the other age groups in the screening programme.</p><p>Patients with potential iatrogenic delay in diagnosis (overlooked or misinterpreted cancers) constituted 25% of all patients with invasive interval cancer, and patients with true interval cancer 49%. The radiological category of interval cancer had no significant influence on the survival (overall comparison, p=0.1202; comparison of true interval with missed interval cancers, p=0.3175). In the present study there was no clear evidence of difference in prognosis between true interval and overlooked or misinterpreted interval cancers.</p><p>The interval between the latest screen and diagnosis was not an independent prognostic factor in patients with true interval cancers (RR=0.47, 95%CI 0.16-1.35 for tumours detected 21 year after the latest screen), and there was no significant difference in survival according to this interval (comparison of tumours detected &lt;1 year with tumours detected 21 year of the latest screen, p=0.3844).</p><p>The study confirmed the association of criteria for referral for further examination with number of false positives. Efforts to reduce the number of interval cancers by lowering the mammographic threshold for recall are likely to be counterproductive. The early quality indicators constitute. an excellent means of monitoring of the quality of screening.</p>
  • Wandt, Birger (författare)
  • Mitral Ring Motion in Assessment of Left Ventricular Function
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>The motion of the mitral ring was studied with M-mode echocardiography using the apical four- and two-chamber views.</p><p>With the purpose of obtaining adequate reference materials for mitral ring motion, 70 healthy subjects were studied. Stepwise multiple regression analysis with age, gender, height, weight, body i surface area and heart rate as independent variables, showed that ring motion amplitude (mm) is best i described as 2.2 + 0.078 x height (cm) (SD = 1.0 mm) in subjects under age 18, and as 12.7- 0.060 [ x age (years)+ 0.031 x height (cm) (SD = 1.2 mm) in subjects over age 18, or if only age is taken ! into account as 18.4-0.065 x age (SD = 1.2 mm).</p><p>Both in children and adults the atrial contribution to the total mitral ring motion was best described as 0.15 + 0.0039 x age (SD = 0.027).</p><p>Comparison between the four sites of measuring showed that the mitral ring "tilts" slightly during the systolic motion towards the apex. The septal point moved significantly less than the lateral point (p&lt;O.OOl).</p><p>In 20 healthy subjects changes in mitral ring motion and in short axis contractions with respiration was studied. It was shown that the decrease in left ventricular stroke volume on inspiration is a net effect of decrease in diastolic short axis diameter by 4.8% (p&lt;0.001) and an increase in mitral ring motion by 5.5% (p&lt;0.001).</p><p>In 40 healthy subjects aged 18 - 70 years changes in long axis and short axis contraction with increasing age was studied. It was shown that from age 18 to age 70 the long axis systolic shortening[ decreases by 20% (p&lt;0.001) and minor axis shortening increases by 18% (p=0.012). These findings have important implications for the calculation of ejection fraction (EF) from M-mode measurements.</p><p>In 16 patients with left ventricular hypertrophy because of hypertension or hypertrophic cardiomyopathy, ejection fraction calculations were made by Teichholz' formula, by the equation EF 1'[ (%)=mitral ring motion (mm) x 5 and by Simpson .. s rule. Radionuclide angiography was used as , gold standard for ejection fraction. The study showed that in patients with hypertrophy Teichholz .. formula overestimates ejection fraction by 10% (6.7 EF%) (p--Q.002). Calculation by using mitral ring motion x 5 underestimates the ejection fraction by 19.3% ( 12.9 EF%) (p=0.002). Compared to healthy controls the hypertrophy group had 28.9% decreased mitral ring motion (p&lt;O.OOl), while there was no significant difference in short axis systolic diameter shortening.</p><p>Maximal longitudinal diastolic relaxation velocity was investigated in 22 patients on day 3-21 after first transmural myocardial infarction. The maximal diastolic slope was measured on the M-mode recording from the mitral ring motion. Compared to healthy controls the patients had significantly decreased relaxation velocity (p&lt;O.OOl), while there was no significant difference in the E/A ratio of inflow over the mitral valve by pulsed Doppler.</p>
  • Warner, Aina M. (författare)
  • Childhood asthma and indoor environment
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p><strong>Background</strong>:</p><p>During the last decades, the prevalence of asthma in childhood has increased in Sweden as well as in the rest of the western world. Some factor or factors in the indoor environment may be responsible for this. Asthma development and the precipitation of asthma symptoms is dependent on sensitivity to inhalation allergens, of which indoor allergens are of special interest because they are not seasonal. Other factors, such as humidity and inorganic compounds may have a direct effect on the development or the symptoms of asthma. This may be due to an enhancing effect on sensitivity.</p><p><strong>Aims</strong>:</p><p>To find relevant indoor factors for asthmatic children with perennial symptoms living in three climatic zones in Sweden. One part of the thesis was a study on the importance of known indoor allergens on the sensitivity and asthmatic symptoms, the other part aimed at finding new potential allergens that may explain the symtomatology.</p><p><strong>Patients and methods</strong>:</p><p>148 children from Helsingborg, Linköping and Umeå, representing three climatic zones in Sweden were enrolled in the project. They answered a questionnaire which recorded their medication and symptoms, computed to an asthma score, their indoor environment, allergic reactions to dust and animal contacts. Skin tests and blood tests were used to assess sensitivity to indoor allergens.</p><p>House dust samples from three locations in the house were analysed with ELISA for detection of indoor allergens (Der p 1, Der f 1, Der m 1, Fe/ d 1, Canf I, Per a !), and for microscopic identification and counting of mites and insects.</p><p>In 60 homes a thorough environmental investigation was done by specialised engineers, who judged the house structure, measured ventilation efficiency, humidity, volatile organical compounds and particles. Dust was collected for analysis of moulds, bacteria and endotoxin levels.</p><p><strong>Results</strong>: Serum IgE antibodies to inhalation allergens were found in 80 % of the children. Aoimal dander allergens dominated in terms of frequency of sensitivity (62%), followed by pollen (54%) and mites (35%). Sensitivity to mites was dominating only in the south, animal dander allergens dominated in the north. Sensitivity to animal dander, pollen and mites was associated to an elevated asthma score.</p><p>Aoimal dander allergens were found in all homes, even in homes without pets. Occasional visits by pets augmented the allergen levels.</p><p>Current level of exposure at home to house dust mites and storage mites was associated with sensitivity, even at low levels, in contrast to animal allergens at home. Mite allergen levels were usually highest in the bedroom samples, but in 115 of the homes the living-room samples had the highest levels in the home. Humid homes had higher mite allergen levels than dry and well ventilated homes. The use of mite allergens as environmental assays of mite may underestimate exposure levels, if all relevant allergens are not included, for example Der m I.</p><p>Other mites as well as insects are potential new allergen sources.</p><p><strong>Discussion and conclusion</strong>:</p><p>The home environment contains allergens from animal dander as well as mites and insects. Insufficient ventilation and excess humidity offers a milieu that enhances growth of mites, and has an effect on asthmatic symptoms in its own right. The outdoor climate has an influence on the indoor climate in the number and species of mites found, but in homes with hi!ih humidity mite allergens may reach very high levels also in regions where mites normally are not founs, such as the northern part. Indoor allergens are important for the sensitivity and symptoms of asthmatic children with perennial symptoms.</p>
  • Wei, Xiaochun (författare)
  • Maturation-dependent normal and injury-induced changes in rabbit knee articular cartilage
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Cartilage injuries are common in sports, and may on the long term develop to osteoarthritis. Prosthetic joint replacement is not satisfactory for young active individuals with extended cartilage injuries in large weight-bearing joints. In these cases, a treatment is needed which reestablishes normal joint surfaces by biologic means. Though different cartilage repair enhancing methods have been tried, up till now none of them has achieved regrowth of hyaline cartilage which duplicates the structure and functions of normal articular cartilage. More knowledge is needed to understand the response of articular cartilage to injury. Moreover, a better understanding of how articular cartilage develops may open ways to improve the repair response. The purpose of this work was to investigate maturation-related changes of articular cartilage during postnatal maturation, and to investigate the natural healing response to full-thickness cartilage injury as a function of maturation stage.</p><p>Physiologically, proteoglycan fragment concentrations in knee joint fluid decreased with maturation, and were inversely correlated with the maturation stage of the rabbits (r =- 0.69). The relatively high proteoglycan fragment concentrations in young animals might be the result of a higher turnover rate of proteoglycans in growing articular cartilage. The stiffness of articular cartilage in the rabbit knee joint decreased with maturation and was associated with an increase of subchondral bone volume fraction, and on the same time a substantial change in subchondral morphology. The results suggest that cartilage mechanics may also depend on the structural characteristics of subchondral bone.</p><p>Cartilage repair in young rabbits showed a faster filling of an osteochondral defect, and an earlier differentiation to hyaline-like cartilage than repairs in adult ones. The higher repair quality in young animals compared with the adults remained up to 48 weeks. Repairs in initially adolescent and adult animals showed furthermore signs of progressing degeneration between 12 and 48 weeks with decrease of the amount of hyaline-like cartilage in the tissue. However, irrespective of age, surface disruption of the repair was common, and no repair achieved regeneration to normal articular cartilage. The compressive stiffness of the repair tissues was always markedly softer compared with normal cartilage.</p><p>In preoperative joint fluid samples, TGF-ß1 decreased with maturation, and was moderately correlated with the proteoglycan fragment concentrations. Shortly after trauma, the concentrations of both substances were found increased, which was followed by a decrease up to 3 months, and then again an increase up to one year. However, meanwhile proteoglycan fragment concentrations had similar magnitude irrespective of age, TGF-ß1 concentrations never reached similarly high levels in adulthood as in infancy or adolescence. The cartilage adjacent to the defect had more signs for degeneration in younger rabbits. The similar patterns of TGF-ß1 and proteoglycan fragment concentrations during postnatal maturation may reflect the stimulatory effect of TGF-ß1 on proteoglycan synthesis. The higher TGF-ß1 concentrations in younger animals may be a reason for their better healing capacity, but also for their higher susceptibility to osteoarthritic change compared with the adult animals</p>
  • Wihlmark, Ulf (författare)
  • The effects of reactive oxygen species and lipofuscin on the function and health of the retinal pigment epithelium
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Age-related macular degeneration (ARJVID) is a common cause of central vision loss in elderly people. Specific treatment is possible only for selected patients. A dysfunction of the retinal pigment epithelial (RPE) cells has been proposed to help explain the pathogenesis of ARMD. In the normal turnover of photoreceptor outer segments (POS), membranes rich in polyunsaturated fatty acids (PUPAs) are shed and phagocytised by the RPE. PUFAs are highly susceptible to free radical damage, causing peroxidation and subsequent formation of products with fluorescence similar to Schiff bases, a component of lipofuscin. With increasing age, lipofuscin accumulates in the RPE cells, and it has been suggested that lipofuscin could be detrimental to RPE function through free radical generation or interference with the autophagocytic capacity of cells having lipofuscin-loaded lysosomes.</p><p>To study the effect of oxidative stress on lipofuscin accumulation, rabbit RPE cell cultures were kept at an ambient oxygen concentration of either 8 % or 40 %. To simulate the normal phagocytic function of RPE cells, bovine POS were added daily. The lipofuscin-specific autofluorescence was measured after 1, 2 and 3 weeks. RPE cells cultured under normobaric hyperoxic conditions (40 % oxygen) showed significantly higher levels of lipofuscin-like autofluorescence than those kept at nonnobaric and probably normooxic conditions (8 % oxygen) after 1, 2 as well as after 3 weeks. For both oxygen concentrations, the lipofuscin accumulation level was increased after 2 weeks of POS exposure and had increased even further after 3 weeks. The results suggest an involvement of oxidative mechanisms in the formation of lipofuscin from phagocytised POS by RPE cells.</p><p>In the second study, bovine POS were photo-oxidised, and turned into a lipofuscin-like material, by irradiation with UV light. Transmission electron microscopy of irradiated POS showed loss of the normal stacks of the disk membranes with conversion into an amorphous osmiophilic, electron dense mass. The formation of thiobarbituric acid reactive substances (TEARS), estimated during the irradiation process, indicated lipid peroxidation. The later decline in TEARS indicates fragmentation of the peroxides and conjugation offonned aldehydes with proteins under the formation of more stable Schiff bases and their secondary reaction products, e.g. lipofuscin. Irradiated POS also showed a strong granular yellow auto-fluorescence. RPE cell cultures, kept at 21 % ambient oxygen, were fed daily for 3, 5 or 7 days with either UVperoxidised POS, native POS or culture medium only. RPE cells fed irradiated POS showed significantly higher levels of lipofuscin-specific autofluorescence compared to cells exposed tonativePOS after 3 days, 5 days and 7 days and to the non-exposed control cells. The lipofuscin content of ce11s exposed to irradiated POS increased significantly between days 3 and 7. Ultrastructural studies showed much more numerous and larger lipofuscin-like inclusions in RPE cells fed irradiated POS compared to cells exposed to native POS. In the control cells, lipofuscin-like granules were small and sparse. It appears that exposing RPE cells to previously peroxidised POS, thus artificially converted into lipofuscin-like material and obviously not digestible by the lysosomal enzymes, accelerates the fonnation of severely lipofuscin-loaded cells.</p><p>A well-known physical property of lipofuscin is its yellowish autofluorescence when irradiated by blue light. Such energy transformation is known to induce photo-oxidative processes since oxygen present in the immediate surroundings would be activated into reactive oxygen metabolites. RPE cells are constantly exposed to visible light during the time the subject is awake. Consequently, in RPE cells exposed to light, the membranes of the lysosomes surrounding enclosed lipofuscin would be subjected to oxidative stress, which may result in damage, with leakage to the cytosol of lysosomal hydrolytic enzymes and ensuing cellular degeneration.</p><p>To test this hypothesis, cultures of heavily lipofuscin-loaded RPE cells were blue-lightirradiated and compared to relevant controls. Following irradiation, lysosomal membrane stability was measured by vital staining with the lysosomotropic weak base, and metachromatic fluorochrome, acridine orange (AO). Quantifying red (high AO concentration within intact lysosomes with preserved proton gradient over their membranes) and green fluorescence (low AO concentration in nuclei, damaged lysosomes with decreased or lost proton gradients, and in the cytosol) allowed an estimation of the lysosomal membrane stability. Cellular viability was estimated with the delayed trypan blue dye exclusion test. Lipofuscin loaded blue-lightexposed RPE cells showed a considerably enhanced loss of both lysosomal stability and viability when compared to control cells. It is concluded that the accumulation of lipofuscin within secondary lysosomes of RPE sensitizes these cells to blue light by inducing photo oxidative alterations of their lysosomal membranes resulting in a presumed leakage of lysosomal contents to the cytosol with ensuing cellular degeneration of apoptotic type.,</p><p>The aim of the last investigation was to study whether heavy loading with lipofuscin of RPE lysosomes would affect the further phagocytic ability of the cells.</p><p>In the first section of the investigation, cultures of rabbit RPE cells were exposed daily to bovine UV-irradiated POS for 4 weeks, resulting in a pronounced lipofuscin accumulation of the cells. Fluorescent latex beads (labelled with a red fluorophore) were added to unloaded control cultures at 0 and 4 weeks after their establishment, and to lipofuscin loaded cells after 4 weeks of feeding with artificial lipofuscin. Cellular amounts of lipofuscin, and their phagocytotic activity, were quantified by static fluorometry measuring lipofuscin-specific and red bead-specific fluorescence, respectively. Unloaded, and thus almost lipofuscin-free, control cells exposed to latex beads showed numerous cytoplasmic particles emitting reddish fluorescence, while few particles were taken up by cells initially loaded with artificial, POSderived, lipofuscin. Measurement of the latex bead-specific fluorescence showed significantly higher levels in unloaded control cells than in lipofuscin-loaded ones.</p><p>In the second part of the investigation, unloaded control cultures and lipofuscin-loaded cultures were exposed to native bovine Texas Red-X-labelled POS 4 weeks after the establishment of the cultures. Unloaded control cells showed a large number of cytoplasmic POS emitting reddish fluorescence, while fewer POS were fagocytosed by cells loaded with artificial lipofuscin. Measurement of the Texas Red-X-specific fluorescence, thus quantifying the fagocytic ability of the cells, showed significantly higher levels in control cells than in lipofuscin-loaded ones. Severe lipofuscin accumulation of RPE cells appears to result in a greatly decreased phagocytic capacity.</p><p>The suggested mechanisms may be of relevance in the pathogenesis of ARMD.</p>
  • Yang, Ping (författare)
  • Perinuclear Antineutrophil Cytoplasmic Antibodies in Inflammatory Bowel Disease
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>Antineutrophil cytoplasmic antibodies (ANCAs) are a group of autoantibodies which are specific for granulocyte antigens. By indirect immunofluorescence (llF) on ethanol-fixed neutrophils, ANCAs can be divided into two types: a cytoplasmic staining pattern (C-ANCA) or a perinuclear staining pattern (P-ANCA). Their pathogenic role and initiating stimuli are unknown.</p><p>This study analysed P-ANCA in monozygotic twins with inflammatory bowel disease. In ulcerative colitis (UC), P-ANCA occurred in 9 of 14 (64.3%) monozygotic twins and in 13 of 21 (61.9%) non-twin subjects, which was significantly different compared with healthy controls who were positive in three of 52 (5.8%) subjects (p&lt;O.OOOl). P-ANCA was found in two of 10 (20%) healthy twin siblings to twins with UC, which was not significantly different from the healthy controls (p=0.18). The results in Crohn's disease (CD) did not differ from healthy controls. This finding does not support the hypothesis that P-ANCA is a subclinical marker of genetic susceptibility to UC.</p><p>Seventy-six UC patients after proctocolectomy with ileal pouch-anal anastomosis (JP AA) including 28 patients who had had pouchitis and 48 patients who had not, were analysed regarding the correlation between P-ANCA and pouchitis. P-ANCA was found in 49n6 (64.5%) iu UC patients after the operation. Furthermore, we found that patients with recent (512 months) or ongoing pouchitis were all P-ANCA positive and pouchitis patients with higher P-ANCA titres were more prone to have frequent relapses.</p><p>To screen the occurrence of P-ANCA and detect the target antigen(s), 36 patients with UC, 37 patients with CD, 38 patients with collagenous colitis (CC) and 190 controls were studied. P-ANCA was found in a higher frequency in UC (23/36. 63.9%) than in CD (2/37. 5.4%). CC (4/38, 10.5%) or controls (4/190. 2.1 %). The antigens of P-ANCA were not found to be associated with reactivity to lactoferrin (L:f), !3-glucuronidase (j3- Glc), myeloperoxidase (M:PO) or proteinase 3 (PR3).</p><p>ANCAs were analysed by IIF on unfixed neutrophils or cells fixed by either ethanol, acetone or parafonnaldehyde in 21 sera from patients with UC, 17 sera from patients with vasculitides including 8 with PR3-positive C-ANCA and 9 with MPO-positive P-ANCA. Established ANCA patterns were most clear with ethanol-fixed neutrophils. The PR3-positive C-ANCA pattern was the same on unfixed or fixed cells irrespective of fixation method. However, the staining was brightest and the serum titres were higher with ethanol-fixed cells. Furthermore, we confirmed that the antigen of UC associated P-ANCA was better exposed on ethanol- than on acetone- or paraformaldehyde-fixed cells. In addition, anti-MPO positive sera tested on the very same day with freshly prepared paraformaldehyde-fixed neutrophils gave a C-ANCA pattern. Two or more days after preparation of the neutrophils anti-MPO-positive sera gave a mixed C- and P-ANCA pattern. Neutrophils kept unfixed for a few days or more and then treated with parafonnaldebyde gave a P-ANCA pattern, indicating diffusion of MPO from the azurophilic granules to the periphery of the nucleus, a process that is strongly enhanced by ethanol fixation.</p><p>Six anti-MPO-negative P-ANCA-positive sera from patients with UC, six antiMMPO-positive P-ANCA, five anti-PR3-positive C-ANCA and ten antinuclear antibody (ANA)-positive serum samples were tested with 15 different GramHnegative and Gram-positive bacterial strains. We found that soluble material from live E. coli and P. mirabilis has the capacity to decompose the anti. genic substrate of neutrophils responsible for both MPOpositive and MPO-negative P-ANCA. most probably brought about by enzymatic activity. Anti-PR3-positive CANCA was not affected which suggests substrate specificity of the proposed enzymatic activity.</p>
  • Yu, Guo (författare)
  • Polyunsaturated fatty acids in relation to childhood and maternal allergic diseases
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>The aim of this thesis was to study polyunsaturated fatty acid (PUPA) in relation to the appem11nce of anergic diseases in children and mothers in late pregnancy and during the lactation period and to the development of atopy in children, as well as the influence of maternal PUF A on their babies.</p><p>The levels of docosahexaenoic acid (DHA, C22:6n-3) and total n-3 long-chain polyunsaturated fatty acids (LCP) were lower (p = 0.01 and&lt; 0.05) and the ratio of total n-6 to n-3 LCP was higher (p &lt; 0.01) in serum phospholipids (PL) in 22 allergic school children than in 23 controls. The levels of docosapentaenoic acid (DPA, C22:5n-3) and the ratio of arachidonic acid (AA, C20:4n-6) to its precursor dihomo-y-linolenic acid (DHGLA, C20:3n-6) were also lower in 12 children with positive skin prick test (SPT), as compared to SPT negative children (both p &lt; 0.05). Higher levels of C20:2n-6 and lower EPA were recorded in allergic children with serum IgE above the median level (56kU/L), as compared to those with lower IgE levels,</p><p>The levels of DHGLA, eicosapentaenoic acid (EPA, C20:5n-3), DPA and DHA were all lower in milk total lipid (TL) obtained from atopic, as compared to non-atopic mothers after one month oflactation (all p &lt; 0.05). Similarly, the lower levels of DHGLA, AA, EPA, DPA and DHA were also observed in serum 1L of the atopic mothers at the time of delivery (all P &lt; 0.05), while the levels of a-linolenic acid and C20:2n-6 were higher. Several ratios of n-6 to n- 3 LCP in mature milk at 1 and 3 months were significantly higher in atopic than non-atopic mothers (all p &lt; 0.05). An n-3 fatty acid C20:4n-3 was present in human milk, but not in the blood samples of the mothers and children.</p><p>The levels of most of the individual PUFA con·elated well in blood of non-allergic children and in colostrum and mature milk of non-atopic mothers (r &gt; 0.5, p &lt; 0.01 as significant), but the correlations were largely absent in the atopic groups. Furthmore, a correlation between linoleic acid (LA, C18:2n-6) and AA levels was observed in serum samples of non-allergic (r = 0.64, p &lt; 0.001), but not allergic mothers at delivery (r = 0.25, p &gt; 0.05).</p><p>There were some correlations between AA and its precursor DHGLA and metabolite C22:4n-6 and between several n-3 and n-6 LCP, i.e. DPA and C22:4n-6, DHA and DHGLA and AA in semm phospholipids from cord blood of children without a family history of allergy (FHA) and who did not develop allergic diseases during the first 6 years of life. These relationships between the LCP levels were not seen in children with a FHA and in those who developed allergic diseases in later life. Furthermore, an abnormal PUF A composition in maternal blood and breast milk was related to the appearance of allergy in their children.</p><p>The LA levels correlated in 22 non-allergic mothers and their babies at the time of delivery (r = 0.53, p = 0.01). Furthermore, the serum levels of maternal DHGLA correlated with some LCP levels in cord serum of their babies, i.e. AA, C22:4 and DHA (all r= 0.65, p = 0.001). None of these relationships were observed in 25 allergic mothers and their babies.</p><p>The findings confirmed an abnormal PUF A composition in allergic children, in allergic mothers at the time of delivery and early lactation period and in newborn infants who developed allergic diseases during the first 6 years of life. The latter finding indicates that an abnormality of PUF A composition may be primary in allergic diseases. An impaired 0-6-desaturase activity in allergic diseases could not be confirmed, The presence of n-3 series fatty acid C20:4n-3 in human milk but not blood samples may contribute to the anti-inflammatory effect of human milk,</p>
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