The occurrence of clinically diagnosed and/or ruptured abdominal aortic aneurysms (AAAs) in the families of 220 patients with AAAs, treated at the Surgical Clinic, University Hospital of Umeå in the northern part of Sweden during the years 1965-82, was studied. A questionnaire concerning the blood relatives was answered by 87/89 patients. 16/87 patients (18%) had blood relatives with AAAs. In 14 families one blood relative was affected, and in 2 families two blood relatives were affected. First degree relatives were affected in 9/87 cases (10%), and second degree relatives in 7/87 cases (8%). 9/468 (1.9%) of the patients' brothers and sisters but only five of all their cousins had AAAs, and 7/204 (3.4%) of the dead brothers and sisters had died of ruptured AAAs. Concerning the patients who were not included in the letter survey at least 14/133had blood relatives with AAAs. However, the great majority of these patients were dead when the study was performed and could not be asked aboutthe occurrence of AAAs in their families. The patients with AAAs had significantly higher serum concentrations of triglyceride and (YLDL + LDL)-cholesterol and a significantly lower serum concentration of HDL-cholesterol than randomly selected healthy controls of the same sex and age as the patients. We also compared the distributions of genetic markers (HLA antigens, the blood group systems ABO, Rh, MNSs, P, Kell, Lewis and Duffy and the serum protein group systems haptoglobin, transferrin, group-specific component, complement C3, properdin factor and alpha-1-antitrypsin) in patients with AAAs with the distributions in controls and in some cases with the expected distributions according to the Hardy-Weinberg law. A significantly decreased frequency of Rh-negative individuals, and significantly increased frequencies of Kell-positi ve individuals, of MN heterozygotes and of heterozygotes concerning haptoglobin type was found. Furthermore, the aneurysm walls of patients with and without AAAs in the family were compared concerning the morphology, but no differences were found. We also studied the occurrence of collagen types I and III in the aneurysm walls, and the occurrence of vimentin and desmin in the smooth muscle cells of the aneurysm walls, but all these components were present in the aneurysm walls of both the patients with and those without AAAs in the family. To summarize the results, there seems to be an increased frequency of AAAs, and especially of ruptured AAAs, among the brothers and sisters of patients with AAAs. Elevated serum concentrations of triglyceride and (VLDL + LDL)- cholesterol and a lowered serum concentration of HDL-cholesterol seems to be common in patients with AAAs. There seems to be a hereditary predisposition to the development of AAAs, because we found associations with four different genetic markers (Rh, MN, Kell, haptoglobin group). However, there is probably no specific "familial" type of AAAs, because we found no differences between the patients with and those without AAAs in the family.Key words: / <p>S. 1-42: sammanfattning, s. 43-103: 5 uppsatser</p> / digitalisering@umu

No description available.

Brominated flame retardants (BFRs) have been used in a variety of consumer products to enhance their fire safety. This has resulted in exposure of the environment, wildlife and humans causing risks of endocrine disruption. The use restrictions of many BFRs have resulted in the introduction of other brominated chemicals (emerging BFRs) on the market. Humans are exposed to BFRs primarily via diet and dust ingestion, but the importance of the different exposure pathways has scarcely been studied. Children in particular have not been studied well due to lack of biomonitoring data. In this thesis, a mother-toddler cohort (n=24) from Uppsala was studied for their exposure to tri-decabrominated diphenyl ethers (tri-decaBDEs), isomer-specific hexabromocyclododecanes (HBCDs) and emerging BFRs (EBFRs). A clean-up and fractionation method was developed for determination of the above-mentioned BFRs in the same sample without dividing the sample. Measures of external exposure from dietary intake and dust ingestion were estimated. These were compared to internal concentrations (serum, feces) to determine which exposure pathways were most important for explaining the different BFR concentrations and patterns found in mothers and toddlers. Taking all the results into account, the toddlers’ higher serum levels of tetra-pentaBDEs seem to be the result of previous breastfeeding and those of octa-decaBDEs from exposure to house dust. For mothers, diet was estimated to be the main exposure route of tri-hexaBDEs and HBCDs. Dust ingestion was estimated to be the main route for BDE-209 exposure in mothers. Significant correlations were found between the tetra-decaBDE concentrations in matched serum and feces samples indicating that feces could be used as a non-invasive sample matrix for biomonitoring of PBDEs in toddlers. EBFRs were detected in the feces of toddlers and in a few serum samples from both mothers and toddlers indicating that exposure to these replacement chemicals occurs. / <p><strong> </strong>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Submitted. Paper 4: Manuscript.</p>

Statement of problem: We have shown that the C677T 5,10 methylenetetrahydrofolate reductase (MTHFR) variant is associated with elevated maternal serum α-fetoprotein (MSAFP), the most common screening test for neural tube defects (NTD). Therefore, past contradictory studies of NTDs and C677T MTHFR may have been biased because of changes in case populations after prenatal diagnosis and termination of pregnancy. Further, an unexplained elevation of MSAFP is known to increase the risk for later pregnancy complications. Is the C677T MTHFR variant a predisposing genetic variant for both NTDs and later complications of pregnancy? Methods: A retrospective study of women with pregnancies resulting in NTD outcome and women with unexplained elevations of MSAFP was undertaken. Women and their partners were genotyped for the C677T MTHFR allele. Couples with a pregnancy resulting in a NTD outcome were compared to couples whose pregnancy outcome did not involve. Couples with unexplained elevations of MSAFP who did and did not have later complications of pregnancy were also compared. Allele frequencies for all groups were then compared against the previously established Manitoba population allele frequency (based on 977 consecutive newborn metabolic screening bloodspots). A review of all studies of NTDs and association with the C677T MTHFR variant was undertaken to determine if the association between the variant and MSAFP is a source of bias. NTD incidence was examined before and after folic acid food fortification introduced in Canada in 1999. Results: There is an increase in the allele frequency of the C677T MTHFR variant in parents with an unexplained elevated MSAFP followed by later complications of pregnancy. The C677T MTHFR variant is also a contributing genetic factor to NTDs worldwide. The incidence of NTDs in Manitoba has decreased by 37% since food fortification with folic acid was introduced. Conclusions: The C677T MTHFR variant is a contributing genetic factor to both later complications of pregnancy after an unexplained elevation of MSAFP and to NTDs. This variant is folate sensitive and folic acid fortification has reduced the incidence of NTDs.

Statement of problem: We have shown that the C677T 5,10 methylenetetrahydrofolate reductase (MTHFR) variant is associated with elevated maternal serum α-fetoprotein (MSAFP), the most common screening test for neural tube defects (NTD). Therefore, past contradictory studies of NTDs and C677T MTHFR may have been biased because of changes in case populations after prenatal diagnosis and termination of pregnancy. Further, an unexplained elevation of MSAFP is known to increase the risk for later pregnancy complications. Is the C677T MTHFR variant a predisposing genetic variant for both NTDs and later complications of pregnancy? Methods: A retrospective study of women with pregnancies resulting in NTD outcome and women with unexplained elevations of MSAFP was undertaken. Women and their partners were genotyped for the C677T MTHFR allele. Couples with a pregnancy resulting in a NTD outcome were compared to couples whose pregnancy outcome did not involve. Couples with unexplained elevations of MSAFP who did and did not have later complications of pregnancy were also compared. Allele frequencies for all groups were then compared against the previously established Manitoba population allele frequency (based on 977 consecutive newborn metabolic screening bloodspots). A review of all studies of NTDs and association with the C677T MTHFR variant was undertaken to determine if the association between the variant and MSAFP is a source of bias. NTD incidence was examined before and after folic acid food fortification introduced in Canada in 1999. Results: There is an increase in the allele frequency of the C677T MTHFR variant in parents with an unexplained elevated MSAFP followed by later complications of pregnancy. The C677T MTHFR variant is also a contributing genetic factor to NTDs worldwide. The incidence of NTDs in Manitoba has decreased by 37% since food fortification with folic acid was introduced. Conclusions: The C677T MTHFR variant is a contributing genetic factor to both later complications of pregnancy after an unexplained elevation of MSAFP and to NTDs. This variant is folate sensitive and folic acid fortification has reduced the incidence of NTDs.

Background: Contribution of dietary sources to vitamin D status is not clearly known. Some studies have shown that dietary intake of certain vitamin D rich foods had a significant positive influence on serum 25-hydroxyvitamin D [25(OH)D] concentrations, whereas other studies have shown no effect. Although sunlight exposure is a major source of circulating serum 25(OH)D, children and adolescents have been advised on the dangers of sun exposure. Diet may therefore be an important contributor of circulating serum 25(OH)D in absence of or reduced sunlight exposure. Objective: The aim of this study was to determine whether serum 25(OH)D concentrations were associated with any specific dietary patterns in US children and adolescents using assay-adjusted serum 25(OH)D data from National Health and Nutrition Examination Survey (NHANES) 2003-2004 and 2005-2006. Methods: Data from 2 cycles of the NHANES 2003-2004 and 2005-2006 for individuals aged 2 to ≤19 y, were used to study the association between dietary patterns and serum 25(OH)D. Dietary patterns were established using factor analysis based on food-frequency questionnaire data. Eigenvalues and Scree plot were used to derive 2 major principal factors. They were labeled as High Fat Low Vegetable (HFLV) and Prudent dietary patterns. Results: Serum 25(OH)D was significantly lower in HFLV dietary pattern group compared to Prudent dietary pattern group (25.1 vs 27.0 ng/mL; P=0.001). The highest serum 25(OH)D concentrations for all subjects were in the low-intake HFLV group or medium and high-intake Prudent groups (P=0.003 and P=0.012, respectively). In multivariate adjusted analysis, children with higher Prudent dietary contribution scores to overall diet showed a significant positive relation with serum 25(OH)D (β=62.01, P=0.016). When data were stratified by sex, a significant positive relation was observed in girls who consumed the Prudent diet (β=86.34, P=0.014) and a significant negative relation was observed in girls who consumed the HFLV diet (β=-84.32, P=0.022). Conclusion: Overall, serum 25(OH)D concentrations were associated with Prudent dietary pattern but not with HFLV dietary pattern in US children and adolescents. When stratified by sex, the relation between dietary patterns and serum 25(OH)D was confined to only girls. Children consuming HFLV pattern diet may benefit from vitamin D supplementation and sunlight exposure (outdoor activities), and should be encouraged to consume more vitamin D fortified foods.

Motivation The objective of the South African Avocado Growers Association (SAAGA) is to increase the demand of avocados by advertising, promoting and other means deemed fit by them. In order to promote and advertise a product, consumer research has to be done to determine the consumers' attitudes towards and beliefs concerning the product. These findings then need to be followed up by scientific studies, targeted at specific problems and target groups to yield scientific evidence. Little consumer research has been done on avocados and studies investigating the health effects of avocados are limited, with available literature only focussing on the cholesterol lowering effect of avocados. Objectives Firstly, the objective is to investigate the beliefs and attitudes of the South African consumer towards avocados and health; to determine whether gender, age group, race or living standard influence the consumers beliefs towards avocados. Secondly, the objective is to dispel the myth that avocados are fattening and should therefore be avoided in energy restricted diets; to examine the effects of avocados, a rich source of monounsaturated fatty acids, as part of an energy restricted diet on weight loss, serum lipids, fibrinogen and vascular function in overweight and obese subjects. Methods Consumer study: One thousand nine hundred and ninety-seven South African individuals, randomly selected from metropolitan areas in South Africa, participated in this survey. Data were weighed to reflect the adult metropolitan population based on gender, age and race distribution. The total population (10 695 000) was representative of both genders (5 423 000 men and 5 272 000 women) and major race groups (2 615 000 whites, 6 252 000 blacks, 1 255 000 coloureds and 573 000 Indians) from different age groups and living standards. The questionnaires were designed by a multidisciplinary team and consisted of seventeen foodrelated questionnaires, of which one questioned the beliefs regarding avocados. Trained field workers administrated questionnaires by conducting face-to-face interviews with consumers. The market research company, MARKINOR, was contracted to collect the data. Quantitative data was statistically analysed in order to generate the relevant descriptive statistics, cross tabulations and statistical tests. SUMMARY Dietary intervention study: Sixty one free-living volunteers (13 men; 48 women), with a mean (standard deviation) body mass index (BMI) of 32 (3.9) kg/m2, participated in this randomised, controlled parallel study. The subjects were paired according to gender, BMI and age and randomly assigned to one of two groups. The experimental group consumed 200 g of avocado (1 avocado) per day, substituting 30 g of other mixed dietary fats, and the control group excluded avocado from their energy restricted diet for six weeks. Seven-day isoenergetic menu plans were given according to mean energy requirements of both genders to provide 30% fat, 55% carbohydrates and 15% protein of total energy intake. Anthropometric measurements, physical activity, dietary intakes, blood pressure and arterial compliance were measured with standard methods at the beginning and end of the intervention. Fasting blood samples were drawn at the beginning and end of the intervention period. Results Consumer study: There were no practical significant differences in the consumers responses in terms of gender or age. Practical significant differences were found between different race and LSM (Living Standard Measure) groups for some variables. The overall response of consumers towards the effect of avocados on health, heart health, children's health and the health effects associated with the fat content of avocados were very positive. However, almost half the consumers are still not convinced of or are uncertain as to the cholesterol content of avocados, while 47% of the consumers still believe that avocados are fattening. More than 80% of the consumers agreed that avocados are a good source of vitamins and minerals, and 76% consider avocados to be a good source of fibre. Almost 70% of the consumers agreed that avocados are good for sportsmen and -women. Avocados were seen by 49% of the consumers to be an aphrodisiac. Dietary intervention study: Fifty-five subjects completed the study. Compliance with avocado intake in the experimental group was 94.6%. Anthropometric measurements (weight, body mass index and percentage body fat) decreased significantly in both groups during the study (p<0.001), and the change was similar in both groups. Serum lipid levels (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides), fibrinogen, blood pressure and arterial compliance did not change significantly within or between the two groups. SUMMARY Conclusions Consumer study: There are still a few myths and misconceptions that exist among some consumers regarding avocados, especially with regard to sexual functioning, cholesterol content, and fattening effect of avocados. The agricultural industry can use these results to plan different marketing campaigns focused on certain target groups to change the misperceptions concerning avocados and convey the positive nutritional value of avocados. Dietary intervention study: The consumption of 200 g avocado per day, within an energy restricted diet, does not compromise weight loss when substituted for 30 g of mixed dietary fat. The serum lipid levels, plasma fibrinogen, arterial compliance, as well as systolic and diastolic blood pressure were not affected by weight loss or avocado intake. / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2004.

Background: Airway fibroblasts have become a critical addition to all facets of structural lung tissue changes such as in human asthma and chronic obstructive pulmonary disease, but little is known about their role in the equine recurrent airway obstruction, a disease that resembles to the human asthma. Since the equine bronchial fibroblasts (EBF) have not been isolated and characterized yet, the use of defined medium was investigated. Results: Primary EBF were cultured on non-collagen coated flasks without serum or in the presence of feta bovine serum (FBS) or horse serum (HS) or in serum depleted medium. EBF cultured in serum-free basal media and those serum deprived were not able to proliferate and even exhibited considerable cell death. In media containing FBS or HS, proliferation of the cells was reproducible between different primary cultures and cells demonstrated expression of vimentin. Large variations were found in the ability of FBS and HS to support growth and differentiation of EBF in monolayer culture. Indications of growth-promoting actions, increasing passage number as well as maintaining fibroblast morphology were found rather in FBS than in HS. EBF culturing in HS needed longer doubling and confluence time. The protein content of the cell pellets was higher in EBF cultured in medium containing HS than FBS. Alpha-smooth muscle actin seemed to be less expressed in EBF cultured in medium containing FBS than those in HS. Conclusions: In sum, serum addition to basal EBF medium enhanced EBF differentiation into myofibroblasts, and these findings are useful to develop in vitro fibroblast culture models that mimic in vivo physiological processes and to study airway disease mechanisms and remodeling.

Embryonic stem cells (ESCs) are derived from the inner cell mass (ICM) of the embryo that have great potential for regenerative therapies because of their ability to self-renew and differentiate into almost all cell types. However, this developmental potential is influenced by the local cellular microenvironment, including cell surface bound ligands. In this study, we synthesized an artificial stem cell niche wherein vascular endothelial growth factor A (VEGFA) was functionally immobilized in an agarose hydrogel. Immobilized VEGFA treatments were able to upregulate mesodermal markers, brachyury and VEGF receptor 2, by day 4 and were CD34+CD41+ by day seven. Subsequently, VEGFA immobilized treatments were able to generate colony forming cells by day fourteen. This work demonstrates our ability to use functionalized hydrogels to guide ESCs toward blood progenitor cells and serves as a useful tool to replicate aspects of the embryonic microenvironment.

Embryonic stem cells (ESCs) are derived from the inner cell mass (ICM) of the embryo that have great potential for regenerative therapies because of their ability to self-renew and differentiate into almost all cell types. However, this developmental potential is influenced by the local cellular microenvironment, including cell surface bound ligands. In this study, we synthesized an artificial stem cell niche wherein vascular endothelial growth factor A (VEGFA) was functionally immobilized in an agarose hydrogel. Immobilized VEGFA treatments were able to upregulate mesodermal markers, brachyury and VEGF receptor 2, by day 4 and were CD34+CD41+ by day seven. Subsequently, VEGFA immobilized treatments were able to generate colony forming cells by day fourteen. This work demonstrates our ability to use functionalized hydrogels to guide ESCs toward blood progenitor cells and serves as a useful tool to replicate aspects of the embryonic microenvironment.