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- Gifford, Aliya, et al.
(author)
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Canine body composition quantification using 3 tesla fat–water MRI
- 2014
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In: Journal of Magnetic Resonance Imaging. - : Wiley. - 1053-1807 .- 1522-2586. ; 39:2, s. 485-491
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Journal article (peer-reviewed)abstract
- PurposeTo test the hypothesis that a whole-body fat–water MRI (FWMRI) protocol acquired at 3 Tesla combined with semi-automated image analysis techniques enables precise volume and mass quantification of adipose, lean, and bone tissue depots that agree with static scale mass and scale mass changes in the context of a longitudinal study of large-breed dogs placed on an obesogenic high-fat, high-fructose diet.Materials and MethodsSix healthy adult male dogs were scanned twice, at weeks 0 (baseline) and 4, of the dietary regiment. FWMRI-derived volumes of adipose tissue (total, visceral, and subcutaneous), lean tissue, and cortical bone were quantified using a semi-automated approach. Volumes were converted to masses using published tissue densities.ResultsFWMRI-derived total mass corresponds with scale mass with a concordance correlation coefficient of 0.931 (95% confidence interval = [0.813, 0.975]), and slope and intercept values of 1.12 and −2.23 kg, respectively. Visceral, subcutaneous and total adipose tissue masses increased significantly from weeks 0 to 4, while neither cortical bone nor lean tissue masses changed significantly. This is evidenced by a mean percent change of 70.2% for visceral, 67.0% for subcutaneous, and 67.1% for total adipose tissue.ConclusionFWMRI can precisely quantify and map body composition with respect to adipose, lean, and bone tissue depots. The described approach provides a valuable tool to examine the role of distinct tissue depots in an established animal model of human metabolic disease.
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- Bohl Kullberg, E, et al.
(author)
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Introductory experiments on ligand liposomes as delivery agents for boronneutron capture therapy
- 2003
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In: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 23:2, s. 461-467
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Journal article (peer-reviewed)abstract
- Liposomes are, when coupled to receptor ligands, candidates for receptor mediated delivery of boron for tumour therapy since they have capacity to deliver large amounts of boron per receptor interaction. With EGF-liposomes we present a pegylated ligand liposome delivery vehicle, containing water soluble boronated phenanthridine, WSP1, or water soluble boronated acridine, WSA1, for EGFR targeting. In the case of WSA1 a ligand dependent uptake was obtained and the boron uptake was as good as if free WSA1 was given. No ligand dependent boron uptake was seen for WSP1 containing liposomes. Thus, WSA1 is a candidate for further studies. Approximately 10(5) boron atoms were in each liposome. A critical assessment indicates that after optimization up to 10(6) boron atoms can be loaded. Since it is known that, for therapeutic effect, approximately 10(8)-10(9) boron atoms are needed in a single tumour cell it is realized that 10(2)-10(3) receptor interactions are needed to meet the demand. Tests applying cultured glioma cells indicate, without optimization of the delivery conditions, a boron uptake in the ppm range, which is necessary for successful BNCT. Thus, it seems possible to kill micro-invasive tumour cells with targeted liposomes if the delivery conditions are optimal.
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- Kullberg, Carin E.
(author)
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Long-term glycaemic control and complications in Type 1 diabetes
- 1995
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Doctoral thesis (other academic/artistic)abstract
- The impact of long-term glycaemic control, assessed by HbA1c measurements for five years or more, on diabetic retinopathy, nephropathy, and impaired vibration perception threshold was investigated in adult patients with Type 1 diabetes mellitus. Type 1 diabetes was defined as onset of diabetes before the age of 31, with insulin therapy introduced within 6 months from onset, and with no other known cause of insulin deficiency. A comparison of glycated haemoglobin values, as assessed in different long-term studies of the relationship between glycaemic control and diabetic complications was also made.High long-term mean HbA1c was shown to be strongly associated to development of proliferative retinopathy and nephropathy, and the severity of background retinopathy and impairment of vibration perception threshold in patients with 5-25 yr duration of diabetes. Patients who developed proliferative retinopathy had a long-tenn mean HbA1, of 8.9% (95% Cl 8.1-9.6%, nonnal range 3.5-5.5% HbA1,), and patients who developed nephropathy had a long-term mean HbA1c of &.8% (95% Cl 7 .8-9.9%) prior to the diagnosis of these complications. Patients with HbA1c >8% also had a relative risk of 6.3 (95% Cl 2.9l00% above the normal range, and no patient with HbA1c below 6.5% had> 100% elevated VPT.Low long-term HbA1c was a beneficial factor for avoidance of retinopathy, but was of less importance to prevent microalbuminuria after more than 20 yr of diabetes. No patient with long-term mean HbA1c above 7.3% avoided retinopathy for such a long period, while patients with normoalbuminuria had HbA1c values in the range 4.6-9.9%.Men tended to have more severe lesions than women, without a corresponding gender difference in glycaemic control. Elevated blood pressure was found to be associated with nephropathy, retinopathy, and impaired vibration perception threshold.In the comparison of glycated haemoglobin values from different long-term studies of glycaemic control and complications of diabetes, the differences between the highest and lowest results of the same sample were, on average 2% HbA1c. This difference is of the same magnitude as the reported difference in glycaemic control between intensified and regular treatment in interventional studies.In conclusion, long-term mean HbA,c is a strong predictor of diabetic complications in the individual patient. Standardisation of HbA1c methods, regular monitoring of HbA1c, and intervention aiming at avoidance of poor glycaemic control is therefore essential.
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| 20. |
- Kullberg, E, et al.
(author)
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Dental hygiene education for nursing staff
- 2009
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In: Geriatric nursing (New York, N.Y.). - : Elsevier BV. - 1528-3984 .- 0197-4572. ; 30:5, s. 329-333
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Journal article (peer-reviewed)
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| 22. |
- Kullberg, Joel, 1979-, et al.
(author)
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Automated analysis of liver fat, muscle and adipose tissue distribution from CT suitable for large-scale studies
- 2017
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Journal article (peer-reviewed)abstract
- Computed Tomography (CT) allows detailed studies of body composition and its association with metabolic and cardiovascular disease. The purpose of this work was to develop and validate automated and manual image processing techniques for detailed and efficient analysis of body composition from CT data. The study comprised 107 subjects examined in the Swedish CArdioPulmonary BioImage Study (SCAPIS) using a 3-slice CT protocol covering liver, abdomen, and thighs. Algorithms were developed for automated assessment of liver attenuation, visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue, thigh muscles, subcutaneous, subfascial (SFAT) and intermuscular adipose tissue. These were validated using manual reference measurements. SFAT was studied in selected subjects were the fascia lata could be visually identified (approx. 5%). In addition, precision of manual measurements of intra-(IPAT) and retroperitoneal adipose tissue (RPAT) and deep-and superficial SAT was evaluated using repeated measurements. Automated measurements correlated strongly to manual reference measurements. The SFAT depot showed the weakest correlation (r = 0.744). Automated VAT and SAT measurements were slightly, but significantly overestimated (<= 4.6%, p <= 0.001). Manual segmentation of abdominal sub-depots showed high repeatability (CV <= 8.1%, r >= 0.930). We conclude that the low dose CT-scanning and automated analysis makes the setup suitable for large-scale studies.
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| 23. |
- Käppi, Timo, 1975, et al.
(author)
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High frequency of concomitant food allergy development and autoantibody formation in children who have undergone liver transplantation
- 2019
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In: Transplantation. - 1534-6080. ; 103:11, s. 2338-2346
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Journal article (peer-reviewed)abstract
- Allergy and other immune-mediated diseases are more frequently reported in children who have undergone liver transplantation. Furthermore, autoantibodies are also prevalent, suggesting a state of immune dysregulation in these patients. Whether or not these processes occur simultaneously in the same individual has not been studied previously.A cohort of 43 children who had undergone liver transplantation for nonautoimmune liver disease at median age of 1.3 years was investigated for allergy and autoimmune disease. Sensitization to food and inhalant allergens was assessed and autoantibodies were measured.The prevalence of food allergy was 26% and that of respiratory allergy was 23%, while 33% and 26% of the subjects were sensitized to food and inhalant allergens, respectively. Autoimmune disease (i.e., autoimmune hepatitis) occurred in a single individual (2%), whereas autoantibodies were present in 44% of the children. Food allergy and autoantibodies occurred concomitantly in 19% of the children, which was almost twice the frequency expected by chance (11%, p=0.04). Respiratory allergy and the presence of autoantibodies were unrelated (12% concurrence vs the expected 10%, p = 0.73). In the logistic regression analysis, autoantibody formation was associated with discontinued immunosuppression and food allergy, with odds ratios of 13 (p=0.01) and 7.1 (p=0.03), respectively.In contrast to respiratory allergy, food allergy and autoantibody formation occurred together in the same children who underwent liver transplantation at a frequency higher than would be expected by chance. This may reflect an underlying immune dysregulation that impairs immune tolerance to both food allergens and autoantigens.
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| 25. |
- Pereira, Maria J., 1981-, et al.
(author)
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CDKN2C expression in adipose tissue is reduced in type II diabetes and central obesity: impact on adipocyte differentiation and lipid storage?
- 2022
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In: Translational Research. - : Elsevier BV. - 1931-5244 .- 1878-1810. ; 242, s. 105-121
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Journal article (peer-reviewed)abstract
- CDKN2C/p18 (Cyclin-Dependent Kinase Inhibitor 2C) is a cell growth regulator that controls cell cycle progression and has previously been associated with increased risk for type II diabetes (T2D) and reduced peripheral adipose tissue (AT) storage capacity. This study explored the role of CDKN2C in AT lipid and glucose metabolism in T2D. Expression of CDKN2C and other genes was analyzed by transcriptomics, or real-time PCR in subcutaneous AT (SAT) samples obtained from T2D and control subjects matched for sex, age and BMI and also in paired SAT and omental AT (OAT) samples. Functional studies included adipocyte glucose uptake and lipolysis rates. CRISPR/Cas9 CDKN2C gene knockdown was performed in human preadipocytes to assess adipogenesis. CDKN2C mRNA expression in SAT and OAT was reduced in T2D and obese subjects compared to controls. CDKN2C expression in SAT was inversely correlated with measures of hyperglycemia, insulin resistance and visceral adiposity and positively correlated with expression of genes in several metabolic pathways, including insulin signaling and fatty acid and carbohydrate metabolism. CDKN2C protein was mainly expressed in adipocytes compared to stromal vascular cells, and its gene and protein expression was up-regulated during adipocyte differentiation. Knockdown of CDKN2C did not affect the percentage of differentiating cells compared to wild type cultures. However, CDKN2C knockdown cultures had significantly lower expression of differentiation markers CEBPA, ADIPOQ and FASN and transiently reduced lipid accumulation per adipocyte during differentiation. Our findings suggest that adipose CDKN2C expression might be reduced as a consequence of insulin resistance and obesity, and this can further contribute to impairment of SAT lipid storage. © 2021 The Authors
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| 27. |
- Silver, Heidi J, et al.
(author)
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Comparison of Gross Body Fat-Water Magnetic Resonance Imaging at 3 Tesla to Dual-Energy X-Ray Absorptiometry in Obese Women
- 2013
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In: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 21:4, s. 765-774
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Journal article (peer-reviewed)abstract
- Improved understanding of how depot-specific adipose tissue mass predisposes to obesity-related comorbidities could yield new insights into the pathogenesis and treatment of obesity as well as metabolic benefits of weight loss. We hypothesized that three-dimensional (3D) contiguous "fat-water" MR imaging (FWMRI) covering the majority of a whole-body field of view (FOV) acquired at 3 Tesla (3T) and coupled with automated segmentation and quantification of amount, type, and distribution of adipose and lean soft tissue would show great promise in body composition methodology. Precision of adipose and lean soft tissue measurements in body and trunk regions were assessed for 3T FWMRI and compared to dual-energy X-ray absorptiometry (DXA). Anthropometric, FWMRI, and DXA measurements were obtained in 12 women with BMI 30-39.9 kg/m(2). Test-retest results found coefficients of variation (CV) for FWMRI that were all under 3%: gross body adipose tissue (GBAT) 0.80%, total trunk adipose tissue (TTAT) 2.08%, visceral adipose tissue (VAT) 2.62%, subcutaneous adipose tissue (SAT) 2.11%, gross body lean soft tissue (GBLST) 0.60%, and total trunk lean soft tissue (TTLST) 2.43%. Concordance correlation coefficients between FWMRI and DXA were 0.978, 0.802, 0.629, and 0.400 for GBAT, TTAT, GBLST, and TTLST, respectively. While Bland-Altman plots demonstrated agreement between FWMRI and DXA for GBAT and TTAT, a negative bias existed for GBLST and TTLST measurements. Differences may be explained by the FWMRI FOV length and potential for DXA to overestimate lean soft tissue. While more development is necessary, the described 3T FWMRI method combined with fully-automated segmentation is fast (<30-min total scan and post-processing time), noninvasive, repeatable, and cost-effective.
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| 29. |
- Titova, Olga E, et al.
(author)
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Dietary intake of eicosapentaenoic and docosahexaenoic acids is linked to gray matter volume and cognitive function in elderly
- 2013
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In: Age (Omaha). - : Springer Science and Business Media LLC. - 0161-9152 .- 1574-4647. ; 35:4, s. 1495-1505
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Journal article (peer-reviewed)abstract
- In the present study, we tested whether elderly with a high dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) would have higher cognitive test scores and greater brain volume than those with low dietary intake of these fatty acids. Data were obtained from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. The dietary intake of EPA and DHA was determined by a 7-day food protocol in 252 cognitively healthy elderly (122 females) at the age of 70 years. At age 75, participants' global cognitive function was examined, and their brain volumes were measured by magnetic resonance imaging (MRI). Three different multivariate linear regression models were applied to test our hypothesis: model A (adjusted for gender and age), model B (additionally controlled for lifestyle factors, e.g., education), and model C (further controlled for cardiometabolic factors, e.g., systolic blood pressure). We found that the self-reported 7-day dietary intake of EPA and DHA at the age of 70 years was positively associated with global gray matter volume (P < 0.05, except for model C) and increased global cognitive performance score (P < 0.05). However, no significant associations were observed between the dietary intake of EPA and DHA and global white matter, total brain volume, and regional gray matter, respectively. Further, no effects were observed when examining cognitively impaired (n = 27) elderly as separate analyses. These cross-sectional findings suggest that dietary intake of EPA and DHA may be linked to improved cognitive health in late life but must be confirmed in patient studies.
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| 30. |
- Titova, Olga E, et al.
(author)
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Mediterranean diet habits in older individuals : Associations with cognitive functioning and brain volumes
- 2013
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In: Experimental Gerontology. - : Elsevier BV. - 0531-5565 .- 1873-6815. ; 48:12, s. 1443-1448
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Journal article (peer-reviewed)abstract
- To examine the association between dietary habits, cognitive functioning and brain volumes in older individuals, data from 194 cognitively healthy individuals who participated in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort were used. At age 70, participants kept diaries of their food intake for 1week. These records were used to calculate a Mediterranean diet (MeDi) score (comprising dietary habits traditionally found in Mediterranean countries, e.g. high intake of fruits and low intake of meat), with higher scores indicating more pronounced MeDi-like dietary habits. Five years later, participants' cognitive capabilities were examined by the seven minute screening (7MS) (a cognitive test battery used by clinicians to screen for dementia), and their brain volumes were measured by volumetric magnetic resonance imaging. Multivariate linear regression analyses were constructed to examine the association between the total MeDi score and cognitive functioning and brain volumes. In addition, possible associations between MeDi's eight dietary features and cognitive functioning and brain volumes were investigated. From the eight dietary features included in the MeDi score, pertaining to a low consumption of meat and meat products was linked to a better performance on the 7MS test (P=0.001) and greater total brain volume (P=0.03), i.e. the sum of white and gray matter. Integrating all dietary features of MeDi into score did not explain additional variance. These observational findings suggest that keeping to a low meat intake could prove to be an impact-driven public health policy to support healthy cognitive aging, when confirmed by longitudinal studies. Further, they suggest that the MeDi score is a construct that may mask possible associations of single MeDi features with brain health domains in elderly populations.
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| 32. |
- Wahlund, CJE, et al.
(author)
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Sarcoidosis exosomes stimulate monocytes to produce pro-inflammatory cytokines and CCL2
- 2020
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 15328-
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Journal article (peer-reviewed)abstract
- Pulmonary sarcoidosis has unknown etiology, a difficult diagnostic procedure and no curative treatment. Extracellular vesicles including exosomes are nano-sized entities released from all cell types. Previous studies of exosomes from bronchoalveolar lavage fluid (BALF) of sarcoidosis patients have revealed pro-inflammatory components and abilities, but cell sources and mechanisms have not been identified. In the current study, we found that BALF exosomes from sarcoidosis patients, but not from healthy individuals, induced a dose-dependent elevation of intracellular IL-1β in monocytes. Analyses of supernatants showed that patient exosomes also induced release of IL-1β, IL-6 and TNF from both PBMCs and enriched monocytes, suggesting that the observed effect is direct on monocytes. The potently chemotactic chemokine CCL2 was induced by exosomes from a subgroup of patients, and in a blocking assay the exosome-induced CCL2 was reduced for 13 out of 19 patients by the asthma drug Montelukast, a cysteinyl leukotriene receptor antagonist. Further, reactive oxygen species generation by PBMCs was induced to a higher degree by patient exosomes compared to healthy exosomes. These findings add to an emerging picture of exosomes as mediators and disseminators of inflammation, and open for further investigations of the link between CCL2 and exosomal leukotrienes in sarcoidosis.
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