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Sökning: hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Klinisk medicin) hsv:(Annan klinisk medicin) > Lantbruksvetenskap

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1.
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2.
  • Landberg, Rikard, 1981, et al. (författare)
  • New alkylresorcinol metabolites in spot urine as biomarkers of whole grain wheat and rye intake in a Swedish middle-aged population
  • 2018
  • Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 72:10, s. 1439-1446
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/objectives: Studies on the health effects of whole grains typically use self-reported intakes which are prone to large measurement errors. Dietary biomarkers that can provide an objective measure of intake are needed. New alkylresorcinol (AR) metabolites (3,5-dihydroxycinnamic acid (DHCA), 2-(3,5-dihydroxybenzamido)acetic acid (DHBA-glycine) and 5-(3,5-dihydroxyphenyl) pentanoic acid (DHPPTA)) in 24 h urine samples have been suggested as biomarkers for whole grain (WG) wheat and rye intake but remain to be evaluated in spot urine samples. Subjects/methods: The reproducibility of the new AR metabolites (DHCA, DHBA-glycine and DHPPTA) was investigated in 4 repeated samples over a period of 2 wk in spot urine from 40 Swedish men and women enroled in the SCAPIS-study, after adjustment of creatinine. Metabolite concentrations were correlated with total whole grain intake estimated during the same period. Results: The medium-term reproducibility determined for DHCA, DHPPTA and DHBA-glycine varied from moderate to excellent (intra-class correlation coefficient = 0.35–0.67). Moreover, DHCA and DHBA-glycine were independently associated with self-reported total WG intake (β = 0.18, P = 0.08 and β = 0.18, P = 0.02, respectively) and all metabolites except for DHPPA were higher among women. Conclusions: This study supports the idea of using AR metabolites in one or several spot urine samples as biomarkers of whole grain intake. These findings need to be confirmed in different populations.
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3.
  • Hilborn, Erik, 1988- (författare)
  • The role of the androgen receptor and hydroxysteroid 17β dehydrogenase in breast cancer : Impact on tamoxifen treatment
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The healthy breast is a tissue composed of centrally located milk producing glands connected to the nipple by ducts, surrounded by fat tissue and connective tissue. The growth of the breast is primarily mediated by the estrogens, while the androgens mediate tissue homeostasis and protect against growth signals. In breast cancer, the cells of the glands or ducts undergo malignant transformation, and start proliferating in an uncontrollable fashion. Breast cancer is the most common malignancy in women, and it is estimated that 10% of all women will be diagnosed with breast cancer during their life-time. The primary classification of breast cancer is based mainly on the expression of the estrogen receptor, and 70-80% of breast cancers are estrogen receptor positive, and are classified as luminal. The remaining breast cancers are classified into HER2 positive or triple negative breast cancer. Out of all breast cancers, ~80% are androgen receptor positive. This varies in different subtypes, however, with the highest expression in luminal and lowest expression in triple negative breast cancers. The role of androgen receptor varies depending on subtype. It is considered tissue-protective in luminal breast cancer, while it’s role in HER2 positive and triple negative breast cancers is less defined, but is generally considered to be associated with worse outcome. The primary treatment for breast cancer is surgery, followed by chemotherapy and/or radiotherapy to reduce the risk of recurrence. Treatment is also subtype specific, and luminal breast cancers in premenopausalwomen are treated using the estrogen receptor blocker (antagonist) tamoxifen, which blocks estrogen signaling. In postmenopausal women, luminal breast  cancers are treated using tamoxifen or aromatase inhibitors, which prevent the formation of estrogen. The knowledge of which patient will respond and who will develop treatment resistance is of great importance, and the development of markers which can be analyzed prior to treatment in order to reduce the risk of unwanted side effects or complications is the focus of a large body of research. One of the primary goals of this thesis was to establish biomarkers for prognosis and tamoxifen treatment in breast cancer, and paper I, paper II and paper III address this aim.Steroid hormones, including estrogens and androgens, are normally synthesized from cholesterol in the adrenal gland, as well as in gender specific tissues such as ovaries in women or the testis or prostate in men. This synthesis takes place as a number of enzymatic conversions, mediated by several different enzymes, and the expression of these enzymes determines the final product of this conversion. In the adrenal gland, testis and prostate, androgens are the end-product, while the ovaries synthesize estrogens. These hormones are transported through the circulation, and upon reaching their target tissues, they mediate their effect. The impact of the steroids on their destination tissue is dependent on their relative concentration and exposure time, which in turn is dependent on the amount in the circulation, but also on the presence of local steroid converting enzymes, which are present in most tissues. The enzymes of the hydroxysteroid 17β dehydrogenase family are present in most tissues, primarily the oxidative member hydroxysteroid 17β dehydrogenase type 2, which facilitate the conversion of estrogens and androgens to the less active forms, thus protecting the tissues from their effect. In breast cancer, the reductive form, hydroxysteroid 17β dehydrogenase type 1 is often up-regulated, and mediates increased activation of estrogens, resulting in increased estrogen signaling, which results in increased proliferation and growth. The second goal of this thesis was to further study the role of hydroxysteroid 17β dehydrogenase enzymes in breast cancer, and paper I and paper IV address different  aspects of their role in breast cancer.Following reduction of the expression of hydroxysteroid 17β dehydrogenase type 14, an oxidative member of the family, in breast cancer, the expression of C-X-C ligand 10 was found to be altered. In paper I, in order to determine the role of C-X-C ligand 10 and C-X-C receptor 3 in breast cancer, their expression was quantified using immunohistochemistry in breast cancer patients randomized to tamoxifen or no endocrine treatment irrespectively of estrogen receptor status. The expression of C-XC ligand 10 and C-X-C receptor 3 was found to be associated with increased tamoxifen treatment benefit in the estrogen receptor positive group of patients, indicating that they could be useful markers for determining which patient would respond well to this treatment. Further, C-X-C receptor 3 expression was associated with worse outcome in patients who did not receive tamoxifen, and could be a potential target for inhibitors in order to improve patient outcome. The role of the androgen receptor in breast cancer was evaluated. In paper II the expression was quantified using immunohistochemistry in the same cohort as in paper I. We show that in patients with estrogen receptor negative tumors, the androgen receptor is associated with worse outcome. In patients with high tumoral androgen receptor expression, tamoxifen signaling results in significant improvement in outcome, despite lack of the estrogen receptor. The opposite was observed in patients without tumoral androgen receptor expression, and tamoxifen treatment was associated with adverse outcome. Similar findings were made in the triple negative cases. In the luminal cases, the androgen receptor does not provide further information pertaining to outcome. In paper III we evaluated the role of mutations in the androgen receptor in the cohort of estrogen receptor-negative and androgen receptorpositive cases from paper II. The role of mutations in the androgen receptor appear to have a modest role in regard to patient outcome, but rs17302090 appear associated with tamoxifen treatment benefit. The modulation of the members of the hydroxysteroid 17β dehydrogenase in breast cancer is associated with changes in the local steroid balance, and has been associated with worse outcome and changes in the response to tamoxifen. Further, the inhibition of hydroxysteroid 17β dehydrogenase type 1 has been proposed as an alternate treatment for breast cancer, but no inhibitors are currently used in the clinic. In paper IV, we evaluated several different mechanisms by which the expression of hydroxysteroid 17β dehydrogenase type 1 and type 2 are modulated in breast cancer. We show that the most potent estrogen estradiol, in an estrogen receptor dependent fashion, can result in decreased hydroxysteroid 17β dehydrogenase type 1 expression, and a short term reduction in type 2 expression or long term increased type 2 expression. We also show that the most potent androgen, dihydrotestosterone, can increase hydroxysteroid 17β dehydrogenase type 2 expression, but has limited impact on hydroxysteroid 17β dehydrogenase type 1. Further, we show that a number of genes involved in breast cancer, and microRNA are involved in modulating the expression of the hydroxysteroid 17β dehydrogenase type 1 and type 2 in breast cancer. These findings could potentially be used as an alternative to inhibitors, and help modulate the steroidal balance in target tissue.
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4.
  • Mardinoglu, Adil, 1982, et al. (författare)
  • An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans
  • 2018
  • Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 27:3
  • Tidskriftsartikel (refereegranskat)abstract
    • A carbohydrate-restricted diet is a widely recommended intervention for non-alcoholic fatty liver disease (NAFLD), but a systematic perspective on the multiple benefits of this diet is lacking. Here, we performed a short-term intervention with an isocaloric low-carbohydrate diet with increased protein content in obese subjects with NAFLD and characterized the resulting alterations in metabolism and the gut microbiota using a multi-omics approach. We observed rapid and dramatic reductions of liver fat and other cardiometabolic risk factors paralleled by (1) marked decreases in hepatic de novo lipogenesis; (2) large increases in serum beta-hydroxybutyrate concentrations, reflecting increased mitochondrial beta-oxidation; and (3) rapid increases in folate-producing Streptococcus and serum folate concentrations. Liver transcriptomic analysis on biopsy samples from a second cohort revealed downregulation of the fatty acid synthesis pathway and upregulation of folate-mediated one-carbon metabolism and fatty acid oxidation pathways. Our results highlight the potential of exploring diet-microbiota interactions for treating NAFLD.
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5.
  • Ekman, Stina (författare)
  • Local Morphological Response of the Distal Femoral Articular–Epiphyseal Cartilage Complex of Young Foals to Surgical Stab Incision and Potential Relevance to Cartilage Injury and Repair in Children
  • 2013
  • Ingår i: Cartilage. - : SAGE Publications. - 1947-6035 .- 1947-6043. ; 4, s. 239-248
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Describe the local morphological response of the articular-epiphyseal cartilage complex to surgical stab incision in the distal femur of foals, with emphasis on the relationship between growth cartilage injury, enchondral ossification, and repair. Design: Nine foals were induced into general anesthesia at the age of 13 to 15 days. Four full-thickness stab incision defects were created in the cartilage on the lateral aspect of the lateral trochlear ridge of the left distal femur. Follow-up examination was carried out from 1 to 49 days postoperatively, including examination of intact bones, sawed slabs, and histological sections. Results: Incision defects filled with cells displaying fibroblast-, chondrocyte-, and osteoblast-like characteristics, potentially validating the rationale behind the drilling of stable juvenile osteochondritis dissecans lesions in children. Incisions induced necrosis within the cartilage on the margins at all depths of the defects. Sharp dissection may therefore be contraindicated in cartilage repair in young individuals. Incisions caused a focal delay in enchondral ossification in 2 foals, apparently related to the orientation of the incision defect relative to the direction of ossification. Defects became progressively surrounded by subchondral bone, in which granulation tissue containing clasts and foci of osteoblast-like cells was observed. Continued enchondral ossification was therefore likely to result in healing of uncomplicated defects to morphologically normal bone. Conclusions: Epiphyseal growth cartilage injury had the potential to exert a negative effect on enchondral ossification. Enchondral ossification exerted a beneficial effect on repair. This relationship warrants consideration in future studies of cartilage injury and repair within the articular-epiphyseal cartilage complex of all species.
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6.
  • Troell, Karin, et al. (författare)
  • Cryptosporidium parvum infections in a cohort of veterinary students in Sweden
  • 2015
  • Ingår i: Epidemiology and Infection. - 0950-2688 .- 1469-4409. ; 143, s. 2748-2756
  • Tidskriftsartikel (refereegranskat)abstract
    • In March 2013, a veterinary student tested positive for Cryptosporidium; four classmates reported similar gastrointestinal symptoms. We aimed to identify source(s) and risk factors for Cryptosporidium infection in university persons symptomatic between 21 January and 14 April 2013. Sixty-four (79%) students from a cohort of 81 fourth-year veterinary students completed questionnaires, identifying 13 cases; four were Cryptosporidium parvum GP60 subtype IIaA16G1R1b, two were IIdA24G1, seven did not submit stool samples. Thirteen cases attended the university's field clinic before symptom onset (13/37 attendees, 35%); 11 visited at least one of four farms where students recalled seeing calves with diarrhoea. C. parvum subtype IIaA16G1R1b was identified in calves at one of the farms. Entering pens of calves with diarrhoea [relative risk (RR) 7.6, 95% confidence interval (CI) 1.7-33.5] and eating in clinic cars (RR 9.1, 95% CI 1.3-65.8) were associated with being a case. Washing hands at least twice per farm visit (0 cases, P = 0.03) was protective. This outbreak investigation was notable for rapid and effective collaboration between public health, veterinary and environmental sectors, leading to swift identification of a microbiological and epidemiological link between cases, infected calves and their farms. We recommend frequent hand-washing using proper technique and dissuasion from eating in clinic cars to minimize possible exposure to contaminated surfaces.
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7.
  • Alminger, Marie, 1957, et al. (författare)
  • Whole-grain cereal products based on a high-fibre barley or oat genotype lower post-prandial glucose and insulin responses in healthy humans
  • 2008
  • Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 47:6, s. 294-300
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Several factors can affect glycemic and insulinemic responses from cereal foods. Some suggested factors lowering the responses are; intact botanical structure, high amylose/high β-glucan cereal varieties, organic acid produced during fermentation and food processes inducing retrogradation of starch. Aim of the study: To evaluate the impact of fermented whole grain cereal kernels with high content of amylose (40%) and/or β-glucan (4.6%) on postprandial glucose and insulin responses in healthy adults. Methods: Thirteen healthy volunteers (4 men and 9 women) were given 25 g available carbohydrate portions of: glucose solution; tempe fermented whole-grain barley and tempe fermented whole-grain oat. Blood samples were collected directly before the meal (fasting) and 15, 30, 45, 60, 90 and 120 min after the start of the meal. The GI (glycemic index) and II (insulin index) of meals were calculated for each subject according to FAO/WHO standards. Results: Peak glucose response was lowest after the tempe meal with high-amylose/ high-β-glucan barley tempe while insulin response was lowest after the meal with high β-glucan oat tempe. The mean blood glucose responses for both the barley and the oat tempe meals were significantly lower than from the reference glucose load (P < 0.0001) during the first 60 min. The calculated GI:s for barley and oat tempe were 30 and 63, respectively. Mean serum insulin responses from barley and oat tempe were significantly lower compared with the glucose load (P < 0.002) during the first 60 min, and the calculated II was lower for oat tempe (21) compared with barley tempe (55). Conclusions: The results suggest that cereal products with beneficial influence on postprandial plasma glucose and insulin responses can be tailored by fermentation and enclosure of high-amylose and/or high-β-glucan barley and oat kernels. © 2008 Spinger.
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8.
  • Boldemann, C., et al. (författare)
  • Preschool outdoor play environment may combine promotion of children's physical activity and sun protection. Further evidence from Southern Sweden and North Carolina
  • 2011
  • Ingår i: Science and Sports. - : Elsevier BV. - 0765-1597. ; 26:2, s. 72-82
  • Konferensbidrag (refereegranskat)abstract
    • Objective. - To study the impact of preschool outdoor environments on children's physical activity and solar ultraviolet (UV) exposure at different latitudes and countries. Methods. Outdoor environments of 11 preschools (two in Raleigh NC, USA, Lat.36 degrees N, nine in Malmo, Sweden, Lat.55 degrees N) were scored (OPEC) regarding space, vegetation, hilly terrain and level of integration between open spaces, vegetation and play structures. Free sky (%) was determined by imaging. Physical activity was measured by pedometers and solar UV-exposure by polysulphone dosimeters during 5 days in spring 2009, and individual background data gathered by questionnaires and anthropometric measurements. Global UV radiation was measured and available individual UV radiation (%) computed. Results. - In Malmo, mean step count/minute was 21.2 in preschools with high-scored environment vs. 17.6 in low-scored environments, and UV-exposure lower, 26% vs. 43% of available UV during outdoor stay. In Raleigh, step count/minute was 12.3 and UV-exposure of available UV 27% during outdoor stay. Conclusions. - Step count/minute was lower in Raleigh than in Malmo, but in Malmo children at low-scored environments ran a higher risk of sunburn than in Raleigh. Trees and shrubbery integrated in children's playscape trigger both physical activity and sun-protective behaviour in Sweden, and previous measurements in Stockholm were confirmed. Such outdoor environment should be recommended, but the role of season and climate needs to be further explored. (C) 2011 Elsevier Masson SAS. All rights reserved.
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9.
  • Jonsson, Karin, 1982, et al. (författare)
  • Rye and health - Where do we stand and where do we go?
  • 2018
  • Ingår i: Trends in Food Science and Technology. - : Elsevier BV. - 0924-2244 .- 1879-3053. ; 79, s. 78-87
  • Forskningsöversikt (refereegranskat)abstract
    • Background: High whole grain intake has consistently been associated with lowered risk of developing a number of chronic diseases. Among cereals, rye has highest content of dietary fiber, together with a wide variety of bioactive compounds. There is accumulating evidence from intervention studies of physiological effects of rye foods with potential health benefits. Scope and approach: This review summarizes the state of the art of rye and health and identifies future directions for research and innovation, based partly on findings presented at the international conference “The Power of Rye” Åland, Finland, 7–8 June 2017. Key findings and conclusions: Rye foods have well-established beneficial effects on insulin metabolism compared with wheat bread under isocaloric conditions and at standardized amounts of available carbohydrates, which may have positive implications for diabetes prevention. Recent findings suggest that alterations in blood glucose flux partly explain these effects. Moreover, several studies have shown beneficial effects of rye-based foods on satiety, which is one plausible mechanism behind recently demonstrated beneficial effects on weight management. Emerging results indicate beneficial effects of rye intake on inflammation and blood lipids. More research is needed to uncover underlying mechanisms for other demonstrated effects and the long-term implications for health. A challenge with rye-based foods is making them palatable and widely acceptable to consumers. Development of innovative and tasty rye products and targeted communication strategies is crucial in increasing awareness and consumption of rye foods. Novel results in this regard are presented in this review.
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10.
  • Lindstedt, Malin, et al. (författare)
  • Genomic and functional delineation of dendritic cells and memory T cells derived from grass pollen-allergic patients and healthy individuals.
  • 2005
  • Ingår i: International Immunology. - : Oxford University Press (OUP). - 1460-2377 .- 0953-8178. ; 17:4, s. 401-409
  • Tidskriftsartikel (refereegranskat)abstract
    • Dendritic cells (DCIs) possess a potent ability to modulate and activate specific T-cell responses to allergens, which play a pivotal role in allergic inflammation by secreting cytokines and other mediators. However, the molecular mechanisms by which allergen-challenged DCs regulate specific T-cell responses are still not well characterized. This study aims at elucidating the molecular mechanisms underlying the DC–T-cell interaction during an allergic immune response to grass pollen, using a genomic and functional approach. Transcriptional analysis was performed on grass allergen Phleum pratense-stimulated DCs and on autologous memory CD4+ T cells co-cultured with allergen-challenged DCs from healthy and allergic donors. DCs from the allergic donors were potent inducers of T-cell proliferation and Th2 polarization, as demonstrated by high IL-4, IL-5 and IL-13, and low IFN- production. A gradual up-regulation of activation markers on both DCs and T cells was evident during the co-culture period, demonstrating an educational element of the DC–T-cell interaction. The global transcriptional analysis revealed a differential gene regulation in DCs and T cells derived from allergic donors after stimulation with allergen, as compared with the healthy donors. Peripheral memory CD4+ T cells from healthy and allergic donors also responded differently after stimulation with allergen-loaded DCs with respect to cytokine production, proliferation, surface marker expression and gene transcription. We found up-regulated genes involved in Th2 cell biology, such as genes important for homing, adhesion, signaling and transcription, in addition to genes previously not described in the context of allergy. The panel of differentially expressed genes in the allergic group will form the basis for an increased understanding of the molecular mechanisms in allergy.
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