92 research outputs found
Glucokinase links Kruppel-like factor 6 to the regulation of hepatic insulin sensitivity in nonalcoholic fatty liver disease
No full textThe polymorphism, KLF6-IVS1-27A, in the Krüppel-like factor 6 (KLF6) transcription factor gene enhances its splicing into antagonistic isoforms and is associated with delayed histological progression of nonalcoholic fatty liver disease (NAFLD). To explore a potential role for KLF6 in the development of insulin resistance, central to NAFLD pathogenesis, we genotyped KLF6-IVS1-27 in healthy subjects and assayed fasting plasma glucose (FPG) and insulin sensitivities. Furthermore, we quantified messenger RNA (mRNA) expression of KLF6 and glucokinase (GCK), as an important mediator of insulin sensitivity, in human livers and in liver tissues derived from a murine Klf6 knockdown model (DeltaKlf6). Klf6 overexpression studies in a mouse hepatocyte line were utilized to mechanistically link KLF6 with Gck promoter activity. KLF6-IVS1-27Gwt (i.e., less KLF6 splicing) was associated with stepwise increases in FPG and insulin and reduced hepatic insulin sensitivity. KLF6 binds to the liver-specific Gck promoter and activates a GCK promoter-reporter, identifying GCK as a KLF6 direct transcriptional target. Accordingly, in DeltaKlf6 hepatocytes Gck expression was reduced and stable transfection of Klf6 led to up-regulation of Gck. GCK and KLF6 mRNAs correlate directly in human NAFLD tissues and immunohistochemistry studies confirm falling levels of both KLF6 and GCK in fat-laden hepatocytes. In contrast to full-length KLF6, splice variant KLF6-SV1 increases in NAFLD hepatocytes and inversely correlates with glucokinase regulatory protein, which negatively regulates GCK activity. Conclusion: KLF6 regulation of GCK contributes to the development of hepatic insulin resistance. The KLF6-IVS1-27A polymorphism, which generates more KLF6-SV1, combats this, lowering hepatic insulin resistance and blood glucose.Lars P. Bechmann, Amalia Gastaldelli, Diana Vetter, Gillian L. Patman, Laura Pascoe, Rebekka A. Hannivoort, Ursula E. Lee, Isabel Fiel, Ursula Muñoz, Demetrio Ciociaro, Young-Min Lee, Emma Buzzigoli, Luca Miele, Kei Y. Hui, Elisabetta Bugianesi, Alastair D. Burt, Christopher P. Day, Andrea Mari, Loranne Agius, Mark Walker, Scott L. Friedman, and Helen L. Reeve
Calibrating, rendering and evaluating the head mounted light field display
No full textThere are several benefits of using a light field display over a traditional HMD; in particular the light field can avoid the vergence-accommodation conflict and can also correct for near- and farsightedness. By rendering only four corner cameras of a subimage array, then these four views can be interpolated in order to create all subimages of the light field. We implement the interpolation of the subimages in the light field with the use of pixel reprojection, while maintaining correct perspective and shading. We give an comprehensive explanation of the construction and calibration of a head mounted light field display, and finally we evaluate the image quality through image difference and conduct a user evaluation of the light field images in order to evaluate if users are able to perceive a difference in the light field images created with the full array of virtual cameras and our method using four cameras and pixel reprojection. In most cases the users were unable to distinguish the images, and we conclude that pixel reprojection is a feasible method for rendering light fields as far as quality is concerned.</p
BoneBio: Breast cancer and bone biomarkers:Poster to abstract #24 BoneBio: The variable sensitivity of breast cancer patients to zoledronic acid
No full text#24 BoneBio: The variable sensitivity of breast cancer patients to zoledronic acid Presenting author: Anaïs Marie Julie Møller Presenting author's affiliation: Clinical Cell Biology, Department of Pathology, Odense University Hospital; Department of Clinical Research, University of Southern Denmark Authors: Møller, A. M. J. (1), Bechmann, T. (2), Madsen, J. M. (3), Jakobsen E. H. (2), Søe K. (4) Affiliations: 1: Clinical Cell Biology, Department of Pathology, Odense University Hospital; Department of Clinical Research,University of Southern Denmark 2: Department of Oncology, Vejle Hospital; Department of Oncology, Hospital of South West Jutland 3: Department of Clinical Immunology and Biochemistry, Vejle Hospital 4: Clinical Cell Biology, Department of Pathology, Odense University Hospital; Department of Clinical Research, University of Southern Denmark; OPEN – Open patient data Explorative Network Abstract: Introduction Breast cancer (BC) is the most prevalent cancer among women in Denmark. BC cells frequently metastasize to bone tissue, where they initiate a “vicious cycle” involving the bone resorbing osteoclasts. This results in local bone loss, increased fracture risk, resistance of cancer cells, a reduced quality of life, and survival. Questions Can bone biomarkers (CTX: degradation, PINP: formation) be used for diagnosis and monitoring? Can it detect those patients that are least sensitive to zoledronic acid? Materials and methods 50 BC patients with newly diagnosed bone metastases (80 years or younger). Primary variables: absolute and delta‐values of CTX and PINP, progression of bone disease, and death. Preliminary results Start of recruitment: May 2016 ‐ status: 49/50 pts. After 3 months of treatment with zoledronic acid the median CTX levels are decreased by 69% from baseline (p<0.0001) while median PINP levels are decreased by 62% (p=0.0008). But the percent change from baseline after 3 months of treatment varies from +170% to ‐90% for CTX and from +300% to ‐92% for PINP, indicating large variations in sensitivity to zoledronic acid among patients. In addition, our results indicate that the 9 patients that have died so far were all amongst the less sensitive. Finally, patients with clinical signs of progression in bone disease show elevated marker levels several months in advance. Conclusions Bone biomarkers CTX and PINP seem promising as a complementary tool for diagnosis and monitoring of BC patients with bone metastases. The trial is still ongoing and the last patient is expected to leave the trial in 1 to 3 years. We hope to determine thresholds for PINP and CTX that can be used to detect relapse in bone disease earlier than today. A future routine use of these markers may lead to new individualized treatment strategies improving quality of life and possibly survival
BoneBio: Breast cancer and bone biomarkers:Poster to abstract #24 BoneBio: The variable sensitivity of breast cancer patients to zoledronic acid
No full text#24 BoneBio: The variable sensitivity of breast cancer patients to zoledronic acid Presenting author: Anaïs Marie Julie Møller Presenting author's affiliation: Clinical Cell Biology, Department of Pathology, Odense University Hospital; Department of Clinical Research, University of Southern Denmark Authors: Møller, A. M. J. (1), Bechmann, T. (2), Madsen, J. M. (3), Jakobsen E. H. (2), Søe K. (4) Affiliations: 1: Clinical Cell Biology, Department of Pathology, Odense University Hospital; Department of Clinical Research,University of Southern Denmark 2: Department of Oncology, Vejle Hospital; Department of Oncology, Hospital of South West Jutland 3: Department of Clinical Immunology and Biochemistry, Vejle Hospital 4: Clinical Cell Biology, Department of Pathology, Odense University Hospital; Department of Clinical Research, University of Southern Denmark; OPEN – Open patient data Explorative Network Abstract: Introduction Breast cancer (BC) is the most prevalent cancer among women in Denmark. BC cells frequently metastasize to bone tissue, where they initiate a “vicious cycle” involving the bone resorbing osteoclasts. This results in local bone loss, increased fracture risk, resistance of cancer cells, a reduced quality of life, and survival. Questions Can bone biomarkers (CTX: degradation, PINP: formation) be used for diagnosis and monitoring? Can it detect those patients that are least sensitive to zoledronic acid? Materials and methods 50 BC patients with newly diagnosed bone metastases (80 years or younger). Primary variables: absolute and delta‐values of CTX and PINP, progression of bone disease, and death. Preliminary results Start of recruitment: May 2016 ‐ status: 49/50 pts. After 3 months of treatment with zoledronic acid the median CTX levels are decreased by 69% from baseline (p<0.0001) while median PINP levels are decreased by 62% (p=0.0008). But the percent change from baseline after 3 months of treatment varies from +170% to ‐90% for CTX and from +300% to ‐92% for PINP, indicating large variations in sensitivity to zoledronic acid among patients. In addition, our results indicate that the 9 patients that have died so far were all amongst the less sensitive. Finally, patients with clinical signs of progression in bone disease show elevated marker levels several months in advance. Conclusions Bone biomarkers CTX and PINP seem promising as a complementary tool for diagnosis and monitoring of BC patients with bone metastases. The trial is still ongoing and the last patient is expected to leave the trial in 1 to 3 years. We hope to determine thresholds for PINP and CTX that can be used to detect relapse in bone disease earlier than today. A future routine use of these markers may lead to new individualized treatment strategies improving quality of life and possibly survival
BoneBio: Breast cancer and bone biomarkers:Poster to abstract #24 BoneBio: The variable sensitivity of breast cancer patients to zoledronic acid
No full text#24 BoneBio: The variable sensitivity of breast cancer patients to zoledronic acid Presenting author: Anaïs Marie Julie Møller Presenting author's affiliation: Clinical Cell Biology, Department of Pathology, Odense University Hospital; Department of Clinical Research, University of Southern Denmark Authors: Møller, A. M. J. (1), Bechmann, T. (2), Madsen, J. M. (3), Jakobsen E. H. (2), Søe K. (4) Affiliations: 1: Clinical Cell Biology, Department of Pathology, Odense University Hospital; Department of Clinical Research,University of Southern Denmark 2: Department of Oncology, Vejle Hospital; Department of Oncology, Hospital of South West Jutland 3: Department of Clinical Immunology and Biochemistry, Vejle Hospital 4: Clinical Cell Biology, Department of Pathology, Odense University Hospital; Department of Clinical Research, University of Southern Denmark; OPEN – Open patient data Explorative Network Abstract: Introduction Breast cancer (BC) is the most prevalent cancer among women in Denmark. BC cells frequently metastasize to bone tissue, where they initiate a “vicious cycle” involving the bone resorbing osteoclasts. This results in local bone loss, increased fracture risk, resistance of cancer cells, a reduced quality of life, and survival. Questions Can bone biomarkers (CTX: degradation, PINP: formation) be used for diagnosis and monitoring? Can it detect those patients that are least sensitive to zoledronic acid? Materials and methods 50 BC patients with newly diagnosed bone metastases (80 years or younger). Primary variables: absolute and delta‐values of CTX and PINP, progression of bone disease, and death. Preliminary results Start of recruitment: May 2016 ‐ status: 49/50 pts. After 3 months of treatment with zoledronic acid the median CTX levels are decreased by 69% from baseline (p<0.0001) while median PINP levels are decreased by 62% (p=0.0008). But the percent change from baseline after 3 months of treatment varies from +170% to ‐90% for CTX and from +300% to ‐92% for PINP, indicating large variations in sensitivity to zoledronic acid among patients. In addition, our results indicate that the 9 patients that have died so far were all amongst the less sensitive. Finally, patients with clinical signs of progression in bone disease show elevated marker levels several months in advance. Conclusions Bone biomarkers CTX and PINP seem promising as a complementary tool for diagnosis and monitoring of BC patients with bone metastases. The trial is still ongoing and the last patient is expected to leave the trial in 1 to 3 years. We hope to determine thresholds for PINP and CTX that can be used to detect relapse in bone disease earlier than today. A future routine use of these markers may lead to new individualized treatment strategies improving quality of life and possibly survival
Evaluation and impact of different biomarkers for early detection of hepatocellular carcinoma
No full textWorldwide, hepatocellular carcinoma (HCC) is a frequent complication of liver diseases and remains a major cause of cancer-related mortality. In addition, the prevalence of nonalcoholic steatohepatitis (NASH) as prerequisite of hepatocarcinogenesis, even in the absence of cirrhosis, is rising rapidly. The early detection of HCC has been crucial in improving the survival outcomes of those patients. However, in the mostly obese NASH population, diagnostic sensitivity of ultrasound-based HCC screening approaches is limited. On the other hand, biomarkers for HCC show promising potential to improve early detection, providing reproducible, investigator-independent results that can be used either alone or integrated with other biomarkers for scoring models. In the past, validation has been limited due to a lack of prospective longitudinal cohort studies. At present, large-scale retrospective phase-III- biomarker- development gives hope for the availability of biomarker-based screening approaches in the near future. This review focuses on the potential impact of biomarkers on surveillance strategies, potentially allowing for earlier HCC diagnosis
Quantity and Quality of Basophil RNA Depend on the RNA Extraction Technique
No full textBasophils have been suggested to express low quantities of RNA, challenging the study of gene expression within these cells. However, the purification technique employed might have an impact on the quantity and quality of RNA purified from basophils. This chapter describes a method which gives an optimal RNA output using a TRIzol-based method in contrast to a commercial kit.</p
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