uu.seUppsala University Publications
Change search
Refine search result
1 - 14 of 14
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Barbu, Andreea
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Jansson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sandberg, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Quach, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Palm, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    The use of hydrogen gas clearance for blood flow measurements in single endogenous and transplanted pancreatic islets2015In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 97, p. 124-129Article in journal (Refereed)
    Abstract [en]

    The blood perfusion of pancreatic islets is regulated independently from that of the exocrine pancreas, and is of importance for multiple aspects of normal islet function, and probably also during impaired glucose tolerance. Single islet blood flow has been difficult to evaluate due to technical limitations. We therefore adapted a hydrogen gas washout technique using microelectrodes to allow such measurements. Platinum micro-electrodes monitored hydrogen gas clearance from individual endogenous and transplanted islets in the pancreas of male Lewis rats and in human and mouse islets implanted under the renal capsule of male athymic mice. Both in the rat endogenous pancreatic islets as well as in the intra-pancreatically transplanted islets, the vascular conductance and blood flow values displayed a highly heterogeneous distribution, varying by factors 6-10 within the same pancreas. The blood flow of human and mouse islet grafts transplanted in athymic mice was approximately 30% lower than that in the surrounding renal parenchyma. The present technique provides unique opportunities to study the islet vascular dysfunction seen after transplantation, but also allows for investigating the effects of genetic and environmental perturbations on islet blood flow at the single islet level in vivo. (C) 2014 The Authors. Published by Elsevier Inc.

  • 2.
    Biglarnia, Alireza
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Emanuelsson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Quach, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Clausen, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Schneider, Mårten K. J.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    The free radical scavenger S-PBN significantly prolongs DSG-mediated graft survival in experimental xenotransplantation2012In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 19, no 3, p. 166-176Article in journal (Refereed)
    Abstract [en]

    Background: Nitrones such as 2-sulfo-phenyl-N-tert-butyl nitrone (S-PBN) are known to trap and stabilize free radicals and to reduce inflammation. Recently, S-PBN was shown to reduce infiltration of T lymphocytes and the expression of adhesion molecules on the endothelium in experimental traumatic brain injury. We hypothesized that S-PBN could reduce infiltration of T lymphocytes during cell-mediated xenograft rejection and thereby increase graft survival. The concordant mouse-to-rat heart transplantation model was used to test the hypothesis. In this model, grafts undergo acute humoral xenograft rejection (AHXR) almost invariably on day 3 and succumb to cell-mediated rejection on approximately day 8 if AHXR is inhibited by treatment with 15-deoxyspergualin (DSG). Material and methods: Hearts from Naval Medical Research Institute (NMRI) mice were transplanted to the neck vessels of Lewis rats. Recipients were treated with S-PBN (n = 9), DSG (n = 9), S-PBN and DSG in combination (n = 10) or left untreated (n = 9) for survival studies. S-PBN was given daily intraperitoneally at a dose of 150 mg/kg body weight (BW) on day -1 to 30, and DSG was given daily intraperitoneally at a dose of 10 mg/kg BW on day -1 to 4 and 5 mg/kg BW on day 5 to 21. Nine additional recipients were given S-PBN only on days -1 and 0 in combination with continuous DSG treatment. Grafts were monitored until they stopped beating. Additional recipients were treated with S-PBN (n = 5), DSG (n = 5), S-PBN and DSG in combination (n = 6) or left untreated (n = 5) for morphological, immunohistochemical and flow cytometry analyses on days 2 and 6 after transplantation. Results: S-PBN treatment in combination with DSG resulted in increased median graft survival compared to DSG treatment alone (14 vs. 7 days; P = 0.019). Lower number of T lymphocytes on day 6 (P = 0.019) was observed by ex vivo propagation and flow cytometry when combining S-PBN with DSG, whereas immunohistochemical analyses demonstrated a significant reduction in the number of infiltrated CD4+, but not TCR+, cells. S-PBN treatment alone had no impact on graft survival compared to untreated rats (3 vs. 3 days). No differences were seen in ICAM-1 and VCAM-1 expression or in morphology between the groups. Conclusion: The combination of S-PBN and DSG treatment increases xenograft survival. The main effect of S-PBN appears to be in direct connection with the transplantation. Because of its low toxicity, S-PBN could become useful in combination with other immunosuppressants to reduce cell-mediated xenograft rejection.

  • 3.
    Chu, Xia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Gao, Xiang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Jansson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Quach, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Barbu, Andreea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Multiple Microvascular Alterations in Pancreatic Islets and Neuroendocrine Tumors of a Men1 Mouse Model2013In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 182, no 6, p. 2355-2367Article in journal (Refereed)
    Abstract [en]

    Vascular therapeutic targeting requires thorough evaluation of the mechanisms activated in the specific context of each particular tumor type. We highlight structural, molecular, and functional microvascular aberrations contributing to development and maintenance of pancreatic neuroendocrine tumors (NETs), with special reference to multiple endocrine neoplasia 1 (MEN1) syndrome, using a Men1 mouse model. Tissue samples were analyzed by immunofluorescence to detect vessel density and pericyte distribution within the endocrine pancreas; expression of angiogenic factors was assessed by immunohistochemistry and quantitative real-time PCR in isolated islets and adenomas cultured under normoxic or hypoxic conditions. The increased vascular density of pancreatic NETs developed in Men1 mice was paralleled by an early and extensive redistribution of pericytes within endocrine tissue. These morphological alterations are supported by, and in some cases preceded by, fine-tuned variations in expression of several angiogenic regulators and are further potentiated by hypoxia. By combining two novel ex vivo and in vivo single-islet and tumor perfusion techniques, we demonstrated that both vascular reactivity and blood perfusion of tumor arterioles are significantly altered in response to glucose and L-nitro-arginine methyl ester. Our findings unravel multiple potential molecular and physiological targets differentially activated in the endocrine pancreas of Men1 mice and highlight the need for in-depth functional studies to fully understand the contribution of each component to development of pancreatic NETs in MEN1 syndrome.

  • 4.
    Espes, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lau, J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Quach, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Ullsten, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Christoffersson, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. La Jolla Inst Allergy & Immunol, La Jolla, CA USA..
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rapid Restoration of Vascularity and Oxygenation in Mouse and Human Islets Transplanted to Omentum May Contribute to Their Superior Function Compared to Intraportally Transplanted Islets2016In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 16, no 11, p. 3246-3254Article in journal (Refereed)
    Abstract [en]

    Transplantation of islets into the liver confers several site-specific challenges, including a delayed vascularization and prevailing hypoxia. The greater omentum has in several experimental studies been suggested as an alternative implantation site for clinical use, but there has been no direct functional comparison to the liver. In this experimental study in mice, we characterized the engraftment of mouse and human islets in the omentum and compared engraftment and functional outcome with those in the intraportal site. The vascularization and innervation of the islets transplanted into the omentum were restored within the first month by paralleled ingrowth of capillaries and nerves. The hypoxic conditions in the islets early posttransplantation were transient and restricted to the first days. Newly formed blood vessels were fully functional, and the blood perfusion and oxygenation of the islets became similar to that of endogenous islets. Furthermore, islet grafts in the omentum showed at 1 month posttransplantation functional superiority to intraportally transplanted grafts. We conclude that in contrast to the liver the omentum provides excellent engraftment conditions for transplanted islets. Future studies in humans will be of great interest to investigate the capability of this site to also harbor larger grafts without interfering with islet functionality.

  • 5.
    Espes, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Lau, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Christoffersson, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Quach, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Restored Vascular Density and Blood Fow in Mouse and Human Islets Experimentally Transplanted to The Greater Omentum2013In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 96, no 6, p. S18-S18Article in journal (Other academic)
  • 6.
    Espes, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Lau, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Quach, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Banerjee, Uddyalok
    Ohio State Univ, William G Lowrie Dept Chem & Biomol Engn, Columbus, OH 43210 USA.
    Palmer, Andre F.
    Ohio State Univ, William G Lowrie Dept Chem & Biomol Engn, Columbus, OH 43210 USA.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Cotransplantation of Polymerized Hemoglobin Reduces β-Cell Hypoxia and Improves β-Cell Function in Intramuscular Islet Grafts2015In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 99, no 10, p. 2077-2082Article in journal (Refereed)
    Abstract [en]

    Background. Muscle is a promising alternative site for islet transplantation that facilitates rapid restoration of islet vascularization. However, the development of fibrosis suggests massive cellular death after transplantation. This study tested the hypothesis that islet graft function is limited by hypoxia-related death early after intramuscular transplantation, but that this can be overcome by cotransplantation of an oxygen carrier, that is, polymerized bovine hemoglobin (PolyHb). Methods. Two hundred islets were transplanted with or without different doses of PolyHb intramuscularly to nondiabetic C57BL/6 and diabetic C57BL/6 nu/nu mice. beta-cell hypoxia and apoptosis were evaluated by immunohistochemistry after injection of the biochemical marker pimonidazole or by staining for caspase-3, respectively. Blood glucose concentrations were monitored for 30 days after islet transplantation and animals were then subjected to an intravenous glucose tolerance test. Results. Substantial hypoxia was observed in control islet grafts during the first 4 days after transplantation. Cotransplantation of PolyHb resulted in a dose-dependent reduction of beta-cell hypoxia, but beta-cell apoptosis was only reduced by cotransplantation of low-dose PolyHb (0.03 mg/g body weight) due to the inflammatory effects of higher PolyHb concentrations. Cotransplantation of low-dose PolyHb resulted in improved islet graft function 30 days after transplantation in diabetic mice, with a glucose tolerance comparable to transplantation of 50% more islets. Conclusion. We conclude that cotransplantation of islets with PolyHb can be used to effectively bridge the critical hypoxic phase immediately after transplantation, improve islet graft function, and reduce the number of islets needed for successful intramuscular transplantation.

  • 7.
    Espes, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Lau, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Quach, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Christoffersson, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Restoration of Islet Vascularity and Oxygenation in Mouse and Human Islets Experimentally Transplanted to the Omentum: A Basis for Superior Function when Compared to Intraportally Transplanted Islets2016In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143Article in journal (Refereed)
  • 8.
    Espes, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Lau, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Quach, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Palmer, Andre F.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hypoxia in Islets After Intramuscular Transplantation can be Overcome by Co-Implantation of Polymerized Hemoglobin2013In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 96, no 6, p. S44-S44Article in journal (Other academic)
  • 9.
    Gao, Xiang
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sandberg, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Quach, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Bodin, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Jansson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Effects of Mn-DPDP and manganese chloride on hemodynamics and glucose tolerance in anesthetized rats2014In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 55, no 3, p. 328-334Article in journal (Refereed)
    Abstract [en]

    Background Previous studies have demonstrated that magnetic resonance imaging may be a method of choice to visualize transplanted pancreatic islets. However, contrast agents may interfere with microcirculation and affect graft function. Purpose To evaluate the effects manganese-containing contrast media on regional blood flow and glucose tolerance. Material and Methods Anesthetized rats were injected intravenously with MnCl2 (10 mu M/kg body weight) or Mn-DPDP (Teslascan; 5 mu M/kg body weight). Blood flow measurements were made with a microsphere technique 10min later. In separate animals vascular arteriolar reactivity in isolated, perfused islets was examined. Furthermore, an intraperitoneal glucose tolerance test was performed in separate rats. Results Glucose tolerance was unaffected by both agents. No changes in regional blood flow were seen after administration of Mn-DPDP, except for an increase in arterial liver blood flow. MnCl2 increased all blood flow values except that of the kidney. MnCl2, but not Mn-DPDP, caused a vasoconstriction in isolated rat islet arterioles but only at very high doses. Conclusion Mn-DPDP administration does not affect glucose tolerance or regional blood flow, besides an increase in arterial hepatic blood flow, and may therefore be suitable for visualization of islets.

  • 10.
    Jansson, Leif
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Barbu, Andreea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Bodin, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Drott, Carl Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Espes, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Gao, Xiang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Grapensparr, Liza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Kallskog, Örjan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Lau, Joey Börjesson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Liljebäck, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Palm, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Quach, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sandberg, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Strömberg, Victoria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Ullsten, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Pancreatic islet blood flow and its measurement2016In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 2, p. 81-95Article, review/survey (Refereed)
    Abstract [en]

    Pancreatic islets are richly vascularized, and islet blood vessels are uniquely adapted to maintain and support the internal milieu of the islets favoring normal endocrine function. Islet blood flow is normally very high compared with that to the exocrine pancreas and is autonomously regulated through complex interactions between the nervous system, metabolites from insulin secreting beta-cells, endothelium derived mediators, and hormones. The islet blood flow is normally coupled to the needs for insulin release and is usually disturbed during glucose intolerance and overt diabetes. The present review provides a brief background on islet vascular function and especially focuses on available techniques to measure islet blood perfusion. The gold standard for islet blood flow measurements in experimental animals is the microsphere technique, and its advantages and disadvantages will be discussed. In humans there are still no methods to measure islet blood flow selectively, but new developments in radiological techniques hold great hopes for the future.

  • 11.
    Johnsson, Cecilia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Quach, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Phenotyping of ex vivo propagated graft-infiltrating cells-a tool to monitor rejection in the early post-operative period2006In: Transplant Immunology, ISSN 0966-3274, E-ISSN 1878-5492, Vol. 16, no 2, p. 81-87Article in journal (Refereed)
    Abstract [en]

    Objective and fast methods to diagnose rejection after organ transplantation are needed. In the present study, the ex vivo propagation technique was evaluated for its ability to detect rejection at two different time-points after experimental heart transplantation.

    Syngeneic and allogeneic heterotopic heart transplantations were performed using inbred rat strains. After 6 or 15 days, cardiac graft biopsies were put in culture and infiltrating cells isolated by the ex vivo propagation technique. The isolated cells were counted and phenotyped by flow cytometry. In parallel, graft sections were analysed with regard to morphology and the presence of infiltrating cells as determined by immunohistochemical stainings.

    On day 15 after transplantation, the number of cells possible to isolate through ex vivo propagation reflected the morphological changes of the graft, i.e. considerably more cells were obtained from allogeneic transplants undergoing rejection (1052 +/- 205) than from allogeneic grafts under cyclosporine protection (513 +/- 135; p<0.05) or from syngeneic grafts (378 +/- 87; p<0.01).

    Six days after transplantation the allogeneic grafts were strongly rejected with massive cellular infiltration, still there was no difference between allogeneic and syngeneic grafts as to the number of ex vivo propagated cells. However, the proportion of IL-2-receptor expressing T lymphocytes was increased (15.4 +/- 1.8% vs. 9.5 +/- 1.4%; p < 0.05) and the CD4/CD8 ratio reduced (1.0 +/- 0.1 vs. 2.8 +/- 0.2; p < 0. 001) in the allogeneic group as compared with the syngeneic.

    We conclude that the ex vivo propagation technique can be used to distinguish rejection from non-rejection both early and later after transplantation, provided that not just cell counting but also phenotyping of the graft-infiltrating cells is performed.

  • 12.
    Liljebäck, Hanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Quach, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Lau, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Fewer Islets Survive from a First Transplant than a Second Transplant: Evaluation of Repeated Intraportal Islet Transplantation in Mice2019In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 28, no 11, p. 1455-1460Article in journal (Refereed)
    Abstract [en]

    Beta cell replacement is an exciting field where new beta cell sources and alternative sites are widely explored. The liver has been the implantation site of choice in the clinic since the advent of islet transplantation. However, in most cases, repeated islet transplantation is needed to achieve normoglycemia in diabetic recipients. This study aimed to investigate whether there are differences in islet survival and engraftment between a first and a second transplantation, performed 1 week apart, to the liver. C57BL/6 mice were accordingly transplanted twice with an initial infusion of syngeneic islets expressing green fluorescent protein (GFP). The second islet transplant was performed 1 week later and consisted of islets isolated from non-GFP C57BL/6-mice. Animals were sacrificed either 1 day or 1 month after the second transplantation. A control group received a saline infusion instead of GFP-expressing islets, 1 week later obtained a standard non-GFP islet transplant, and was subsequently sacrificed 1 month later. Islet engraftment in the liver was assessed by immunohistochemistry and serum was analyzed for angiogenic factors induced by the first islet transplantation. Almost 70% of islets found in the liver following repeated islet transplantation originated from the second transplantation. The vascular density in the transplanted non-GFP-expressing islets did not differ depending on whether their transplantation was preceded by a primary islet transplantation or saline administration only nor did angiogenic factors in serum prior to the transplantation of non-GFP islets differ between animals that had received a previous islet transplantation or a saline infusion. We conclude that first islet transplantation creates, by unknown mechanisms, favorable conditions for the survival of a second transplant to the liver.

  • 13.
    Medina, Anya
    et al.
    Lund Univ, Ctr Diabet, Clin Res Ctr, Skane Univ Hosp SUS, Jan Waldentromsgata 35, SE-20502 Malmo, Sweden..
    Parween, Saba
    Umea Univ, Umea Ctr Mol Med, Umea, Sweden..
    Ullsten, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Vishnu, Neelanjan
    Lund Univ, Ctr Diabet, Clin Res Ctr, Skane Univ Hosp SUS, Jan Waldentromsgata 35, SE-20502 Malmo, Sweden..
    Siu, Yuk Ting
    Lund Univ, Ctr Diabet, Clin Res Ctr, Skane Univ Hosp SUS, Jan Waldentromsgata 35, SE-20502 Malmo, Sweden..
    Quach, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Bennet, Hedvig
    Lund Univ, Ctr Diabet, Clin Res Ctr, Skane Univ Hosp SUS, Jan Waldentromsgata 35, SE-20502 Malmo, Sweden..
    Balhuizen, Alexander
    Lund Univ, Ctr Diabet, Clin Res Ctr, Skane Univ Hosp SUS, Jan Waldentromsgata 35, SE-20502 Malmo, Sweden..
    Åkesson, Lina
    Lund Univ, Ctr Diabet, Clin Res Ctr, Skane Univ Hosp SUS, Jan Waldentromsgata 35, SE-20502 Malmo, Sweden..
    Wierup, Nils
    Lund Univ, Ctr Diabet, Clin Res Ctr, Skane Univ Hosp SUS, Jan Waldentromsgata 35, SE-20502 Malmo, Sweden..
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Ahlgren, Ulf
    Umea Univ, Umea Ctr Mol Med, Umea, Sweden..
    Lernmark, Åke
    Lund Univ, Ctr Diabet, Clin Res Ctr, Skane Univ Hosp SUS, Jan Waldentromsgata 35, SE-20502 Malmo, Sweden..
    Fex, Malin
    Lund Univ, Ctr Diabet, Clin Res Ctr, Skane Univ Hosp SUS, Jan Waldentromsgata 35, SE-20502 Malmo, Sweden..
    Early deficits in insulin secretion, beta cell mass and islet blood perfusion precede onset of autoimmune type 1 diabetes in BioBreeding rats2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, no 4, p. 896-905Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Genetic studies show coupling of genes affecting beta cell function to type 1 diabetes, but hitherto no studies on whether beta cell dysfunction could precede insulitis and clinical onset of type 1 diabetes are available. Methods We used 40-day-old BioBreeding (BB) DRLyp/Lyp rats (a model of spontaneous autoimmune type 1 diabetes) and diabetes-resistant DRLyp/+ and DR+/+ littermates (controls) to investigate beta cell function in vivo, and insulin and glucagon secretion in vitro. Beta cell mass was assessed by optical projection tomography (OPT) and morphometry. Additionally, measurements of intra-islet blood flow were performed using microsphere injections. We also assessed immune cell infiltration, cytokine expression in islets (by immunohistochemistry and qPCR), as well as islet Glut2 expression and ATP/ADP ratio to determine effects on glucose uptake and metabolism in beta cells. Results DRLyp/Lyp rats were normoglycaemic and without traces of immune cell infiltrates. However, IVGTTs revealed a significant decrease in the acute insulin response to glucose compared with control rats (1685.3 +/- 121.3 vs 633.3 +/- 148.7; p < 0.0001). In agreement, insulin secretion was severely perturbed in isolated islets, and both first- and second-phase insulin release were lowered compared with control rats, while glucagon secretion was similar in both groups. Interestingly, after 5-7 days of culture of islets from DRLyp/Lyp rats in normal media, glucose-stimulated insulin secretion (GSIS) was improved; although, a significant decrease in GSIS was still evident compared with islets from control rats at this time (7393.9 +/- 1593.7 vs 4416.8 +/- 1230.5 pg islet(-1) h(-1); p < 0.0001). Compared with controls, OPT of whole pancreas from DRLyp/Lyp rats revealed significant reductions in medium (4.1 x 10(9) +/- 9.5 x 10(7) vs 3.8 x 10(9) +/- 5.8 x 10(7) mu m(3); p = 0.044) and small sized islets (1.6 x 10(9) +/- 5.1 x 10(7) vs 1.4 x 10(9) +/- 4.5 x 10(7) mu m(3); p = 0.035). Finally, we found lower intra-islet blood perfusion in vivo (113.1 +/- 16.8 vs 76.9 +/- 11.8 mu l min(-1) [g pancreas](-1); p = 0.023) and alterations in the beta cell ATP/ADP ratio in DRLyp/Lyp rats vs control rats. Conclusions/interpretation The present study identifies a deterioration of beta cell function and mass, and intra-islet blood flow that precedes insulitis and diabetes development in animals prone to autoimmune type 1 diabetes. These underlying changes in islet function may be previously unrecognised factors of importance in type 1 diabetes development.

  • 14. Sun, Zuyue
    et al.
    Li, Xiujuan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
    Massena, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Kutschera, Simone
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
    Padhan, Narendra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
    Gualandi, Laura
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
    Sundvold-Gjerstad, Vibeke
    Gustafsson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Choy, Wing Wen
    Zang, Guangxiang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Quach, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Jansson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Phillipson, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Abid, Md Ruhul
    Spurkland, Anne
    Claesson-Welsh, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
    VEGFR2 induces c-Src signaling and vascular permeability in vivo via the adaptor protein TSAd2012In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 209, no 7, p. 1363-1377Article in journal (Refereed)
    Abstract [en]

    Regulation of vascular endothelial (VE) growth factor (VEGF)-induced permeability is critical in physiological and pathological processes. We show that tyrosine phosphorylation of VEGF receptor 2 (VEGFR2) at Y951 facilitates binding of VEGFR2 to the Rous sarcoma (Src) homology 2-domain of T cell-specific adaptor (TSAd), which in turn regulates VEGF-induced activation of the c-Src tyrosine kinase and vascular permeability. c-Src was activated in vivo and in vitro in a VEGF/TSAd-dependent manner, and was regulated via increased phosphorylation at pY418 and reduced phosphorylation at pY527. Tsad silencing blocked VEGF-induced c-Src activation, but did not affect pathways involving phospholipase C gamma, extracellular regulated kinase, and endothelial nitric oxide. VEGF-induced rearrangement of VE-cadherin-positive junctions in endothelial cells isolated from mouse lungs, or in mouse cremaster vessels, was dependent on TSAd expression, and TSAd formed a complex with VE-cadherin, VEGFR2, and c-Src at endothelial junctions. Vessels in tsad(-/-) mice showed undisturbed flow and pressure, but impaired VEGF-induced permeability, as measured by extravasation of Evans blue, dextran, and microspheres in the skin and the trachea. Histamine-induced extravasation was not affected by TSAd deficiency. We conclude that TSAd is required for VEGF-induced, c-Src-mediated regulation of endothelial cell junctions and for vascular permeability.

1 - 14 of 14
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf