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  • 1. Abdel-Halim, S M
    et al.
    Ostenson, C-G
    Andersson, A
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Andersson, A
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Andersson, A
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Jansson, L
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Efendic, S
    A defective stimulus-secretion coupling rather than glucotoxicity mediates the impaired insulin secretion in the mildly diabetic F1 hybrids of GK-Wistar rats.1995Inngår i: Diabetes, Vol. 44, s. 1280-Artikkel i tidsskrift (Fagfellevurdert)
  • 2.
    Abels, M.
    et al.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Riva, M.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Poon, W.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Bennet, H.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Nagaraj, V.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Dyachok, Oleg
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Isomaa, B.
    Folkhalsan Res Ctr, Helsinki, Finland.;Dept Social Serv & Hlth Care, Jacobstad, Finland..
    Tuomi, T.
    Folkhalsan Res Ctr, Helsinki, Finland.;Dept Med, Helsinki, Finland..
    Ahren, B.
    Lund Univ, Ctr Diabet, Lund, Sweden..
    Tengholm, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Fex, M.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Renstrom, E.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Groop, L.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Lyssenko, V.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Wierup, N.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    CART is a novel glucose-dependent peptide with antidiabetic actions in humans2015Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr Suppl. 1, s. S279-S280Artikkel i tidsskrift (Annet vitenskapelig)
  • 3.
    Abels, Mia
    et al.
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Riva, Matteo
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Bennet, Hedvig
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Ahlqvist, Emma
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Dyachok, Oleg
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Nagaraj, Vini
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Shcherbina, Liliya
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Fred, Rikard G.
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Poon, Wenny
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Sorhede-Winzell, Maria
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Fadista, Joao
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Lindqvist, Andreas
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Kask, Lena
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Sathanoori, Ramasri
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Dekker-Nitert, Marloes
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Kuhar, Michael J.
    Emory Univ, Yerkes Res Ctr, Atlanta, GA 30322 USA..
    Ahren, Bo
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Wollheim, Claes B.
    Univ Med Ctr, Dept Cell Physiol & Metab, Geneva, Switzerland..
    Hansson, Ola
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Tengholm, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Fex, Malin
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Renström, Erik
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Groop, Leif
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Lyssenko, Valeriya
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden.;Steno Diabet Ctr AS, Gentofte, Denmark..
    Wierup, Nils
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden.;Lund Univ, Clin Res Ctr 91 12, Ctr Diabet, Skane Univ Hosp,Dept Clin Sci Malmo,Unit Neuroend, Jan Waldenstroms Gata 35, S-20502 Malmo, Sweden..
    CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion2016Inngår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, nr 9, s. 1928-1937Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims/hypothesis Insufficient insulin release and hyperglucagonaemia are culprits in type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART, encoded by Cartpt) affects islet hormone secretion and beta cell survival in vitro in rats, and Cart(-/-) mice have diminished insulin secretion. We aimed to test if CART is differentially regulated in human type 2 diabetic islets and if CART affects insulin and glucagon secretion in vitro in humans and in vivo in mice. Methods CART expression was assessed in human type 2 diabetic and non-diabetic control pancreases and rodent models of diabetes. Insulin and glucagon secretion was examined in isolated islets and in vivo in mice. Ca2+ oscillation patterns and exocytosis were studied in mouse islets. Results We report an important role of CART in human islet function and glucose homeostasis in mice. CART was found to be expressed in human alpha and beta cells and in a subpopulation of mouse beta cells. Notably, CART expression was several fold higher in islets of type 2 diabetic humans and rodents. CART increased insulin secretion in vivo in mice and in human and mouse islets. Furthermore, CART increased beta cell exocytosis, altered the glucose-induced Ca2+ signalling pattern in mouse islets from fast to slow oscillations and improved synchronisation of the oscillations between different islet regions. Finally, CART reduced glucagon secretion in human and mouse islets, as well as in vivo in mice via diminished alpha cell exocytosis. Conclusions/interpretation We conclude that CART is a regulator of glucose homeostasis and could play an important role in the pathophysiology of type 2 diabetes. Based on the ability of CART to increase insulin secretion and reduce glucagon secretion, CART-based agents could be a therapeutic modality in type 2 diabetes.

  • 4.
    Abrahamsson, Niclas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Lau Börjesson, Joey
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Wiklund, Urban
    Umea Univ, Biomed Engn, Dept Radiat Sci, Umea, Sweden.
    Karlsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Eriksson, Jan W.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Gastric bypass reduces symptoms and hormonal responses to hypoglycemia2016Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, nr 9, s. 2667-2675Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.

  • 5.
    Abshir, Hawa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Evaluating the Accuracy of Chloride Meters, The ChloroChek instrument in Sweat Testing for Cystic Fibrosis2023Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Background: Cystic fibrosis (CF) is a hereditary disorder caused by genetic mutations, which affect the chloride ion channels, leading to disrupted salt balance in different organs. A lack of properly functioning chloride ion channels can lead to formation of thick mucus, which hinders organ function, especially in the lungs where repeated inflammation occurs. Early diagnosis is critical to prevent further deterioration of the patient's condition. Current method of analysis of CF diagnostics uses conductivity meters to measure sweat electrolytes. However, current guidelines suggest using a chloridometer to directly measure chloride concentration, is the most reliable marker of cystic fibrosis. The aim of this project was to conduct a comprehensive evaluation of the new instrument's safety, reliability, validity, and conformity of the reference range to international chloride meter guidelines. Additional aims were to investigate the effect of storage conditions on sweat chloride concentration levels and examine the effect of increased salt intake on sweat test results. The study recruited healthy participants and took samples of their sweat by inducing sweat gland secretion. The chloride ion concentration was determined using a coulometric method.

    The results of the study found that the new method was reliable and matched international protocols. It also revealed that an increased salt consumption can impact chloride concentration in sweat, but not to an extent that it can affect medical decisions. Additionally, the study demonstrated that sweat samples can be frozen for up to two weeks without affecting the outcome of the chloride determination. 

    Fulltekst (pdf)
    fulltext
  • 6.
    Adam, Lina N.
    et al.
    Univ Zakho, Coll Sci, Dept Biol, Duhok, Kurdistan Regio, Iraq..
    Al-Habib, Omar A. M.
    Univ Nawroz, Coll Sci, Dept Biol, Duhok, Kurdistan Regio, Iraq..
    Oraha, Ashur Y.
    Univ Duhok, Coll Med, Dept Cardiothorac & Vasc Surg, Duhok, Kurdistan Regio, Iraq..
    Shekha, Mudhir S.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Salahaddin Univ Erbil, Coll Sci, Dept Biol, Erbil, Kurdistan Regio, Iraq..
    Genetic and clinical study of myeloperoxidase's association with coronary artery disease2024Inngår i: EGYPTIAN HEART JOURNAL, ISSN 1110-2608, Vol. 76, nr 1, artikkel-id 27Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BackgroundUnraveling myeloperoxidase's (MPO) correlation with coronary artery disease (CAD) and genetic variations, this study seeks to enhance diagnostic precision and therapeutic strategies.ResultsCAD patients were found to be older and more male than controls. Several clinical parameters, including glucose, total bilirubin, alkaline phosphatase, creatinine, and troponin levels, showed significant variations. Moreover, CAD patients had lower red cell distribution width (RDW%) and mean platelet volume (MPV) than controls. Serum MPO levels did not differ significantly between CAD patients and controls, and no correlation was found with other clinical parameters except for glucose, creatinine, and total bilirubin.ConclusionsThe data suggest that serum MPO levels are not substantially related to CAD patients, as indicated by lower MPO levels in CAD patients compared to controls. While highlighting the potential of MPV and RDW% as predictors of severe atherosclerosis in CAD. Further research is needed to validate the diagnostic and prognostic value of RDW%, MPV, and MPO levels in CAD.Trial registration: 15092021-9-12. Registered 15 September 2021.ConclusionsThe data suggest that serum MPO levels are not substantially related to CAD patients, as indicated by lower MPO levels in CAD patients compared to controls. While highlighting the potential of MPV and RDW% as predictors of severe atherosclerosis in CAD. Further research is needed to validate the diagnostic and prognostic value of RDW%, MPV, and MPO levels in CAD.Trial registration: 15092021-9-12. Registered 15 September 2021.

    Fulltekst (pdf)
    FULLTEXT01
  • 7.
    Adam, Lina N.
    et al.
    Univ Zakho, Fac Sci, Dept Biol, Duhok, Kurdistan, Iraq..
    Oraha, Ashur Y.
    Univ Duhok, Coll Med, Dept Cardiothorac & Vasc Surg, Duhok, Kurdistan, Iraq..
    Shekha, Mudhir S.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Salahaddin Univ Erbil, Coll Sci, Dept Biol, Erbil, Kurdistan, Iraq..
    Al-Habib, Omar A. M.
    Univ Nawroz, Coll Sci, Dept Biol, Duhok, Kurdistan, Iraq..
    Exploring nitric oxide as a crucial prognostic biomarker of coronary artery disease2023Inngår i: Prostaglandins & other lipid mediators, ISSN 1098-8823, E-ISSN 2212-196X, Vol. 165, artikkel-id 106717Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: The study aimed to examine if the polymorphism of the endothelial nitric oxide synthase (eNOS) gene variable number of tandem repeats (VNTR) and the serum NO levels are associated with CAD.

    Materials/methods: Case-control study, 70 CAD and 30 control subjects were enrolled. The eNOS gene poly-morphism was measured by polymerase chain reaction-agarose gel electrophoresis and the serum NO was assessed by using an ELISA plate and reader covering 540 nm.

    Results: Uncovering the area under curve (AUC) for serum NO, which was (0.6821), indicating that NO seemed to be a critical prognostic biomarker of CAD; also, glucose, serum creatinine and total bilirubin proved to be sig-nificant predictors of CAD with AUC (0.6793, 0.6717 and 0.6662) respectively. Furthermore, higher serum NO levels were associated with the eNOS (ab) genotype. Revealing the intron (a) allele was protective against CAD. Moreover, diminished levels of serum NO in CAD groups compared to controls (P < 0.05). Additionally, Multiple logistic regression analysis shows a significantly high Odds ratio associated with CAD in the Duhok population.

    Conclusions: The eNOS (ab) variant seems to be a protective CAD factor for patients. Low serum NO levels are another risk factor for the advancement of CAD, suggesting their involvement in atherosclerosis. The (a) allele's protective effect is mediated through changes in eNOS promoter activity and higher NO levels.

  • 8.
    Adler, Jeremy
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala Univ, Dept Immunol Genet & Pathol, BioVis, Uppsala, Sweden..
    Huang, Ainsley
    Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Med Biochem & Cell Biol, Gothenburg, Sweden..
    Parmryd, Ingela
    Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Med Biochem & Cell Biol, Gothenburg, Sweden..
    Find_plasma_membrane and measure_plasma_membrane: ImageJ macros for efficient identification of and measurements at and around the plasma membrane2023Inngår i: SoftwareX, E-ISSN 2352-7110, Vol. 24, artikkel-id 101570Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The plasma membrane that encloses cells is difficult to precisely delineate but this is often required for quantitation of fluorescence images. We have created an ImageJ macro that efficiently maps the plasma membrane based on a few imprecisely marked points as the user input, to generate a one-pixel-wide region of interest. A second macro makes measurements from the plasma membrane and optionally from additional regions of interest, offset both inwards and outwards from the plasma membrane. While we are interested in membrane order quantified by generalized polarization, any measurements from two or more channels could easily be implemented.

  • 9.
    Adler, Jeremy
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancer och vaskulärbiologi.
    Parmryd, Ingela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Colocalization Analysis in Fluorescence Microscopy2012Inngår i: Cell Imaging Techniques: Methods and Protocols / [ed] Taatjes, Douglas J. & Roth, Jürgen, New York: Humana Press, 2012, s. 97-109Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    The measurement of colocalization requires images of two fluorophores that are aligned, with no cross talk, and that the intensities remain within the response range of the microscope. Quantitation depends upon differentiating between the presence and absence of fluorescence, and measurements should be made within biologically relevant regions of interest. Co-occurrence can be measured simply by area or with the M1 and M2 coefficients, and should be compared to random distributions. Correlation analysis should use the Pearson and Spearman coefficients, which need to be measured by replicate based noise corrected correlation to eliminate errors arising from differences in image quality. Ideally, both co-occurrence and correlation should be reported.

    Fulltekst (pdf)
    fulltext
  • 10.
    Adler, Jeremy
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Cancer och vaskulärbiologi.
    Parmryd, Ingela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Quantification of Colocalisation; Co-Occurrence, Correlation, Empty Voxels, Regions of Interest and Thresholding2014Inngår i: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 106, nr 2, s. 602A-602AArtikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Measuring colocalisation is not straightforward with a plethora of coefficients that encapsulate different definitions. Measurements may also be implemented differently. Not only do measurements differ; interconversion is impossible making comparisons challenging. There is a need to cull coefficients and for clear definitions of what precisely is meant by colocalisation in individual studies. Colocalisation can be considered to have two components; co-occurrence which reports whether the fluorophores are found together and correlation which reports on the similarity in their patterns of intensity.

  • 11.
    Adler, Jeremy
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Parmryd, Ingela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Quantifying colocalization: thresholding, void voxels and the H-coef2014Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 9, nr 11, s. e111983-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A critical step in the analysis of images is identifying the area of interest e.g. nuclei. When the nuclei are brighter than the remainder of the image an intensity can be chosen to identify the nuclei. Intensity thresholding is complicated by variations in the intensity of individual nuclei and their intensity relative to their surroundings. To compensate thresholds can be based on local rather than global intensities. By testing local thresholding methods we found that the local mean performed poorly while the Phansalkar method and a new method based on identifying the local background were superior. A new colocalization coefficient, the Hcoef, highlights a number of controversial issues. (i) Are molecular interactions measurable (ii) whether to include voxels without fluorophores in calculations, and (iii) the meaning of negative correlations. Negative correlations can arise biologically (a) because the two fluorophores are in different places or (b) when high intensities of one fluorophore coincide with low intensities of a second. The cases are distinct and we argue that it is only relevant to measure correlation using pixels that contain both fluorophores and, when the fluorophores are in different places, to just report the lack of co-occurrence and omit these uninformative negative correlation. The Hcoef could report molecular interactions in a homogenous medium. But biology is not homogenous and distributions also reflect physico-chemical properties, targeted delivery and retention. The Hcoef actually measures a mix of correlation and co-occurrence, which makes its interpretation problematic and in the absence of a convincing demonstration we advise caution, favouring separate measurements of correlation and of co-occurrence.

    Fulltekst (pdf)
    fulltext
  • 12.
    Adler, Jeremy
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Sintorn, Ida-Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion.
    Strand, Robin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion.
    Parmryd, Ingela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Conventional analysis of movement on non-flat surfaces like the plasma membrane makes Brownian motion appear anomalous2019Inngår i: Communications Biology, E-ISSN 2399-3642, Vol. 2, artikkel-id 12Artikkel i tidsskrift (Fagfellevurdert)
  • 13.
    Adolfsson, Viktor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Optimization of immunohistochemistry staining of MDM2 and CDK4, to facilitate differential diagnostics of liposarcoma2023Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
  • 14.
    Ahl, David
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Eriksson, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Sedin, John
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Seignez, Cedric
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Schwan, Emil
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Kreuger, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Christoffersson, Gustaf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Phillipson, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Turning Up the Heat: Local Temperature Control During in vivo Imaging of Immune Cells2019Inngår i: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 10, artikkel-id 2036Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Intravital imaging is an invaluable tool for studying the expanding range of immune cell functions. Only in vivo can the complex and dynamic behavior of leukocytes and their interactions with their natural microenvironment be observed and quantified. While the capabilities of high-speed, high-resolution confocal and multiphoton microscopes are well-documented and steadily improving, other crucial hardware required for intravital imaging is often developed in-house and less commonly published in detail. In this report, we describe a low-cost, multipurpose, and tissue-stabilizing in vivo imaging platform that enables sensing and regulation of local tissue temperature. The effect of tissue temperature on local blood flow and leukocyte migration is demonstrated in muscle and skin. Two different models of vacuum windows are described in this report, however, the design of the vacuum window can easily be adapted to fit different organs and tissues.

    Fulltekst (pdf)
    FULLTEXT01
  • 15.
    Ahl, David
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Liu, Haoyu
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Schreiber, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Roos, S.
    Swedish Univ Agr Sci, Uppsala BioCtr, Dept Microbiol, Uppsala, Sweden..
    Phillipson, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Holm, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Lactobacillus reuteri increases mucus thickness and ameliorates dextran sulphate sodium-induced colitis in mice2016Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 217, nr 4, s. 300-310Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: The aim of this study was to investigate whether two Lactobacillus reuteri strains (rat-derived R2LC and human-derived ATCC PTA 4659 (4659)) could protect mice against colitis, as well as delineate the mechanisms behind this protection.

    Methods: Mice were given L.reuteri R2LC or 4659 by gavage once daily for 14days, and colitis was induced by addition of 3% DSS (dextran sulphate sodium) to drinking water for the last 7days of this period. The severity of disease was assessed through clinical observations, histological evaluation and ELISA measurements of myeloperoxidase (MPO) and pro-inflammatory cytokines from colonic samples. Mucus thickness was measured invivo with micropipettes, and tight junction protein expression was assessed using immunohistochemistry.

    Results: Colitis severity was significantly reduced by L.reuteri R2LC or 4659 when evaluated both clinically and histologically. The inflammation markers MPO, IL-1, IL-6 and mKC (mouse keratinocyte chemoattractant) were increased by DSS and significantly reduced by the L.reuteri strains. The firmly adherent mucus thickness was reduced by DSS, but significantly increased by L.reuteri in both control and DSS-treated mice. Expression of the tight junction proteins occludin and ZO-1 was significantly increased in the bottom of the colonic crypts by L.reuteri R2LC.

    Conclusion: These results demonstrate that each of the two different L. reuteri strains, one human-derived and one-rat-derived, protects against colitis in mice. Mechanisms behind this protection could at least partly be explained by the increased mucus thickness as well as a tightened epithelium in the stem cell area of the crypts.

  • 16.
    Ahl, David
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Roos, Stefan
    Phillipson, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Holm, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    CX3CR1 deficiency alters response to L-reuteri treatment of DSS-induced colitis in mice2014Inngår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 28, nr 1, artikkel-id 902.10Artikkel i tidsskrift (Annet vitenskapelig)
  • 17.
    Ahlen, K
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Berg, A
    Stiger, F
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Tengholm, A
    Institutionen för medicinsk cellbiologi.
    Siegbahn, A
    Institutionen för medicinska vetenskaper.
    Gylfe, E
    Institutionen för medicinsk cellbiologi.
    Reed, R.K.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Rubin, K
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Cell interactions with collagen matrices in vivo and in vitro depend on phosphatidylinositol 3-kinase and free cytoplasmic calcium1998Inngår i: Cell Adhesion and Communication, Vol. 5, s. 461-Artikkel i tidsskrift (Fagfellevurdert)
  • 18.
    Ahlström, Björn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Ing-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Strandberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    One-year functional recovery from severe Covid-19 is severely affected in the Swedish intensive care and hospital admitted working age cohortManuskript (preprint) (Annet vitenskapelig)
  • 19.
    Ahlström, Björn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning Dalarna.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Ing-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Strandberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    The swedish covid-19 intensive care cohort: Risk factors of ICU admission and ICU mortality2021Inngår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 65, nr 4, s. 525-533Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Several studies have recently addressed factors associated with severe Coronavirus disease 2019 (COVID-19); however, some medications and comorbidities have yet to be evaluated in a large matched cohort. We therefore explored the role of relevant comorbidities and medications in relation to the risk of intensive care unit (ICU) admission and mortality.

    Methods: All ICU COVID-19 patients in Sweden until 27 May 2020 were matched to population controls on age and gender to assess the risk of ICU admission. Cases were identified, comorbidities and medications were retrieved from high-quality registries. Three conditional logistic regression models were used for risk of ICU admission and three Cox proportional hazards models for risk of ICU mortality, one with comorbidities, one with medications and finally with both models combined, respectively.

    Results: We included 1981 patients and 7924 controls. Hypertension, type 2 diabetes mellitus, chronic renal failure, asthma, obesity, being a solid organ transplant recipient and immunosuppressant medications were independent risk factors of ICU admission and oral anticoagulants were protective. Stroke, asthma, chronic obstructive pulmonary disease and treatment with renin-angiotensin-aldosterone inhibitors (RAASi) were independent risk factors of ICU mortality in the pre-specified primary analyses; treatment with statins was protective. However, after adjusting for the use of continuous renal replacement therapy, RAASi were no longer an independent risk factor.

    Conclusion: In our cohort oral anticoagulants were protective of ICU admission and statins was protective of ICU death. Several comorbidities and ongoing RAASi treatment were independent risk factors of ICU admission and ICU mortality.

    Fulltekst (pdf)
    fulltext
  • 20.
    Ahlström, Björn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Falun Cent Hosp, Ctr Clin Res Dalarna, Reg Dalarna, Nissers V6g 3, S-79182 Falun, Sweden..
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Ing-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Strandberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård, Hedenstiernalaboratoriet.
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    A comparison of impact of comorbidities and demographics on 60-day mortality in ICU patients with COVID-19, sepsis and acute respiratory distress syndrome2022Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 12, artikkel-id 15703Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Severe Coronavirus disease 2019 (COVID-19) is associated with several pre-existing comorbidities and demographic factors. Similar factors are linked to critical sepsis and acute respiratory distress syndrome (ARDS). We hypothesized that age and comorbidities are more generically linked to critical illness mortality than a specific disease state. We used national databases to identify ICU patients and to retrieve comorbidities. The relative importance of risk factors for 60-day mortality was evaluated using the interaction with disease group (Sepsis, ARDS or COVID-19) in logistic regression models. We included 32,501 adult ICU patients. In the model on 60-day mortality in sepsis and COVID-19 there were significant interactions with disease group for age, sex and asthma. In the model on 60-day mortality in ARDS and COVID-19 significant interactions with cohort were found for acute disease severity, age and chronic renal failure. In conclusion, age and sex play particular roles in COVID-19 mortality during intensive care but the burden of comorbidity was similar between sepsis and COVID-19 and ARDS and COVID-19.

    Fulltekst (pdf)
    FULLTEXT01
  • 21.
    Ahmed, M
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Grapengiesser, E
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Ca2+ handling of rat pancreatic beta-cells exposed to ryanodine, caffeine,and glucagon.2002Inngår i: Endocrine, Vol. 17, s. 103-Artikkel i tidsskrift (Fagfellevurdert)
  • 22.
    Ahmed, M
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Grapengiesser, E
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Hellman, B
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Amino acid transformation of oscillatory Ca2+ signals in mouse pancreatic B-cells1999Inngår i: J Endocrinol, Vol. 160, s. 191195-Artikkel i tidsskrift (Fagfellevurdert)
  • 23.
    Ahmed, Meftun
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Oscillatory Ca2+ signaling in glucose-stimulated murine pancreatic b-cells.2001Inngår i: Acta Univ Upsal, Vol. 1064Annet (Annet vitenskapelig)
  • 24.
    Ahmed, Meftun
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Oscillatory Ca2+ signaling in glucose-stimulated murine pancreatic β-cells: Modulation by amino acids, glucagon, caffeine and ryanodine2001Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Oscillations in cytoplasmic Ca2+ concentration ([Ca2+]i) is the key signal in glucose-stimulated β-cells governing pulsatile insulin release. The glucose response of mouse β-cells is often manifested as slow oscillations and rapid transients of [Ca2+] i. In the present study, microfluorometric technique was used to evaluate the role of amino acids, glucagon, ryanodine and caffeine on the generation and maintenance of [Ca2+] i oscillations and transients in individual murine β-cells and isolated mouse pancreatic islets. The amino acids glycine, alanine and arginine, at around their physiological concentrations, transformed the glucose-induced slow oscillations of [Ca2+] i in isolated mouse β-cells into sustained elevation. Increased Ca2+ entry promoted the reappearance of the slow [Ca2+] i oscillations. The [Ca2+] i oscillations were more resistant to amino acid transformation in intact islets, supporting the idea that cellular interactions are important for maintaining the oscillatory activity. Individual rat β-cells responded to glucose stimulation with slow [Ca2+] i oscillations due to periodic entry of Ca2+ as well as with transients evoked by mobilization of intracellular stores. The [Ca2+] i oscillations in rat β-cells had a slightly lower frequency than those in mouse β-cells and were more easily transformed into sustained elevation in the presence of glucagon or caffeine. The transients of [Ca2+] i were more common in rat than in mouse β-cells and often appeared in synchrony also in cells lacking physical contact. Depolarization enhanced the generation of [Ca2+] i transients. In accordance with the idea that β-cells have functionally active ryanodine receptors, it was found that ryanodine sometimes restored oscillatory activity abolished by caffeine. However, the IP3 receptors are the major Ca2+ release channels both in β-cells from rats and mice. Single β-cells from ob/ob mice did not differ from those of lean controls with regard to frequency, amplitudes and half-widths of the slow [Ca2+] i oscillations. Nevertheless, there was an excessive firing of [Ca2+] i transients in the β-cells from the ob/ob mice, which was suppressed by leptin at close to physiological concentrations. The enhanced firing of [Ca2+] i transients in ob/ob mouse β-cells may be due to the absence of leptin and mediated by activation of the phospholipase C signaling pathway.

    Fulltekst (pdf)
    FULLTEXT01
  • 25.
    Ahmed, Meftun
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Bergsten, Peter
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Glucose-induced changes of multiple mouse islet proteins analysed by two-dimensional gel electrophoresis and mass spectrometry.2005Inngår i: Diabetologia, ISSN 0012-186X, Vol. 48, nr 3, s. 477-85Artikkel i tidsskrift (Fagfellevurdert)
  • 26.
    Ahmed, Meftun
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Forsberg, Jens
    Institutionen för medicinsk biokemi och mikrobiologi.
    Bergsten, Peter
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Protein profiling of human pancreatic islets by two-dimensional gel electrophoresis and mass spectrometry.2005Inngår i: J Proteome Res, ISSN 1535-3893, Vol. 4, nr 3, s. 931-40Artikkel i tidsskrift (Fagfellevurdert)
  • 27.
    Ahmed, Meftun
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Grapengiesser, Eva
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Pancreatic b-cells from obese-hyperglycemic mice are characterized by excessive firing of cytoplasmic Ca+ transients.2001Inngår i: Endocrine, Vol. 15Artikkel i tidsskrift (Fagfellevurdert)
  • 28.
    Ahooghalandari, Parvin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Hanke, Nina
    Thorpe, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Witte, Andreas
    Messinger, Josef
    Hellman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Mutations in Arg143 and Lys192 of the Human Mast Cell Chymase Markedly Affect the Activity of Five Potent Human Chymase Inhibitors2013Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 8, nr 6, s. e65988-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chymotrypsin-like serine proteases are found in high abundance in mast cell granules. By site-directed mutatgenesis, we have previously shown that basic amino acids in positions 143 and 192 (Arg and Lys respectively) of the human mast cell chymase are responsible for an acidic amino acid residue preference in the P2' position of substrates. In order to study the influence of these two residues in determining the specificity of chymase inhibitors, we have synthesized five different potent inhibitors of the human chymase. The inhibitory effects of these compounds were tested against the wild-type enzyme, against two single mutants Arg143Gln and Lys192Met and against a double mutant, Arg143Gln+Lys192Met. We observed a markedly reduced activity of all five inhibitors with the double mutant, indicating that these two basic residues are involved in conferring the specificity of these inhibitors. The single mutants showed an intermediate phenotype, with the strongest effect on the inhibitor by the mutation in Lys192. The Lys192 and the double mutations also affected the rate of cleavage of angiotensin I but did not seem to affect the specificity in the cleavage of the Tyr(4)-Ile(5) bond. A more detailed knowledge about which amino acids that confer the specificity of an enzyme can prove to be of major importance for development of highly specific inhibitors for the human chymase and other medically important enzymes.

    Fulltekst (pdf)
    fulltext
  • 29.
    Akdag, Ajda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    The association between oral tamoxifen treatment and cell differentiation in vaginal mucosa2022Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Introduction: Women diagnosed with estrogen-receptor-positive breast cancer are treated with antiestrogens, for example tamoxifen or aromatase inhibitor, to reduce the risk of the cancer spreading or recurring. A common side effect of antiestrogen treatment is vaginal atrophy symptoms such as vaginal dryness, itching, and pain, since estrogen is important in the regulation of cell proliferation as well as cell differentiation in the female genitalia. The aim of this project was to study the association between tamoxifen treatment and vaginal mucosal cell differentiation in women with estrogen-receptor-positive breast cancer to gain a better understanding of the possible effect of tamoxifen in the genital tract.

    Methods: In this study, vaginal biopsies from four different study groups were used: breast cancer patients treated with tamoxifen (n = 24), breast cancer patients with tamoxifen treatment plus vaginal estrogen (n = 8), control group consisting of healthy postmenopausal women without treatment (n = 37), or with vaginal estrogen (n = 29). Immunohistochemistry was used to study the staining intensity of the differentiation markers filaggrin and involucrin in the vaginal mucosa. 

    Results: The results of the study showed no significant differences between any of the study groups regarding the staining intensity of involucrin in the vaginal mucosa. Filaggrin results were excluded due to unreliable results.

    Conclusions: The results indicate that no negative association between tamoxifen treatment and cell differentiation in the vaginal mucosa could be observed, which may be due to the agonistic effects of tamoxifen on estrogen receptors in vaginal tissue. 

    Keywords: Antiestrogen treatment; Breast cancer; Estrogen receptor; Filaggrin; Involucrin.  

  • 30.
    Alehagen, Urban
    et al.
    Linköping Univ, Fac Hlth Sci, Dept Med & Hlth Sci, Div Cardiovasc Med, SE-58185 Linköping, Sweden..
    Shamoun, Levar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Dept Lab Med, Div Med Diagnost, SE-55305 Jönköping, Sweden..
    Dimberg, Jan Ingvar
    Jönköping Univ, Sch Hlth & Welf, Dept Nat Sci & Biomed, SE-55318 Jönköping, Sweden..
    Wågsäter, Dick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Increased mortality in the A/A genotype of the SNP rs28372698 of interleukin 322021Inngår i: Experimental and Therapeutic Medicine, ISSN 1792-0981, E-ISSN 1792-1015, Vol. 21, nr 2, artikkel-id 127Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    One of the major causes of mortality in the western hemisphere is cardiovascular disease. Therefore, a variety of markers to identify those at risk are required. Interleukin-32 (IL-32) is a cytokine that is associated with inflammation. The aim of the current study was to investigate variations in single nucleotide polymorphisms (SNPs) of IL-32 and plasma expression, and their associations with mortality. A population of 486 elderly community-living persons were evaluated. The participants were followed for 7.1 years and underwent a clinical examination and blood sampling. SNP analyses of IL-32 rs28372698 using allelic discrimination and plasma measurement of IL-32, using ELISA, were performed. During the follow-up period, 140 (28.8%) all-cause and 87 (17.9%) cardiovascular deaths were registered. No significant difference between mortality and plasma concentration of IL-32 was observed. The A/A genotype group exhibited significantly higher all-cause mortality (P=0.036), and an almost two-fold increased risk in a multivariate Cox regression model for all-cause and cardiovascular mortality. A highly significant difference in all-cause and cardiovascular mortality between the A/A and the T/T groups was demonstrated (P=0.015 resp. P=0.014). In the present study, the cytokine IL-32 was demonstrated to have prognostic information, with an increased risk of all-cause and cardiovascular mortality for those with the A/A genotype rs28372698 of IL-32. The A/A genotype could therefore be regarded as a possible biomarker for mortality risk that may be used to offer optimized cardiovascular patient handling in the future. However, the present study sample was small, and the results should be regarded as hypothesis-generating.

    Fulltekst (pdf)
    FULLTEXT01
  • 31.
    Alehagen, Urban
    et al.
    Linköping Univ, Fac Med, Dept Hlth Med & Caring Sci, Div Cardiovasc Med, SE-58185 Linköping, Sweden.
    Shamoun, Levar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Jönköping Cty, Div Med Diagnost, Dept Lab Med, SE-55305 Jönköping, Sweden.
    Wågsäter, Dick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Genetic variance and plasma concentration of CD93 is associated with cardiovascular mortality: Results from a 6.7-year follow-up of a healthy community-living elderly population2020Inngår i: Molecular Medicine Reports, ISSN 1791-2997, E-ISSN 1791-3004, Vol. 22, nr 6, s. 4629-4636Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Inflammation is one of the fundamental processes in numerous diseases. Cluster of differentiation (CD) 93, a glycoprotein, has been reported to be associated with a number of these diseases. There are reports indicating that a high plasma level of CD93 is associated with adverse events in ischaemic heart disease. Additionally, there are reports indicating different cardiovascular risks between different single nucleotide polymorphisms (SNPs) of CD93. Therefore, the present study aimed to determine whether the plasma concentration of CD93 and polymorphism of rs2749812 in CD93 were associated with clinical conditions and mortality in an elderly population. In 470 healthy elderly community-living individuals a novel clinical examination involving echocardiography and blood sampling was performed. The population was followed for 6.7 years. Plasma levels of CD93 and SNP analyses of rs2749812 of CD93 using PCR methodology were used. During the follow-up period, 106 (22.6%) all-cause and 61 (13.0%) cardiovascular deaths were registered. Those with the highest plasma concentration had markedly higher all-cause mortality. Evaluating the A/A, A/G and G/G genotypes, the G/G group exhibited significantly higher cardiovascular mortality (P=0.026), and an almost two-fold increased risk in a multivariate Cox regression model compared with the A/G genotype. Evaluation of subgroups with respect to sex, diabetes and hypertension revealed markedly increased cardiovascular risk in the G/G genotype in all subgroups. All results persisted in the multiple models used. In the present study, the glycoprotein CD93 was demonstrated to have prognostic cardiovascular information, with increased risk for those with a high plasma concentration. Furthermore, the G/G genotype of rs2749812 of CD93 has a significantly higher cardiovascular risk, as demonstrated here, and could therefore be regarded as a possible cardiovascular risk biomarker that might in the future be used to offer optimised cardiovascular patient handling. However, this was a small study, and more research is required.

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    FULLTEXT01
  • 32.
    Alehagen, Urban
    et al.
    Linköping Univ, Inst Med & Hlth Sci, Div Cardiovasc Med, Dept Med & Hlth Sci, Fac Hlth Sci, SE-58185 Linköping, Sweden.
    Shamoun, Levar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Jönköping Cty, Div Med Diagnost, Dept Lab Med, Jönköping, Sweden.
    Wågsäter, Dick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Increased cardiovascular mortality in females with the a/a genotype of the SNPs rs1478604 and rs2228262 of thrombospondin-12020Inngår i: BMC Medical Genetics, E-ISSN 1471-2350, Vol. 21, nr 1, artikkel-id 179Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Cardiovascular diseases are still the major cause of death in the Western world, with different outcomes between the two genders. Efforts to identify those at risk are therefore given priority in the handling of health resources. Thrombospondins (TSP) are extracellular matrix proteins associated with cardiovascular diseases. The aim of this study was to investigate variations in single nucleotide polymorphisms (SNPs) of TSP-1 and plasma expression, and associations with mortality from a gender perspective.

    Methods

    A population of 470 community-living persons were invited to participate. The participants were followed for 7.9 years and underwent a clinical examination and blood sampling. SNP analyses of TSP-1 rs1478604 and rs2228262 using allelic discrimination and plasma measurement of TSP-1 using ELISA were performed,

    Results

    During the follow-up period, 135 (28.7%) all-cause and 83 (17.7%) cardiovascular deaths were registered.

    In the female population, the A/A genotype of rs2228262 and the T/T genotype of rs1478604 exhibited significantly more cardiovascular deaths compared with the A/G and G/G, or the T/C and C/C genotypes amalgamated (rs2228262: 13.7% vs 2.0%; Χ2:5.29; P = 0.02; rs1478604:17.7% vs 4.7%; Χ2:9.50; P = 0.002). Applied in a risk evaluation, the A/A, or T/T genotypes exhibited an increased risk of cardiovascular mortality (rs2228262: HR: 7.1; 95%CI 1.11–45.8; P = 0.04; rs1478604: HR: 3.18; 95%CI 1.35–7.50; p = 0.008). No differences among the three genotypes could be seen in the male group.

    Conclusion

    In this study the female group having the A/A genotype of rs2228262, or the T/T genotype of rs1478604 of TSP-1 exhibited higher cardiovascular mortality after a follow-up of almost 8 years. No corresponding genotype differences could be found in the male group. Genotype evaluations should be considered as one of the options to identify individuals at risk. However, this study should be regarded as hypothesis-generating, and more research in the field is needed.

    Fulltekst (pdf)
    FULLTEXT01
  • 33.
    Alehagen, Urban
    et al.
    Linkoping Univ, Div Cardiovasc Med, Fac Med & Hlth Sci, SE-58185 Linkoping, Sweden.
    Wågsäter, Dick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Gender difference and genetic variance in lipoprotein receptor-related protein 1 is associated with mortality2019Inngår i: BIOMEDICAL REPORTS, ISSN 2049-9434, Vol. 11, nr 1, s. 3-10Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cardiovascular diseases are an important health resource problem and studies have shown a genetic association between single nucleotide polymorphisms (SNPs) and cardiovascular diseases. According to the literature, lipoprotein receptor-related protein 1 (LRP1) is associated with coronary artery disease. The aim of the present study was to evaluate a possible association between different genotypes of LRP1 and all-cause and cardiovascular mortality from a gender perspective. In the present study, 489 elderly community-living people were invited to participate. Clinical examination, echocardiography and blood sampling including SNP analyses of LRP1 (rs1466535) were performed, including the T/T, C/T and C/C genotypes, and the participants were followed for 6.7 years. During the follow-up period, 116 (24%) all-cause and 75 (15%) cardiovascular deaths were registered. In the female population, the LRP1 of the T/T or C/T genotype exhibited a 5.6-fold increased risk of cardiovascular mortality and a 2.8-fold increased risk of all-cause mortality compared with the C/C genotype. No such genotype differences could be seen in the male population. Gender differences could be seen regarding the risk of mortality in the different genotypes. Females with the LRP1 T/T or C/T genotypes exhibited a significantly increased risk of both all-cause and cardiovascular mortality compared with the C/C genotypes. Therefore, more individualized cardiovascular prevention and treatment should be prioritized. However, since this was a small study, the observations should only be regarded as hypothesis-generating.

    Fulltekst (pdf)
    FULLTEXT01
  • 34.
    Alenkvist, Ida
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Epac2 signaling at the β-cell plasma membrane2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Secretion of appropriate amounts of insulin from pancreatic β-cells is crucial for glucose homeostasis. The β-cells release insulin in response to glucose and other nutrients, hormones and neurotransmitters, which trigger intracellular signaling cascades, that result in exocytotic fusion of insulin-containing vesicles with the plasma membrane. Increases of the intracellular concentration of calcium ions ([Ca2+]i) trigger exocytosis, whereas the messenger cyclic adenosine monophosphate (cAMP) amplifies various steps of the secretion process. The protein Epac2 mediates some effects of cAMP, but little is known about its regulation in β-cells. In this study, the spatio-temporal dynamics of Epac2 was investigated in insulin-secreting MIN6-cells and primary β-cells using various cell signaling biosensors and live-cell fluorescence microscopy approaches. Increases in the cAMP concentration triggered translocation of Epac2 from the cytoplasm to the plasma membrane. Oscillations of cAMP induced by glucose and the insulin-releasing hormone GLP-1 were associated with cyclic translocation of Epac2. Analyses of Epac2 mutants showed that the high-affinity cyclic nucleotide-binding domain and Ras-association domains were crucial for the translocation, whereas neither the DEP domain, nor the low-affinity cAMP-binding domain were required for membrane binding. However, the latter domain targeted Epac2 to insulin granules at the plasma membrane, which promoted their priming for exocytosis. Depolarization-induced elevations of [Ca2+]i also stimulated Epac2 translocation, but the effects were complex and in the presence of high cAMP concentrations, [Ca2+]i increases often reduced membrane binding. The stimulatory effect of Ca2+ was mediated by increased Ras activity, while the inhibitory effect reflected reduced concentrations of the membrane phospholipid PtdIns(4,5)P2. Anti-diabetic drugs of the sulfonylurea class, suggested to directly activate Epac2, induced translocation indirectly by depolarizing β-cells to increase [Ca2+]i. Epac2 is an activator of Rap GTPases, and its translocation increased Rap activity at the plasma membrane. It is concluded that the subcellular localization of Epac2 is controlled by a complex interplay between cAMP, Ca2+ and PtdIns(4,5)P2 and that the protein controls insulin release by binding to the exocytosis machinery. These results provide new insights into the regulation of β-cell function and may facilitate the development of new anti-diabetic drugs that amplify insulin secretion.

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  • 35.
    Alenkvist, Ida
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Dyachok, Oleg
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Tian, Geng
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Li, Jia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Mehrabanfar, Saba
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Jin, Yang
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Birnir, Bryndis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Tengholm, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Welsh, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Absence of Shb impairs insulin secretion by elevated FAK activity in pancreatic islets2014Inngår i: Journal of Endocrinology, ISSN 0022-0795, E-ISSN 1479-6805, Vol. 223, nr 3, s. 267-275Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The Src homology-2 domain containing protein B (SHB) has previously been shown to function as a pleiotropic adapter protein, conveying signals from receptor tyrosine kinases to intracellular signaling intermediates. The overexpression of Shb in β-cells promotes β-cell proliferation by increased insulin receptor substrate (IRS) and focal adhesion kinase (FAK) activity, whereas Shb deficiency causes moderate glucose intolerance and impaired first-peak insulin secretion. Using an array of techniques, including live-cell imaging, patch-clamping, immunoblotting, and semi-quantitative PCR, we presently investigated the causes of the abnormal insulin secretory characteristics in Shb-knockout mice. Shb-knockout islets displayed an abnormal signaling signature with increased activities of FAK, IRS, and AKT. β-catenin protein expression was elevated and it showed increased nuclear localization. However, there were no major alterations in the gene expression of various proteins involved in the β-cell secretory machinery. Nor was Shb deficiency associated with changes in glucose-induced ATP generation or cytoplasmic Ca(2) (+) handling. In contrast, the glucose-induced rise in cAMP, known to be important for the insulin secretory response, was delayed in the Shb-knockout compared with WT control. Inhibition of FAK increased the submembrane cAMP concentration, implicating FAK activity in the regulation of insulin exocytosis. In conclusion, Shb deficiency causes a chronic increase in β-cell FAK activity that perturbs the normal insulin secretory characteristics of β-cells, suggesting multi-faceted effects of FAK on insulin secretion depending on the mechanism of FAK activation.

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    fulltext
  • 36.
    Alenkvist, Ida
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Gandasi, Nikhil R
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Barg, Sebastian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Tengholm, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Recruitment of Epac2A to Insulin Granule Docking Sites Regulates Priming for Exocytosis2017Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 66, nr 10, s. 2610-2622Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Epac is a cAMP-activated guanine nucleotide exchange factor that mediates cAMP signaling in various types of cells, including -cells, where it is involved in the control of insulin secretion. Upon activation, the protein redistributes to the plasma membrane, but the underlying molecular mechanisms and functional consequences are unclear. Using quantitative high-resolution microscopy, we found that cAMP elevation caused rapid binding of Epac2A to the -cell plasma membrane, where it accumulated specifically at secretory granules and rendered them more prone to undergo exocytosis. cAMP-dependent membrane binding required the high-affinity cyclic nucleotide-binding (CNB) and Ras association domains, but not the disheveled-Egl-10-pleckstrin domain. Although the N-terminal low-affinity CNB domain (CNB-A) was dispensable for the translocation to the membrane, it was critical for directing Epac2A to the granule sites. Epac1, which lacks the CNB-A domain, was recruited to the plasma membrane but did not accumulate at granules. We conclude that Epac2A controls secretory granule release by binding to the exocytosis machinery, an effect that is enhanced by prior cAMP-dependent accumulation of the protein at the plasma membrane.

  • 37.
    Alenkvist, Ida
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Gandasi, Nikhil R
    Barg, Sebastian
    Tengholm, Anders
    Two-step membrane recruitment of Epac2 primes secretory granules for exocytosisManuskript (preprint) (Annet vitenskapelig)
  • 38.
    Alenkvist, Ida
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Idevall-Hagren, Olof
    Tengholm, Anders
    Localization of Epac2 to the plasma membrane is controlled by an interplay between cAMP, Ca2+ and PtdIns(4,5)P2Manuskript (preprint) (Annet vitenskapelig)
  • 39.
    Alenkvist, Ida
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Xu, Yunjian
    Tengholm, Anders
    Sulfonylureas trigger Ca2+-dependent Epac2 recruitment and Rap activation at the plasma membrane in β-cellsManuskript (preprint) (Annet vitenskapelig)
  • 40.
    Alexander, Stephen P. H.
    et al.
    Univ Nottingham, Med Sch, Sch Life Sci, Nottingham NG7 2UH, England..
    Christopoulos, Arthur
    Monash Univ, Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia.;Monash Univ, Dept Pharmacol, Parkville, Vic 3052, Australia..
    Davenport, Anthony P.
    Univ Cambridge, Clin Pharmacol Unit, Cambridge CB2 0QQ, England..
    Kelly, Eamonn
    Univ Bristol, Sch Physiol Pharmacol & Neurosci, Bristol BS8 1TD, Avon, England..
    Mathie, Alistair A.
    Univ Suffolk, Sch EAST Engn Arts Sci & Technol, Ipswich IP4 1QJ, Suffolk, England..
    Peters, John A.
    Univ Dundee, Ninewells Hosp & Med Sch, Med Educ Inst, Neurosci Div, Dundee DD1 9SY, Angus, Scotland..
    Veale, Emma L.
    Univ Greenwich, Medway Sch Pharm, Anson Bldg,Cent Ave, Chatham ME4 4TB, Kent, England.;Univ Kent, Medway, Anson Bldg,Cent Ave, Chatham ME4 4TB, Kent, England..
    Armstrong, Jane F.
    Univ Edinburgh, Ctr Discovery Brain Sci, Edinburgh EH8 9XD, Midlothian, Scotland..
    Faccenda, Elena
    Univ Edinburgh, Ctr Discovery Brain Sci, Edinburgh EH8 9XD, Midlothian, Scotland..
    Harding, Simon D.
    Univ Edinburgh, Ctr Discovery Brain Sci, Edinburgh EH8 9XD, Midlothian, Scotland..
    Davies, Jamie A.
    Univ Edinburgh, Ctr Discovery Brain Sci, Edinburgh EH8 9XD, Midlothian, Scotland..
    Abbracchio, Maria Pia
    Univ Milan, Milan, Italy..
    Abraham, George
    Univ Cambridge, Clin Pharmacol Unit, Cambridge CB2 0QQ, England..
    Agoulnik, Alexander
    Florida Int Univ, Miami, FL 33199 USA..
    Alexander, Wayne
    Emory Univ, Atlanta, GA 30322 USA..
    Al-hosaini, Khaled
    King Saud Univ, Riyadh, Saudi Arabia..
    Baeck, Magnus
    Karolinska Univ Hosp, Stockholm, Sweden..
    Baker, Jillian G.
    Univ Nottingham, Med Sch, Sch Life Sci, Nottingham NG7 2UH, England..
    Barnes, Nicholas M.
    Univ Birmingham, Birmingham, Warwickshire, England..
    Bathgate, Ross
    Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia..
    Beaulieu, Jean-Martin
    Univ Toronto, Toronto, ON, Canada..
    Beck-Sickinger, Annette G.
    Univ Leipzig, Leipzig, Germany..
    Behrens, Maik
    Tech Univ Munich, Freising Weihenstephan, Germany..
    Bernstein, Kenneth E.
    Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA..
    Bettler, Bernhard
    Univ Basel, Basel, Switzerland..
    Birdsall, Nigel J. M.
    Francis Crick Inst, London, England..
    Blaho, Victoria
    Sanford Burnham Prebys Med Discovery Inst, La Jolla, CA USA..
    Boulay, Francois
    Univ Grenoble Alpes, Grenoble, France..
    Bousquet, Corinne
    French Inst Hlth & Med Res INSERM, Toulouse, France..
    Braeuner-Osborne, Hans
    Univ Copenhagen, Copenhagen, Denmark..
    Burnstock, Geoffrey
    UCL, London, England..
    Calo, Girolamo
    Univ Padua, Padua, Italy..
    Castano, Justo P.
    Univ Cordoba, Cordoba, Spain..
    Catt, Kevin J.
    NIH, Bldg 10, Bethesda, MD 20892 USA..
    Ceruti, Stefania
    Univ Milan, Milan, Italy..
    Chazot, Paul
    Univ Durham, Durham, England..
    Chiang, Nan
    Harvard Univ, Boston, MA 02115 USA..
    Chini, Bice
    Univ Milano Bicocca, Vedano Al Lambro, Italy..
    Chun, Jerold
    Univ Calif San Diego, La Jolla, CA 92093 USA..
    Cianciulli, Antonia
    Univ Bari, Bari, Italy..
    Civelli, Olivier
    Univ Calif Irvine, Irvine, CA USA..
    Clapp, Lucie H.
    UCL, London, England..
    Couture, Rejean
    Univ Montreal, Montreal, PQ, Canada..
    Cox, Helen M.
    Kings Coll London, London, England..
    Csaba, Zsolt
    French Inst Hlth & Med Res INSERM, Paris, France..
    Dahlgren, Claes
    Univ Gothenburg, Gothenburg, Sweden..
    Dent, Gordon
    Keele Univ, Keele, Staffs, England..
    Douglas, Steven D.
    Univ Penn, Philadelphia, PA 19104 USA..
    Dournaud, Pascal
    French Inst Hlth & Med Res INSERM, Paris, France..
    Eguchi, Satoru
    Temple Univ, Philadelphia, PA 19122 USA..
    Escher, Emanuel
    Univ Sherbrooke, Sherbrooke, PQ, Canada..
    Filardo, Edward J.
    Univ Iowa, Iowa City, IA USA..
    Fong, Tung
    Labcorp Drug Dev, Somerset, NJ USA..
    Fumagalli, Marta
    Univ Milan, Milan, Italy..
    Gainetdinov, Raul R.
    St Petersburg State Univ, St Petersburg, Russia..
    Garelja, Michael L.
    Univ Otago, Dunedin, New Zealand..
    de Gasparo, Marc
    MG Consulting Co, Basel, Switzerland..
    Gerard, Craig
    Harvard Univ, Boston, MA 02115 USA..
    Gershengorn, Marvin
    NIH, Bldg 10, Bethesda, MD 20892 USA..
    Gobeil, Fernand
    Univ Sherbrooke, Sherbrooke, PQ, Canada..
    Goodfriend, Theodore L.
    Univ Wisconsin, Madison, WI USA..
    Goudet, Cyril
    French Natl Ctr Sci Res, Montpellier, France..
    Graetz, Lukas
    Karolinska Inst, Stockholm, Sweden..
    Gregory, Karen J.
    Monash Univ, Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia.;Monash Univ, Dept Pharmacol, Parkville, Vic 3052, Australia..
    Gundlach, Andrew L.
    Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia..
    Hamann, Joerg
    Univ Amsterdam, Amsterdam, Netherlands..
    Hanson, Julien
    Univ Liege, Liege, Belgium..
    Hauger, Richard L.
    Univ Calif San Diego, La Jolla, CA 92093 USA..
    Hay, Debbie L.
    Univ Otago, Dunedin, New Zealand..
    Heinemann, Akos
    Med Univ Graz, Graz, Austria..
    Herr, Deron
    San Diego State Univ, San Diego, CA 92182 USA..
    Hollenberg, Morley D.
    Univ Calgary, Calgary, AB, Canada..
    Holliday, Nicholas D.
    Univ Nottingham, Med Sch, Sch Life Sci, Nottingham NG7 2UH, England..
    Horiuchi, Mastgugu
    Ehime Univ, Matsuyama, Ehime, Japan..
    Hoyer, Daniel
    Univ Melbourne, Melbourne, Vic, Australia..
    Hunyady, Laszlo
    Semmelwe Univ, Budapest, Hungary..
    Husain, Ahsan
    Emory Univ, Atlanta, GA 30322 USA..
    Ijzerman, Adriaan P.
    Leiden Univ, Leiden, Netherlands..
    Inagami, Tadashi
    Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Jacobson, Kenneth A.
    NIH, Bldg 10, Bethesda, MD 20892 USA..
    Jensen, Robert T.
    NIH, Bldg 10, Bethesda, MD 20892 USA..
    Jockers, Ralf
    French Inst Hlth & Med Res INSERM, Paris, France..
    Jonnalagadda, Deepa
    Sanford Burnham Prebys Med Discovery Inst, La Jolla, CA USA..
    Karnik, Sadashiva
    Lerner Res Inst, Cleveland, OH USA..
    Kaupmann, Klemens
    Novartis, Basel, Switzerland..
    Kemp, Jacqueline
    Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA..
    Kennedy, Charles
    Strathclyde Univ, Glasgow, Lanark, Scotland..
    Kihara, Yasuyuki
    Sanford Burnham Prebys Med Discovery Inst, La Jolla, CA USA..
    Kitazawa, Takio
    Rakuno Gakuen Univ, Ebetsu, Hokkaido, Japan..
    Kozielewicz, Pawel
    Karolinska Inst, Stockholm, Sweden..
    Kreienkamp, Hans-Juergen
    Univ Hamburg, Hamburg, Germany..
    Kukkonen, Jyrki P.
    Univ Helsinki, Helsinki, Finland..
    Langenhan, Tobias
    Univ Leipzig, Leipzig, Germany..
    Larhammar, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Forskargrupp Dan Larhammar.
    Leach, Katie
    Monash Univ, Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia.;Monash Univ, Dept Pharmacol, Parkville, Vic 3052, Australia..
    Lecca, Davide
    Univ Milan, Milan, Italy..
    Lee, John D.
    Univ Queensland, Brisbane, Qld, Australia..
    Leeman, Susan E.
    Boston Univ, Boston, MA 02215 USA..
    Leprince, Jerome
    Univ Rouen, Rouen, France..
    Li, Xaria X.
    Univ Queensland, Toowoomba, Qld, Australia..
    Lolait, Stephen J.
    Univ Bristol, Sch Physiol Pharmacol & Neurosci, Bristol BS8 1TD, Avon, England..
    Lupp, Amelie
    Friedrich Schiller Univ Jena, Jena, Germany..
    Macrae, Robyn
    Univ Cambridge, Cambridge, England..
    Maguire, Janet
    Univ Cambridge, Clin Pharmacol Unit, Cambridge CB2 0QQ, England..
    Malfacini, Davide
    Univ Padua, Padua, Italy..
    Mazella, Jean
    French Natl Ctr Sci Res CNRS, Valbonne, France..
    Mcardle, Craig A.
    Univ Bristol, Sch Physiol Pharmacol & Neurosci, Bristol BS8 1TD, Avon, England..
    Melmed, Shlomo
    Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA..
    Michel, Martin C.
    Johannes Gutenberg Univ Mainz, Mainz, Germany..
    Miller, Laurence J.
    Mayo Fdn Med Educ & Res, Scottsdale, AZ USA..
    Mitolo, Vincenzo
    Univ Bari, Bari, Italy..
    Mouillac, Bernard
    French Natl Ctr Sci Res, Montpellier, France..
    Mueller, Christa E.
    Univ Bonn, Bonn, Germany..
    Murphy, Philip M.
    Edge Hill Univ, Bethesda, MD USA..
    Nahon, Jean-Louis
    French Natl Ctr Sci Res CNRS, Valbonne, France..
    Ngo, Tony
    Sanford Burnham Prebys Med Discovery Inst, La Jolla, CA USA..
    Norel, Xavier
    French Inst Hlth & Med Res INSERM, Paris, France..
    Nyimanu, Duuamene
    Univ Cambridge, Cambridge, England..
    O'Carroll, Anne-Marie
    Univ Bristol, Sch Physiol Pharmacol & Neurosci, Bristol BS8 1TD, Avon, England..
    Offermanns, Stefan
    Max Planck Inst Heart & Lung Res, Bad Nauheim, Germany..
    Panaro, Maria Antonietta
    Univ Bari, Bari, Italy..
    Parmentier, Marc
    Free Univ Brussels, Brussels, Belgium..
    Pertwee, Roger G.
    Univ Aberdeen, Aberdeen, Scotland..
    Pin, Jean-Philippe
    Univ Montpellier, Montpellier, France..
    Prossnitz, Eric R.
    Univ New Mexico, Albuquerque, NM 87131 USA..
    Quinn, Mark
    Montana State Univ, Bozeman, MT 59717 USA..
    Ramachandran, Rithwik
    Univ Calgary, Calgary, AB, Canada..
    Ray, Manisha
    Sanford Burnham Prebys Med Discovery Inst, La Jolla, CA USA..
    Reinscheid, Rainer K.
    Friedrich Schiller Univ Jena, Jena, Germany..
    Rondard, Philippe
    Univ Montpellier, Montpellier, France..
    Rovati, G. Enrico
    Univ Milan, Milan, Italy..
    Ruzza, Chiara
    Univ Ferrara, Ferrara, Italy..
    Sanger, Gareth J.
    Queen Mary Univ London, London, England..
    Schoeneberg, Torsten
    Univ Leipzig, Leipzig, Germany..
    Schulte, Gunnar
    Karolinska Inst, Stockholm, Sweden..
    Schulz, Stefan
    Friedrich Schiller Univ Jena, Jena, Germany..
    Segaloff, Deborah L.
    Univ Iowa, Iowa City, IA USA..
    Serhan, Charles N.
    Harvard Univ, Boston, MA 02115 USA..
    Singh, Khuraijam Dhanachandra
    Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA..
    Smith, Craig M.
    Deakin Univ, Waurn Ponds, Australia..
    Stoddart, Leigh A.
    Univ Nottingham, Med Sch, Sch Life Sci, Nottingham NG7 2UH, England..
    Sugimoto, Yukihiko
    Kumamoto Univ, Kumamoto, Japan..
    Summers, Roger
    Monash Univ, Melbourne, Vic, Australia..
    Tan, Valerie P.
    Univ Calif San Diego, La Jolla, CA 92093 USA..
    Thal, David
    Monash Univ, Melbourne, Vic, Australia..
    Thomas, Walter ( Wally)
    Univ Queensland, Toowoomba, Qld, Australia..
    Timmermans, Pieter B. M. W. M.
    Kosan Biosci Inc, San Francisco, CA USA..
    Tirupula, Kalyan
    Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA..
    Toll, Lawrence
    Florida Atlantic Univ, Jupiter, FL USA..
    Tulipano, Giovanni
    Univ Brescia, Brescia, Italy..
    Unal, Hamiyet
    Cleveland Clin, Cleveland, OH 44106 USA..
    Unger, Thomas
    Maastricht Univ, Maastricht, Netherlands..
    Valant, Celine
    Monash Univ, Melbourne, Vic, Australia..
    Vanderheyden, Patrick
    Free Univ Brussels, Brussels, Belgium..
    Vaudry, David
    Univ Rouen, Rouen, France..
    Vaudry, Hubert
    Univ Rouen, Rouen, France..
    Vilardaga, Jean-Pierre
    Univ Pittsburgh, Pittsburgh, PA USA..
    Walker, Christopher S.
    Univ Auckland, Auckland, New Zealand..
    Wang, Ji Ming
    NCI, Frederick, MD 21701 USA..
    Ward, Donald T.
    Univ Manchester, Manchester, Lancs, England..
    Wester, Hans-Juergen
    Tech Univ Munich, Munich, Germany..
    Willars, Gary B.
    Univ Leicester, Leicester, Leics, England..
    Williams, Tom Lloyd
    Univ Cambridge, Cambridge, England..
    Woodruff, Trent M.
    Univ Queensland, Toowoomba, Qld, Australia..
    Yao, Chengcan
    Univ Edinburgh, Edinburgh, Midlothian, Scotland..
    Ye, Richard D.
    Chinese Univ Hong Kong, Shenzhen, Hong Kong, Peoples R China..
    The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors2023Inngår i: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 180, nr Suppl. 2, s. S23-S144Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

    Fulltekst (pdf)
    fulltext
  • 41.
    Alkamiasy, Muataz
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    A Study To Investigate Differences In Walking Speed Of Overweight Children By Using A Six-Minute Walking Test2022Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Overweight and obesity are a major problem today. It is a growing problem that harms health and is present in all ages. This study was designed to investigate the relationship between ISO-Body Mass Index in overweight children both boys and girls, and walking speed regardless of height. In addition, examine the relationship between weight, height and walking speed by using a six-minute walking test. The study included already collected measurements from the patients' first visit at the Energy Metabolic Laboratory, which is a research unit at the Department of Women's and Children's Health at the academic Hospital in Uppsala, between the years 2008–2021. Results were collected on 195 patients, 122 boys and 73 girls. Data collected were age, weight, height, walking speed, walking distance, heart rate, level of exertion and dyspnea. The results showed that the ISO-Body Mass Index affects walking speed in obese children. Regarding how walking speed differs between both genders of obese children, the results showed that higher ISO-Body Mass Index in boys leads to them walking more slowly compared to girls who are less affected. To be able to demonstrate how walking speed is affected by other continuous variables such as encouragement or motivation, more studies with greater focus on smaller age groups are needed to gain a better understanding of how the various variables affect walking speed.

  • 42. Allagnat, F.
    et al.
    Fukaya, M.
    Nogueira, T. C.
    Delaroche, D.
    Welsh, Nils
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Marselli, L.
    Marchetti, P.
    Haefliger, J. A.
    Eizirik, D. L.
    Cardozo, A. K.
    C/EBP homologous protein contributes to cytokine-induced pro-inflammatory responses and apoptosis in beta-cells2012Inngår i: Cell Death and Differentiation, ISSN 1350-9047, E-ISSN 1476-5403, Vol. 19, nr 11, s. 1836-1846Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Induction of the C/EBP homologous protein (CHOP) is considered a key event for endoplasmic reticulum (ER) stress-mediated apoptosis. Type 1 diabetes (T1D) is characterized by an autoimmune destruction of the pancreatic beta-cells. Pro-inflammatory cytokines are early mediators of beta-cell death in T1D. Cytokines induce ER stress and CHOP overexpression in beta-cells, but the role for CHOP overexpression in cytokine-induced beta-cell apoptosis remains controversial. We presently observed that CHOP knockdown (KD) prevents cytokine-mediated degradation of the anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia sequence 1 (Mcl-1), thereby decreasing the cleavage of executioner caspases 9 and 3, and apoptosis. Nuclear factor-kappa B (NF-kappa B) is a crucial transcription factor regulating beta-cell apoptosis and inflammation. CHOP KD resulted in reduced cytokine-induced NF-kappa B activity and expression of key NF-kappa B target genes involved in apoptosis and inflammation, including iNOS, FAS, IRF-7, IL-15, CCL5 and CXCL10. This was due to decreased I kappa B degradation and p65 translocation to the nucleus. The present data suggest that CHOP has a dual role in promoting beta-cell death: (1) CHOP directly contributes to cytokine-induced beta-cell apoptosis by promoting cytokine-induced mitochondrial pathways of apoptosis; and (2) by supporting the NF-kappa B activation and subsequent cytokine/chemokine expression, CHOP may contribute to apoptosis and the chemo attraction of mononuclear cells to the islets during insulitis. Cell Death and Differentiation (2012) 19, 1836-1846; doi:10.1038/cdd.2012.67; published online 1 June 2012

  • 43.
    Al-Lashi, Lord Laith Zuhair
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    GABA and SGLT2 inhibitor modulate human T lymphocyte effector function2023Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    Sodium Glucose Co-Transporter 2 (SGLT2) inhibitors are one of the dominant drug groups used today for treatment of type 2 diabetes. There are several agents within the group that were investigated in this project: Phlorizin, Empagliflozin, Canagliflozin, Dapagliflozin and Ipragliflozin. SGLT2 inhibitors influence immune cells such as CD4+ T cells, and Gamma Aminobutyric Acid (GABA) also affects CD4+ T cells functions. This study aims to investigate how different SGLT2 inhibitors together with GABA in the presence/absence of insulin affect the effector function of CD4+ T cells. As these are very popular and usable substances in medical fields, it becomes an important basis to study what effect they have on CD4+ T cells effector functions.

    Peripheral Blood Mononuclear Cells (PBMCs) were collected from buffy coat of healthy donors to isolate CD4+ T cells. Cells were activated with anti-CD3 antibody and incubated with different concentrations of SGLT2 inhibitors at 5 mM and 16.7 mM glucose and examined by MTT assay and culture supernatant was collected. Empagliflozin (1uM and 10 uM) was chosen to proceed with to test together with GABA and insulin on CD4+ T cells. Western blot was performed to detect the SGLT2 protein and Sandwich IFNg ELISA was also performed to examine how cytokines such as IFNg were affected in the samples. 

    The presented results show that the SGLT2 protein can be detected in the samples and the IFNg levels were decreased in samples without insulin and increased with the addition of insulin as expected. This should be further investigated, and additional experiments need to be performed to confirm the effect on the CD4+ T cell effector functions.

  • 44.
    Allegrucci, C
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ronquist, G
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ove Nilsson, B
    Institutionen för medicinsk cellbiologi.
    Carlsson, L
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lundqvist, M
    Minelli, A
    Larsson, A
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Circulating human antisperm antibodies recognize prostasomes.2001Inngår i: Am. J. Reprod. Immunol., Vol. 46, s. 211-Artikkel i tidsskrift (Fagfellevurdert)
  • 45. Alm, P
    et al.
    Sharma, H S
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Hedlund, S
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Sjoquist, P-O
    Westman, J
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Nitric oxide in the pathophysiology of hypertermic brain injury. Influence of a new antioxidant compound H-290/51.1998Inngår i: Amino Acids, Vol. 14, s. 95-Artikkel i tidsskrift (Fagfellevurdert)
  • 46. Alm, P
    et al.
    Sharma, H S
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Sjoquist, P-O
    Westman, J
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    A new antioxidant compound H-290/51 attenuates nictric oxide synthase and heme oxygenase expression following hyperhermic brain injury.2000Inngår i: Amino Acids, Vol. 19, s. 383-Artikkel i tidsskrift (Fagfellevurdert)
  • 47.
    Al-Mashhadi, Ammar
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnkirurgisk forskning.
    Häggman, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Läckgren, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnkirurgisk forskning.
    Ladjevardi, Sam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Nevéus, Tryggve
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammationsforskning.
    Stenberg, Arne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnkirurgisk forskning.
    Persson, A. Erik G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Carlstrom, Mattias
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Changes of arterial pressure following relief of obstruction in adults with hydronephrosis2018Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, nr 4, s. 216-224Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: As much as 20% of all cases of hypertension are associated with kidney malfunctions. We have previously demonstrated in animals and in pediatric patients that hydronephrosis causes hypertension, which was attenuated by surgical relief of the ureteropelvic junction (UPJ) obstruction. This retrospective cohort study aimed to investigate: (1) the proposed link between hydronephrosis, due to UPJ obstruction, and elevated arterial pressure in adults; and (2) if elevated blood pressure in patients with hydronephrosis might be another indication for surgery.

    Materials and methods: Medical records of 212 patients undergoing surgical management of hydronephrosis, due to UPJ obstruction, between 2000 and 2016 were assessed. After excluding patients with confounding conditions and treatments, paired arterial pressures (i.e. before/after surgery) were compared in 49 patients (35 years old; 95% CI 29–39). Split renal function was evaluated by using mercaptoacetyltriglycine (MAG3) renography before surgical management of the hydronephrotic kidney.

    Results: Systolic (−11 mmHg; 95% CI 6–15 mmHg), diastolic (−8 mmHg; 95% CI 4–11 mmHg), and mean arterial (-9 mmHg; 95% CI 6–12) pressures were significantly reduced after relief of the obstruction (p < 0.001). Split renal function of the hydronephrotic kidney was 39% (95% CI 37–41). No correlations were found between MAG3 and blood pressure level before surgery or between MAG3 and the reduction of blood pressure after surgical management of the UPJ obstruction.

    Conclusions: In adults with hydronephrosis, blood pressure was reduced following relief of the obstruction. Our findings suggest that elevated arterial pressure should be taken into account as an indication to surgically correct hydronephrosis.

    Fulltekst (pdf)
    FULLTEXT01
  • 48.
    Al-Mashhadi, Ammar Nadhom Farman
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Reduction of arterial pressure following relief of obstruction in patients with hydronephrosisManuskript (preprint) (Annet vitenskapelig)
  • 49.
    Al-Mashhadi, Ammar Nadhom Farman
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Barnkirurgi.
    Checa, Antonio
    Karolinska Institute.
    Wåhlin, Nils
    Karolinska Institute.
    Nevéus, Tryggve
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammationsforskning.
    Fossum, Magdalena
    Karolinska institute.
    Wheelock, Craig E.
    Karolinska Institute.
    Karanikas, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Barnkirurgi.
    Stenberg, Arne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Barnkirurgi.
    Persson, A. Erik G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Carlström, Mattias
    Karolinska Institute.
    Changes in arterial pressure and markers of nitric oxide homeostasis and oxidative stress following surgical correction of hydronephrosis in children2018Inngår i: Pediatric nephrology (Berlin, West), ISSN 0931-041X, E-ISSN 1432-198X, Vol. 33, nr 4, s. 639-649Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective Recent clinical studies have suggested an increased risk of elevated arterial pressure in patients with hydronephrosis. Animals with experimentally induced hydronephrosis develop hypertension, which is correlated to the degree of obstruction and increased oxidative stress. In this prospective study we investigated changes in arterial pressure, oxidative stress, and nitric oxide (NO) homeostasis following correction of hydronephrosis.

    Methods Ambulatory arterial pressure (24 h) was monitored in pediatric patients with hydronephrosis (n = 15) before and after surgical correction, and the measurements were compared with arterial pressure measurements in two control groups, i.e. healthy controls (n = 8) and operated controls (n = 8). Markers of oxidative stress and NO homeostasis were analyzed in matched urine and plasma samples.

    Results The preoperative mean arterial pressure was significantly higher in hydronephrotic patients [83 mmHg; 95% confidence interval (CI) 80–88 mmHg] than in healthy controls (74 mmHg; 95% CI 68–80 mmHg; p < 0.05), and surgical correction of ureteral obstruction reduced arterial pressure (76 mmHg; 95% CI 74–79 mmHg; p < 0.05). Markers of oxidative stress (i.e., 11- dehydroTXB2, PGF2α, 8-iso-PGF2α, 8,12-iso-iPF2α-VI) were significantly increased (p < 0.05) in patients with hydronephrosis compared with both control groups, and these were reduced following surgery (p < 0.05). Interestingly, there was a trend for increased NO synthase activity and signaling in hydronephrosis, which may indicate compensatory mechanism(s).

    Conclusion This study demonstrates increased arterial pressure and oxidative stress in children with hydronephrosis compared with healthy controls, which can be restored to normal levels by surgical correction of the obstruction. Once reference data on ambulatory blood pressure in this young age group become available, we hope cut-off values can be defined for deciding whether or not to correct hydronephrosis surgically.

    Keywords Blood pressure . Hydronephrosis . Hypertension . Nitric oxide . Oxidative stress . Ureteral obstruction 

    Fulltekst (pdf)
    fulltext
  • 50.
    Al-Mashhadi, Ammar Nadhom Farman
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Nevéus, Tryggve
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Stenberg, Arne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Karanikas, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Persson, A. Erik G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Carlstrom, Mattias
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Wahlin, Nils
    Department of Pediatric Surgery, Astrid Lindgren Hospital, Karolinska Institutet, Stockholm, Sweden.
    Surgical treatment reduces blood pressure in children with unilateral congenital hydronephrosis2015Inngår i: Journal of Pediatric Urology, ISSN 1477-5131, E-ISSN 1873-4898, Vol. 11, nr 2, s. 91.e1-91.e6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective Renal disorders can cause hypertension, but less is known about the influence of hydronephrosis on blood pressure. Hydronephrosis due to pelvo-ureteric junction obstruction (PUJO) is a fairly common condition (incidence in newborns of 0.5-1%). Although hypertensive effects of hydronephrosis have been suggested, this has not been substantiated by prospective studies in humans [1-3]. Experimental studies with PUJO have shown that animals with induced hydronephrosis develop salt-sensitive hypertension, which strongly correlate to the degree of obstruction [4-7]. Moreover, relief of the obstruction normalized blood pressure [8]. In this first prospective study our aim was to study the blood pressure pattern in pediatric patients with hydronephrosis before and after surgical correction of the ureteral obstruction. Specifically, we investigated if preoperative blood pressure is reduced after surgery and if split renal function and renographic excretion curves provide any prognostic information. Patients and methods Twelve patients with unilateral congenital hydronephrosis were included in this prospective study. Ambulatory blood pressure (24 h) was measured preoperatively and six months after surgery. Preoperative evaluations of bilateral renal function by Tc99m-MAG3 scintigraphy, and renography curves, classified according to O'Reilly, were also performed. Results As shown in the summary figure, postoperative systolic (103 +/- 2 mmHg) and diastolic (62 +/- 2 mmHg) blood pressure were significantly lower than those obtained preoperatively (110 +/- 4 and 69 +/- 2 mmHg, respectively), whereas no changes in circadian variation or pulse pressure were observed. Renal functional share of the hydronephrotic kidney ranged from 11 to 55%. There was no correlation between the degree of renal function impairment and the preoperative excretory pattern, or between the preoperative excretory pattern and the blood pressure reduction postoperatively. However, preoperative MAG3 function of the affected kidney correlated with the magnitude of blood pressure change after surgery. Discussion Correction of the obstruction lowered blood pressure, and the reduction in blood pressure appeared to correlate with the degree of renal functional impairment, but not with the excretory pattern. Thus, in the setting of hypertension, it appears that the functional share of the hydronephrotic kidney should be considered an indicator of the need for surgery, whereas the renography curve is less reliable. The strength of the present study is the prospective nature and that ambulatory blood pressure monitoring was used. Future longitudinal prolonged follow-up studies are warranted to confirm the present findings, and to understand if a real nephrogenic hypertension with potential necessity of treatment will develop. Conclusion This novel prospective study in patients with congenital hydronephrosis demonstrates a reduction in blood pressure following relief of the obstruction. Based on the present results, we propose that the blood pressure level should also be taken into account when deciding whether to correct hydronephrosis surgically or not.

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