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Sökning: WFRF:(Larsson Lars Torsten)

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  • Gabrielsson, Britt, 1957, et al. (författare)
  • High expression of complement components in omental adipose tissue in obese men.
  • 2003
  • Ingår i: Obesity research. - : Wiley. - 1071-7323 .- 1550-8528. ; 11:6, s. 699-708
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Accumulation of visceral fat is recognized as a predictor of obesity-related metabolic disturbances. Factors that are predominantly expressed in this depot could mediate the link between visceral obesity and associated diseases. RESEARCH METHODS AND PROCEDURES: Paired subcutaneous and omental adipose tissue biopsies were obtained from 10 obese men. Gene expression was analyzed by DNA microarrays in triplicate and by real-time polymerase chain reaction. Serum C3 and C4 were analyzed by radial immunodiffusion assays in 91 subjects representing a cross section of the general population. Body composition was measured by computerized tomography. RESULTS: Complement components C2, C3, C4, C7, and Factor B had higher expression in omental compared with subcutaneous adipose tissue ( approximately 2-, 4-, 17-, 10-, and 7-fold, respectively). In addition, adipsin, which belongs to the alternative pathway, and the classical pathway components C1QB, C1R, and C1S were expressed in both depots. Analysis of tissue distribution showed high expression of C2, C3, and C4 in omental adipose tissue, and only liver had higher expression of these genes. Serum C3 levels correlated with both visceral and subcutaneous adipose tissue in both men (r = 0.65 and p < 0.001 and r = 0.52 and p < 0.001, respectively) and women (r = 0.34 and p = 0.023 and r = 0.49 and p < 0.001, respectively), whereas C4 levels correlated with only visceral fat in men (r = 0.36, p = 0.015) and with both depots in women (visceral: r = 0.58, p < 0.001; and subcutaneous: r = 0.51, p < 0.001). DISCUSSION: Recent studies show that the metabolic syndrome is associated with chronically elevated levels of several immune markers, some of which may have metabolic effects. The high expression of complement genes in intra-abdominal adipose tissue might suggest that the complement system is involved in the development of visceral adiposity and/or contributes to the metabolic complications associated with increased visceral fat mass.
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  • Jordan, Stanley C, et al. (författare)
  • IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation.
  • 2017
  • Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 377:5, s. 442-453
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Donor-specific antibodies create an immunologic barrier to transplantation. Current therapies to modify donor-specific antibodies are limited and ineffective in the most highly HLA-sensitized patients. The IgG-degrading enzyme derived from Streptococcus pyogenes (IdeS), an endopeptidase, cleaves human IgG into F(ab')2 and Fc fragments inhibiting complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, which suggests that IdeS might be useful for desensitization. We report on the combined experience of two independently performed open-label, phase 1-2 trials (conducted in Sweden and the United States) that assessed the efficacy of IdeS with regard to desensitization and transplantation of a kidney from an HLA-incompatible donor.METHODS: We administered IdeS to 25 highly HLA-sensitized patients (11 patients in Uppsala or Stockholm, Sweden, and 14 in Los Angeles) before the transplantation of a kidney from an HLA-incompatible donor. Frequent monitoring for adverse events, outcomes, donor-specific antibodies, and renal function was performed, as were renal biopsies. Immunosuppression after transplantation consisted of tacrolimus, mycophenolate mofetil, and glucocorticoids. Patients in the U.S. study also received intravenous immune globulin and rituximab after transplantation to prevent antibody rebound.RESULTS: Recipients in the U.S. study had a significantly longer cold ischemia time (the time elapsed between procurement of the organ and transplantation), a significantly higher rate of delayed graft function, and significantly higher levels of class I donor-specific antibodies than those in the Swedish study. A total of 38 serious adverse events occurred in 15 patients (5 events were adjudicated as being possibly related to IdeS). At transplantation, total IgG and HLA antibodies were eliminated. A total of 24 of 25 patients had perfusion of allografts after transplantation. Antibody-mediated rejection occurred in 10 patients (7 patients in the U.S. study and 3 in the Swedish study) at 2 weeks to 5 months after transplantation; all these patients had a response to treatment. One graft loss, mediated by non-HLA IgM and IgA antibodies, occurred.CONCLUSIONS: IdeS reduced or eliminated donor-specific antibodies and permitted HLA-incompatible transplantation in 24 of 25 patients. (Funded by Hansa Medical; ClinicalTrials.gov numbers, NCT02224820 , NCT02426684 , and NCT02475551 .).
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4.
  • Lorant, Tomas, 1975-, et al. (författare)
  • Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti-HLA antibodies by IdeS (imlifidase) in chronic kidney disease patients
  • 2018
  • Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 18:11, s. 2752-2762
  • Tidskriftsartikel (refereegranskat)abstract
    • Safety, immunogenicity, pharmacokinetics, and efficacy of the IgG-degrading enzyme of Streptococcus pyogenes (IdeS [imlifidase]) were assessed in a single-center, open-label ascending-dose study in highly sensitized patients with chronic kidney disease. Eight patients with cytotoxic PRAs (median cytotoxic PRAs of 64%) at enrollment received 1 or 2 intravenous infusions of IdeS on consecutive days (0.12 mg/kg body weight ×2 [n = 3]; 0.25 mg/kg ×1 [n = 3], or 0.25 mg/kg ×2 [n = 2]). IgG degradation was observed in all subjects after IdeS treatment, with <1% plasma IgG remaining within 48 hours and remaining low up to 7 days. Mean fluorescence intensity values of HLA class I and II reactivity were substantially reduced in all patients, and C1q binding to anti-HLA was abolished. IdeS also cleaved the IgG-type B cell receptor on CD19+ memory B cells. Anti-IdeS antibodies developed 1 week after treatment, peaking at 2 weeks. A few hours after the second IdeS infusion, 1 patient received a deceased donor kidney offer. At enrollment, the patient had a positive serum crossmatch (HLA-B7), detected by complement-dependent cytotoxicity, flow cytometry, and multiplex bead assays. After IdeS infusion (0.12 mg/kg ×2) and when the HLA-incompatible donor (HLA-B7+) kidney was offered, the HLA antibody profile was negative. The kidney was transplanted successfully.
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5.
  • Sarlin, Paul-Edouard, et al. (författare)
  • Back to the Feature: Learning Robust Camera Localization from Pixels to Pose
  • 2021
  • Ingår i: Proceedings of the IEEE Computer Society Conference on Computer Vision and Pattern Recognition. - 1063-6919. ; , s. 3246-3256
  • Konferensbidrag (refereegranskat)abstract
    • Camera pose estimation in known scenes is a 3D geometry task recently tackled by multiple learning algorithms. Many regress precise geometric quantities, like poses or 3D points, from an input image. This either fails to generalize to new viewpoints or ties the model parameters to a specific scene. In this paper, we go Back to the Feature: we argue that deep networks should focus on learning robust and invariant visual features, while the geometric estimation should be left to principled algorithms. We introduce PixLoc, a scene-agnostic neural network that estimates an accurate 6-DoF pose from an image and a 3D model. Our approach is based on the direct alignment of multiscale deep features, casting camera localization as metric learning. PixLoc learns strong data priors by end-to-end training from pixels to pose and exhibits exceptional generalization to new scenes by separating model parameters and scene geometry. The system can localize in large environments given coarse pose priors but also improve the accuracy of sparse feature matching by jointly refining keypoints and poses with little overhead. The code will be publicly available at github.com/cvg/pixloc.
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7.
  • Arnbjörnsson, Einar, et al. (författare)
  • Video vägleder vid anläggning av gastrostomiknapp hos barn. Tio års erfarenheter visar metodens fördelar
  • 2005
  • Ingår i: Läkartidningen. - 0023-7205. ; 102:46, s. 5-3451
  • Tidskriftsartikel (refereegranskat)abstract
    • Tio års erfarenheter av att anlägga gastrostomier på barn med hjälp av videoendoskop redovisas. I patientgruppen ingår 300 barn i åldern 3 månader till 18 år med neurologiska åkommor, metabola sjukdomar, medfödda hjärtmissbildningar och maligna sjukdomar. Operationen görs i intubationsnarkos med en videoassisterad anläggning av gastrostomi där en s k gastrostomiknapp placeras direkt i stomat och används så fort barnet har vaknat. Några svåra operativa eller postoperativa komplikationer, såsom blödningar, fistlar till kolon eller behov av akut reoperation, har inte förekommit. Lokala problem runt själva stomat är vanliga, liksom vid andra gastrostomimetoder. Vi rekommenderar den här beskrivna videoassisterade tekniken för användning på barn om de anatomiska förutsättningarna så tillåter.
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8.
  • Backman, Torbjorn, et al. (författare)
  • Video-assisted gastrostomy in infants less than 1 year.
  • 2006
  • Ingår i: Pediatric Surgery International. - : Springer Science and Business Media LLC. - 1437-9813 .- 0179-0358. ; 22:3, s. 243-246
  • Tidskriftsartikel (refereegranskat)abstract
    • The objectives of this study were to report our experience with the laparoscopic video-assisted gastrostomy technique in infants operated during their first year of life. A total of 53 infants (35 males, 18 females) aged 6 +/- 3 months, varying from 3 weeks to 11 months, underwent video-assisted gastrostomy. They were prospectively followed up. Included are infants with neurological dysfunction, chromosomal anomalies, metabolic disorders, cardiac anomalies or respiratory insufficiency. All the infants were operated under general and local anaesthesia. Gastrostomy tube feeding began within 4 h after the operation. The infants were followed with a scheduled control at 1 and 6 months postoperatively documenting complications and weight gain. The main outcome measure was the number and type of complications as well as weight gain using the age-adjusted Z-score of weight to normalize the data relative to a reference population. The weight before and 6 months after the video-assisted gastrostomy was 5.5 +/- 1.6 and 8.5 +/- 1.6 kg, respectively. The Z-score increased significantly (P < 0.001) from -2.7 +/- 1.5 to -1.7 +/- 1.0. This illustrates the postoperative weight gain and catch-up. Short and long-term complications included minor local wound infection, leakage around the gastrostomy tube and granuloma, but no severe complications. Our results encourage the use of video-assisted gastrostomy as a safe technique to provide a route for long-term nutritional support even in infants less than 1 year.
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9.
  • Bäckryd, Emmanuel, 1974-, et al. (författare)
  • Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma
  • 2017
  • Ingår i: Journal of Pain Research. - : DOVE MEDICAL PRESS LTD. - 1178-7090. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • In addition to central hyperexcitability and impaired top-down modulation, chronic inflammation probably plays a role in the pathophysiology of fibromyalgia (FM). Indeed, on the basis of both animal experiments and human studies involving the analysis of cytokines and other inflammation-related proteins in different body fluids, neuroinflammatory mechanisms are considered to be central to the pathophysiology of many chronic pain conditions. However, concerning FM, previous human plasma/serum and/or cerebrospinal fluid (CSF) cytokine studies have looked only at a few predetermined cytokine candidates. Instead of analyzing only a few substances at a time, we used a new multiplex protein panel enabling simultaneous analysis of 92 inflammation-related proteins. Hence, we investigated the CSF and plasma inflammatory profiles of 40 FM patients compared with CSF from healthy controls (n= 10) and plasma from blood donor controls (n= 46). Using multivariate data analysis by projection, we found evidence of both neuroinflammation (as assessed in CSF) and chronic systemic inflammation (as assessed in plasma). Two groups of proteins (one for CSF and one for plasma) highly discriminating between patients and controls are presented. Notably, we found high levels of CSF chemokine CX3CL1 (also known as fractalkine). In addition, previous findings concerning IL-8 in FM were replicated, in both CSF and plasma. This is the first time that such an extensive inflammatory profile has been described for FM patients. Hence, FM seems to be characterized by objective biochemical alterations, and the lingering characterization of its mechanisms as essentially idiopathic or even psychogenic should be seen as definitively outdated.
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