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1.
  • Bergman, Peter, et al. (författare)
  • Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial
  • 2021
  • Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 74
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients with immunocompromised disorders have mainly been excluded from clinical trials of vaccination against COVID-19. Thus, the aim of this prospective clinical trial was to investigate safety and efficacy of BNT162b2 mRNA vaccination in five selected groups of immunocompromised patients and healthy controls.Methods: 539 study subjects (449 patients and 90 controls) were included. The patients had either primary (n=90), or secondary immunodeficiency disorders due to human immunodeficiency virus infection (n=90), allogeneic hematopoietic stem cell transplantation/CAR T cell therapy (n=90), solid organ transplantation (SOT) (n=89), or chronic lymphocytic leukemia (CLL) (n=90). The primary endpoint was seroconversion rate two weeks after the second dose. The secondary endpoints were safety and documented SARS-CoV-2 infection.Findings: Adverse events were generally mild, but one case of fatal suspected unexpected serious adverse reaction occurred. 72.2% of the immunocompromised patients seroconverted compared to 100% of the controls (p=0.004). Lowest seroconversion rates were found in the SOT (43.4%) and CLL (63.3%) patient groups with observed negative impact of treatment with mycophenolate mofetil and ibrutinib, respectively.Interpretation: The results showed that the mRNA BNT162b2 vaccine was safe in immunocompromised patients. Rate of seroconversion was substantially lower than in healthy controls, with a wide range of rates and antibody titres among predefined patient groups and subgroups. This clinical trial highlights the need for additional vaccine doses in certain immunocompromised patient groups to improve immunity.
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3.
  • Bi, Zhaoxia, et al. (författare)
  • Self-assembled InN quantum dots on side facets of GaN nanowires
  • 2018
  • Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 123:16
  • Tidskriftsartikel (refereegranskat)abstract
    • Self-assembled, atomic diffusion controlled growth of InN quantum dots was realized on the side facets of dislocation-free and c-oriented GaN nanowires having a hexagonal cross-section. The nanowires were synthesized by selective area metal organic vapor phase epitaxy. A 3 Å thick InN wetting layer was observed after growth, on top of which the InN quantum dots formed, indicating self-assembly in the Stranski-Krastanow growth mode. We found that the InN quantum dots can be tuned to nucleate either preferentially at the edges between GaN nanowire side facets, or directly on the side facets by tuning the adatom migration by controlling the precursor supersaturation and growth temperature. Structural characterization by transmission electron microscopy and reciprocal space mapping show that the InN quantum dots are close to be fully relaxed (residual strain below 1%) and that the c-planes of the InN quantum dots are tilted with respect to the GaN core. The strain relaxes mainly by the formation of misfit dislocations, observed with a periodicity of 3.2 nm at the InN and GaN hetero-interface. The misfit dislocations introduce I1 type stacking faults (...ABABCBC...) in the InN quantum dots. Photoluminescence investigations of the InN quantum dots show that the emissions shift to higher energy with reduced quantum dot size, which we attribute to increased quantum confinement.
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4.
  • Hakansson, HO, et al. (författare)
  • Synthesis and localization of pancreatic secretory proteins in pancreatic acinar-like metaplasia in the distal part of the oesophagus
  • 2003
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 38:1, s. 41560-41560
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Pancreatic acinar-like metaplasia has previously been described in the gastric mucosa and in the distal part of the oesophagus. The resemblance to pancreatic acinar cells prompted us to study the possible occurrence of secretory pancreatic proteins in these cells. Methods: Seven specimens obtained from the distal oesophagus at gastroscopy where routine microscopy showed pancreatic acinar-like metaplasia were selected for this study. Sections were subjected to immunohistochemical detection of trypsinogen, pancreatic elastase, procarboxypeptidase B and pancreatic secretory trypsin inhibitor using specific antisera. An alkaline-phosphatase-conjugated oligodeoxynucleotide probe, complementary to the transcript for trypsinogen 2 (anionic) was used for in situ hybridization. Results: Cells with pancreatic acinar-like metaplasia were immunoreactive to all pancreatic secretory proteins studied. In situ hybridization showed the presence of trypsinogen 2 mRNA in pancreatic acinar-like metaplasia. The pancreatic proteins were not seen in other cells in the distal oesophagus. Conclusion: Pancreatic acinar-like metaplasia is common in the distal oesophagus and pancreatic secretory proteins, including trypsininogen 2, are produced in the oesophageal metaplastic acinar cells. The biological significance of this finding has yet not been thoroughly studied.
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5.
  • Paju, A, et al. (författare)
  • Expression and characterization of trypsinogen produced in the human male genital tract
  • 2000
  • Ingår i: American Journal of Pathology. - 1525-2191. ; 157:6, s. 2011-2021
  • Tidskriftsartikel (refereegranskat)abstract
    • Trypsinogen is a serine proteinase produced mainly by the pancreas, but it has recently been found to be expressed also in several cancers such as ovarian and colon cancer and in vascular endothelial cells. In this study, we found that trypsinogen-1 and -2 are present at high concentrations (median levels, 0.4 and 0.5 mg/L, respectively) in human seminal fluid and purified them to homogeneity by immunoaffinity and anion exchange chromatography. Purified trypsinogen isoenzymes displayed a M(r) of 25 to 28 kd in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. Most of the trypsinogen-1 purified from seminal fluid was enzymatically active whereas trypsinogen-2 occurred as the proform, which could be activated by enteropeptidase in vitro. Immunohistochemically, trypsinogen protein was detected in the human prostate, urethra, utriculus, ejaculatory duct, seminal vesicles, deferent duct, epididymal glands, and testis. Expression of trypsinogen mRNA in the same organs was demonstrated by in situ hybridization. Trypsinogen mRNA was also detected in the prostate and seminal vesicles by reverse transcriptase-polymerase chain reaction and Northern blotting. Isolated trypsin was shown to activate the proenzyme form of prostate-specific antigen. These results suggest that trypsinogen isoenzymes found in seminal fluid are produced locally in the male genital tract and that they may play a physiological role in the semen.
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6.
  • Andrén Sandberg, Ake, et al. (författare)
  • Early prediction of severity in acute pancreatitis. Is this possible?
  • 2002
  • Ingår i: Journal of the Pancreas. - 1590-8577. ; 3:5, s. 25-116
  • Tidskriftsartikel (refereegranskat)abstract
    • One out of ten cases of acute pancreatitis develops into severe acute pancreatitis which is a life threatening disorder with a high mortality rate. The other nine cases are self limiting and need very little therapy. The specificity of good clinical judgement on admission, concerning the prognosis of the attack, is high (high specificity) but misses a lot of severe cases (low sensitivity). The prediction of severity in acute pancreatitis was first suggested by John HC Ranson in 1974. Much effort has been put into finding a simple scoring system or a good biochemical marker for selecting the severe cases of acute pancreatitis immediately on admission. Today C-reactive protein is the method of choice although this marker is not valid until 48-72 hours after the onset of pain. Inflammatory mediators upstream from CRP like interleukin-6 and other cytokines are likely to react faster and preliminary results for some of these mediators look promising. Another successful approach has been to study markers for the activation of trypsinogen such as TAP and CAPAP. This is based on studies showing that active trypsin is the initial motor of the inflammatory process in acute pancreatitis. In the near future a combined clinical and laboratory approach for early severity prediction will be the most reliable. Clinical judgement predicts 1/3 of the severe cases on admission and early markers for either inflammation or trypsinogen activation should accurately identify 50-60% of the mild cases among the rest, thus missing only 2-4% of the remaining severe cases. One problem is that there is no simple and fast method to analyze any of these parameters.
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7.
  • Appelros, Stefan, et al. (författare)
  • Activation peptide of carboxypeptidase B and anionic trypsinogen as early predictors of the severity of acute pancreatitis.
  • 2001
  • Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 88:2, s. 216-221
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary Background Early prediction of severity is important in the management of patients with acute pancreatitis. The presence of activation peptides and certain pancreatic proenzymes in plasma and urine has been shown to correlate with severity. This study was designed to assess the value of measuring levels of the activation peptide of carboxypeptidase B (CAPAP) and of anionic trypsinogen. Methods Concentrations of CAPAP and anionic trypsinogen were measured in the urine and serum in 60 patients with acute pancreatitis. Preset cut-off levels were used to analyse the accuracy of the tests. Severity was classified retrospectively according to the Atlanta classification. Results Concentrations of CAPAP in urine and serum and of anionic trypsinogen in urine correlated with the severity of the pancreatitis. CAPAP in urine showed the highest accuracy. The overall accuracy was 90 per cent, with a positive predictive value of 69 per cent and a negative predictive value of 98 per cent. Conclusion In this study, measurement of CAPAP in urine was an accurate way to predict the severity of acute pancreatitis, and was superior to assay of anionic trypsinogen in urine and serum. Measurement of CAPAP in urine may be of value in the management of individual patients with pancreatitis and in the selection of patients for therapeutic trials.
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8.
  • Appelros, Stefan, et al. (författare)
  • Activation peptide of carboxypeptidase B in serum and urine in acute pancreatitis
  • 1998
  • Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 42:1, s. 97-102
  • Tidskriftsartikel (refereegranskat)abstract
    • The pathophysiology of acute pancreatitis involves activation of the pancreatic proenzymes. Levels of the trypsinogen activation peptide in urine in acute pancreatitis has been shown to correlate with the severity of disease. However, this peptide is unstable in urine and, because of its low molecular mass, difficult to measure. Procarboxypeptidase B has a larger activation peptide which could be more suitable for analysis in serum and urine.
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9.
  • Appelros, Stefan, et al. (författare)
  • Incidence, aetiology and mortality rate of acute pancreatitis over 10 years in a defined urban population in Sweden
  • 1999
  • Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 86:4, s. 465-470
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: There is a wide range (5-50 per 100 000) in the reported annual incidence of acute pancreatitis. Furthermore, the predominant aetiology varies in different reports. This study was undertaken to establish the current incidence, aetiology and associated mortality rate in a defined population. METHODS: A retrospective study of all cases of acute pancreatitis admitted over a 10-year period to a single institution was performed. In addition the autopsy and forensic materials were reviewed. RESULTS: Altogether 883 attacks of acute pancreatitis were recorded, of which 547 were first attacks. The annual incidence of first attacks was 23.4 per 100 000. Including relapses, the incidence was 38.2 per 100 000. Biliary disease was the main aetiological factor in first attacks whereas alcohol was the predominant factor when relapses were included. The mean annual mortality rate for acute pancreatitis in the population was 1.3 per 100 000. Of 31 patients who died from acute pancreatitis only 15 were diagnosed before death. For recurrent disease the mortality rate was 0.3 per cent. In 12 patients the pancreatitis was associated with pancreatic carcinoma. CONCLUSION: It is important to differentiate between first attacks and relapses, since both incidence and aetiology figures are influenced by this, and it is important to include autopsy and forensic material in population-based mortality studies.
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10.
  • Appelros, Stefan, et al. (författare)
  • Short and long term outcome of severe acute pancreatitis.
  • 2001
  • Ingår i: European Journal of Surgery. - : Oxford University Press (OUP). - 1102-4151. ; 167:4, s. 281-286
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Between 1985 and 1994, 883 cases of acute pancreatitis were treated in Malmö, Sweden (population 233,000). The purpose of this study was to report the short- and long-term outcome of the 79 cases that were severe, according to the Atlanta classification. DESIGN: Retrospective and follow-up study a median time of 7 years since the attack. SETTING: University hospital, Sweden. SUBJECTS: 79 patients with severe acute pancreatitis. MAIN OUTCOME MEASURES: Mortality, cause of death, organ failure, local complications, surgical procedures, mortality since the attack, and endocrine and exocrine dysfunction. RESULTS: Twenty-one patients died from their attack. Organ failure was the predominant cause of death in the 13 patients who died during the first 10 days after admission, whereas infection was the most common cause of death in patients who died later. Mortality was low under the age of 60 and increased with age. Organ failure developed in 72 patients. Twenty-four patients developed pancreatic necrosis or abscesses and 18 patients were treated by necrosectomy and open or closed drainage. At follow-up, 13 patients had died, 2 from pancreatic carcinoma. 35 patients were included in the follow-up survey. 15 of these had diabetes and an additional 4 had impaired glucose tolerance. 9 patients had signs of severe exocrine dysfunction. CONCLUSIONS: There was a high incidence of endocrine and exocrine dysfunction together with, in many patients, ongoing social problems related to chronic alcoholism several years after an attack of severe acute pancreatitis.
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