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  • 1.
    Abednazari, Hossein
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Xu, Junyang
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Millinger, Eva
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Respiratory Medicine. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Department of Clinical Physiology, County Hospital, Kalmar, Sweden.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nayeri, Fariba
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Hepatocyte growth factor is a better indicator of therapeutic response than C-reactive protein within the first day of treatment in pneumonia2006In: Chemotherapy, ISSN 0009-3157, E-ISSN 1421-9794, Vol. 52, no 5, p. 260-263Article in journal (Refereed)
    Abstract [en]

    Acute bacterial infectious diseases are mostly treated empirically at admission before the culture results are available. According to the risk for serious complications in the case of therapeutic failure, it is important to evaluate the therapy results and change to a more appropriate antibiotic regime as soon as possible. In the present study, 40 patients with X-ray-verified community-acquired pneumonia were examined and blood specimens were collected before and within 24 h of treatment. Body temperature, C-reactive protein (CRP) and hepatocyte growth factor (HGF) were investigated. Thirty-two patients received an appropriate initial antibiotic therapy regarding clinical outcome, but in 8 patients the treatment was changed because of therapy failure. Changes of HGF levels after 18–24 h of treatment could predict the therapeutic results accurately in 38 of 40 cases (sensitivity 100%, specificity 94%, positive likelihood ratio 16.0). HGF was significantly better to predict therapy outcome than CRP (p < 0.0001).

  • 2.
    Abednazari, Hossin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. PEAS Institute, Linköping.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Almroth, Gabriel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Nilsson, Ingela
    Kalmar County Hospital, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Hepatocyte growth factor is a reliable marker for efficient anti-bacterial therapy within the first day of treatment2014In: Advances in Bioscience and Biotechnology, ISSN 2156-8456, E-ISSN 2156-8502, Vol. 5, no 10, p. 823-830Article in journal (Refereed)
    Abstract [en]

    Rapid diagnosis and choice of appropriate antibiotic treatment might be life-saving in serious infectious diseases. Still the available markers that can evaluate and monitor the diagnosis and treatment are few. Hepatocyte growth factor (HGF) has been studied as a potent regenerative factor produced and released during injuries such as infectious diseases. Monitoring of HGF levels might predict therapy results better than C-reactive protein (CRP) within the first day of treatment in pneumonia. For further investigation of previous observations we aimed to study HGF as a first-day marker in over-representing infectious diseases in comparison to procalcitonin (PCT), CRP and body temperature. Fifty-one patients with community acquired infectious diseases were included consequently at admittance and the serum samples were collected before and within 18 - 24 hours of treatment. HGF levels decreased significantly in case of efficient antibiotic therapy and HGF was shown to be better than PCT, CRP and body temperature to evaluate treatment. In patients with pneumonia, monitoring of HGF was most reasonable. HGF might be used as a therapeutic marker within the first day of empiric antibiotic treatment during infection.

  • 3.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Lonn, J
    University of Örebro, Sweden .
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Andersson, B
    Sahlgrens University Hospital, Sweden .
    Hahn-Zoric, M
    Sahlgrens University Hospital, Sweden .
    Fibroblast Growth Factor 23, Hepatocyte Growth Factor, Interleukin-6, High-Sensitivity C-Reactive Protein and Soluble Urokinase Plasminogen Activator Receptor. Inflammation Markers in Chronic Haemodialysis Patients?2013In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 78, no 3, p. 285-290Article in journal (Refereed)
    Abstract [en]

    Sera from 84 haemodialysis (HD) patients and 68 healthy blood donors were analysed with commercially available ELISA techniques for fibroblast growth factor 23 (FGF-23), hepatocyte growth factor (HGF), interleukin-6 (Il-6), high-sensitivity C-reactive protein (hs-CRP) and soluble urokinase plasminogen activator receptor (suPAR), to find a possible correlation of FGF-23 and HGF with the earlier recognized inflammatory markers Il-6 and hs-CRP or suPAR. All patients studied had significantly elevated levels of FGF-23, HGF, hs-CRP and suPAR as compared to the controls. Il-6 and hs-CRP correlated for patients (R=0.6) as well as for patients and controls altogether. Ln (natural logarithm) of HGF correlated weakly with Ln Il-6 and Ln CRP (R 0.28-0.37). Ln FGF-23 correlated only with Ln HGF (r=-0.25) in controls. Ln HGF correlated with ln suPAR (r=0.6) in both patients and controls. Although elevated as compared to controls, we found no correlation of FGF-23 with the recognized inflammatory markers Il-6, hs-CRP, nor HGF or the new marker suPAR in HD patients. Ln HGF correlated with Ln Il-6, Ln CRP and Ln suPAR. Although probably involved in vessel disease, FGF-23 and HGF may play other roles than acting in inflammatory vessel disease in HD patients. Further studies are necessary to evaluate the role of these immunological markers in chronic haemodialysis patients with atherosclerosis.

  • 4.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medical and Health Sciences, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Lönn, J
    School of Health and Medical Sciences, Örebro, Sweden.
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Andersson, B
    Hahn-Zoric, M
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Tillväxtfaktorer och inflammationsmarkörer vid kronisk njursvikt2013In: Njurmedicinskt vårmöte Jönköping 12-14 maj 2013, 2013Conference paper (Refereed)
  • 5.
    Börgeson, Emma
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Lönn, Johanna
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Bergström, Ida
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Brodin Patcha, Veronika
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Sarndahl, Eva
    University Orebro.
    Bengtsson, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Lipoxin A(4) Inhibits Porphyromonas gingivalis-Induced Aggregation and Reactive Oxygen Species Production by Modulating Neutrophil-Platelet Interaction and CD11b Expression2011In: INFECTION AND IMMUNITY, ISSN 0019-9567, Vol. 79, no 4, p. 1489-1497Article in journal (Refereed)
    Abstract [en]

    Porphyromonas gingivalis is an etiological agent that is strongly associated with periodontal disease, and it correlates with numerous inflammatory disorders, such as cardiovascular disease. Circulating bacteria may contribute to atherogenesis by promoting CD11b/CD18-mediated interactions between neutrophils and platelets, causing reactive oxygen species (ROS) production and aggregation. Lipoxin A(4) (LXA(4)) is an endogenous anti-inflammatory and proresolving mediator that is protective of inflammatory disorders. The aim of this study was to investigate the effect of LXA(4) on the P. gingivalis-induced activation of neutrophils and platelets and the possible involvement of Rho GTPases and CD11b/CD18 integrins. Platelet/leukocyte aggregation and ROS production was examined by lumiaggregometry and fluorescence microscopy. Integrin activity was studied by flow cytometry, detecting the surface expression of CD11b/CD18 as well as the exposure of the high-affinity integrin epitope, whereas the activation of Rac2/Cdc42 was examined using a glutathione S-transferase pulldown assay. The study shows that P. gingivalis activates Rac2 and Cdc42 and upregulates CD11b/CD18 and its high-affinity epitope on neutrophils, and that these effects are diminished by LXA(4). Furthermore, we found that LXA(4) significantly inhibits P. gingivalis-induced aggregation and ROS generation in whole blood. However, in platelet-depleted blood and in isolated neutrophils and platelets, LXA(4) was unable to inhibit either aggregation or ROS production, respectively. In conclusion, this study suggests that LXA(4) antagonizes P. gingivalis-induced cell activation in a manner that is dependent on leukocyte-platelet interaction, likely via the inhibition of Rho GTPase signaling and the downregulation of CD11b/CD18. These findings may contribute to new strategies in the prevention and treatment of periodontitis-induced inflammatory disorders, such as atherosclerosis.

  • 6.
    Ljunggren, Stefan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Bengtsson, Torbjorn
    Orebro Univ, Sweden.
    Karlsson, Helen
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center. Linköping University, Faculty of Medicine and Health Sciences.
    Starkhammar Johansson, Carin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Public Dental Health Care.
    Palm, Eleonor
    Orebro Univ, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Davies, Julia
    Malmo Univ, Sweden.
    Svensater, Gunnel
    Malmo Univ, Sweden.
    Lönn, Johanna
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences. Orebro Univ, Sweden; Malmo Univ, Sweden.
    Modified lipoproteins in periodontitis: a link to cardiovascular disease?2019In: Bioscience Reports, ISSN 0144-8463, E-ISSN 1573-4935, Vol. 39, no 3, article id BSR20181665Article in journal (Refereed)
    Abstract [en]

    There is a strong association between periodontal disease and atherosclerotic cardiovascular disorders. A key event in the development of atherosclerosis is accumulation of modified lipoproteins within the arterial wall. We hypothesise that patients with periodontitis have an altered lipoprotein profile towards an atherogenic form. Therefore, the present study aims at identifying modifications of plasma lipoproteins in periodontitis. Lipoproteins from ten female patients with periodontitis and gender- and age-matched healthy controls were isolated by density-gradient ultracentrifugation. Proteins were separated by 2D gel-electrophoresis and identified by map-matching or by nano-LC followed by MS. Apolipoprotein (Apo) A-I (ApoA-I) methionine oxidation, Oxyblot, total antioxidant capacity and a multiplex of 71 inflammation-related plasma proteins were assessed. Reduced levels of apoJ, phospholipid transfer protein, apoF, complement C3, paraoxonase 3 and increased levels of alpha-1-antichymotrypsin, apoA-II, apoC-III were found in high-density lipoprotein (HDL) from the patients. In low-density lipoprotein (LDL)/very LDL (VLDL), the levels of apoL-1 and platelet-activating factor acetylhydrolase (PAF-AH) as well as apo-B fragments were increased. Methionine oxidation of apoA-I was increased in HDL and showed a relationship with periodontal parameters. alpha-1 antitrypsin and alpha-2-HS glycoprotein were oxidised in LDL/VLDL and antioxidant capacity was increased in the patient group. A total of 17 inflammation-related proteins were important for group separation with the highest discriminating proteins identified as IL-21, Fractalkine, IL-17F, IL-7, IL-1RA and IL-2. Patients with periodontitis have an altered plasma lipoprotein profile, defined by altered protein levels as well as post-translational and other structural modifications towards an atherogenic form, which supports a role of modified plasma lipoproteins as central in the link between periodontal and cardiovascular disease (CVD).

  • 7.
    Lönn, J.
    et al.
    Division of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Starkhammar Johansson, Carin
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Kälvegren, Hanna
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Skoglund, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, The Institute of Technology.
    Garvin, Peter
    Linköping University, Department of Medical and Health Sciences, Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Särndahl, E.
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Ravald, Nils
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Richter, Arina
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Bengtsson, T.
    Division of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Hepatocyte growth factor in patients with coronary artery disease and its relation to periodontal condition2012In: Results in Immunology, ISSN 2211-2839, Vol. 2, p. 7-12Article in journal (Refereed)
    Abstract [en]

    Hepatocyte growth factor (HGF) is an angiogenic, cardioprotective factor important for tissue and vascular repair. High levels of HGF are associated with chronic inflammatory diseases, such as coronary artery disease (CAD) and periodontitis, and are suggested as a marker of the ongoing atherosclerotic event in patients with CAD. Periodontal disease is more prevalent among patients with CAD than among healthy people. Recent studies indicate a reduced biological activity of HGF in different chronic inflammatory conditions. Biologically active HGF has high affinity to heparan sulfate proteoglycan (HSPG) on cell-membrane and extracellular matrix. The aim of the study was to investigate the serum concentration and the biological activity of HGF with ELISA and surface plasmon resonance (SPR), respectively, before and at various time points after percutaneous coronary intervention (PCI) in patients with CAD, and to examine the relationship with periodontal condition. The periodontal status of the CAD patients was examined, and the presence of P. gingivalis in periodontal pockets was analyzed with PCR. The HGF concentration was significantly higher, at all time-points, in patients with CAD compared to the age-matched controls (P< 0.001), but was independent of periodontal status. The HGF concentration and the affinity to HSPG adversely fluctuated over time, and the biological activity increased one month after intervention in patients without periodontitis. We conclude that elevated concentration of HGF but with reduced biological activity might indicate a chronic inflammatory profile in patients with CAD and periodontitis.

  • 8.
    Lönn, J.
    et al.
    Division of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Starkhammar Johansson, Carin
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Sridhar, Sravya
    Division of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Bengtsson, T.
    PEAS Institute, Linköping, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Ravald, Nils
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    High concentrations of hepatocyte growth factor but low biological activity in patients with periodontitisManuscript (preprint) (Other academic)
    Abstract [en]

    Background: High levels of hepatocyte growth factor (HGF), a healing factor with regenerative and cytoprotective effects, has been associated to inflammatory diseases including periodontitis. To induce cellular responses, biologic active HGF requires binding to its receptor c-Met and the co-receptor heparan sulphate proteoglycan (HSPG) on cell membranes and extracellular matrix. The aim of this study was to investigate the concentration and the biological activity of HGF and the relationship with subgingival microbiota in medically healthy subject with / without periodontitis.

    Methods: Saliva, gingival crevicular fluid (GCF) and blood samples from thirty patients with severe periodontitis and thirty periodontally healthy controls were analysed for the concentration of HGF and the binding affinity to HSPG and c-Met, using ELISA and surface plasmon resonance (SPR). Subgingival plaque were analysed for the presence of 18 bacterial species.

    Results: Compared to controls, patients with periodontitis showed higher concentrations of HGF in all three locations (P<0.001), however the binding affinity to HSPG and c-Met were markedly reduced in GCF and in saliva (P<0.002). The patients had higher prevalence of periodontal related bacterial species.

    Conclusion: The increased concentration of HGF in GCF and saliva in patients with severe periodontitis was also reflected in the circulation indicating a systemic effect by periodontitis. However, the biological activity of HGF at local sites of inflammation was reduced. A loss of function of healing factors such as HGF may be one important mechanism in the dominant degenerative processes in periodontally susceptible subjects.

  • 9.
    Lönn, Johanna
    et al.
    PEAS Institute, Linköping, Sweden.
    Almroth, Gabriel
    Linköping University, Department of Medical and Health Sciences, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    An antithrombin III product containing biologically active hepatocyte growth factor may be beneficial in depp ulcer infections2012In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 60, no 2, p. 478-486Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Widely studied for the past 20 years, hepatocyte growth factor (HGF) has been identified as a regenerative marker and an important factor in the development and healing of injuries. Antithrombin III (AT III) is a protein in the blood stream with anti-thrombotic and anti-inflammatory properties and has been used as an adjuvant treatment along with antibiotics in severe sepsis.

    OBJECTIVE:

    To study the content and properties of HGF in plasma-derived AT III products, and the regenerative effect in severe deep ulcer infections.

    METHODS:

    Commercial AT III products were analyzed for the presence and biological activity of HGF. One AT III product containing biologically active HGF was used to treat 18 cases of critical, deep ulcer infections scheduled for major invasive intervention. The patients were followed up for 6-60 months.

    RESULTS:

    The AT III products contained HGF with different biological activity. No adverse reactions were observed after local administration of AT III during the study or follow-up period. In 16 of 18 cases no surgical intervention was needed within the first 6 month of inclusion.

    CONCLUSION:

    AT III products containing biologically active HGF may contribute to regeneration and healing in severe deep ulcer infections which do not respond adequately to different combinations of antibiotics alone.

  • 10.
    Lönn, Johanna
    et al.
    PEAS Institut AB, Linköping, Sweden.
    Shahzad, Faisal
    PEAS Institut AB, Linköping, Sweden.
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Bengtsson, Torbjörn
    Örebro University, Sweden.
    Almroth, Gabriel
    Linköping University, Department of Medical and Health Sciences, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    High concentration but low biological activity of hepatocyte growth factor in patients with chronic renal failure2012In: Advances in Bioscience and Biotechnology, ISSN 2156-8456, E-ISSN 2156-8502, Vol. 3, no 4, p. 516-523Article in journal (Refereed)
    Abstract [en]

    Hepatocyte growth factor (HGF) is a renotropic, an- tifibrotic and regenerative factor with cytoprotective effects that is produced by mesenchymal cells and shows high affinity to components of extra cellular matrix, such as heparan sulphate proteoglycan (HS- PG), in healthy. Patients with chronic renal failure (CRF) suffer from a chronic inflammatory disorder. In order to assess the underlying mechanisms for de- velopment of CRF we aimed to assess the amounts and affinity of HGF in this patient group. ELISA, western blot and surface plasmon resonance (SPR) were used to study HGF in blood samples, as well as in isolated neutrophils, in CRF patients compared to healthy controls. Patients with CRF showed higher HGF levels in serum (P < 0.0001), but decreased af- finity to HSPG (P < 0.0001). Addition of protease in-hibitors decreased the difference between patients with CRF compared to healthy individuals. HGF with potent regenerative function during injury lacks af-finity to HSPG in patients with CRF that may depend on production of proteases from activated immune cells. This information might be used to highlight un-derlying mechanisms for chronicity and leading to new strategies for treatment of chronic injuries.

     

     

  • 11.
    Lönn, Johanna
    et al.
    Univ Orebro, Sch Hlth & Med Sci, Div Clin Med, Orebro, Sweden; PEAS Institute, Linköping and Örebro University, Sweden.
    Starkhammar Johansson, Carin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Public Dental Health Care.
    Nakka, Sravya
    PEAS Institute, Linköping, Sweden.
    Palm, Elenor
    Örebro University, Sweden.
    Bengtsson, Torbjörn
    Örebro University, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases. PEAS Inst, Inst Prot Environm Affin Surveys, Linkoping, Sweden.
    Ravald, Nils
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Public Dental Health Care.
    High Concentration but Low Activity of Hepatocyte Growth Factor in Periodontitis2014In: Journal of Periodontology, ISSN 0022-3492, E-ISSN 1943-3670, Vol. 85, no 1, p. 113-122Article in journal (Refereed)
    Abstract [en]

    Background: High levels of hepatocyte growth factor (HGF), a healing factor with regenerative and cytoprotective effects, are associated with inflammatory diseases, including periodontitis. HGF biologic activity requires binding to its receptors, the proto-oncogene c-Met and heparan sulfate proteoglycan (HSPG). This study investigates HGF expression and its relationship to subgingival microbiota in medically healthy individuals with and without periodontitis.

    Methods: Saliva, gingival crevicular fluid (GCF), and blood samples from 30 patients with severe periodontitis and 30 healthy controls were analyzed for HGF concentration using enzyme-linked immunosorbent assay and binding affinity for HSPG and c-Met using surface plasmon resonance. The regenerative effects of saliva from three patients and controls were analyzed in an in vitro model of cell injury. Subgingival plaques were analyzed for the presence of 18 bacterial species.

    Results: Patients with periodontitis showed higher HGF concentrations in saliva, GCF, and serum (P <0.001); however, the binding affinities for HSPG and c-Met were reduced in GCF and saliva (P <0.002). In contrast to the controls, saliva from patients showed no significant regenerative effect over time on gingival epithelial cells. Compared with controls, patients had a higher prevalence of periodontally related bacteria.

    Conclusions: Higher circulatory HGF levels indicate a systemic effect of periodontitis. However, the HGF biologic activity at local inflammation sites was reduced, and this effect was associated with the amount of periodontal bacteria. Loss of function of healing factors may be an important mechanism in degenerative processes in periodontally susceptible individuals.

  • 12.
    Nayeri, Fariba
    Linköping University, Department of Molecular and Clinical Medicine. Linköping University, Faculty of Health Sciences.
    Hepatocyte growth factor: Studies on local and systemic release and effects during infectious disease; in vivo and in vitro2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The interaction of mesenchymal and epithelial cells that occurs after organ injuries results in enhanced production of cytokines, such as hepatocyte growth factor (HGF). HGF is a glycoprotein with unique properties that contribute to wound healing after injuries. In the present thesis, the release and role of HGF during infectious diseases have been investigated with particular emphasis on pneumonia and meningitis. First, a standard method for serum handling of HGF was determined. It was shown that HGF was stable in the serum after separation and several freeze-thaw cycles, keeping at room temperature for several hours or storage at -70 °C for several months, shaking or adding heparin and albumin did not affect HGF levels in serum. However, for reliable results whole blood had to be separated within one hour after venipuncture at room temperature or kept at 4-8 °C in the case of longer storage before separation. Following this standard method, the concentration of HGF during infectious diseases was studied. In another study we had previously shown that levels of HGF in serum increased during the acute phase of several infectious diseases. In this thesis a simultaneous enhanced production of HGF locally at the site of injury was studied. It was shown that concentration of HGF increased locally in cerebrospinal fluid during meningitis. Levels of HGF were significantly higher during bacterial meningitis than viral meningitis and concentration of HGF in cerebrospinal fluid might be used as a tool in diagnosis of bacterial meningitis. It was shown an enhanced local production of HGF in exhaled breath condensate in pneumonia that did not decrease significantly after 4 weeks in spite of the fact that the patient had recovered clinically and in the X-ray controls. This might show a long repair and healing process after pneumonia. Serum levels of HGF were significantly higher in pneumonia caused by Streptococcus pneumoniae than in other causes of pneumonia. In pneumonia, serum levels ofHGF decreased within 48 hours after efficient antibiotic therapy was started and normalized at convalescence. However, the levels of HGF in serum increased when treatment was ineffective and no clinical improvement was observed. When the appropriate therapy was initiated, the levels of HGF decreased followed by clinical recovery. Serum levels of HGF were able to predict therapy results at least as reliably as CRP within 48 hours after treatment. Thus HGF was shown to be a diagnostic moment for acute bacterial infections, and following levels of HGF in serum may perhaps be used as a prognostic marker in the course of treatment of infectious diseases such as pneumonia. The physiological effects of HGF on chronic leg ulcers(> 1 år) in 11 elderly patients were studied and an enhanced microcirculation that was significantly correlated to the healing percentage was observed after local HGF treatment. The infected ulcers that received a combined treatment of HGF and appropriate antibiotic responded with a high percentage of healing in three patients with chronic leg ulcers that had not responded to other treatments (including antibiotics) previously. The effect of HGF on injured mouse melanoma cell monolayer was investigated in vitro and showed that HGF caused migration of neighbouring cells towards the nude injured area in a dose-dependent manner. Concomitant morphogenic effects were observed. The actin structure in the cytoskeleton was changed by HGF treatment as studied by confocal microscopy. According to these results it could be cocluded that injuries caused by infectious organisms enhance the local and systemic production of HGF. This might be beneficial in healing of damage after such injuries. Determination of natural HGF in serum might be used as a diagnostic and prognostic marker during infectious diseases. Exogenous administration of recombinant HGF could be a beneficial treatment for injuries such as chronic leg ulcers particularly combined with the appropriate antibiotic in the case of obvious infection.

    List of papers
    1. Sample handling and stability of hepatocyte growth factor in blood samples
    Open this publication in new window or tab >>Sample handling and stability of hepatocyte growth factor in blood samples
    2002 (English)In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 19, no 4, p. 201-205Article in journal (Refereed) Published
    Abstract [en]

    As regards clinical studies performed on hepatocyte growth factor (HGF) during recent years, we have aimed in the present study to investigate the eventual differences in sample handling of this cytokine that might influence the results of serum concentrations. Venous blood from patients with current infectious diseases and controls was used in different sub-studies. Compared with samples separated within one hour, no significant changes in serum HGF levels were observed when whole blood stayed 4, or 24 h at 6°C before or 6 h in room temperature after separation but HGF levels were significantly higher (P<0.01) when whole blood was kept at room temperature 4 and 24 h before separation. Serum HGF was stable up to 20 freeze-thaw cycles. The serum concentrations of HGF were significantly higher than levels in the plasma (19%; P<0.05). A significant increase in serum HGF levels (12%, P<0.05) was observed after shaking the whole blood sample to a visible haemolysis, although the HGF concentration in blood cells was around half of that in serum. HGF tolerated storage at −70°C for at least 4 months. We conclude that standardized methods in sample handling are important in the study of HGF concentrations in blood samples.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26446 (URN)10.1006/cyto.2002.1050 (DOI)10989 (Local ID)10989 (Archive number)10989 (OAI)
    Note

    On the day of the defence day the status of this article was in press.

    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13
    2. Hepatocyte Growth Factor Levels in Cerebrospinal Fluid: A Comparison between Acute Bacterial and Nonbacterial Meningitis
    Open this publication in new window or tab >>Hepatocyte Growth Factor Levels in Cerebrospinal Fluid: A Comparison between Acute Bacterial and Nonbacterial Meningitis
    Show others...
    2000 (English)In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 181, no 6, p. 2092-2094Article in journal (Refereed) Published
    Abstract [en]

    The organotrophic functions of the hepatocyte growth factor (HGF) have been the subject of several studies. In the more recent studies, this function has been reported in the brain. In the present study, we have measured the levels of HGF in cerebrospinal fluid (CSF) and sera from 78 patients divided into 6 different groups according to central nervous system (CNS) infection and control. Quantitative measurements of HGF in the CSF and serum were performed by an enzyme-linked immunosorbent assay. Elevated values of CSF HGF were found in the patients with acute bacterial/probable bacterial meningitis (P < .001), compared with nonbacterial CNS infections and facial palsy, as well as with a control group without signs of CNS involvement. The values of CSF HGF were not correlated to blood-brain-barrier disruption in the groups. These observations might indicate an intrathecal production of HGF in acute bacterial/probable bacterial meningitis.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-25911 (URN)10.1086/315506 (DOI)10353 (Local ID)10353 (Archive number)10353 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    3. Hepatocyte growth factor may act as an early therapeutic predictor in pneumonia
    Open this publication in new window or tab >>Hepatocyte growth factor may act as an early therapeutic predictor in pneumonia
    Show others...
    2002 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 34, no 7, p. 500-504Article in journal (Refereed) Published
    Abstract [en]

    High serum levels of hepatocyte growth factor (HGF) may reflect the regenerative effect and enhanced local and systemic production of this cytokine after organ injuries. The possibility of using serial serum HGF values in order to predict the results of therapy for pneumonia was investigated in this study. In a prospective multicenter study we investigated the serum levels of HGF and CRP before and within 48 h after treatment in 70 patients with pneumonia. Serum levels of HGF before treatment were significantly higher than the HGF levels of a normal population (p < 0.0001). Within 48 h serum HGF levels had decreased significantly in those patients who ultimately responded to the initial antibiotic therapy (p < 0.0001). Serum HGF levels at 48 h were unchanged or increased in cases in whom the initial therapy was ineffective and had to be changed. CRP and HGF levels were significantly correlated. Using multivariate logistic regression analysis it was found that individual changes in acute serum HGF levels and serum HGF levels obtained within 48 h could predict the results of therapy at least as significantly (p < 0.003) as CRP (p = 0.05), although CRP levels were known and used by the physician to decide whether or not to change the initial therapy. We conclude that serial control of serum HGF levels can be used as an early indicator to predict the results of therapy during treatment of pneumonia.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26409 (URN)10.1080/00365540110080890 (DOI)10950 (Local ID)10950 (Archive number)10950 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    4. Exhaled breath condensate and serum levels of hepatocyte growth factor in pneumonia
    Open this publication in new window or tab >>Exhaled breath condensate and serum levels of hepatocyte growth factor in pneumonia
    Show others...
    2002 (English)In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 96, no 2, p. 115-119Article in journal (Refereed) Published
    Abstract [en]

    Hepatocyte growth factor (HGF) is a protein produced by mesenchymal cells in many organs, which can stimulate epithelial growth. An enhanced production and concentration of HGF is observed after injuries. The lung is one of the major sources of HGF. By cooling exhaled air, a condensate is formed containing molecules from bronchi and alveoli. In order to investigate HGF concentration and time course in pneumonia, paired serum and exhaled breath condensate was collected from 10 patients with pneumonia, 10 patients with non-respiratory infections and 11 healthy controls. The concentration of HGF was measured by an immunoassay kit. In the acute phase HGF-levels in breath condensate and serum were significantly higher in the patients with pneumonia compared to the control groups. Similar concentrations in breath condensate were seen in healthy controls and in patients with non-respiratory infections. In the patients with pneumonia a decrease in serum HGF was seen already after 4–7 days while HGF values in breath condensate remained elevated even after 4–6 weeks. These results might imply local production of HGF in the lungs and a long repair and healing process after pneumonia.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26447 (URN)10.1053/rmed.2001.1225 (DOI)10991 (Local ID)10991 (Archive number)10991 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    5. Hepatocyte growth factor may accelerate healing in chronic leg ulcers: a pilot study
    Open this publication in new window or tab >>Hepatocyte growth factor may accelerate healing in chronic leg ulcers: a pilot study
    Show others...
    2002 (English)In: Journal of dermatological treatment (Print), ISSN 0954-6634, E-ISSN 1471-1753, Vol. 13, no 2, p. 81-86Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND : Hepatocyte growth factor (HGF) is a heparin-binding protein with mitogenic, motogenic and morphogenic activities for various cell types. The regenerative properties of HGF have been the object of several animal and in vitro studies in recent years.

    OBJECTIVE : To investigate the physiological and therapeutic effects of HGF on chronic leg ulcers.

    METHODS : HGF in gel form was locally applied, once daily for 7 days, to 15 of 19 chronic leg ulcers in 11 elderly patients. All patients had previously been treated by conventional methods and their leg ulcers had been in stable conditions for between 1 and 14 years. Any signs of allergy, discomfort or pain were reported daily. Microcirculation perfusion in the ulcers, compared to the intact contiguous skin, was determined by laser Doppler at the beginning of the study, after 1 week and again after 3 months (in seven patients). Ulcer size and characteristics were also documented.

    RESULTS : It was observed that microcirculatory perfusion, which might reflect the angiogenic effect of HGF, was statistically significantly correlated ( r = 0.94, p < 0.002) to ulcer area reduction in the treated ulcers. Excellent (84-100% area reduction) or partial healing (58-59%) was seen in eight out of 11 patients. No control group was included in this pilot study, which must be completed by proper control studies.

    CONCLUSION : This study suggests that HGF may heal chronic leg ulcers, possibly by improving the microcirculation. Proper control studies need to be performed.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-32893 (URN)10.1080/095466302317584449 (DOI)18838 (Local ID)18838 (Archive number)18838 (OAI)
    Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13Bibliographically approved
    6. Hepatocyte growth factor accelerates restitution of damaged mouse melanocyte monolayer in vitro
    Open this publication in new window or tab >>Hepatocyte growth factor accelerates restitution of damaged mouse melanocyte monolayer in vitro
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    In a recent pilot study we observed enhanced wound repair properties in chronic leg ulcers after HGF administration. The aim of the present study was to assess the mechanism of HGF in the wound-healing process by an in vitro study of HGF on a transformed mouse skin epithelial cell line (CCL-53. 1) that expresses the HGF receptor, c-Met. HGF did not enhance cell proliferation, judged by [3H}thymidine incorporation. The restitution of injured epithelial cells was significantly increased by HGF. This effect was dose-dependant, beginning at low concentrations (1ng/ml) of HGF, and was inhibited by heparin. HGF enhanced migration of epithelial cells compared to untreated controls. The actin structure was changed by HGF, with less F-actin in the dense peripheral structures compared to untreated cells. Corresponding morphological changes in cells were found showing spread morphology with smaller intracellular spaces after HGF addition. We conclude that HGF may contribute to restitution of the damaged mouse epithelial cell monolayer by morphologic changes and enhanced motility of cells towards the injured area.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81260 (URN)
    Available from: 2012-09-10 Created: 2012-09-10 Last updated: 2012-09-10
  • 13.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Nayeri, Tayeb
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Xu, Junyang
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Lundström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Åkerlind, Britt
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Health Sciences.
    Hepatocyte growth factor (HGF) in fecal samples: rapid detection by surface plasmon resonance2005In: BMC Gastroenterology, ISSN 1471-230X, E-ISSN 1471-230X, Vol. 5, no 13Article in journal (Refereed)
    Abstract [en]

    Background

    The development of biosensors, based on surface plasmon resonance (SPR) technology, enables monitoring of a variety of biospecific interactions without the need for chemical-, biological- or radiological-labelled reagents.

    Method

    We utilised SPR to detect hepatocyte growth factor (HGF) in reconstituted faecal samples and studied samples from patients with infectious gastroenteritis (n = 20) and normal controls (n = 10). Mouse anti-human HGF monoclonal antibodies and recombinant human HGF receptor (c-Met)/Fc chimera were immobilised in flow cells of a CM5 biosensor chip.

    Results

    We found that infectious gastroenteritis produced a higher signal response compared to controls, due to binding of HGF to monoclonal anti-HGF antibody as well as binding of HGF to c-Met receptor (p < 0.01). The SPR signal response correlated with results from ELISA (r = 72%, p > 0.001). The signal response decreased significantly (p < 0.05) when samples were diluted with dextran, because of reduction in both specific as well as unspecific binding of HGF to dextran. The decrease in the specific response might imply that the dextran- binding site for HGF overlaps with the antibody binding epitope, or that dextran binding induces a conformational change of the HGF molecule. Bands corresponding to HGF were found by gel electrophoresis of purified faeces in an affinity chromatography column immobilised by HGF ligands.

    Conclusion

    Determination of HGF by SPR might be beneficial in diagnosis of acute situations that present with symptoms of gastroenteritis and may, possibly, guide appropriate medical treatments. This is to our knowledge the first report on the use of SPR for detection of HGF in faeces samples.

  • 14.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Almer, Sven
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Department of Clinical Physiology, County Hospital, Kalmar.
    Nilsson, Ingela
    Department of Clinical Chemistry, County Hospital, Kalmar.
    Åkerlind, Britt
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    High hepatocyte growth factor levels in faeces during acute infectious gastroenteritis2003In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 35, no 11-12, p. 858-862Article in journal (Refereed)
    Abstract [en]

    Hepatocyte growth factor (HGF) is a potent mitogen of mature epithelial cells which is produced after organ injuries and acts as a trigger for regeneration in the impaired organ. The aim of the present study was to investigate local production of HGF during infectious gastroenteritis. We measured the concentration of HGF in serum and faeces in 49 patients with acute infectious gastroenteritis (bacterium=30, virus=10, amoebae=1, and probable infection=8) at the time of referral to hospital and at convalescence (n=31). The values were compared with normal healthy vaccination volunteers (n=11) as well as patients with acute non-infectious diarrhoea (n=10). The presence of HGF in faeces was confirmed by ELISA and Western immunoblot. HGF concentrations in faeces was significantly higher in the patients with infectious gastroenteritis compared to the control groups (p<0.0001). Using a cut-off concentration of 20 ng/g, the overall sensitivity of faeces HGF to distinguish infectious gastroenteritis (bacterial, viral, probable infection) was 98% with a specificity of 100%. At convalescence all patients had normal values. There was no significant correlation between HGF concentrations in faeces and serum. Determination of faeces HGF may identify cases of transmittable diarrhoea requiring isolation at an early stage.

  • 15.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Department of Clinical Physiology, County Hospital, Kalmar.
    Darelid, Johan
    Department of Infectious Diseases, County Hospital, Jönköping.
    Nilsson, Ingela
    Department of Clinical Chemistry, County Hospital, Kalmar, Sweden.
    Frydén, Aril
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Söderström, Claes
    Department of Infectious Diseases, County Hospital, Kalmar, Sweden.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Hepatocyte growth factor may act as an early therapeutic predictor in pneumonia2002In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 34, no 7, p. 500-504Article in journal (Refereed)
    Abstract [en]

    High serum levels of hepatocyte growth factor (HGF) may reflect the regenerative effect and enhanced local and systemic production of this cytokine after organ injuries. The possibility of using serial serum HGF values in order to predict the results of therapy for pneumonia was investigated in this study. In a prospective multicenter study we investigated the serum levels of HGF and CRP before and within 48 h after treatment in 70 patients with pneumonia. Serum levels of HGF before treatment were significantly higher than the HGF levels of a normal population (p < 0.0001). Within 48 h serum HGF levels had decreased significantly in those patients who ultimately responded to the initial antibiotic therapy (p < 0.0001). Serum HGF levels at 48 h were unchanged or increased in cases in whom the initial therapy was ineffective and had to be changed. CRP and HGF levels were significantly correlated. Using multivariate logistic regression analysis it was found that individual changes in acute serum HGF levels and serum HGF levels obtained within 48 h could predict the results of therapy at least as significantly (p < 0.003) as CRP (p = 0.05), although CRP levels were known and used by the physician to decide whether or not to change the initial therapy. We conclude that serial control of serum HGF levels can be used as an early indicator to predict the results of therapy during treatment of pneumonia.

  • 16.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Department of Clinical Physiology, County Hospital, Kalmar, Sweden.
    Nilsson, Ingela
    Department of Clinical Chemistry, County Hospital, Kalmar, Sweden.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Sample handling and stability of hepatocyte growth factor in blood samples2002In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 19, no 4, p. 201-205Article in journal (Refereed)
    Abstract [en]

    As regards clinical studies performed on hepatocyte growth factor (HGF) during recent years, we have aimed in the present study to investigate the eventual differences in sample handling of this cytokine that might influence the results of serum concentrations. Venous blood from patients with current infectious diseases and controls was used in different sub-studies. Compared with samples separated within one hour, no significant changes in serum HGF levels were observed when whole blood stayed 4, or 24 h at 6°C before or 6 h in room temperature after separation but HGF levels were significantly higher (P<0.01) when whole blood was kept at room temperature 4 and 24 h before separation. Serum HGF was stable up to 20 freeze-thaw cycles. The serum concentrations of HGF were significantly higher than levels in the plasma (19%; P<0.05). A significant increase in serum HGF levels (12%, P<0.05) was observed after shaking the whole blood sample to a visible haemolysis, although the HGF concentration in blood cells was around half of that in serum. HGF tolerated storage at −70°C for at least 4 months. We conclude that standardized methods in sample handling are important in the study of HGF concentrations in blood samples.

  • 17.
    Nayeri, Fariba
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Cameron, Robert
    Chryssanthou, Erja
    Johansson, Lars
    Söderström, Claes
    Candida glabrata prosthesis infection following pyelonephritis and septicaemia.1997In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 29, p. 635-638Article in journal (Refereed)
  • 18.
    Nayeri, Fariba
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Eriksson, Örjan
    Endotoxin kan sänka nivån av antikroppar mot lipopolysackarid.1998In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 95, p. 3975-3976Article in journal (Other academic)
  • 19.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Holmgren Peterson, Kajsa
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Perskvist, Nasrin
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Peterson, Curt
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    An in vitro model for assessment of the biological activity of hepatocyte growth factor2007In: Growth Factors, ISSN 0897-7194, E-ISSN 1029-2292, Vol. 25, no 1, p. 33-40Article in journal (Refereed)
    Abstract [en]

    Hepatocyte growth factor (HGF) is a multifunctional growth factor with potent wound-healing properties that functions in the healing of chronic injuries. However, there may be a loss of HGF activity in certain chronic cases; this might be indicated by the presence of high amounts of HGF in body fluids and by the elevated expression of the HGF receptor in tissue biopsies. In such cases, a reliable means of assessing the activity of endogenous HGF would be valuable in allowing clinicians to decide if treatment with HGF would be useful. In this study, we developed an in vitro wound assay that used a mouse skin epithelial cell line to evaluate the biological activity of HGF. We showed that HGF accelerated the motility of the epithelial cells in a dose-dependent fashion with high sensitivity and specificity. This in vitro assay might be used to determine the activity of both endogenous and recombinant HGF.

  • 20.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Millinger, Eva
    Linköping University, Department of Medicine and Care, Pulmonary Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Ingela
    Departments of Clinical Chemistry, County Hospital, Kalmar, Sweden.
    Zetterström, Olle
    Linköping University, Department of Molecular and Clinical Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Departments of Clinical Physiology, County Hospital, Kalmar, Sweden.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Exhaled breath condensate and serum levels of hepatocyte growth factor in pneumonia2002In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 96, no 2, p. 115-119Article in journal (Refereed)
    Abstract [en]

    Hepatocyte growth factor (HGF) is a protein produced by mesenchymal cells in many organs, which can stimulate epithelial growth. An enhanced production and concentration of HGF is observed after injuries. The lung is one of the major sources of HGF. By cooling exhaled air, a condensate is formed containing molecules from bronchi and alveoli. In order to investigate HGF concentration and time course in pneumonia, paired serum and exhaled breath condensate was collected from 10 patients with pneumonia, 10 patients with non-respiratory infections and 11 healthy controls. The concentration of HGF was measured by an immunoassay kit. In the acute phase HGF-levels in breath condensate and serum were significantly higher in the patients with pneumonia compared to the control groups. Similar concentrations in breath condensate were seen in healthy controls and in patients with non-respiratory infections. In the patients with pneumonia a decrease in serum HGF was seen already after 4–7 days while HGF values in breath condensate remained elevated even after 4–6 weeks. These results might imply local production of HGF in the lungs and a long repair and healing process after pneumonia.

  • 21.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nayeri, Tayeb
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Clinical impact of real-time evaluation of the biological activity and degradation of hepatocyte growth factor2008In: Growth Factors, ISSN 0897-7194, E-ISSN 1029-2292, Vol. 26, no 3, p. 163-171Article in journal (Refereed)
    Abstract [en]

    Hepatocyte growth factor (HGF) is essential for injury repair. Despite high HGF levels in chronic ulcers, up-regulation of HGF receptor in ulcer tissue and decreased biological activity of HGF in ulcer secretions have been observed. With a surface plasmon resonance-based method, we assessed the binding of HGF to antibodies, receptors, and the basement membrane and identified binding interactions that are indispensable for the biological activity of HGF. Recombinant HGF (rHGF) lots were tested for activity, structural integrity, and degradation, and the results were verified in an in vitro model of cell injury. Biologically active rHGF, as well as plasma from healthy volunteers, bound to heparan sulphate proteoglycan (HSPG) and to anti-HGF antibodies. Decreased binding to HSPG was the first event in rHGF degradation. This study established the feasibility of identifying patients with chronic inflammation who need exogenous HGF and of using ligand-binding assessment to evaluate rHGF lots for biological activity.

  • 22.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nilsson, I.
    Laboratories of Clinical Chemistry, Kalmar County Hospital Hospital, Kalmar, Sweden.
    Brudin, L.
    Department of Physiology, County Hospital, Kalmar, Sweden.
    Almer, Sven
    Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences.
    Stability of faecal hepatocyte growth factor determination2004In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 64, no 6, p. 589-597Article in journal (Refereed)
    Abstract [en]

    In order to evaluate the accuracy and reproducibility of determination of hepatocyte growth factor (HGF) levels in faeces, the stability of HGF in samples processed in different ways was investigated. An ELISA method was used for determination of HGF concentrations. Faeces samples from healthy controls and patients with infectious diarrhoea were studied. It was found that faeces HGF concentration remained stable irrespective of whether samples were freeze‐thawed several times, kept for 6, 12 or 24 h at room temperature or refrigerated for 6, 12, 24 or 36 h; the levels of HGF did not change significantly when samples were freeze‐dried. Adding protease inhibitor to the faeces samples did not affect the HGF levels. There were no significant differences between HGF levels using phosphate buffered saline (PBS) (pH 7.4) or NaCL as buffer, but it was observed that levels of HGF were significantly lower in the samples that were diluted in distilled water. Although both HGF and albumin through various mechanisms may increase in faeces during infectious diarrhoea, there was no significant correlation between faeces HGF levels and albumin levels, which might indicate local production of HGF in the bowel in response to infection. It is concluded that determination of faeces HGF levels is feasible with a high degree of stability. Increased HGF levels in faeces might represent a local production of HGF during bowel injury and might be of use as a diagnostic and monitoring assay.

  • 23.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nilsson, I.
    Department of Clinical Chemistry, County Hospital, Kalmar.
    Brudin, Lars
    Department of Clinical Physiology, County Hospital, Kalmar.
    Frydén, Aril
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Söderström, C.
    Departmenf of Infectious Diseases, Count Hospital, Kalmar, Sweden.
    High serum hepatocyte growth factor levels in the acute stage of community-acquired infectious diseases2002In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 34, no 2, p. 127-130Article in journal (Refereed)
    Abstract [en]

    Acute serum levels of hepatocyte growth factor (HGF) were studied in 6 clinical groups with (i) gastroenteritis, (ii) skin and soft tissue infection, (iii) urinary tract infection, (iv) septicemia, (v) influenza, and (vi) chronic hepatitis C in comparison with a normal control group using an enzyme-linked immunosorbent assay method. We found that serum HGF levels were significantly higher in patients with acute infectious diseases (p < 0.0001) compared to patients with chronic viral hepatitis and healthy controls. Serum HGF and CRP levels were correlated significantly (r = 0.65, p < 10-7). We conclude that serum HGF levels are elevated in patients with acute infectious diseases.

  • 24.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Nilsson, Ingela
    Department of Clinical Chemistry, County Hospital, Kalmar.
    Hagberg, Lars
    Department of Infectious Diseases, Sahlgrenska Hospital, Göteborg.
    Brudin, Lars
    Department of Clinical Physiology, County Hospital, Kalmar.
    Roberg, Magnus
    Department of Infectious Diseases, County Hospital, Norrköping, Sweden .
    Söderström, Claes
    Department of Infectious Diseases, County Hospital, Kalmar.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Hepatocyte Growth Factor Levels in Cerebrospinal Fluid: A Comparison between Acute Bacterial and Nonbacterial Meningitis2000In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 181, no 6, p. 2092-2094Article in journal (Refereed)
    Abstract [en]

    The organotrophic functions of the hepatocyte growth factor (HGF) have been the subject of several studies. In the more recent studies, this function has been reported in the brain. In the present study, we have measured the levels of HGF in cerebrospinal fluid (CSF) and sera from 78 patients divided into 6 different groups according to central nervous system (CNS) infection and control. Quantitative measurements of HGF in the CSF and serum were performed by an enzyme-linked immunosorbent assay. Elevated values of CSF HGF were found in the patients with acute bacterial/probable bacterial meningitis (P < .001), compared with nonbacterial CNS infections and facial palsy, as well as with a control group without signs of CNS involvement. The values of CSF HGF were not correlated to blood-brain-barrier disruption in the groups. These observations might indicate an intrathecal production of HGF in acute bacterial/probable bacterial meningitis.

  • 25.
    Nayeri, Fariba
    et al.
    Department of Infectious Diseases, Count Hospital, Kalmar, Sweden.
    Nilsson, Ingela
    Department of Clinical Chemistry, County Hospital, Kalmar.
    Skude, Gunnar
    Department of Clinical Chemistry, County Hospital, Kalmar.
    Brudin, Lars
    Department of Clinical Physiology, County Hospital, Kalmar, Sweden.
    Söderström, Claes
    Department of Infectious Diseases, Count Hospital, Kalmar, Sweden.
    Hepatocyte growth factor (HGF) in patients with pneumonia: a comparison between survivors and non-survivors1998In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 30, no 4, p. 405-409Article in journal (Refereed)
    Abstract [en]

    Hepatocyte growth factor (HGF) is a multifunctional growth factor. After lung injury HGF is secreted in the lung and promotes reconstruction of the damaged organ. We measured, retrospectively, the serum HGF concentrations collected on admission in 55 patients with bacterial pneumonia, using an enzyme-linked immunosorbent assay (ELISA). The patients were divided into 3 groups: Group 1 was survivors with normal liver function (n=14), Group 2 was survivors with abnormal liver function (n=31) and Group 3 was non-survivors (n=10). Median concentrations of HGF were elevated in Groups 1 and 2; and no statistically significant difference between these 2 groups was found. Group 3 had a median HGF concentration within the reference range, significantly lower than both Group 1 and Group 2. In addition LDH was significantly higher in non-survivors as compared with survivors. The combination of LDH and HGF concentrations discriminated between survivors and non-survivors (sensitivity 0.90 and specificity 0.96). The results support the hypothesis that increased levels of HGF might be a natural part of the healing process of lung injury, irrespective of liver involvement, and that patients without increased HGF levels, especially those with concomitant liver function impairment, may have a poor prognosis.

  • 26.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Olsson, Hans
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Peterson, Curt
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Hepatocyte growth factor, expression, concentration and biological activity in chronic leg ulcers2005In: Journal of dermatological science (Amsterdam), ISSN 0923-1811, E-ISSN 1873-569X, Vol. 37, no 2, p. 75-85Article in journal (Refereed)
    Abstract [en]

    Background:

    Hepatocyte growth factor (HGF) is a multifunctional cytokine that is involved in recovery process after organ injuries.

    Objective:

    We studied HGF and the membrane bound receptor, c-met locally in patients who suffered from chronic leg ulcers (≥1 year) caused by venous insufficiency.

    Methods:

    Skin biopsies from the edge of the ulcers were taken from patients (n = 13) and studied by immunohistochemical staining for detection of HGF and c-met. Skin biopsies from healthy volunteers (n = 10) were used as the control material. Ulcer secretion from chronic ulcers (n = 11) was examined for the presence of HGF by ELISA and the concentration of HGF was compared with acute ulcers in healthy controls (n = 10) and in patients operated for a non-invasive breast cancer (n = 12).

    Results:

    We observed that c-met expression in the ulcer area increased significantly in chronic ulcers compared to controls (p = 0.005). Concentration of ulcer-HGF in the patients with chronic ulcer was significantly higher than acute ulcers (p < 0.01). The biological activity of HGF in ulcer secret was assessed in-vitro in transferred, mouse skin epithelial cell monolayer. Enhanced migration and morphologic changes were seen after adding ulcer secret from acute ulcers (>1 ng/mL) that was inhibited by anti-HGF antibodies. No biological activity was observed by adding ulcer secret from chronic ulcers irrespective HGF concentration.

    Conclusion:

    We conclude that in chronic skin ulcers decreased biological activity of endogenous HGF and overexpression of c-met is seen which might explain fibrosis and delayed recovery. Administration of exogenous active HGF might contribute to accelerated healing in these patients.

  • 27.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Olsson, Hans
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Söderström, Claes
    Department of Infectious Diseases, County Hospital in Kalmar, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Department of Clinical Physiology, County Hospital in Kalmar, Sweden.
    Peterson, Curt
    Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Hepatocyte growth factor in chronic leg ulcers – no biological activity – no improvement2005In: Journal of dermatological science (Amsterdam), ISSN 0923-1811, E-ISSN 1873-569X, Vol. 39, no 1, p. 62-64p. 62-64Article in journal (Other academic)
    Abstract [en]

    No abstract available.

  • 28.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Perskvist, Nasrin
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Holmgren-Pettersson, Kajsa
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Hepatocyte growth factor accelerates restitution of damaged mouse melanocyte monolayer in vitroManuscript (preprint) (Other academic)
    Abstract [en]

    In a recent pilot study we observed enhanced wound repair properties in chronic leg ulcers after HGF administration. The aim of the present study was to assess the mechanism of HGF in the wound-healing process by an in vitro study of HGF on a transformed mouse skin epithelial cell line (CCL-53. 1) that expresses the HGF receptor, c-Met. HGF did not enhance cell proliferation, judged by [3H}thymidine incorporation. The restitution of injured epithelial cells was significantly increased by HGF. This effect was dose-dependant, beginning at low concentrations (1ng/ml) of HGF, and was inhibited by heparin. HGF enhanced migration of epithelial cells compared to untreated controls. The actin structure was changed by HGF, with less F-actin in the dense peripheral structures compared to untreated cells. Corresponding morphological changes in cells were found showing spread morphology with smaller intracellular spaces after HGF addition. We conclude that HGF may contribute to restitution of the damaged mouse epithelial cell monolayer by morphologic changes and enhanced motility of cells towards the injured area.

  • 29.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Health Sciences.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Department of Clinical Physiology, County Hospital, Kalmar, Sweden.
    Söderström, Charlotte
    Department of Infectious Diseases, County Hospital, Kalmar, Sweden.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Hepatocyte growth factor may accelerate healing in chronic leg ulcers: a pilot study2002In: Journal of dermatological treatment (Print), ISSN 0954-6634, E-ISSN 1471-1753, Vol. 13, no 2, p. 81-86Article in journal (Refereed)
    Abstract [en]

    BACKGROUND : Hepatocyte growth factor (HGF) is a heparin-binding protein with mitogenic, motogenic and morphogenic activities for various cell types. The regenerative properties of HGF have been the object of several animal and in vitro studies in recent years.

    OBJECTIVE : To investigate the physiological and therapeutic effects of HGF on chronic leg ulcers.

    METHODS : HGF in gel form was locally applied, once daily for 7 days, to 15 of 19 chronic leg ulcers in 11 elderly patients. All patients had previously been treated by conventional methods and their leg ulcers had been in stable conditions for between 1 and 14 years. Any signs of allergy, discomfort or pain were reported daily. Microcirculation perfusion in the ulcers, compared to the intact contiguous skin, was determined by laser Doppler at the beginning of the study, after 1 week and again after 3 months (in seven patients). Ulcer size and characteristics were also documented.

    RESULTS : It was observed that microcirculatory perfusion, which might reflect the angiogenic effect of HGF, was statistically significantly correlated ( r = 0.94, p < 0.002) to ulcer area reduction in the treated ulcers. Excellent (84-100% area reduction) or partial healing (58-59%) was seen in eight out of 11 patients. No control group was included in this pilot study, which must be completed by proper control studies.

    CONCLUSION : This study suggests that HGF may heal chronic leg ulcers, possibly by improving the microcirculation. Proper control studies need to be performed.

  • 30.
    Nayeri, Fariba
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Xu, Junjang
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Abdiu, Avni
    Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Linköping University, Faculty of Health Sciences.
    Nayeri, Tayeb
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Carlsson, Uno
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Health Sciences.
    Autocrine production of biologically active hepatocyte growth factor (HGF) by injured human skin2006In: Journal of dermatological science (Amsterdam), ISSN 0923-1811, E-ISSN 1873-569X, Vol. 43, no 1, p. 49-56Article in journal (Refereed)
    Abstract [en]

    Background

    Hepatocyte growth factor (HGF) is a potent regenerative factor involved in wound healing. Previous studies have shown that mesenchymal cells produce HGF, stimulating epithelial cells in a paracrine fashion.

    Objective

    To examine whether autocrine HGF production by keratinocytes can occur upon skin injury.

    Methods

    A 31-year-old male patient sustained a burn affecting 80% of his total body surface area. Biopsies were taken from intact skin near the injured area, and skin keratinocytes were separated and cultured. Conditioned medium from keratinocytes was analyzed for HGF by ELISA, surface plasmon resonance (SPR), and dot blotting. Binding of HGF from conditioned medium to its receptor, c-Met, was compared with recombinant HGF by SPR. Finally, we examined the motogenic effect on mouse transformed skin epithelial cells (CCL-53.1) of HGF from conditioned medium.

    Results

    HGF was detected in the cultured keratinocyte medium. Similar to recombinant HGF, HGF from conditioned medium had a high affinity for dextran sulfate and albumin, and the same epitopes were engaged by the interaction of HGF with the c-Met receptor. The conditioned medium from keratinocytes obtained from the burn patient, but not medium from keratinocytes obtained from healthy volunteers, accelerated the motogenesis of CCL-53.1 cells. Unexpectedly, anti-HGF antibodies did not prevent this effect. However, anti-c-Met antibodies completely inhibited the motogenic effect.

    Conclusion

    Upon injury, human skin keratinocytes might produce biologically active HGF in an autocrine fashion. This HGF might have different structural and/or biological properties from HGF produced by mesenchymal cells.

  • 31.
    Ramezani, Amir
    et al.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Nägga, Katarina
    Department of Clinical Sciences Malmö, Lunds University, Malmö.
    Hansson, Oskar
    Department of Clinical Sciences Malmö, Lunds University, Malmö.
    Lönn, Johanna
    , School of Health and Medical Sciences, Örebro University.
    Sjöwall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Katoozian, Fateme
    PEAS Institut, Linköping .
    Mansouri, Sepahdar
    PEAS Institut, Linköping .
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. PEAS Institut, Linköping .
    Hepatocyte growth factor in cerebrospinal fluid differentiates community-acquired or nosocomial septic meningitis from other causes of pleocytosis2015In: Fluids and Barriers of the CNS, ISSN 2045-8118, E-ISSN 2045-8118, Vol. 12, no 1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Due to anatomical restrictions, the inflammatory response to intracerebral bacterial infections exposes swollen brain tissues to pressure and ischemia, resulting in life-threatening damage. Rapid diagnosis and immediate empirical antibiotic therapy is highly important. However, diagnosing meningitis in patients after neurosurgery is complicated, due to brain tissue damage and changes in cerebrospinal fluid (CSF) caused by surgery. Hepatocyte growth factor (HGF) is a local, acute-phase protein with healing properties. Previous studies on community-acquired septic meningitis reported high levels of intrathecally produced HGF. The present study focused on nosocomial meningitis in assessing the levels of HGF in the CSF.

    METHODS: HGF concentrations (ELISA) and HGF binding to receptors; c-Met receptor and heparan sulfate proteoglycan were determined in CSF samples (surface plasmon resonance). CSF samples from patients with community-acquired or nosocomial meningitis (217 samples from 135 patients) were compared to those from controls without signs of cerebral nervous system involvement (N = 36) and patients with Alzheimer's disease (N = 20).

    RESULTS: Compared to samples from patients that had undergone neurosurgery and had other infectious diseases, CSF samples from patients with nosocomial meningitis had significantly higher HGF concentrations (p < 0.001) and binding affinity to c-Met (p < 0.001) and HSPG (p = 0.043) receptors. The sensitivity and specificity to identify nosocomial septic meningitis were 69.7 and 93.4 %, respectively. The HGF concentration and binding affinity to HGF receptors were significantly higher in CSF from patients with community-acquired septic meningitis compared to patients with aseptic (viral and subacute) meningitis as well as controls (p < 0.001). The sensitivity and specificity to identify community-acquired septic meningitis were 95.4 and 95.7 %, respectively.

    DISCUSSION: In febrile nosocomial infections that occurred post neurosurgery, HGF assessment could substantially improve the differentiation of meningitis from other infections and therefore might be a tool for rapid diagnosis, limiting injuries and guiding antibiotic therapy.

  • 32.
    Sorour, Ashraf E
    et al.
    Cairo University, Egypt.
    Lönn, Johanna
    Örebro University, Sweden .
    Nakka, Sravya Sowdamini
    Örebro University, Sweden .
    Nayeri, Tayeb
    PEAS Institut, Linköping.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging. PEAS Institut, Linköping.
    Evaluation of hepatocyte growth factor as a local acute phase response marker in the bowel: The clinical impact of a rapid diagnostic test for immediate identification of acute bowel inflammation2014In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 71, no 1, p. 8-15Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There are no rapid tests that can distinguish contagious gastroenteritis, which requires isolation at its onset, from exacerbation of chronic inflammatory bowel disease (IBD) or bowel engagement in the course of systemic inflammatory response syndrome (SIRS). Hepatocyte growth factor (HGF) is an acute phase cytokine that is produced at the site of injury. It has high affinity to sulfated glycan, and this binding affinity is lost during chronic inflammation. The fecal pH strongly impacts the prognosis for severe bowel disease. We developed a strip test to evaluate HGF as a local acute phase response marker in the bowel. This test assessed the binding affinity of HGF to sulfated glycans in fecal samples and determined fecal pH as an indicator of illness severity.

    METHODS: Fresh feces from patients with diarrhea (n=513) were collected and tested blindly, and information about patient illness course and outcome was collected. Patients were classified based on the focus of inflammation and the cause of the symptoms. Objectively verified diagnoses of infectious gastroenteritis (n=131) and IBD onset/exacerbation and bowel cancer (n=44) were used to estimate the performance of the test strip. ELISA was performed on 101 freeze-thawed feces samples to determine the fecal HGF levels.

    RESULTS: The test rapidly distinguished infectious gastroenteritis from non-infectious inflammatory causes of diarrhea (sensitivity, 87.96%; specificity, 90.9%; positive predictive value, 96.6%; negative predictive value, 71.4%; accuracy, 89.1%). Fecal pH (p<0.0001) and mortality within 28days of sampling (p<0.04) was higher in patients with sepsis/SIRS and diarrhea. The concentration of HGF was higher in strip test-positive stool samples (p<0.01).

    CONCLUSIONS: HGF is a good local acute phase response marker of acute bowel inflammation. Test-strip determination of the binding affinity of fecal HGF to sulfated glycan was a rapid, equipment-free way to assess patients with diarrhea and to guide the diagnostic and therapeutic approaches on admission.

  • 33.
    Sowdamini Nakka, Sravya
    et al.
    PEAS Institut, Linköping, Sweden.
    Johansson, Jessica
    Örebro University, Sweden.
    Shahzad, Fasial
    PEAS Institut, Linköping, Sweden.
    Hanning, Anders
    Episentec AB, Sollentuna, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases. PEAS Institut, Linköping.
    A methachromatic-based experimental model for identification of bowel as the focus of an acute inflammation2013In: Open Journal of Gastroenterology, ISSN 2163-9450, E-ISSN 2163-9469, Vol. 3, no 1, p. 42-48Article in journal (Refereed)
    Abstract [en]

    Diarrhea is the most common symptom of acute inflammation in gastrointestinal tract and the patients are isolated in order to inhibit transmission and to conduct investigations. Yet there is no standard test to distinguish gastrointestinal infection from more generalized diseases at admittance which might cause delay in therapy. Hepatocyte growth factor (HGF) is produced upon injury by mesenchymal cells. On the contrary to chronic inflammation, HGF produced in the course of acute inflammation is biologically active and shows binding affinity to heparan sulphate proteoglycan (HSPG) and dextran sulphate (DS). Based on this phenomenon, an agarose gel containing DS was prepared and immobilized on loops to investigate the feces samples for the presence or absence of growth factors such as HGF with affinity to DS. The study is conducted as a clinical evaluation of an experimental model to distinguish acute infectious gastroenteritis from other causes of diarrhea. 656 fecal samples gathered consequently from patients seeking for bowel disturbances and healthy were tested by the test and the medical reports were investigated. Upon interaction with DS, methylene blue changes color to pink. This phenomenon was inhibited by HGF and converted by addition of anti-HGF antibodies to the samples. The test distinguished acute infectious gastroenteritis with high sensitivity and specificity (96% and 92% respectively) from other causes of diarrhea. We introduce a metachromatic experimental model that might distinguish acute inflammation in alimentary tract from other causes of diarrhea. This model might be used in developing rapid diagnostic tests.

  • 34.
    Uhlin, Fredrik
    et al.
    Östergötlands Läns Landsting, Centre for Medicine, Department of Nephrology UHL. Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    Nayeri, Tayeb
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    Brudin, Lars
    Department of Clinical Physiology, Kalmar County Hospital.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Almroth, Gabriel
    Östergötlands Läns Landsting, Centre for Medicine, Department of Nephrology UHL. Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    Decreased Biological Activity of Hepatocyte Growth Factor during Chronic Renal Failure2009In: J Am Soc Nephrol, 2009Conference paper (Refereed)
  • 35.
    Williams, George Sie
    et al.
    World Health Organization, Liberia Mission, Liberia .
    Naiene, Jeremias
    World Health Organization, Liberia Mission, Liberia .
    Gayflor, Joseph
    Ministry of Health & Social Welfare, Liberia .
    Malibiche, Theophil
    African Union-ASEOWA Liberia, Liberia .
    Zoogley, Bentoe
    World Health Organization, Liberia Mission, Liberia .
    Frank, Wimot G
    Ministry of Health & Social Welfare, Liberia .
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Twenty-one days of isolation: A prospective observational cohort study of an Ebola-exposed hot zone community in Liberia2015In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 71, no 2, p. 150-7Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: As West Africa continues to suffer from a deadly Ebola epidemic, the national health sectors struggle to minimize the damages and stop the spread of disease.

    METHODS: A cohort of inhabitants of a small village and an Ebola hot zone in Sinoe County of Liberia was followed on a day-by-day basis to search for new cases and to minimize the spread of Ebola to the other community members or to other regions. Technical, clinical, and humanistic aspects of the response are discussed in this report.

    RESULTS: Of the 22 confirmed Ebola cases in Sinoe County since the beginning of outbreak (June 16, 2014), 7 cases were inhabitants of Polay Town, a small village 5.5 miles east of Greenville, the Sinoe County capital. After the last wave of outbreak at the beginning of December, enhanced response activity provided essential coordination and mobilized the resources to stop the epidemic. Despite unprotected contacts in crowded houses, no new cases were detected among the contact families, or in the surrounding houses or communities.

    CONCLUSIONS: Strong national mobilization in a decentralized but harmonized system at the community level has been of great value in controlling the epidemic in Liberia. The major interventions include epidemiological surveillance, public information dissemination, effective communication, case management, and infection control.

  • 36. Xu, Junyang
    et al.
    Jiang, Fengxia
    Nayeri, Fariba
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Zetterström, Olle
    Linköping University, Department of Molecular and Clinical Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Allergy Centre UHL.
    Apoptotic eosinophils in sputum from asthmatic patients correlate negatively with levels of IL-5 and eotaxin2007In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 101, no 7, p. 1447-1454Article in journal (Refereed)
    Abstract [en]

    Background: Eosinophilic inflammation of the airways is a key characteristic of asthma. A defect in eosinophil apoptosis might contribute to the chronic tissue eosinophilia associated with asthma. Objective: Our purpose was to examine whether the occurrence of apoptotic eosinophils in induced sputum from asthmatic patients correlate with interleukin (IL)-5 and eotaxin. Methods: Thirty stable and 30 exacerbated asthmatic patients were recruited. Twenty healthy subjects were enrolled as a control group. Induced sputum was obtained from asthmatic patients and from control subjects. The number of apoptotic eosinophils in sputum was assessed by flow cytometry. In sputum supernatant, eosinophil cationic protein (ECP) was measured by sensitive radioimmunoassay, and IL-5 and eotaxin by sandwich enzyme linked immunosorbant assay. Results: Levels of eosinophils, apoptotic eosinophils, IL-5, ECP and eotaxin from asthmatic patients were higher than those from healthy subjects. Thirty exacerbated asthmatics showed higher proportions of eosinophils (median 29.3%, range 13.4%-40.9%), more detectable levels of IL-5 (50.44, 32.99-67.01 pg/ml) and eotaxin (644.6, 197.4-937.7 pg/ml) in their sputum than the patients with stable asthma (P < 0.05). There were significant inverse correlations between the levels of sputum IL-5 and the proportion of sputum eosinophil apoptosis in patients with exacerbated and stable asthma (r = - 0.85 and -0.79, P < 0.01 and P < 0.05, respectively). Also inverse correlations were found between the levels of eotaxin and the proportion of sputum eosinophil apoptosis in exacerbated (r = - 0.85, P < 0.01), or stable asthma (r = - 0.69, P < 0.05). Additional positive corrlations between the levels of sputum IL-5 and eotaxin in either exacerbatated (r = 0.93, P < 0.01) or stable asthma (r = 0.82, P < 0.05) were observed. Conclusions: Apoptosis of eosinophils might be suppressed by proinflammatory cytokines and chemokines such as IL-5 and eotaxin leading to their accumulation in the lung. Stimulation of eosinophils in airway with IL-5 and eotaxin may play a crucial role in allergic inflammation. © 2007 Elsevier Ltd. All rights reserved.

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