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  • 1.
    Andersson, B.
    et al.
    University of Gothenburg, Sweden.
    Swolin-Eide, D.
    University of Gothenburg, Sweden.
    Kristroem, B.
    Umeå University, Sweden.
    Gelander, L.
    University of Gothenburg, Sweden; Angered Hospital, Sweden.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Region Östergötland, Diagnostikcentrum, Klinisk kemi. Linköpings universitet, Medicinska fakulteten.
    Albertsson-Wikland, K.
    University of Gothenburg, Sweden.
    Seasonal variations in vitamin D in relation to growth in short prepubertal children before and during first year growth hormone treatment2015Ingår i: Journal of Endocrinological Investigation, ISSN 0391-4097, E-ISSN 1720-8386, Vol. 38, nr 12, s. 1309-1317Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose This study investigated the relationship between seasonal variations in 25-hydroxyvitamin D (25(OH) D) levels and growth in prepubertal children during both the pretreatment year and the first year of GH treatment. Methods The study included 249 short prepubertal children with a broad range of GH secretion, GH(max) during a 24 h profile median 23; range 1-127 mU/L, 191 boys (mean age +/- SD, 8.6 +/- 2.6 years), 58 girls (7.5 +/- 1.9 years) receiving GH treatment (mean 43 mu g/kg/day; range 17-99 mu g/kg/day). Serum 25(OH) D was measured using an automated IDS-iSYS immunoassay. Results 25(OH) D levels showed seasonal variation, and decreased significantly during GH treatment. 25(OH) D levels at start and first year reduction in 25(OH) D, correlated (-) with the first year growth response during treatment. The degree of GH secretion capacity within our study population of mainly non-GH deficient children and 25(OH) D sufficient (67 +/- 29 nmol/L) had no influence on 25(OH) D levels. Growth during GH treatment were independent of seasonal variations in 25(OH) D. Multiple regression analysis showed that 25(OH) D levels at treatment start, together with auxological data and IGF-binding protein-3(SDS), explained 61 % of the variation in first year gain in height(SDS). Conclusion 25(OH) D levels were associated with first year growth response to GH and may be a useful contribution to future growth prediction models.

  • 2.
    Andersson, Bjorn
    et al.
    University of Gothenburg, Sweden.
    Swolin-Eide, Diana
    University of Gothenburg, Sweden.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Albertsson-Wikland, Kerstin
    University of Gothenburg, Sweden.
    Short-term changes in bone formation markers following growth hormone (GH) treatment in short prepubertal children with a broad range of GH secretion2015Ingår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 82, nr 1, s. 91-99Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ObjectivesGrowth hormone (GH) promotes longitudinal growth and bone modelling/remodelling. This study investigated the relationship between levels of bone formation markers and growth during GH treatment in prepubertal children with widely ranging GH secretion levels. MethodsThe study group comprised 113 short prepubertal children (mean ageSD, 937213years; 99 boys) on GH treatment (330 +/- 006g/kg/day) for 1year. Blood samples were taken at baseline and 1 and 2weeks, 1 and 3months, and 1year after treatment start. Intact amino-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (BALP) and osteocalcin were measured using an automated IDS-iSYS immunoassay system. ResultsIntact amino-terminal propeptide of type I procollagen (PINP), BALP and osteocalcin, increased in the short-term during GH treatment. PINP after 1week (P=000077), and BALP and osteocalcin after 1month (Pless than00001 and P=00043, respectively). PINP levels at 1 and 3months correlated positively, and osteocalcin levels at 1week and percentage change after 1month correlated negatively, with first year growth response. No significant correlations were found between BALP and first year growth. Multiple regression analysis showed that bone marker levels together with auxological data and insulin-like growth factor binding protein-3 explained the variation in first year growth response to 36% at start, 32% after 2weeks and 48% at 3months. ConclusionShort-term increases in levels of the bone formation markers PINP, BALP and osteocalcin showed different temporal patterns, but all correlated with first year growth response during GH treatment. These markers may be a useful addition to existing prediction models for growth response.

  • 3.
    Aspenberg, Per
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Ortopedicentrum, Ortopedkliniken Linköping.
    Agholme, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet.
    Fahlgren, Anna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Targeting RANKL for reduction of bone loss around unstable implants: OPG-Fc compared to alendronate in a model for mechanically induced loosening2011Ingår i: BONE, ISSN 8756-3282, Vol. 48, nr 2, s. 225-230Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Orthopedic joint prostheses may loosen because of localized bone resorption. Despite initial optimism, there are no reports showing that bisphosphonates can stop the progression of prosthetic loosening once it has begun. This might be due to the strong resorptive stimulus, which continuously recruits new osteoclasts. Therefore, we hypothesized that a treatment targeting osteoclast recruitment would be more efficacious than a treatment reducing osteoclast activity. We used a previously described rat model for instability-induced bone resorption, and compared OPG-Fc with alendronate at a clinically relevant or an extreme dose. A titanium plate was osseointegrated at the rat tibial surface. Instability was simulated by a piston, moving perpendicularly to the bone surface. Piston movement induced bone loss via hydrostatic pressure or fluid flow. Rats were randomized to 5 groups (total n = 56), of which 4 were subjected to instability and one was stable. The unstable groups were injected with either high-dose OPG-Fc (10 mg/kg, twice weekly), a high dose of alendronate (20 mu g /kg/day), an extreme dose of alendronate (200 mu g/kg/day) or saline. Significant protection against resorption could only be shown for OPG-Fc and the extreme alendronate dose. Both alendronate doses reduced serum levels of tartrate-resistant acid phosphatase isoform 5b to a similar extent, demonstrating that the lower dose was able to reduce resorption in the normally remodeling skeleton, although not in the osteolytic lesions caused by instability. Osteoclast numbers in the lesion were increased by the lower bisphosphonate dose and reduced by OPG-Fc. The results suggest the possibility of targeting osteoclast recruitment via the RANKL system in patients with impending prosthetic loosening.

  • 4.
    Astrom, E
    et al.
    Karolinska Institute.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Eksborg, S
    Karolinska University Hospital.
    Soderhall, S
    Karolinska Institute.
    Biochemical bone markers in the assessment and pamidronate treatment of children and adolescents with osteogenesis imperfecta2010Ingår i: ACTA PAEDIATRICA, ISSN 0803-5253, Vol. 99, nr 12, s. 1834-1840Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: To assess the role of biochemical bone markers in classification of children with osteogenesis imperfecta (OI), their possible association with vertebral compression fractures in milder forms of OI and their role in monitoring of intravenous pamidronate (APD) treatment. Methods: Serum total alkaline phosphatase (ALP), bone ALP isoforms (in a subgroup), osteocalcin, type I procollagen carboxy-terminal propeptide, carboxy-terminal telopeptide of type I collagen, and urine deoxypyridinoline (DPD) were measured in a cross-sectional study of 130 untreated individuals, 0.25-20.9 years (median 6.7), with OI types I, III and IV. Of those, sixty-nine were also assessed longitudinally during monthly APD treatment. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Results: Significant differences in bone markers, however not sufficient for individual clinical use, were found in the larger untreated group but not between subgroups with or without vertebral compressions. All bone markers decreased during treatment for 1.0-12.5 years, but with different relative amounts. Changes were not correlated to the improvement in BMD, mobility or pain. Conclusion: Bone markers are, despite significant differences, not useful for the classification of OI type in the individual child and are not associated with vertebral compressions. Serum ALP and urinary DPD are sensitive in monitoring bisphosphonate treatment.

  • 5. Ellnebo-Svedlund, Katarina
    et al.
    Larsson, Lasse
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Jonasson, Jon
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Molekylär och immunologisk patologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och klinisk genetik.
    Magnusson, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Rapid genotyping of the osteoporosis-associated polymorphic transcription factor Sp1 binding site in the COL1A1 gene by pyrosequencing2004Ingår i: Molecular Biotechnology, ISSN 1073-6085, E-ISSN 1559-0305, Vol. 26, s. 87-90Artikel i tidskrift (Refereegranskat)
  • 6. Farley, JR
    et al.
    Magnusson, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Effects of tunicamycin, mannosamine, and other inhibitors of glycoprotein processing on skeletal alkaline phosphatase in human osteoblast-like cells2005Ingår i: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 76, nr 1, s. 63-74Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Skeletal alkaline phosphatase (sALP) is a glycoprotein - ∼20% carbohydrate by weight, with five presumptive sites for N-linked glycosylation, as well as a carboxy-terminal site for attachment of the glycolipid structure (glycosylphosphatidylinositol, GPI), which anchors sALP to the outer surface of osteoblasts. The current studies were intended to characterize the effects of inhibiting glycosylation and glycosyl-processing on the synthesis, plasma membrane attachment, cellular-extracellular distribution, and reaction kinetics of sALP in human osteosarcoma (SaOS-2) cells. sALP synthesis, glycosylation, and GPI-anchor attachment were assessed as total protein synthesis/immunospecific sALP synthesis, sialic acid content (i.e., wheat germ agglutinin precipitation), and insolubility (i.e., temperature-dependent phase-separation), respectively. sALP reaction kinetics were characterized by analysis of dose-dependent initial velocity data, with a phosphoryl substrate. The results of these studies revealed that the inhibition of either N-linked glycosylation or oligosaccharide synthesis for GPI-anchor addition could affect the synthesis and the distribution of sALP, but not the kinetics of the phosphatase reaction. Tunicamycin - which blocks N-linked glycosylation by inhibiting core oligosaccharide synthesis - decreased cell layer protein and the total amount of sALP in the cells, while increasing the relative level of sALP in the cell-conditioned culture medium (CM, i.e., the amount of sALP released). These effects were attributed to dose- and time-dependent decreases in sALP synthesis and N-linked glycosylation, and an increase in apoptotic cell death (P < 0.001 for each). In contrast to the effects of tunicamycin on N-linked glycosylation, the effects of mannosamine, which inhibits GPI-anchor glycosylation/formation, included (1) an increase in cell layer protein, (2) decreases in sALP specific activity, in the cells and in the CM, and (3) increases in the percentages of both anchorless and wheat germ agglutinin (WGA)-soluble sALP in the medium, but not in the cells (P < 0.005 for each). These effects of mannosamine were, presumably, a consequence of inhibiting the insertion/attachment of sALP to the outside of the plasma membrane surface. Neither mannosammine nor tunicamycin had any effect on the reaction kinetics of sALP or on the apparent affinity (the value of KM) for the phosphoryl substrate.

  • 7.
    Haarhaus, Mathias
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Njurmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Njurmedicinska kliniken US.
    Arnqvist, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Endokrinmedicinska enheten.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Calcifying Human Aortic Smooth Muscle Cells Express Different Bone Alkaline Phosphatase Isoforms, Including the Novel B1x Isoform2013Ingår i: Journal of Vascular Research, ISSN 1018-1172, E-ISSN 1423-0135, Vol. 50, nr 2, s. 167-174Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Vascular calcification, causing cardiovascular morbidity and mortality, is associated with hyperphosphatemia in chronic kidney disease (CKD). In vitro, phosphate induces transdifferentiation of vascular smooth muscle cells to osteoblast-like cells that express alkaline phosphatase (ALP). In vivo, raised serum ALP activities are associated with increased mortality. A new bone ALP isoform (B1x) has been identified in serum from CKD patients. The present study investigated the different ALP isoforms in calcifying human aortic smooth muscle cells (HAoSMCs). Methods: HAoSMCs were cultured for 30 days in medium containing 5 or 10 mmol/l beta-glycerophosphate in the presence or absence of the ALP-specific inhibitor tetramisole. Results: All known bone-specific ALP (BALP) isoforms (B/I, B1x, B1 and B2) were identified in HAoSMCs. beta-Glycerophosphate stimulated calcification of HAoSMCs, which was associated with increased BALP isoforms B/I, B1x and B2. Tetramisole inhibited the beta-glycerophosphate-induced HAoSMC calcification, which was paralleled by the inhibition of the B1x and B/I, but not the other isoforms. Conclusions: HAoSMCs express the four known BALP isoforms. B/I, B1x and B2 could be essential for soft tissue calcification. B/I and B1x were more affected by tetramisole than the other isoforms, which suggests different biological functions during calcification of HAoSMCs.

  • 8.
    Haarhaus, Mathias
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Njurmedicin. Östergötlands Läns Landsting, Medicincentrum, Njurmedicinska kliniken US.
    Fernström, Anders
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Njurmedicin. Östergötlands Läns Landsting, Rekonstruktionscentrum, Neurokirurgiska kliniken US.
    Larsson, Lasse
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Magnusson, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Magnusson, Martin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Njurmedicin.
    Evaluation of bio-intact (1-84) parathyroid hormone, vitamin D status and bond mineral density in patients with predialysis chronic renal failure2004Ingår i: ASN Renal Week,2004, 2004Konferensbidrag (Övrigt vetenskapligt)
  • 9.
    Haarhaus, Mathias
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Njurmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Njurmedicinska kliniken.
    Fernström, Anders
    Linköpings universitet, Institutionen för medicin och vård, Njurmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Njurmedicinska kliniken US.
    Magnusson, Martin
    Linköpings universitet, Institutionen för medicin och vård, Njurmedicin. Linköpings universitet, Hälsouniversitetet.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Clinical significance of bone alkaline phosphatase isoforms, including the novel B1x isoform, in mild to moderate chronic kidney disease2009Ingår i: NEPHROLOGY DIALYSIS TRANSPLANTATION, ISSN 0931-0509, Vol. 24, nr 11, s. 3382-3389Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Mineral bone disorder (MBD) is a common complication of chronic kidney disease (CKD) even during the early stages. Bone alkaline phosphatase (BALP) is a marker of bone fort-nation and plays a pivotal role in the mineralization process. Three BALP isoforms (B/I, B1 and B2) have been identified in healthy individuals and a fourth isoform (B1x) has been discovered in serum from dialysis patients. We investigated these BALP isoforms, type I procollagen intact amino-terminal propeptide (PINP), carboxy-terminal telopeptide of type I collagen (CTX) and tartrate-resistant acid phosphatase isoform 5b (TRACP5b), as well as bone mineral density (BMD) in predialysis CKD patients. Methods. PINP, CTX, TRACP5b and BALP isoforms were analysed in serum from 46 patients within CKD stages 3-5. BMD was determined by dual-energy x-ray absorptiometry. Results. PINP, TRACP5b and the BALP isoforms, B/I, B1 and B2, were independent predictors of total hip BMD in all patients. Furthermore, B/I predicted osteopaenia in the hip and in the distal 1/3 of the radius in CKD stage 3. The B1x isoform was detected in nine patients (20%), who had lower GFR, higher phosphate and calcium x phosphate product. Conclusion. We found an association of BALP isoforms and other markers of bone turnover with total hip BMD, which predominantly comprises trabecular bone. The association of the new BALP isoform B1x with risk factors for vascular calcification leads us to hypothesize a possible role for B1x in this process. The significance of the BALP isoforms in CKD remains to be further explored in experimental and clinical settings in conjunction with bone histomorphometry.

  • 10.
    Haarhaus, Mathias
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Njurmedicinska kliniken US. Department of Nephrology, Karolinska University Hospital, Stockholm, Sweden.
    Fernström, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Njurmedicinska kliniken US. Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Albert B. Chandler Medical Center, USA.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi. Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Albert B. Chandler Medical Center, USA.
    A multicenter prospective study of bone alkaline phosphatase isoforms and arterial calcification in chronic kidney disease patients on dialysis2014Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Chronic kidney disease – mineral and bone disorder (CKD-MBD) is associated with high morbidity and mortality due to frequent cardiovascular (CV) complications. Accelerated arterial stiffening and calcification are associated with serum alkaline phosphatase (ALP) in advanced CKD. We have previously described three bone ALP (BALP) isoforms in healthy individuals and detected a novel isoform, B1x, exclusively in serum from some CKD patients, in bone and in calcifying vascular smooth muscle cells. We investigated the association of these BALP isoforms, abdominal aortic calcification (AAC) score and carotid – femoral pulse wave velocity (PWV), with outcome in a 2-year prospective multicenter study of 68 prevalent dialysis patients participating in the Calcification Outcome in Renal Disease (CORD) study. Twenty-one patients experienced a combined event of all-cause mortality or a first nonfatal CV event during follow-up. PWV (hazard ratio 1.067, P = 0.03) was independently associated with the combined event. B1x was detected in 53 patients and was associated with baseline PWV (Kendall's tau 0.23, P = 0.007) and with variation of PWV over time (estimate 14.14, P = 0.03). Patients with B1x had lower levels of PTH and total ALP, indicating a possible association with low bone turnover. We found no association of BALP isoforms with AAC score. Cox regression revealed B1x as a positive predictor of event free survival (hazard ratio 0.98, P = 0.01). In conclusion, B1x is associated with vascular stiffness in CKD 5D. This finding is contrasted by the ability of B1x to predict longer event free survival in the current study.

  • 11.
    Haarhaus, Mathias
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Njurmedicinska kliniken US. Department of Nephrology, Karolinska University Hospital, Stockholm, Sweden.
    Monier-Faugere, Marie-Claude
    Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Albert B. Chandler Medical Center, USA.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi. Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Albert B. Chandler Medical Center, USA.
    Malluche, Hartmut H.
    Bone alkaline phosphatase isoforms in CKD patients on hemodialysis with low and high bone turnover2014Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Background: Renal osteodystrophy encompasses the bone histologic abnormalities seen in patients with chronic kidney disease (CKD). The bone-specific alkaline phosphatase (BALP) isoform B1x is exclusively found in serum of some CKD patients.

    Study Design: The aim of this cross-sectional diagnostic test study was to examine the relationship between serum BALP isoform activities and histomorphometric parameters of bone in patients with CKD on chronic hemodialysis.

    Setting & Participants: Anterior iliac crest bone biopsy samples from 40 CKD patients were selected on the basis of bone turnover for histomorphometric analysis. There were samples from 20 patients with low and 20 with non-low bone turnover.

    Index Test: In serum, BALP, BALP isoforms (B/I, B1x, B1 and B2), and parathyroid hormone (PTH) were measured.

    Reference Test or Outcome: Indices of osteoblastic activity and number.

    Other Measurements: Parathyroid hormone

    Results: B1x was found in 21 patients (53%) who had lower median levels of BALP, 18.6 versus 46.9 U/L; B/I, 0.10 versus 0.22 μkat/L; B1, 0.40 versus 0.88 μkat/L; B2, 1.21 versus 2.66 μkat/L; and PTH, 49 versus 287 pg/mL, compared to patients without B1x (p<0.001). B1x correlated inversely with osteoblast number and activity. ROC curves showed that B1x (AUC 0.83) can be used for diagnosis of low osteoblastic activity, while BALP (AUC 0.78) and PTH (AUC 0.77) are useful for diagnosis of high osteoblast number seen with high bone turnover.

    Limitations: Small number of study participants.

    Conclusions: The presence of B1x in serum may be a sign of perturbed osteoblast activity and it may be useful as a diagnostic parameter for low bone turnover rate.

  • 12.
    Haarhaus, Mathias
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Njurmedicinska kliniken US. Karolinska University Hospital, Sweden.
    Monier-Faugere, Marie-Claude
    University of Kentucky, KY 40536 USA.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Malluche, Hartmut H.
    University of Kentucky, KY 40536 USA.
    Bone Alkaline Phosphatase Isoforms in Hemodialysis Patients With Low Versus Non-Low Bone Turnover: A Diagnostic Test Study2015Ingår i: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 66, nr 1, s. 99-105Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Renal osteodystrophy encompasses the bone histologic abnormalities seen in patients with chronic kidney disease (CKD). The bone-specific alkaline phosphatase (bALP) isoform B1x is exclusively found in serum of some patients with CKD. Study Design: The aim of this cross-sectional diagnostic test study was to examine the relationship between serum bALP isoform activity and histomorphometric parameters of bone in patients with CKD receiving maintenance hemodialysis. Settings and Participants: Anterior iliac crest bone biopsy samples from 40 patients with CKD were selected on the basis of bone turnover for histomorphometric analysis. There were samples from 20 patients with low and 20 with non-low bone turnover. Index Test: In serum, bALP, bALP isoforms (B/I, B1x, B1, and B2), and parathyroid hormone (PTH) were measured. Reference Test: Low bone turnover was defined by mineral apposition rate, 0.36 mu m/d. Non-low bone turnover was defined by mineral apposition rate greater than= 0.36 mu m/d. Other Measurements: PTH. Results: B1x was found in 21 patients (53%) who had lower median levels of bALP, 18.6 versus 46.9 U/L; B/I, 0.10 versus 0.22 mu kat/L; B1, 0.40 versus 0.88 mu kat/L; B2, 1.21 versus 2.66 mu kat/L; and PTH, 49 versus 287 pg/mL, compared with patients without B1x (P less than 0.001). 13 patients (65%) with low bone turnover and 8 patients (40%) with non-low bone turnover (P less than 0.2) had detectable B1x. B1x correlated inversely with histomorphometric parameters of bone turnover. Receiver operating characteristic curves showed that B1x can be used for the diagnosis of low bone turnover (area under the curve [AUC], 0.83), whereas bALP (AUC, 0.89) and PTH (AUC, 0.85) are useful for the diagnosis of non-low bone turnover. Limitations: Small number of study participants. Requirement of high-performance liquid chromatography methods for measurement of B1x. Conclusions: B1x, PTH, and bALP have similar diagnostic accuracy in distinguishing low from non-low bone turnover. The presence of B1x is diagnostic of low bone turnover, whereas elevated bALP and PTH levels are useful for the diagnosis of non-low bone turnover.

  • 13.
    Halling Linder, Cecilia
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Enander, Karin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Glycation Contributes to Interaction Between Human Bone Alkaline Phosphatase and Collagen Type I2016Ingår i: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 98, nr 3, s. 284-293Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bone is a biological composite material comprised primarily of collagen type I and mineral crystals of calcium and phosphate in the form of hydroxyapatite (HA), which together provide its mechanical properties. Bone alkaline phosphatase (ALP), produced by osteoblasts, plays a pivotal role in the mineralization process. Affinity contacts between collagen, mainly type II, and the crown domain of various ALP isozymes were reported in a few in vitro studies in the 1980s and 1990s, but have not attracted much attention since, although such interactions may have important implications for the bone mineralization process. The objective of this study was to investigate the binding properties of human collagen type I to human bone ALP, including the two bone ALP isoforms B1 and B2. ALP from human liver, human placenta and E. coli were also studied. A surface plasmon resonance-based analysis, supported by electrophoresis and blotting, showed that bone ALP binds stronger to collagen type I in comparison with ALPs expressed in non-mineralizing tissues. Further, the B2 isoform binds significantly stronger to collagen type I in comparison with the B1 isoform. Human bone and liver ALP (with identical amino acid composition) displayed pronounced differences in binding, revealing that post-translational glycosylation properties govern these interactions to a large extent. In conclusion, this study presents the first evidence that glycosylation differences in human ALPs are of crucial importance for protein–protein interactions with collagen type I, although the presence of the ALP crown domain may also be necessary. Different binding affinities among the bone ALP isoforms may influence the mineral-collagen interface, mineralization kinetics, and degree of bone matrix mineralization, which are important factors determining the material properties of bone.

  • 14.
    Halling Linder, Cecilia
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Narisawa, Sonoko
    Sanford Children's Health Research Center.
    Millán, José Luis
    Sanford Children's Health Research Center.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Glycosylation differences contribute to distinct catalytic properties among bone alkaline phosphatase isoforms.2009Ingår i: Bone, ISSN 1873-2763, Vol. 45, nr 5, s. 987-993Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Three circulating human bone alkaline phosphatase (BALP) isoforms (B1, B2, and B/I) can be distinguished in healthy individuals and a fourth isoform (B1x) has been discovered in patients with chronic kidney disease and in bone tissue. The present study was designed to correlate differing glycosylation patterns of each BALP isoform with their catalytic activity towards presumptive physiological substrates and to compare those properties with two recombinant isoforms of the tissue-nonspecific ALP (TNALP) isozyme, i.e., TNALP-flag, used extensively for mutation analysis of hypophosphatasia mutations and sALP-FcD(10), a chimeric enzyme recently used as therapeutic drug in a mouse model of infantile hypophosphatasia. The BALP isoforms were prepared from human osteosarcoma (SaOS-2) cells and the kinetic properties were evaluated using the synthetic substrate p-nitrophenylphosphate (pNPP) at pH 7.4 and 9.8, and the three suggested endogenous physiological substrates, i.e., inorganic pyrophosphate (PP(i)), pyridoxal 5'-phosphate (PLP), and phosphoethanolamine (PEA) at pH 7.4. Qualitative glycosylation differences were also assessed by lectin binding and precipitation. The k(cat)/K(M) was higher for B2 for all the investigated substrates. The catalytic activity towards PEA was essentially undetectable. The kinetic activity for TNALP-flag and sALP-FcD(10) was similar to the activity of the human BALP isoforms. The BALP isoforms differed in their lectin binding properties and dose-dependent lectin precipitation, which also demonstrated differences between native and denatured BALP isoforms. The observed differences in lectin specificity were attributed to N-linked carbohydrates. In conclusion, we demonstrate significantly different catalytic properties among the BALP isoforms due to structural differences in posttranslational glycosylation. Our data also suggests that PEA is not an endogenous substrate for the BALP isoforms or for the recombinant TNALP isoforms. The TNALP-flag and the sALP-FcD(10) isoforms faithfully mimic the biological properties of the human BALP isoforms in vivo validating the use of these recombinant enzymes in studies aimed at dissecting the pathophysiology and treating hypophosphatasia.

  • 15.
    Islam, Quamrul
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi.
    Meirelles, L DA S
    Nardi, NB
    Magnusson, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Islam, Khaleda
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi.
    Polyethylene glycol-mediated fusion between primary mouse mesenchymal stem cells and mouse fibroblasts generates hybrid cells with increased proliferation and altered differentiation2006Ingår i: Stem Cells and Development, ISSN 1547-3287, Vol. 15, nr 6, s. 905-919Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bone marrow-derived mesenchymal stem cells (MSCs) can differentiate into different cell lineages with the appropriate stimulation in vitro. Transplantation of MSCs in human and other animal models was found to repair tissues through the fusion of transplanted MSCs with indigenous cells. We have generated mouse-mouse hybrid cell lines in vitro by polyethylene glycol-mediated fusion of primary mouse MSCs with mouse fibroblasts to investigate the characteristics of hybrid cells, including their potentials for proliferation and differentiation. Similar to the parental MSCs, hybrid cells are positive for the cell-surface markers CD29, CD44, CD49e, and Sca-1, aed negative for Gr1, CD11b, CD13, CD18, CD31, CD43, CD45, CD49d, CD90.2, CD445M/B220, and CD117 markers. The hybrid cells also produce a high level of tissue nonspecific alkaline phosphatase compared to the parental cells. Conditioned medium of hybrid cells contain biologically active factors that are capable of stimulating proliferation of other cells. Although the parental MSCs can differentiate into adipogenic and osteogenic lineages, hybrid cells held disparate differentiation capacity. Hybrid cell lines in general have increased proliferative capacity than the primary MSCs. Our study demonstrates that proliferative hybrid cell lines can be generated in vitro by induced fusion of both im-mortal and primary somatic cells with primary MSCs. © Mary Ann Liebert, Inc.

  • 16.
    Islam, Quamrul
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi.
    Ringe, J
    Reichmann, E
    Migotti, R
    Sittinger, M
    da S. Meirelles, L
    Nardi, N B
    Magnusson, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Islam, Khaleda
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi.
    Functional characterization of cell hybrids generated by induced fusion of primary porcine mesenchymal stem cells with an immortal murine cell line2006Ingår i: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 326, nr 1, s. 123-137Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bone marrow mesenchymal stem cells (MSC) integrate into various organs and contribute to the regeneration of diverse tissues. However, the mechanistic basis of the plasticity of MSC is not fully understood. The change of cell fate has been suggested to occur through cell fusion. We have generated hybrid cell lines by polyethylene-glycol-mediated cell fusion of primary porcine MSC with the immortal murine fibroblast cell line F7, a derivative of the GM05267 cell line. The hybrid cell lines display fibroblastic morphology and proliferate like immortal cells. They contain tetraploid to hexaploid porcine chromosomes accompanied by hypo-diploid murine chromosomes. Interestingly, many hybrid cell lines also express high levels of tissue-nonspecific alkaline phosphatase, which is considered to be a marker of undifferentiated embryonic stem cells. All tested hybrid cell lines retain osteogenic differentiation, a few of them also retain adipogenic potential, but none retain chondrogenic differentiation. Conditioned media from hybrid cells enhance the proliferation of both early-passage and late-passage porcine MSC, indicating that the hybrid cells secrete diffusible growth stimulatory factors. Murine F7 cells thus have the unique property of generating immortal cell hybrids containing unusually high numbers of chromosomes derived from normal cells. These hybrid cells can be employed in various studies to improve our understanding of regenerative biology. This is the first report, to our knowledge, describing the generation of experimentally induced cell hybrids by using normal primary MSC. © Springer-Verlag 2006.

  • 17. Jansson, Ulf
    et al.
    Kristiansson, Bengt
    Magnusson, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi.
    Larsson, Lasse
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Albertsson-Wikland, Kerstin
    Bjarnason, Ragnar
    The decrease of IGF-I, IGF-binding protein-3 and bone alkaline phosphatase isoforms during gluten challenge correlates with small intestinal inflammation in children with coeliac disease.2001Ingår i: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 144, s. 417-423Artikel i tidskrift (Refereegranskat)
  • 18.
    Jia, Ting
    et al.
    Karolinska Institute, Sweden .
    Rashid Qureshi, Abdul
    Karolinska Institute, Sweden .
    Brandenburg, Vincent
    Aachen University Hospital, Germany .
    Ketteler, Markus
    Klinikum Coburg, Germany .
    Barany, Peter
    Karolinska Institute, Sweden .
    Heimburger, Olof
    Karolinska Institute, Sweden .
    Uhlin, Fredrik
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Njurmedicinska kliniken US.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Fernström, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Njurmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Njurmedicinska kliniken US.
    Lindholm, Bengt
    Karolinska Institute, Sweden .
    Stenvinkel, Peter
    Karolinska Institute, Sweden .
    Larsson, Tobias E.
    Karolinska Institute, Sweden .
    Determinants of Fibroblast Growth Factor-23 and Parathyroid Hormone Variability in Dialysis Patients2013Ingår i: American Journal of Nephrology, ISSN 0250-8095, E-ISSN 1421-9670, Vol. 37, nr 5, s. 462-471Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Aims: Treatment strategies for abnormal mineral metabolism in chronic kidney disease are largely based on achieving target ranges of biomarkers that vary considerably over time, yet determinants of their variability are poorly defined. Methods: Observational study including 162 patients of three dialysis cohorts (peritoneal dialysis, n = 78; hemodialysis, n = 49; hemodiafiltration, n = 35). Clinical and biochemical determinants of parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) variability were analyzed in the peritoneal dialysis cohort. All cohorts were used for comparison of PTH and FGF23 intra-subject variability (intra-class correlation), and their intra-subject variability in different modes of dialysis was explored. Results: High PTH variability was independently associated with lower 25-hydroxyvitamin D concentration and factors of lipid and glucose metabolism, whereas high FGF23 variability was mainly associated with lower baseline serum phosphorous. These results were consistent in multivariate and sensitivity analyses. The intra-subject variability of FGF23 was lower than for PTH irrespective of dialysis mode. Conclusions: Baseline vitamin D status and serum phosphorous are independent determinants of the longitudinal variation in PTH and FGF23, respectively. The clinical utility of FGF23 measurement remains unknown, yet it appears favorable based on its greater temporal stability than PTH in dialysis patients.

  • 19.
    Kalén, Anders
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Östergötlands Läns Landsting, Ortopedicentrum, Ortopedkliniken Linköping.
    Wahlström, Ola
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Östergötlands Läns Landsting, Ortopedicentrum, Ortopedkliniken Linköping.
    Linder, Cecilia
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Magnusson, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    The content of bone morphogenetic proteins in platelets varies greatly between different platelet donors2008Ingår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 375, nr 2, s. 261-264Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Platelet derivates and platelet rich plasma have been used to stimulate bone formation and wound healing because of the rich content of potent growth factors. However, not all reports have been conclusive since some have not been able to demonstrate a positive effect. We investigated the interindividual variation of bone morphogenetic proteins (BMPs) in platelets from healthy donors, and the pH-dependent effect on the release of BMPs in preparations of lysed platelets in buffer (LPB). Platelet concentrates from 31 healthy donors were prepared in pH 4.3 and pH 7.4 buffers and investigated with respect to BMP-2, -4, -6, and -7. BMP-2 and BMP-4 were significantly more common in acidic LPBs in comparison with neutral preparations. We also observed a considerable variation among platelet donors with respect to the release of BMPs at pH 4.3 and 7.4. In conclusion, a considerable variation was found among platelet donors, which may be of importance considering the ambiguous results previously reported on osteoblast proliferation and differentiation. © 2008 Elsevier Inc. All rights reserved.

  • 20.
    Kilebrant, Sophie
    et al.
    Regional Vastra Gotaland Child and Youth Habilitat, Sweden.
    Braathen, Gunnar
    Regional Vastra Gotaland Child and Youth Habilitat, Sweden.
    Emilsson, Roger
    Regional Vastra Gotaland Child and Youth Habilitat, Sweden.
    Glansen, Ulla
    Regional Vastra Gotaland Child and Youth Habilitat, Sweden.
    Soderpalm, Ann-Charlott
    University of Gothenburg, Sweden.
    Zetterlund, Bo
    Regional Vastra Gotaland Child and Youth Habilitat, Sweden.
    Westerberg, Barbro
    Regional Vastra Gotaland Child and Youth Habilitat, Sweden.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Swolin-Eide, Diana
    University of Gothenburg, Sweden.
    WHOLE-BODY VIBRATION THERAPY IN CHILDREN WITH SEVERE MOTOR DISABILITIES2015Ingår i: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 47, nr 3, s. 223-228Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To study the effect of whole-body vibration therapy on bone mass, bone turnover and body composition in severely disabled children. Methods: Nineteen non-ambulatory children aged 5.1-16.3 years (6 males, 13 females) with severe motor disabilities participated in an intervention programme with standing exercise on a self-controlled dynamic platform, which included whole-body vibration therapy (vibration, jump and rotation movements). Whole-body vibration therapy was performed at 40-42 Hz, with an oscillation amplitude of 0.2 mm, 5-15 min/treatment, twice/week for 6 months. Bone mass parameters and bone markers were measured at the study start, and after 6 and 12 months. Results: Whole-body vibration therapy was appreciated by the children. Total-body bone mineral density increased during the study period (p less than0.05). Z-scores for total-body bone mineral density ranged from -5.10 to -0.60 at study start and remained unchanged throughout. Approximately 50% of the subjects had increased levels of carboxy-terminal telopeptides of type I collagen and decreased levels of osteocalcin at the start. Body mass index did not change during the intervention period, but had increased by the 12-month follow-up (pless than 0.05). Conclusion: Whole-body vibration therapy appeared to be well tolerated by children with severe motor disabilities. Total-body bone mineral density increased after 6 months of whole-body vibration therapy. Higher carboxy-terminal telopeptides of type I collagen and lower osteocalcin values indicated that severely disabled children have a reduced capacity for bone acquisition.

  • 21. Larsson, L
    et al.
    Fremner, E
    Magnusson, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi.
    Rosenquist, U
    Seven year experience with point-of-care testing (POCT) of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in primary health care laboratories.2003Ingår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 49, nr 6, s. A151-A151Konferensbidrag (Övrigt vetenskapligt)
  • 22.
    Larsson, Lasse
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Larsson, Lasse
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Magnusson, Per
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Magnusson, Per
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Letter to the Editor. Ionized calcium or corrected total calcium?2003Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 18, nr 8, s. 1554-1555Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 23.
    Larsson, Lasse
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi.
    Magnusson, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi.
    Calcium status and supplementation2004Ingår i: Metal ions in biological systems, ISSN 0161-5149, E-ISSN 2154-9214, Vol. 41, s. 71-102Artikel, forskningsöversikt (Refereegranskat)
  • 24.
    Larsson, Lasse
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Magnusson, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Joniserat kalcium ger bättre beslutsunderlag än albuminkorrigerat kalcium2004Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, s. 2289-2290Artikel i tidskrift (Övrigt vetenskapligt)
  • 25.
    Linder, Cecilia
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Englund, Ulrika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Narisawa, Sonoko
    Sanford Burnham Medical Research Institute, CA USA .
    Luis Millan, Jose
    Sanford Burnham Medical Research Institute, CA USA .
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Isozyme profile and tissue-origin of alkaline phosphatases in mouse serum2013Ingår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 53, nr 2, s. 399-408Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mouse serum alkaline phosphatase (ALP) is frequently measured and interpreted in mammalian bone research. However, little is known about the circulating ALPs in mice and their relation to human ALP isozymes and isoforms. Mouse ALP was extracted from liver, kidney, intestine, and bone from vertebra, femur and calvaria tissues. Serum from mixed strains of wild-type (WT) mice and from individual ALP knockout strains were investigated, i.e., Alpl(-/-) (a.k.a. Akp2 encoding tissue-nonspecific ALP or TNALP), Akp3(-/-) (encoding duodenum-specific intestinal ALP or dIALP), and Alpi(-/-) (a.k.a. Akp6 encoding global intestinal ALP or gIALP). The ALP isozymes and isoforms were identified by various techniques and quantified by high-performance liquid chromatography. Results from the WT and knockout mouse models revealed identical bone-specific ALP isoforms (B/I. B1, and B2) as found in human serum, but in addition mouse serum contains the B1x isoform only detected earlier in patients with chronic kidney disease and in human bone tissue. The two murine intestinal isozymes, dIALP and gIALP, were also identified in mouse serum. All four bone-specific ALP isoforms (B/I, B1x, B1, and B2) were identified in mouse bones, in good correspondence with those found in human bones. All mouse tissues, except liver and colon, contained significant ALP activities. This is a notable difference as human liver contains vast amounts of ALP. Histochemical staining, Northern and Western blot analyses confirmed undetectable ALP expression in liver tissue. ALP activity staining showed some positive staining in the bile canaliculi for BALB/c and FVB/N WT mice, but not in C57BI/6 and ICR mice. Taken together, while the main source of ALP in human serum originates from bone and liver, and a small fraction from intestine (andlt;5%), mouse serum consists mostly of bone ALP, including all four isoforms, B/I, B1x, B1, and B2, and two intestinal ALP isozymes dIALP and gIALR We suggest that the genetic nomenclature for the Alpl gene in mice (i.e., ALP liver) should be reconsidered since murine liver has undetectable amounts of ALP activity. These findings should pave the way for the development of user-friendly assays measuring circulating bone-specific ALP in mouse models used in bone and mineral research.

  • 26.
    Ljungdahl, Nina
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Haarhaus, Mathias
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Linder, Cecilia
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Magnusson, Per
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Comparison of 3 Third-Generation Assays for Bio-intact Parathyroid Hormone2006Ingår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 52, nr 5, s. 903-904Artikel i tidskrift (Refereegranskat)
  • 27.
    Löfman, Owe
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Folkhälsovetenskapligt centrum, Folkhälsovetenskapligt centrum. Linköpings universitet, Hälsouniversitetet.
    Magnusson, Per
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Toss, Göran
    Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Larsson, Lasse
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Common biochemical markers of bone turnover predict future bone loss: A 5-year follow-up study2005Ingår i: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 356, nr 1-2, s. 67-75Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    Bone mineral density (BMD) is used to follow gain or loss of bone mass but cannot detect changes within a short period of time. Biochemical markers of bone turnover may be of value for prediction of individual bone loss.

    Methods

    We studied the relation between common inexpensive markers of bone turnover (serum alkaline phosphatase (ALP), osteocalcin (OC), urinary hydroxyproline (OHPr), and calcium (Ca)), BMD, age, and menopause in a combined cross-sectional and longitudinal design comprising 429 pre- and postmenopausal randomly selected women aged 21–79 years (mean 50 years). A follow-up was initiated after 5 years (including 192 of these women), which focused on changes in bone mass and the ability of these four common markers of bone turnover (sampled at baseline) to predict future bone loss.

    Results

    A marked increase was observed for all markers at the beginning of menopause. During the postmenopausal period ALP and Ca decreased to near premenopausal levels, while OC and OHPr remained high even 15 years after menopause. We also found inverse correlations at baseline between the bone markers and BMD, independent of the selected marker or skeletal site, r=−0.14 to −0.46, P<0.05. The correlations between ALP, OC, OHPr, and subsequent bone loss over 5 years, was significant for arm, r=−0.23 to −0.36, P<0.01. Baseline levels of all bone markers correlated significantly at group level with the 5-year follow-up of BMD for all sites. The ability of markers to predict individual bone loss was estimated by a multivariate regression model, which included baseline BMD, age, and body mass index as independent variables. ROC analysis showed a validity of approximately 76% for the forearm model, but was lower for the hip (55%) and lumbar spine (65%).

    Conclusions

    These data show that the common inexpensive biochemical markers of bone turnover ALP, OC, OHPr, and Ca were related to the current bone mass and, moreover, provides information about future bone loss at the individual level. Future investigations should include an evaluation of the clinical relevance of markers of bone turnover in relation to fracture risk.

  • 28.
    Magnusson, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Essä över kunskapsutvecklingsprocessen som forskarhandledare - en reflektion om handledning av doktorander2002Ingår i: Bredd och djup. 6:e universitetspedagogiska konferensen vid Linköpings universitet 14 november 2002 / [ed] Håkan Hult, Linköping: Linköpings universitet , 2002, s. 102-111Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [sv]

    Årets CUL-dag, den sjätte i ordningen, har temat Bredd och djup. Det är ingen slump. I den definition av pedagogisk skicklighet som Linköpings universitet använder sägs att lärare ska ha breda och djupa ämneskunskaper. I detta ligger en utmaning. Forskningen leder vanligtvis till att man får stora kunskaper inom ett begränsat område av ämnet, men i undervisning behövs både ”forskningsfrontskunskaper” och breda kunskaper inom ämnet. Det är en ekvation som kan vara svår att lösa.

    I vår definition av pedagogisk skicklighet sägs vidare att lärare ska ha ett pedagogiskt ledarskap, vilket betyder att han/hon ska ha

    • förmåga att sprida engagemang och intresse för ämnet
    • förmåga att strukturera och organisera kunskapsmassan tillkurser
    • förmåga att aktivera studenterna till egen inlärning
    • förmåga att kommunicera med studenter och andra lärare

    Vidare sägs i definitionen att lärare ska ha förmåga till helhetssyn och förnyelse.

  • 29.
    Magnusson, Per
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Human Bone Alkaline Phosphatase Isoforms1998Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Determination of serum total alkaline phosphatase (ALP) is frequently requested in clinical routine, mostly to estimate skeletal and hepatobiliary status. In this respect, clarification of the various ALP isoenzymes and isoforms contributing to the total ALP activity could be valuable in daily medical decision making. The general aim of this thesis was to investigate methodological, metabolic, and clinical aspects of bone ALP (BALP) isoforms in human bone and mineral metabolism. BALP is a glycoprotein and functions as an ectoenzyme attached to the osteoblast cell membrane by a glycosyl-phosphatidylinositol (GPI) anchor. The precise function of BALP is not known, however, there is evidence that BALP is necessary for initiating bone mineralization.

    A weak anion-exchange high-performance liquid chromatography (HPLC) assay was developed for the determination of BALP and liver ALP (LALP) isoforms. Six peaks with ALP activity were separated and quantified in serum from healthy individuals: B/I, a minor fraction composed of bone (70%) and intestinal (30%) ALP, and two major BALP isoforms B 1 and B2, and three LALP isoforms. Reference intervals were reported for healthy children, adolescents, and adults (range 7-65 years). In healthy adults the BALP isoforms, B/I, Bl, and B2, contributed to 4, 16, and 37%, respectively, of the total ALP activity. Bone samples were prepared from human femora in order to characterize and investigate the origin of these BALP isoforms found in serum. Cortical bone had about 2-fold higher activities of Bl compared with B2, and trabecular bone had about 2-fold higher activities of B2 compared with Bl. Treatment with GPI -specific phospholipase C did not influence the activities or retention times of Bland B2. Thus, the biochemical differences between Bland B2 are likely to be due to different glycosylation patterns, rather than the presence of GPI cell membrane anchor fragments.

    Decreased B I activity was observed after I week of IGF-I administration, and after I month of GH therapy, followed by an increase after 3 months. B2 was not influenced by IGF-I administration, but was similarly increased after 3 months of GH therapy. It was proposed that the initial decrease of B 1 could be an effect of endocrine IGF-I action mediated by GH. Different responses of B 1 and B2 during IGF-I and during GH therapy suggest different regulations of these BALP isoforms in vivo. Differences of BALP isoforms in metastatic bone disease were found, as well as discrepant effects of clodronate on different skeletal sites indicated by the location of bone pain. Patients with skeletal metastases and healthy males had B2 activities corresponding to 75% and 35% of the total ALP activity, respectively.

    Taken together, the BALP isoforms B I and B2 can be used as early indicators of pharmacological efficacy and, possibly provide information relating to specific bone compartments. Future investigations have to elucidate if they also reflect different stages in osteoblast differentiation during osteogenesis where one isoform is presented before the other during extracellular matrix maturation.

  • 30.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Tillförlitliga referensintervall krävs för värdering av P-ALP: Nya pediatriska referensintervall för alkaliskt fosfatas har klinisk betydelse för att hitta rätt till diagnosen2017Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, nr 42, s. 1750-1751, artikel-id ETTHArtikel i tidskrift (Refereegranskat)
    Abstract [sv]

    Age- and gender-specific reference intervals are pivotal to ensure appropriate interpretation of plasma alkaline phosphatase activities in the lower range Hypophosphatasia (HPP) is an inborn error of metabolism caused by loss-of-function mutations of the ALPL gene that mainly express alkaline phosphatase (ALP) in bone and liver. The clinical expression of HPP is highly variable and is classified into six different forms mainly affecting bone and tooth mineralization. The prognosis for each of these HPP forms depends upon the severity of the skeletal disease which reflects the age at presentation. The biochemical hallmark of HPP is low plasma ALP activity (hypophosphatasemia); however, HPP is often misdiagnosed because of low awareness and sometimes absence of age- and gender-specific ALP reference intervals. Children and adolescents have higher ALP levels in comparison with adults. Reliable reference intervals are pivotal for any clinical laboratory test. Harmonized age- and gender-specific plasma ALP reference intervals ought to be used to ensure appropriate interpretation of plasma ALP activities in the lower range.

  • 31.
    Magnusson, Per
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi.
    Arlestig, L.
    Ärlestig, L., Department of Immunology, University of Umeå, Umeå, Sweden, Burnham Institute, La Jolla Cancer Research Center, San Diego, CA, United States.
    Paus, E.
    Central Laboratory, Norwegian Radium Hospital, Oslo, Norway.
    Di, Mauro S.
    Di Mauro, S., Burnham Institute, La Jolla Cancer Research Center, San Diego, CA, United States.
    Testa, M.P.
    Burnham Institute, La Jolla Cancer Research Center, San Diego, CA, United States.
    Stigbrand, T.
    Department of Immunology, University of Umeå, Umeå, Sweden.
    Farley, J.R.
    Musculoskeletal Disease Center, Jerry L. Pettis Mem. VA Med. Center, Loma Linda, CA, United States.
    Nustad, K.
    Central Laboratory, Norwegian Radium Hospital, Oslo, Norway.
    Millan, J.L.
    Millán, J.L., Burnham Institute, La Jolla Cancer Research Center, San Diego, CA, United States.
    Monoclonal antibodies against tissue-nonspecific alkaline phosphatase: Report of the ISOBM TD9 Workshop2002Ingår i: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 23, nr 4, s. 228-248Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Nineteen monoclonal antibodies (MAbs) against tissue-nonspecific (liver/bone/kidney) alkaline phosphatase (TNALP) were investigated in the ISOBM TD-9 Workshop. These MAbs were generated with antigens obtained from human bone tissue (n = 9), human osteosarcoma cell lines (SaOS-2 and TPX, n = 7) and human liver tissue (n = 3). The evaluation included the following antigen forms: (a) commercially available preparations of human bone ALP (BALP) and liver ALP (LALP), (b) human BALP isoforms, B/I, B1 and B2, and (c) soluble secreted epitope-tagged recombinant human TNALP (setTNALP) expressed in COS-1, osteosarcoma (SaOS-2) and hepatoma (Huh2) cell lines. In addition, 16 TNALP mutant cDNAs corresponding to a wide spectrum of reported hypophosphatasia mutations were used in an attempt to map specific immunoreactive epitopes on the surface of the TNALP molecule. The TD-9 MAbs were evaluated by immunoradiometric (IRMA) assays, cross-inhibition and different enzyme immunoassay designs. No indications of explicit tissue discriminatory immunoreactivities of the investigated MAbs against TNALP were found. However, certain IRMA combinations of MAbs increased the specificity of BALP measurements. All MAbs bound to the three BALP isoforms B/I, B1 and B2, but none of the investigated MAbs were specific for any of the isoforms. Significant differences were, however, found in immunoreactivity between these isoforms, with cross-reactivities ranging from 21 to 109% between the two major BALP isoforms B1 and B2. Desialylation with neuraminidase significantly increased the MAb affinity for the BALP isoforms B/I, B1 and B2, and also decreased the observed differences in cross-reactivity between these isoforms. We suggest, therefore, that the MAb affinity is dependent on the amount/number of terminal sialic acid residues located at the five putative N-glycosylation sites. Based on the overall results, we present a putative three-dimensional model of the TNALP molecule with positioning of the four major antigenic domains (designated A-D) of the investigated MAbs. The TNALP molecule is depicted as a homodimer, hence most, but not necessarily all, epitopes are displayed twice. The antigenic domains were positioned with the following assumptions: domain A was positioned close to the active site since most of these MAbs interfered with the catalytic activity. Interestingly, both MAbs included in the commercial BALP kits were grouped with domain A. Moreover, 4 of the 5 putative N-glycosylation sites (with terminal sialic acid residues) are located within, or with close proximity to, domain A. Domain B was localized at the top flexible loop (crown domain) of the TNALP molecule. Domain C was clearly defined by the IRMA assay combinations and by site-directed mutants of TNALP to be close to residue E281, which is located near the fourth metal binding site, likely to be occupied by a calcium ion. Domain D was positioned close to residues A115, A162 and E174, but this domain was also close to the GPI anchor site. In conclusion, none of the 19 investigated TD-9 MAbs were entirely specific for BALP or LALP, thus indicating that all MAbs bind mainly to epitopes on the common protein core of BALP and LALP and/or common glycosylated epitopes. However, some MAbs (either single or in combination with other MAbs) work sufficiently well to measure BALP when the assayed samples do not contain elevated levels of LALP. Copyright © 2002 S. Karger AG, Basel.

  • 32.
    Magnusson, Per
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Davie, Michael W J
    Robert Jones and Agnes Hunt Orthopaed and Dist Hospital N.
    Sharp, Christopher A
    Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Circulating and tissue-derived isoforms of bone alkaline phosphatase in Pagets disease of bone2010Ingår i: SCANDINAVIAN JOURNAL OF CLINICAL and LABORATORY INVESTIGATION, ISSN 0036-5513, Vol. 70, nr 2, s. 128-135Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Alkaline phosphatase (ALP) is routinely used in the assessment of Pagets disease of bone (PDB); however, the individual bone ALP isoforms (B/I, B1, and B2) have not been investigated in this disorder. Methods. Subjects comprised 37 patients (mean age 74 years) with symptomatic PDB confirmed by radiograph and stratified into high and low total ALP activity groups and 66 healthy individuals (mean age 64 years). Extracts of human cancellous and cortical bone tissues were also investigated. The bone ALP isoforms, measured by HPLC, were compared with two bone ALP immunoassays (Metra (R) and Ostase (R)), and the bone formation marker intact amino-terminal procollagen type I propeptide (iPINP). Results. All bone ALP isoforms were increased in high ALP activity PDB compared with the low ALP activity and control groups (p andlt; 0.0001). The B2 isoform had the greater relative activity representing 36%, 50%, and 71%, of the total ALP activity in the control, low and high ALP activity groups, respectively. Compared with controls, B2 was increased in the low ALP activity PDB group (p andlt; 0.05). ROC analysis showed a validity of approximately 80% for B2 to discriminate patients with PDB. Conclusion. All bone ALP isoforms were increased in patients with high ALP activity PDB and the B2 isoform was even elevated in the low ALP activity PDB group. The bone ALP isoform B2 may be of use in the management of PDB but that has to be further elucidated in subsequent studies.

  • 33.
    Magnusson, Per
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Farley, JR
    Differences in sialic acid residues among bone alkaline phosphatase isoforms: A physical, biochemical, and immunological characterization2002Ingår i: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 71, nr 6, s. 508-518Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    High-performance liquid chromatography (HPLC) separates three human bone alkaline phosphatase (BALP) isoforms in serum, two major BALP isoforms, B1 and B2, and a minor fraction, B/I, which is composed on average of 70% bone and 30% intestinal ALP. The current studies were intended to identify an in vitro source of the BALP isoforms for physical, biochemical, and immunological characterizations. The three BALP isoforms were identified in extracts of human osteosarcoma (SaOS-2) cells, by HPLC, after separation by anion-exchange chromatography. All three BALP isoforms were similar with respect to freeze-thaw stability, solubility, heat inactivation, and inhibition by L-phenylalanine, L-homoarginine, and levamisole. The isoforms were also kinetically similar (i.e., maximal velocity and KM at pH 8.8 and pH 10.0). The isoforms differed, however, with respect to sensitivity to precipitation with wheat germ agglutinin (WGA), P < 0.001, but not Concanavalin A. At 3.0 mg/ml, WGA precipitated approximately 25% of B/I but more than 80% of B1 and B2. Molecular weights were estimated by native gradient gel electrophoresis: B/I, 126 kDa, B1, 136 kDa, and B2, 141 kDa. Desialylation with neuraminidase reduced the apparent sizes of B1 and B2 to 127 kDa (i.e., approximately to that of B/I). The total carbohydrate content was calculated to be 18 kDa, 28 kDa, and 33 kDa (i.e., 14%, 21%, and 23%) for the BALP isofonns, B/I, B1, and B2, respectively. The number of sialic acid residues was estimated to be 29 and 45, for each B1 and B2 homodimer, respectively. Apparent discrepancies between these estimates of molecular weight and estimates based on gel filtration chromatography were attributed to nonspecific interactions between carbohydrate residues and the gel filtration beads. All three BALP isoforms showed similar dose-dependant linearity in the commercial Alkphase-B and Tandem-MP Ostase immunoassays, r = 0.944 and r = 0.985, respectively (P < 0.001). In summary, our data indicate that B1 and B2 have more (or more reactive) sialic acid residues compared with B/I, which mainly explains the apparent differences in molecular weight. Future investigations will focus on the clinical and functional significance of the revealed differences in sialic acid residues.

  • 34.
    Magnusson, Per
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Hansson, Sverker
    University Gothenburg.
    Swolin-Eide, Diana
    University Gothenburg.
    A prospective study of fibroblast growth factor-23 in children with chronic kidney disease2010Ingår i: SCANDINAVIAN JOURNAL OF CLINICAL and LABORATORY INVESTIGATION, ISSN 0036-5513, Vol. 70, nr 1, s. 15-20Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Fibroblast growth factor-23 (FGF-23) is a novel regulator of phosphate metabolism; however, the clinical knowledge is limited in children with chronic kidney disease (CKD) who are at risk of developing mineral bone disorder. Methods: This prospective study over 2 years investigated the development of bone mass and bone turnover in relation to serum FGF-23 in children with CKD. Thirteen patients, 4-15 years, were included with a median corrected glomerular filtration rate (GFR) of 38 (range 7-74) mL/min/1.73 m(2). Results: Median FGF-23 was 127 RU/mL at baseline and 70 RU/mL at follow-up. Five patients had FGF-23 levels exceeding the upper reference limit of 141 RU/mL for healthy children. No correlation with age or puberty was found. FGF-23 was inversely correlated with GFR, r = -0.73 (p andlt;0.05). Four of the five patients within CKD stages 4-5 (GFR andlt;30 mL/min/1.73 m(2)) had elevated FGF-23 levels and two patients with end-stage renal disease had markedly high levels of FGF-23 (1333 and 1700 RU/mL). One of these patients was transplanted after 1 year, which normalized FGF-23 to 70 RU/mL at follow-up. FGF-23 was significantly associated with PTH, r = 0.69 (p andlt;0.01). FGF-23 correlated with osteocalcin, but not with other markers of bone turnover. Total body bone mineral density (BMD) was not correlated with FGF-23, however, the lumber spine BMD Z-score correlated with FGF-23 at baseline, r = 0.61 (p andlt;0.05). Conclusions: Although a small study group, this prospective study suggests that FGF-23 is associated with GFR, PTH, and lumbar spine BMD in pediatric patients with various degrees of CKD.

  • 35.
    Magnusson, Per
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Larsson, Lasse
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Magnusson, Martin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Östergötlands Läns Landsting, Medicincentrum, Njurmedicinska kliniken US.
    Davie, Michael W J
    Sharp, Christopher A
    Isoforms of bone alkaline phosphatase: carachterization and origin in human trabecular and cortical bone.1999Ingår i: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 14, s. 1926-1933Artikel i tidskrift (Refereegranskat)
  • 36.
    Magnusson, Per
    et al.
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Nilsen, Per
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Schedvin, Göran
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Appropriate Use of Vitamin D Assessments in Primary Health Care: Impact of New Strategies for the Introduction and Follow-Up of Analyses in Östergötland2019Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116, nr 14, artikel-id FFPXArtikel i tidskrift (Refereegranskat)
  • 37.
    Magnusson, Per
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Nilsen, Per
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Schedvin, Göran
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    D-vitaminanalyser i primärvård måste användas ändamålsenligt [Appropriate use of vitamin D assessments in primary health care]: Ny strategi i Östergötland för införande och uppföljning av analyser gav bra resultat [Impact of new strategies for the introduction and follow-up of analyses in Östergötland]2019Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 116, s. 1-4Artikel i tidskrift (Refereegranskat)
    Abstract [sv]

    Hälso- och sjukvårdslagen föranstaltar om en kostnadseffektiv och jämlik diagnostik inom den svenska hälso- och sjukvården. Samtidigt ökar efterfrågan på laboratorietest mer än annan medicinsk aktivitet, och utvecklingen leder även till att utbudet av laboratorietest ökar [1]. Vårdens generella resursbrist har lett till ökad betoning på värdeskapande testanvändning globalt [2] med fokus på såväl underanvändning av test (försenar korrekt diagnos och adekvat behandling) som överanvändning (medför överdiagnostik och resursslöseri) [3].Som en följd av denna utveckling har laboratorieverksamheten inom Region Östergötland initierat strategier med syfte att åstadkomma en mer rationell användning av laboratoriemedicinska analyser. Detta har skett genom en aktivare uppföljning av beställningsmönster åtföljd av information och feedback i relation till observerade beställningsmönster. År 2016 initierades s k KRAMA-strategier (KRAMA = Kompetensgruppen för rationell användning av medicinsk diagnostik i alla delar av vårdkedjan) (Figur 1). En viktig ambition var att överge ett passivt testinförande till förmån för ett mer effektivt införande i kombination med aktiv uppföljning av beställningsmönster.

  • 38.
    Magnusson, Per
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi.
    Sharp, CA
    Linkoping Univ Hosp, Dept Biomed & Surg, Div Clin Chem, Bone & Mineral Metab Unit, SE-58185 Linkoping, Sweden.
    Magnusson, M
    Risteli, J
    Linkoping Univ Hosp, Dept Biomed & Surg, Div Clin Chem, Bone & Mineral Metab Unit, SE-58185 Linkoping, Sweden.
    Davie, MWJ
    Linkoping Univ Hosp, Dept Biomed & Surg, Div Clin Chem, Bone & Mineral Metab Unit, SE-58185 Linkoping, Sweden.
    Larsson, Lasse
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi.
    Bone alkaline phosphatase isoforms in chronic renal failure - Reply2002Ingår i: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 61, nr 3, s. 1179-1179Övrigt (Övrigt vetenskapligt)
  • 39.
    Magnusson, Per
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Sharp, Christopher
    Farley, John
    Different distributions of human bone alkaline phosphatase isoforms in serum and bone tissue extracts2002Ingår i: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 325, nr 1-2, s. 59-70Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In vitro, bone alkaline phosphatase (BALP) is released from the osteoblast membrane with its glycosylphosphatidylinositol (GPI) anchor still attached (i.e., in an anchor-intact form), however, in vivo, BALP circulates as a variable mixture of anchorless isoforms, which can be identified by high-performance liquid chromatography (HPLC). Previous studies have shown that the relative abundance of these BALP isoforms in serum may be clinically useful for the diagnosis and management of metabolic bone disease. Methods: In the current studies, we describe a method for the determination of anchorless BALP isoforms in extracts of bone and we present novel data on the conversion of anchor-intact to anchorless BALP by incubation with endogenous circulating GPI-specific phospholipase D (GPI-PLD). Results: A 72-h extraction with 0.1% Triton X-100 released approximately 90% of the BALP activity from powdered bone. An average of 19% of this activity was anchorless, but essentially all of the activity could be converted to the anchorless form by incubation with partially purified GPI-PLD from human serum. Using HPLC, we detected four BALP isoforms (B/I, B1x, B1, and B2) in these GPI-PLD-treated extracts of bone. An additional BALP fraction was also detected in the samples during the initial phase of GPI-PLD treatment. Conclusions: The abundance of the BALP isoforms differed between bone and serum, particularly for the B/I isoform, which comprised, on average, 18% of the BALP in GPI-PLD-treated extracts of healthy bone tissue, but only 6% of the total BALP activity in serum from healthy individuals. Based on our recent finding of differences in the number of sialic acid residues between the BALP isoforms, we hypothesize that this difference between BALP isoforms in serum and extracts of bone is due to the different patterns of glycosylation, which results in different biological half-lives in the circulation. A preliminary application of our method to the extraction of BALP isoforms from a small number of human bone samples suggests that the method should be useful for studies of human skeletal site-specific and metabolic bone disease-specific differences in the amounts and distributions of the BALP isoforms in bone.

  • 40.
    Magnusson, Per
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi.
    Sharp, Christopher
    Magnusson, Martin
    Risteli, Juha
    Davie, Michael WJ
    Larsson, Lasse
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Bone alkaline phosphatase isoforms in chronic renal failure2002Ingår i: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 61, s. 1178-1181Artikel i tidskrift (Refereegranskat)
  • 41.
    Magnusson, Per
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi.
    Sharp, Christopher
    Magnusson, Martin
    Ristell, Juha
    Davie, Michael
    Larsson, Lasse
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Effect of chronic renal failure on bone turnover and bone alkaline phosphatase isoforms.2001Ingår i: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 60, s. 257-265Artikel i tidskrift (Refereegranskat)
  • 42. Narisawa, S
    et al.
    Harmey, D
    Magnusson, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Millan, JL
    Conserved epitopes in human and mouse tissue-nonspecific alkaline phosphatase - Second report of the ISOBM TD-9 Workshop2005Ingår i: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 26, nr 3, s. 113-120Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A panel of 19 monoclonal antibodies (MAbs) against human tissue-nonspecific (liver/bone/kidney) alkaline phosphatase (TNAP) was obtained through the ISOBM TD-9 workshop. In the present study, the reactivity of these MAbs has been characterized against mouse TNAP. A mouse embryonic stem cell line, frozen sections of long bones, alkaline phosphatase extracted from mouse bone, and serum were used as the source of TNAP for individual assays. Each MAb was tested for immunoreactivity to mouse TNAP by Western blot analysis, immunohistochemistry and enzyme immunoassay. Antibodies 314 and 315 reacted strongly with mouse TNAP in Western blots, while all other antibodies were negative. By immunohistochemistry, antibodies 314, 315 and 333 produced strong positive staining using frozen sections, while antibody 334 was moderately positive. Enzyme immunoassays indicated that MAb 333 was also able to bind to serum TNAP. These antibodies represent very useful reagents to study the pathophysiological expression of TNAP in mouse tissues and in mouse serum. Copyright (C) 2005 S. Karger AG, Basel.

  • 43.
    Osman, Abdimajid
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Uhlin, Fredrik
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Njurmedicinska kliniken US.
    Frånlund, Ebba
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Fernström, Anders
    Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Njurmedicinska kliniken US. Linköpings universitet, Institutionen för medicin och hälsa, Njurmedicin. Linköpings universitet, Hälsouniversitetet.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Exon resequencing of the gene encoding UCMA/GRP reveals a common carboxy-terminal 138Thr > Ser Polymorphism2013Ingår i: Clinical Laboratory, ISSN 1433-6510, Vol. 59, nr 11-12, s. 1397-1401Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The upper zone of growth plate and cartilage matrix-associated protein (UCMA), also called Gla-rich protein (GRP), is a novel protein found at sites af-fected by pathological calcifications.Methods: We performed a full exon resequencing on DNA samples from 17 chronic kid-ney disease (CKD) patients (stage 5) and compared the results with 121 healthy con-trols in a Swedish population.Results: A novel non-synonymous single nucleotide polymorphism (SNP) causing a car-boxy-terminal amino acid exchange was found. This SNP involves an alteration of the last ACC codon for threonine in exon 5 (adjacent to the stop codon) to an AGC ser-ine codon (138Thr > Ser). Six controls and two CKD patients were heterozygous for the 138Thr > Ser polymorphism. Both patients had histories of vascular calcifica-tion; however, it is uncertain whether this SNP has any significance for the func-tional domains of the UCMA protein. In addition, a heterozygous transversion muta-tion was found in a patient at SNP rs4750328 (A/G) in intron 2, involving an ex-change of the ancestral A allele to a T base.Conclusions: The 138Thr > Ser polymorphism seems to be the only non-synonymous SNP found in the UCMA gene in a Swedish population.

  • 44.
    Pettersson, Cecilia
    et al.
    Sahlgrens University Hospital, Sweden.
    Tubic, Bojan
    Gothenburg University, Sweden.
    Svedlund, Anna
    Gothenburg University, Sweden.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Ellegard, Lars
    Gothenburg University, Sweden.
    Swolin-Eide, Diana
    Gothenburg University, Sweden.
    Berteus Forslund, Helene
    Gothenburg University, Sweden.
    Description of an intensive nutrition therapy in hospitalized adolescents with anorexia nervosa2016Ingår i: Eating Behaviors, ISSN 1471-0153, E-ISSN 1873-7358, Vol. 21, s. 172-178Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To describe an intensive nutrition therapy for hospitalized adolescents and young adults with anorexia nervosa (AN) in terms of body weight, body composition, energy balance and food related anxiety. Method: Twenty-six young females, 16-24 years of age, with AN were invited to participate at admission to a specialized eating disorder unit in Goteborg, Sweden. Intensive nutrition therapy comprised 12 weeks on a structured meal plan. Six meals were served daily, in combination with high-energy liquid nutritional supplements from start. Energy and nutrient intakes, energy expenditure, body composition and food related anxiety were measured during the study. A 3-month follow-up of body weight and food related anxiety was conducted. Results: Twenty-one patients participated. The total daily energy intake was, during the first week of treatment, (mean +/- SD) 3264 +/- 196 kcal (74 kcal/kg), and decreased gradually during treatment to 2622 +/- 331 kcal (49 kcal/kg). Total daily energy expenditure was initially 1568 +/- 149 kcal and increased gradually to 2034 +/- 194 kcal. Patients gained on average 9.8 +/- 2.1 kg and body mass index increased from 15.5 +/- 0.9 to 19.0 +/- 0.9 kg/m(2). Body fat increased from 13 +/- 6% to 26 +/- 6%. Fat free mass remained unchanged, but skeletal muscle mass increased from 16.7 +/- 2.0 to 17.6 +/- 2.4 kg, p = 0.009. Patients food related anxiety decreased significantly during treatment and was still unchanged 3 months later. Conclusion: The presented intensive nutrition therapy with initially high energy and nutrient intakes produced substantial weight gain, increased fat and muscle mass and decreased food related anxiety in AN patients, without any clinical side effects. (C) 2016 Elsevier Ltd. All rights reserved.

  • 45. Rudberg, A
    et al.
    Magnusson, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Larsson, Lasse
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Joborn, H
    Serum isoforms of bone alkaline phosphatase increase during physical exercise in women2000Ingår i: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 66, nr 5, s. 342-347Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Physical activity is an important factor for maintaining and probably increasing bone mass in humans. However, the mechanism by which this takes place is not completely understood. The purpose of this study was to examine the influence of physical exercise on serum alkaline phosphatase (ALP) and in particular, the bone isoforms of ALP. Six ALP isoforms were quantified by high-performance liquid chromatography: three bone (B/I, B1, and B2), and three liver ALP isoforms. In addition, serum calcium, parathyroid hormone (PTH), and other markers of bone formation and degradation, as measured by osteocalcin and cross-linked carboxyterminal telopeptide of type I collagen (ICTP), were analyzed. The study groups comprised 15 women, 8 postmenopausal (range 51-62 years) and 7 near age of peak bone mass (range 21-27 years). When the postmenopausal women exercised on an ergometer cycle until exhaustion we found significant increases in serum of bone ALP isoforms B1 and B2, and phosphate, even considering the hemoconcentration that occurred during the exercise. When the young women jogged in a moderate tempo for 40- 40 minutes the levels of serum B2 and PTH increased. All changes turned towards baseline within 20 minutes after exercise. In conclusion, exercise increased serum ALP bone isoforms B1 and B2, and their responses were differentiated. As B1 and B2 are known to represent specific bone compartments, cortical and trabecular bone, the present findings may indicate different effects on bone of weight- and nonweight-bearing exercise.

  • 46.
    Sardiwal, Sunita
    et al.
    East Kent Hospital University of NHS Fdn Trust, England .
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Goldsmith, David J A.
    Guys Hospital, England .
    Lamb, Edmund J.
    East Kent Hospital University of NHS Fdn Trust, England .
    Bone Alkaline Phosphatase in CKD-Mineral Bone Disorder2013Ingår i: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 62, nr 4, s. 810-822Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Overall and cardiovascular mortality in patients with chronic kidney disease (CKD) is greatly increased, without obvious current effective treatments. Mineral and bone disorder (MBD) is a common manifestation of CKD and contributes to the high risk of fracture and cardiovascular mortality in these patients. Traditionally, clinical management of CKD-MBD focused on attenuation of secondary hyperparathyroidism due to impaired renal activation of vitamin D and phosphate retention, although recently, adynamic forms of renal bone disease have become more prevalent. Definitive diagnosis was based on histologic (histomorphometric) analysis of bone biopsy material supported by radiologic changes and changes in levels of surrogate laboratory markers. Of these various markers, parathyroid hormone (PTH) has been considered to be the most sensitive and currently is the most frequently used; however, the many pitfalls of measuring PTH in patients with CKD increasingly are appreciated. We propose an alternative or complementary approach using bone alkaline phosphatase (ALP), which is directly related to bone turnover, reflects bone histomorphometry, and predicts outcomes in hemodialysis patients. Here, we consider the overall merits of bone ALP as a marker of bone turnover in adults with CKD-MBD, examine published bone histomorphometric data comparing bone ALP to PTH, and discuss possible pathogenic mechanisms by which bone ALP may be linked to outcomes in patients with CKD.

  • 47. Sharp, CA
    et al.
    Brown, SJ
    Davie, MWJ
    Magnusson, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Mohan, S
    Increased matrix concentrations of IGFBP-5 in cancellous bone in osteoarthritis2004Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 63, nr 9, s. 1162-1165Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In osteoarthritis cancellous bone adapts to meet altered mechanical loading. These changes may be mediated by insulin-like growth factors (IGF-I and IGF-II), but the matrix bound binding protein, IGFBP-5 has not been investigated. Objectives: To measure IGF-I, IGF-II, and IGFBP-5 in femoral head bone from non-OA controls and patients with OA, and to relate these to apparent density (PA) and elastic modulus (Ec). Methods: ρA, Ec, and IGF system components were measured in cancellous bone from superior and inferior regions of femoral heads from 31 patients with OA and 11 age selected controls. Results: Ec and ρA were greater (p<0.05) in the superior region of all femoral heads. In primary OA, ρA was increased in the inferior region (p<0.05). IGFBP-5 was increased, about twofold, at superior and inferior regions in primary OA (1.60 and 1.54 ng/mg bone, respectively, both p<0.05) and in Paget's disease (2.44 and 1.75 ng/mg bone, both p<0.05) compared with controls (0.73 and 0.95 ng/mg bone). In controls, inverse correlations between IGFBP-5 and both ρA and Ec at superior (rs = -0.64 and -0.73, both p<0.05) and inferior regions (rs = -0.72, p<0.05 and -0.24 (NS)) were seen, but these were lost in OA. Conclusions: IGFBP-5 may modulate cancellous bone formation by negative feedback. In end stage OA this is disrupted, but has little influence on material properties.

  • 48.
    Sharp, C.A.
    et al.
    Charles Salt Centre for Human Metabolism, Robert Jones and Agnes Hunt Orthopaedic and District Hospital NHS Trust, Oswestry, Shropshire, United Kingdom, Charles Salt Centre for Human Metabolism, Robert Jones and Agnes Hunt Orthopaedic and District Hospital NHS Trust, Oswestry, Shropshire SY10 7AG, United Kingdom.
    Magnusson, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Isoforms of bone alkaline phosphatase, stem cells, and osteoblast phenotypes2008Ingår i: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 17, nr 5, s. 857-858s. 857-858Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    [No abstract available]

  • 49. Sharp, Christopher A
    et al.
    Linder, Cecilia
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Magnusson, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Analysis of human bone alkaline phosphatase isoforms: Comparison of isoelectric focusing and ion-exchange high-performance liquid chromatography2007Ingår i: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 379, nr 1-2, s. 105-112Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Several isoforms of alkaline phosphatase (ALP) can be identified in human tissues and serum after separation by anion-exchange HPLC and isoelectric focusing (IEF). Methods: We purified four soluble bone ALP (BALP) isoforms (B/I, B1x, B1 and B2) from human SaOS-2 cells, determined their specific pI values by broad range IEF (pH 3.5-9.5), compared these with commercial preparations of bone, intestinal and liver ALPs and established the effects of neuraminidase and wheat germ lectin (WGA) on enzyme activity. Results: Whilst the isoforms B1x (pI = 4.48), B1 (pI = 4.32) and B2 (pI = 4.12) resolved as well-defined bands, B/I resolved as a complex (pI = 4.85-6.84). Neuraminidase altered the migration of all BALP isoforms to pI = 6.84 and abolished their binding to the anion-exchange matrix, but increased their enzymatic activities by 11-20%. WGA precipitated the BALP isoforms in IEF gels and the HPLC column and attenuated their enzymatic activities by 54-73%. IEF resolved the commercial BALP into 2 major bands (pI = 4.41 and 4.55). Conclusions: Migration of BALP isoforms is similar in IEF and anion-exchange HPLC and dependent on sialic acid content. HPLC is preferable in smaller scale research applications where samples containing mixtures of BALP isoforms are analysed. Circulating liver ALP (pI = 3.85) can be resolved from BALP by either method. IEF represents a simpler approach for routine purposes even though some overlapping of the isoforms may occur. © 2007 Elsevier B.V. All rights reserved.

  • 50.
    Sharp, Christopher
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Magnusson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Davie, Michael W. J.
    Robert Jones and Agnes Hunt Orthopaed Hospital, England.
    Oginni, Lawrence M.
    Obafemi Awolowo University, Nigeria.
    Editorial Material: We are what we eat - is it time to reconsider calcium-deficiency rickets in Nigeria? (FA)2015Ingår i: Tropical medicine & international health, ISSN 1360-2276, E-ISSN 1365-3156, Vol. 20, nr 4, s. 408-410Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

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