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L O Hansson

Publications and source records attributed to L O Hansson.

At least 19 recordsLinked to original sources
PubMed2006

Treatment with combined oral contraceptives induces a rise in serum C-reactive protein in the absence of a general inflammatory response.

BACKGROUND: The role of inflammation in the pathogenesis of cardiovascular disease is well established. C-reactive protein (CRP) is the strongest independent predictor of myocardial infarction and stroke in women. Recent studies have indicated that CRP levels are raised during use of combined oral contraceptives (COCs). OBJECTIVES: The aim of the study was to investigate the effect of COCs on serum CRP levels and to indicate the underlying mechanisms of an expected increase. METHOD: In a prospective randomized cross over-study 35 women used two different preparations of COC, one second and one third generation. Serum levels of CRP, serum amyloid A (SAA), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), antibodies against oxidized LDL, insulin and insulin-like growth factor-I (IGF-I) along with insulin-like growth factor binding protein-1 (IGFBP-1) and IGFBP-3 were analyzed before and during the two treatments. E-selectin, von Willebrand factor and factor VIII concentrations in plasma were also measured. RESULTS: A rise in serum CRP was observed during both treatments; the median level increased from 0.45 mg L(-1) at baseline to 1.48 mg L(-1) with second generation and to 2.02 mg L(-1) with third generation COC. The serum levels of SAA increased slightly during treatment with the third generation COC. IL-6 and TNFalpha were unaffected by treatment. Both preparations lowered IGF-I and raised IGFBP-1 and IGFBP-3 concentrations. CONCLUSION: The raised serum CRP concentration during treatment with COCs appears to be related to a direct effect on hepatocyte CRP synthesis and does not reflect IL-6 mediated inflammation, endothelial activation or induction of insulin resistance.

Adolescent↗
PubMed2004

Calculation of glomerular filtration rate expressed in mL/min from plasma cystatin C values in mg/L.

The Cockcroft Gault formula is often used to calculate the glomerular filtration rate (GFR) from plasma creatinine results. In Sweden this calculation is not usually done in the laboratory, but locally in the wards. These manual calculations could cause erroneous results. In several studies plasma cystatin C has been shown to be superior to plasma creatinine for estimation of GFR. One limitation of using cystatin C as a GFR marker is that there is no conversion formula transforming cystatin C expressed as mg/L to GFR expressed as mL/min. In this study plasma creatinine and cystatin C were compared with iohexol clearance. A stronger correlation (p < 0.0001) was found between cystatin C and iohexol clearance (r2 = 0.91) than between creatinine and iohexol clearance (r2 = 0.84). From the correlation data a formula was calculated to convert cystatin C expressed as mg/L to GFR (mL/min). The formulas y = 77.24x(-1.2623) (Dade Behring cystatin C calibration) or y = 99.43x(-1.5837) (DakoCytomation cystatin C calibration) are used to calculate GFR expressed in mL/min from the cystatin C value in mg/L and both results are reported to the referral doctor. These formulas can provide the clinicians with reliable and readily available GFR data based on single measurements of cystatin C concentrations.

Adolescent↗
PubMed2004

Reference intervals for plasma levels of fibronectin, von Willebrand factor, free protein S and antithrombin during third-trimester pregnancy.

During pregnancy, significant changes occur in the hemostatic system and in the plasma levels for several plasma proteins, especially towards term. In this study changes occurring during normal pregnancy and immediately postpartum were investigated to establish adequate reference intervals for important hemostatic parameters. Blood samples were collected during pregnancy weeks 33, 36, 39 and 1-3 h after delivery from 153 healthy pregnant women with at least one previous normal pregnancy. The plasma samples were analyzed for antithrombin, von Willebrand factor (vWf), free protein S and fibronectin. Fibronectin and vWf are contact-promoting proteins responsible for adhesion and aggregation during primary hemostasis, but are also released from thrombocytes during activation of the coagulation process. Antithrombin is the most important primary physiological inhibitor of activated serine proteases related to the coagulation cascade. Protein S is a co-factor to protein C and in cooperation is also an important inhibitor of the coagulation cascade. During third-trimester pregnancy, vWf was higher than in non-pregnant women, and continued to increase postpartum. The fibronectin plasma level was mostly unchanged in comparison with non-pregnant values. Within this reference interval it gradually increased during the third trimester, but fell slightly postpartum. Antithrombin decreased slightly during the third trimester and even further, postpartum. Free protein S decreased markedly but to a stable level from week 33 to 39, decreasing even more postpartum. The present results are concordant with clinical knowledge of increased risk of thrombosis during pregnancy and early puerperium, with increased levels of vWf and fibronectin and decreased levels of antithrombin and free protein S. Clearly, current reference values based on healthy non-pregnant subjects are not usable during late pregnancy and immediately postpartum.

Adult↗
PubMed2003

High sensitivity CRP and serum amyloid A as expressions of low grade inflammation do not correlate with bFGF or VEGF.

High sensitivity CRP (hsCRP) and serum amyloid component A (SAA) are two acute phase proteins that have been shown to be prognostic markers in cardiovascular diseases. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are two angiogenic growth factors involved in the growth and invasion of solid tumors and hematological malignancies. They also play an important role in cardiovascular and inflammatory diseases. The acute phase response induces the production of angiogenic peptides and angiogenic peptides have also been shown to induce the synthesis of inflammatory cytokines. HsCRP and SAA, bFGF and VEGF in serum and EDTA plasma were measured in samples from 80 human blood donors. There were strong correlations between hsCRP and SAA but there were no significant correlation between hsCRP or SAA and any of the angiogenic peptides. Low-grade inflammation did not induce bFGF or VEGF production.

Adult↗
PubMed2001

Serum S-100b protein as a prognostic marker in malignant cutaneous melanoma.

PURPOSE: To evaluate whether S-100B protein in serum is an independent prognostic marker in malignant melanoma. MATERIALS AND METHODS: S-100B protein in serum was analyzed in 1,007 consecutive patients with histologically verified cutaneous malignant melanoma. At the time of blood sampling, 876 patients were in clinical stage I, 35 were in stage II, and 96 were in stage III. The serum concentrations of S-100B protein were measured by a luminescence immunoassay (LIA). RESULTS: The mean serum concentration of S-100B protein was significantly related to clinical stage, with the lowest level in stage I and the highest in stage III. In a multivariate analysis, S-100B protein levels in serum showed the strongest prognostic impact of the factors analyzed with respect to disease-specific survival in clinical stages II to III, followed by clinical stage. Serum S-100B protein was not a significant independent prognostic factor in clinical stage I, where tumor thickness showed the strongest relation to melanoma-specific survival, followed by ulceration and satellites. CONCLUSION: This investigation contains the largest material of patients so far analyzed with the new LIA assay of S-100B protein in serum and confirms that S-100B protein in serum is correlated with clinical stage and is an independent prognostic marker in clinical stages II and III.

Adolescent↗
PubMed2001

Increase in serum S100A1-B and S100BB during cardiac surgery arises from extracerebral sources.

BACKGROUND: Elevated levels of serum S100B after coronary artery bypass grafting may arise from extracerebral contamination. Serum S100B content was analyzed in several tissues, and the two dimers S100A1-B and S100BB were analyzed separately in blood. METHODS: Serum, shed blood, marrow, fat, and muscle were studied in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass using suction either to the cardiotomy reservoir (group 1, n = 10) or to a cell-saving device (group 2, n = 10), or operated on off-pump (group 3, n = 10). RESULTS: Serum S100B was sixfold higher in group 1 than in groups 2 and 3, which were identical. The same ratio between S100A1-B and S100BB was found in all groups. When compared with serum, S100B was 10(2) to 10(4) times higher in marrow, fat, muscle tissue, and shed blood. CONCLUSIONS: Separate analysis of S100A1-B and S100BB did not distinguish between S100B of cerebral and extracerebral origin. The concept that S100B only originates in astroglial and Schwann cells is wrong. Fat, muscle, and marrow in mediastinal blood contain high levels of S100B. Cardiopulmonary bypass caused no increase in S100B.

Adult↗
PubMed2001

Fibronectin is a marker for organ involvement and may reflect the severity of preeclampsia.

OBJECTIVE: We have studied whether plasma fibronectin is related to a rise in blood pressure during normal pregnancy, whether it can be used for the early prediction of preeclampsia, and whether plasma fibronectin is a marker for organ involvement in preeclampsia. STUDY DESIGN: Two hundred twenty-eight healthy pregnant nullipara women were examined prospectively during pregnancy. Analyses of fibronectin in plasma were performed in pregnancy weeks 16, 24, 28, 32, and 36. During the same period, 177 patients with suspected preeclampsia and/or intrauterine growth retardation (IUGR) were tested for plasma fibronectin, mainly in the third trimester. RESULTS: In the normal population of pregnant women (n=222/228), fibronectin levels were 0.35 +/- 0.06 g/L in pregnancy week 16 and 0.43 +/- 0.12 g/L in week 36. These levels showed a positive correlation to blood pressure elevation during pregnancy (r=0.21, p=0.006). The six patients in this group (n=6/228) who later developed preeclampsia had higher fibronectin values 0.42 +/- 0.07 g/L already in week 16 (p=0.023). In the population of women with suspected preeclampsia (preeclampsia, n=129; IUGR alone, n=17; hypertension or proteinuria during pregnancy, n=31), fibronectin values were significantly higher, 0.75 +/- 0.27 g/L than in the normal population. Patients with preeclampsia and laboratory signs of organ involvement (n=56) showed significantly higher fibronectin values (0.85 +/- 0.27 g/L) compared to preeclampsia without organ involvement (n=73) [0.76 +/- 0.22 g/L (p=0.03)]. CONCLUSION: Our data show that fibronectin is related to blood pressure in pregnancy. Fibronectin values in women who develop preeclampsia are elevated already in pregnancy week 16 and were higher in those with laboratory signs of organ involvement.

Adolescent↗
PubMed2001

High serum S100B levels for trauma patients without head injuries.

OBJECTIVE: Studies of patients with head trauma have demonstrated a correlation between a serum marker of brain tissue damage, namely S100B, and neuroradiological findings. It was recently demonstrated that the increases in serum S100B levels after heart surgery have extracerebral origins, probably surgically traumatized fat, muscle, and bone marrow. The current study examined multitrauma patients without head trauma, to determine whether soft-tissue and bone damage might confound the interpretation of elevated serum S100B concentrations for patients after head trauma. METHODS: A commercial assay was used to determine serum S100B concentrations for a normal population (n = 459) and multitrauma patients without head injury (n = 17). Concentrations of the two subtypes of S100B (S100A1B and S100BB) were determined using separate noncommercial assays. RESULTS: The mean serum S100B concentration for a normal healthy population was 0.032 microg/L (median, 0.010 microg/L; standard deviation, 0.040 microg/L). The upper 97.5% and 95% reference limits were 0.13 and 0.10 microg/L, respectively. No major age or sex differences were observed. Among trauma patients, serum S100B levels were highest after bone fractures (range, 2-10 microg/L) and thoracic contusions without fractures (range, 0.5-4 microg/L). Burns (range, 0.8-5 microg/L) and minor bruises also produced increased S100B levels. S100A1B and S100BB were detected in all samples. CONCLUSION: Trauma, even in the absence of head trauma, results in high serum concentrations of S100B. Interpretation of elevated S100B concentrations immediately after multitrauma may be difficult because of extracerebral contributions. S100B may have a negative predictive value to exclude brain tissue damage after trauma. Similarly, nonacute S100B measurements may be of greater prognostic value than acute measurements.

Adolescent↗
PubMed2000

The effect of cardiotomy suction on the brain injury marker S100beta after cardiopulmonary bypass.

BACKGROUND: An increase of S100beta in serum during cardiopulmonary bypass (CPB) has been interpreted as a sign of brain injury. Cardiotomy suction may cause fat embolization, and its role in the S100beta increase was examined. METHODS: Twenty coronary artery operation patients were randomly assigned to two groups, 10 with suction during CPB to cardiotomy reservoir (CR), 10 to cell saving device (CS). S100beta was measured (immunoassay) in blood from the patients and from cell saving device after processing. In 7 additional patients S100beta was measured in the cell saving device before processing and directly from the wound at sternotomy. RESULTS: Before anesthesia, serum S100beta was 0.03+/-0.06 microg/L. At the end of CPB it was 2.47+/-1.31 microg/L and 0.44+/-0.27 microg/L (CR vs CS; p < 0.001). S100beta was 33+/-12 microg/L in CS reservoir and 42+/-18 microg/L in blood from the wound. CONCLUSIONS: Most serum S100beta after CPB with cardiotomy suction may be of extracerebral origin. S100beta after CPB with cell saving device was the same as after off-pump operation. The interpretation that an increase in S100beta during CPB in patients reflects cerebral injury must be questioned.

Aged↗
PubMed2000

Effects of cardiac surgery on some clinically used inflammation markers and procalcitonin.

One hundred and ten patients were investigated prospectively in a study aimed at creating reference curves for inflammation markers (serum C-reactive protein (CRP), blood leukocyte count, iron, transthyretin and procalcitonin). Blood samples were taken daily and the patients were monitored for signs of infection. Ninety-six patients had no postoperative infections. CRP and leukocyte counts peaked on the third and second postoperative days, respectively. Neither patients operated on off-pump (n = 4) nor patients with minor infections (n = 11) differed from the non-infected group. Two out of three patients with major postoperative infection exhibited a secondary peak in CRP and leukocyte count. Iron and transthyretin decreased initially, followed by a slow increase without any difference between the groups. Procalcitonin was high in some non-infected patients and low in some infected patients. CRP and leukocyte count had a predictable course with a secondary peak in major infections but the other markers did not provide any valuable information.

Adult↗
PubMed2000

The birth process initiates an acute phase reaction in the fetus-newborn infant.

UNLABELLED: Our goal was to investigate whether the normal birth process stimulated an acute phase response in healthy infants with physiological changes in the circulating levels of acute phase cytokines and acute phase proteins. We also monitored body temperature, body weight and behavioural state in order to investigate if clinical signs of acute phase reaction were present. We made cross-sectional measurements of interleukin-1beta, interleukin-6, C-reactive protein, serum amyloid A, procalcitonin, prealbumin, body weight, body temperature and the duration of the sleeping period during the first four postnatal days. We found an increase in interleukin-6 (p < 0.001) during the first day, followed by an increase in C-reactive protein, serum amyloid A and procalcitonin on the second postnatal day (p < 0.01). The level of prealbumin fell after birth and reached its lowest value at 3 d of age (p < 0.001). Interleukin-1beta remained unchanged. The duration of the sleeping period was longer during the first day (p < 0.01). There was an increase in body temperature during the first day (p < 0.01). Maximal weight loss was during the first 2 d. CONCLUSIONS: The normal birth process and extra-uterine adaptation stimulates an acute phase reaction in the newborn infant with a release of interleukin-6 and acute phase proteins and a depression of prealbumin. This reaction, as the body's first line inflammatory defence system, probably affects the infant's behaviour, nutritional state as well as the regulation of body temperature.

Acute-Phase Reaction↗
PubMed1999

An approach to optimizing the active site in a glutathione transferase by evolution in vitro.

A glutathione transferase (GST) mutant with four active-site substitutions (Phe(10)-->Pro/Ala(12)-->Trp/Leu(107)-->Phe/Leu(108)-->Arg) (C36) was isolated from a library of active-site mutants of human GST A1-1 by the combination of phage display and mechanism-based affinity adsorption [Hansson, Widersten and Mannervik (1997) Biochemistry 36, 11252-11260]. C36 was selected on the basis of its affinity for the transition-state analogue 1-(S-glutathionyl)-2,4, 6-trinitrocyclohexadienate. C36 affords a 10(5)-fold rate enhancement over the uncatalysed reaction between reduced glutathione and 1-chloro-2,4-dinitrobenzene (CDNB), as evidenced by the ratio between k(cat)/K(m) and the second-order rate constant k(2). The present study shows that C36 can evolve to an even higher catalytic efficiency by an additional site-specific mutation. Random mutations of the fifth active-site residue 208 allowed the identification of 18 variants, of which the mutant C36 Met(208)-->Cys proved to be the most active form. The altered activity was substrate selective such that the catalytic efficiency with CDNB and with 1-chloro-6-trifluoromethyl-2,4-dinitrobenzene were increased 2-3-fold, whereas the activity with ethacrynic acid was decreased by a factor of 8. The results show that a single-point mutation in the active site of an enzyme may modulate the catalytic activity without being directly involved as a functional group in the enzymic mechanism. Such limited modifications are relevant both to the natural evolution and the in vitro redesign of proteins for novel functions.

Amino Acid Substitution↗
PubMed1999

Probing the kinetic mechanism and coenzyme specificity of glutathione reductase from the cyanobacterium Anabaena PCC 7120 by redesign of the pyridine-nucleotide-binding site.

Glutathione reductase from the cyanobacterium Anabaena PCC 7120 contains a pyridine-nucleotide-binding motif differing from that of the enzyme from other sources and an insertion of 10 amino acid residues. Homology modeling was used to obtain a model of the enzyme structure. It revealed that in the Anabaena enzyme Lys(203) replaces Arg, found to interact with the 2'-phosphate of NADP(H) in the enzyme from other sources, and that it has an extra loop near the entrance of the pyridine-nucleotide-binding site. The steady-state and preequilibrium kinetic properties were characterized for the wild-type enzyme, a K203R, and a loop deletion mutant. All enzyme forms had higher catalytic efficiency with NADPH than with NADH, although the difference was less than for glutathione reductase from other sources. The specificity was most pronounced in the formation of the charge-transfer complex between the pyridine nucleotide and oxidized enzyme-bound FAD, as compared to later steps in the reaction. Unexpectedly, by replacing Lys(203) with Arg, the specificity for NADPH was diminished in the complete redox reaction. Ser(174) appears to interact with the 2'-phosphate of NADPH and introduction of arginine instead of lysine, therefore, has little effect on the interaction with this coenzyme. However, the efficiency in forming the charge-transfer complex between the pyridine nucleotide and oxidized enzyme-bound FAD was increased in the K203R mutant using NADPH but not with NADH. The lack of affinity toward 2',5'-ADP-Sepharose by the wild-type enzyme was not changed by replacing Lys(203) with Arg but deletion of the loop resulted in an enzyme that bound to the immobilized ligand. Removal of the loop increased the efficiency of the enzyme in the reductive half-reaction with both pyridine-nucleotides as well as in the overall catalytic mechanism.

Amino Acid Sequence↗
PubMed1999

Evolution of differential substrate specificities in Mu class glutathione transferases probed by DNA shuffling.

A library of variant enzymes was created by combined shuffling of the DNA encoding the human Mu class glutathione transferases GST M1-1 and GST M2-2. The parental GSTs are 84 % sequence identical at the protein level, but their specific activities with the substrates aminochrome and 2-cyano-1,3-dimethyl-1-nitrosoguanidine (cyanoDMNG) differ by more than 100-fold. Aminochrome is of particular interest as an oxidation product of dopamine and of possible significance in the etiology of Parkinson's disease, and cyanoDMNG is a model for genotoxic and potentially carcinogenic nitroso compounds. GST M2-2 has at least two orders of magnitude higher catalytic activity with both of the substrates than any of the other known GSTs, including GST M1-1. The DNA library of variant Mu class GST sequences contained "mosaic" structures composed of alternating segments of both parental sequences. All clones contained the 5'-end of a GST M1-1 clone optimized for high-level expression in Escherichia coli. The remainder of the sequences derived from segments of GST M2-2 and GST M1-1 DNA. All of the clones analyzed contained between two and seven distinct DNA segments. In addition, each clone contained an average of approximately one point mutation. None of the library clones analyzed was identical with either of the two parental structures. Variant GST sequences were expressed in E. coli, and their enzymatic activities with aminochrome, cyanoDMNG, and 1-chloro-2,4-dinitrobenzene (CDNB) were determined in bacterial lysates. Such screening of more than 70 clones demonstrated a continuous range of activities covering at least two orders of magnitude for each of the substrates. For a given clone, the activities with aminochrome and cyanoDMNG, in spite of their different chemistries, were clearly correlated, whereas no strong correlation was found with CDNB. This functional correlation suggests a common structural basis for the enzymatic mechanisms for conjugation of aminochrome and denitrosation of cyanoDMNG. From an evolutionary perspective, the results show that recombination of segments from homologous proteins gives rise to a large proportion of functionally competent proteins with a range of activities. The data support the proposal that natural evolution of protein functions may involve recombination of DNA segments followed by selection for advantageous functional properties of the resulting proteins. Clearly, the same approach can be utilized in the engineering of proteins displaying novel functions by in vitro evolution.

Amino Acid Sequence↗
PubMed1999

Release of S100B during coronary artery bypass grafting is reduced by off-pump surgery.

BACKGROUND: S100B, a plasma marker of brain injury, was compared after coronary artery bypass grafting with and without cardiopulmonary bypass (CPB). METHODS: Fourteen patients with off-pump operations and 18 patients with CPB were compared. Seven patients in the off-pump group underwent a minithoracotomy and received only an arterial graft, whereas 7 patients underwent sternotomy and received both an arterial and one or two vein grafts. S100B was measured in arterial plasma using an immunoassay with enhanced sensitivity. RESULTS: S100B before the operation was 0.03 microg/L. At wound closure, S100B in patients of the off-pump and CPB groups reached a maximum level of 0.22 +/- 0.07 and 2.4 +/- 1.5 microg/L, respectively (p < 0.001). No strokes occurred. Patients without CPB receiving arterial and vein grafts released slightly more S100B (p < 0.05) than patients with only arterial grafting. In patients undergoing CPB, S100B increased slightly before aortic cannulation (p < 0.001), to the same level as the maximum reached for the non-CPB group. CONCLUSIONS: Coronary artery bypass grafting with CPB caused a 10-fold greater increase in S100B than off-pump grafting. S100B release after off-pump sternotomy with vein grafting was slightly greater than in arterial grafting through a minithoracotomy.

Aged↗
PubMed1999

Structural determinants in domain II of human glutathione transferase M2-2 govern the characteristic activities with aminochrome, 2-cyano-1,3-dimethyl-1-nitrosoguanidine, and 1,2-dichloro-4-nitrobenzene.

Two human Mu class glutathione transferases, hGST M1-1 and hGST M2-2, with high sequence identity (84%) exhibit a 100-fold difference in activities with the substrates aminochrome, 2-cyano-1,3-dimethyl-1-nitrosoguanidine (cyanoDMNG), and 1,2-dichloro-4-nitrobenzene (DCNB), hGST M2-2 being more efficient. A sequence alignment with the rat Mu class GST M3-3, an enzyme also showing high activities with aminochrome and DCNB, demonstrated an identical structural cluster of residues 164-168 in the alpha6-helices of rGST M3-3 and hGST M2-2, a motif unique among known sequences of human, rat, and mouse Mu class GSTs. A putative electrostatic network Arg107-Asp161-Arg165-Glu164(-Gln167) was identified based on the published three-dimensional structure of hGST M2-2. Corresponding variant residues of hGSTM1-1 (Leu165, Asp164, and Arg167) as well as the active site residue Ser209 were targeted for point mutations, introducing hGST M2-2 residues to the framework of hGST M1-1, to improve the activities with substrates characteristic of hGST M2-2. In addition, chimeric enzymes composed of hGST M1-1 and hGST M2-2 sequences were analyzed. The activity with 1-chloro-2,4-dinitrobenzene (CDNB) was retained in all mutant enzymes, proving that they were catalytically competent, but none of the point mutations improved the activities with hGST M2-2 characteristic substrates. The chimeric enzymes showed that the structural determinants of these activities reside in domain II and that residue Arg165 in hGST M2-2 appears to be important for the reactions with cyanoDMNG and DCNB. A mutant, which contained all the hGST M2-2 residues of the putative electrostatic network, was still lacking one order of magnitude of the activities with the characteristic substrates of wild-type hGST M2-2. It was concluded that a limited set of point mutations is not sufficient, but that indirect secondary structural affects also contribute to the hGST M2-2 characteristic activities with aminochrome, cyanoDMNG, and DCNB.

Amino Acid Sequence↗