Publications (17)39.05 Total impact
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Article: Quantitative proteomics comparison of arachnoid cyst fluid and cerebrospinal fluid collected perioperatively from arachnoid cyst patients.
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ABSTRACT: BACKGROUND: There is little knowledge concerning the content and the mechanisms of filling of arachnoid cysts. The aim of this study was to compare the protein content of arachnoid cysts and cerebrospinal fluid by quantitative proteomics to increase the understanding of arachnoid cysts. METHODS: Arachnoid cyst fluid and cerebrospinal fluid from five patients were analyzed by quantitative proteomics in two separate experiments. In a label-free experiment arachnoid cyst fluid and cerebrospinal fluid samples from individual patients were trypsin digested and analyzed by Orbitrap mass spectrometry in a label-free manner followed by data analysis using the Progenesis software. In the second proteomics experiment, a patient sample pooling strategy was followed by MARS-14 immunodepletion of high abundant proteins, trypsin digestion, iTRAQ labelling, and peptide separation by mix-phase chromatography followed by Orbitrap mass spectrometry analysis. The results from these analyzes were compared to previously published mRNA microarray data obtained from arachnoid membranes. RESULTS: We quantified 348 proteins by the label-free individual patient approach and 1425 proteins in the iTRAQ experiment using a pool from five patients of arachnoid cyst fluid and cerebrospinal fluid. This is by far the largest number of arachnoid cyst fluid proteins ever identified, and the first large-scale quantitative comparison between the protein content of arachnoid cyst fluid and cerebrospinal fluid from the same patients at the same time. Consistently in both experiment, we found 22 proteins with significantly increased abundance in arachnoid cysts compared to cerebrospinal fluid and 24 proteins with significantly decreased abundance. We did not observe any molecular weight gradient over the arachnoid cyst membrane. Of the 46 proteins we identified as differentially abundant in our study, 45 were also detected from the mRNA expression level study. None of them were previously reported as differentially expressed. We did not quantify any of the proteins corresponding to gene products from the ten genes previously reported as differentially abundant between arachnoid cysts and control arachnoid membranes. CONCLUSIONS: From our experiments, the protein content of arachnoid cyst fluid and cerebrospinal fluid appears to be similar. There were, however, proteins that were significantly differentially abundant between arachnoid cyst fluid and cerebrospinal fluid. This could reflect the possibility that these proteins are affected by the filling mechanism of arachnoid cysts or are shed from the membranes into arachnoid cyst fluid. Our results do not support the proposed filling mechanisms of oncotic pressure or valves.Fluids and barriers of the CNS. 04/2013; 10(1):17. -
Article: [Dietary supplement of iron for iron deficiency].
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ABSTRACT: BACKGROUND A low supply of iron in the diet may result in iron deficiency and mild iron-deficiency anaemia in healthy individuals. Women are more susceptible than men because of menstrual iron loss. We compared the effect of a low dose of iron, administered as a dietary supplement, with a high pharmacological dose of iron to otherwise healthy individuals with iron deficiency and mild iron deficiency anaemia.MATERIAL AND METHOD In a randomised, double-blind trial conducted in 2000 - 2001, 73 women and three men with iron deficiency received either 27.6 mg of iron consisting of ferrous fumarate enriched with 13 % haem iron, or 100 mg ferrosulphate daily for 12 weeks. Blood samples were analysed four times in the course of the treatment.RESULTS The median ferritin value rose by 13 and 7 μg/l in the high-dose and low-dose group, respectively. The increase in ferritin was significantly higher in the high-dose than in the low dose group ( < 0.001). There was no statistically significant difference between the groups in the change in Hb, serum-iron or serum-iron binding capacity. The median haemoglobin value increased by 0.4 g/100 ml in both groups. Gastrointestinal side effects were experienced by 58 % in the high-dose group and 35 % in the low-dose group. Four subjects in the high-dose group and one in the low-dose group broke off the treatment because of side effects.INTERPRETATION A supplement of low-dose iron is enough to increase iron stores in cases of nutritional iron deficiency in healthy individuals and to optimise haemoglobin. High-dose iron caused the largest increase in iron stores. Low-dose iron resulted in the least side effects.Tidsskrift for den Norske laegeforening 04/2013; 133(8):845-9. -
Article: Discovery and initial verification of differentially abundant proteins between multiple sclerosis patients and controls using iTRAQ and SID-SRM.
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ABSTRACT: In the present study, we aimed to discover cerebrospinal fluid (CSF) proteins with significant abundance difference between early multiple sclerosis patients and controls, and do an initial verification of these proteins using selected reaction monitoring (SRM). iTRAQ and Orbitrap MS were used to compare the CSF proteome of patients with clinically isolated syndrome (CIS) (n=5), patients with relapsing-remitting multiple sclerosis that had CIS at the time of lumbar puncture (n=5), and controls with other inflammatory neurological disease (n=5). Of more than 1200 identified proteins, five proteins were identified with significant abundance difference between the patients and controls. In the initial verification using SRM we analyzed a larger patient and control cohort (n=132) and also included proteins reported as differentially abundant in multiple sclerosis in the literature. We found significant abundance difference for 11 proteins after verification, of which the five proteins alpha-1-antichymotrypsin, contactin-1, apolipoprotein D, clusterin, and kallikrein-6 were significantly differentially abundant in several of the group comparisons. This initial study form the basis for further biomarker verification studies in even larger sample cohorts, to determine if these proteins have relevance as diagnostic or prognostic biomarkers for multiple sclerosis.Journal of proteomics 10/2012; · 5.07 Impact Factor -
Article: Protein profiling reveals inter-individual protein homogeneity of arachnoid cyst fluid and high qualitative similarity to cerebrospinal fluid.
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ABSTRACT: The mechanisms behind formation and filling of intracranial arachnoid cysts (AC) are poorly understood. The aim of this study was to evaluate AC fluid by proteomics to gain further knowledge about ACs. Two goals were set: 1) Comparison of AC fluid from individual patients to determine whether or not temporal AC is a homogenous condition; and 2) Evaluate the protein content of a pool of AC fluid from several patients and qualitatively compare this with published protein lists of cerebrospinal fluid (CSF) and plasma. AC fluid from 15 patients with temporal AC was included in this study. In the AC protein comparison experiment, AC fluid from 14 patients was digested, analyzed by LC-MS/MS using a semi-quantitative label-free approach and the data were compared by principal component analysis (PCA) to gain knowledge of protein homogeneity of AC. In the AC proteome evaluation experiment, AC fluid from 11 patients was pooled, digested, and fractionated by SCX chromatography prior to analysis by LC-MS/MS. Proteins identified were compared to published databases of proteins identified from CSF and plasma. AC fluid proteins not found in these two databases were experimentally searched for in lumbar CSF taken from neurologically-normal patients, by a targeted protein identification approach called MIDAS (Multiple Reaction Monitoring (MRM) initiated detection and sequence analysis). We did not identify systematic trends or grouping of data in the AC protein comparison experiment, implying low variability between individual proteomic profiles of AC.In the AC proteome evaluation experiment, we identified 199 proteins. When compared to previously published lists of proteins identified from CSF and plasma, 15 of the AC proteins had not been reported in either of these datasets. By a targeted protein identification approach, we identified 11 of these 15 proteins in pooled CSF from neurologically-normal patients, demonstrating that the majority of abundant proteins in AC fluid also can be found in CSF. Compared to plasma, as many as 104 proteins in AC were not found in the list of 3017 plasma proteins. Based on the protein content of AC fluid, our data indicate that temporal AC is a homogenous condition, pointing towards a similar AC filling mechanism for the 14 patients examined. Most of the proteins identified in AC fluid have been identified in CSF, indicating high similarity in the qualitative protein content of AC to CSF, whereas this was not the case between AC and plasma. This indicates that AC is filled with a liquid similar to CSF. As far as we know, this is the first proteomics study that explores the AC fluid proteome.Fluids and barriers of the CNS. 01/2011; 8:19. -
Article: Natural killer cells as biomarkers of hyperbaric stress during a dry heliox saturation dive.
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ABSTRACT: Diving, hyperbaric oxygen, and decompression have been described as inducers of alterations in various components of the human immune system, such as the distribution of circulating lymphocytes. Hypothetically, the monitoring of specific lymphocyte subsets during hyperbaric exposure, including T- and NK-cell subsets, can serve as biomarkers of hyperbaric stress. Eight experienced saturation divers and eight reference subjects, naive to deep saturation diving, were examined. Peripheral blood mononuclear cells were isolated before and at different points during a 19.3-d dry heliox saturation dive to 2.64 MPa (254 msw). The NK cell cytotoxicity was estimated in a 4-h 51Cr-release assay using the NK cell sensitive tumor cell-line K562 as target cells. The major lymphocyte subpopulations, with special emphasis on the NK cell subsets, were phenotypically delineated by the use of 4-color flow cytometry. Although NK cell cytotoxicity increased significantly in the divers during the compression phase and the reference subjects who remained in normoxic conditions outside the chamber, the NK cell cytotoxicity was significantly higher in the divers. This finding, together with augmentation in the absolute number of circulating NK cells in the divers due to a possible activation of specific parts of the innate cellular immune system during hyperbaric exposure, suggests the monitoring of specific immune functions can be useful as biomarkers of hyperbaric-induced inflammatory stress.Aviation Space and Environmental Medicine 05/2010; 81(5):467-74. · 0.88 Impact Factor -
Article: Blood donors with hereditary hemochromatosis.
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ABSTRACT: The distribution of C282Y and H63D variants of the HFE gene was determined in donors with evidence of phenotypical hemochromatosis. The ferritin level and the effect of a donation on iron status in the different HFE genotypes were studied. Forty women and 107 men with hemochromatosis were compared to HFE wild-type donors. The influence of a blood donation was assessed by the change in ferritin between two consecutive donations. In women and men, 85 and 59%, respectively, were C282Y homozygote. None of the women had H63D alleles. There was no significant difference in the donation history or the ferritin level between the HFE genotypes. Donation frequencies were, respectively, 3.3 and 3.7 per year for women and men. The ferritin level was significantly higher in women with hemochromatosis, while in men it was similar compared to the respective wild types. The negative influence of a donation on iron status was similar in hemochromatotic and wild-type women, while men with hemochromatosis were significantly less vulnerable to a blood donation than genetically wild-type men. Subjects with hemochromatosis are valuable as blood donors independent of their HFE genotype. In general, the ferritin level tended to be higher in those with hemochromatosis than in wild types. The negative influence of a blood donation on iron status was less in male donors with hemochromatosis than in wild types.Transfusion 03/2010; 50(8):1787-93. · 3.22 Impact Factor -
Article: Arachnoid cysts do not contain cerebrospinal fluid: A comparative chemical analysis of arachnoid cyst fluid and cerebrospinal fluid in adults.
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ABSTRACT: Arachnoid cyst (AC) fluid has not previously been compared with cerebrospinal fluid (CSF) from the same patient. ACs are commonly referred to as containing "CSF-like fluid". The objective of this study was to characterize AC fluid by clinical chemistry and to compare AC fluid to CSF drawn from the same patient. Such comparative analysis can shed further light on the mechanisms for filling and sustaining of ACs. Cyst fluid from 15 adult patients with unilateral temporal AC (9 female, 6 male, age 22-77y) was compared with CSF from the same patients by clinical chemical analysis. AC fluid and CSF had the same osmolarity. There were no significant differences in the concentrations of sodium, potassium, chloride, calcium, magnesium or glucose. We found significant elevated concentration of phosphate in AC fluid (0.39 versus 0.35 mmol/L in CSF; p = 0.02), and significantly reduced concentrations of total protein (0.30 versus 0.41 g/L; p = 0.004), of ferritin (7.8 versus 25.5 ug/L; p = 0.001) and of lactate dehydrogenase (17.9 versus 35.6 U/L; p = 0.002) in AC fluid relative to CSF. AC fluid is not identical to CSF. The differential composition of AC fluid relative to CSF supports secretion or active transport as the mechanism underlying cyst filling. Oncotic pressure gradients or slit-valves as mechanisms for generating fluid in temporal ACs are not supported by these results.Cerebrospinal Fluid Research 01/2010; 7:8. · 1.81 Impact Factor -
Article: Pharmacology and safety of tetradecylthioacetic acid (TTA): phase-1 study.
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ABSTRACT: This study describes the clinical, hematological, and biochemical safety of tetradecylthioacetic acid (TTA). A total of 18 healthy volunteers were included. Subjects were randomly assigned into 3 groups according to the daily given dose of TTA: group 1 (200 mg), group 2 (600 mg), and group 3 (1000 mg). TTA was given as a single oral dose for 7 consecutive days. Safety was evaluated by following the adverse events, vital signs, and hematological and biochemical parameters in blood and urine samples. Efficacy was estimated through its effects on plasma lipids profile. Few adverse events of mild severity were reported. No clinically significant changes were observed in the hematological or clinical chemical parameters in blood/urine. TTA did not induce significant changes in the blood lipids or free fatty acids, but it did result in an increase in plasma concentration of Delta9 desaturated TTA (TTA: 1n-8). Serum concentration pattern of TTA at day 1 showed a 1.5-hour lag time followed by a rapid absorption and a slower elimination phase. The median peak values were 2.9 mg/L (range, 1.1 to 5.4 mg/L), 11.5 mg/L (range, 4 to 35 mg/L), and 11 mg/L (range, 5 to 25 mg/L), in groups 1, 2, and 3, respectively (P = 0.006). The time to peak levels were 3.5 hours (range, 2.5 to 6.5 hours), 2.5 hours (range, 2.5 to 4.5 hours), and 4.5 hours (range, 2.5 to 12 hours), respectively (P = 0.2). TTA is safe and well tolerated.Journal of Cardiovascular Pharmacology 05/2008; 51(4):410-7. · 2.29 Impact Factor -
Article: Pretreatment of mass spectral profiles: application to proteomic data.
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ABSTRACT: Mass spectral profiles are influenced by several factors that have no relation to compositional differences between samples: baseline effects, shifts in mass-to-charge ratio (m/z) (synchronization/alignment problem), structured noise (heteroscedasticity), and, differences in signal intensities (normalization problem). Different procedures for pretreatment of whole mass spectral profiles described by almost 50,000 m/z values are investigated in order to find optimal approaches with respect to revealing the information content in the data. In order to quantitatively assess the impact of different procedures for pretreatment of mass spectral profiles, we use factorial designs with the ratio between intergroup and intragroup (replicate) variance as response. We have examined the influence of smoothing, binning, alignment/synchronization, noise pattern, and normalization on data interpretation. Our analysis shows that the spectral profiles have to be corrected for heteroscedastic noise prior to normalization. An nth root transform, where n is a small, positive integer, is used to create a homoscedastic noise structure without destroying the linear correlation structures describing individual components when using whole mass spectral profiles. The choice of n is decided by a simple graphic procedure using replicate information. Log transform is shown to change the heteroscedastic noise structure from being dominant in high-intensity regions, to produce the largest noise in the low-intensity regions. In addition, log transform has a negative effect on the collinearity in the profiles. Factorial designs reveal strong interactions between several of the pretreatment steps, e.g., noise structure and normalization. This underlines the limited usability of looking at the different pretreatment steps in isolation. Binning turns out to be able to substitute smoothing of spectra by, for example, moving average or Savitsky-Golay, while, at the same time, reducing the data point description of the profiles by 1 order of magnitude. Thus, if the sampling density is high, binning seems to be an attractive option for data reduction without the risk of losing information accompanying the integration of profiles into peaks. In the absence of smoothing, binning should be executed prior to alignment. If binning is not performed, the order of pretreatment should be smoothing, alignment, nth root transform, and normalization.Analytical Chemistry 10/2007; 79(18):7014-26. · 5.86 Impact Factor -
Article: Pre-analytical influence on the low molecular weight cerebrospinal fluid proteome.
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ABSTRACT: Cerebrospinal fluid (CSF) is a perfect source to search for new biomarkers to improve early diagnosis of neurological diseases. Standardization of pre-analytical handling of the sample is, however, important to obtain acceptable analytical quality. In the present study, MALDI-TOF MS was used to examine the influence of pre-analytical sample procedures on the low molecular weight (MW) CSF proteome. Different storage conditions like temperature and duration or the addition of as little as 0.2 µL blood/mL neat CSF caused significant changes in the mass spectra. The performance of different types of MW cut-off spin cartridges from different suppliers used to enrich the low MW CSF proteome showed great variance in cut-off accuracy, stability and reproducibility. The described analytical method achieved a polypeptide discriminating limit of approximately 800 pM, two to three orders of magnitude lower than reported for plasma. Based on this study, we recommend that CSF is centrifuged immediately after sampling, prior to storage at -80ºC without addition of protease inhibitors. Guanidinium hydrochloride is preferred to break protein-protein interactions. A spin cartridge with cut-off limit above the intended analytical mass range is recommended. Our study contributes to the important task of developing standardized pre-analytical protocols for the proteomic study of CSF.Proteomics. Clinical applications 07/2007; 1(7):699-711. · 1.97 Impact Factor -
Article: Changes in erythropoietin and haemoglobin concentrations in response to saturation diving.
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ABSTRACT: A reduction in haemoglobin concentration is consistently reported after deep saturation dives. This may be due to a downregulation of erythropoietin (EPO) concentration or to a toxic effect of the hyperoxia associated with the dives resulting in an increased destruction rate of erythrocytes. In this study haemoglobin concentration, blood cell counts, serum ferritin, bilirubin, haptoglobin and EPO concentrations were measured before, during and after a 19 day saturation dive to 240 m. The partial pressure of oxygen (PO(2)) was 35-70 kPa during the 7 day compression and bottom phase, and 30-50 kPa during the 12 day decompression phase. There was a reduction in EPO concentration from 8.4+/-1.4 (mean +/- 1SD) to 6.3 +/- 1.9 U.L(-1) on Dive day 2. On Dive days 7 and 17 EPO concentrations were not significantly different from baseline despite the continued exposure to hyperoxia. Immediately after the dive and return to a normoxic environment there was an increase in the EPO concencentration to 14.5 +/- 4.7 U.L(-1). Haemoglobin concentration, erythrocyte and reticulocyte counts were decreased at the end of the dive, and there was an increase in serum ferritin. There were no changes in bilirubin or haptoglobin concentrations indicative of haemolysis. It appears that the change in PO(2), rather than the sustained exposure to a hyperoxic environment, induces the changes in the EPO concentrations and erythropoietic activity.Arbeitsphysiologie 11/2005; 95(2-3):191-6. · 2.15 Impact Factor -
Article: Oral ferrous fumarate or intravenous iron sucrose for patients with inflammatory bowel disease.
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ABSTRACT: Iron therapy may reinforce intestinal inflammation by catalysing production of reactive oxygen species. The effects of oral ferrous fumarate and intravenous iron sucrose on clinical disease activity and plasma redox status were investigated in patients with inflammatory bowel disease (IBD). Nineteen patients with iron deficiency anaemia and Crohn's disease (11) or ulcerative colitis (8) were included in a crossover study. The patients were randomly assigned to start treatment with ferrous fumarate (Neo-fer) 120 mg orally once daily or iron sucrose (Venofer) 200 mg intravenously 3 times during a period of 14 days. Clinical disease activity assessment and blood and faecal analysis were performed on days 1 and 15. Following oral ferrous fumarate clinical disease activity (p=0.037), general well-being score (i.e. patients felt worse) (p=0.027) and abdominal pain score (p=0.027) increased, while no changes were seen following iron sucrose treatment. C-reactive protein (CRP) and faecal calprotectin were unchanged after both treatments. As compared with iron sucrose, ferrous fumarate increased Crohn's disease activity index (CDAI) scores of general well-being (p=0.049), whereas alterations in clinical disease activity (p=0.14) and abdominal pain score (p=0.20) did not differ. Ferrous fumarate did not significantly alter plasma malondialdehyde (MDA) or plasma antioxidants. Iron sucrose increased plasma MDA (p=0.004) and decreased plasma vitamin C (p=0.017) and betacarotene (p=0.008). Oral ferrous fumarate, but not intravenous iron sucrose, increased clinical disease activity in IBD patients. Intravenous iron sucrose increased intravascular oxidative stress.Scandinavian Journal of Gastroenterology 10/2005; 40(9):1058-65. · 2.02 Impact Factor -
Article: Low-dose oral ferrous fumarate aggravated intestinal inflammation in rats with DSS-induced colitis.
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ABSTRACT: Oral ferrous iron therapy may reinforce intestinal inflammation. One possible mechanism is by catalyzing the production of reactive oxygen species. We studied the effects of low-dose oral ferrous fumarate on intestinal inflammation and plasma redox status in dextran sulfate sodium (DSS)-induced colitis in rats. Forty male Wistar rats were divided into 5 groups: no intervention, sham gavage (distilled water), ferrous fumarate, DSS, and ferrous fumarate + DSS. Ferrous fumarate was dissolved in distilled water (0.60 mg Fe/kg per day) and administered by gavage on days 1 to 14. All rats were fed a standard diet. Colitis was induced by 5% DSS in drinking water on days 8 to 14. Rats were killed on day 16. Histologic colitis scores, fecal granulocyte marker protein, plasma malondialdehyde, plasma antioxidant vitamins, and plasma aminothiols were measured. DSS significantly increased histologic colitis scores (P < 0.001) and fecal granulocyte marker protein (P < 0.01). Ferrous fumarate further increased histologic colitis scores (P < 0.01) in DSS-induced colitis. DSS + ferrous fumarate decreased plasma vitamin A compared with controls (P < 0.01). Otherwise, no changes were seen in plasma malondialdehyde, plasma antioxidant vitamins, or plasma aminothiols. Low-dose oral ferrous iron enhanced intestinal inflammation in DSS-induced colitis in rats.Inflammatory Bowel Diseases 08/2005; 11(8):744-8. · 4.86 Impact Factor -
Article: Effects of tonsillectomy and adenoidectomy on hemoglobin and iron metabolism.
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ABSTRACT: To investigate a possible effect of adenoidectomy, tonsillectomy, or both operations combined in children on hemoglobin concentration and iron metabolism. Children eligible for surgery due to recurrent tonsillitis or upper airway obstruction had a venous blood sample drawn at the time of the operation and 6 months later. One hundred and three preoperative and 91 blood samples at follow-up from patients not given iron supplementation were available for analysis of hemoglobin concentration, serum-ferritin and protoporphyrin-IX in erythrocytes. A 1.4g/dl median increase in hemoglobin concentration during the observation period was associated with a significant reduction of protoporphyrin-IX, while serum-ferritin remained unchanged and low. A preoperative prevalence of anemia of 56.3% was reduced to 7.71%. All combinations of normal and pathological values of serum-ferritin and protoporphyrin-IX were found in anemic and non-anemic patients. A beneficial effect of tonsillectomy and adenoidectomy on hemoglobin and iron metabolism was demonstrated. Iron deficiency was common.International Journal of Pediatric Otorhinolaryngology 05/2004; 68(4):419-23. · 1.17 Impact Factor -
Article: Intestinal and systemic immune responses to an oral cholera toxoid B subunit whole-cell vaccine administered during zinc supplementation.
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ABSTRACT: Zinc plays a critical role in the normal functioning of the immune system. We investigated whether zinc sulfate administered orally to adult zinc-replete volunteers modulates systemic and intestinal immune responses to an oral killed cholera toxoid B subunit (CTB) whole-cell cholera vaccine. The 30 participants were immunized twice, with a 17-day interval. The vaccinees in the intervention group ingested 45 mg of elemental zinc thrice daily for 9 days starting 2 days before each vaccine dose. The median serum anti-CTB immunoglobulin A (IgA) and IgG responses from day 0 to day 30, i.e. after two vaccine doses, were 13-fold lower (P value for identical distribution, <0.005) in the zinc-supplemented compared to the nonsupplemented vaccinees. The median serum vibriocidal responses from baseline to after one (day 0 to day 17) and two (day 0 to day 30) vaccine doses were at least sixfold (P = 0.033) and fourfold (P = 0.091) higher, while the median fecal anti-CTB IgA response after two doses was estimated to be fourfold higher (P = 0.084) in the zinc-supplemented vaccinees. These observations show that zinc reduces the antitoxin and may enhance the antibacterial responses in serum. Zinc may also improve the intestinal antitoxin immune response. Oral zinc administration has the potential to modify critical immune responses to antigens applied to mucosal surfaces.Infection and Immunity 07/2003; 71(7):3909-13. · 4.16 Impact Factor -
Article: Multi-element analysis of trace element levels in human autopsy tissues by using inductively coupled atomic emission spectrometry technique (ICP-AES).
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ABSTRACT: Autopsy tissue samples from the brain front lobe, cerebellum, heart, kidney (cortex and medulla), liver, pancreas, spleen and ovary were analysed for AL, B, Ba, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Se, Sr and Zn in 30 (17 women and 13 men) subjects ranging in age from 17 to 96 years at Haukeland University Hospital in Norway. The tissues were selected from macroscopically normal organs and samples were handled according to guidelines recommended to avoid contamination in the pre-analytical phase. Concentration of the trace elements were determined by the inductively coupled plasma atomic emission spectrometry technique (ICP-AES). In most tissues the concentrations of the essential trace elements followed the order Fe> Zn> Cu> Mn> Se> Cr> Co except in the ovary where Se was higher than Mn. The liver was the major site of deposition for Co, Cu and Mn as well as the spleen for Co, brain front lobe for Cu and pancreas for Mn. Ba, Sr and Ni built up in the ovary foLLowed by the kidney. Older subjects accumulated Ba and Sr in most tissues, whereas Al accumulated in the kidney cortex and Cd in the brain cerebellum. Generally males had higher concentrations of trace elements in the different tissue sampLes than females with the exception of Mn in the brain front lobe and heart and Sr in the liver. ICP-AES is a useful method to assess the concentration and the profiLe of trace elements in human autopsy tissues.Journal of Trace Elements in Medicine and Biology 01/2002; 16(1):15-25. · 1.68 Impact Factor -
Article: Biomarker discovery in mass spectral profiles by means of selectivity ratio plot
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ABSTRACT: This work presents a new method for variable selection in complex spectral profiles. The method is validated by comparing samples from cerebrospinal fluid (CSF) with the same samples spiked with peptide and protein standards at different concentration levels. Partial least squares discriminant analysis (PLS-DA) attempts to separate two groups of samples by regressing on a y-vector consisting of zeros and ones in the PLS decomposition. In most cases, several PLS components are needed to optimize the discrimination between groups. This creates difficulties for the interpretation of the model. By using the y-vector as a target, it is possible to transform the PLS components to obtain a single predictive target-projected component analogously to the predictive component in orthogonal partial least squares discriminant analysis (OPLS-DA). By calculating the ratio between explained and residual variance of the spectral variables on the target-projected component, a selectivity ratio plot is obtained that can be used for variable selection. Used on whole mass spectral profiles of pure and spiked CSF, we can detect peptide in the low molecular mass range (740–9000 Da) at least down to 400 pM level without severe problems with false biomarker candidates. Similarly, we detect added proteins at least down to 2 nM level in the medium mass range (6000–17,500 Da). Target projection represents the optimal way to fit a latent variable decomposition to a known target, but the selectivity ratio plot can be used for OPLS as well as other methods that produce a single predictive component. Comparison with some commonly used tools for variable selection shows that the selectivity ratio plot has the best performance. This observation is attributed to the fact that target projection utilizes both the predictive ability (regression coefficients) and the explanatory ability (spectral variance/covariance matrix) for the calculation of the selectivity ratio.Chemometrics and Intelligent Laboratory Systems 95(1):35-48. · 1.92 Impact Factor
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2002
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Haukeland University Hospital
Bergen, Hordaland Fylke, Norway
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