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Biomedical subjects

M Hansson

Publications and source records attributed to M Hansson.

At least 19 recordsLinked to original sources
PubMed2006

Southern Ocean sea-ice extent, productivity and iron flux over the past eight glacial cycles.

Sea ice and dust flux increased greatly in the Southern Ocean during the last glacial period. Palaeorecords provide contradictory evidence about marine productivity in this region, but beyond one glacial cycle, data were sparse. Here we present continuous chemical proxy data spanning the last eight glacial cycles (740,000 years) from the Dome C Antarctic ice core. These data constrain winter sea-ice extent in the Indian Ocean, Southern Ocean biogenic productivity and Patagonian climatic conditions. We found that maximum sea-ice extent is closely tied to Antarctic temperature on multi-millennial timescales, but less so on shorter timescales. Biological dimethylsulphide emissions south of the polar front seem to have changed little with climate, suggesting that sulphur compounds were not active in climate regulation. We observe large glacial-interglacial contrasts in iron deposition, which we infer reflects strongly changing Patagonian conditions. During glacial terminations, changes in Patagonia apparently preceded sea-ice reduction, indicating that multiple mechanisms may be responsible for different phases of CO2 increase during glacial terminations. We observe no changes in internal climatic feedbacks that could have caused the change in amplitude of Antarctic temperature variations observed 440,000 years ago.

Calcium↗
PubMed2006

Determination of intrathyroidal iodine by X-ray fluorescence analysis in 60- to 65-year olds living in an iodine-sufficient area.

OBJECTIVES: X-ray fluorescence (XRF) is a non-invasive method for determining the iodine content of the thyroid gland in vivo. In spite of the obvious clinical value of such a method in situations of iodine deficiency or iodine overload, the method has not so far been widely used. The objective was to investigate the applicability of the XRF method in a larger number of subjects. DESIGN AND SUBJECTS: The study comprised 37 individuals, aged 60-65 years, who had spent their entire life with iodine supplementation through iodinated table salt. Individuals with (previous) thyroid disease were excluded. The individual thyroid function had previously been evaluated by measurements of thyroid-related hormones, thyroid volume and 131-Iodine (131I) uptake which indicated a sufficient iodine intake of the population in the area. Iodine in the right thyroid lobe in each subject was examined using XRF. RESULTS: The mean thyroid iodine concentration was 0.4 mg mL(-1), corresponding to a mean total iodine content of 5.2 mg (range 0.9-20.2). There was a pronounced difference between individuals. No correlation was found between iodine concentration and 131I uptake or thyroid volume. Neither was iodine content and 131I uptake correlated. CONCLUSIONS: In a population living under iodine-sufficient conditions, a large variation of iodine stored in the thyroid is compatible with euthyroidism. Determination of the iodine pool by XRF investigation is feasible in a clinical setting and the method offers a unique possibility to study the intrathyroidal iodine pool in subjects with thyroid disease. The low radiation dose enables the use of the method in pregnant women and also in young individuals.

Aged↗
PubMed2005

Sorbent-assisted liquid-liquid extraction (Chem-Elut) of polychlorinated biphenyls, dibenzo-p-dioxins and dibenzofurans in the lipid fraction of human blood plasma.

This work compares two lipid extraction methods for determining 24 polychlorinated biphenyls (PCBs), seven dibenzo-p-dioxins (PCDDs) and ten dibenzofurans (PCDFs) in human blood plasma. The first method was based on conventional liquid-liquid partitioning with chloroform-methanol and the other made use of a sorbent (Chem-Elut) to facilitate the partitioning of lipids into a mixture of hexane and 2-propanol. A multi-layer-silica column including acid- and base-impregnated silica gel was used to reduce the amounts of lipid present in the samples before a basic alumina clean-up step and activated carbon fractionation of planar analytes (PCDD/Fs and non-ortho-PCBs) and non-planar analytes (including ortho-chlorinated PCBs). Gas chromatography coupled to high resolution mass spectrometry was used to identify and quantify the analytes in the two fractions. The wet weight based concentrations obtained by the two methods were in agreement but both methods suffer from large organic solvent consumption. The toxic equivalencies derived for PCBs and PCDD/Fs using the two methods were also in agreement. However, the chloroform-methanol method gave slightly higher lipid recoveries, although with greater variation, than the sorbent-assisted method. Nevertheless, despite giving lower lipid recoveries, the sorbent-assisted method has advantages in ease of use and applicability to whole blood samples. The formation of emulsions was avoided with the Chem-Elut method, which probably explains the lower variability in the lipid determinations.

Adsorption↗
PubMed2005

Soluble thrombomodulin activity and soluble thrombomodulin antigen in plasma.

Endothelial cell membrane-bound thrombomodulin (TM) plays a critical role as a cofactor in the protein C pathway, important in regulating coagulation as well as inflammation. Heterogeneous soluble TM fragments circulate in the plasma and are found at increased levels in various diseases such as cardiovascular disease and diabetes, and in ischemic and/or inflammatory endothelial injuries. The anticoagulant function of these soluble fragments has not been measured in healthy individuals or in patients. Using an immobilized monoclonal antibody against TM and a microtiter plate format, an assay was designed to capture the soluble TM fragments in plasma and measure their cofactor activity in the thrombin-mediated activation of protein C. In addition, soluble TM antigen levels were measured by enzyme-linked immunosorbent assay. Both assays were used to investigate a group of healthy blood donors. TM fragments released into plasma were shown to retain significant cofactor activity, and reference intervals for healthy men and women were established. Furthermore, a statistically significant correlation was observed between soluble TM antigen levels and soluble TM cofactor activity. This notwithstanding, soluble TM activity only accounted for a minor part of all variation in soluble TM antigen levels (R2 = 22% in men and R2 = 16% in women).

Adolescent↗
PubMed2004

High-resolution record of Northern Hemisphere climate extending into the last interglacial period.

Two deep ice cores from central Greenland, drilled in the 1990s, have played a key role in climate reconstructions of the Northern Hemisphere, but the oldest sections of the cores were disturbed in chronology owing to ice folding near the bedrock. Here we present an undisturbed climate record from a North Greenland ice core, which extends back to 123,000 years before the present, within the last interglacial period. The oxygen isotopes in the ice imply that climate was stable during the last interglacial period, with temperatures 5 degrees C warmer than today. We find unexpectedly large temperature differences between our new record from northern Greenland and the undisturbed sections of the cores from central Greenland, suggesting that the extent of ice in the Northern Hemisphere modulated the latitudinal temperature gradients in Greenland. This record shows a slow decline in temperatures that marked the initiation of the last glacial period. Our record reveals a hitherto unrecognized warm period initiated by an abrupt climate warming about 115,000 years ago, before glacial conditions were fully developed. This event does not appear to have an immediate Antarctic counterpart, suggesting that the climate see-saw between the hemispheres (which dominated the last glacial period) was not operating at this time.

Journal Article↗
PubMed2004

Development of a technology platform for large-scale clinical grade production of DC.

BACKGROUND: Clinical studies require protocols where a sufficient number of well-characterized highly immunogenic DC are produced according to good manufacturing practice (GMP) guidelines. METHODS: In the present study, using leukapheresis products from 10 cancer patients, we validated an elutriation technology for large-scale clinical grade production of monocyte-derived DC. RESULTS: The elutriation method gave a very high purity (mean+/-SD) (86+/-5.3%) and recovery (66+/-10.4%) of monocytes. Specifically for the two monocyte-rich fractions (3 and 4,) the recovery was 42+/-13% of viable cells that could be further differentiated into immature DC in hydrophobic culture bags using GM-CSF and IL-4. The immature DC exhibited<1% CD83+ expression and >98% phagocytic activity. Maturation with TNF-alpha or poly I:C resulted in DC with expression of CD80+, CD86+ and HLA-DR+ (>99%) and CD83+ (80+/-11.9%), as well as producing IL-12p70 and lacking phagocytic activity (<5%). This cell product can be cryopreserved with cell viability >85% and cell recovery >80% after thawing. DISCUSSION: The elutriation procedure, when optimized and if the monocyte content of the starting material exceeds 5%, does not require further selection or depletion using affinity approaches.

Antigens, CD↗
PubMed2004

Mercuric chloride induces a strong immune activation, but does not accelerate the development of dermal fibrosis in tight skin 1 mice.

In susceptible mice, mercuric chloride induces a systemic autoimmune disease characterized by increased serum levels of immunoglobulin (Ig) G1 and IgE, production of anti-nucleolar autoantibodies (ANolA) and formation of renal IgG deposits. We have previously hypothesized that mercury confers more adverse immunological effects on those mouse strains, which are genetically prone to develop spontaneous autoimmune diseases than on normal strains. In this study, we tested our hypothesis in tight skin 1 (Tsk1/+) mice, a murine model for human scleroderma. As a support for our hypothesis, we observed that in Tsk1/+ mice, B cells were spontaneously hyperactive and that treatment with mercury induced a strong immune/autoimmune response in these mice, but not in their non-Tsk (+/+) littermates. This response was characterized by the formation of high numbers of splenic IgG1, IgG2b and IgG3 antibody-secreting cells, increased serum levels of IgE, production of IgG1 antibodies against single-stranded DNA (ssDNA), trinitrophenol (TNP) as well as thyroglobulin and the development of renal IgG1 deposits. Neither Tsk1/+ mice nor F1 hybrid crosses between this strain, and mercury susceptible B10.S (H-2(s)) were able to produce IgG1-ANolA in response to mercury. Moreover, mercury-induced immune activation in Tsk1/+ was not able to potentiate the progression of skin fibrosis in this strain. Thus, exposure to mercury accelerates the immune dysregulation, but not the development of skin fibrosis in Tsk1/+ mice.

Animals↗
PubMed2003

Xenobiotic metal-induced autoimmunity: mercury and silver differentially induce antinucleolar autoantibody production in susceptible H-2s, H-2q and H-2f mice.

Xenobiotic-metals such as mercury (Hg) and silver (Ag) induce an H-2 linked antinucleolar autoantibody (ANolA) production in susceptible mice. The mechanism for induction of ANolA synthesis is not well understood. However, it has been suggested that both metals interact with nucleolar proteins and reveal cryptic self-peptides to nontolerant autoreactive T cells, which in turn stimulate specific autoreactive B cells. In this study, we considered this suggestion and asked if mercury and silver display, if not identical, similar cryptic self-peptides, they would induce comparable ANolA responses in H-2 susceptible mice. We analysed the development of ANolA production in mercury- and/or silver-treated mice of H-2s, H-2q and H-2f genotypes. We found that while mercury stimulated ANolA synthesis in all strains tested, silver induced ANolA responses of lower magnitudes in only H-2s and H-2q mice, but not in H-2f mice. Resistance to silver in H-2f mice was independent of the dosage/time-period of silver-treatment and non-H-2 genes. Further studies showed that F1 hybrid crosses between silver-susceptible A.SW (H-2s) and -resistant A.CA (H-2f) mice were resistant to silver, but not mercury with regard to ANolA production. Additionally, the magnitudes of mercury-induced ANolA responses in the F1 hybrids were lower than those of their parental strains. The above differential ANolA responses to mercury and silver can be explained by various factors, including the different display of nucleolar cryptic peptides by these xenobiotics, determinant capture and coexistence of different MHC molecules. Our findings also suggest that the ability of a xenobiotic metal merely to create cryptic self-peptides may not be sufficient for the induction of an ANolA response.

Animals↗
PubMed2003

Nicotinamide inhibits endotoxin-induced monocyte tissue factor expression.

BACKGROUND: Tissue factor (TF) is the main initiator of blood coagulation in vivo. Its increased expression on activated monocytes is associated with thrombotic complications and mortality in conditions such as sepsis, disseminated intravascular coagulation and coronary artery disease. OBJECTIVE: The effect of the vitamin B derivative nicotinamide on endotoxin-induced monocyte TF and CD11b expression, soluble interleukin(IL)-6, and clotting onset time (COT) was studied. METHODS: Experiments were conducted in human peripheral blood leukocyte suspensions and in whole blood from eight healthy volunteers. Free oscillating rheometry (measuring COT) and flow cytometry were applied to evaluate the effect of endotoxin on TF, CD11b, IL-6 and the overall coagulation response of plasma supplemented with activated autologous leukocytes. RESULTS: In response to endotoxin, there was an increase in IL-6, TF and CD11b expression and a procoagulant shift of COT. At 4 mmol L-1 nicotinamide, inhibition of TF expression and IL-6 and a normalization of COT were seen. At 16 mmol L-1 nicotinamide, CD11b decreased also. The level of monocyte TF expression correlated with the COT readings, and the endotoxin-induced procoagulant shift of COT could be totally inhibited by blocking TF with an inhibitory antibody. CONCLUSIONS: These results demonstrate the ability of nicotinamide to inhibit the activation of coagulation associated with endotoxemia. We have previously shown that nicotinamide exerts strong anti-inflammatory effects. Evidence is accumulating for nicotinamide to have a therapeutic potential in modulating disease states in which there is a profound activation of coagulation and inflammation, such as in sepsis and disseminated intravascular coagulation.

Adult↗
PubMed2003

On-line NIR monitoring during anaerobic treatment of municipal solid waste.

An anaerobic digester (81) was fed with the organic fraction of municipal solid waste and monitored intermittently for two years with on-line near-infrared (NIR) spectroscopy and traditional chemical parameters analysed off-line. The dynamics that occurred due to changes in substrate composition (changed C:N ratio) and changes in operating conditions (overloading) could be followed using principal component analysis of the obtained NIR-spectra. In addition, process disturbances such as failed stirring and increased foaming were readily detected by the NIR-spectra. Using PLS regression the propionate concentration could be predicted in the range 0.1-3.6 g/l, RMSEP 0.53 g/l with slope 0.74 and correlation coefficient 0.85. The response on changes in the digester fluid was reproducible and could be detected within 2.5 minutes, which can be considered as real-time monitoring.

Automation↗
PubMed2002

Three semidominant barley mutants with single amino acid substitutions in the smallest magnesium chelatase subunit form defective AAA+ hexamers.

Many enzymes of the bacteriochlorophyll and chlorophyll biosynthesis pathways have been conserved throughout evolution, but the molecular mechanisms of the key steps remain unclear. The magnesium chelatase reaction is one of these steps, and it requires the proteins BchI, BchD, and BchH to catalyze the insertion of Mg(2+) into protoporphyrin IX upon ATP hydrolysis. Structural analyses have shown that BchI forms hexamers and belongs to the ATPases associated with various cellular activities (AAA(+)) family of proteins. AAA(+) proteins are Mg(2+)-dependent ATPases that normally form oligomeric ring structures in the presence of ATP. By using ATPase-deficient BchI subunits, we demonstrate that binding of ATP is sufficient to form BchI oligomers. Further, ATPase-deficient BchI proteins can form mixed oligomers with WT BchI. The formation of BchI oligomers is not sufficient for magnesium chelatase activity when combined with BchD and BchH. Combining WT BchI with ATPase-deficient BchI in an assay disrupts the chelatase reaction, but the presence of deficient BchI does not inhibit ATPase activity of the WT BchI. Thus, the ATPase of every WT segment of the hexamer is autonomous, but all segments of the hexamer must be capable of ATP hydrolysis for magnesium chelatase activity. We suggest that ATP hydrolysis of each BchI within the hexamer causes a conformational change of the hexamer as a whole. However, hexamers containing ATPase-deficient BchI are unable to perform this ATP-dependent conformational change, and the magnesium chelatase reaction is stalled in an early stage.

Adenosine Triphosphate↗
PubMed2002

Early warning of disturbances in a laboratory-scale MSW biogas process.

The use of near-infrared spectroscopy (NIR) to monitorthe dynamics of a biogas process was evaluated using multivariate data analysis. The digester was a completely stirred 8 I tank reactor fed with the organic fraction of source-sorted MSW. Intermittently the digester was overloaded with feed. Before and after overload on-line monitoring of NIR spectra and off-line analysis in the liquid and the gas phase of traditional chemical variables and microbial biomass, determined as total concentration of phospholipid fatty acids (PLFA and PLEL), were done. The dynamics that occurred due to overloading could be followed using principal component analysis of the obtained NIR-spectra. In addition, the response to changes in the digester fluid was reproducible and could be detected within five minutes, which can be considered as real-time monitoring. Selected wavelengths in the region 800-2,000 nm were used to make a PLS1 -regression with propionate. The regression resulted in a good correlation for propionate (R= 0.94 and RMSEP of 0.21 g/l in the range of 0.3-3 g/l). The results indicate the possibility to develop an early warning biogas control system based on near-infrared spectroscopy monitoring of propionate.

Automation↗
PubMed2001

Interplay between an AAA module and an integrin I domain may regulate the function of magnesium chelatase.

In chlorophyll biosynthesis, insertion of Mg(2+) into protoporphyrin IX is catalysed in an ATP-dependent reaction by a three-subunit (BchI, BchD and BchH) enzyme magnesium chelatase. In this work we present the three-dimensional structure of the ATP-binding subunit BchI. The structure has been solved by the multiple wavelength anomalous dispersion method and refined at 2.1 A resolution to the crystallographic R-factor of 22.2 % (R(free)=24.5 %). It belongs to the chaperone-like "ATPase associated with a variety of cellular activities" (AAA) family of ATPases, with a novel arrangement of domains: the C-terminal helical domain is located behind the nucleotide-binding site, while in other known AAA module structures it is located on the top. Examination by electron microscopy of BchI solutions in the presence of ATP demonstrated that BchI, like other AAA proteins, forms oligomeric ring structures. Analysis of the amino acid sequence of subunit BchD revealed an AAA module at the N-terminal portion of the sequence and an integrin I domain at the C terminus. An acidic, proline-rich region linking these two domains is suggested to contribute to the association of BchI and BchD by binding to a positively charged cleft at the surface of the nucleotide-binding domain of BchI. Analysis of the amino acid sequences of BchI and BchH revealed integrin I domain-binding sequence motifs. These are proposed to bind the integrin I domain of BchD during the functional cycle of magnesium chelatase, linking porphyrin metallation by BchH to ATP hydrolysis by BchI. An integrin I domain and an acidic and proline-rich region have been identified in subunit CobT of cobalt chelatase, clearly demonstrating its homology to BchD. These findings, for the first time, provide an insight into the subunit organisation of magnesium chelatase and the homologous colbalt chelatase.

Adenosine Triphosphatases↗
PubMed2001

Living with spine-related pain in a changing society--a qualitative study.

PURPOSE: To elucidate life lived with recurrent, spine-related pain and to explore the development from work to disability pension. METHOD: A qualitative design at individual level was chosen. Nineteen people--five on disability pension, four physicians and ten rehabilitation officials--were interviewed. Data were analysed using grounded theory. RESULTS: A process of 'coming to terms with pain' with four phases was identified. During the phases pain had a deteriorating course and was combined with other medical problems. Together with changes on the labour market these factors caused the persons to leave their employment and also hindered reorientation on the labour market. Committed as they were to social norms, the persons found adjustment to a place outside the labour market difficult. CONCLUSIONS: Our findings suggest how recurrent back and neck pain can develop, interact with medical, individual, work-related and structural factors and result in incapacity to work. To avoid this incapacity pain has to be followed and the other factors considered in the design and timing of rehabilitation.

Disability Evaluation↗
PubMed2001

Ingrowth of sympathetic innervation occurs concomitantly with a decrease of ANP in the growing rat cardiac ventricles.

The relationship between the immunohistochemical expression of atrial natriuretic peptide and the occurrence of sympathetic nerve fibres, as visualized by staining for tyrosine hydroxylase, in the growing rat heart was evaluated. Rats were investigated at four different stages from birth to 21 days postnatally. The effects of chemical destruction of sympathetic nerve terminals in neonatal rats on the cardiac atrial natriuretic peptide content were furthermore examined by use of radioimmunoassay. There was in principle a reciprocal pattern of immunoreaction for atrial natriuretic peptide and tyrosine hydroxylase positive innervation in the ventricular myocardium, atrial natriuretic peptide reaction becoming less and less pronounced with the ingrowth of innervation positive for tyrosine hydroxylase. Furthermore, in the peripheral Purkinje fibre network, there was a marked atrial natriuretic peptide immunoexpression and scarce or no nerve fibres throughout the examination period. The radioimmunoassay measurements showed that chemical sympathectomy lead to elevated cardiac levels of atrial natriuretic peptide. The study shows that sympathetic innervation grows into the ventricular parts concomitantly with the occurrence of a decline in atrial natriuretic peptide expression during development of the heart. Furthermore, it is shown that a reversion of the in growth of sympathetic innervation by destruction of cardiac sympathetic nerves at an early stage leads to increased levels of atrial natriuretic peptide in the heart. The results give new evidence to the phenomenon that the atrial natriuretic peptide levels in the ventricular myocardium and the peripheral parts of the conduction system are under influence of the presence of sympathetic innervation.

Animals↗
PubMed2001

Mammalian cell production of a respiratory syncytial virus (RSV) candidate vaccine recovered using a product-specific affinity column.

The recombinant production of a respiratory syncytial virus (RSV) candidate vaccine BBG2Na in baby hamster kidney cells (BHK-21 cells) was investigated. BBG2Na consists of a serum-albumin-binding region (BB) fused to a 101-amino-acid fragment of the RSV G-protein. Semliki Forest virus-based expression vectors encoding both intracellular and secreted forms of BBG2Na were constructed and found to be functional. Affinity recovery of BBG2Na employing human serum albumin columns was found to be inefficient due to the abundance of BSA in the applied samples. Instead, a strategy using a tailor-made affinity ligand based on a combinatorially engineered Staphylococcus aureus protein A domain, showing specific binding to the G-protein part of the product, was evaluated. In conclusion, a strategy for production and successful recovery of BBG2Na in mammalian cells was created, through the development of a product-specific affinity column.

Animals↗