Biomedical subjects

S Karlsson

Publications and source records attributed to S Karlsson.

At least 19 recordsLinked to original sources

PubMed2006

Historical pollution of seldom monitored trace elements in Sweden--Part A: sediment properties and chronological indicators.

Sediment cores from four small oligotrophic boreal lakes, with minor acidification, in remote regions of central Sweden were used for historical interpretation of their metal content, with focus on Cu, Cd, Pb and Zn in Lake Stensjön, which has the longest sediment record (at least two centuries according to (210)Pb dating). Comparison is made with the other three lakes. Major and trace elements in lake water, porewater and the acid-leached (HNO(3)) solid sediment phase was analysed with ICP-MS. In addition, general lake water chemistry, TOC and principal anions were measured in the aqueous phases. Redistribution processes were interpreted from geochemical modelling. The solid/solution distribution of pe/pH sensitive elements, indicates a minor diagenetic redistribution and the concentration profiles are therefore suitable for chronological evaluation. The ratios of Al, Ti, Sc and V, indicated a qualitative shift of sedimenting material a century ago, which did not have any impact on the retention of trace elements. Lead had a concentration profile, supported by the (206)Pb/(207)Pb ratio, where it was possible to distinguish preindustrial conditions, early industrialisation in Europe, industrialisation in Sweden, and the use of leaded petrol after the Second World War. Cadmium showed a similar concentration pattern. The zinc profile resembled that of cadmium, but with less enrichment. Local lithogenic sources are believed to be quantitatively important. The solid/solution distribution (K(d)) was independent of depth for all four elements. The sediment concentrations of copper and zinc are not related to early industrialisation but its concentration has doubled since the Second World War.

Environmental Monitoring↗

PubMed2006

Historical pollution of seldom monitored trace elements in Sweden--Part B: sediment analysis of silver, antimony, thallium and indium.

Sediment cores from four boreal and remote lakes in a south to north transect in central Sweden were analysed for acid leachable silver, antimony, thallium and indium in the solid sediment phase and the corresponding porewater. Dating of the cores was made by their content of acid leachable lead and the (206)Pb/(207)Pb ratio, in one lake also by (210)Pb. The impact of diagenesis on element redistribution in the sediments was included and found to be minor except for thallium. The results show lowered concentrations towards the north and most intense accumulation after the Second World War, which is taken as evidence for atmospheric deposition being the primary source. Indium has declining concentrations in recent strata while silver and antimony increase. Thallium has lowered acid-leachable concentrations in recent strata. For all metals the impact of domestic industrialisation as well as the early industrialisation of central Europe is discernible. Only thallium appears to reach a geological background at depths that correspond to the late 18th century. For the other metals elevated levels are concluded.

Environmental Monitoring↗

PubMed2006

Sediment reference concentrations of seldom monitored trace elements (Ag, Be, In, Ga, Sb, Tl) in four Swedish boreal lakes--comparison with commonly monitored elements.

This paper presents reference and recent acid-leachable concentrations of some seldom monitored trace elements (SMTE; Ag, Be, Ga, In, Sb and Tl) in sediments from four boreal oligotrophic lakes in a south to north transect in Sweden. For comparison commonly monitored trace elements (As, Cd, Co, Cr, Cu, Ni, Pb and Zn) are included as well as those of relevance for redistribution processes (Al, Ca, Fe, Mg and Mn). Pore water pH and the corresponding solid/solution distribution coefficients (Kd) indicated that redistribution of the elements due to acidification is minor. The depth of impact was defined as the level in the sediment where the mean values became constant on successive exclusion of metal concentrations in overlying strata. Reference concentrations were calculated below the depth of impact. The present concentration changes are estimated by the ratio between the average concentration above the depth of impact and the reference concentration. Reference concentration ranges for the SMT-elements are (mg/kg, dry wt.): Ag 0.16-0.66; Be 1.6-3.7; Ga 2.0-5.1; In 0.05-0.22; Sb 0.05-0.11 and Tl 0.17-0.70. The concentration ratios for these elements ranged in the two most southern lakes from 1.5 to 4.5 and in the two northern ones from 0.6 to 1.6. A high correlation between Kd for the SMT-elements, and iron, except for Sb and Tl, infer that the biogeochemistry of iron is quantitatively important for the accumulation of these elements. The reference concentration ranges for the commonly monitored trace elements are (mg/kg, dry wt.): As 7.0-29.6; Cd 0.33-0.98; Co 5.7-23.8; Cr 15.2-26.1; Cu 27.6-58.4; Ni 5.4-20.8; Pb 44-96. The corresponding concentration ratios were 1.2-18 (second highest 3.9) in the two most southern lakes and 0.8-1.6 in the two northern ones. Declining ratios were found from south to north, most obvious for cobalt and zinc. The copper ratios did not show a regional pattern, partly because of the impact from old mine waste. Increased concentrations of Ag, Be, Ga, In, Sb and Tl in recent sediments up to 4.5 times the reference levels in combination with the geographical pattern infer an elevated loading of these elements.

Environmental Monitoring↗

PubMed2006

Erythropoiesis in the Rps19 disrupted mouse: Analysis of erythropoietin response and biochemical markers for Diamond-Blackfan anemia.

The human ribosomal protein S19 gene (RPS19) is mutated in approximately 20% of patients with Diamond-Blackfan anemia (DBA), a congenital disease with a specific defect in erythropoiesis. The clinical expression of DBA is highly variable, and subclinical phenotypes may be revealed by elevated erythrocyte deaminase (eADA) activity only. In mice, complete loss of Rps19 results in early embryonic lethality whereas Rps19+/- mice are viable and without major abnormalities including the hematopoietic system. We have performed a detailed analysis of the Rps19+/- mice. We estimated the Rps19 levels in hematopoietic tissues and we analyzed erythrocyte deaminase activity and globin isoforms which are used as markers for DBA. The effect of a disrupted Rps19 allele on a different genetic background was investigated as well as the response to erythropoietin (EPO). From our results, we argue that the loss of one Rps19 allele in mice is fully compensated for at the transcriptional level with preservation of erythropoiesis.

Anemia, Diamond-Blackfan↗

PubMed2005

Fungus covered insulator materials studied with laser-induced fluorescence and principal component analysis.

A method combining laser-induced fluorescence and principal component analysis to detect and discriminate between algal and fungal growth on insulator materials has been studied. Eight fungal cultures and four insulator materials have been analyzed. Multivariate classifications were utilized to characterize the insulator material, and fungal growth could readily be distinguished from a clean surface. The results of the principal component analyses make it possible to distinguish between algae infected, fungi infected, and clean silicone rubber materials. The experiments were performed in the laboratory using a fiber-optic fluorosensor that consisted of a nitrogen laser and an optical multi-channel analyzer system.

Equipment Contamination↗

PubMed2004

Multicentre study of validity and interrater reliability of the modified Nursing Care Recording System (NCR11) for assessment of workload in the ICU.

BACKGROUND: Reliable assessment of nursing workload is necessary for the quantitative approach to staffing of intensive care units. The Nursing Care Recording System (NCR11) scores both the nursing contribution to patient care and those related to medical procedures. The purpose of the present work was to compare NCR11 scoring with the Therapeutic Intervention Scoring System (TISS) and Nine Equivalents of Nurse Manpower use Score (NEMS) and to examine the interrater reliability of NCR11 scoring. METHODS: Bias and precision of workload scores (NCR11 vs. TISS or NEMS) were assessed for 6126 consecutive admissions (23910 ICU-days) at three intensive care units. Inter-rater reliability was analyzed by having nurses at nine ICUs score workload using NCR11 for three dummy intensive care patient cases presented over a 3-year period. Variability in scoring was analyzed using the coefficient of variation. RESULTS: Agreement between NCR11 and TISS or NEMS was poor and limits of agreement were wide. Linear relationships between NCR11 and TISS or NEMS scores differed between units. Variability in NCR11 scoring decreased significantly from 10.4% to 5.9% between dummy cases 1 and 2 and remained low for patient case 3. CONCLUSION: The NCR11 does not measure the same elements of workload in the ICU as do TISS and NEMS. Inter-rater reliability with NCR11 is good, showing little variation in scoring between nurses.

Analysis of Variance↗

PubMed2003

Phase behavior in the system water-butylammonium decanoate-decane.

The phase diagram at 298.2 and 281.2 K for the ternary system water-butylammonium decanoate-decane has been determined. An isotropic solution phase extending from the water corner to the decane corner was obtained without any macroscopic phase separation. A large two-phase region extending from the water-decane axis was also observed. In addition to these phases, an anisotropic and optically birefrigent liquid crystalline phase is formed below 290.3 K. Sound velocity, conductivity, and viscosity measurements were used successfully for studies of microstructural transitions in the isotropic solution phase. From these measurements, it was concluded that a transition from normal micelles to reverse micelles takes place while passing through a bicontinuous region.

Journal Article↗

PubMed2003

Test-retest reliability of EMG and peak torque during repetitive maximum concentric knee extensions.

The aim of this study was to investigate the reliability of peak torque and surface electromyography (EMG) variable's root mean square (RMS) and mean frequency (MNF) during an endurance test consisting of repetitive maximum concentric knee extensions. Muscle fatigue has been quantified in several ways, and in isokinetic testing it is based on a set of repetitive contractions. To assess test-retest reliability, two sets of 100 dynamic maximum concentric knee extensions were performed using an isokinetic dynamometer. The two series were separated by 7-8 days. The subjects relaxed during the passive flexion phase. Twenty (10 men and 10 women) clinically healthy subjects volunteered. Peak torque and EMG from rectus femoris, vastus medialis, vastus lateralis and biceps femoris were recorded. RMS and MNF were calculated from the EMG signal. The reliability was calculated with intraclass correlation coefficient ICC (1.1) and standard error of measurements (SEM). The reliability of peak torque was good (ICC=0.93) and SEM showed low values. ICC was good for absolute RMS of rectus femoris (ICC>/=0.80), vastus medialis (ICC>/=0.88) and vastus lateralis (ICC>/=0.82) and MNF of rectus femoris (ICC>/=0.82) and vastus medialis (ICC>/=0.83). Peak torque, and MNF and RMS of rectus femoris and vastus medialis are reliable variables obtained from an isokinetic endurance test of the knee extensors.

Adult↗

PubMed2003

On the surface elemental composition of non-corroded and corroded dental ceramic materials in vitro.

Dental ceramics are traditionally looked upon as inert materials. As many are glass phased, it may be hypothesized that they will be subjected to glass corrosion in aqueous environments. The aim of the study was therefore to analyze the surface elemental composition of glass-phased and all-crystalline ceramics, before and after low- and high-intensity, in vitro corrosion (milli-Q-water at 37+/-2 degrees C for 18 h and 4% acetic acid at 80+/-2 degrees C for 18 h, respectively). The analysis of the surface elemental composition was performed using ESCA. The hypothesis was confirmed. After high-intensity corrosion, the complete wash out of alkali ions, alkaline-earth ions and elemental alumina was found, leaving behind a surface totally dominated by silica. The all-crystalline ceramics, densely sintered alumina and yttria-partially stabilized tetragonal zirconia, displayed only minor surface changes, even after high-intensity corrosion. In comparison to the corrosion testing in acid, the corrosion process in milli-Q-water did not produce different results in principle, except for the lower magnitude of the depletion of alkali ions and the virtually unchanged level of elemental alumina. Unexpectedly, no substantial difference in surface degradation was found between the glass ceramic and the ordinary porcelain-fused-to-metal ceramic or between ceramics of higher sintering temperature and those of low or ultra-low sintering temperature. The composition and microstructure alone did not appear to provide a full explanation for the inter-individual differences in surface corrosion when exposed to comparable environmental conditions.

Journal Article↗

PubMed2003

Selection-induced variation at the pantophysin locus (PanI) in a Norwegian fjord population of cod (Gadus morhua L.).

A total of 1290 cod (Gadus morhua L.), sampled between 1985 and 1999 from a spawning area in the Trondheimsfjord, Norway, were assayed for the nuclear-encoded locus PanI (pantophysin). The majority of samples were taken during the spawning season at two nearby sampling locations at depths of 100 and 60 m, respectively. Genetic analysis revealed significant effects of cohort, sex and sampling location on allele frequencies at PanI. The contribution of each of these three factors to the total among-sample diversity (FST) of 8.01% at PanI was estimated to be 3.78, 2.55 and 1.68%, respectively. Sign tests revealed a significant excess of heterozygotes at both sampling locations in females; a significant excess of heterozygotes in males was observed at one of the localities. Mutation, genetic drift and immigration do not appear to contribute significantly to the observed genetic heterogeneity at PanI, leaving natural selection as the main explanatory factor for the Hardy-Weinberg imbalance. The dynamics of the selection at PanI appear to be complex. Analysis of age, sex and cohort proved crucial to disentangle putative explanatory factors from their secondary effects.

Animals↗

PubMed2002

Activation of mitogen-activated protein kinases in experimental cerebral ischemia.

OBJECTIVES: Mitogen-activated protein kinases (MAPK) regulate cell survival and differentiation. The aim of the present study is to investigate the activation pattern of different MAPKs [extracellular signal-regulated kinase (ERK), c-jun-N-terminal kinase (JNK) and p38] after cerebral ischemia. MATERIAL AND METHODS: Rats were subjected to cerebral ischemia using a model for transient (2 h) and permanent middle cerebral artery occlusion (MCAO). The rats were allowed 6 h to 1 week of survival before immunohistochemical evaluation with phospho-specific antibodies, recognizing activated MAPKs. RESULTS: ERK was activated in ipsilateral blood vessels, neurons and glia, but also in contralateral vessels. JNK activation was absent in neurons but appeared in arterial blood vessels and glia at the lesion side. Active p38 was observed in macrophages in maturing infarcts. CONCLUSIONS: ERK and JNK may participate in the angiogenic response to cerebral ischemia. ERK, but not JNK, was activated in neurons, possibly indicating a pathophysiologic role. Active p38 might be involved in the inflammatory reaction.

Animals↗

PubMed2002

Development of gene therapy for hematopoietic stem cells using lentiviral vectors.

Lentiviral vectors are promising tools for the development of gene therapy since they can transduce both quiescent and dividing target cells. Lentiviral vectors may be particularly promising gene delivery tools for hematopoietic stem cells since these target cells tend to be quiescent and are therefore difficult target cells for vectors that require dividing targets. Human hematopoietic stem cells that can repopulate NOD/SCID mice have been efficiently transduced using HIV-1-based lentiviral vectors and similar vectors can also transduce murine hematopoietic stem cells. HIV-1 vectors that contain strong general promoters can generate high levels of transgene expression and very high expression levels can be generated in erythroid cells in vivo using beta-globin regulatory sequences to control the expression of the transgene. Current lentiviral vectors have a similar level of biosafety as oncoretroviral vectors and can therefore theoretically be used in clinical gene therapy protocols. Future challenges include the generation of lentiviral vectors that can express more than one transgene at high levels and the generation of safe permanent packaging cells for practical use in clinical gene therapy trials.

Animals↗

PubMed2002

Development of gene therapy for blood disorders by gene transfer into haematopoietic stem cells.

Haematopoietic stem cells (HSCs) are important target cells for gene therapy of blood disorders due to their pluripotency and ability to reconstitute haematopoiesis following myeloablation and transplantation. HSCs can 'self-renew' and generate new stem cells. Genetically modified stem cells are therefore expected to last a lifetime in the recipient following blood and marrow transplantation, and can potentially cure haematological disorders. Oncoretroviral vectors have been the main vectors used for HSCs because of their ability to integrate into the chromosomes of their target cells. Because oncoretroviral vectors require dividing target cells for successful localization of the preintegration complex and subsequent chromosomal integration of the provirus, only the dividing fraction of the target cells can be transduced. As only a small fraction of haematopoietic stem cells is dividing at any one time, oncoretroviral vector transduction of human HSCs has been low in clinical trials. However, patients with severe combined immune deficiency-X1 (SCID-X1) have recently been treated successfully by gene therapy of autologous bone marrow cells using oncoretroviral vectors containing the common gamma chain gene. While several additional disorders may potentially be treated successfully using oncoretroviral gene transfer to HSCs, many disorders may require much higher gene transfer efficiency than was achieved in the SCID-X1 study. Therefore, lentiviral vectors have recently emerged as promising vectors for human HSCs because they can transduce dividing and nondividing HSCs efficiently, and may become the vectors of choice in the future for treatment of blood disorders where a large fraction of HSCs has to be corrected.

Animals↗

PubMed2001

Proliferation of primitive myeloid progenitors can be reversibly induced by HOXA10.

Recent studies show that several Hox transcription factors are important for regulation of proliferation and differentiation in hematopoiesis. Among these is H0XA10, which is selectively expressed at high levels in the most primitive subpopulation of human CD34(+) bone marrow cells. When overexpressed, H0XA10 increases the proliferation of early progenitor cells and can lead to the development of myeloid leukemia. To study the effects of H0XA10 on primitive hematopoietic progenitors in more detail, transgenic mice were generated with regulatable H0XA10 expression. The transgenic mouse model, referred to as tetO-HOXA10, contains the H0XA10 gene controlled by a tetracycline-responsive element and a minimal promoter. Thus, the expression of H0XA10 is inducible and reversible depending on the absence or presence of tetracycline or its analog, doxycycline. A retroviral vector containing the tetracycline transactivator gene (tTA) was used to induce expression of the H0XA10 gene in bone marrow cells from the transgenic mice. Reverse transcription-polymerase chain reaction analysis confirmed regulatable H0XA10 expression in several transgenic lines. H0XA10 induction led to the formation of hematopoietic colonies containing blastlike cells and megakaryocytes. Moreover, the induction of H0XA10 resulted in significant proliferative advantage of primitive hematopoietic progenitors (spleen colony-forming units [CFU-S(12)]), which was reversible on withdrawal of induction. Activation of H0XA10 expression in tet0-H0XA10 mice will therefore govern proliferation of primitive myeloid progenitors in a regulated fashion. This novel animal model can be used to identify the target genes of HOXA10 and better clarify the specific role of HOXA10 in normal and malignant hematopoiesis.

Animals↗

PubMed2001

Abnormal angiogenesis but intact hematopoietic potential in TGF-beta type I receptor-deficient mice.

Deletion of the transforming growth factor beta1 (TGF-beta1) gene in mice has previously suggested that it regulates both hematopoiesis and angiogenesis. To define the function of TGF-beta more precisely, we inactivated the TGF-beta type I receptor (TbetaRI) gene by gene targeting. Mice lacking TbetaRI die at midgestation, exhibiting severe defects in vascular development of the yolk sac and placenta, and an absence of circulating red blood cells. However, despite obvious anemia in the TbetaRI(-/-) yolk sacs, clonogenic assays on yolk sac-derived hematopoietic precursors in vitro revealed that TbetaRI(-/-) mice exhibit normal hematopoietic potential compared with wild-type and heterozygous siblings. Endothelial cells derived from TbetaRI-deficient embryos show enhanced cell proliferation, improper migratory behavior and impaired fibronectin production in vitro, defects that are associated with the vascular defects seen in vivo. We thus demonstrate here that, while TbetaRI is crucial for the function of TGF-beta during vascular development and can not be compensated for by the activin receptor-like kinase-1 (ALK-1), functional hematopoiesis and development of hematopoietic progenitors is not dependent on TGF-beta signaling via TbetaRI.

Activin Receptors, Type I↗

PubMed2001

Direct cytoplasmic CA(2+) responses to gastrin-releasing peptide in single beta cells.

The neuropeptide gastrin releasing peptide (GRP) stimulates insulin secretion and induces oscillations of the cytoplasmic Ca(2+) concentration ([Ca(2+)](cyt)) in clonal insulinoma cells. It is not known whether GRP affects [Ca(2+)](cyt) in normal beta cells. We investigated, in single, normal, mouse islet beta cells, the effects of GRP on [Ca(2+)](cyt), by dual wavelength spectrophotofluorometry. Beta cells were identified by their typical response to glucose or tolbutamide. At 15 mM glucose, GRP (100 nM) evoked an immediate [Ca(2+)](cyt) transient to 423 +/- 48 nM compared to 126 +/- 18 nM before GRP (P < 0.001). After the initial transient, [Ca(2+)](cyt) exhibited either a sustained elevation or oscillations. At 3.3 mM glucose, in cells with a non-oscillating [Ca(2+)](cyt), GRP stimulated a prompt increase in [Ca(2+)](cyt) (from 60 +/- 6 to 285 +/- 30 nM, P = 0.024) followed by either a sustained increase in [Ca(2+)](cyt) or [Ca(2+)](cyt) oscillations. We conclude that GRP promptly elevates [Ca(2+)](cyt) by a direct action in normal mouse pancreatic beta cells.

Animals↗

PubMed2001

Clinical gene therapy in hematology: past and future.

Gene transfer into hematopoietic cells using viral vectors has focused mostly on lymphocytes and hematopoietic stem cells (HSCs). HSCs have been considered particularly important as target cells because of their pluripotency and ability to reconstitute hematopoiesis after myeloablation and transplantation. HSCs are believed to have the ability to live a long time, perhaps a lifetime, in the recipient following bone marrow transplantation. Genetic correction of HSCs can therefore potentially last a lifetime and permanently cure hematologic disorders in which genetic deficiencies cause the pathology. Oncoretroviral vectors have been the main vectors used for HSCs because of their ability to integrate into the chromosomes of their target cells. Gene-transfer efficiency of murine HSCs is high using oncoretroviral vectors. In contrast, gene-transfer efficiency using the same viral vectors to transduce human HSCs or HSCs from large animals has been much lower. Although these difficulties may have several causes, the main reason for the low efficiency of human HSC transduction with oncoretroviral vectors is probably because of the nondividing nature of HSCs. Murine HSCs can be easily stimulated to divide in culture, whereas it is more problematic to stimulate human HSCs to divide rapidly in vitro. Because oncoretroviral vectors require dividing target cells for successful nuclear import of the preintegration complex and subsequent integration of the provirus, only the dividing fraction of the target cells can be transduced. This review focuses on gene transfer into human hematopoietic cells, particularly human HSCs. We review the clinical studies that have been reported, including the recent successful gene therapy for X-linked severe combined immunodeficiency. We discuss how the gene-transfer efficiency of human HSCs can be improved using oncoretroviral and lentiviral vectors.

Clinical Trials as Topic↗

PubMed2001

Reactivity of Trametes laccases with fatty and resin acids.

Lipophilic extractives commonly referred to as wood pitch or wood resin can have a negative impact on paper machine runnability and product quality. The lipophilic extractives are composed mainly of fatty acids, resin acids, sterols, steryl esters and triglycerides. In this work, the suitability of laccases for the modification of fatty and resin acids was studied, using two model fractions. In the treatments, resin and fatty acid dispersions were treated with two different laccases, i.e. laccases from Trametes hirsuta and T. villosa. Different chromatographic methods were used to elucidate the effects of laccase treatments on the chemistry of the fatty and resin acids. Both laccases were able to modify the fatty and resin acids to some extent. In the case of fatty acids, a decrease in the amount of linoleic, oleic and pinolenic acids was observed, whereas the modification of resin acids resulted in a reduced amount of conjugated resin acids.

Abietanes↗