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J Nilsson

Publications and source records attributed to J Nilsson.

At least 19 recordsLinked to original sources

High-power, low-noise, Yb-doped, cladding-pumped, three-level fiber sources at 980 nm.

We present results on a high-power, cladding-pumped, Yb-doped fiber emitting at 977 nm in laser and ampllified-spontaneous-emission source configurations. We obtained up to 1.4 W of fiber-coupled, single-mode output power and slope efficiency as high as 68%. To our knowledge these are the highest powers efficiencies achieved from a single-mode fiber laser at approximately 980 nm and the first demonstrated results on a high-power amplified-spontaneous-emission source in this wavelength range. High power and high slope efficiency are achieved by using a high numerical aperture (> 0.7), a jacketed air-clad fiber, and a high-brightness pump source. Both types of sources exhibit relative intensity noise below -130 dB/Hz and are thus suitable for a wide range of applications.

Journal Article↗

Studies on semicarbazide-sensitive amine oxidase in patients with diabetes mellitus and in transgenic mice.

Patients with diabetes mellitus and with vascular complications in particular, exhibit higher plasma activities of semicarbazide-sensitive amine oxidase (SSAO) compared to control subjects. It has been speculated that production of cytotoxic products of SSAO may cause endothelial damage and thus contribute to the development of diabetic vascular complications such as retino-, nephro-, and neuropathies as a result of SSAO activity.In order to explore the possibility that high SSAO activity contributes to the development of vascular complications in diabetes, we have performed two studies in patients with Type-2 diabetes quantifying plasma SSAO activity, HbA(1c), and urinary levels of the SSAO substrate, methylamine. We also examined the prevalence of retinopathy in these patients. Additionally, we have studied a model of transgenic mice expressing human SSAO in smooth muscle cells. The transgenic mice have an increased SSAO activity as well as mRNA expression. Histological studies revealed a specific aorta phenotype with a condensed and rigid vessel wall in some of the transgenic mice. No wild-type animals displayed this phenotype.In conclusion, we suggest that this transgenic mouse model may be of great value for increasing the knowledge about to what extent human SSAO contributes to vascular complications in diabetes, and also to which extent inhibition of SSAO can prevent the development of such complications.

Amine Oxidase (Copper-Containing)↗

Plasma oxidized LDL: a predictor for acute myocardial infarction?

OBJECTIVES: Oxidized LDL has been attributed a key role in the development of atherosclerosis. Previous studies have demonstrated increased plasma levels of oxidized LDL in patients with established coronary artery disease. The aim of the present study was to investigate if plasma oxidized LDL also predicts risk for development of coronary heart disease (CHD). DESIGN: We used a nested case-control design to study the association between plasma levels of oxidized LDL and risk for development of acute myocardial infarction (AMI) and/or death by CHD. SUBJECTS: Oxidized LDL was analysed by ELISA in cases (n = 26), controls (n = 26) and controls with LDL cholesterol >5.0 mmol L-1 (n = 26). RESULTS: Oxidized LDL correlated with total plasma and LDL cholesterol in both cases (r = 0.72, P < 0.01, r = 0.69, P < 0.01, respectively) and controls (r = 0.71, P < 0.01, r = 0.77, P < 0.01, respectively). The oxidized LDL/plasma cholesterol ratio was higher amongst cases (13.5, range 10.7-19.8) than in controls (12.6, range 9.5-15.8, P < 0.05) and hypercholesterolaemic controls (12.2, range 8.0-16.0, P < 0.01). CONCLUSIONS: These findings identify high plasma oxidized LDL/total cholesterol ratio as a possible indicator of increased risk for AMI.

Aged↗

Echolucency of carotid plaques correlates with plaque cellularity.

OBJECTIVE: To analyse the relationship between carotid plaque echolucency and cellularity. METHODS: Carotid plaques (14 symptomatic and 16 asymptomatic) were snap frozen after endarterectomy and defined on the basis of their grey-scale-median (GSM), obtained from pre-operative high-definition ultrasonography, as either echolucent (<32) or echogenic (>or=32). DNA and total soluble protein were determined to assess cellularity. RESULTS: After correcting for wet weight, symptomatic plaques had significantly more DNA (0.400 +/- 0.07 vs 0.335 +/- 0.07 mg/g; p = 0.03) and soluble protein (34.1 +/- 6.6 vs 29.7 +/- 3.4 mg/g; p = 0.03) than asymptomatic plaques. Predominantly echolucent (Grey-Weale classification) plaques had more DNA (0.404 +/- 0.06 vs 0.332 +/- 0.08 mg/g; p = 0.03) than echogenic plaques. Plaques with GSM < 32 also had more DNA (0.386 +/- 0.08 vs 0.319 +/- 0.06 mg/g; p = 0.04) and soluble protein (34.7 +/- 7.3 vs 29.6 +/- 4.2 mg/g; p = 0.03) than those with GSM >or= 32. Inverse relations were found between GSM and plaque DNA (r = -0.47; p = 0.02) and soluble protein (r = -0.45; p = 0.02) as well as between age and DNA (r = 0.39; p = 0.04) and soluble protein (r = -0.50; p = 0.003). CONCLUSIONS: Echolucency of carotid plaques as assessed by ultrasonography reflects plaque cellularity. This observation support the notion that ultrasonography can be used to identify high-risk plaques and evaluate effect of interventions on plaque structure.

Aged↗

Calibration of a radioactive ink-based stack phantom and its applications in nuclear medicine.

This paper describes a stack phantom useful for imaging complex activity distributions. It is based on images printed with radioactive ink using a commercial ink-jet printer. The application for the phantom is in the evaluation of planar and SPECT scintillation camera images and for validation of Monte Carlo simulated images. The accuracy in generating the activity distributions on paper sheets is especially important. Here we describe the calibration procedure for the ink-jet printer. The goal of the printer calibration is to find the relationship between the digital image count (voxel grey level) and its corresponding activity on the paper sheets (radioactivity). The relationship between the voxel grey level and the radioactivity on the paper sheets (measured by scanning technique and well counter) was found to be logarithmic, and a 3rd degree polynomial was found to fit the relationship. The distribution of radioactivity in the ink cartridge was investigated by pinhole SPECT. The distribution of (99m)Tc solution was found to be homogeneous in the ink solution. Experimental studies were done directly on Monte Carlo simulated heart images from the NCAT phantom. The result showed that the simulated images are similar to the images measured using the ink-jet technique. This stack phantom could be a promising solution with an advantage that the exact geometry generated in Monte Carlo could be imitated in the phantom. The phantom is a very flexible device and clearly much more versatile than conventional phantoms which have a fixed geometry and spatial limitation.

Calibration↗

Microsatellite data resolve phylogeographic patterns in European grayling, Thymallus thymallus, Salmonidae.

The phylogeography of an endangered salmonid, European grayling (Thymallus thymallus), was studied based on analysis of 17 nuclear microsatellite DNA loci. In agreement with earlier mitochondrial DNA (mtDNA) studies, phylogenetic relationships of the populations suggested that northern Europe was colonized from two distinct Pleistocene refugia. Furthermore, microsatellites revealed highly supported grouping of mainland Swedish, Norwegian, Danish, German and Slovenian populations, suggesting that grayling from the northwestern and central Europe have descended from their southern conspecifics. The level of divergence between populations was substantial, even across short geographical distances. Although this was in part due to postglacial colonization patterns and contemporary barriers for gene flow, the high divergence estimates between hydrologically connected sampling locations implied efficient interpopulation reproductive isolation. Microsatellites revealed that the populations exhibited, on average, only 3.5 (+/-2.2) alleles per locus, indicating that T. thymallus has strikingly low levels of intrapopulation genetic diversity as compared with other freshwater fish species. Accordingly, as indicated by analysis of molecular variance (AMOVA), only 49.1-58.0% of the total grayling microsatellite diversity resided within populations. A latitudinal genetic diversity gradient, potentially resulting from glaciation-mediated founder events, was not evident. Alternatively, it is possible that grayling display limited dispersal behaviour/capability, leading to low long-term effective population sizes and, consequently, depauperate intrapopulation polymorphism. These findings have implications for conservation of T. thymallus. Importantly, they exemplify that microsatellites can be highly informative for intraspecific phylogeography studies dealing with substantial divergence scales.

Animals↗

Percutaneous fine-needle aspiration cytology in the diagnosis and management of liver tumours.

BACKGROUND: The aim of the study was to investigate the value of percutaneous fine-needle aspiration cytology (FNAC) in the diagnosis and management of liver tumours. METHODS: FNAC followed by histopathological examination was carried out in 216 patients with suspected liver tumours. The final diagnosis was primary liver cancer in 106, colorectal metastases in 51, non-colorectal metastases in 46, benign tumour in nine and no tumour in four patients. RESULTS: Cytology resulted in correct classification of the lesion as benign or malignant in 87 per cent of patients, correct discrimination between primary and secondary malignancy in half of the patients, and a correct diagnosis of tumour type in one-third of patients. The tumour was erroneously classified as benign or malignant in 22 patients (11 per cent) and four patients (2 per cent) respectively. When FNAC showed malignancy, the predictive value was 98 per cent, whereas the predictive value was 27 per cent when it did not. FNAC guided investigations and treatment in one-quarter of patients. Implantation metastases were recorded in seven patients (3 per cent), including five (10 per cent) of 51 patients with colorectal liver metastases, and caused major local problems and death in four patients. CONCLUSION: FNAC was valuable in about a quarter of patients with liver tumour. The risks of implantation metastases and a false-negative finding do not justify its use in candidates for curative therapy of liver tumours.

Adult↗

Myelin protein P0-specific IgM producing monoclonal B cell lines were established from polyneuropathy patients with monoclonal gammopathy of undetermined significance (MGUS).

Monoclonal expansion of B cells and plasma cells, producing antibodies against 'self' molecules, can be found not only in different autoimmune diseases, such as peripheral neuropathy (PN), but also in malignancies, such as Waldenström's macroglobulinaemia and B-type of chronic lymphocytic leukaemia (B-CLL), as well as in precancerous conditions including monoclonal gammopathy of undetermined significance (MGUS). About 50% of patients with PN-MGUS have serum antibodies against peripheral nerve myelin, but the specific role of these antibodies remains uncertain. The aims of the study were to establish, and characterize, myelin-specific B cell clones from peripheral blood of patients with PN-MGUS, by selection of cells bearing specific membrane Ig-receptors for myelin protein P0, using beads coated with P0. P0-coated magnetic beads were used for selection of cells, which subsequently were transformed by Epstein--Barr virus. The specificity of secreted antibodies was tested by ELISA. Two of the clones producing anti-P0 antibodies were selected and expanded. The magnetic selection procedure was repeated and new clones established. The cells were CD5+ positive, although the expression declined in vitro over time. The anti-P0 antibodies were of IgM-lambda type. The antibodies belonged to the VH3 gene family with presence of somatic mutations. The IgM reacted with P0 and myelin-associated glycoprotein (MAG), and showed no evidence for polyreactivity, in contrast to other IgM CD5+ clones included in the study as controls. The expanded clones expressed CD80 and HLA-DR, which is compatible with properties of antigen-presenting cells. The immunomagnetic selection technique was successfully used for isolation of antimyelin protein P0-specific clones. The cell lines may provide useful tools in studies of monoclonal gammopathies, leukaemia, and autoimmune diseases, including aspects of antigen-presentation by these cells followed by T cell activation.

Aged↗

Plasma tumour necrosis factor-alpha and early carotid atherosclerosis in healthy middle-aged men.

AIMS: Tumour necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine, which is implicated in some metabolic disorders and may play a role in the development of cardiovascular disease. We examined whether plasma TNF-alpha is related to established cardiovascular risk indicators, plasma levels of soluble cellular adhesion molecules and carotid artery intima-media thickness determined by ultrasound examination in a population-based cohort of 96 healthy 50-year-old men. METHODS AND RESULTS: TNF-alpha and cellular adhesion molecules were measured with enzyme-linked immunosorbent assays. Plasma TNF-alpha concentration was associated with systolic and diastolic blood pressure, degrees of alimentary lipaemia, plasma very low density lipoprotein triglyceride, low density lipoprotein (LDL) cholesterol concentrations and peak LDL particle size. Two indices of insulin resistance as well as all soluble cellular adhesion molecules correlated positively with TNF-alpha. The plasma TNF-alpha concentration was associated with common carotid intima-media thickness in univariate analysis. In contrast, soluble E-selectin and postprandial triglycerides, but not TNF-alpha, were independent determinants of common carotid intima--media thickness. CONCLUSION: The plasma TNF-alpha concentration is associated with degrees of early atherosclerosis and correlates with metabolic and cellular perturbations that are considered important for the vascular process.

ATPases Associated with Diverse Cellular Activitie↗

Efficacy and tolerability of prucalopride in patients with constipation due to spinal cord injury.

BACKGROUND: Chronic constipation (CC) often occurs after spinal cord injury (SCI). Prucalopride is a novel, highly selective, specific serotonin4 receptor agonist with enterokinetic properties. We evaluate the tolerability and pilot efficacy of prucalopride in the treatment of CC due to SCL. METHODS: Double-blind, placebo-controlled, pilot, phase 11, dose-escalation study. After 4 weeks' run in, patients received prucalopride 1 mg (n = 8) or placebo (n = 4); 11 new patients were randomized to prucalopride 2 mg (n = 8) or placebo (n = 3) once daily for 4 weeks. Patients recorded bowel function (diary) and assessed constipation severity and treatment efficacy (visual analogue scale (VAS) 0-100 mm). Colonic transit times were determined. RESULTS: Compared with run in. mean changes in constipation severity (VAS) increased with placebo, but decreased with prucalopride 1 and 2 mg. The VAS score for treatment efficacy showed a clear dose response (medians 4, 52 and 73 for placebo, 1 and 2 mg, respectively). Diary data showed an improvement in average weekly frequency of all bowel movements over 4 weeks within the 2 mg group (median 0.6; 95% CI 0.2; 1.2). There was a significant reduction in median colonic transit time with 2 mg (n = 4; -38.5 h (95% CI -80; -5)). Four patients (2 mg) reported moderate/severe abdominal pain, and two of these discontinued treatment. There were no clinically relevant effects on any of the safety parameters. CONCLUSION: This pilot study indicates that prucalopride can play an important role in the management of patients with CC due to SCI.

Adolescent↗

Prostate-specific antigen for prostate cancer staging in a population-based register.

OBJECTIVE: Previous studies have shown a relationship between serum prostate-specific antigen (PSA) level and prostate tumour volume. Reports based on selected case series have also indicated that serum PSA may be used for staging, although a varying prevalence of metastasizing tumours complicates the interpretation of these studies. In order to determine the accuracy of the serum level of PSA in predicting the presence of metastases we performed a prospective cohort study of a geographically defined population of men with prostate cancer. METHODS: Serum level of PSA and the results of investigations for regional lymph node and distant metastases were recorded for all 8328 men with prostate cancer registered in the Swedish National Prostate Cancer Register 1996-1997. RESULTS: The prevalence of lymph node metastases among men who had undergone lymph node exploration was 4%, 16% and 33% for well, moderately and poorly differentiated tumours. The corresponding prevalence of distant metastases was 12%, 30% and 48%. With serum PSA <20 ng/ml as a cut-off point the negative likelihood ratios for well and moderately differentiated tumours were found to be 0.47 and 0.45 for lymph node metastases and 0.24 and 0.18 for distant metastases, resulting in post-test probabilities >92% for the exclusion of metastases. In men with poorly differentiated tumours, the negative likelihood ratio would need to be even lower to safely exclude disseminated disease. CONCLUSION: For well to moderately differentiated tumours, further investigations to assess the presence of metastases may be omitted with no great risk for understaging if serum PSA <20 ng/ml.

Aged↗

Prostate-specific antigen as surrogate for characterizing prostate cancer subgroups.

OBJECTIVE: To evaluate how serum prostate-specific antigen (PSA) levels in a population-based cohort of men with prostate cancer vary with age and intensity in the diagnostic activity and to describe the treatment selection processes associated with PSA level. MATERIAL AND METHODS: All men in the Swedish National Prostate Cancer Register diagnosed during 1996-1997 were included. In 1996 the register included 19 counties, covering 61% of the Swedish male population, and in 1997 21 counties with 79% of the Swedish male population. RESULTS: A total of 8328 men were registered. PSA levels were missing in 341 cases. With increasing PSA there was a shift towards more advanced and poorly differentiated tumours. PSA at diagnosis increased with age, with the exception of patients younger than 50 years who had higher PSA values. The mean logarithm of PSA correlated negatively with the percentage of localized tumours (p < 0.005) and the age-adjusted incidence (p < 0.05) in each respective county in 1997. PSA was higher in men receiving radiotherapy compared with those treated with radical prostatectomy as well as in the group treated with bilateral orchiectomy compared with those receiving GnRH-analogues. CONCLUSIONS: If PSA is used as a surrogate measure of extent of tumour volume in a population of prostate cancer patients, our findings indicate that age distribution and differences in incidence (possibly due to variation in diagnostic activity) should be taken into account. In our cohort there was a selection process, probably in part guided by PSA level, when choosing type of curative or palliative treatment.

Age Factors↗

Radiation response of hypoxic and generally heterogeneous tissues.

PURPOSE: Biologically based treatment optimisation can be based on the local mean values of the number of clonogenic cells and the cellular radiation response taken over macroscopic tissue voxels. Steep oxygen gradients in tumours may often lead to microscopic distributions of radiation resistance at the cellular level, far beyond the geometrical resolution of current diagnostic and radiotherapeutic methods. The present work focuses on quantifying the radiobiological effect of such microscopic distributions through tissue-oxygenation modelling and on calculating the corresponding radiation response on both micro- and macroscopic scales. MATERIALS AND METHODS: A simple model of tissue vasculature was developed with microvascular density and heterogeneity as its main parameters. New analytical expressions are presented for calculating the effective radiation response of tissues with generally heterogeneous radiation resistance and clonogen density. RESULTS: The oxygen distributions derived for different parameter sets agree very well with clinically measured oxygen distributions for both tumours and normal tissues. In addition to the vascular density, vascular heterogeneity is an important factor while estimating the hypoxic fraction in tissue. It is shown that both the local and global dose-response relation for tissues with heterogeneous radiation resistance can be accurately calculated from the effective initial clonogen number N(0,eff) and the effective radiation resistance D(0,eff). New equations are derived for calculating these quantities, for instance, from measured oxygen distributions. CONCLUSIONS: With the new methods presented here, existing techniques to measure the micro- and macroscopic oxygen distribution either using standard tumour-type or patient-specific oxygenation data can be used for biologically based treatment plan optimisation.

Cell Survival↗

Development of silicon microstructures and thin-film MALDI target plates for automated proteomics sample identifications.

Here we report on the development of a proteomic platform utilizing a piezoelectric flow-through dispensing unit made from silicon microstructures. The use of a novel surface coating, where matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI MS) targets were uniformly precoated with a thin film of matrix/nitrocellulose, made the sample preparation straightforward and enabled the enrichment and analysis of proteins at low levels in proteomics samples. We demonstrate this by analyzing excised spots in a biological sample originating from a human fetal fibroblast cell line that was subjected to 2D gel-electrophoresis. Furthermore, a sample deposition rate below 30 Hz results in an increased analyte density on the dispensed sample spot, rendering signal amplification. In general, the sensitivity for proteins and peptides can be enhanced 10-50 times compared to traditional MALDI sample preparation techniques.

Animals↗

Cloning, characterization, and expression of human LIG1.

Growth factor receptors are frequently amplified and over-expressed in various human cancers. Recently, a Drosophila cell surface protein, Kekkon-1, was found to participate in an epidermal growth factor (EGF) driven negative feedback loop. Kekkon-1 is induced by EGF, binds to the EGF-receptor, and inhibits receptor-mediated signaling. Here, we have searched for human genes with homologies to Kekkon-1 and identified human LIG1. The gene is the human homologue of mouse Lig-1 and is located on chromosome band 3p14, a region frequently deleted in various human cancers. It is predicted to encode a transmembrane cell-surface protein with extracellular leucine-rich repeats and immunoglobulin-like domains. LIG1 mRNA was detected in all tissues analyzed. The highest and lowest relative expression levels were found in brain and spleen, respectively, and differed by more than 200-fold. Taken together, our data are compatible with a role for LIG1 as a growth and tumor suppressor in human tissues.

Amino Acid Sequence↗

Determination of diffusion coefficients of electroactive species in time-of-flight experiments using a microdispenser and microelectrodes.

Two novel methods for the determination of diffusion coefficients of redox species combining the special properties of microdispensing devices and microelectrodes are presented. Both are based on the local application of tiny volumes of the redox-active species by means of a dispenser nozzle at a defined distance from the surface of a microelectrode. The microelectrode, which is inserted through the bottom into an electrochemical cell, is held at a constant potential sufficient to oxidize or reduce the electro-active species under diffusional control. The dispenser, which is filled with the electro-active species, can be positioned by means of micrometer screws over the microelectrode. After dispensing a defined number of droplets near the microelectrode surface, the current through the microelectrode is recorded, usually yielding a peak-shaped curve having a defined time delay between the shooting of the droplets and the maximum current. The time that is necessary to attain maximum current, together with the known distance between two dispensing points, can be used to determine the diffusion coefficient of the electroactive species without knowledge of any system parameters, such as concentration of the redox species, diameter of the electroactive surface or number of transferred electrons. A similar method for the determination of diffusion coefficient of redox species involves a second redox species for calibration purposes. A mixture of both species is shot close to the microelectrode surface. Due to the different formal potentials of the redox species that are used, they can be distinguished in sequential experiments by variation of the potentials that are applied to the microelectrode, and it is thus possible to determine the individual transit times of the redox species independently. The difference in the transit times, together with the known diffusion coefficient of one of the redox species, can be used to calculate the unknown diffusion coefficient of the second one.

Journal Article↗