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Biomedical subjects

Staffan Nilsson

Publications and source records attributed to Staffan Nilsson.

At least 19 recordsLinked to original sources
PubMed2005

Fibrinolytic gene polymorphism and ischemic stroke.

BACKGROUND AND PURPOSE: The tissue-type plasminogen activator (tPA) -7351C>T and the plasminogen activator inhibitor type 1 (PAI-1) -675 4G>5G polymorphisms influence transcriptional activity. Both variants have been associated with myocardial infarction, with increased risk for the T and 4G allele, respectively. In this study we investigated the possible association between these polymorphisms, the respective plasma protein levels, and ischemic stroke. METHODS: In the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), 600 patients with acute ischemic stroke aged 18 to 69 years and 600 matched community controls were recruited. Stroke subtype was determined using Trial of Org 10172 in Acute Treatment criteria. RESULTS: There were no associations between individual genetic variants and ischemic stroke. The multivariate-adjusted odds ratio for overall ischemic stroke was 1.11 (95% CI 0.87 to 1.43) for tPA T allele carriers, and 0.84 (95% CI, 0.64 to 1.11) for subjects homozygous for the PAI-1 4G allele. When genotypes were combined, a protective effect for the tPA CC/PAI-1 4G4G genotype combination was observed (odds ratio 0.65, 95% CI 0.43 to 0.98; P<0.05). Plasma levels of tPA and PAI-1 antigen at follow-up were independently associated with overall ischemic stroke. tPA-antigen differed by stroke subtype and was highest among those with large-vessel disease and cardioembolic stroke. CONCLUSIONS: Neither the tPA -7351C>T nor the PAI-1 to 675 4G>5G polymorphism showed significant association with ischemic stroke. For the tPA CC/PAI-1 4G4G genotype combination, a protective effect was observed. Collectively, these results are consistent with a more complex role for tPA and PAI-1 in the brain as compared with the heart.

Adolescent↗
PubMed2005

Interaction of polymorphisms in the genes encoding interleukin-6 and estrogen receptor beta on the susceptibility to Parkinson's disease.

The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system and increased levels of IL-6 have been found in patients with Parkinson's disease (PD). It is known that estrogen inhibits the production of IL-6, via action on estrogen receptors, thereby pointing to an important influence of estrogen on IL-6. In a previous study, we reported an association between a G/A single nucleotide polymorphism (SNP) at position 1730 in the gene coding for estrogen receptor beta (ERbeta) and age of onset of PD. To investigate the influence of a G/C SNP at position 174 in the promoter of the IL-6 gene, and the possible interaction of this SNP and the ERbeta G-1730A SNP on the risk for PD, the G-174C SNP was genotyped, by pyrosequencing, in 258 patients with PD and 308 controls. A significantly elevated frequency of the GG genotype of the IL-6 SNP was found in the patient group and this was most obvious among patients with an early age of onset (</=50 years) of PD. When the GG genotypes of the IL-6 and ERbeta SNPs were combined, the combination was much more robustly associated with PD, and especially with PD with an early age of onset, than respective GG genotype when analyzed separately. Our results indicate that the G-174C SNP in the IL-6 promoter may influence the risk for developing PD, particularly regarding early age of onset PD, and that the effect is modified by interaction of the G-1730A SNP in the ERbeta gene.

Age of Onset↗
PubMed2005

Investigation of genes coding for inflammatory components in Parkinson's disease.

Several findings obtained recently indicate that inflammation may contribute to the pathogenesis in Parkinson's disease (PD). Genetic variants of genes coding for components involved in immune reactions in the brain might therefore influence the risk of developing PD or the age of disease onset. Five single nucleotide polymorphisms (SNPs) in the genes coding for interferon-gamma (IFN-gamma; T874A in intron 1), interferon-gamma receptor 2 (IFN-gamma R2; Gln64Arg), interleukin-10 (IL-10; G1082A in the promoter region), platelet-activating factor acetylhydrolase (PAF-AH; Val379Ala), and intercellular adhesion molecule 1 (ICAM-1; Lys469Glu) were genotyped, using pyrosequencing, in 265 patients with PD and 308 controls. None of the investigated SNPs was found to be associated with PD; however, the G1082A polymorphism in the IL-10 gene promoter was found to be related to the age of disease onset. Linear regression showed a significantly earlier onset with more A-alleles (P = 0.0095; after Bonferroni correction, P = 0.048), resulting in a 5-year delayed age of onset of the disease for individuals having two G-alleles compared with individuals having two A-alleles. The results indicate that the IL-10 G1082A SNP could possibly be related to the age of onset of PD.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2005

Defining women who are prone to have twins in in vitro fertilization--a necessary step towards single embryo transfer.

PURPOSE: The aim of the present study was to identify subsets of women undergoing two-embryo transfer in in vitro fertilization (IVF) who are prone to give birth to twins. METHODS: During 1990 to 2002 4580 day 2 or day 3 two-embryo transfers were conducted and these constituted the study population. RESULTS: By selecting combinations of factors, some subsets of patients where single-embryo transfer might be conducted would reduce the estimated twin rate by 60%, but requiring single-embryo transfer in only approximately one third of the patients. Examples of such selected groups were patients less than 33 years of age with two top quality embryos, patients less than 39 years of age with two top quality embryos and conducting their first IVF cycle, and patients less than 39 years of age with two top quality embryos and two optimal cleavage cells. CONCLUSION: By combining factors, subsets of patients with both a high birth and twin rate that could be recommended single embryo transfer were identified.

Adult↗
PubMed2005

Low expression of reduced folate carrier-1 and folylpolyglutamate synthase correlates with lack of a deleted in colorectal carcinoma mRNA splice variant in normal-appearing mucosa of colorectal carcinoma patients.

BACKGROUND: Cellular folate deficiency leads to DNA strand breaks, mutations, and aberrant methylation and might be a risk factor for colorectal cancer (CRC). The putative tumor suppressor gene deleted in colorectal carcinoma (DCC) is one of several genes the expression of which seems to be affected by the folate concentration at the tissue level. Decreased expression of DCC may be caused by LOH or hypermethylation, i.e. by events that might be linked to folate deficiency. The purpose of this study was to analyze if the folate level and the gene expression levels of reduced folate carrier (RFC-1) and folylpolyglutamate synthase (FPGS) had impact on the expression of DCC splice variants. METHODS: Quantification of RFC-1 and FPGS expression in mucosa of 53 CRC patients was performed using real-time PCR whereas DCC splicing variants were detected by automated capillary gel electrophoresis. Total reduced folate concentration was measured with the FdUMP-binding assay (n = 22). RESULTS: Significantly higher expression levels of RFC-1 (p = 0.026) and FPGS (p = 0.05) were found in mucosa expressing the splice variant DCC342 compared to mucosa that did not. Furthermore, multivariate analysis showed that RFC-1 and FPGS (r = 0.49, p = 0.01) as well as folate and RFC-1 (r = 0.56, p = 0.023) were correlated only in mucosa expressing DCC342. CONCLUSIONS: In conclusion, the present study points to a potential influence of folates in regulating DCC expression at multiple levels involving post-transcriptional pathways. The results may provide a basis for a detailed investigation of molecular mechanisms involved in folate regulation of DCC expression.

Adenocarcinoma↗
PubMed2005

Imbalance of the mitochondrial pro- and anti-apoptotic mediators in neuroblastoma tumours with unfavourable biology.

It has been proposed that a lack of apoptosis plays an important role in neuroblastoma (NB) progression. We therefore screened cDNA array filters, including 198 apoptotic genes, in order to identify mRNA transcripts that are differentially expressed in tumours with unfavourable versus favourable biology. Twenty-one genes were analysed further using real-time reverse-transcriptase-polymerase chain reaction (RT-PCR). Significantly lower levels of DNCL1 (PIN; P(c)(corrected) = 0.0054) and NTRK1 (TrkA; P(c) = 0.039) were found in NB tumours with unfavourable biology. In addition, BID, BCL2, APAF1, CASP2, CASP3 and CASP9 were found to be preferentially expressed in tumours with favourable biology, whereas CDKN1A (p21), IL2RA, and MCL1, were found to be preferentially expressed in NB tumours with unfavourable biology. In conclusion, mRNA levels of transcripts encoding pro-apoptotic mediators of the mitochondrial apoptotic pathway were found to be expressed to a lower extent in tumours with unfavourable biology. Our data also suggest that the mitochondrial pathway is suppressed in advanced stages of NB tumours, due to an imbalance between anti-apoptotic and pro-apoptotic mediators which is a finding that may have therapeutic significance.

Apoptosis↗
PubMed2005

Promising results with 306 single blastocyst transfers.

Single blastocyst transfer was performed in 306 IVF patients during 2002 to August 2003 in women younger than 39 years of age with at least five fertilized oocytes. Viable pregnancy rate per single blastocyst transfer was 40.7% during 2002 and 47.6% during 2003 (amounting to 35% of all IVF cycles), which in our experience are acceptable results.

Adult↗
PubMed2005

Sex steroid-related genes and male-to-female transsexualism.

Transsexualism is characterised by lifelong discomfort with the assigned sex and a strong identification with the opposite sex. The cause of transsexualism is unknown, but it has been suggested that an aberration in the early sexual differentiation of various brain structures may be involved. Animal experiments have revealed that the sexual differentiation of the brain is mainly due to an influence of testosterone, acting both via androgen receptors (ARs) and--after aromatase-catalyzed conversion to estradiol--via estrogen receptors (ERs). The present study examined the possible importance of three polymorphisms and their pairwise interactions for the development of male-to-female transsexualism: a CAG repeat sequence in the first exon of the AR gene, a tetra nucleotide repeat polymorphism in intron 4 of the aromatase gene, and a CA repeat polymorphism in intron 5 of the ERbeta gene. Subjects were 29 Caucasian male-to-female transsexuals and 229 healthy male controls. Transsexuals differed from controls with respect to the mean length of the ERbeta repeat polymorphism, but not with respect to the length of the other two studied polymorphisms. However, binary logistic regression analysis revealed significant partial effects for all three polymorphisms, as well as for the interaction between the AR and aromatase gene polymorphisms, on the risk of developing transsexualism. Given the small number of transsexuals in the study, the results should be interpreted with the utmost caution. Further study of the putative role of these and other sex steroid-related genes for the development of transsexualism may, however, be worthwhile.

Adult↗
PubMed2005

Long-term results with tension-free vaginal tape on mixed and stress urinary incontinence.

OBJECTIVE: To compare outcome of the tension-free vaginal tape (TVT) procedure in women with urinary mixed and stress incontinence. METHODS: A mailed questionnaire was answered by 760 of 970 women who had undergone TVT surgery 2-8 years ago (78% response rate). Seventeen women had unclassified incontinence, and 51 women who developed de novo urgency were excluded, giving 580 (83.8%) with stress incontinence and 112 (16.2%) women with mixed incontinence eligible for analysis. Demographic, reproductive factors, and medical history were obtained. The questionnaire included detailed questions about urinary symptoms. Analysis of outcome was done for cohorts by number of years since the operation. RESULTS: The women with stress incontinence had a persistent cure rate of 85% from 2 to 8 years after the TVT procedure. The women with mixed incontinence had a persistent cure rate of 60% up to 4 years postoperatively, but the cure rate then steadily declined to 30% from 4 to 8 years after surgery. The increased rate of incontinence was due to urgency symptoms. CONCLUSION: The results of this study indicate that initial good cure rates of TVT for mixed incontinence do not persist after 4 years. LEVEL OF EVIDENCE: III.

Aged↗
PubMed2005

Sleep apnea and hormone replacement therapy: a pilot study and a literature review.

BACKGROUND: Sleep apnea syndrome (SAS) is a common condition and a risk factor of cardiovascular and cerebrovascular diseases. The purpose of this pilot study was to investigate the effect of a gestagen (trimegeston) and estradiol hormone combination on perimenopausal and postmenopausal women with SAS. METHODS: Four postmenopausal and one perimenopausal women were studied by polysomnography before and after treatment with hormone replacement therapy (HRT). RESULTS: The subjects had a mean reduction of the severity of their sleep apnea by 75% measured by apnea/hypopnea index. CONCLUSIONS: HRT might be an alternative in the treatment of SAS.

Estradiol↗
PubMed2004

Nanospray mass spectrometry with indirect conductive graphite coating.

An easy and cost-effective method to manufacture a robust conductive graphite coating for nanospray mass spectrometry (nESI-MS) and capillary electrophoresis (CE)-nESI-MS is described. The method involves graphite coating of a tube sleeve, into which the nESI emitter is inserted and connected to a transfer capillary, instead of coating the actual emitter. The coating, made of graphite from a pencil and epoxy glue, was stable over long periods of use (>80 h) and showed excellent resistance toward various solvents. Stable electrospray was achieved in the investigated flow range (150-900 nL x min(-)(1)), and salbutamol, diphenhydramine, and nortriptyline (M(w): 239-263 g x mol(-)(1)) were detected in the nanomole per liter range during continuous pumping. CE-nESI-MS analysis gave excellent signal-to-noise ratios for 100-fmol injections. The technique allows simple exchange of the nESI emitter to suit a specific flow rate, and it minimizes risk of corona discharge.

Journal Article↗
PubMed2004

Laser techniques in acoustically levitated micro droplets.

Laser techniques were applied to an acoustically levitated droplet for remote investigation of the diameter, species concentration and temperature of the suspended droplet. To this end, the third and the fourth harmonic of a Nd:YAG laser were used for investigation of elastic, fluorescence and phosphorescence signals from the droplet. The droplet was seeded with thermographic phosphors and acetone for the phosphorescence and fluorescence measurements, respectively. The techniques were applied simultaneously using an imaging stereoscope. The imaging device allowed for an identical visualization of incoming signal through separate optical filters. Temperature measurements in droplets is important in the study of e.g. exothermic chemical reactions, spray processes, combustion, and in bioanalytical applications where the biological material is temperature sensitive or dependent on optimal temperature for function. Results from these investigations showed that temperature measurements in acoustically levitated droplets using laser-induced phosphorescence are feasible. The results also show the potential of simultaneous laser based measurements on levitated droplets. Diameter variation (surface area), mixture concentration and temperature were measured simultaneously.

Lasers↗
PubMed2004

Molecularly imprinted polymer formats for capillary electrochromatography.

The research aimed towards the adaptation of molecularly imprinted polymers (MIPs) to the capillary format and the use of these highly selective matrices for capillary electrochromatography (CEC) is reviewed in this article. The MIP is prepared by incorporation of a template molecule into a polymerization protocol. After polymerization and extraction of the template from the resulting polymer a highly selective material with recognition cavities complementary to the template in size, shape and chemical functionality is obtained. MIPs have been used as recognition elements in several different analytical techniques. In combination with CEC a novel separation system with a unique selectivity towards a predetermined target (the template) is achieved. The merge of molecular imprinting technology (MIT) and CEC have introduced several interesting polymer formats, due to the adaptation of the MIP to the miniaturized capillary format. The polymer formats can be classified according to their preparation protocols and appearance into three conceptually different categories, i.e. the monolith, the coating and the nanoparticles. The preparation protocols, characteristics and applications of these formats will be discussed.

Chromatography, Micellar Electrokinetic Capillary↗
PubMed2004

Airborne chemistry: acoustic levitation in chemical analysis.

This review with 60 references describes a unique path to miniaturisation, that is, the use of acoustic levitation in analytical and bioanalytical chemistry applications. Levitation of small volumes of sample by means of a levitation technique can be used as a way to avoid solid walls around the sample, thus circumventing the main problem of miniaturisation, the unfavourable surface-to-volume ratio. Different techniques for sample levitation have been developed and improved. Of the levitation techniques described, acoustic or ultrasonic levitation fulfils all requirements for analytical chemistry applications. This technique has previously been used to study properties of molten materials and the equilibrium shape()and stability of liquid drops. Temperature and mass transfer in levitated drops have also been described, as have crystallisation and microgravity applications. The airborne analytical system described here is equipped with different and exchangeable remote detection systems. The levitated drops are normally in the 100 nL-2 microL volume range and additions to the levitated drop can be made in the pL-volume range. The use of levitated drops in analytical and bioanalytical chemistry offers several benefits. Several remote detection systems are compatible with acoustic levitation, including fluorescence imaging detection, right angle light scattering, Raman spectroscopy, and X-ray diffraction. Applications include liquid/liquid extractions, solvent exchange, analyte enrichment, single-cell analysis, cell-cell communication studies, precipitation screening of proteins to establish nucleation conditions, and crystallisation of proteins and pharmaceuticals.

Journal Article↗
PubMed2004

In-capillary micro solid-phase extraction and capillary electrophoresis separation of heterocyclic aromatic amines with nanospray mass spectrometric detection.

A miniaturised technique to analyse and detect heterocyclic aromatic amines (HAs) using micro solid-phase extraction ( microSPE) coupled on-line (in-capillary) to capillary electrophoresis (CE) separation with nanospray (nESI) mass spectrometry (MS) detection has been developed. HAs are mutagenic and carcinogenic compounds formed at low levels in protein-rich food during cooking. Due to the low concentrations of HAs and the high complexity of the matrix in which they exist, sensitive and selective analytical methods are required for quantification. microSPE was performed on a packed bed of C(18 )particles inside the CE capillary, which minimised the dead volume. The on-line coupling of SPE, CE and nESI-MS reduced the time for extraction and identification to less than half an hour, which will allow for screening of several samples per day. The new technique provides short analysis time, low sample and solvent consumption, and HAs in standard solutions were easily detected at 12-17 fmol injections, and in spiked urine samples at 750-810 fmol injections.

Journal Article↗
PubMed2004

Affinity two-phase partitioning in acoustically levitated drops.

Miniaturized (<1 microL) biospecific affinity two-phase partitioning in an acoustically levitated drop is described. Miniaturization commonly gives unfavorable surface/volume ratios, but in the levitation approach adsorption problems are minimized since the only surrounding wall is the liquid/air interface of the drop. Biotinylated liposomes were partitioned in aqueous poly(ethylene glycol)/dextran two-phase drops with NeutrAvidin-dextran as the affinity ligand. A two-phase drop was trapped and manipulated in a node of a standing ultrasonic wave. Alternatively, a two-phase system was formed by levitation and evaporation of a polymer one-phase drop. Phase mixing was achieved by adjusting the ultrasonic field and phase separation by readjusting the field. NeutrAvidin-dextran brought about the redistribution of biotinylated liposomes from the poly(ethylene glycol)-rich phase into the dextran-rich phase. Thus, an entire affinity two-phase separation procedure, including mixing of the phases and incubation to allow affinity interactions to develop under constant volume, followed by phase separation under controlled evaporation, can be performed in a single levitated drop. This miniaturized technique would allow the separation of biologically active membranes or organelles from individual cells for analysis.

Journal Article↗