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Biomedical subjects

S Nilsson

Publications and source records attributed to S Nilsson.

At least 19 recordsLinked to original sources
PubMed2006

Nucleostemin mRNA is expressed in both normal and malignant renal tissues.

Nucleostemin (NS), a p53-binding protein, has been shown essential for stem and cancer cell proliferation and implicated in oncogenesis. To explore potential contributions of NS to the development of clear cell renal cell carcinomas (ccRCCs), we determined NS expression in ccRCC cell lines, and in paired normal and malignant renal tissues from 31 patients with ccRCC. Nucleostemin mRNA and/or protein expression was observed in all four cell lines and 27 of 31 (87%) tumour specimens. Surprisingly, 16 of 31 (52%) adjacent normal renal samples also expressed NS mRNA and its levels in four of them were comparable with those in paired tumour tissues. Three of the patients had detectable NS mRNA in their normal renal tissues whereas lacked its expression in the matched tumours. Compared to the oncogene c-MYC expression in these same samples, NS expression showed a much less specificity for ccRCC. We further demonstrated that NS mRNA expression was closely associated with cellular proliferation in normal fibroblasts or T lymphocytes and renal cell carcinoma cell lines. Collectively, NS expression widely occurs in normal and malignant renal tissues, and is likely a proliferation marker rather than a unique regulator of cell proliferation and survival in stem and cancer cells.

Adult↗
PubMed2006

Evidence that oestrogen receptor-alpha plays an important role in the regulation of glucose homeostasis in mice: insulin sensitivity in the liver.

AIMS/HYPOTHESIS: We used oestrogen receptor-alpha (ERalpha) knockout (ERKO) and receptor-beta (ERbeta) knockout (BERKO) mice to investigate the mechanism(s) behind the effects of oestrogens on glucose homeostasis. METHODS: Endogenous glucose production (EGP) was measured in ERKO mice using a euglycaemic-hyperinsulinaemic clamp. Insulin secretion was determined from isolated islets. In isolated muscles, glucose uptake was assayed by using radiolabelled isotopes. Genome-wide expression profiles were analysed by high-density oligonucleotide microarray assay, and the expression of the genes encoding steroyl-CoA desaturase and the Leptin receptor (Scd1 and Lepr, respectively) was confirmed by RT-PCR. RESULTS: ERKO mice had higher fasting blood glucose, plasma insulin levels and IGT. The plasma leptin level was increased, while the adiponectin concentration was decreased in ERKO mice. Levels of both glucose- and arginine-induced insulin secretion from isolated islets were similar in ERKO and wild-type mice. The euglycaemic-hyperinsulinaemic clamp revealed that suppression of EGP by increased insulin levels was blunted in ERKO mice, which suggests a pronounced hepatic insulin resistance. Microarray analysis revealed that in ERKO mice, the genes involved in hepatic lipid biosynthesis were upregulated, while genes involved in lipid transport were downregulated. Notably, hepatic Lepr expression was decreased in ERKO mice. In vitro studies showed a modest decrease in insulin-mediated glucose uptake in soleus and extensor digitorum longus (EDL) muscles of ERKO mice. BERKO mice demonstrated normal glucose tolerance and insulin release. CONCLUSIONS/INTERPRETATION: We conclude that oestrogens, acting via ERalpha, regulate glucose homeostasis mainly by modulating hepatic insulin sensitivity, which can be due to the upregulation of lipogenic genes via the suppression of Lepr expression.

Adiponectin↗
PubMed2006

Quality of life after tension-free vaginal tape surgery for female stress incontinence.

OBJECTIVE: To undertake a long-term follow-up evaluation of the quality of life (QOL) of women who had undergone a tension-free vaginal tape (TVT) procedure. MATERIAL AND METHODS: During the period 1995-2001, 970 women with urinary stress incontinence underwent TVT surgery at the Department of Obstetrics and Gynecology, Falun Hospital. A questionnaire was mailed on average 5.7 years after the TVT procedure. Two incontinence-specific QOL instruments--the Incontinence Impact Questionnaire-7 (IIQ-7) and the Urogenital Distress Inventory-6 (UDI-6)--were administered. An additional questionnaire included general questions and questions about chronic diseases that may be associated with urinary incontinence. RESULTS: The mean age at surgery was 58.7 years (range 29-89 years). Of 913 eligible women, 768 (78.9%) responded. Mean IIQ-7 and IDU-6 scores as estimated by the women improved dramatically at follow-up as compared to preoperative values: from 43.7 to 11.5 for the IIQ-7 and from 54.2 to 24.0 for the UDI-6 on a scale from 0 to 100 (p = 0.0001 for both). There were few differences in mean QOL scores even 8 years after TVT surgery, compared to those determined a shorter time after the operation. Women with diabetes, chronic constipation, chronic bronchitis and preoperative recurrent urinary infections had a relative improvement in QOL of the same magnitude as that of the remaining study population. Advanced age was negatively associated with an improvement in QOL scores. CONCLUSIONS: Improvements in measures of QOL after TVT surgery are dramatic and persist for years. Women with concomitant diseases that may be associated with urinary incontinence can be assured that there is a good chance of success with TVT surgery.

Adult↗
PubMed2006

High dose-rate brachytherapy of prostate cancer utilising Iridium-192 after-loading technique: technical and methodological aspects.

The aim of this study was to focus on certain characteristic problems associated with Iridium-192 high dose-rate brachytherapy (Ir-192 HDR-BT) in combination with external beam radiation therapy (EBRT) in the treatment of patients with localised prostate cancer. Over a period of 16 years, >2,000 patients with prostate cancer have been treated in Sweden with a combination of two fractions of 10 Gy Ir-192 HDR-BT and 50 Gy of fractionated EBRT. Although this treatment is usually well tolerated, there are biological and technical factors to be considered before and during the treatment of the patient to avoid side effects or under-treatment of the target volume. Some of the problems facing the doctors are transducer stability, needle deviation, target definition, target motion, pubic arch interference, concomitant diseases and tolerance doses for different organs at risk. These problems are discussed and possible solutions are presented in this study.

Brachytherapy↗
PubMed2005

The couple's decision-making in IVF: one or two embryos at transfer?

BACKGROUND: The aim of this study was to evaluate the decision-making process and factors that contribute to the decision of IVF participants to choose one or two embryos at transfer. METHODS: Two hundred and seventy-four IVF patients equally distributed in males and females were personally interviewed using a semi-structured questionnaire which included 82 items. RESULTS: In the whole study population, previous childbirth [odds ratio (OR) 2.1; 95% confidence interval (CI) 1.9-3.6], and spare embryos to freeze (OR 23.6; 95% CI 11.2-54.5) emerged as the most important variables in patients who had one embryo transferred, while previous IVF treatments (OR 0.3; 95% CI 0.1-0.6) and the assumed increased pregnancy chance (OR 0.1; 95% CI 0.05-0.3) were the most important decision-making factors among those who had two embryos. The women were more satisfied with the information (83 versus 71%; P = 0.02), and more aware of the risks with twin pregnancies (77 versus 66%; P = 0.03) than the males. The women were also more concerned about their age. Knowledge about risks of multiple pregnancies was higher in females (77%) than in males (66%, P = 0.03). CONCLUSION: The results of this study indicate that despite good information about the risks for complications with multiple pregnancies, many patients wish to have two embryos transferred. Spare embryos to freeze, improvement of pregnancy rate in single embryo transfer and young age of the woman are predictive of choosing single embryo transfer. However, the final decision must always be made in agreement with the physician.

Decision Making↗
PubMed2005

Plasma carotenoids as biomarkers of intake of fruits and vegetables: individual-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE: The aim in this study was to assess the association between individual plasma carotenoid levels (alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, lutein, zeaxanthin) and fruit and vegetable intakes recorded by a calibrated food questionnaire (FQ) and 24-h dietary recall records (24HDR) in nine different European countries with diverse populations and widely varying intakes of plant foods. DESIGN: A stratified random subsample of 3089 men and women from nine countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), who had provided blood samples and dietary and other lifestyle information between 1992 and 2000, were included. RESULTS: beta-Cryptoxanthin was most strongly correlated with total fruits (FQ r = 0.52, 24HDR r = 0.39), lycopene with tomato and tomato products (FQ r = 0.38, 24HDR r = 0.25), and alpha-carotene with intake of root vegetables (r = 0.39) and of total carrots (r = 0.38) for FQ only. Based on diet measured by FQ and adjusting for possible confounding by body mass index (BMI), age, gender, smoking status, alcohol intake, and energy intake, the strongest predictors of individual plasma carotenoid levels were fruits (R(partial)(2) = 17.2%) for beta-cryptoxanthin, total carrots ((partial)(2) = 13.4%) and root vegetables (R(partial)(2) = 13.3%) for alpha-carotene, and tomato products (R(partial)(2) = 13.8%) for lycopene. For 24HDR, the highest R(partial)(2) was for fruits in relation to beta-cryptoxanthin (7.9%). CONCLUSIONS: Intakes of specific fruits and vegetables as measured by food questionnaires are good predictors of certain individual plasma carotenoid levels in our multicentre European study. At individual subject levels, FQ measurements of fruits, root vegetables and carrots, and tomato products are, respectively, good predictors of beta-cryptoxanthin, alpha-carotene, and lycopene in plasma.

Alcohol Drinking↗
PubMed2005

Estren-mediated inhibition of T lymphopoiesis is estrogen receptor-independent whereas its suppression of T cell-mediated inflammation is estrogen receptor-dependent.

Estrogen has extensive effects on the immune system. The aim of the present experiments was to compare the effects of 17beta-estradiol (E2) and 4-estren-3alpha,17beta-diol (estren) on T lymphopoiesis and T cell-dependent inflammation. In order to investigate the role of estrogen receptors (ER) in the effects of E2 and estren on the immune system, ER knock-out mice lacking both ERalpha and ERbeta (DERKO) were used. T lymphopoiesis and T cell-dependent inflammation were studied by investigating thymus cellularity, the delayed-type hypersensitivity (DTH) reaction, CD4(+) T cells in spleen and serum levels of interleukin (IL)-6. As expected, the presence of ERs was mandatory for all the effects of E2. In contrast, treatment with estren reduced thymus cellularity in ER knock-out mice, indicating an effect through ER-independent pathways. Interestingly, estren suppressed only DTH, the frequency of CD4(+) T cells in spleen and serum levels of IL-6 in wild-type (WT) mice, but not in mice lacking ERs. Thus, our study is the first to show that estren inhibits T lymphopoiesis via ER-independent pathways, whereas its suppressive effects on inflammation are ER-dependent.

Animals↗
PubMed2004

A phase I trial of DNA vaccination with a plasmid expressing prostate-specific antigen in patients with hormone-refractory prostate cancer.

Prostate-specific antigen (PSA) is a serine protease secreted at low levels by normal luminal epithelial cells of the prostate and in significantly higher levels by prostate cancer cells. Therefore, PSA is a potential target for various immunotherapeutical approaches against prostate cancer. DNA vaccination has been investigated as immunotherapy for infectious diseases in patients and for specific treatment of cancer in certain animal models. In animal studies, we have demonstrated that vaccination with plasmid vector pVAX/PSA results in PSA-specific cellular response and protection against tumour challenge. The purpose of the trial was to evaluate the safety, feasibility and biological efficacy of pVAX/PSA vaccine in the clinic. A phase I trial of pVAX/PSA, together with cytokine granulocyte/macrophage-colony stimulating factor (GM-CSF) (Molgramostim) and IL-2 (Aldesleukin) as vaccine adjuvants, was carried out in patients with hormone-refractory prostate cancer. To evaluate the biologically active dose, the vaccine was administered during five cycles in doses of 100, 300 and 900 microg, with three patients in each cohort. Eight patients were evaluable. A PSA-specific cellular immune response, measured by IFN-gamma production against recombinant PSA protein, and a rise in anti-PSA IgG were detected in two of three patients after vaccination in the highest dose cohort. A decrease in the slope of PSA was observed in the two patients exhibiting IFN-gamma production to PSA. No adverse effects (WHO grade >2) were observed in any dose cohort. We demonstrate that DNA vaccination with a PSA-coding plasmid vector, given with GM-CSF and IL-2 to patients with prostate cancer, is safe and in doses of 900 microg the vaccine can induce cellular and humoral immune responses against PSA protein.

Adenocarcinoma↗
PubMed2004

Association between the estrogen receptor beta gene and age of onset of Parkinson's disease.

The purpose of this study was to investigate the potential contribution of genetic variants in the estrogen receptor beta gene to the aetiology of Parkinson's disease (PD). Several lines of evidence from human and animal studies suggest a protective role for estrogen in PD. Recently the estrogen receptor beta subtype was reported to be an important mediator of estrogen actions in the nigrostriatal dopamine system. Two single nucleotide polymorphisms at position 1730 and 1082 in the ER beta gene were genotyped, using pyrosequencing, in 260 patients with PD and 308 controls recruited from the Swedish population. Neither of the two estrogen receptor beta polymorphisms was associated with an increased risk for PD. However, the G allele of the A1730G polymorphism was more frequent in patients with an early age of onset than in patients with a late age of onset of PD (P = 0.006). Patients carrying the GG genotype had an odds ratio of 2.2 for having an early onset of PD compared to non-carriers. In conclusion, our results indicate that genetic variation in the estrogen receptor beta gene may influence the age of onset of PD.

Adult↗
PubMed2004

Gender differences in depression: a study of older unlike-sex twins.

Gender differences in depressive symptoms, in the diagnosis of major/minor depression, and in the use of antidepressant medication were investigated. The sample included 249 pairs of unlike-sex twins, who were between 70 and 80 years of age at the initial, baseline assessment. A follow-up, in which both members of 145 twin pairs participated, was carried out four years later. Participants completed the Centre for the Epidemiologic Studies Depression Scale (CES-D) for depressive symptoms. Current use of antidepressant medicine was assessed. Medical records of major/minor depression from the period 1985-1998, including a summary of those diagnoses in earlier years, were gathered from several sources. Women had a higher frequency of depressive symptoms and depression diagnoses than their twin brothers. Depressive symptoms and diagnosis of depression increased over time, slightly more among men. The gender difference and increase over time in the depressive symptoms were related to differences in socio-economic status and physical functioning in men and women. No gender difference was found in the use of antidepressant medication.

Aged↗
PubMed2004

Phase I trial on sms-D70 somatostatin analogue in advanced prostate and renal cell cancer.

Plasma concentrations and tolerability of a novel somatostatin analogue sms-D70 were studied in patients with metastatic hormone-resistant prostate cancer (HRPC) or metastatic renal cell cancer. To overcome the limitations of the octapeptides having affinity only to somatostatin receptor subtypes 2 and 5, HRPC expressing mainly somatostatin receptors 1 and 4, a somatostatin derivative based on the natural somatostatin having affinity to all five somatostatin receptor subtypes, was developed. The in vivo stability of this dextran-conjugated derivative, somatostatin-D70, was confirmed previously in animal studies, and the nanomolar "panaffinity" has been shown in in vitro receptor binding studies on cell lines transfected with the somatostatin receptor genes. Sms-D70 was given with subcutaneous injection once a week at dose levels of 5, 10, 20, 35, and 50 mg. For pharmacokinetic studies, sms-D70 was labeled with 131I. Fourteen patients were treated, of whom 10 had prostate and 4 renal cell cancer. The kinetic data revealed high stability with a long half-life in the blood. The drug was well tolerated, and no grade 4 (WHO) toxicity was observed. The maximal tolerated dose could not be established due to the lack of dose-limiting toxicities. Objective PSA responses were not recorded in these heavily treated patients, but subjective stabilization of pain was observed and urinary symptoms were alleviated in four patients. Three patients with metastatic HRPC received 5-10-mg intravenous injections of sms-D70 once weekly for 4-14 months on a compassionate use basis. In all cases, serum PSA values decreased more than 50% from the pretreatment level, but these results are difficult to interpret due to concomitant treatments given to these patients. In conclusion, sms-D70 was well tolerated in the treatment of metastatic prostate and renal cell cancer, but no responses were found in these heavily treated patients.

Adult↗
PubMed2003

Global structure and dynamics of human apolipoprotein CII in complex with micelles: evidence for increased mobility of the helix involved in the activation of lipoprotein lipase.

Apolipoprotein CII (apoCII), a surface constituent of plasma lipoproteins, is the activator for lipoprotein lipase (LPL) and is therefore central for lipid transport in blood. The three-dimensional structure of (13)C-, (15)N-enriched human full-length apoCII in complex with sodium dodecyl sulfate (SDS) micelles is reported. In addition to the structure determination, (15)N-relaxation measurements have been performed at two magnetic fields to characterize the dynamics of the backbone of apoCII in the complex. The relaxation data also provided global structural constraints, viz. the orientation of helices in the complex. In addition, global constraints were derived from the fact that apoCII helices are attached to the surface of the SDS micelle and that the hydrophobic moments of each helix faces the interior of the micelle. These three categories of global constraints, together with the local classical NMR constraints, were sufficient to define the 3D structure of the apoCII-SDS micelle complex. To our knowledge, this presents the first example in which the global structure of a protein-SDS micelle complex has been determined. The C-terminal helix of apoCII is known to be responsible for the activation of LPL. This helix is distinguished from the other helices by a higher degree of internal motion on the nanosecond time scale as shown by the relaxation data. The overall structure and the internal dynamics, combined with previous mutation data, give important clues toward a possible mechanism for the activation of LPL by apoCII.

Amino Acid Sequence↗
PubMed2003

Ultrasonic-trap-enhanced selectivity in capillary electrophoresis.

We combine ultrasonic trapping and capillary electrophoresis (CE) with the goal to detect ultra-low concentrations of proteins via size-selective separation and enrichment of antibody-coated latex spheres. An 8.5 MHz standing ultrasonic wave is longitudinally coupled into the sub-100- micro m diam capillary of the CE system. Competition between acoustic and viscous forces result in in-flow separation of micro m-diam spheres according to their size. Experiments separating 2.8- and 2.1- micro m-diam fluorescent latex particles, which model a protein-specific immunocomplex/free particle mixture, indicate a potential improvement of the concentration limit of detection of 10(4) compared to current CE systems. Theoretical calculations show room for further improvement.

Electrophoresis, Capillary↗
PubMed2003

Genetic variation at the human tissue-type plasminogen activator (tPA) locus: haplotypes and analysis of association to plasma levels of tPA.

Tissue-type plasminogen activator (tPA) plays a key role in thrombus dissolution and plasma levels of tPA have been associated with cardiovascular disease. We have previously resequenced regulatory and coding regions of the human tPA gene (PLAT) and identified eight single-nucleotide polymorphisms (SNPs). In a small experimental study, four common variants were associated with invasively determined vascular tPA release rates. The aim of the present study was to investigate whether there is an association between genetic variants at this locus and plasma levels of tPA. To this end, 240 Swedish individuals without cardiovascular disease were typed for the eight SNPs and an Alu insertion polymorphism at the PLAT locus, as well as for a polymorphism in the plasminogen activator inhibitor type 1 (PAI-1) promoter (PAI-1 -675 4G>5G). Stepwise regression analysis, with established predictors of plasma tPA including plasma PAI-1 and genetic variants, showed that neither genotypes nor haplotypes were major contributors to plasma tPA. The results also showed that the level of linkage disequilibrium was high at the PLAT locus, as demonstrated by the fact that only three haplotypes had a frequency above 5%. In conclusion, in the present study neither genetic variation at the PLAT locus nor the PAI-1 -675 4G>5G polymorphism was strong predictors of plasma tPA levels, which suggests that variations in other genes contribute to the heritability of this phenotype. The results also show that three haplotypes at the PLAT locus accounted for nearly 90% of the chromosomes and that they could be defined by typing only two SNPs.

Base Sequence↗
PubMed2003

Association between a dinucleotide repeat polymorphism of the estrogen receptor alpha gene and personality traits in women.

Estrogens are known to play a key role in the regulation of various aspects of behavior. In order to study the potential contribution of genetic variation in the estrogen receptor (ER) alpha to specific personality traits, we investigated a repeat polymorphism in the ER alpha gene in 172 42-year-old women who had been assessed using the Karolinska Scales of Personality (KSP). Based on the hypothesis that there is a relationship between the length of a repeat polymorphism and gene function,(1) the alleles were divided into two groups: short and long. In order to elucidate the possible influence of the ER alpha gene on the different aspects of personality measured by means of the KSP, the possible association between this gene and four different factors ('neuroticism', 'psychoticism', 'non-conformity', and 'extraversion') was analysed. 'Neuroticism', 'psychoticism', and 'non-conformity' all appeared to be associated with the ER alpha gene. After correction for multiple comparisons by means of permutation analysis, the associations with the factor 'non-conformity'--including the subscales 'indirect aggression' and 'irritability'--and the factor 'psychoticism'--including the subscale 'suspicion'--remained significant. The results suggest that the studied dinucleotide repeat polymorphism of the ER alpha gene may contribute to specific components of personality.

Adult↗
PubMed2003

Optimization of ECG gating in quantitative femoral angiography.

PURPOSE: To determine which phase of the heart cycle would yield the highest reproducibility in measuring atherosclerosis-related variables such as arterial lumen volume and edge roughness. MATERIAL AND METHODS: 35 patients with hypercholesterolemia underwent select- ive femoral angiography, repeated four times at 10-min intervals. The angiographies were performed with ECG-gated exposures. In angiographies 1 and 2 the delay from R-wave maximum to each exposure was 0.1 s, in angiographies 3 and 4 the delay was 0.1, 0.3, 0.5 or 0.7 s or the exposures were performed 1/s without ECG gating. Arterial lumen volume and edge roughness were measured in a 20-cm segment of the superficial femoral artery using a computer-based densitometric method. Measurement reproducibility was determined by comparing angiographies 1-2 and angiographies 3-4. RESULTS: When measuring arterial lumen volume and edge roughness of a 20-cm segment of the femoral artery, reproducibility was not dependent on ECG gating. In measuring single arterial diameters and cross-sectional areas, the reproducibility was better when exposures were made 0.1 s after the R-wave maximum than when using other settings of the ECG gating device or without ECG gating. CONCLUSION: The influence of pulsatile flow upon quantitative measurement in femoral angiograms seems to be the smallest possible in early systole, as can be demonstrated when measuring single diameters and cross-sectional areas. In variables based on integration over longer segments, measurement reproducibility seems to be independent of phase.

Adult↗