| 1. |
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| 2. |
- Adam, A, et al.
(författare)
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Abstracts from Hydrocephalus 2016.
- 2017
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Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 14:Suppl 1
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Tidskriftsartikel (refereegranskat)
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| 3. |
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| 10. |
- Gehlen, J., et al.
(författare)
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First genome-wide association study of esophageal atresia identifies three genetic risk loci at CTNNA3, FOXF1/FOXC2/FOXL1, and HNF1B
- 2022
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Ingår i: Human Genetics and Genomics Advances. - : Elsevier BV. - 2666-2477. ; 3:2
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Tidskriftsartikel (refereegranskat)abstract
- Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10−8; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10–5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10−10; OR = 1.47; 95% CI, 1.38–1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10−16; OR = 1.75; 95% CI, 1.64–1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes. © 2022 The Authors
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| 11. |
- Semb, G, et al.
(författare)
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Erratum
- 2017
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Ingår i: Journal of plastic surgery and hand surgery. - 2000-6764. ; 51:2, s. 158-158
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Tidskriftsartikel (refereegranskat)
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| 12. |
- Smith Byrne, K., et al.
(författare)
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The role of plasma microseminoprotein-beta in prostate cancer : An observational nested case-control and Mendelian randomization study in the European prospective investigation into cancer and nutrition
- 2019
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 30:6, s. 983-989
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Tidskriftsartikel (refereegranskat)abstract
- Background: Microseminoprotein-beta (MSP), a protein secreted by the prostate epithelium, may have a protective role in the development of prostate cancer. The only previous prospective study found a 2% reduced prostate cancer risk per unit increase in MSP. This work investigates the association of MSP with prostate cancer risk using observational and Mendelian randomization (MR) methods. Patients and methods: A nested case-control study was conducted with the European Prospective Investigation into Cancer and Nutrition (EPIC) with 1871 cases and 1871 matched controls. Conditional logistic regression analysis was used to investigate the association of pre-diagnostic circulating MSP with risk of incident prostate cancer overall and by tumour subtype. EPIC-derived estimates were combined with published data to calculate an MR estimate using two-sample inverse-variance method. Results: Plasma MSP concentrations were inversely associated with prostate cancer risk after adjusting for total prostate-specific antigen concentration [odds ratio (OR) highest versus lowest fourth of MSP = 0.65, 95% confidence interval (CI) 0.51-0.84, Ptrend = 0.001]. No heterogeneity in this association was observed by tumour stage or histological grade. Plasma MSP concentrations were 66% lower in rs10993994 TT compared with CC homozygotes (per allele difference in MSP: 6.09 ng/ml, 95% CI 5.56-6.61, r2=0.42). MR analyses supported a potentially causal protective association of MSP with prostate cancer risk (OR per 1 ng/ml increase in MSP for MR: 0.96, 95% CI 0.95-0.97 versus EPIC observational: 0.98, 95% CI 0.97-0.99). Limitations include lack of complete tumour subtype information and more complete information on the biological function of MSP. Conclusions: In this large prospective European study and using MR analyses, men with high circulating MSP concentration have a lower risk of prostate cancer. MSP may play a causally protective role in prostate cancer.
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| 13. |
- Stenman, U H, et al.
(författare)
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Summary report of the TD-3 workshop: characterization of 83 antibodies against prostate-specific antigen
- 1999
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Ingår i: Tumor Biology. - : Springer Science and Business Media LLC. - 1423-0380 .- 1010-4283. ; 20:Suppl. 1, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Twelve research groups participated in the ISOBM TD-3 Workshop in which the reactivity and specificity of 83 antibodies against prostate-specific antigen (PSA) were investigated. Using a variety of techniques including cross-inhibition assays, Western blotting, BIAcore, immunoradiometric assays and immunohistochemistry, the antibodies were categorized into six major groups which formed the basis for mapping onto two- and three-dimensional (2-D and 3-D) models of PSA. The overall findings of the TD-3 Workshop are summarized in this report. In agreement with all participating groups, three main antigenic domains were identified: free PSA-specific epitopes located in or close to amino acids 86-91; discontinuous epitopes specific for PSA without human kallikrein (hK2) cross-reactivity located at or close to amino acids 158-163; and continuous or linear epitopes shared between PSA and hK2 located close to amino acids 3-11. In addition, several minor and partly overlapping domains were also identified. Clearly, the characterization of antibodies from this workshop and the location of their epitopes on the 3-D model of PSA illustrate the importance of selecting appropriate antibody pairs for use in immunoassays. It is hoped that these findings and the epitope nomenclature described in this TD-3 Workshop are used as a standard for future evaluation of anti-PSA antibodies.
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| 14. |
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| 15. |
- Stenström, P, et al.
(författare)
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Total colonic aganglionosis: multicentre study of surgical treatment and patient-reported outcomes up to adulthood.
- 2020
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Ingår i: BJS open. - 2474-9842. ; 4:5, s. 943-953
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Tidskriftsartikel (refereegranskat)abstract
- Surgery for total colonic aganglionosis (TCA) is designed to preserve continence and achieve satisfactory quality of life. This study evaluated a comprehensive group of clinical and social outcomes.An international multicentre study from eight Nordic hospitals involving examination of case records and a patient-reported questionnaire survey of all patients born with TCA between 1987 and 2006 was undertaken.Of a total of 116 patients, five (4·3 per cent) had died and 102 were traced. Over a median follow-up of 12 (range 0·3-33) years, bowel continuity was established in 75 (73·5 per cent) at a median age of 11 (0·5-156) months. Mucosectomy with a short muscular cuff and straight ileoanal anastomosis (SIAA) (29 patients) or with a J pouch (JIAA) (26) were the most common reconstructions (55 of 72, 76 per cent). Major early postoperative complications requiring surgical intervention were observed in four (6 per cent) of the 72 patients. In 57 children aged over 4 years, long-term functional bowel symptoms after reconstruction included difficulties in holding back defaecation in 22 (39 per cent), more than one faecal accident per week in nine (16 per cent), increased frequency of defaecation in 51 (89 per cent), and social restrictions due to bowel symptoms in 35 (61 per cent). Enterocolitis occurred in 35 (47 per cent) of 72 patients. Supplementary enteral and/or parenteral nutrition was required by 51 (55 per cent) of 93 patients at any time during follow-up. Of 56 responders aged 2-20 years, true low BMI for age was found in 20 (36 per cent) and 13 (23 per cent) were short for age.Reconstruction for TCA was associated with persistent bowel symptoms, and enterocolitis remained common. Multidisciplinary follow-up, including continuity of care in adulthood, might improve care standards in patients with TCA.
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| 16. |
- Adler, Jan-Olof, et al.
(författare)
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The upgraded photon tagging facility at the MAX IV Laboratory
- 2013
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 715, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- A description is given of the upgraded photon tagging facility at the MAX IV Laboratory. Two magnetic spectrometers are used to momentum analyze post-bremsstrahlung electrons. The tagged photon range extends from 10 to 180 MeV with an energy resolution of about 300 keV. The system has been operated at rates up to 4 x 10(6) photons s(-1) MeV (-1). Different diagnostic tools are described as well as the experimental program.
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| 17. |
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| 18. |
- Becker, Charlotte, et al.
(författare)
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Discrimination of men with prostate cancer from those with benign disease by measurements of human glandular kallikrein 2 (HK2) in serum
- 2000
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Ingår i: Journal of Urology. - 1527-3792. ; 163:1, s. 311-316
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate the clinical value of measuring human glandular kallikrein 2 (hK2) compared with free and total prostate specific antigen (PSA-F and PSA-T) in serum from patients with prostate disease. MATERIALS AND METHODS: Serum from healthy controls, from men with benign prostate hyperplasia (BPH), clinically localized prostate cancer (PCa), and advanced PCa were analyzed for hK2 (using an in-house-research assay with detection limit of 0.05 ng./mL and <0.1% cross-reaction with PSA) and for PSA-F and PSA-T (using the Dual Prostatus assay from EG&G Wallac). RESULTS: HK2 concentrations were <0.05 ng./mL in 50/50 healthy volunteers but significantly higher (p <0.0001) and > or =0.05 ng./mL in 28/54 (52%) patients with BPH. In comparison to these men, the hK2 levels were significantly higher (p <0.0001, median 0.085 ng./mL) and > or =0.05 ng./mL in 100/136 (74%) men with clinically localized PCa. Compared with localized PCa, the hK2 levels were significantly higher (p <0.0001, median 0.57 ng./mL) and > or =0.05 ng./mL in 55/57 (96%) patients with advanced PCa. The median hK2 levels ranged from 1.3 to 1.6% of those of PSA-T in all three patient groups, whereas percent hK2/PSA-F and hK2 x PSA-T/PSA-F levels were significantly higher in cancer patients compared with those with BPH. In the discrimination of clinically localized PCa from BPH, hK2 x PSA-T/PSA-F gave the largest area under the receiver operating curve (AUC = 0.81) and significantly (p = 0.025) larger AUC than PSA-T alone (0.70). Further, at 95% sensitivity there was significant gain in specificity, and at specificity levels of 90 to 95% there was significant gain in sensitivity using the measurements of PSA-T+PSA-F+hK2 compared with analysis of PSA-T and/or percent free PSA. CONCLUSIONS: Discrimination of patients with benign prostate disease from those with prostate cancer was significantly enhanced using measurements of hK2 in addition to those of PSA-T and PSA-F. Percent hK2/PSA-F was higher in PCa than in BPH, a phenomena not yet understood.
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| 19. |
- Bjartell, A., et al.
(författare)
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Time-resolved fluorescence imaging (TRFI) for direct immunofluorescence of PSA and alpha-1-antichymotrypsin in prostatic tissue sections
- 1999
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Ingår i: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1365-7852 .- 1476-5608. ; 2:3, s. 140-147
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Tidskriftsartikel (refereegranskat)abstract
- We have developed a direct immunofluorescence technique utilising chelates of the lanthanide ions europium and terbium conjugated to monoclonal IgGs (Mabs) against prostate-specific antigen (PSA) and alpha-1- antichymotrypsin (ACT) for the detection and quantification on the same tissue section. Strong signals without disturbance from tissue autofluorescence were demonstrated in paraffin sections of ten benign and six malignant prostate tissue specimens. The signal intensity increased linearly with the amount of labelled Mab until epitope saturation began. The highest concentrations of bound IgG in tissue sections were 27.3 fmol/pixel for ACT and 7.2 for PSA. Time-resolved fluorescence imaging (TRFI) offers an attractive method for histochemical studies based on specific and quantitative detection of fluorescent lanthanide chelates.
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| 20. |
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| 21. |
- Dahlman, A., et al.
(författare)
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Effect of androgen deprivation therapy on the expression of prostate cancer biomarkers MSMB and MSMB-binding protein CRISP3
- 2010
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Ingår i: Prostate Cancer and Prostatic Diseases. - : Nature Publishing Group. - 1365-7852 .- 1476-5608. ; 13:4, s. 369-375
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the effects of short-term neoadjuvant and long-term androgen deprivation therapies (ADTs) on β-microseminoprotein (MSMB) and cysteine-rich secretory protein-3 (CRISP3) expression in prostate cancer patients. We also studied if MSMB expression was related to genotype and epigenetic silencing. Using an Affymetrix cDNA microarray analysis, we investigated the expression of MSMB, CRISP3, androgen receptor (AR), KLK3 and Enhancer of Zeste Homologue-2 (EZH2) in tissue from prostate cancer patients receiving (n=17) or not receiving (n=23) ADT before radical prostatectomy. MSMB, CRISP3 and AR were studied in tissue from the same patients undergoing TURP before and during ADT (n=16). MSMB genotyping of these patients was performed by TaqMan PCR. MSMB and KLK3 expression levels decreased during ADT. Expression levels of AR and CRISP3 were not affected by short-term ADT but were high in castration-resistant prostate cancer (CRPC) and metastases. Levels of EZH2 were also high in metastases, where MSMB was low. Genotyping of the MSMB rs10993994 polymorphism showed that the TT genotype conveys poor MSMB expression. MSMB expression is influenced by androgens, but also by genotype and epigenetic silencing. AR and CRISP3 expression are not influenced by short-term ADT, and high levels were found in CRPC and metastases.
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| 22. |
- Fielding, R. A., et al.
(författare)
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Effect of structured physical activity and nutritional supplementation on physical function in mobility-limited older adults : Results from the VIVE2 randomized trial
- 2017
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Ingår i: The Journal of Nutrition, Health & Aging. - : Springer Science and Business Media LLC. - 1279-7707 .- 1760-4788. ; 21:9, s. 936-942
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Tidskriftsartikel (refereegranskat)abstract
- The interactions between nutritional supplementation and physical activity on changes in physical function among older adults remain unclear. The primary objective of this study was to examine the impact of nutritional supplementation plus structured physical activity on 400M walk capacity in mobility-limited older adults across two sites (Boston, USA and Stockholm, Sweden). All subjects participated in a physical activity program (3x/week for 24 weeks), involving walking, strength, balance, and flexibility exercises. Subjects were randomized to a daily nutritional supplement (150kcal, 20g whey protein, 800 IU vitamin D) or placebo (30kcal, non-nutritive). Participants were recruited from urban communities at 2 field centers in Boston MA USA and Stockholm SWE. Mobility-limited (Short Physical Performance Battery (SPPB) ae9) and vitamin D insufficient (serum 25(OH) D 9 - 24 ng/ml) older adults were recruited for this study. Primary outcome was gait speed assessed by the 400M walk. Results: 149 subjects were randomized into the study (mean age=77.5 +/- 5.4; female=46.3%; mean SPPB= 7.9 +/- 1.2; mean 25(OH)D=18.7 +/- 6.4 ng/ml). Adherence across supplement and placebo groups was similar (86% and 88%, respectively), and was also similar across groups for the physical activity intervention (75% and 72%, respectively). Both groups demonstrated an improvement in gait speed with no significant difference between those who received the nutritional supplement compared to the placebo (0.071 and 0.108 m/s, respectively (p=0.06)). Similar effects in physical function were observed using the SPPB. Serum 25(OH)D increased in supplemented group compared to placebo 7.4 ng/ml versus 1.3 ng/ml respectively. Results suggest improved gait speed following physical activity program with no further improvement with added nutritional supplementation.
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| 23. |
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| 24. |
- Gustafson, Stefan, et al.
(författare)
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ICAM-1 is a cell-surface receptor for hyaluronan.
- 1995
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Ingår i: 6th Interscience World Conference on Inflammation, Antirheumatics, Analgesics, Immunomodulators, Geneva, Switzerland, 28-30 March, Abstract. ; 160, s. 28-
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Recension (övrigt vetenskapligt/konstnärligt)
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| 25. |
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| 26. |
- Hoffmann, Thomas J., et al.
(författare)
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Genome-wide association study of prostate-specific antigen levels identifies novel loci independent of prostate cancer
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Prostate-specific antigen (PSA) levels have been used for detection and surveillance of prostate cancer (PCa). However, factors other than PCa - such as genetics - can impact PSA. Here we present findings from a genome-wide association study (GWAS) of PSA in 28,503 Kaiser Permanente whites and 17,428 men from replication cohorts. We detect 40 genome-wide significant (P<5 × 10-8) single-nucleotide polymorphisms (SNPs): 19 novel, 15 previously identified for PSA (14 of which were also PCa-associated), and 6 previously identified for PCa only. Further analysis incorporating PCa cases suggests that at least half of the 40 SNPs are PSA-associated independent of PCa. The 40 SNPs explain 9.5% of PSA variation in non-Hispanic whites, and the remaining GWAS SNPs explain an additional 31.7%; this percentage is higher in younger men, supporting the genetic basis of PSA levels. These findings provide important information about genetic markers for PSA that may improve PCa screening, thereby reducing over-diagnosis and over-treatment.
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| 27. |
- Hoffmann, Thomas J, et al.
(författare)
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Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves cross-ancestry prediction
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We conducted a multi-ancestry genome-wide association study of prostate-specific antigen (PSA) levels in 296,754 men (211,342 European ancestry; 58,236 African ancestry; 23,546 Hispanic/Latino; 3,630 Asian ancestry; 96.5% of participants were from the Million Veteran Program). We identified 318 independent genome-wide significant (p≤5e-8) variants, 184 of which were novel. Most demonstrated evidence of replication in an independent cohort (n=95,768). Meta-analyzing discovery and replication (n=392,522) identified 447 variants, of which a further 111 were novel. Out-of-sample variance in PSA explained by our new polygenic risk score reached 16.9% (95% CI=16.1%-17.8%) in European ancestry, 9.5% (95% CI=7.0%-12.2%) in African ancestry, 18.6% (95% CI=15.8%-21.4%) in Hispanic/Latino, and 15.3% (95% CI=12.7%-18.1%) in Asian ancestry, and lower for higher age. Our study highlights how including proportionally more participants from underrepresented populations improves genetic prediction of PSA levels, with potential to personalize prostate cancer screening.
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| 28. |
- Hugosson, Jonas, 1955, et al.
(författare)
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A 16-yr Follow-up of the European Randomized study of Screening for Prostate Cancer
- 2019
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 76:1, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- Background: The European Randomized study of Screening for Prostate Cancer (ERSPC) has previously demonstrated that prostate-specific antigen (PSA) screening decreases prostate cancer (PCa) mortality. Objective: To determine whether PSA screening decreases PCa mortality for up to 16 yr and to assess results following adjustment for nonparticipation and the number of screening rounds attended. Design, setting, and participants: This multicentre population-based randomised screening trial was conducted in eight European countries. Report includes 182 160 men, followed up until 2014 (maximum of 16 yr), with a predefined core age group of 162 389 men (55-69 yr), selected from population registry. Outcome measurements and statistical analysis: The outcome was PCa mortality, also assessed with adjustment for nonparticipation and the number of screening rounds attended. Results and limitations: The rate ratio of PCa mortality was 0.80 (95% confidence interval [CI] 0.72-0.89, p < 0.001) at 16 yr. The difference in absolute PCa mortality increased from 0.14% at 13 yr to 0.18% at 16 yr. The number of men needed to be invited for screening to prevent one PCa death was 570 at 16 yr compared with 742 at 13 yr. The number needed to diagnose was reduced to 18 from 26 at 13 yr. Men with PCa detected during the first round had a higher prevalence of PSA >20 ng/ml (9.9% compared with 4.1% in the second round, p < 0.001) and higher PCa mortality (hazard ratio = 1.86, p < 0.001) than those detected subsequently. Conclusions: Findings corroborate earlier results that PSA screening significantly reduces PCa mortality, showing larger absolute benefit with longer follow-up and a reduction in excess incidence. Repeated screening may be important to reduce PCa mortality on a population level. Patient summary: In this report, we looked at the outcomes from prostate cancer in a large European population. We found that repeated screening reduces the risk of dying from prostate cancer. (C) 2019 Published by Elsevier B.V. on behalf of European Association of Urology.
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| 29. |
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| 30. |
- Iacobaeus, E, et al.
(författare)
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Short and Long Term Clinical and Immunologic Follow up after Bone Marrow Mesenchymal Stromal Cell Therapy in Progressive Multiple Sclerosis-A Phase I Study
- 2019
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- Bone marrow derived mesenchymal stromal cells (BM-MSCs) have emerged as a possible new therapy for Multiple Sclerosis (MS), however studies regarding efficacy and in vivo immune response have been limited and inconclusive. We conducted a phase I clinical study assessing safety and clinical and peripheral immune responses after MSC therapy in MS. Seven patients with progressive MS were intravenously infused with a single dose of autologous MSC (1–2 × 106 MSCs/kg body weight). The infusions were safe and well tolerated when given during clinical remission. Five out of seven patients completed the follow up of 48 weeks post-infusion. Brain magnetic resonance imaging (MRI) showed the absence of new T2 lesions at 12 weeks in 5/6 patients, while 3/5 had accumulated new T2 lesions at 48 weeks. Patient expanded disability status scales (EDSS) were stable in 6/6 at 12 weeks but declined in 3/5 patients at 48 weeks. Early changes of circulating microRNA levels (2 h) and increased proportion of FOXP3+ Tregs were detected at 7 days post-infusion compared to baseline levels. In conclusion, MSC therapy was safe and well tolerated and is associated with possible transient beneficial clinical and peripheral immunotolerogenic effects.
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| 31. |
- Johanson, G., et al.
(författare)
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Quantitative relationships of perfluoroalkyl acids in drinking water associated with serum concentrations above background in adults living near contamination hotspots in Sweden
- 2023
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 219
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Tidskriftsartikel (refereegranskat)abstract
- Contaminated drinking water (DW) is a major source of exposure to per- and polyfluoroalkyl substances (PFAS) at locations around PFAS production/use facilities and military airports. This study aimed to investigate quantitative relationships between concentrations in DW and serum of nine perfluoroalkyl acids (PFAAs) in Swedish adult populations living near contamination hotspots. Short-chained (PFPeA, PFHxA, PFHpA, and PFBS) and long-chained PFAAs (PFOA, PFNA, PFDA, PFHxS and PFOS) were measured in DW and serum. We matched DW and serum concentrations for a total of 398 subjects living or working in areas receiving contaminated DW and in one non-contaminated area. Thereafter, linear regression analysis with and without adjustments for co-variates was conducted. This enabled to derive (i) serum concentrations at background exposure (CB) from sources other than local DW exposure (i.e. food, dust and textiles) at 0 ng/L DW concentration, (ii) population-mean PFAA serum:water ratios (SWR) and (iii) PFAA concentrations in DW causing observable elevated serum PFAA concentrations above background variability. Median concentrations of the sum of nine PFAAs ranged between 2.8 and 1790 ng/L in DW and between 7.6 and 96.9 ng/mL in serum. DW concentration was the strongest predictor, resulting in similar unadjusted and adjusted regression coefficients. Mean CB ranged from <0.1 (PFPeA, PFHpA, PFBS) to 5.1 ng/mL (PFOS). Serum concentrations increased significantly with increasing DW concentrations for all PFAAs except for PFPeA with SWRs ranging from <10 (PFHxA, PFHpA and PFBS) to 111 (PFHxS). Observed elevated serum concentrations above background variability were reached at DW concentrations between 24 (PFOA) and 357 ng/L (PFHxA). The unadjusted linear regression predictions agreed well with serum concentrations previously reported in various populations exposed to low and high DW levels of PFOA, PFHxS and PFOS. The quantitative relationships derived herein should be helpful to translate PFAA concentrations in DW to concentrations in serum at the population level.
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| 32. |
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| 33. |
- Laurent, Torvald C., et al.
(författare)
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Urinary excretion of hyaluronan in man
- 1987
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - 0036-5513 .- 1502-7686. ; 47:8, s. 793-799
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Tidskriftsartikel (refereegranskat)abstract
- A specific assay for hyaluronan (hyaluronic acid) has been applied to the determination of the polysaccharide in urine. The excretion in 22 healthy subjects was 330 micrograms/24 h (SD 77). The excretion was correlated with body weight and was therefore somewhat higher in males than in females. The molecular weight of the main fraction of urinary hyaluronan was in the range of 4000 to 12,000 in accordance with the hypothesis that it originates from blood and arises by glomerular filtration. A small fraction was of higher molecular weight and could have been produced in the urinary tract. Hyaluronan in male and female urine displayed the same molecular weight distributions. Patients with rheumatoid arthritis and primary biliary cirrhosis showed a two-fold and three-fold increase, respectively, of hyaluronan in urine with concurrently high levels of the polysaccharide in serum. A patient with Werner's syndrome displayed a ten-fold increase of the polysaccharide in both serum and urine.
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| 34. |
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| 35. |
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| 36. |
- Piironen, T, et al.
(författare)
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Determination and analysis of antigenic epitopes of prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2) using synthetic peptides and computer modeling
- 1998
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Ingår i: Protein Science. - : Wiley. - 1469-896X .- 0961-8368. ; 7:2, s. 259-269
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Tidskriftsartikel (refereegranskat)abstract
- Prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2), produced essentially by the prostate gland, are 237-amino acid monomeric proteins, with 79% identity in primary structure. Twenty-five anti-PSA monoclonal antibodies (Mabs) were studied for binding to a large array of synthetic linear peptides selected from computer models of PSA and hK2, as well as to biotinylated peptides covering the entire PSA sequence. Sixteen of the Mabs were bound to linear peptides forming four independent binding regions (I-IV). Binding region I was localized to amino acid residues 1-13 (identical sequence for PSA and hK2), II (a and b) was localized to residues 53-64, III (a and b) was localized to residues 80-91 (= kallikrein loop), and IV was localized to residues 151-164. Mabs binding to regions I and IIa were reactive with free PSA, PSA-ACT complex, and with hK2; Mabs binding to regions IIb, IIIa, and IV were reactive with free PSA and PSA-ACT complex, but unreactive with hK2; Mabs binding to region IIIb detected free PSA only. All Mabs tested (n = 7) specific for free PSA reacted with kallikrein loop (binding region IIIb). The presence of Mabs interacting with binding region I did not inhibit the catalytic activity of PSA, whereas Mabs interacting with other binding regions inhibited the catalysis. Theoretical model structures of PSA, hK2, and the PSA-ACT complex were combined with the presented data to suggest an overall orientation of PSA with regard to ACT.
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| 37. |
- Steuber, T, et al.
(författare)
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Association of free-prostate specific antigen subfractions and human glandular kallikrein 2 with volume of benign and malignant prostatic tissue
- 2005
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 63:1, s. 13-18
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND. We investigated the association of different subfractions of prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2), such as total PSA (tPSA), complexed PSA (cPSA), free PSA (fPSA), "single-chain Intact fPSA" (fPSA-I), "multi-chain nicked fPSA" (fPSA-N), and total hK2 with volumes of total prostate gland, transition zone (tz), and prostate cancer (PCa) tissue in patients with benign and malignant prostatic disease. METHODS. Serum samples were collected from men with negative biopsy (n = 164) and PCa (n = 252). Total and fPSA were measured using a commercially immunoassay. We measured hK2 and fPSA-I by previously reported in-house research assays specific for hK2 and single-chain, non-cleaved fPSA, respectively. Levels of fPSA-N (=fPSA-fPSA-I) and cPSA (=tPSA-fPSA) were calculated. Total prostate and tz volume were measured using transrectal ultrasound (TRUS); PCa volume was calculated using a computer assisted volumetric program. Association with tz and cancer volumes (CaVols) was performed by linear regression analysis. RESULTS. All PSA subfractions and hK2 were associated with tz volume in multivariable linear regression analysis. Only hK2, fPSA, and fPSA-N were significantly associated with CaVol in multivariable analysis, fPSA-I seemed to be cancer related. CONCLUSIONS. The multi-chain fPSA-N subfractions of fPSA may be a valuable predictor of both benign prostate hyperplasia (BPH) and CaVol that is likely to be more useful in predicting tz volumes than CaVols. fPSA-I may provide information on cancer without being influenced by the presence of BPH.
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| 38. |
- Sävblom, C, et al.
(författare)
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Association between polymorphisms in the prostate-specific antigen (PSA) promoter and release of PSA
- 2009
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Ingår i: International Journal of Andrology. - : Wiley-Blackwell. - 0105-6263 .- 1365-2605. ; 32:5, s. 479-485
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Tidskriftsartikel (refereegranskat)abstract
- Variations in serum prostate-specific antigen (PSA) have been ascribed to A/G nucleotide polymorphisms located at -158 bp (rs266882) and -4643 bp (rs925013), relative to the transcription start site within the promoter of the PSA gene. PSA is also an androgen receptor target (AR) gene and polymorphisms in AR gene are known to affect AR function. Our objective was to compare the impact of these A/G polymorphisms separately or in combination with AR CAG micro satellite on regulation of PSA secretion into seminal plasma and blood in young men. Leukocyte DNA was extracted from 291 conscripts and genotyping performed with the Sequenom Mass Array System. PSA was measured with an immunofluorometric assay. Linear regression analysis was used to test the association of polymorphism frequencies with serum and seminal plasma levels of PSA. PSA gene polymorphisms at -158 bp or -4643 bp did not alone influence total PSA (tPSA) levels in seminal plasma or in blood. Homozygotes for the A-allele at -158 bp in combination with CAG > 22 had significantly higher serum levels of tPSA than subjects carrying the G-allele (p = 0.01). In conclusion, the PSA gene polymorphisms did not importantly influence the levels of tPSA in seminal plasma or in blood. tPSA in serum was influenced by interactions between PSA promoter variants and AR CAG polymorphism.
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| 39. |
- Xu, Yiyi, et al.
(författare)
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Serum Half-Lives for Short- and Long-Chain Perfluoroalkyl Acids after Ceasing Exposure from Drinking Water Contaminated by Firefighting Foam
- 2020
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 128:7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Firefighting foam-contaminated ground water, which contains high levels of perfluoroalkyl substances (PFAS), is frequently found around airports. In 2018 it was detected that employees at a municipal airport in northern Sweden had been exposed to high levels of short-chain PFAS along with legacy PFAS (i.e., PFOA, PFHxS, and PFOS) through drinking water. OBJECTIVES: In this study. we aimed to describe the PFAS profile in drinking water and biological samples (paired serum and urine) and to estimate serum half-lives of the short-chain PFAS together with legacy PFAS. METHODS: Within 2 weeks after provision of clean water, blood sampling was performed in all 26 airport employees. Seventeen of them were then followed up monthly for 5 months. PFHxA, PFHpA, PFBS, PFPeS, and PFHpS together with legacy PFAS in water and biological samples were quantified using LC/MS/MS. Half-lives were estimated by assuming one compartment, first-order elimination kinetics. RESULTS: The proportions of PFHxA, PFHpA, and PFBS were higher in drinking water than in serum. The opposite was found for PFHxS and PFOS. The legacy PFAS accounted for about 50% of total PFAS in drinking water and 90% in serum. Urinary PFAS levels were very low compared with serum. PFBS showed the shortest half-life (average 44 d [95% confidence interval (CI): 37, 55 d]}, followed by PFHpA [62 d (95% CI: 51, 80 d)]. PFPeS and PFHpS showed average half-lives as 0.63 and 1.46 y, respectively. Branched PFOS isomers had average half-lives ranging from 1.05 to 1.26 y for different isomers. PFOA, PFHxS, and linear PFOS isomers showed average half-lives of 1.77, 2.87, and 2.93 y, respectively. DISCUSSION: A general pattern of increasing half-lives with increasing chain length was observed. Branched PFOS isomers had shorter half-lives than linear PFOS isomers.
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| 40. |
- Yim, K., et al.
(författare)
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Free PSA and Clinically Significant and Fatal Prostate Cancer in the PLCO Screening Trial
- 2023
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Ingår i: Journal of Urology. - 0022-5347. ; 210:4, s. 630-637
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We studied whether adding percent free PSA to total PSA improves prediction of clinically significant prostate cancer and fatal prostate cancer. Materials and Methods: A total of 6,727 men within the intervention arm of PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial) had baseline percent free PSA. Of this cohort, 475 had clinically significant prostate cancer and 98 had fatal prostate cancer. Cumulative incidence and Cox analyses were conducted to evaluate the association between percent free PSA/PSA and clinically significant prostate cancer/fatal prostate cancer. Harrell's C index evaluated predictive ability. Kaplan-Meier analysis assessed survival. Results: Median follow-up was 19.7 years, median baseline PSA was 1.19 ng/mL, median percent free PSA was 18%. Cumulative incidence of fatal prostate cancer formen with baseline PSA >= 2 ng/mL and percent free PSA <= 10 was 3.2% and 6.1% at 15 and 25 years, respectively, compared to 0.03% and 1.1% for men with percent free PSA >25%. In younger men (55-64 years) with baseline PSA 2-10 ng/mL, C index improved from 0.56 to 0.60 for clinically significant prostate cancer and from 0.53 to 0.64 for fatal prostate cancer with addition of percent free PSA. In older men (65-74 years), C index improved for clinically significant prostate cancer from 0.60 to 0.66, with no improvement in fatal prostate cancer. Adjusting for age, digital rectal exam, family history of prostate cancer, and total PSA, percent free PSA was associated with clinically significant prostate cancer (HR 1.05, P <.001) per 1% decrease. Percent free PSA improved prediction of clinically significant prostate cancer and fatal prostate cancer for all race groups. Conclusions: In a large U.S. screening trial, the addition of percent free PSA to total PSA in men with baseline PSA >= 2 ng/mL improved prediction of clinically significant prostate cancer and fatal prostate cancer. Free PSA should be used to risk-stratify screening and decrease unnecessary prostate biopsies.
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| 41. |
- Ylikoski, A, et al.
(författare)
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Simultaneous quantification of prostate-specific antigen and human glandular kallikrein 2 mRNA in blood samples from patients with prostate cancer and benign disease
- 2002
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Ingår i: Clinical Chemistry. - 0009-9147. ; 48:8, s. 1265-1271
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Tidskriftsartikel (refereegranskat)abstract
- Background: Detection or quantification of circulating cancer cells has been proposed as an aid in detection and monitoring of several solid tumors. We investigated the classification accuracy of prostate-specific antigen (PSA) and human glandular kallikrein 2 (hK2) mRNA copy numbers in blood for the differentiation of patients with prostate cancer (PC) and benign disease. Methods: PSA and hK2 mRNA expression was studied in blood samples from 51 men with PC and 19 men with benign disease. Among the PC patients, 10 had organ-confined disease (pT1-pT2). We used a multiplexed reverse transcription-PCR assay with two highly target-like mRNA internal standards for the simultaneous quantification of PSA and hK2 mRNA. An external calibration curve covered the range of 10(2)-10(6) mRNA copies. Results: PSA and hK2 mRNA were detected in 41 of 51 (median, 1200 copies/0.5 mL of blood) and 43 of 51 (median, 3800 copies/0.5 mL of blood) patients with PC, respectively, whereas only 1 of 19 men with benign disease was positive for both mRNAs (1500 PSA and 3100 hK2 mRNA copies/0.5 mL of blood; P < 0.0001, Mann-Whitney U-test). Of the 10 patients with organ-confined PC, only 3 with low Gleason scores (less than or equal to5) were negative for both PSA and hK2 (P = 0.02, Mann-Whitney U-test). Conclusions: The presence of PC cells in the blood circulation is an early event in PC progression, and quantitative assays for PSA and hK2 mRNA discriminate benign from PC cases. Further studies are needed to determine the diagnostic accuracy and prognostic value of the assays.
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| 42. |
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| 43. |
- Aladdin Haglund, Berit, et al.
(författare)
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Unexpected out-of-hospital deliveries--experiences from the Gothenburg area. Centralized obstetrical care requires competent ambulance staff
- 2004
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Ingår i: Lakartidningen. ; 101:41, s. 3148-50
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Tidskriftsartikel (refereegranskat)abstract
- One hundred and sixty-seven women gave birth before arrival at the hospital during a six-year period in the Goteborg area. Most of these women had given birth before. The actual delivery most often started at term during the night, proceeded normally but rapidly and the neonatal outcome was good. Sixty-two per cent of the women delivered at home. Complicated lacerations or major hemorrhages were uncommon. The distance to the delivery ward was one of the risk factors for prehospital delivery. This is important to take into consideration in the ongoing process of centralizing the delivery clinics. Basic knowledge in obstetrics is mandatory for the ambulance personnel, as well as regular observation visits to the delivery ward and practice in birth simulators.
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| 44. |
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| 45. |
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| 46. |
- Arkadopoulos, N, et al.
(författare)
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Intrasplenic transplantation of allogeneic hepatocytes prolongs survival in anhepatic rats
- 1998
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 28:5, s. 1365-1370
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Tidskriftsartikel (refereegranskat)abstract
- To examine whether hepatocytes transplanted in the spleen can function as an ectopic liver, we performed hepatocyte transplantation in rats that were rendered anhepatic, Total hepatectomy was performed by using a novel single-stage technique. Following hepatectomy, Group 1 rats (n = 16) were monitored until death to determine survival time without prior intervention. Group 2 anhepatic rats (n = 20) were sacrificed at various times to measure blood hepatocyte growth factor (HGF) and transforming growth factor beta 1 (TGF-beta 1) levels. Group 3 (n = 16) rats received intrasplenic injection of isolated hepatocytes (2.5 x 10(7) cells/rat) followed by total hepatectomy after 3 days. Group 4 (n = 12) sham-transplanted rats received intrasplenic saline infusion, and after 3 days they were rendered anhepatic, Group 2, 3, and 4 rats were maintained on daily Cyclosporine A (10 mg/kg; intramuscularly). Group I anhepatic rats survived for 22.4 +/- 5.2 hours (standard deviation). The anhepatic state was associated with a progressive and statistically significant rise in blood HGF and TGF-beta 1 levels. Rats that received hepatocyte transplantation before total hepatectomy had a significantly longer survival time than sham-transplanted anhepatic controls (34.1 +/- 8.5 vs. 15.5 +/- 4.8 hrs, P < .01), Additionally, at 12 hours post-hepatectomy, transplanted rats had significantly lower blood ammonia, prothrombin time, international normalized ratio, and TGF-beta 1 levels when compared with sham-transplanted controls, In conclusion, intrasplenic transplantation of allogeneic hepatocytes prolonged survival, improved blood chemistry, and lowered blood TGF-beta 1 levels in rats rendered anhepatic.
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| 47. |
- Aumüller, G., et al.
(författare)
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Species‐ and organ‐specificity of secretory proteins derived from human prostate and seminal vesicles
- 1990
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 17:1, s. 31-40
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Tidskriftsartikel (refereegranskat)abstract
- Polyclonal antibodies against semenogelin (SG) isolated from human seminal vesicle secretion and acid phosphatase (PAP), β‐microseminoprotein (β‐MSP), and Prostate‐Specific Antigen (PSA) derived from human prostatic fluid, as well as a monoclonal antibody against β‐MSP were used for immunocytochemical detection of the respective antigens in different organs from different species. SG immunoreactivity was detected in the epithelium of the pubertal and adult human and in monkey seminal vesicle, ampulla of the vas deferens, and ejaculatory duct. PAP, β‐MSP, and PSA immunoreactivities were detected in the pubertal and adult human prostate and the cranial and caudal monkey prostate. With the exception of a weak PSA immunoreactivity in the proximal portions of the ejaculatory duct, none of the latter antisera reacted with seminal vesicle, ampullary, and ejaculatory duct epithelium. Among the non‐primate species studied (dog, bull, rat, guinea pig) only the canine prostatic epithelium displayed a definite immunoreactivity with the PAP antibody and a moderate reaction with the PSA antibody. No immunoreaction was seen in bull and rat seminal vesicle and canine ampulla of the vas deferens with the SG antibody. The same was true for the (ventral) prostate of rat, bull, and dog for β‐MSP. The epithelium of the rat dorsal prostate showed a slight cross‐reactivity with the monoclonal antibody against β‐MSP and one polyclonal antibody against PSA. The findings indicate a rather strict species‐dependent expression of human seminal proteins which show some similarities in primates, but only marginal relationship to species with different physiology of seminal fluid.
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| 48. |
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| 49. |
- Becker, Charlotte, et al.
(författare)
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Clinical value of human glandular kallikrein 2 and free and total prostate-specific antigen in serum from a population of men with prostate-specific antigen levels 3.0 ng/mL or greater
- 2000
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Ingår i: Urology. - 1527-9995. ; 55:5, s. 694-699
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate the clinical value of human glandular kallikrein 2 (hK2) compared with free (f) and total (t) prostate-specific antigen (PSA) in the early detection of prostate cancer (PCa). METHODS: In PCa screening conducted in 1995 to 1996 in Goteborg, Sweden, 5853 of 9811 randomly selected men (aged 50 to 66 years; median 61) accepted PSA testing; those with tPSA levels of 3. 0 ng/mL or greater were offered digital rectal examination, transrectal ultrasound, and sextant biopsies. Serum from 604 of 611 biopsied men (18% with positive digital rectal examinations, tPSA range 3.0 to 220 ng/mL, 144 men with PCa) was analyzed for hK2 (research assay) and tPSA and fPSA (Prostatus). Sera were stored at -20 degrees C for a maximum of 2 weeks for tPSA and fPSA and 3 years for hK2. RESULTS: hK2 levels and hK2 x tPSA/fPSA values were significantly elevated in men with PCa. Receiver operating characteristic data revealed that the area under the curve for hK2 x tPSA/fPSA was significantly greater than that for tPSA and greater, but not significantly greater, than that for percent fPSA. Also, the cancer-detecting sensitivity was significantly improved (P <0.05) using hK2 x tPSA/fPSA compared with tPSA and percent fPSA at specificity levels of 75% to 90%. At 75% specificity, a sensitivity of 74% was obtained compared with 64% or 54% using percent fPSA or tPSA; at 90% specificity, the corresponding sensitivity level was 55%, 41%, and 36%, respectively. CONCLUSIONS: Discrimination of men with and without PCa in a randomly selected population was improved by measuring hK2 in addition to tPSA and fPSA.
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| 50. |
- Becker, Charlotte, et al.
(författare)
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Sensitive and specific immunodetection of human glandular kallikrein 2 in serum
- 2000
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Ingår i: Clinical Chemistry. - 0009-9147. ; 46:2, s. 198-206
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Human glandular kallikrein 2 (hK2) is expressed in the prostate and is present in serum from men with prostate cancer. Specific detection in serum is difficult mainly because of low concentrations and immunological cross-reactivity with prostate-specific antigen (PSA). Our objectives were to design an assay with improved analytical detection and functional sensitivity and nonsignificant cross-reactivity with PSA, and to characterize different immunoreactive forms of hK2. METHODS: In the assay, critical PSA epitopes were blocked with four monoclonal antibodies (MAbs) specific for PSA. Subsequently, hK2 was captured using a MAb against hK2 (5% cross-reactivity with PSA), and after washing, hK2 was detected by a europium-labeled MAb with identical affinity for hK2 and PSA. RESULTS: The analytical detection limit was <10 ng/L, and functional sensitivity was 30 ng/L. Cross-reaction with PSA was <0.01%. Between-assay imprecision was 3.1% for 1600 ng/L hK2 and 4. 8% for 160 ng/L hK2; corresponding values for within-assay precision were 1.9% and 4.5%, respectively. Complexes of hK2-alpha(1)-antichymotrypsin (ACT) were detected in vitro with -6% bias compared with the free form of hK2. Gel filtration of patient samples showed that hK2 correlated in size mainly with free hK2; only 4-19% corresponded to hK2 possibly complexed with ACT or protein C inhibitor. CONCLUSIONS: Our assay had extremely low cross-reactivity with PSA, provided a very low detection limit, and allowed close to equimolar detection of the free and complexed forms of hK2. Moreover, we found that free hK2 is the predominant immunoreactive form of hK2 in serum.
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