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1.
  • Adamczak, Desiree, et al. (författare)
  • Influence of synthetic pathway, molecular weight and side chains on properties of indacenodithiophene-benzothiadiazole copolymers made by direct arylation polycondensation
  • 2021
  • Ingår i: Journal of Materials Chemistry C. - : Royal Society of Chemistry (RSC). - 2050-7534 .- 2050-7526. ; 9:13, s. 4597-4606
  • Tidskriftsartikel (refereegranskat)abstract
    • Atom-economic protocols for the synthesis of poly(indacenodithiophene-alt-benzothiadiazole) (PIDTBT) are presented in which all C-C coupling steps are achieved by direct arylation. Using two different synthetic pathways, PIDTBT copolymers with different side chains (hexylphenyl, octylphenyl, dodecyl, methyl/2-octyldodecylphenyl, 2-octyldodecylphenyl/2-octyldodecylphenyl) and molecular weight (MW) are prepared. Route A makes use of direct arylation polycondensation (DAP) of indacenodithiophene (IDT) and 4,7-dibromo-2,1,3-benzothiadiazole (BTBr2) leading to PIDTBT in high yields, with adjustable MW and without indications for structural defects. Route B starts from a polyketone precursor also prepared by DAP following cyclization. While route B allows introduction of asymmetric side chains at the IDT unit, polymer analogous cyclization gives rise to defect formation. The absorption coefficient of PIDTBT with alkylphenyl side chains made by route A increases with MW. Field-effect hole mobilities around similar to 10(-2) cm(2) V-1 s(-1) are molecular weight-independent, which is ascribed to a largely amorphous thin film morphology. PIDTBT with linear dodecyl side (C12) chains exhibits a bathochromic shift (20 nm), in agreement with theory, and more pronounced vibronic contributions to absorption spectra. In comparison to alkylphenyl side chains, C12 side chains allow for increased order in thin films, a weak melting endotherm and lower energetic disorder, which altogether explain substantially higher field-effect hole mobilities of similar to 10(-1) cm(2) V-1 s(-1).
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2.
  • Almqvist, Erik, et al. (författare)
  • Early parathyroidectomy increases bone mineral density in patients with mild primary hyperparathyroidism: A prospective and randomized study
  • 2004
  • Ingår i: Surgery. - : Elsevier BV. - 1532-7361 .- 0039-6060. ; 136:6, s. 1281-1287
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. There is an ongoing controversy regarding how to take care of patients with mild primary hyperparathyroidism (PHPT) and how to grade their disease activity in terms of bone parameters. This prospective and randomized study was undertaken to evaluate skeletal effects of delayed surgical treatment in such patients. Methods. Fifty patients with mild PHPT (serum calcium, 2.55 to 2.95 mmol/L, 10.2 to 11.8 mg/dL) were randomized to parathyroidectomy either at diagnosis or 1 year later. Hip and spine bone mineral density (BMD, determined by dual energy x-ray absorptiometry), bone alkaline phosphatase in serum, osteocalcin and P-CrossLaps in plasma, and calcium in urine were measured in all patients at inclusion in the study and 1 and 2 years later. Results. The skeletal effects of mild PHPT varied with anatomy and time of exposure. Parathyroidectomy decreased all biochemical bone markers (P <.0001) and increased lumbar spine BAW (P <.05) equally in both groups, even in patients without overt osteoporosis, whereas hip BAM was increased (P <.05) in the early intervention group only. Conclusion. Prolonged exposure to mild and seemingly stable PHPT is a risk factor for hip fractures, which adds to other reasons for surgical treatment of this condition without delay regardless of serum calcium levels.
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3.
  • Almqvist, Erik, et al. (författare)
  • Increase of bioavailable testosterone is associated with gain in bone mineral density after cure of primary hyperparathyroidism in postmenopausal women
  • 2006
  • Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 64:1, s. 58-62
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective The recovery of bone mineral density (BMD) after surgical cure of primary hyperparathyroidism (PHPT) seems to be multifactorial and not just dependent on declining PTH. The aim of the present study was to evaluate the role of sex steroids in this context. Design and patients Thirty-six postmenopausal women with PHPT were examined before and 1 year after curative parathyroidectomy. Their mean age at inclusion in the study was 71.7 +/- 1.1 years (range 54-83). BMD was measured in hip and lumbar spine using dual energy X-ray absorptiometry. No patient received any replacement therapy with sex hormones or treatment with corticosteroids, oestrogen receptor modulators or bisphosphonates. Measurements Serum concentrations of oestradiol, testosterone, androstenedione, dehydroepiandrosterone sulphate, SHBG, PTH and calcium. Results Postoperative increase of free (bioavailable) testosterone was positively correlated to the change of BMD in the hip (P < 0.01), whereas the change of PTH in serum correlated to the change of BMD in the lumbar spine (P < 0.05). Multiple regression analysis showed that bioavailable testosterone was the most important determinant of change in BMD in both spine and hip (femoral neck: P < 0.05; Ward's triangle: P < 0.001; trochanter: P < 0.01; lumbar spine: P < 0.05). The increase of bioavailable testosterone after curative parathyroidectomy was related to declining SHBG. Conclusions An increase of bioavailable testosterone following surgical cure of PHPT is related to improvement of hip and lumbar spine BMD in postmenopausal women. This previously unknown hormonal interaction may also be important to other aspects of hyperparathyroidism.
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4.
  • Almqvist, Erik, et al. (författare)
  • Increased plasma concentrations of N-terminal pro-B-type natriuretic peptide in patients with mild primary hyperparathyroidism.
  • 2006
  • Ingår i: Clinical endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 65:6, s. 760-6
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Primary hyperparathyroidism (PHPT) is associated with heart disease. The aims of the present study were to evaluate how cardiac function and secretion of N-terminal pro-B-type natriuretic peptide (NT-proBNP) correlate in patients with mild PHPT, and how the plasma level of NT-proBNP is influenced by cure of the parathyroid disease. DESIGN AND PATIENTS: Forty-two patients with PHPT without symptoms of heart disease were examined before and 1 year after curative parathyroidectomy. MEASUREMENTS: Plasma or serum concentrations of NT-proBNP, calcium, PTH, creatinine, oestradiol, testosterone and SHBG were measured. Cardiac function was evaluated by equilibrium radionuclide angiography (ERNA). RESULTS: At baseline, NT-proBNP levels correlated negatively with systolic function [left ventricular ejection fraction (LVEF), P < 0.001]. Twelve per cent of the patients had NT-proBNP levels above normal reference values preoperatively. One year postoperatively, the corresponding proportion was 21%. The mean plasma concentration of NT-proBNP increased after parathyroidectomy (P < 0.01) in parallel with a dip in diastolic function (peak filling rate, P < 0.05) and a falling trend in systolic function (LVEF, P = 0.08). The postoperative percentage changes in circulating NT-proBNP and total oestradiol correlated positively (P < 0.05). CONCLUSIONS: Patients with mild PHPT and normal renal function may have high levels of circulating NT-proBNP despite the absence of symptomatic heart disease. Cure of the parathyroid disease is followed by a further increase in NT-proBNP secretion in parallel with ERNA measures, indicating subclinical changes in heart function. These results are in line with data indicating an association between PHPT and increased risk of premature death.
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5.
  • Ankarberg-Lindgren, Carina, 1963, et al. (författare)
  • Methodological considerations in determining sex steroids in children: comparison of conventional immunoassays with liquid chromatography-tandem mass spectrometry.
  • 2024
  • Ingår i: Clinical chemistry and laboratory medicine. - 1437-4331. ; 62:1, s. 85-96
  • Tidskriftsartikel (refereegranskat)abstract
    • In laboratory medicine, external quality assessment (EQA) schemes have become versatile tools for detecting analytical flaws. However, EQA schemes are lacking for pediatric sex steroid levels. We aimed to investigate the suitability of different estradiol and testosterone immunoassays in a pediatric setting in comparison with clinical liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays.The study was conducted by staff and the advisory group on endocrinology at Equalis, the Swedish provider of EQA schemes for laboratory medicine. The test material consisted of five pooled serum samples from children who were either prepubertal or in puberty. Clinical laboratories enrolled in Equalis EQA schemes for estradiol and testosterone were invited to participate, as were clinical laboratories using LC-MS/MS-assays. Samples were analyzed by either routine immunoassays (n=18) or in-house LC-MS/MS assays (n=3).For estradiol, LC-MS/MS assays showed a high degree of conformity with interlaboratory coefficients of variation (CV) below 24.2%. Reported levels were between 4.9±1.2 and 33.9±1.6pmol/L (group mean±standard deviation). The direct immunoassays had lower precision; their CVs were up to 81.4%. Reported concentrations were between 25.3±18.1 and 45.7±19.4pmol/L, an overestimation compared to LC-MS/MS. Testosterone LC-MS/MS also showed a high degree of conformity, CVs were below 13.4%, and reported concentrations were from 0.06±0.00 to 1.00±0.11nmol/L. The direct immunoassays had a larger discrepancy between results; CVs were up to 95.8%. Concentrations were between 0.12±0.11 and 0.85±0.23nmol/L.For the safe diagnosis and determination of sex steroids in children, analysis with mass spectrometry-based methods is recommended.
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6.
  • Arndt, D. S., et al. (författare)
  • State of the Climate in 2016
  • 2017
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
  • Tidskriftsartikel (refereegranskat)abstract
    • In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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7.
  • Arndt, D. S., et al. (författare)
  • STATE OF THE CLIMATE IN 2017
  • 2018
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
  • Forskningsöversikt (refereegranskat)
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8.
  • Aus, G, et al. (författare)
  • Cumulative prostate cancer risk assessment with the aid of the free-to-total prostate specific antigen ratio
  • 2004
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 45:2, s. 160-165
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To evaluate the cumulative risk of having a prostate cancer diagnosis in a repeated screening situation in relation to the free-to-total prostate specific antigen ratio (F/T-PSA). Patients and Methods: The present study includes 1385 men (aged 50-70 years) who underwent prostate biopsy for the first time in the screening program that started in 1995. In case of a benign finding, the men have been followed biennially and new biopsies performed in case of persistently elevated PSA. The cumulative risk to be diagnosed with prostate cancer until July 1, 2002 was calculated by the Kaplan-Meier method and comparison was made between different levels of T-PSA and F/T-PSA ratios. Results: Of 2129 biopsies 469 showed cancer. The cumulative 5-year risk to be diagnosed with prostate cancer was significantly dependent of the F/T-ratio. The risk for men with a T-PSA of 3-5.99 ng/ml was 16% [6-25%] for those who had a ratio of >30% and 44% [34-60%] for those with a ratio of <10%. The corresponding difference for patients with a T-PSA of 6-9.99 ng/ml was even more pronounced: 21% [0-42%] vs. 80% [64-96%]. Conclusion: By completing the T-PSA measurement with the F/T-PSA ratio it is possible to significantly better assess the cumulative prostate cancer risk within the next five years (without the aid of further urological work-up).
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9.
  • Aus, G, et al. (författare)
  • Free-to-total prostate-specific antigen ratio as a predictor of non-organ-confined prostate cancer (stage pT3)
  • 2003
  • Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 37:6, s. 466-470
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To evaluate whether the free-to-total prostate-specific antigen (F/T-PSA) ratio can be used to differentiate between stage pT2 and pT3 prostate cancer. Material and Methods: A total of 176 consecutive patients from the Goteborg Screening Study (median T-PSA 4.2 ng/ml) who underwent radical prostatectomy (without neoadjuvant hormonal therapy) were included in the study. The pT stage was correlated with classical risk factors such as T-PSA and Gleason sum and the impact of the F/T-PSA ratio was evaluated. Results: A total of 42/176 patients (23.9%) had stage pT3 prostate cancer. Patients with an F/T-PSA ratio in the lowest quartile (<10.7%) had extracapsular tumor growth in 46.5% of cases, compared to 16.7% for those with an F/T-PSA ratio >10.7% ( p = 0.0002). Patients with high-risk features (T-PSA >10 ng/ml or Gleason sum greater than or equal to7) had a high risk (54-60%) for stage pT3 prostate cancer. In low-risk patients, the subgroup with an F/T-PSA ratio <10.7% had a risk of 37.0%, compared to only 13.3% for those with a ratio of >10.7% (p = 0.0092). Conclusions: In patients with low-risk early-stage prostate cancer, the F/T-PSA ratio provides statistically significant, independent and clinically relevant preoperative information about the risk of extracapsular tumor growth.
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10.
  • Becker, Charlotte, et al. (författare)
  • Characterization of epitope structure for 53 monoclonal antibodies against prostate-specific antigen
  • 1999
  • Ingår i: Tumor Biology. - : Springer Science and Business Media LLC. - 1423-0380 .- 1010-4283. ; 20:Suppl. 1, s. 13-17
  • Tidskriftsartikel (refereegranskat)abstract
    • Prostate-specific antigen (PSA) is the most widely used marker of prostate cancer. Assays for PSA are based on anti-PSA antibodies, and the characterization and selection of these antibodies is important for determining their optimum performance. In our study, we characterized the reactivity of 53 antibodies, submitted to the ISOBM TD-3 PSA Workshop, using free PSA, PSA complexed to alpha1-antichymotrypsin (ACT) and purified ACT. Immunoblotting was performed after native agarose gel or reducing sodium dodecyl polyacrylamide gel electrophoresis. Immunoblotting after agarose gel electrophoresis revealed 10 antibodies that recognized only the free form of PSA, and 43 antibodies that detected both free PSA and PSA-ACT. Immunoblotting of reducing sodium dodecyl-polyacrylamide gels showed the linear or conformation-dependent nature of the epitopes. Two antibodies specific for free PSA and 18 antibodies that recognized both free PSA and PSA-ACT complex recognized linear epitopes. Moreover, 7 antibodies also detected fragmented forms of PSA.
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11.
  • Becker, Charlotte, et al. (författare)
  • 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
  • Ingår i: Urology. - 1527-9995. ; 55:5, s. 694-699
  • 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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12.
  • Becker, Charlotte, et al. (författare)
  • Discrimination of men with prostate cancer from those with benign disease by measurements of human glandular kallikrein 2 (HK2) in serum
  • 2000
  • Ingår i: Journal of Urology. - 1527-3792. ; 163:1, s. 311-316
  • 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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13.
  • Becker, Charlotte (författare)
  • Human glandular kallikrein 2 (hK2) in prostate cancer: Clinical and Methodological studies
  • 2000
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Human glandular kallikrein 2 (hK2) is a predominantly prostate produced protein with many similarities to prostate-specific antigen (PSA). Just like for PSA elevated levels of hK2 can be found in men with protate cancer. We created an assay where hK2 in serum could reliably and with negligible cross-reactivity with PSA, be measured down to 0.030 ng/mL. The assay measured free hK2 and hK2 complexed to ACT with a –6% bias to free hK2. Gel-filtration of serum with elevated hK2 concentrations showed that the predominant form found in serum was free hK2. We then studied the utility of hK2 measurements in the differentiation of men with benign prostatic hyperplasia (BPH) from men with prostate cancer (PCa). The addition of hK2 to measurements to free and total PSA improved the differentiation of men with BPH from men with clinically localized prostate cancer. In order to study weather hK2 was useful in the clinical staging of prostate cancer, we measured hK2 in preoperative sera derived from prostatectomized men. The levels of hK2 was found to be significantly different in men with organ confined prostate cancer compared to men with nonorgan confined prostate cancer. High concentrations of hK2 makes a nonorgan confined prostate cancer likely. The utility of hK2 measurements were also studied in a population of men participating in the Göteborg screening study for prostate cancer. The men studied were all biopsied due to PSA concentrations of 3.0 ng/mL of higher. We could demonstrate that hK2 used in combination with free and total PSA (hK2 x total PSA / free PSA) improved the differentiation of men with and without prostate cancer. By this combination we saw a significant improvement in sensitivity at high levels of specificity compared to by use of percent free PSA or total PSA.Two years after the first screening, the same cohort of men were called for a new serum PSA test. Again, we studied the men biopsied due to elevated PSA and found that hK2 in combination with free and total PSA improved the separation of men with and without cancer, however less significant than in the first round of screening. We found that hK2 increased almost two-fold, and significantly higher, in men with cancer over a two year period compared to in men without cancer.
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14.
  • Becker, Charlotte, et al. (författare)
  • Individual prostate-specific antigen (PSA) forms as prostate tumor markers
  • 1997
  • Ingår i: Clinica Chimica Acta. - 0009-8981. ; 257:1, s. 117-132
  • Tidskriftsartikel (refereegranskat)abstract
    • Prostate-specific antigen (PSA) is a kallikrein-like serine protease mainly expressed in the human prostate. It is responsible for the proteolysis of the gel-forming proteins in human semen. Two major extracellular protease inhibitors, alpha-1-antichymotrypsin (ACT) and alpha-2-macroglobulin (AMG) may inactivate PSA escaping from the prostate. The predominant immunodetected form of PSA in serum is complexed to ACT but PSA exists also in a free non-complexed form despite the large excess of inhibitors. The concentrations of PSA in serum are normally less than 4 micrograms/l. but elevated concentrations are found in a majority of patients with prostate cancer (CAP) and the analysis of PSA in serum has become invaluable in the detection and monitoring of patients with CAP. However, it is not an ideal tumor marker in the sense that there are CAP patients with normal PSA concentrations in serum and patients with benign hyperplasia of the prostate (BPH) with elevated PSA concentrations. Analysis of the various PSA forms in serum attracts much interest as there is a higher proportion of PSA in complex with ACT in patients with CAP than in those with BPH. Optimal combinations of monoclonal antibodies have been used to design sensitive noncross-reacting immunoassays for the detection of free PSA, PSA-ACT complexes and the detection of both free PSA and PSA complexes in an equimolar fashion (i.e. total PSA). Several studies have demonstrated that the analysis of the proportions of the free-to-total PSA in serum may increase the diagnostic specificity by 15-20% without significant loss in the sensitivity for detection of CAP.
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15.
  • Becker, Charlotte, et al. (författare)
  • Sensitive and specific immunodetection of human glandular kallikrein 2 in serum
  • 2000
  • Ingår i: Clinical Chemistry. - 0009-9147. ; 46:2, s. 198-206
  • 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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16.
  • Becker, Charlotte, et al. (författare)
  • Testing in serum for human glandular kallikrein 2, and free and total prostate specific antigen in biannual screening for prostate cancer.
  • 2003
  • Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 170:4 Pt 1, s. 1169-1174
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: We investigated the value of serum measurements for glandular kallikrein 2 (hK2), and free (f) and total (t) prostate specific antigen (PSA) in a second round of biannual screening for prostate cancer. Materials and Methods: In 1995 to 1996, 5,853 of 9,811 randomly selected men in Goteborg, Sweden 50 to 66 years old had PSA measurements. Of 660 men 611 with tPSA 3 ng/ml or greater underwent biopsy and 145 had cancer. All were re-invited 2 years later for PSA testing, and 506 of 596 men with tPSA 3 ng/ml or greater underwent biopsy and 113 cancers were detected. We analyzed hK2, tPSA and fPSA in 423 of 453 (93%) men who underwent biopsy in 1997 to 1998 who were also screened in 1995 to 1996. Results: The 99 of 423 (23%) men who underwent biopsy diagnosed with prostate cancer in 1997 to 1998 had significantly different tPSA, percent fPSA and hK2 x tPSA/fPSA compared to the men with negative biopsies from 2 years earlier. The largest area under curve was obtained for hK2 x tPSA/fPSA in serum from 1995 to 1996 and from 1997 to 1998, but the difference was not significant compared to tPSA and percent fPSA. In serum from 1997 to 1998 measurements of hK2 x tPSA/fPSA gave significantly higher specificity than tPSA at 85% sensitivity, and significantly higher specificity than tPSA and percent fPSA at 70% to 75% sensitivity. In addition, levels of hK2 and hK2 x tPSA/fPSA manifested a significantly greater 2-year increase in men with cancer compared to those with benign biopsies. Conclusions: In men with tPSA levels 3.0 ng/ml or greater who were not diagnosed with cancer during a first round of screening, hK2 measurements enhanced specificity compared to tPSA testing at moderately high sensitivity, and manifested a greater 2-year increase in men with cancer.
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17.
  • Becker, Charlotte, et al. (författare)
  • The role of molecular forms of prostate-specific antigen (PSA or hK3) and of human glandular kallikrein 2 (hK2) in the diagnosis and monitoring of prostate cancer and in extra-prostatic disease
  • 2001
  • Ingår i: Critical Reviews in Clinical Laboratory Sciences. - : Informa UK Limited. - 1549-781X .- 1040-8363. ; 38:5, s. 357-399
  • Tidskriftsartikel (refereegranskat)abstract
    • Prostate-specific antigen (PSA or hK3) is a glandular kallikrein with abundant expression in the prostate that is widely used to detect and monitor prostate cancer (PCa), although the serum level is frequently elevated also in benign and inflammatory prostatic diseases. PSA testing is useful for early detection of localized PCa and for the detection of disease recurrence after treatment. However, PSA has failed to accurately estimate cancer volume and preoperative staging. There is no PSA level in serum that definitively distinguishes men with benign conditions from those with prostate cancer, although PCa is rare in men with PSA levels in serum < 2.0 ng/ml. This prompted searches for enhancing parameters to combine with PSA testing, such as PSA density, PSA velocity, and age-specific reference ranges. Due to the protease structure, PSA occurs in different molecular forms in serum and their concentrations vary according to the type of prostatic disease. Human glandular kallikrein 2 (hK2) is very similar to PSA, but expressed at higher levels in prostate adenocarcinoma than in normal prostate epithelium. Blood testing for hK2 combined with different PSA forms improves discrimination of men with benign prostatic disease from those with prostate cancer. Many data have also been reported on the extra-prostatic expression of both PSA and hK2, and it is now believed that they may both have functions in tissues outside the prostate.
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18.
  • Becker, Kerstin, et al. (författare)
  • De novo microdeletions of chromosome 6q14.1-q14.3 and 6q12.1-q14.1 in two patients with intellectual disability : further delineation of the 6q14 microdeletion syndrome and review of the literature
  • 2012
  • Ingår i: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212 .- 1878-0849. ; 55:8-9, s. 490-497
  • Tidskriftsartikel (refereegranskat)abstract
    • Interstitial 6q deletions can cause a variable phenotype depending on the size and location of the deletion. 6q14 deletions have been associated with intellectual disability and a distinct pattern of minor anomalies, including upslanted palpebral fissures with epicanthal folds, a short nose with broad nasal tip, anteverted nares, long philtrum, and thin upper lip. In this study we describe two patients with overlapping 6q14 deletions presenting with developmental delay and characteristic dysmorphism. Molecular karyotyping using array CGH analysis revealed a de novo 8.9 Mb deletion at 6q14.1-q14.3 and a de novo 11.3 Mb deletion at 6q12.1-6q14.1, respectively. We provide a review of the clinical features of twelve other patients with 6q14 deletions detected by array CGH analysis. By assessing all reported data we could not identify a single common region of deletion. Possible candidate genes in 6q14 for intellectual disability might be FILIP1, MYO6, HTR1B, and SNX14.
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19.
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20.
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21.
  • Bergkvist, Charlotte, et al. (författare)
  • Exposure to dioxin-like pollutants via different food commodities in Swedish children and young adults.
  • 2008
  • Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 46:11, s. 3360-3367
  • Tidskriftsartikel (refereegranskat)abstract
    • The dietary intake of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) in terms of toxic equivalents (TEQs) was investigated in Swedish children and young adults. Exposure was estimated from concentration data of six groups of individual food commodities (meat, fish, dairy products, egg, edible fats and other foodstuff) combined with food intake data from a 7-day record book obtained from 670 individuals aged 1-24 years. The results showed that Swedish boys and girls, up to the age of ten, had a median TEQ intake that exceeded the tolerable daily intake (TDI) of 2 pg TEQ/kg body weight. Children exceeding the TDI varied from almost all individuals among the youngest children to about 20% among young men and women. Dairy and fish products were the main sources of exposure for the average child, accounting for 59% of the total TEQ intake. The individuals most highly exposed were, on the other hand, characterized by a high consumption of fish. Since children constitute a vulnerable group, results obtained from the present study show that it is essential to perform age specific dietary intake assessments of pollutants and more carefully consider sensitive and/or highly exposed groups in the population in the risk management processes.
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22.
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23.
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24.
  • Blumel, Edda, et al. (författare)
  • Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma
  • 2019
  • Ingår i: Oncoimmunology. - : Taylor & Francis. - 2162-4011 .- 2162-402X. ; 8:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Staphylococcus aureus is implicated in disease progression in cutaneous T-cell lymphoma (CTCL). Here, we demonstrate that malignant T cell lines derived from CTCL patients as well as primary malignant CD4+ T cells from Sézary syndrome patients are considerably more resistant to alpha-toxin-induced cell death than their non-malignant counterparts. Thus, in a subset of Sézary syndrome patients the ratio between malignant and non-malignant CD4+ T cells increases significantly following exposure to alpha-toxin. Whereas toxin-induced cell death is ADAM10 dependent in healthy CD4+ T cells, resistance to alpha-toxin in malignant T cells involves both downregulation of ADAM10 as well as other resistance mechanisms. In conclusion, we provide first evidence that Staphylococcus aureus derived alpha-toxin can tilt the balance between malignant and non-malignant CD4+ T cells in CTCL patients. Consequently, alpha-toxin may promote disease progression through positive selection of malignant CD4+ T cells, identifying alpha-toxin as a putative drug target in CTCL.
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25.
  • Blunden, Jessica, et al. (författare)
  • State of the Climate in 2012
  • 2013
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:8, s. S1-S258
  • Tidskriftsartikel (refereegranskat)abstract
    • For the first time in serveral years, the El Nino-Southern Oscillation did not dominate regional climate conditions around the globe. A weak La Ni a dissipated to ENSOneutral conditions by spring, and while El Nino appeared to be emerging during summer, this phase never fully developed as sea surface temperatures in the eastern conditions. Nevertheless, other large-scale climate patterns and extreme weather events impacted various regions during the year. A negative phase of the Arctic Oscillation from mid-January to early February contributed to frigid conditions in parts of northern Africa, eastern Europe, and western Asia. A lack of rain during the 2012 wet season led to the worst drought in at least the past three decades for northeastern Brazil. Central North America also experienced one of its most severe droughts on record. The Caribbean observed a very wet dry season and it was the Sahel's wettest rainy season in 50 years. Overall, the 2012 average temperature across global land and ocean surfaces ranked among the 10 warmest years on record. The global land surface temperature alone was also among the 10 warmest on record. In the upper atmosphere, the average stratospheric temperature was record or near-record cold, depending on the dataset. After a 30-year warming trend from 1970 to 1999 for global sea surface temperatures, the period 2000-12 had little further trend. This may be linked to the prevalence of La Ni a-like conditions during the 21st century. Heat content in the upper 700 m of the ocean remained near record high levels in 2012. Net increases from 2011 to 2012 were observed at 700-m to 2000-m depth and even in the abyssal ocean below. Following sharp decreases in to the effects of La Ni a, sea levels rebounded to reach records highs in 2012. The increased hydrological cycle seen in recent years continued, with more evaporation in drier locations and more precipitation in rainy areas. In a pattern that has held since 2004, salty areas of the ocean surfaces and subsurfaces were anomalously salty on average, while fresher areas were anomalously fresh. Global tropical cyclone activity during 2012 was near average, with a total of 84 storms compared with the 1981-2010 average of 89. Similar to 2010 and 2011, the North Atlantic was the only hurricane basin that experienced above-normal activity. In this basin, Sandy brought devastation to Cuba and parts of the eastern North American seaboard. All other basins experienced either near-or below-normal tropical cyclone activity. Only three tropical cyclones reached Category 5 intensity-all in Bopha became the only storm in the historical record to produce winds greater than 130 kt south of 7 N. It was also the costliest storm to affect the Philippines and killed more than 1000 residents. Minimum Arctic sea ice extent in September and Northern Hemisphere snow cover extent in June both reached new record lows. June snow cover extent is now declining at a faster rate (-17.6% per decade) than September sea ice extent (-13.0% per decade). Permafrost temperatures reached record high values in northernmost Alaska. A new melt extent record occurred on 11-12 July on the Greenland ice sheet; 97% of the ice sheet showed some form of melt, four times greater than the average melt for this time of year. The climate in Antarctica was relatively stable overall. The largest maximum sea ice extent since records begain in 1978 was observed in September 2012. In the stratosphere, warm air led to the second smallest ozone hole in the past two decades. Even so, the springtime ozone layer above Antarctica likely will not return to its early 1980s state until about 2060. Following a slight decline associated with the global 2 emissions from fossil fuel combustion and cement production reached a record 9.5 +/- 0.5 Pg C in 2011 and a new record of 9.7 +/- 0.5 Pg C is estimated for 2012. Atmospheric CO2 concentrations increased by 2.1 ppm in 2012, to 392.6 ppm. In spring 2012, 2 concentration exceeded 400 ppm at 7 of the 13 Arctic observation sites. Globally, other greenhouse gases including methane and nitrous oxide also continued to rise in concentration and the combined effect now represents a 32% increase in radiative forcing over a 1990 baseline. Concentrations of most ozone depleting substances continued to fall.
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26.
  • Borghammar, Camilla, et al. (författare)
  • Prevalence of refractoriness when testing growth hormone levels in children
  • 2023
  • Ingår i: Growth Hormone and IGF Research. - 1096-6374. ; 71
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Late night spontaneous growth hormone (GH) pulses may influence the pituitary GH response to provocation tests. We evaluated GH response during arginine-insulin-tolerance test (AITT) after a GH peak during a short spontaneous nocturnal profile (SSNP) in children with short stature or low growth velocity. Design: Using SSNP and subsequent AITT, we examined 257 children 4–18 years old (138 (53.7%) males) recruited from three hospitals. Medical records were reviewed retrospectively. Refractory children were defined as a GH peak ≥7 μg/L during SSNP but no GH peak ≥7 μg/L during AITT. Results: In total, 201/257 children had a GH peak ≥7 μg/L at SSNP and/or AITT. Of these, 21.9% were refractory. The proportion of males (p = 0.033) and body mass index (BMI) standard deviation score (SDS) (p = 0.037) were higher in the refractory group than in children with a GH peak ≥7 μg/L during AITT. The median period between last GH peak ≥7 μg/L during SSNP and GHmax at AITT was 210 (30–390) minutes. The GHmax at AITT occurred 30 min earlier for children without a peak ≥7 μg/L during the SSNP (p = 0.004). The number of refractoriness differed somewhat between the hospitals (p = 0.025). Conclusions: Many children with short stature were refractory at testing; among them we found few clinical characteristics. Refractoriness might be influenced by some differences in procedure, but needs to be considered when evaluating GH response in children.
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27.
  • Bousquet, Jean, et al. (författare)
  • ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
  • 2021
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
  • Forskningsöversikt (refereegranskat)abstract
    • Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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28.
  • Bousquet, J. Jean, et al. (författare)
  • Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
  • 2019
  • Ingår i: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
  • Forskningsöversikt (refereegranskat)abstract
    • Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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29.
  • Brattsand, Göran, et al. (författare)
  • Endokrina sjukdomar
  • 2018. - 10
  • Ingår i: Laurells Klinisk kemi i praktisk medicin. - Lund : Studentlitteratur AB. - 9789144119748 ; , s. 283-344
  • Bokkapitel (refereegranskat)
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30.
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31.
  • Brattsand, Göran, et al. (författare)
  • Equalis/SFKK rekommenderar harmonisering av enheter vid hormonbestämningar -Något också för Norden?
  • 2012
  • Ingår i: Klinisk Biokemi i Norden. - 1101-2013. ; 24:4, s. 20-27
  • Tidskriftsartikel (refereegranskat)abstract
    • Equalis och Svensk Förening för Klinisk Kemi (SFKK) rekommenderar att de kliniska laboratorierna i Sverige använder enhetliga måttenheter vid hormonbestämningar för ökad jämförbarhet och patientsäkerhet. Vid analys i serum eller plasma med nuvarande metoder rekommenderas följande enheter:• Adrenokortikotropt hormon (ACTH): pmol/L• Insulin: mIE/L• Parathormon (PTH): pmol/L• Prolaktin: mIE/L• Tillväxthormon (GH): μg/L• Östradiol: pmol/L• Aldosteron: pmol/L• Reninkoncentration: mIE/L
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32.
  • Bruun, Laila, et al. (författare)
  • Assessment of intra-individual variation in prostate-specific antigen levels in a biennial randomized prostate cancer screening program in Sweden.
  • 2005
  • Ingår i: Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 65:3, s. 216-221
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract BACKGROUND The degree of variability in prostate-specific antigen (PSA) measurements is important for interpreting test results in screening programs, and particularly for interpreting the significance of changes between repeated tests. This study aimed to determine the long-term intra-individual variation for PSA in healthy men. METHODS A randomly selected cohort of men in a biennial prostate cancer screening program (ERSPC) conducted in Sweden from 1995-1996 to 2001-2002. We studied men who had total PSA (tPSA) levels < 2.0 ng/ml in 2001-2002. This included 791 men with tPSA 0.61 ng/ml (group A), 1,542 men with tPSA 0.99 ng/ml (group B), and 1,029 men with tPSA 1.00-1.99 ng/ml (group C). The intra-individual variability of free PSA (fPSA) and tPSA was assessed by calculating coefficients of variation (CV) for each individual's PSA measurements from the first and second round of screening (1995-1996 and 1997-1998). RESULTS Intra-individual CV (geometric means) for tPSA were 13.7%, 12.7%, and 11.5% in groups A, B, and C, respectively. Corresponding CVs for fPSA were significantly lower, ranging from 12.1% to 10.4%. The estimated biological variation of tPSA and fPSA in groups A to C were 12.5%, 11.4%, 10.0% and 9.7%, 7.8%, 7.5%, respectively. CONCLUSIONS In healthy men with PSA levels less than 2 ng/ml, the natural long-term variability for tPSA was less than 14%, and with 95% probability, a change in tPSA greater than 30% indicates a change beyond normal random variation. © 2005 Wiley-Liss, Inc.
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33.
  • Bruun, Laila, et al. (författare)
  • Percent-free prostate specific antigen is elevated in men on haemodialysis or peritoneal dialysis treatment.
  • 2003
  • Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385. ; 18:3, s. 598-602
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Men with chronic renal failure evaluated for transplantation are often tested for prostate specific antigen (PSA) to detect prostate cancer. PSA occurs in several different molecular forms in serum: free PSA (fPSA) and complexed PSA (cPSA), the sum of which corresponds to total PSA (tPSA). In addition to tPSA, percent fPSA to tPSA (%fPSA) is widely used to enhance discrimination of benign disorders from prostate cancer. The low molecular mass of fPSA suggests elimination by renal glomerular filtration and that renal failure may significantly influence %fPSA. We evaluated whether established reference levels for %fPSA are applicable also to patients treated with haemodialysis or continuous ambulatory peritoneal dialysis (CAPD).Methods: The study included 20 men on intermittent haemodialysis with low-flux membranes and 25 men on CAPD, without known history of prostate cancer. The control group included 3129 men without known prostate cancer. We analysed fPSA and tPSA in serum by dual-label immunofluorometric assays, from which we calculated %fPSA and cPSA. Serum levels of different PSA forms were adjusted for age and presented as geometric means.Results: Percent fPSA was significantly higher in patients on either haemodialysis (39.5%) or CAPD (39.6%) compared with controls (28.1%). Haemodialysis patients, but not CAPD patients, had significantly higher mean levels of fPSA. Levels of tPSA and cPSA for haemodialysis or CAPD patients did not differ significantly compared with controls.Conclusions: Recommended reference ranges for %fPSA, based on men with normal renal function, do not apply to uraemic men on dialysis. In these men, a high %fPSA should not be considered as a sign of benign disease. This is clinically important in the evaluation of dialysis patients for transplantation, as %fPSA is often used as a tool for detection of prostate cancer.
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34.
  • Bungum, Leif, et al. (författare)
  • Circadian variation in concentration of anti-Mullerian hormone in regularly menstruating females: relation to age, gonadotrophin and sex steroid levels.
  • 2011
  • Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 26, s. 678-684
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Anti-Müllerian hormone (AMH) is a promising marker of ovarian reserve. The aim of the study is to assess the circadian variation in AMH, and to evaluate its clinical relevance and biological aspects as an effect of age and other endocrine mechanisms involved in the regulation of AMH secretion. METHODS Nineteen healthy non-smoking, regularly menstruating female volunteers with body mass index below 30 kg/m(2), 10 aged 20-30 years (Group A) and 9 aged 35-45 (Group B) were included. Blood sampling, initiated at 8:00 a.m. on Days 2-6 of the menstrual cycle, was continued every second hour until 8:00 a.m. the following day. Serum levels of AMH, FSH, LH, progesterone and estradiol were measured. RESULTS With 8:00 a.m. values at the first day of investigation as a reference, the mean concentrations in the pooled data revealed a significantly lower level at 4:00 a.m. (P = 0.021) and 6:00 a.m. (P = 0.005) with a maximum mean difference of 1.9 pmol/l (10.6%). The same pattern was seen in both the age groups. Including both the age groups, the overall circadian variation of the AMH levels did not reach statistical significance (P = 0.059). A significant positive correlation between AMH and LH concentration was seen over the 24-h period (P < 0.001). CONCLUSIONS A slight decrease in serum AMH levels during the late night appears not clinically relevant. Co-variation in the levels of LH and AMH might indicate joint regulatory mechanisms for the latter hormone and gonadotrophins.
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35.
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36.
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37.
  • Carlén, Lina M, et al. (författare)
  • Proteome analysis of skin distinguishes acute guttate from chronic plaque psoriasis.
  • 2005
  • Ingår i: Journal of Investigative Dermatology. - 0022-202X .- 1523-1747. ; 124:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Psoriasis is a disease with considerable heterogeneity in clinical presentation. This is the first study using two-dimensional gel electrophoresis to compare global protein expression patterns in lesional and non-lesional skin from subjects with acute guttate psoriasis associated with streptococcal throat infection and chronic plaque psoriasis. Samples from experimentally induced contact eczema and normal skin from healthy controls were also included. Proteins with statistically significant differences in expression were used in hierarchical cluster analyses resulting in separation of the different samples into groups. Chronic plaque and guttate psoriasis samples were distinctly separated, indicating that they represent discrete phenotypes at the protein expression level. Interestingly, there was a trend in which guttate psoriasis lesions clustered closer to eczema than to chronic plaque psoriasis lesions, indicating that the duration of the inflammatory reaction may affect clustering. Several of the differentially expressed proteins were identified by mass spectrometry.
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38.
  • Dossus, Laure, et al. (författare)
  • Hormonal, metabolic, and inflammatory profiles and endometrial cancer risk within the EPIC cohort--a factor analysis.
  • 2013
  • Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 177:8, s. 787-799
  • Tidskriftsartikel (refereegranskat)abstract
    • A "Western" lifestyle characterized by physical inactivity and excess weight is associated with a number of metabolic and hormonal dysregulations, including increased circulating estrogen levels, hyperinsulinemia, hyperglycemia, and chronic inflammation. The same hormonal and metabolic axes might mediate the association between this lifestyle and the development of endometrial cancer. Using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC), a prospective cohort study carried out in 10 European countries during 1992-2000, we conducted a factor analysis to delineate important components that summarize the variation explained by a set of biomarkers and to examine their association with endometrial cancer risk. Prediagnostic levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, sex hormone-binding globulin, estrone, estradiol, C-peptide, insulin-like growth factor-binding proteins 1 and 2, adiponectin, high- and low-density lipoprotein cholesterol, glucose, triglycerides, tumor necrosis factor (TNF) α, soluble TNF receptors 1 and 2, C-reactive protein, interleukin-6, and interleukin-1 receptor antagonist were measured in 233 incident endometrial cancer cases and 446 matched controls. Factor analysis identified 3 components associated with postmenopausal endometrial cancer risk that could be labeled "insulin resistance/metabolic syndrome," "steroids," and "inflammation" factors. A fourth component, "lipids," was not significantly associated with endometrial cancer. In conclusion, besides the well-known associations of risk with sex hormones and insulin-regulated physiological axes, our data further support the hypothesis that inflammation factors play a role in endometrial carcinogenesis.
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39.
  • Dossus, Laure, et al. (författare)
  • Obesity, inflammatory markers, and endometrial cancer risk : a prospective case-control study
  • 2010
  • Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 17:4, s. 1007-1019
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity, a major risk factor for endometrial cancer, is a low-grade inflammatory state characterized by elevated concentrations of cytokines and acute phase reactants. The current study had two aims: first to investigate the associations of C-reactive protein (CRP), interleukin 6 (IL6), and IL1 receptor antagonist (IL1Ra) with endometrial cancer risk and second to examine to which extent these markers can influence the association between obesity and endometrial cancer. We conducted a case-control study, nested within the European Prospective Investigation into Cancer and Nutrition, which comprised 305 incident cases of endometrial cancer and 574 matched controls. CRP, IL6, and IL1Ra were measured in prospectively collected blood specimens by immunoassays. Data were analyzed using conditional logistic regression. All statistical tests were two-sided, and P values <0.05 were considered statistically significant. We observed a significant increase in risk of endometrial cancer with elevated levels of CRP (odds ratio (OR) for top versus bottom quartile: 1.58, 95% confidence interval (CI): 1.03-2.41, P(trend)=0.02), IL6 (OR for top versus bottom quartile: 1.66, 95% CI: 1.08-2.54, P(trend)=0.008), and IL1Ra (OR for top versus bottom quartile: 1.82, 95% CI: 1.22-2.73, P(trend)=0.004). After adjustment for body mass index (BMI), the estimates were strongly reduced and became non-significant. The association between BMI and endometrial cancer was also substantially attenuated (∼10-20%) after adjustment for inflammatory markers, even when the effects of C-peptide or estrone had already been taken into account. We provided epidemiological evidence that chronic inflammation might mediate the association between obesity and endometrial cancer and that endometrial carcinogenesis could be promoted by an inflammatory milieu.
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40.
  • Dossus, Laure, et al. (författare)
  • Tumor necrosis factor (TNF)-α, soluble TNF receptors and endometrial cancer risk : the EPIC study
  • 2011
  • Ingår i: International Journal of Cancer. - Geneve : International union against cancer. - 0020-7136 .- 1097-0215. ; 129:8, s. 2032-2037
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic inflammation has been hypothesized to play a role in endometrial cancer development. Tumor necrosis factor-α (TNF-α), one of the major pro-inflammatory cytokines, has also been implicated in endometrial physiology. We conducted a case-control study nested within the European prospective investigation into cancer and nutrition (EPIC) to examine the association of TNF-α and its two soluble receptors (sTNFR1 and sTNFR2) with endometrial cancer risk. Two-hundred-seventy cases and 518 matched controls were analyzed using conditional logistic regression. All statistical tests were two-sided. We observed an increased risk of endometrial cancer among women in the highest versus lowest quartile of TNF-α (odds ratio [OR]: 1.73, 95% CI: 1.09-2.73, Ptrend = 0.01), sTNFR1 (OR: 1.68, 95% CI: 0.99-2.86, Ptrend = 0.07) and sTNFR2 (OR: 1.53, 95%CI: 0.92-2.55, Ptrend = 0.03) after adjustment for body-mass-index, parity, age at menopause and previous postmenopausal hormone therapy use. Further adjustments for estrogens and C-peptide had minor effect on risk estimates. Our data show that elevated prediagnostic concentrations of TNF-α and its soluble receptors are related to a higher risk of endometrial cancer, particularly strong in women diagnosed within 2 years of blood donation. This is the first study of its kind and therefore deserves replication in further prospective studies.
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41.
  • Ekström, Simon, et al. (författare)
  • Integrated selective enrichment target - a microtechnology platform for matrix-assisted laser desorption/ionization-mass spectrometry applied on protein biomarkers in prostate diseases
  • 2004
  • Ingår i: Electrophoresis. - : Wiley. - 0173-0835. ; 25:21-22, s. 3769-3777
  • Tidskriftsartikel (refereegranskat)abstract
    • The performance of a miniaturized sample processing platform for matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS), manufactured by silicon microfabrication, called integrated selective enrichment target (ISET) technology was evaluated in a biological context. The ISET serves as both sample treatment device and MALDI-MS target, and contains an array of 96 perforated nanovials, which each can be filled with 40 nL of reversed-phase beads. This methodology minimizes the number of sample transfers and the total surface area available for undesired adsorption of the analytes in order to provide high-sensitivity analysis. ISET technology was successfully applied for characterization of proteins coisolated by affinity chromatography of prostate-specific antigen (PSA) from human seminal fluid. The application of ISET sample preparation enabled multiple analyses to be performed on a limited sample volume, which resulted in the discovery that prolactin inducible protein (PIP) was coisolated from the samples.
  •  
42.
  • Elzanaty, Saad, et al. (författare)
  • Seminal plasma albumin: origin and relation to the male reproductive parameters.
  • 2007
  • Ingår i: Andrologia. - : Hindawi Limited. - 0303-4569 .- 1439-0272. ; 39:2, s. 60-65
  • Tidskriftsartikel (refereegranskat)abstract
    • We wanted to investigate the origin of seminal plasma albumin and its relation to the male reproductive parameters. Semen samples from 916 men, under infertility assessment, were analysed according to guidelines of the World Health Organization. Seminal plasma constituents, i.e. albumin, markers of the epididymal (neutral alpha-glucosidase, NAG), prostatic (prostate-specific antigen, PSA, and zinc) and seminal vesicle function (fructose), as well as levels of reproductive hormones in plasma were measured. The sperm chromatin structure assay (SCSA) was applied on 267 of the 916 samples. A negative correlation was seen for seminal albumin and plasma follicle-stimulating hormone (r = -0.1, P = 0.02) and a positive correlation for seminal albumin and serum inhibin B (r = 0.2, P = 0.004). Albumin exhibited positive correlations with the epididymal marker, NAG (r = 0.5, P < 0.001) and with the prostatic markers, PSA and zinc (r = 0.1, P = 0.001; r = 0.2, P < 0.001 respectively) as well as with age (r = 0.2, P < 0.001). A negative significant association was seen for seminal albumin and semen volume (beta = -0.60; 95% CI -0.80 to -0.30). The opposite trend was found regarding sperm concentration (beta = 0.34; 95% CI 0.30-0.40), total sperm count (beta = 0.30; 95% CI 0.20-0.40), and percentage morphologically normal spermatozoa (beta = 0.70; 95% CI 0.10-1.0). No association was found between albumin and sperm motility, SCSA parameters, or fructose, the marker of seminal vesicles. Our results suggest testicular, epididymal and prostatic origin of seminal plasma albumin, in addition to the contribution from blood. This is the first study to demonstrate an association between seminal plasma albumin and sperm morphology. Further studies are needed to elucidate the role of seminal albumin in sperm morphology.
  •  
43.
  • Fredholm, Simon, et al. (författare)
  • SATB1 in Malignant T Cells
  • 2018
  • Ingår i: Journal of Investigative Dermatology. - : Elsevier. - 0022-202X .- 1523-1747. ; 138:8, s. 1805-1815
  • Tidskriftsartikel (refereegranskat)abstract
    • Deficient expression of SATB1 hampers thymocyte development and results in inept T-cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides, the most frequent variant of cutaneous T-cell lymphoma. Here, we report on a disease stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. STAT5 inhibited SATB1 expression through induction of microRNA-155. Decreased SATB1 expression triggered enhanced expression of IL-5 and IL-9 (but not IL-6 and IL-32), whereas increased SATB1 expression had the opposite effect, indicating that the microRNA-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5 and its upstream activator JAK3 triggered increased SATB1 expression and a concomitant suppression of IL-5 and IL-9 expression in malignant T cells. In conclusion, we provide a mechanistic link between the proto-oncogenic JAK3/STAT5/microRNA-155 pathway, SATB1, and cytokines linked to CTCL severity and progression, indicating that SATB1 dysregulation is involved in cutaneous T-cell lymphoma pathogenesis.
  •  
44.
  • Gluud, Maria, et al. (författare)
  • MicroRNAs in the Pathogenesis, Diagnosis, Prognosis and Targeted Treatment of Cutaneous T-Cell Lymphomas
  • 2020
  • Ingår i: Cancers. - : MDPI. - 2072-6694. ; 12:5
  • Forskningsöversikt (refereegranskat)abstract
    • Cutaneous T-cell lymphoma (CTCL) represents a heterogeneous group of potentially devastating primary skin malignancies. Despite decades of intense research efforts, the pathogenesis is still not fully understood. In the early stages, both clinical and histopathological diagnosis is often difficult due to the ability of CTCL to masquerade as benign skin inflammatory dermatoses. Due to a lack of reliable biomarkers, it is also difficult to predict which patients will respond to therapy or progress towards severe recalcitrant disease. In this review, we discuss recent discoveries concerning dysregulated microRNA (miR) expression and putative pathological roles of oncogenic and tumor suppressive miRs in CTCL. We also focus on the interplay between miRs, histone deacetylase inhibitors, and oncogenic signaling pathways in malignant T cells as well as the impact of miRs in shaping the inflammatory tumor microenvironment. We highlight the potential use of miRs as diagnostic and prognostic markers, as well as their potential as therapeutic targets. Finally, we propose that the combined use of miR-modulating compounds with epigenetic drugs may provide a novel avenue for boosting the clinical efficacy of existing anti-cancer therapies in CTCL.
  •  
45.
  • Haese, A, et al. (författare)
  • Human glandular kallikrein 2: a potential serum marker for predicting the organ confined versus non-organ confined growth of prostate cancer
  • 2000
  • Ingår i: Journal of Urology. - 1527-3792. ; 163:5, s. 1491-1497
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: We measured serum levels of human glandular kallikrein 2 (hK2) in patients with prostate cancer treated with radical retropubic prostatectomy for clinically localized prostate cancer to determine whether preoperative hK2 levels discriminate stage pT2a/b from pathological stage T3a or greater cancer. This finding would help to predict preoperatively the organ confined versus non-organ confined growth of prostate cancer. MATERIALS AND METHODS: A total of 68 consecutive men underwent radical retropubic prostatectomy for clinically localized prostate cancer. Serum was obtained 1 day preoperatively before prostatic manipulation. hK2, and total and free prostate specific antigen (PSA) were measured using immunofluorometric assays. Mean, median and range of hK2, total and free PSA, and the ratio of free-to-total PSA (percent free PSA) were calculated. Each analyte or combination of analytes was evaluated to determine whether it significantly contributed to enhance the discrimination of organ confined from non-organ confined cancer. We calculated the statistical significance of observed differences using the Mann-Whitney U and Kruskal-Wallis tests. Sensitivity and specificity calculations were performed for hK2, total PSA and the algorithm, (hK2) x (total PSA/free PSA) in addition to receiver operating characteristics curves and the respective areas under the curves. Multivariate logistic regression analysis was done for hK2, and total and free PSA RESULTS: Disease was organ and non-organ (extraprostatic extension) confined in 38 and 30 men, respectively. In organ confined cancer mean hK2 was significantly lower than in non-organ confined cancer (0.09 ng./ml., range less than 0.03 to 0.23 versus 0.30, range 0.04 to 0.94, p <0.0001). In addition, there was significantly higher free and total but not percent free PSA in non-organ than in organ confined cases. There were also statistically significant differences in hK2, free PSA and total PSA at each pathological disease stage (p <0.001, <0.01 and <0.05, respectively). Sensitivity for detecting organ confined disease was 37% at 100% specificity (correct identification of all non-organ confined cancer) using hK2 measurements compared with a sensitivity of 14% for total PSA. At a specificity of 95%, sensitivity was 40% for hK2 versus 23% for total PSA, which was a statistically significant gain in sensitivity (p <0.05). Receiver operating characteristics curves demonstrated that hK2 had the largest area under the curve, followed by the algorithm, (hK2) x (total PSA/free PSA), and total PSA (0.76, 0.75 and 0.72, respectively). However, none of area under the curve differences was statistically significant. CONCLUSIONS: Compared with total and free PSA hK2 testing improved the preoperative evaluation of patients who underwent radical retropubic prostatectomy due to the superior discrimination of organ from non-organ confined cancer.
  •  
46.
  • Haese, Alexander, et al. (författare)
  • Human glandular kallikrein 2 levels in serum for discrimination of pathologically organ-confined from locally-advanced prostate cancer in total PSA-levels below 10 ng/ml
  • 2001
  • Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 49:2, s. 101-109
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: We measured serum levels of human glandular kallikrein 2 (hK2) in patients treated with radical retropubic prostatectomy (rrP) for clinically localized prostate cancer (PCa) with a total PSA (tPSA)-level below 10 ng/ml to investigate whether hK2 can be applied to preoperatively distinguish organ-confined (pT2a/b) from nonorgan-confined (> or = pT3a)-PCa more accurately than total PSA. Further, we evaluated hK2, free- and tPSA-concentrations in all pathologic stages of PCa. METHODS: 161 serum samples from men scheduled for rrP were collected 1 day before surgery prior to any prostatic manipulation. Pathologic work-up revealed > or = pT3a-PCa in 48 and pT2a/b-PCa in 113 patients. HK2-levels in serum were measured using an immunofluorometric assay with an analytical sensitivity of 0.5 pg/ml, a functional sensitivity of 5 pg/ml and insignificant cross-reactivity with PSA (< 0.005%). Total (tPSA) and free PSA (fPSA) levels were measured using a commercially available assay from which we calculated %fPSA and an algorithm that combined hK2 and PSA-levels [hK2] x [tPSA/fPSA]. Means, medians, and ranges were calculated for pT2a/b vs. >/= pT3a-PCa and for all pathologic stages. Statistical significance of differences was calculated using Mann-Whitney-U and Kruskal-Wallis tests. Calculation of receiver-operator-characteristic (ROC) curves were performed for hK2, [hK2] x [tPSA/fPSA] and tPSA to compare diagnostic performance. RESULTS: A mean tPSA level in serum of 6.12 ng/ml in > or = pT3a-PCa was not significantly different (P = 0.366) from 5.78 ng/ml in pT2a/b-PCa. Also, there were no statistically significantly different levels of fPSA (P = 0.947) or %fPSA (0.292) for these two groups. By contrast, mean hK2-level in pT2a/b-PCa of 80 pg/ml was significantly different (P = 0.004) from a mean hK2 level of 120 pg/ml in > or = pT3a-PCa as shown by Mann-Whitney-analysis Moreover, the algorithm of [hK2] x [tPSA/fPSA] was significantly lower (P = 0.0004) in pT2a/b-PCa vs. > or = pT3a-PCa. Calculation of areas under curve (AUC) by receiver-operator-characteristics (ROC) demonstrated that the AUC for hK2 (0.64) was larger and the AUC for [hK2] x [tPSA/fPSA] (=0.68) significantly larger (P = 0.007) compared to the AUC of tPSA (0.55). Furthermore, Kruskal-Wallis Test revealed a highly significant correlation to pathologic stage using hK2 (P = 0.008) and [hK2] x [tPSA/fPSA] (P = 0.0015) compared to no significant differences in serum concentration of tPSA (P = 0.296). Also at tPSA-levels from 10-20 ng/ml, the hK2-levels in pT2a/b-PCa were close to significantly different (P = 0.051) from those in men with >/= pT3a-PCa, while the algorithm of [hK2] x [tPSA/fPSA] in that tPSA-range was significantly lower (P = 0.002) in pT2a/b-PCa compared to > or = pT3a0-PCa. CONCLUSIONS: Highly significant differences in serum concentration enable hK2 to be a powerful predictor of organ-confined disease and pathologic stage of clinically localized prostate cancer, especially in the PSA-range below 10 ng/ml. As such, there are important clinical consequences for the application of hK2 for the adequate treatment of prostate cancer patients, i.e., the option of nerve-sparing surgery.
  •  
47.
  • Haese, A, et al. (författare)
  • The role of human glandular kallikrein 2 for prediction of pathologically organ confined prostate cancer
  • 2003
  • Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 54:3, s. 181-186
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND. In recent studies serum levels of human glandular kallikrein 2 (hK2) demonstrated significant differences in pathologically organ-confined versus non-organ-confined prostate cancer (Pca). In this study we investigated whether hK2 adds independent information when considered together with traditionally used parameters to predict organ confined (pT2a/b) PCa. METHODS. Serum levels of hK2, total and free prostate-specific antigens (PSA) were obtained one day before radical prostatectomy in 245 consecutive men. These were included with clinical stage and biopsy Gleason grade into univariate analysis and multivariate logistic regression models. RESULTS. pT2a/b PCa was found in n = 148 patients. In univariate analysis all preoperative parameters demonstrated significant association with the presence of pT2a/b PCa. Using multivariate logistic regression model hK2 (P = 0.022), clinical stage (P < 0.0001), and Gleason grade (P < 0.0001) were independent predictors of pT2a/b PCa whereas PSA (P = 0.3) was not. In bootstrap corrected logistic regression based nomograms the addition of hK2 density marginally enhanced predictive accuracy when PSA, PSA density, clinical stage, and Gleason grade were considered (AUC = 0.879 without hK2 density and 0.883 with hK2 density). CONCLUSIONS. hK2 and hK2 density could independently predict pT2a/b PCa. However, improvement in predictive accuracy was marginal when nomograms based on traditional variables were complemented with this serum marker. (C) 2002 Wiley-Liss, Inc.
  •  
48.
  • Haese, A, et al. (författare)
  • Total and Gleason grade 4/5 cancer volumes are major contributors of human kallikrein 2, whereas free prostate specific antigen is largely contributed by benign gland volume in serum from patients with prostate cancer or benign prostatic biopsies
  • 2003
  • Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 170:6, s. 2269-2273
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: We measured concentrations of human glandular kallikrein 2 (hK2), total prostate specific antigen (tPSA), free PSA (fPSA) and percent fPSA to evaluate their relationship to total prostate gland volume, benign prostatic hyperplasia (BPH) volume, total prostate cancer (PCa) volume (CaVol) and the volume of Gleason grades 4/5 cancer (CaVolG14) in the serum of 256 patients with PCa undergoing radical retropubic prostatectomy and 185 with negative systematic sextant biopsies. Materials and Methods: Free and total PSA was measured using the Delfia Prostatus (Perkin-Elmer, Turku, Finland) total/free PSA assay and hK2 was measured using a research immunofluorometric assay. Transrectal ultrasound was used to determine total prostate and BPH volume. Total CaVol and CaVolG14/5 were calculated using a volumetric program in specimens from 158 men with pT2a/b and 98 with pT3a or greater PCa. The Pearson correlation was performed after logarithmic conversion of PSA and hK2 levels. Benign gland, and pT2a/b and pT3a or greater PCa cases were subdivided into small vs large prostate gland volumes (42 cc or less vs greater than 42 cc). Results: Total prostate and BPH volumes correlated closely with free PSA (r=0.64 to 0.65, p<0.0001) in 143 patients with negative biopsy and a prostate of greater than 42 cc. Correlations of hK2 and tPSA with total prostate and BPH volumes were weaker (r=0.35 to 0.36 and 0.45 to 0.46, respectively). In pT2a/b and pT3a or greater PCa cases hK2 most closely correlated with CaVol (range 0.31 to 0.62, p=0.0072 and <0.0001) and with CaVolG14/5 (range 0.26 to 0.56, p=0.021 and <0.0001, respectively). The tPSA level correlated significantly with CaVol and CaVolG14/5 except in glands 42 cc or greater harboring pT2a/b PCa (p=0.08). Free PSA correlated significantly with CaVolG14/5 only in pT3a or greater PCa (p<0.05), and with CaVol in pT3a or greater PCa and in small prostates harboring pT2a/b PCa. Conclusions: Large benign prostate gland volume affects fPSA more than tPSA in serum. In PCa hK2 more closely correlates with total cancer volume and high grade PCa volume compared with tPSA or fPSA.
  •  
49.
  • Hugosson, J, et al. (författare)
  • Would prostate cancer detected by screening with prostate-specific antigen develop into clinical cancer if left undiagnosed? A comparison of two population-based studies in Sweden
  • 2000
  • Ingår i: BJU International. - : Wiley. - 1464-4096. ; 85:9, s. 1078-1084
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To assess the risk of over-diagnosing and over-treating prostate cancer if population-based screening with serum prostate-specific antigen (PSA) is instituted. PATIENTS AND METHODS: From a serum bank stored in 1980, PSA was analysed in 658 men with no previously known prostate cancer from a well-defined cohort from Goteborg, Sweden (men born in 1913); the incidence of clinical prostate cancer was registered until 1995. From the same area, and with the same selection criteria, another cohort of 710 men born in 1930-31, who in 1995 accepted an invitation for PSA screening, was also analysed. RESULTS: Of men born in 1913, 18 (2.7%) had died from prostate cancer and the cumulative probability of being diagnosed with clinical prostate cancer was 11.1% (5.0% in those with a PSA level of < 3 ng/mL vs 32.9% in those with a PSA level of > 3 ng/mL, P < 0.01). The mean lead-time from increased PSA (> 3 ng/mL) to clinical diagnosis was 7 years. The prostate cancer detection rate in men born in 1930-31 was 4.4% (22% among those with increased PSA levels) and 30 of 31 detected cancers were clinically localized. CONCLUSIONS: Screening and sextant biopsies resulted in a lower detection rate (22%) than the cumulative risk of having clinical prostate cancer (33%) in men with increased PSA levels, indicating that under-diagnosis rather than over-diagnosis is the case at least with 'one-time' screening. Even if the stage distribution in screening-detected cancers seems promising (and thus may result in reduced mortality) it is notable that screening 67-year-old men will result in treatment a mean of 7 years before clinical symptoms occur and only one in four men anticipated to develop prostate cancer will die from the disease within 15 years. Large randomized screening trials seem mandatory to further explore the benefits and hazards of PSA screening.
  •  
50.
  • Johansson, Jesper, et al. (författare)
  • C-peptide in dried blood spots.
  • 2010
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 70, s. 404-409
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract The aim was to evaluate if the Dried Blood Spot (DBS)-technique can be used to analyse C-peptide. S-C-peptide and paired whole blood clotted on filters, dried, punched out and eluted were sampled from 198 healthy subjects. Six subjects with S-C-peptide values outside the reference range were excluded. A conversion formula using log-DBS-C-peptide was generated in a subset of 156 ( approximately 80%) subjects with predictions made using also storage time (eluates) and age of subjects: (log S-C-peptide = 1.696 + 1.367 log DBS-C-peptide + 0.058 (storage time/month) + 0.014 (age/10 years). This formula was cross validated into the original population. Using Bland-Altman plots, mean difference between converted log DBS-C-peptide and log S-C-peptide at baseline was 0 and limits of agreements were -0.18 to +0.18. Mean difference between converted log DBS-C-peptide values after six months and log S-C-peptide value from baseline was -0.01 and limits of agreement were -0.20-0.19. The lowest value detected with the DBS-technique corresponded to serum C-peptide 0.44 nmol/L. We concluded that DBS-C-peptide can be used as a first line screening test to monitor normal beta cell function. C-peptide on filters remained stable for six months.
  •  
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