| 1. |
- Tjernberg, Ivar, 1973-
(författare)
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Laboratory Diagnosis of Lyme Borreliosis : Anti-Borrelia Antibodies and the Chemokine CXCL13
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lyme borreliosis (LB), the most common tick-borne disease in Europe and North America, is caused by spirochetes of the Borrelia burgdorferi sensu lato complex. The spirochetes can invade several different organs, thereby causing many different symptoms and signs. Diagnosis of LB relies on patient history, physical examination, and detection of anti-Borrelia antibodies. However, anti-Borrelia antibodies are not always detectable, and they commonly persist even after LB is successfully treated or spontaneously healed.The aim of my work was to study diagnostic aspects on clinical cases of LB and control subjects in an area endemic to LB, with a focus on newly developed anti-Borrelia antibody tests. A total of 617 patients with symptoms and/or signs consistent with LB, as well as 255 control subjects, were studied. The diagnostic panel included the following new LB tests: Immunetics Quick ELISA C6 Borrelia assay kit (C6), invariable region 6 peptide antibody assays (IR6), Liaison Borrelia CLIA (Li) and the chemokine CXCL13. Results were compared with the older Virotech Borrelia burgdorferi ELISA (VT) and with a Western blot method, the Virotech Borrelia Ecoline IgG/IgM Line Immunoblot (WB EL), when appropriate.In general, no significant differences were noted between the C6, VT and Li tests regarding serosensitivity in various LB manifestations. However, the seropositivity rate was lower for the C6 test compared with the VT and Li tests 2–3 and 6 months after diagnosis of erythema migrans (EM), indicating normalization of antibody levels. In addition, EM patients reporting a previous LB episode had a C6 seropositivity rate similar to that of patients without a previous LB episode, and seroprevalence in healthy blood donors was lower in the C6 test than the VT and Li tests. Taken together, these results support the recommendation of the serum C6 test as a Borrelia serological test due to its ability to reflect ongoing or recent infection.Although the majority of EM patients at presentation showed concordant serological responses to IR6 peptides representing the three main Borrelia species and the C6 peptide, there were also clinical EM cases that were C6-negative and could be detected mainly by a seroresponse to a B. burgdorferi sensu stricto-derived IR6 peptide. Thus, an antibody test combining antigens could be of value in the serodiagnosis of LB in Europe.The serosensitivity of the C6 test in cases of Lyme neuroborreliosis (LNB) was shown to be associated with symptom duration. A serosensitivity rate of 93% was found in LNB patients ³ 12 years of age with a symptom duration of more than 30 days. Therefore, a negative C6 test in serum in such a patient argues against an LNB diagnosis.The presence of chemokine CXCL13 in cerebrospinal fluid was confirmed to be a reliable marker of LNB. CXCL13 differentiated LNB from other conditions and also indicated a high probability of LNB in children with short symptom duration where anti-Borrelia antibodies were still lacking in the cerebrospinal fluid.A two-tiered approach (C6 test in combination with WB EL) showed no significant improvement in specificity over the C6 test alone. However, WB EL may be useful in diagnosing suspected cases of acrodermatitis chronicum atrophicans and Lyme arthritis, usually displaying multiple IgG bands.In conclusion, although the serodiagnosis of LB remains to be settled, this thesis provides some practical tools regarding the use and interpretation of Borrelia serology including proposed diagnostic routines.
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| 2. |
- Abé, Christoph, et al.
(författare)
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Cortical brain structure and sexual orientation in adult females with bipolar disorder or attention deficit hyperactivity disorder
- 2018
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Ingår i: Brain and Behavior. - : Wiley. - 2162-3279 .- 2162-3279. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nonheterosexual individuals have higher risk of psychiatric morbidity. Together with growing evidence for sexual orientation‐related brain differences, this raises the concern that sexual orientation may be an important factor to control for in neuroimaging studies of neuropsychiatric disorders.Methods: We studied sexual orientation in adult psychiatric patients with bipolar disorder (BD) or ADHD in a large clinical cohort (N = 154). We compared cortical brain structure in exclusively heterosexual women (HEW, n = 29) with that of nonexclusively heterosexual women (nHEW, n = 37) using surface‐based reconstruction techniques provided by FreeSurfer.Results: The prevalence of nonheterosexual sexual orientation was tentatively higher than reported in general population samples. Consistent with previously reported cross‐sex shifted brain patterns among homosexual individuals, nHEW patients showed significantly larger cortical volumes than HEW in medial occipital brain regions.Conclusion: We found evidence for a sex‐reversed difference in cortical volume among nonheterosexual female patients, which provides insights into the neurobiology of sexual orientation, and may provide the first clues toward a better neurobiological understanding of the association between sexual orientation and mental health. We also suggest that sexual orientation is an important factor to consider in future neuroimaging studies of populations with certain mental health disorders.
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| 3. |
- Ahmed, Degmo Said, et al.
(författare)
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Quantitative determination of cerebrospinal fluid bilirubin on a high throughput chemistry analyzer
- 2009
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Ingår i: Clinical laboratory. - 1433-6510. ; 55:7-8, s. 283-288
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subarachnoid hemorrhage is a condition with high rates of mortality and morbidity. The diagnosis requires an urgent cerebral computed tomography scan and also a lumbar puncture if the scan fails to demonstrate intracranial blood. In Sweden the cerebrospinal fluid (CSF) is analyzed by spectrophotometric scanning for the presence of hemoglobin and bilirubin. The aim of the study was to develop a quantitative diazo reagent based analysis of cerebrospinal fluid bilirubin as a replacement for spectrophotometric scanning. METHODS: The CSF bilirubin assay on an Architect C8000 chemistry analyzer was compared with spectrophotometry using patient samples. RESULTS: The method correlates with spectrophotometry, has a good linearity and precision. CONCLUSIONS: Quantitative bilirubin measurement offers shorter turnaround times, simplifies the interpretation of the results and reduces work load in comparison with spectrophotometry.
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| 4. |
- Aldén, Anna, et al.
(författare)
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HPLC analysis of carbohydrate deficient transferrin isoforms isolated by the Axis-Shield %CDT method
- 2005
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Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981 .- 1873-3492. ; 356:1-2, s. 143-146
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Tidskriftsartikel (refereegranskat)abstract
- Background: Carbohydrate-deficient transferrin (CDT) is elevated during prolonged overconsumption of alcohol and CDT is considered to be the most specific biochemical marker for alcohol overconsumption. However, an accurate method for analysing CDT is necessary because the test is frequently used for example in legal matters. Methods: Patient serum samples were analysed with the Axis-Shield %CDT and eluates were pooled together. Transferrin was purified from the pool by affinity chromatography and further analysed with HPLC to determine the ratios of different transferrin isoforms. Results: In the eluates using the Axis-Shield %CDT method, a substantial amount of trisialo transferrin was found, which is generally not considered a CDT isoform. Conclusions: The fact that trisialo transferrin is present may generate falsely elevated CDT results and it could at least partly explain the discrepancy between results of the Axis-Shield %CDT assay and HPLC in routine analysis. © 2005 Elsevier B.V. All rights reserved.
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| 5. |
- Bergström, Maria, et al.
(författare)
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Lectin affinity capillary electrophoresis in glycoform analysis applying the partial filling technique
- 2004
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Ingår i: Journal of chromatography. B. - : Elsevier BV. - 1570-0232 .- 1873-376X. ; 809:2, s. 323-329
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Tidskriftsartikel (refereegranskat)abstract
- The study of protein glycosylation and its significance in biological interactions is a field of growing interest. This work demonstrates a lectin-based separation of protein glycoforms of α1-acid glycoprotein (AGP or orosomucoid) with capillary electrophoresis. Glycoform analysis was performed with a "partial filling technique" with the lectin Concanavalin A (Con A) as affinity ligand. Con A separated human AGP into two peaks, the first peak included AGP glycoforms without biantennary glycans, and the second peak represented the fraction that had one or more biantennary glycans. The applicability of the method was demonstrated with the analysis of AGP from clinical samples and AGP treated with N-glycosidase F. The AGP separation was also used as a reporter system to estimate the dissociation constant (KD) between Con A and a competing sugar. © 2004 Elsevier B.V. All rights reserved.
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| 6. |
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| 7. |
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| 8. |
- Evaldsson, Chamilly, et al.
(författare)
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4-Thiouridine induces dose-dependent reduction of oedema, leucocyte influx and tumour necrosis factor in lung inflammation
- 2009
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 155:2, s. 330-338
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Tidskriftsartikel (refereegranskat)abstract
- Recent reports demonstrate a role for nucleotides as inflammatory modulators. Uridine, for example, reduces oedema formation and leucocyte infiltration in a Sephadex-induced lung inflammation model. Tumour necrosis factor (TNF) concentration was also reduced. Previous in vivo observations indicated that 4-thiouridine might have similar effects on leucocyte infiltration and TNF release. The aim of this study was thus to investigate the effects of 4-thiouridine in greater detail. We used a Sephadex-induced acute lung inflammation model in Sprague-Dawley rats. The dextran beads were instilled intratracheally into the lungs, which were excised and examined after 24 h. Sephadex alone led to massive oedema formation and infiltration of macrophages, neutrophils and eosinophils. Microgranulomas with giant cell formations were clearly visible around the partially degraded beads. A significant increase in bronchoalveolar lavage fluid (BALF) content of TNF and leukotrienes was also seen. 4-Thiouridine co-administration affected all variables investigated in this model, i.e. oedema, microscopic and macroscopic appearance of lung tissue, total leucocyte and differential leucocyte counts in BALF, TNF and leukotrienes C-4 (LTC4), LTD4 and LTE4 in BALF, indicating a reproducible anti-inflammatory effect. In conclusion, we have demonstrated that 4-thiouridine has anti-inflammatory effects similar to those of uridine. To our knowledge, this is the first demonstration of pharmacological 4-thiouridine effects in vivo. The results suggest nucleoside/nucleotide involvement in inflammatory processes, warranting further studies on nucleoside analogues as attractive new alternatives in the treatment of inflammatory diseases.
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| 9. |
- Evaldsson, Chamilly, 1978-, et al.
(författare)
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Isomaltitol exacerbates neutrophilia but reduces eosinophilia : New insights into the Sephadex model of lung inflammation
- 2011
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Ingår i: International Archives of Allergy and Immunology. - : Karger. - 1018-2438 .- 1423-0097. ; 154:4, s. 286-294
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Tidskriftsartikel (refereegranskat)abstract
- We have previously examined isomaltitol in an in vitro static adhesion assay between isolated granulocytes and cultured human umbilical cord vein cells and were interested in investigating whether the potentially anti-inflammatory effects observed there could be reproduced in vivo. The Sephadex-induced lung inflammation model was considered a suitable model due to the significant changes in global inflammatory endpoints, like oedema and leukocyte migration, usually seen upon provocation with Sephadex. Male Sprague-Dawley rats were instilled intratracheally with Sephadex (5 mg/ml), vehicle (0.9% NaCl), isomaltitol (50 mg/ml) or a combination of isomaltitol and Sephadex. After 24 h, the lungs were weighed to measure oedema and preserved for histology. Bronchoalveolar lavage fluid was used for analysis of tumour necrosis factor, cysteinyl leukotrienes, and differential and total leukocyte counts. In addition, blood differential counts and thymus weights were analysed. Contrary to what we expected from in vitro experiments, differential counts showed that isomaltitol increased the neutrophil component while decreasing the eosinophilia. Isomaltitol thus asserted a modulatory role on the usually eosinophil-dominated Sephadex-induced cell profile. Isomaltitol alone also increased several inflammatory parameters, including oedema and cysteinyl leukotrienes, and generally aggravated total inflammation in combination with Sephadex. Although the mechanisms were not investigated in this study, the effects could relate to a combination of isomaltitol's osmotic and structure-specific properties. Our results indicate that isomaltitol can modulate the inflammatory response induced by Sephadex instillation in addition to have pro-inflammatory effects on it its own, and may therefore provide new insights into the mechanisms of this widely used animal model. Sugar alcohols similar to isomaltitol have already been used to aid mucus clearance in cystic fibrosis patients, and it is possible that isomaltitol could also be used for this purpose.
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| 10. |
- Falck, Anna-Karin, et al.
(författare)
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Analysis of and prognostic information from disseminated tumour cells in bone marrow in primary breast cancer: a prospective observational study
- 2012
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Disseminated tumour cells (DTCs) in the bone marrow of patients with breast cancer have been identified as an independent predictor of poor prognosis in patients with non-metastatic disease. This prospective study aimed to evaluate the presence and prognostic value of DTCs in the bone marrow of female patients with primary breast cancer. Methods: Between 1999 and 2003, bone marrow aspirates were obtained from patients at the time of surgery for primary invasive breast cancer. DTCs in bone marrow were identified using monoclonal antibodies against cytokeratins for detection of epithelial cells. The detection of DTCs was related to clinical follow-up with distant disease-free survival (DDFS) and breast cancer-specific survival as endpoints. Bone marrow aspirates from adult healthy bone marrow donors were analysed separately. Results: DTCs were analysed in 401 patients, and cytokeratin-positive cells were found in 152 of these (38%). An immunofluorescence (IF) staining procedure was used in 327 patients, and immunocytochemistry (IC) was performed in 74 patients. The IF-based method resulted in 40% DTC-positive cases, whereas 30% were positive using IC (p = 0.11). The presence of DTCs in bone marrow was not significantly related to patient or tumour characteristics. The presence of DTCs was not a prognostic factor for DDFS (IF: hazards ratio [HR], 2.2; 95% confidence interval [CI], 0.63-2.2; p = 0.60; IC: HR, 0.84; 95% CI, 0.09-8.1; p = 0.88). Significant prognostic factors were lymph node metastases, oestrogen receptor positivity, Nottingham histological grade, and tumour size using Cox univariate analysis. The analyses were positive for epithelial cells in bone marrow from adult healthy donors in 19 (25%) samples. Conclusions: The detection of DTCs in bone marrow in primary breast cancer was previously shown to be a predictor of poor prognosis. We were not able to confirm these results in a prospective cohort including unselected patients before the standard procedure was established. Future studies with a standardised patient protocol and improved technique for isolating and detecting DTCs may reveal the clinical applications of DTC detection in patients with micrometastases in the bone marrow.
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| 11. |
- Ferrandis, Maria-José, et al.
(författare)
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Ruling out cardiac failure : Cost-benefit analysis of a sequential testing strategy with NT-proBNP before echocardiography
- 2013
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Ingår i: Upsala Journal of Medical Sciences. - : Informa Healthcare. - 0300-9734 .- 2000-1967. ; 118:2, s. 75-79
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To estimate the possible economic benefit of a sequential testing strategy with NT-proBNP to reduce the number of echocardiographies.Methods. Retrospective study in a third-party payer perspective. The costs were calculated from three Swedish counties: Blekinge, Östergötland, and Uppland. Two cut-off levels of NT-proBNP were used: 400 and 300 pg/mL. The cost-effectiveness of the testing strategy was estimated through the short-term cost avoidance and reduction in demand for echocardiographies.Results. The estimated costs for NT-proBNP tests and echocardiographies per county were reduced by 33%–36% with the 400 pg/mL cut-off and by 28%–29% with the 300 pg/mL cut-off. This corresponded to a yearly cost reduction of approximately €2–5 million per million inhabitants in these counties.Conclusion. The use of NT-proBNP as a screening test could substantially reduce the number of echocardiographies in the diagnostic work-up of patients with suspected cardiac failure, as well as the associated costs.
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| 12. |
- Förnvik, Daniel, et al.
(författare)
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No evidence for shedding of circulating tumor cells to the peripheral venous blood as a result of mammographic breast compression.
- 2013
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 141:2, s. 187-195
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Tidskriftsartikel (refereegranskat)abstract
- This pilot study aimed to investigate whether mammographic compression procedures might cause shedding of tumor cells into the circulatory system as reflected by circulating tumor cell (CTC) count in peripheral venous blood samples. From March to October 2012, 24 subjects with strong suspicion of breast malignancy were included in the study. Peripheral blood samples were acquired before and after mammography. Enumeration of CTCs in the blood samples was performed using the CellSearch(®) system. The pressure distribution over the tumor-containing breast was measured using thin pressure sensors. The median age was 66.5 years (range, 51-87 years). In 22 of the 24 subjects, breast cancer was subsequently confirmed. The difference between the average mean tumor pressure 6.8 ± 5.3 kPa (range, 1.0-22.5 kPa) and the average mean breast pressure 3.4 ± 1.6 kPa (range, 1.5-7.1 kPa) was statistically significant (p < 0.001), confirming that there was increased pressure over the tumor. The median pathological tumor size was 19 mm (range, 9-30 mm). Four subjects (17 %) were CTC positive before compression and two of these (8 %) were also CTC positive after compression. A total of seven CTCs were isolated with a mean size of 8 × 6 μm(2) (range of the longest diameter, 5-12 μm). The study supports the view that mammography is a safe procedure from the point of view of tumor cell shedding to the peripheral blood.
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| 13. |
- Grabau, Dorthe, et al.
(författare)
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Analysis of sentinel node biopsy - a single-institution experience supporting the use of serial sectioning and immunohistochemistry for detection of micrometastases by comparing four different histopathological laboratory protocols.
- 2011
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Ingår i: Histopathology. - : Wiley. - 0309-0167. ; 59, s. 129-138
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Tidskriftsartikel (refereegranskat)abstract
- Histopathology Analysis of sentinel node biopsy - a single-institution experience supporting the use of serial sectioning and immunohistochemistry for detection of micrometastases by comparing four different histopathological laboratory protocols Aims: Detecting micrometastases (>0.2 and ≤2 mm/>200 cells) and isolated tumour cells (ITCs; ≤0.2 mm/<200 cells) is important for staging of breast cancer patients. The aim of this study was to systematically compare several laboratory protocols used to detect metastases after initial intraoperative frozen section examination. Methods and results: Four different protocols for the work-up of sentinel lymph nodes (SLNs) after frozen sectioning were applied in the routine diagnostic process from 2001 to 2009. In addition, team-work with a limited number of laboratory technicians and pathologists handling SLNs was introduced in 2008. The present study shows that there were, overall, significantly more node-positive patients in the period when team-work and intensive step sections including immunohistochemistry (IHC) were used (P = 0.01). This resulted in 13% more patients being found to have ITCs and micrometastases than in a time period when only step sections were performed. No increase in the number of false-negative frozen sections was seen. Conclusions: Future guidelines for pathological work-up of sentinel nodes in women with breast cancer might include team-work and IHC if frozen sections are used intraoperatively.
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| 14. |
- Grabau, Dorthe, et al.
(författare)
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Completion axillary dissection can safely be omitted in screen detected breast cancer patients with micrometastases. A decade's experience from a single institution.
- 2013
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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 1532-2157 .- 0748-7983. ; 39:6, s. 601-607
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The need for completion axillary lymph node dissection (ALND) in breast cancer patients with micrometastases in the sentinel nodes (SNs) is controversial. The aim of this retrospective observational study is to determine if the method of detection of early breast cancer is predictive for additional positive nodes in patients with micrometastases in the SNs. METHODS: Between 2001 and 2011 a total of 1993 women with primary unilateral breast cancer had surgery at Skåne University Hospital, Lund. Of 1993 patients, 1458 had an SN biopsy and nearly all patients with micro- and macrometastases had ALND. RESULTS: Micrometastases defined as >0.2 mm/>200 cells and ≤2.0 mm were found in 62 of 757 screen-detected patients and in 81 of 701 patients with symptomatic breast cancer. Only 3 of the screen-detected patients with micrometastases, all with tumour size >15 mm (range 18-39 mm), had metastases in the completion ALND whereas this was found in 18 of the symptomatic patients with micrometastases (p = 0.01), (tumour size, range 10-30 mm). Logistic regression analysis adjusted for method of detection, tumour size and histological grade showed 5 times higher odds for further metastases in ALND in patients with symptomatic presentation vs. screen-detected breast cancer. CONCLUSION: Despite the small number of patients with micrometastases in this large cohort of breast cancer patients, these results support the contention that completion ALND can safely be omitted in screen-detected breast cancer patients with micrometastases in the SNs.
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| 15. |
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| 16. |
- Hultqvist, Viktor, et al.
(författare)
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High seroprevalence of SARS-CoV-2 antibodies in healthcare workers in COVID-19 wards indicates an occupational hazard-a prospective cohort study during the first year of the COVID-19 pandemic in Kalmar County, Sweden
- 2023
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : WILEY. - 0903-4641 .- 1600-0463. ; 131:9, s. 491-497
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is to report the seroprevalence of SARS-CoV-2 antibodies in healthcare workers with various risk of occupational exposure in Kalmar County, Sweden, during the first year of the coronavirus disease 2019 (COVID-19) pandemic. We performed SARS-CoV-2 antibody measurements at four time points, from May 2020 to May 2021, in 401 healthcare workers (HCW) at seven hospital wards and two residential care facilities, with different risk of SARS-CoV-2 exposure. Overall, the prevalence of SARS-CoV-2 antibodies in HCW in Kalmar County was high compared to similar studies from other countries and increased from May 2020 to May 2021. Initially, 14% of the participants were SARS-CoV-2 seropositive. This number increased to 18% in September and 21% in December 2020. In May 2021, the prevalence of antibodies to nucleocapsid antigen had increased to 28%, while antibodies to spike protein had increased to 95% due to vaccination. A large variation in seroprevalence between different wards was detected and HCW in a COVID-19 designated ward had significantly higher seroprevalence than HCW working in wards without COVID-19 patients, with a risk ratio of 7.28, (95% CI 2.38-22.33) in May 2020. Our findings suggest a relationship between occupational COVID-19 exposure and seropositivity which implies that efficient hygiene routines for health- and social care workers are essential to avoid that COVID-19 care will constitute an occupational hazard.
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| 17. |
- Landberg, Eva, 1966-, et al.
(författare)
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Detection of molecular variants of prolactin in human serum, evaluation of a method based on ultrafiltration
- 2007
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Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981 .- 1873-3492. ; 376:1-2, s. 220-225
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn human blood, there are several molecular variants of prolactin with different biological effects. There is a need for new methods to detect and quantify these variants in order to fully understand the pathophysiological role of prolactin.MethodsA method based on ultrafiltration was optimized, validated and compared to PEG precipitation. Serum samples from 84 patients were analyzed before and after pre treatment on two immunoassays, Elecsys (Roche) and Access (Beckman). Protein G precipitation was used to confirm presence of macroprolactin.ResultsThe recovery of prolactin after ultrafiltration was lower than after PEG precipitation. A limit of 40% recovery after PEG precipitation corresponded to 27% recovery after ultrafiltration. Using these limits there were total agreement regarding detection of macroprolactin (rs = 0.96). In contrast, recovery of prolactin in samples without macroprolactin showed a considerable disagreement between ultrafiltration and PEG precipitation (rs = 0.48). Within-run CV was 4% for the ultrafiltration method. The correlation coefficient (r) between the immunoassays was 0.96 after ultrafiltration.ConclusionsUltrafiltration can be used to compare different prolactin immunoassays and to detect macroprolactin in assays with interference from PEG. For samples without macroprolactin ultrafiltration may give additional information reflecting individual variations of other molecular variants of prolactin.
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| 18. |
- Liljeblad, Mathias, et al.
(författare)
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A Lectin Immunosensor Technique for Determination of α1-Acid Glycoprotein Fucosylation
- 2001
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 288:2, s. 216-224
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Tidskriftsartikel (refereegranskat)abstract
- The fucosylation of α1-acid glycoprotein (AGP), an acute-phase protein, is known to change in association with inflammatory diseases. Thus, fucosylation of AGP could be a potential diagnostic or prognostic marker. The change in fucosylation has previously been investigated using crossed affinoimmunoelectrophoresis, high-pH anion-exchange chromatography, and lectin ELISA. This study describes a surface plasmon resonance-based affinity biosensor assay for quantification of the fucosylation of AGP. Diluted EDTA plasma or serum was injected directly in a BIACORE 2000 biosensor. AGP was captured on the sensor surface using immobilized antibodies and a fucose-binding lectin from Aleuria aurentia was then used for the detection of fucosylation. The feature of the biosensor makes it possible to determine both the amount of bound AGP and the amount of bound lectin. Using a calibration curve it was possible to obtain a fucosylation ratio that was independent of AGP concentration. The assay was validated against a lectin ELISA and used to follow inflammation in patients with severe burns.
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| 19. |
- Narbe, Ulrik, et al.
(författare)
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AIB1 is a new putative prognostic biomarker in the luminal A and B-like (HER2-negative) classification of invasive lobular carcinoma
- 2017
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Ingår i: ; , s. 1-07
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Konferensbidrag (refereegranskat)abstract
- Body: Background: Estrogen receptor (ER) positive HER2-negative breast cancer comprises 75–80% of all breast cancer. Thisfraction is even higher (>90%) in invasive lobular carcinoma (ILC). According to the St Gallen surrogate definitions of the intrinsicsubtypes, Ki67 and progesterone receptor (PgR) are used to classify these tumors as luminal A- and luminal B-like(HER2-negative). These guidelines are based on information derived from patient materials with mixed histological types, wherethe vast majority of the patients have invasive ductal carcinoma. The `luminal-like classification´ together with histological grade,tumor size and lymph node status is widely used in the clinic for prognostication. The aim of the present study was to investigateif the same markers are applicable for ILC, and furthermore, if additional biomarkers involved in the endocrine signaling system,e.g. Amplified in breast cancer 1 (AIB1) and the putative G protein-coupled estrogen receptor (GPER), might providecomplementary prognostic information.Patients: Two hundred and thirty-three (N = 233) well-characterized patients with primary ILC, diagnosed between 1980 and1991 were included. Forty-two percent of the patients received adjuvant endocrine treatment and 2 % received adjuvantchemotherapy. All biomarkers were analyzed immunohistochemically on tissue microarray, whereas histological grade wasevaluated on whole sections according to Elston and Ellis (NHG). The primary endpoint was breast cancer mortality (BCM).Results: In univariable analyses with 10-year follow-up, Ki67 (high vs. low), NHG (3 vs. 1+2) and AIB1 (high vs. low) weresignificantly associated to BCM (Hazard Ratio: 4.7, 95% CI: 2.1–10.4, p 95% CI: 1.4–7.2, p = 0.005 respectively), whereas PgR (respectively). Essentially the same effect was seen after multivariable adjustment for lymph node status (+ vs. -), tumor size (>20mm vs. according to St Gallen surrogate definitions did not show significant prognostic differences between the two groups (p = 0.12).Patients with AIB1) had a 10-year BCM of 4.2% (95% CI: 1.4–12%). This group constituted 34% of the patients included in the present study.Conclusions: In contrast to other previous studies, where breast cancers of mixed histological types were included, PgR was notsignificantly associated to prognosis in the ER-positive HER2-negative subgroup in the present study, consisting only of ILC. Theprognostic role of PgR and the clinical usefulness of the luminal A and B-like (HER2-negative) classification (using only Ki67 andPgR) in ILC is still to be further investigated. The prognostic importance of Ki67 and NHG in this subgroup was, however,confirmed also in ILC, and AIB1 might be a new putative prognostic factor. By combining Ki67, NHG, and AIB1, together withlymph node status and tumor size, a group of patients with an excellent prognosis could be identified.
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| 20. |
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| 21. |
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| 22. |
- Narbe, U., et al.
(författare)
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St Gallen 2019 guidelines understage the axilla in lobular breast cancer : a population-based study
- 2021
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 108:12, s. 1465-1473
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The St Gallen 2019 guidelines for primary therapy of early breast cancer recommend omission of completion axillary lymph node dissection (cALND), regardless of histological type, in patients with one or two sentinel lymph node (SLN) metastases. Concurrently, adjuvant chemotherapy is endorsed for luminal A-like disease with four or more axillary lymph node (ALN) metastases. The aim of this study was to estimate the proportion of patients with invasive lobular cancer (ILC) versus invasive ductal cancer of no special type (NST) with one or two SLN metastases for whom cALND would have led to a recommendation for adjuvant chemotherapy. METHODS: Patients with ILC and NST who had surgery between 2014 and 2017 were identified in the National Breast Cancer Register of Sweden. After exclusion of patients with incongruent or missing data, those who fulfilled the St Gallen 2019 criteria for cALND omission were included in the population-based study cohort. RESULTS: Some 1886 patients in total were included in the study, 329 with ILC and 1507 with NST. Patients with ILC had a higher metastatic nodal burden and were more likely to have a luminal A-like subtype than those with NST. The prevalence of at least four ALN metastases was higher in ILC (31.0 per cent) than NST (14.9 per cent), corresponding to an adjusted odds ratio of 2.26 (95 per cent c.i. 1.59 to 3.21). Luminal A-like breast cancers with four or more ALN metastases were over-represented in ILC compared with NST, 52 of 281 (18.5 per cent) versus 43 of 1299 (3.3 per cent) (P < 0.001). CONCLUSION: Patients with ILC more often have luminal A-like breast cancer with at least four nodal metastases. Omission of cALND in patients with luminal A-like invasive lobular cancer and one or two SLN metastases warrants future attention as there is a risk of nodal understaging and undertreatment in one-fifth of patients.
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| 23. |
- Narbe, Ulrik, et al.
(författare)
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The estrogen receptor coactivator AIB1 is a new putative prognostic biomarker in ER-positive/HER2-negative invasive lobular carcinoma of the breast
- 2019
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 175:2, s. 305-316
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: According to the 2017 St Gallen surrogate definitions of the intrinsic subtypes, Ki67, progesterone receptor (PR) and Nottingham histological grade (NHG) are used for prognostic classification of estrogen receptor (ER) positive/HER2-negative breast cancer into luminal A- or luminal B-like. The aim of the present study was to investigate if additional biomarkers, related to endocrine signaling pathways, e.g., amplified in breast cancer 1 (AIB1), androgen receptor (AR), and G protein-coupled estrogen receptor (GPER), can provide complementary prognostic information in a subset of ER-positive/HER-negative invasive lobular carcinoma (ILC). Methods: Biomarkers from 224 patients were analyzed immunohistochemically on tissue microarray. The primary endpoint was breast cancer mortality (BCM), analyzed with 10- and 25-year follow-up (FU). In addition, the prognostic value of gene expression data for these biomarkers was analyzed in three publicly available ILC datasets. Results: AIB1 (high vs. low) was associated to BCM in multivariable analysis (adjusted for age, tumor size, nodal status, NHG, Ki67, luminal-like classification, and adjuvant systemic therapy) with 10-year FU (HR 6.8, 95% CI 2.3–20, P = 0.001) and 25-year FU (HR 3.0, 95% CI 1.1–7.8, P = 0.03). The evidence of a prognostic effect of AIB1 could be confirmed by linking gene expression data to outcome in independent publicly available ILC datasets. AR and GPER were neither associated to BCM with 10-year nor with 25-year FU (P > 0.33). Furthermore, Ki67 and NHG were prognostic for BCM at both 10-year and 25-year FU, whereas PR was not. Conclusions: AIB1 is a new putative prognostic biomarker in ER-positive/HER2-negative ILC.
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| 24. |
- Nasr, Patrik, et al.
(författare)
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A rapid, non-invasive, clinical surveillance for CachExia, sarcopenia, portal hypertension, and hepatocellular carcinoma in end-stage liver disease : the ACCESS-ESLD study protocol
- 2023
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Ingår i: BMC Gastroenterology. - : BioMed Central (BMC). - 1471-230X. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Liver cirrhosis, the advanced stage of many chronic liver diseases, is associated with escalated risks of liver-related complications like decompensation and hepatocellular carcinoma (HCC). Morbidity and mortality in cirrhosis patients are linked to portal hypertension, sarcopenia, and hepatocellular carcinoma. Although conventional cirrhosis management centered on treating complications, contemporary approaches prioritize preemptive measures. This study aims to formulate novel blood- and imaging-centric methodologies for monitoring liver cirrhosis patients.METHODS: In this prospective study, 150 liver cirrhosis patients will be enrolled from three Swedish liver clinics. Their conditions will be assessed through extensive blood-based markers and magnetic resonance imaging (MRI). The MRI protocol encompasses body composition profile with Muscle Assement Score, portal flow assessment, magnet resonance elastography, and a abbreviated MRI for HCC screening. Evaluation of lifestyle, muscular strength, physical performance, body composition, and quality of life will be conducted. Additionally, DNA, serum, and plasma biobanking will facilitate future investigations.DISCUSSION: The anticipated outcomes involve the identification and validation of non-invasive blood- and imaging-oriented biomarkers, enhancing the care paradigm for liver cirrhosis patients. Notably, the temporal evolution of these biomarkers will be crucial for understanding dynamic changes.TRIAL REGISTRATION: Clinicaltrials.gov, registration identifier NCT05502198. Registered on 16 August 2022. Link: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05502198 .
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| 25. |
- Nilsson, Per H., 1980-, et al.
(författare)
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Quartz Crystal Microbalance Platform for SARS-CoV-2 Immuno-Diagnostics
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:23
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Tidskriftsartikel (refereegranskat)abstract
- Rapid and accurate serological analysis of SARS-CoV-2 antibodies is important for assessing immune protection from vaccination or infection of individuals and for projecting virus spread within a population. The quartz crystal microbalance (QCM) is a label-free flow-based sensor platform that offers an opportunity to detect the binding of a fluid-phase ligand to an immobilized target molecule in real time. A QCM-based assay was developed for the detection of SARS-CoV-2 antibody binding and evaluated for assay reproducibility. The assay was cross-compared to the Roche electrochemiluminescence assay (ECLIA) Elecsys (R) Anti-SARS-CoV-2 serology test kit and YHLO's chemiluminescence immunoassay (CLIA). The day-to-day reproducibility of the assay had a correlation of r(2) = 0.99, p < 0.001. The assay linearity was r(2) = 0.96, p < 0.001, for dilution in both serum and buffer. In the cross-comparison analysis of 119 human serum samples, 59 were positive in the Roche, 52 in the YHLO, and 48 in the QCM immunoassay. Despite differences in the detection method and antigen used for antibody capture, there was good coherence between the assays, 80-100% for positive and 96-100% for negative test results. In summation, the QCM-based SARS-CoV-2 IgG immunoassay showed high reproducibility and linearity, along with good coherence with the ELISA-based assays. Still, factors including antibody titer and antigen-binding affinity may differentially affect the various assays' responses.
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| 26. |
- Olsson, Eleonor, et al.
(författare)
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Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease.
- 2015
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Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 7:8, s. 1034-1047
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Tidskriftsartikel (refereegranskat)abstract
- Metastatic breast cancer is usually diagnosed after becoming symptomatic, at which point it is rarely curable. Cell-free circulating tumor DNA (ctDNA) contains tumor-specific chromosomal rearrangements that may be interrogated in blood plasma. We evaluated serial monitoring of ctDNA for earlier detection of metastasis in a retrospective study of 20 patients diagnosed with primary breast cancer and long follow-up. Using an approach combining low-coverage whole-genome sequencing of primary tumors and quantification of tumor-specific rearrangements in plasma by droplet digital PCR, we identify for the first time that ctDNA monitoring is highly accurate for postsurgical discrimination between patients with (93%) and without (100%) eventual clinically detected recurrence. ctDNA-based detection preceded clinical detection of metastasis in 86% of patients with an average lead time of 11 months (range 0-37 months), whereas patients with long-term disease-free survival had undetectable ctDNA postoperatively. ctDNA quantity was predictive of poor survival. These findings establish the rationale for larger validation studies in early breast cancer to evaluate ctDNA as a monitoring tool for early metastasis detection, therapy modification, and to aid in avoidance of overtreatment.
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| 27. |
- Olsson, H, et al.
(författare)
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Proliferation of the breast epithelium in relation to menstrual cycle phase, hormonal use, and reproductive factors
- 1996
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Ingår i: Breast Cancer Research and Treatment. - 1573-7217. ; 40:2, s. 187-196
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Tidskriftsartikel (refereegranskat)abstract
- The proliferative rate in normal breast epithelium from 58 women undergoing reduction mammoplastics was studied using the formalin resistant antibody Ki-S5, and related to age at operation, menstrual cycle phase, family history of breast cancer, height and weight, parity, and hormonal use. The breast tissue from women operated on in the luteal menstrual cycle phase (day 15-28 among oral contraceptive (OC) users) had significantly higher proliferative rate than breast tissue removed from women in the follicular phase (day 1-14) (p = 0.01). Among women presently exposed to hormones, those with a positive family history of breast cancer among first and second degree relatives had significantly higher values than cases without such history (p = 0.02). Weight was not significantly related to proliferation rate, while a short height was associated with a significantly higher proliferation rate (p = 0.04). Women who used OCs before the first full-term pregnancy (FFTP) had a significantly higher proliferation rate compared with never users or late users (p = 0.04). No significant difference was seen between parous versus nulliparous women. The results from the univariate analysis persisted in multivariate models. An especially high proliferation rate was seen in young women with both a positive family history and present hormonal use (p = 0.001). Overall, it was found that young women had a non-significantly higher proliferation rate than older women (p = 0.10). Due to small sample size, these results must be regarded as preliminary, especially in the subgroup analyses.
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| 28. |
- Oltmanns, Carlos, et al.
(författare)
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Elevation of S2-bound a1-acid glycoprotein is associated with chronic hepatitis C virus infection and hepatocellular carcinoma
- 2024
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Ingår i: Journal of Viral Hepatitis. - : WILEY. - 1352-0504 .- 1365-2893.
-
Tidskriftsartikel (refereegranskat)abstract
- There is an urgent need for new high-quality markers for the early detection of hepatocellular carcinoma (HCC). angstrom strom et al. suggested that S2-bound alpha 1-acid glycoprotein (AGP) might be a promising marker. Consequently, we evaluated the predictive advantage of S2-bound AGP in the early detection of HCC. In a retrospective case-control study of patients chronically infected with hepatitis C virus (HCV) and treated with direct-acting antiviral agents (n = 93), we measured S2-bound AGP using the HepaCheC (R) ELISA kit (Glycobond AB, Linkoping, SE) at the start of treatment, end of treatment and follow-up (maximum: 78 months). Patients were retrospectively propensity score matched (1:2). Thirty-one patients chronically infected with HCV developed HCC after a sustained virological response, while 62 did not. In addition, samples of patients with chronic hepatitis B virus infection, metabolic dysfunction-associated steatotic liver disease and HCC of different etiologies were analysed. S2-bound AGP elevation in HCC patients was confirmed. However, we did not observe a predictive advantage of S2-bound AGP for the early detection of HCC during treatment and follow-up. Interestingly, S2-bound AGP levels correlated with aspartate aminotransferase (rho = .56, p = 9.5x10-15) and liver elastography (rho = .67, p = 2.2x10-16). Of note, S2-bound AGP decreased in patients chronically infected with HCV after treatment-induced HCV clearance. Fucosylated S2-bound AGP levels were elevated in patients with chronic HCV and HCC. The potential role of S2-bound AGP as a novel tumour marker requires further investigation.
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| 29. |
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| 30. |
- Romero, Quinci, et al.
(författare)
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Ki67 proliferation in core biopsies versus surgical samples - a model for neo-adjuvant breast cancer studies
- 2011
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: An increasing number of neo-adjuvant breast cancer studies are being conducted and a novel model for tumor biological studies, the "window-of-opportunity" model, has revealed several advantages. Change in tumor cell proliferation, estimated by Ki67-expression in pre-therapeutic core biopsies versus post-therapeutic surgical samples is often the primary end-point. The aim of the present study was to investigate potential differences in proliferation scores between core biopsies and surgical samples when patients have not received any intervening anti-cancer treatment. Also, a lack of consensus concerning Ki67 assessment may raise problems in the comparison of neo-adjuvant studies. Thus, the secondary aim was to present a novel model for Ki67 assessment. Methods: Fifty consecutive breast cancer cases with both a core biopsy and a surgical sample available, without intervening neo-adjuvant therapy, were collected and tumor proliferation (Ki67, MIB1 antibody) was assessed immunohistochemically. A theoretical model for the assessment of Ki67 was constructed based on sequential testing of the null hypothesis 20% Ki67-positive cells versus the two-sided alternative more or less than 20% positive cells.. Results: Assessment of Ki67 in 200 tumor cells showed an absolute average proliferation difference of 3.9% between core biopsies and surgical samples (p = 0.046, paired t-test) with the core biopsies being the more proliferative sample type. A corresponding analysis on the log-scale showed the average relative decrease from the biopsy to the surgical specimen to be 19% (p = 0.063, paired t-test on the log-scale). The difference was significant when using the more robust Wilcoxon matched-pairs signed-ranks test (p = 0.029). After dichotomization at 20%, 12 of the 50 sample pairs had discrepant proliferation status, 10 showed high Ki67 in the core biopsy compared to two in the surgical specimen (p = 0.039, McNemar's test). None of the corresponding results for 1000 tumor cells were significant - average absolute difference 2.2% and geometric mean of the ratios 0.85 (p = 0.19 and p = 0.18, respectively, paired t-tests, p = 0.057, Wilcoxon's test) and an equal number of discordant cases after dichotomization. Comparing proliferation values for the initial 200 versus the final 800 cancer cells showed significant absolute differences for both core biopsies and surgical samples 5.3% and 3.2%, respectively (p < 0.0001, paired t-test). Conclusions: A significant difference between core biopsy and surgical sample proliferation values was observed despite no intervening therapy. Future neo-adjuvant breast cancer studies may have to take this into consideration.
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| 31. |
- Rydén, Ingvar
(författare)
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Clinical studies on α1-acid glycoprotein glycosylation - with focus on fucose
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- α1-Acid glycoprotein (AGP, orosomucoid) is a heavily glycosylated protein found in blood plasma in all humans. AGP is one of the major acute phase proteins, and its concentration is frequently measured in clinical laboratories as a marker for inflammatory disease. For several years it has been known that the glycosylation of AGP is altered in different physiological and pathological conditions. However, methods for analysis of the glycosylation changes have been time-consuming and at best semi-quantitative. Consequently, clinical studies have been limited to small numbers of patients, and have not confirmed the usefulness of routine analysis of A GP glycosylation in clinical investigations. In the present study, two major issues were addressed: the need for new methods that would allow quantitative measurements of specific glycosylation changes, and the need for clinical studies with sufficient numbers of study subjects to evaluate the potential advantages and drawbacks of analyzing AGP glycosylation in a clinical laboratory.High-pH anion-exchange chromatography (HPAEC) separates oligosaccharides with high resolution and was used to study N-linked oligosaccharides (N-glycans) released from AGP obtained from patients with different inflannnatory conditions. We showed that HPAEC is a very reproducible and useful method for profiling of AGP N-glycans, providing infmmation on N-glycan sialylation and fucosylation simultaneously. In particular, we found a typical pattern with a sharp increase in fucosylated, tri-sialylated N-glycans in patients with rheumatoid arthritis (RA). The laborious preparation of samples prior to analysis is a drawback for the use ofHPAEC as a routine method in a clinical laboratory. However, HPAEC has a great potential as a tool for profiling AGP glycosylation in different pathologic conditions, and it was used as a reference for the development of other analytical methods. In order to analyze a larger number of patient samples, we developed a lectin immunoassay using a fucose specific lectin from the A!euria aurantia mushroom. The lectin immunoassay was well suited for use in a clinical laboratory and was used to study AGP fucosylation in patients with severe bmns, recent onset rheumatoid arthritis (RA), liver disease, and alcohol abuse. In a time study of 10 patients with severe bums, changes in AGP fucosylation showed a typical pattern, without con-elation to acute phase protein synthesis. This confirmed the results of previous studies indicating that glycosylation is regulated independently from protein synthesis in the acute phase response.We studied AGP fucosylation in 131 patients with recent onset RA. In these patients, AGP fucosy lation was increased, but the con elation with disease activity according to a clinical score (DAS28) was not superior to previously used biochemical markers of inflammation. However, in men with RA who had increased AGP fucosylation at the time of diagnosis, the degree of fucosylation conelated to disease progression during the first year following diagnosis. It remains to be confumed whether AGP fucosylation can provide prognostic information for this patient category.When we studied AGP fucosylation in 261 patients investigated for suspected liver disease, fucosylation was heavily increased in patients with histopathological signs of liver cirrhosis. In addition, AGP fucosylation coiTelated to the severity of disease. By calculating an AGP fucosylation index (AGP-Fl, AGP fucosylation/AGP serum concentration), a high diagnostic accuracy was found for liver cinhosis. Even in patients with cinhosis without any symptoms related to liver disease, AGP-FI was significantly higher than in patients with steatosis or chronic hepatitis. When compared with other biochemical markers of liver disease, AGP fucosylation was among the most specific in discriminating liver cin·hosis, and may be useful in clinical investigations of liver disease.We also studied AGP fucosylation in 21 patients with heavy alcohol abuse admitted to hospital for detoxification. fu the 16 male patients that were studied, AGP fucosylation was significantly increased compared to healthy controls. Furthermore, in these men there was a significant con·elation between AGP fucosylation and other biochemical markers previously used for detection of liver cirrhosis. This study should be extended with a larger number of patients, and histopathological examination following liver biopsy, in order to confirm the value of increased AGP fucosylation as an early marker for cirrhosis in this patient categmy.
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| 32. |
- Rydén, Ingvar, et al.
(författare)
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Diagnostic accuracy of a1-acid glycoprotein fucosylation for liver cirrhosis in patients undergoing hepatic biopsy
- 2002
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Ingår i: Clinical Chemistry. - 0009-9147 .- 1530-8561. ; 48:12, s. 2195-2201
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Tidskriftsartikel (refereegranskat)abstract
- Background: Increased fucosylation of serum glycoproteins has previously been reported in patients with liver disease. We analyzed a1-acid glycoprotein (AGP) fucosylation in serum samples from patients investigated for suspected liver disease to evaluate its value as a biochemical marker for liver cirrhosis. Methods: We used a novel lectin immunoassay adapted to the AutoDELFIA system to analyze AGP fucosylation in 261 consecutive patients admitted for liver biopsy at Malm÷ University Hospital in Southern Sweden. The results were compared with histopathologic findings. In addition, AGP fucosylation was compared with other biochemical markers described as useful in the diagnosis of liver cirrhosis. The biochemical markers were compared by ROC curve analysis. Results: AGP fucosylation was significantly (P <0.05) higher in patients with liver cirrhosis (n = 65) than in healthy controls (n = 72), patients with normal histology (n = 29), patients with steatosis only (n = 38), patients with viral or chronic hepatitis without cirrhosis (n = 71), and patients with other liver diseases without histologic signs of cirrhosis (n = 58). By calculating the AGP fucosylation index (AGP-FI = AGP fucosylation/AGP serum concentration), we obtained a high diagnostic accuracy. The areas under the ROC curves for AGP-FI were 0.83 and 0.74 for men and women, respectively, compared with 0.82 for hyaluronic acid and 0.77 for the aspartate aminotransferase/alanine aminotransferase ratio in both men and women. Conclusions: AGP fucosylation appears to be useful in identifying patients with liver cirrhosis among patients investigated for liver disease. The lectin immunoassay showed satisfactory reproducibility and is suitable for routine use in a clinical laboratory.
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| 33. |
- Rydén, Ingvar, et al.
(författare)
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Fucosylation of α1-acid glycoprotein (orosomucoid) compared with traditional biochemical markers of inflammation in recent onset rheumatoid arthritis
- 2002
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Ingår i: Clinica Chimica Acta. - 0009-8981 .- 1873-3492. ; 317:1-2, s. 221-229
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fucosylation of α1-acid glycoprotein (AGP, orosomucoid) has previously been found to be increased in patients with rheumatoid arthritis. Furthermore, the degree of fucosylation has been suggested to reflect disease activity. Therefore, we investigated the fucosylation of AGP in 131 patients (96 women and 35 men) with recent onset rheumatoid arthritis (RA). We compared the results with traditional biochemical markers of inflammation, i.e. plasma concentrations of AGP (P-AGP), and C-reactive protein (P-CRP).Methods: AGP fucosylation measured with a novel lectin enzyme-linked immunosorbent assay (ELISA) was compared with a disease activity score (DAS28) and its components, and with P-AGP, and P-CRP at the time of diagnosis, and at a follow-up visit 1 year later.Results: Both men and women with RA had increased AGP fucosylation compared to healthy individuals. We found a weak correlation between AGP fucosylation and DAS28 only in men. In men with initially increased AGP fucosylation, the level of fucosylation correlated with the change in DAS28 during the first year following diagnosis. Conclusion: We conclude that AGP fucosylation is not superior to traditional markers of disease activity in RA. However, AGP fucosylation may give some additional information to traditional biochemical markers on the disease progression in men.
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| 34. |
- Rydén, Ingvar, et al.
(författare)
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Glycosylation of α1-acid glycoprotein in inflammatory disease : analysis by high-pH anion-exchange chromatography and concanavalin A crossed affinity immunoelectrophoresis
- 1997
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Ingår i: Glycoconjugate Journal. - 0282-0080 .- 1573-4986. ; 14:4, s. 481-488
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Tidskriftsartikel (refereegranskat)abstract
- High-pH anion-exchange chromatography with pulsed amperometric detection is a highly sensitive technique that can be used for detecting changes in sialylation and fucosylation, as well as different branching patterns of N-linked oligosaccharides in glycoproteins. We examined the N-glycans of α1-acid glycoprotein obtained from twelve patients with various inflammatory conditions with this technique, as well as traditional concanavalin A crossed affinity immunoelectrophoresis. We found the chromatographic profiles of N-glycans in all patients with rheumatoid arthritis to be very similar, but significantly different from normal controls. N-glycans from patients with ulcerative colitis also showed specific alterations in their chromatographic profiles. However, some heterogeneity was found between these patients, perhaps reflecting changes in glycosylation secondary to certain states of the disease, or to medical treatment. We conclude that this technique is useful for detailed mapping of glycosylation changes in α1-acid glycoprotein in clinical samples, and that it may be used to further increase our knowledge about glycosylation changes in response to inflammatory disease.
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| 35. |
- Rydén, Ingvar, et al.
(författare)
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Increased α1-acid glycoprotein fucosylation in patients with high alcohol consumption
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Changes in glycosylation of senun glycoproteins have been described in different pathologic conditions, and increased fucosylation has previously been reported in patients with liver disease. We analyzed serwn samples from patients admitted to hospital for detoxification of excessive alcohol consumption in order to study α1-acid glycoprotein (AGP) fucosylation and its correlation to other biochemical markers of alcoholism and liver damage.Methods: We used a novel lectin innmmoassay to analyze AGP fucosylation (AGP-F) in a prospective study of 21 consecutive patients admitted for treatment at Linköping University Hospital in the Southeast of Sweden. The results were compared with markers conunonly used for detecting alcoholism and liver cirrhosis, such as carbohydrate deficient transferrin, aminotransferase activity, including aspartate aminotransferase/alanine aminotransferase ratio (AST/ALT), and with hyaluronic acid (HA). In addition, ultrasonography of the liver was performed in 16 of the 21 patients.Results: AGP-F was significantly higher in the male study patients than in normal controls. In addition, in these patients AGP-F correlated to the levels of AST/ALT-ratio and HA No correlation was found between AGP-F and steatosis of the liver, as indicated by ultrasonography, or between AGP-F and CDT.Conclusion: We conclude that AGP-F is increased in men with a high alcohol intake and correlates with AST/ALT ratio and HA, which previously have been found to be indictors of liver cirrhosis. AGP-F should be further evaluated as a potential early indicator ofliver cirrhosis in this patient category.
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| 36. |
- Rydén, Ingvar, et al.
(författare)
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Increased α1-acid glycoprotein fucosylation in patients with liver cirrhosis
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Increased fucosylation of serum glycoproteins has previously been reported in patients with liver disease. We analyzed α1-acid glycoprotein (AGP) fucosylation in serum samples from patients investigated for suspected liver disease, in order to evaluate its value as a biochemical marker for liver cirrhosis.Methods: We used a novel lectin innnunoassay adapted to the Auto-DELFIA system to analyze AGP fucosylation in 261 consecutive patients admitted for liver biopsy at Malmö university hospital in Southern Sweden. The results were compared with histopathological findings. In addition, AGP fucosylation was compared to other biochemical markers described to be useful in the diagnosis of liver cirrhosis. The different biochemical markers were compared by ROC curve analysis.Results: AGP fucosylation was significantly higher in patients with liver cirrhosis (n=65) than in nmmal controls (n=72), patients with normal histology (n=29), patients with steatosis only (n=38), patients with viral or chronic hepatitis without ciiThosis (n=71), and patients with other liver diseases without histological signs of cirrhosis (n=58). By calculating an AGP fucosylation index (AGP-FI = AGP fucosylation/AGP serum concentration), a high diagnostic accuracy was obtained. The area under the curve for AGP-FI was 0.83 and 0.74 for men and women respectively, compared to 0.82 for hyaluronic acid, and 0.77 for AST/ALT ratio in both men and women.Conclusion: We conclude that AGP fucosylation appears to be useful in identifying patients with liver cirrhosis among patients investigated for liver disease. The lectin immunoassay showed satisfactory reproducibility, and is suitable for routine use in a clinical laboratory.
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| 37. |
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| 38. |
- Ryden, Ingvar, et al.
(författare)
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Reference values of thirty-one frequently used laboratory markers for 75-year-old males and females
- 2012
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 117:3, s. 264-272
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Tidskriftsartikel (refereegranskat)abstract
- Background.We have previously reported reference values for common clinical chemistry tests in healthy 70-year-old males and females. We have now repeated this study 5 years later to establish reference values also at the age of 75. It is important to have adequate reference values for elderly patients as biological markers may change over time, and adequate reference values are essential for correct clinical decisions.Methods.We have investigated 31 frequently used laboratory markers in 75-year-old males (n = 354) and females (n = 373) without diabetes. The 2.5 and 97.5 percentiles for these markers were calculated according to the recommendations of the International Federation of Clinical Chemistry.Results. Reference values are reported for 75-year-old males and females for 31 frequently used laboratory markers.Conclusion.There were minor differences between reference intervals calculated with and without individuals with cardiovascular diseases. Several of the reference intervals differed from Scandinavian reference intervals based on younger individuals (Nordic Reference Interval Project).
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| 39. |
- Sandholm, Kerstin
(författare)
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Development and evaluation of immunoassays for complement diagnostics
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Laboratory analyses of human body fluids play an important role in clinical diagnosis. This thesis comprises projects in which various immune assays have been developed and evaluated as complement diagnostics in both plasma and cerebrospinal fluid (CSF). Various methods have been used, such as ELISA, Western blot, flow cytometry, and xMAP technology.In paper 1, we monitored complement parameters in EDTA-plasma and CSF from patients with suspected neuroborreliosis (NB) by using in-house sandwich ELISAs. We found significantly elevated levels of C1q, C4, C3, and C3a in CSF, but not in plasma, suggesting that complement plays a role in the intrathecal immune response in NB.Complement is a main player in early inflammation, and in paper 2, we investigated the role of complement activation in phagocytosis and the release of cytokines and chemokines in response to two clinical isolates: Borrelia afzelii K78 and Borrelia garinii LU59. Our results show that complement activation plays an important role in the initial process of phagocytosis, but not in the subsequent cytokine release that occurs in response to live Borrelia spirochetes. C1q, a valuable biomarker of disease activity in systemic lupus erythematosus (SLE), can be quantitated using a number of different immunochemical techniques.In paper 3, we developed and validated a magnetic bead-based immunoassay for quantifying C1q in EDTA-plasma and CSF. In contrast to soluble immunoprecipitation assays such as nephelometry and turbidimetry, this new assay was not hampered by the interaction between C1q and detecting antibodies. The novel assay was shown to give a clear correlation between nephritis and SLEDAI score in SLE.Warfarin is a commonly used but complicated treatment in patients with thrombosis. It reduces the function of vitamin K-dependent coagulation proteins, including protein S, which is a ligand for C4b-binding protein (C4BP). In paper 4, we demonstrated a decrease in various isoforms of C4BP that resulted in a strong complement activation in patients treated with warfarin, but not in patients treated with other anticoagulants.Taken together, the results from the papers included in this thesis stress the importance of validated assays with high sensitivity and specificity in enabling accurate diagnosis in patients with various inflammatory diseases.
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| 40. |
- Svanberg, Ingvar, et al.
(författare)
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Kabblekans namn
- 2012
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Ingår i: Svensk Botanisk Tidskrift. - 0039-646X. ; :106, s. 321-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 41. |
- Wallengren, Ola, et al.
(författare)
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Comparison of the 2010 and 2019 diagnostic criteria for sarcopenia by the European Working Group on Sarcopenia in Older People (EWGSOP) in two cohorts of Swedish older adults.
- 2021
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Ingår i: BMC geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- The operational definition of sarcopenia has been updated (EWGSOP2) and apply different cut-off points compared to previous criteria (EWGSOP1). Therefore, we aim to compare the sarcopenia prevalence and the association with mortality and dependence in activities of daily living using the 2010 (EWGSOP1 and 2019 (EWGSOP2 operational definition, applying cut-offs at two levels using T-scores.Two birth cohorts, 70 and 85-years-old (n=884 and n=157, respectively), were assessed cross-sectionally (57% women). Low grip strength, low muscle mass and slow gait speed were defined below -2.0 and-2.5 SD from a young reference population (T-score). Muscle mass was defined as appendicular lean soft tissue index by DXA. The EWGSOP1 and EWGSOP2 were applied and compared with McNemar tests and Cohen's kappa. All-cause mortality was analyzed with the Cox-proportional hazard model.Sarcopenia prevalence was 1.4-7.8% in 70-year-olds and 42-62% in 85years-old's, depending on diagnostic criteria. Overall, the prevalence of sarcopenia was 0.9-1.0 percentage points lower using the EWGSOP2 compared to EWGSOP1 when applying uniform T-score cut-offs (P<0.005). The prevalence was doubled (15.0 vs. 7.5%) using the -2.0 vs. -2.5T-scores with EWGSOP2 in the whole sample. The increase in prevalence when changing the cut-offs was 5.7% (P<0.001) in the 70-year-olds and 17.8% (P<0.001) in the 85-year-olds (EWGSP2). Sarcopenia with cut-offs at -2.5T-score was associated with increased mortality (hazard ratio 2.4-2.8, P<0.05) but not at T-score-2.0.The prevalence of sarcopenia was higher in 85-year-olds compared to 70-year-olds. Overall, the differences between the EWGSOP1 and EWGSOP2 classifications are small. Meaningful differences between EWGSOP1 and 2 in the 85-year-olds could not be ruled out. Prevalence was more dependent on cut-offs than on the operational definition.
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| 42. |
- Zenlander, Robin, et al.
(författare)
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A wide scan of plasma proteins demonstrates thioredoxin reductase 1 as a potential new diagnostic biomarker for hepatocellular carcinoma
- 2023
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 58:9, s. 998-1008
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with liver cirrhosis are recommended ultrasonography screening for early detection of hepatocellular carcinoma to increase the chances of curative treatment. However, ultrasonography alone lacks in sensitivity. Adding plasma biomarkers may increase the detection rate. We performed a broad exploratory analysis to find new plasma proteins with potential applicability for HCC screening in patients with cirrhosis. Methods: In a protein discovery cohort of 172 patients with cirrhosis or HCC, we screened for 481 proteins with suspension bead array or proximity extension assay. From these, 24 proteins were selected for further analysis in a protein verification cohort (n = 160), using ELISA, Luminex or an electrochemiluminescence platform. A cut-off model and a stepwise logistic regression model were used to find combinations of proteins with the best discriminatory performance between HCC and cirrhosis. Results: Stepwise logistic regression revealed alpha-fetoprotein (AFP), decarboxy-prothrombin (DCP), thioredoxin reductase 1 (TXNRD1), and fibroblast growth factor 21 (FGF21) as the proteins with the best discriminatory performance between HCC and cirrhosis. Adding TXNRD1 to DCP and AFP increased the AUC from 0.844 to 0.878, and combining AFP, DCP and TXNRD1 with age and sex resulted in an AUC of 0.920. FGF21, however, did not further increase the performance when including age and sex. Conclusion: In the present study, TXNRD1 improves the sensitivity and specificity of AFP and DCP as HCC screening tools in patients with cirrhosis. We suggest that TXNRD1 should be validated in prospective settings as a new complementary HCC biomarker together with AFP and DCP.
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| 43. |
- Åström, Eva, et al.
(författare)
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Reverse lectin ELISA for detecting fucosylated forms of alpha 1-acid glycoprotein associated with hepatocellular carcinoma
- 2017
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Altered fucosylation of glycoproteins is associated with development of hepatocellular carcinoma (HCC). Lectins have been commonly used to assay changes in fucosylation of plasma glycoproteins. In the present study a recombinantly engineered form of the fucose binding lectin Aleuria aurantia (AAL) consisting of a single binding site for fucose (S2), was used to construct a reverse lectin ELISA method. Microtiter plates coated with the S2 lectin were used to capture glycoproteins from plasma samples followed by antibody detection of S2-bound fucosylated alpha 1-acid glycoprotein (S2-bound AGP). The method was used to compare the level of S2-bound AGP in serum samples from a small cohort of patients with hepatitis, cirrhosis or HCC. Using the reverse S2 lectin ELISA it was shown that the levels of S2-bound AGP was significantly higher in HCC patients compared to non-cancer patients and that there was also a significant elevation of S2-bound AGP in HCC patients compared to cirrhosis patients. There was no correlation between the level of S2-bound AGP and total AGP concentration. The performance of S2-bound AGP in differentiating HCC from cirrhosis samples or hepatitis samples were compared to other markers. A combination of S2-bound AGP, alpha-fetoprotein and AGP concentration showed performances giving area under receiver operating curves of 0.87 and 0.95 respectively.
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