| 1. |
- Abrahamson, Magnus, et al.
(författare)
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Structure and expression of the human cystatin C gene
- 1990
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Ingår i: Biochemical Journal. - 1470-8728. ; 268:2, s. 287-294
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Tidskriftsartikel (refereegranskat)abstract
- The structural organization of the gene for the human cysteine-proteinase inhibitor cystatin C was studied. Restriction-endonuclease digests of human genomic DNA hybridized with human cystatin C cDNA and genomic probes produced patterns consistent with a single cystatin C gene and, also, the presence of six closely related sequences in the human genome. A 30 kb restriction map covering the genomic region of the cystatin C gene was constructed. The positions of three polymorphic restriction sites, found at examination of digests of genomic DNA from 79 subjects, were localized in the flanking regions of the gene. The gene was cloned and the nucleotide sequence of a 7.3 kb genomic segment was determined, containing the three exons of the cystatin C structural gene as well as 1.0 kb of 5'-flanking and 2.0 kb of 3'-flanking sequences. Northern-blot experiments revealed that the cystatin C gene is expressed in every human tissue examined, including kidney, liver, pancreas, intestine, stomach, antrum, lung and placenta. The highest cystatin C expression was seen in seminal vesicles. The apparently non-tissue-specific expression of this cysteine-proteinase inhibitor gene is discussed with respect to the structure of its 5'-flanking region, which shares several features with those of housekeeping genes.
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| 2. |
- Leion, Felicia, et al.
(författare)
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Estimating glomerular filtration rate (GFR) in children. The average between a cystatin C- and a creatinine-based equation improves estimation of GFR in both children and adults and enables diagnosing Shrunken Pore Syndrome.
- 2017
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 77:5, s. 338-344
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Tidskriftsartikel (refereegranskat)abstract
- Estimating glomerular filtration rate (GFR) in adults by using the average of values obtained by a cystatin C- (eGFRcystatin C) and a creatinine-based (eGFRcreatinine) equation shows at least the same diagnostic performance as GFR estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparison of eGFRcystatin C and eGFRcreatinine plays a pivotal role in the diagnosis of Shrunken Pore Syndrome, where low eGFRcystatin C compared to eGFRcreatinine has been associated with higher mortality in adults. The present study was undertaken to elucidate if this concept can also be applied in children. Using iohexol and inulin clearance as gold standard in 702 children, we studied the diagnostic performance of 10 creatinine-based, 5 cystatin C-based and 3 combined cystatin C-creatinine eGFR equations and compared them to the result of the average of 9 pairs of a eGFRcystatin C and a eGFRcreatinine estimate. While creatinine-based GFR estimations are unsuitable in children unless calibrated in a pediatric or mixed pediatric-adult population, cystatin C-based estimations in general performed well in children. The average of a suitable creatinine-based and a cystatin C-based equation generally displayed a better diagnostic performance than estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparing eGFRcystatin and eGFRcreatinine may help identify pediatric patients with Shrunken Pore Syndrome.
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| 3. |
- Malmgren, Linnea, et al.
(författare)
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The complexity of kidney disease and diagnosing it - Cystatin C, selective glomerular hypofiltration syndromes and proteome regulation.
- 2023
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 293:3, s. 293-308
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Tidskriftsartikel (refereegranskat)abstract
- Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous GFR-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterised by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules < 1kDa dominating the glomerular filtrate e.g., water, urea, creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterised by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.
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| 4. |
- Sällman Almén, Markus, et al.
(författare)
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Shrunken Pore Syndrome Is Associated With Increased Levels of Atherosclerosis-Promoting Proteins
- 2019
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Ingår i: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 4:1, s. 67-79
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Shrunken pore syndrome (SPS), originally defined by cystatin C-based estimated glomerular filtration rate (eGFRcystatin C) being less than 60% of creatinine-based estimated glomerular filtration rate (eGFRcreatinine) in the absence of extrarenal influences on the plasma levels of cystatin C or creatinine, is associated with a high increase in mortality, even in the absence of reduced glomerular filtration rate (GFR). The objective of the present study was to determine whether the proteome of patients with SPS shows differences from that of patients with normal or reduced measured GFR (mGFR) without SPS.Methods: Four patient cohorts were included: 1 cohort with normal mGFR without SPS, 1 with normal mGFR with SPS, 1 with reduced mGFR without SPS, and 1 with reduced mGFR with SPS. The plasma levels of 177 selected proteins were analyzed.Results: Differences in the levels of 30 proteins were specific for SPS; 31 differences were specific for patients with both SPS and reduced mGFR; and 27 were specific for reduced mGFR. Eighteen of the differences specific for SPS concerned proteins described as promoting, or being associated with, atherosclerosis. Twelve of the differences specific for patients with both SPS and reduced mGFR and 10 of the differences specific for reduced mGFR also concerned proteins described as promoting, or being associated with, atherosclerosis. Almost all (82 of 88) of the concentration differences represented increased levels. For SPS, but not for reduced mGFR, a correlation between protein size and increase in level was observed, with smaller proteins being associated with higher levels.Conclusion: The high mortality in shrunken pore syndrome might be caused by the accumulation of atherosclerosis-promoting proteins in this condition.
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| 5. |
- Åkesson, Anna, et al.
(författare)
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Shrunken pore syndrome and mortality : a cohort study of patients with measured GFR and known comorbidities
- 2020
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 80:5, s. 412-422
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Tidskriftsartikel (refereegranskat)abstract
- Shrunken pore syndrome (SPS) is defined by a cystatin C-based estimation of glomerular filtration rate (eGFRCYS) being less than 60% or 70% of a creatinine-based GFR estimation (eGFRCR) in the absence of extrarenal influences on cystatin C or creatinine concentrations. SPS has been associated with a substantial increase in mortality or morbidity in all investigated populations. However, in these studies, neither the diagnoses, nor causes of death were described, and only estimated GFR was available. The present study concerns 2781 individuals with measured GFR (mGFR), known diagnoses, and known causes of death during 5.6 years in median. Cox multivariate proportional hazards regression model was used to estimate hazard ratios (HR) for all-cause and cancer, cardiovascular, diabetes or chronic kidney disease (CKD) as cause-specific mortality among patients with SPS. At an eGFRCYS/eGFRCR-ratio <0.70, the adjusted SPS death risk in the total cohort (HR 3.0, 95% CI 2.4-3.7) was clearly higher than that for the other diagnosis groups. In a sub-cohort of 1300 persons with or without diagnosis, but with normal mGFR, the all-cause mortality of SPS was markedly increased (HR 4.1, 95% CI 2.6-6.5). In a sub-cohort of 567 persons with normal mGFR and no diagnosis, the all-cause mortality of SPS was even more increased (HR 7.3, 95% CI 2.3-23). The prevalence of SPS in the total cohort was 23% and in the sub-cohorts 17 and 12%, respectively. As SPS is associated with a high mortality, occurs in the absence of reduced mGFR and albuminuria, it expands the spectrum of kidney disorders.
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| 6. |
- Åkesson, Per, et al.
(författare)
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Streptococcal inhibitor of complement-mediated lysis (SIC): an anti-inflammatory virulence determinant
- 2010
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Ingår i: Microbiology. - : Microbiology Society. - 1465-2080 .- 1350-0872. ; 156, s. 3660-3668
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Tidskriftsartikel (refereegranskat)abstract
- Since the late 1980s, a worldwide increase of severe Streptococcus pyogenes infections has been associated with strains of the M1 serotype, strains which all secrete the streptococcal inhibitor of complement-mediated lysis (SIC). Previous work has shown that SIC blocks complement-mediated haemolysis, inhibits the activity of antibacterial peptides and has affinity for the human plasma proteins clusterin and histidine-rich glycoprotein; the latter is a member of the cystatin protein family. The present work demonstrates that SIC binds to cystatin C, high-molecular-mass kininogen (HK) and low-molecular-mass kininogen, which are additional members of this protein family. The binding sites in HK are located in the cystatin-like domain D3 and the endothelial cell-binding domain D5. Immobilization of HK to cellular structures plays a central role in activation of the human contact system. SIC was found to inhibit the binding of HK to endothelial cells, and to reduce contact activation as measured by prolonged blood clotting time and impaired release of bradykinin. These results suggest that SIC modifies host defence systems, which may contribute to the virulence of S. pyogenes strains of the M1 serotype.
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| 7. |
- Abrahamson, Magnus
(författare)
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Att förlåta det oförlåtliga
- 2002
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Ingår i: Budbäraren. ; :21, s. 12-
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 8. |
- Abrahamson, Magnus
(författare)
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Cystatins
- 1994
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Ingår i: Methods in Enzymology. - : Elsevier. - 0076-6879. ; 244, s. 685-700
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Abrahamson, Magnus, et al.
(författare)
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Cystatins.
- 2003
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Ingår i: Biochemical Society Symposia. - 0067-8694. ; 70, s. 179-199
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Tidskriftsartikel (refereegranskat)
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| 10. |
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