| 1. |
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| 2. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 3. |
- Möller, C A, et al.
(författare)
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Distribution of cystatin C (gamma-trace), an inhibitor of lysosomal cysteine proteinases, in the anterior lobe of simian and human pituitary glands
- 1985
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 41:5, s. 400-404
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Tidskriftsartikel (refereegranskat)abstract
- Cystatin C, a protein inhibitor of lysosomal cysteine proteinases, was demonstrated by immunohistochemical techniques to be present in most luteinizing hormone- (LH-)containing cells in simian and human adenohypophyses. Immunoreactivity of cystatin C was also found in simian adrenocorticotrophic hormone- (ACTH-)containing cells localized to an area corresponding to the pars intermedia but not in the ACTH-containing cells of the anterior pituitary lobe of monkey. No immunoreactivity of cystatin C was detected in the growth hormone- (GH-) and prolactin-containing cells of monkey and man.
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| 4. |
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| 5. |
- Löfberg, H, et al.
(författare)
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gamma-trace in human pituitary adenomas
- 1984
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 59:1, s. 8-113
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Tidskriftsartikel (refereegranskat)abstract
- gamma-Trace, a small protein occurring in body fluids and in secretory and neuroendocrine cells, was demonstrated by immunohistochemical techniques in the cytoplasm of the tumor cells of 13 pituitary adenomas obtained at surgery and autopsy. Seven of the adenomas also contained LH immunoreactivity. FSH, TSH, and ACTH were each found in one gamma-trace-containing adenoma. gamma-Trace was also demonstrated in extracts of 1 pituitary adenoma and of 5 nontumorous adenohypophyses. The immunoreactive protein found in the extracts had a molecular weight and electrophoretic mobility characteristic of gamma-trace. Computerized amino acid sequence comparisons between the primary structure of gamma-trace and those of known hormonal peptides showed no significant similarities.
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| 6. |
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| 7. |
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| 8. |
- Jensson, O, et al.
(författare)
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Hereditary cystatin C (gamma-trace) amyloid angiopathy of the CNS causing cerebral hemorrhage
- 1987
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 76:2, s. 102-114
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary CNS amyloid angiopathy occurring in Icelanders is the first human disorder known to be caused by deposition of cystatin C amyloid fibrils in the walls of the brain arteries leading to single or or multiple strokes with fatal outcome. One or more affected members have been verified by histological examination in 8 families containing 127 affected. These originated from the same geographic area. Abnormally low value of cystatin C found in the cerebrospinal fluid of those affected can be used to support or make diagnosis of this disease, also in asymptomatic relatives. By amino acid sequence analysis the amyloid fibrils in the patients are found to be a variant of cystatin C (gamma-trace), a major cysteine proteinase inhibitor. The variant protein has an amino acid substitution (glutamine for leucine) at position 58 in the amyloid molecule. It is postulated that a point mutation has occurred leading to production of amyloidogenic protein causing the disorder.
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| 9. |
- Palsdottir, A, et al.
(författare)
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Mutation in cystatin C gene causes hereditary brain haemorrhage
- 1988
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Ingår i: The Lancet. - 1474-547X. ; 332:8611, s. 603-604
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disorder in which a cysteine proteinase inhibitor, cystatin C, is deposited as amyloid fibrils in the cerebral arteries of patients and leads to massive brain haemorrhage and death in young adults. A full length cystatin C cDNA probe revealed a mutation in the codon for leucine at position 68 which abolishes an Alu I restriction site in the cystatin C gene of HCCAA patients. The Alu I marker has been used to show that this mutation is transmitted only in affected members of all eight families investigated, and that the mutated cystatin C gene causes HCCAA.
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| 10. |
- Palsdottir, A, et al.
(författare)
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Mutation in the cystatin C gene causes hereditary brain hemorrhage
- 1989
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Ingår i: Progress in Clinical and Biological Research. - 0361-7742. ; 317, s. 241-246
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Tidskriftsartikel (refereegranskat)abstract
- Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disorder leading to massive brain hemorrhage and death in young adults (Jensson et al., 1987). A variant of a potent inhibitor of cysteine proteinases, cystatin C (Barrett et al., 1984), is deposited as amyloid fibrils in the cerebral arteries of the patients (Ghiso et al., 1986). We have used the full length cystatin C cDNA probe (Abrahamson et al., 1987) to demonstrate a mutation in the codon for leucine at position 68, which abolishes an Alu I restriction site in cystatin C gene of the HCCAA patients. The Alu I marker has been used to show that this mutation is transmitted only in the affected members in all eight families investigated, proving that the mutated cystatin C gene causes HCCAA. This DNA marker will be useful for the diagnosis of HCCAA in patients, asymptomatic affected individuals and also for pre-natal diagnosis. HCCAA is the first human disorder known to be caused by an abnormal gene for a cysteine proteinase inhibitor
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| 11. |
- Palsdottir, A, et al.
(författare)
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Study of restriction fragment length polymorphism in the cystatin C gene of elderly patients with dementia and aged Down's syndrome patients
- 1989
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Ingår i: Progress in Clinical and Biological Research. - 0361-7742. ; 317, s. 235-239
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Tidskriftsartikel (refereegranskat)abstract
- Using a full length cystatin C cDNA probe and the Alu I restriction enzyme a total of 33 patients with senile dementia, Alzheimer type and 31 Down's syndrome patients have been investigated for the presence of the 630 bp Alu I restriction fragment length polymorphism in the cystatin C gene detected in Icelandic patients with hereditary cystatin C amyloid angiopathy. Results showed that all the patients had normal cystatin C fragment length of 600 bp.
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| 12. |
- Tenstad, O, et al.
(författare)
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Renal handling of radiolabelled human cystatin C in the rat
- 1996
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 56:5, s. 409-414
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Tidskriftsartikel (refereegranskat)abstract
- Serum cystatin C concentration correlates negatively with glomerular filtration rate as well as or better than that of serum creatinine, suggesting a constant formation, and elimination from extracellular fluid mainly by glomerular filtration. It is not known, however, how well the renal plasma clearance of this 13-kDa basic polypeptide matches the glomerular filtration rate. This was investigated in rats during control conditions and after reduced renal perfusion pressure. 125I-cystatin C and an indicator for glomerular filtration (51Cr-EDTA or 131I-aprotinin) were injected intravenously. The renal accumulation and urinary excretion of the tracers were recorded in periods of 2.5 to 20.0 min. The renal plasma clearance of 125I-cystatin C (Ccy) based on the renal content of 125I correlated well with the glomerular filtration rate (CCr-EDTA) in periods up to 6 min; i.e. Ccy = 0.94 x CCr-EDTA, r = 0.99. Less than 0.5% of the filtered amount appeared in the urine. During more prolonged periods, Ccy increasingly underestimated glomerular filtration rate, reaching about 0.4 x CCr-EDTA in a 20-min period. Free 125I relative to total plasma 125I activity increased from about 2% at 5 min to about 70% at 20 min. In nephrectomized rats, free 125I accumulated in plasma at a slower rate, accounting for about 15% of the total activity 20 min after injection of 125I-cystatin C. We conclude that cystatin C is (a) mainly removed from the extracellular fluid by the kidneys, (b) practically freely filtered in the glomeruli, and (c) completely absorbed and rapidly broken down by the proximal tubular cells.
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| 13. |
- Wallmark, A, et al.
(författare)
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Feasibility of extracorporeal on-line large-scale plasma adsorptions on protein A-sepharose columns in cancer patients
- 1984
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Ingår i: Artificial Organs. - : Wiley. - 0160-564X .- 1525-1594. ; 8:1, s. 72-81
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Tidskriftsartikel (refereegranskat)abstract
- The feasibility of extracorporeal adsorption of 1.5-3 L plasma on protein A-Sepharose was investigated in six patients with advanced cancer. Anticoagulation with heparin was associated with respiratory distress syndrome in two patients, most likely caused by complement activation as indicated by a transient leukopenia during plasma reinfusion and appearance of C3 degradation products in the extracorporeal circulation. Addition of citrate abolished the respiratory symptoms, C3 degradation, and leukopenia, and no adverse reactions were observed. No objective tumor regression was observed in any of the patients. Three patients progressed during therapy. In one of these, multifocal central tumor necrosis was observed as a possible, although unproven, therapeutic effect. Increased natural killer and/or killer cell activities were recorded in three patients and increased complement-dependent serum cytotoxicity in one patient. The level of circulating immune complexes decreased significantly (18-28%) in three patients studied. It is concluded that extracorporeal plasma adsorption on protein A-Sepharose is feasible when citrate is added to the extracorporeal system, but its therapeutic efficacy is uncertain.
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| 14. |
- Glad, C, et al.
(författare)
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Immunocapillarymigration with enzyme-labeled antibodies : rapid quantification of C-reactive protein in human plasma
- 1981
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697. ; 116:2, s. 40-335
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Tidskriftsartikel (refereegranskat)abstract
- Various procedures to improve the sensitivity and precision of antigen quantitation by immunocapillarymigration are investigated. The best results are obtained when using porous strips of cellulose acetate with covalently attached antibodies and when enzyme-labeled antibodies are used to expose the antigen-covered areas of the strips. Such a system has a sensitivity of 0.15 mg/liter and a precision of 7%. It allows a rapid quantitation of human C-reactive protein without the use of laboratory instrumentation.
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| 15. |
- Grubb, A O, et al.
(författare)
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Isolation of human complex-forming glycoprotein, heterogeneous in charge (protein HC), and its IgA complex from plasma. Physiochemical and immunochemical properties, normal plasma concentration
- 1983
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Ingår i: The Journal of biological chemistry. - 0021-9258. ; 258:23, s. 707-14698
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Tidskriftsartikel (refereegranskat)abstract
- Human complex-forming glycoprotein, heterogeneous in charge (protein HC) has previously been isolated from urine and immunochemically shown to be present in low and high molecular weight forms in blood plasma (Tejler, L., and Grubb, A. O. (1976) Biochim. Biophys. Acta 439, 82-94). In the present work, the major low and high molecular weight forms of the protein were isolated from plasma by immunosorption followed by gel chromatography. The plasma low molecular weight protein HC and the urinary protein had similar, if not identical, molecular weight, amino acid composition, NH2-terminal and carboxyl-terminal amino acid sequences and electrophoretic mobility. The low molecular weight plasma protein HC carried a yellow chromophore like the urinary protein, but its molar extinction coefficient at 280 nm was lower and its charge heterogeneity less pronounced than that of urinary protein HC. The plasma high molecular weight protein HC had a hydrodynamic volume which was greater than that of monomeric IgA but smaller than that of dimeric IgA. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the isolated high molecular weight protein followed by electrophoretic blotting and immunochemical analysis demonstrated that the protein contained four polypeptide chains: two light immunoglobulin chains (Mr = 23,000), one IgA alpha-chain (Mr = 54,000), and one chain with Mr approximately 90,000 which carried both alpha-chain and protein HC antigenic determinants. Whether the protein HC X IgA complex is a functionally significant part of the humoral immune system cannot be decided without further experimentation, but the complex was found to be completely absent from the blood plasma of patients with a selective deficiency of IgA-secreting immunocytes. The isolated low and high molecular weight plasma protein HC components were used as standard proteins in the construction of a quantitative crossed immunoelectrophoretic assay for the simultaneous quantitation of the two major protein HC components in blood plasma. The plasma concentrations of the low and high molecular weight protein HC components were measured by this method in 13 healthy Caucasians. The results for the low molecular weight protein HC were: mean, 20.3 mg/liter, S.D., 3.2 mg/liter, range, 13.6-26.0 mg/liter; and for the protein HC X IgA complex: mean, 293 mg/liter, S.D., 176 mg/liter, range, 36-620 mg/liter.
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| 16. |
- Grubb, A O, et al.
(författare)
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The gamma-trace concentration of normal human seminal plasma is thirty-six times that of normal human blood plasma
- 1983
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - 0036-5513. ; 43:5, s. 5-421
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Tidskriftsartikel (refereegranskat)abstract
- Fresh human seminal plasma was demonstrated to contain a basic microprotein with the same size, electrophoretic mobility, isoelectric point and immunochemical properties as isolated human gamma-trace. The concentration of gamma-trace in 24 normal seminal plasma samples was found to be (mean +/- SD): 51 +/- 8.1 mg/l which is 36 times higher than the normal human blood plasma concentration of gamma-trace.
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| 17. |
- Larsson, A, et al.
(författare)
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Calculation of glomerular filtration rate expressed in mL/min from plasma cystatin C values in mg/L
- 2004
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 64:1, s. 25-30
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Tidskriftsartikel (refereegranskat)abstract
- The Cockcroft-Gault formula is often used to calculate the glomerular filtration rate (GFR) from plasma creatinine results. In Sweden this calculation is not usually done in the laboratory, but locally in the wards. These manual calculations could cause erroneous results. In several studies plasma cystatin C has been shown to be superior to plasma creatinine for estimation of GFR. One limitation of using cystatin C as a GFR marker is that there is no conversion formula transforming cystatin C expressed as mg/L to GFR expressed as mL/min. In this study plasma creatinine and cystatin C were compared with iohexol clearance. A stronger correlation (p<0.0001) was found between cystatin C and iohexol clearance (r(2) =0.91) than between creatinine and iohexol clearance (r(2) =0.84). From the correlation data a formula was calculated to convert cystatin C expressed as mg/L to GFR (mL/min). The formulas y=77.24x -1.2623 (Dade Behring cystatin C calibration) or y=99.43x -1.5837 (DakoCytomation cystatin C calibration) are used to calculate GFR expressed in mL/min from the cystatin C value in mg/L and both results are reported to the referral doctor. These formulas can provide the clinicians with reliable and readily available GFR data based on single measurements of cystatin C concentrations.
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| 18. |
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| 19. |
- Lindstedt, G, et al.
(författare)
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Specialistexamen i klinisk kemi. Frivillig examination för ökad kompetens
- 1993
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Ingår i: Lakartidningen. - 0023-7205. ; 90:7, s. 599-602
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- The Swedish Society for Clinical Chemistry has now completed its second board examination for voluntary specialist diploma in clinical chemistry. The first day comprised a 6 hour written examination (about 20 essay questions). The second day was an oral examination in front of five clinical chemists representing different aspects of the specialty, firstly as questions on the subject as a whole and secondly in the form of a seminar where original research work carried out by the examinee was discussed.
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| 20. |
- López-Otin, C, et al.
(författare)
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Neutral microprotein, a novel human plasma and urinary protein associated with a yellow-brown chromophore. Isolation from protein HC preparations and partial characterization
- 1983
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X. ; 117:1, s. 9-202
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Tidskriftsartikel (refereegranskat)abstract
- An apparently novel human plasma and urinary protein of low molecular weight was isolated from several highly purified preparations of protein HC by gel chromatography and high voltage electrophoresis with a yield of about 8 mg/g. The protein has a molecular weight of about 20,000, neutral electrophoretic mobility at pH 6.5 and a high content of half-cystine. It is associated with a yellow-brown chromophore like protein HC and could be demonstrated in all investigated preparations of isolated human, rabbit and guinea-pig protein HC and alpha 1-microglobulin.
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| 21. |
- López Otin, C, et al.
(författare)
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The complete amino acid sequence of human complex-forming glycoprotein heterogeneous in charge (protein HC) from one individual
- 1984
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Ingår i: Archives of Biochemistry and Biophysics. - : Elsevier BV. - 0003-9861. ; 228:2, s. 54-544
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Tidskriftsartikel (refereegranskat)abstract
- The complete amino acid sequence of the single polypeptide chain of human complex-forming glycoprotein heterogeneous in charge (protein HC) isolated from a single individual is reported with the supporting data. The primary structure was determined by automatic degradation of the intact chain and of fragments obtained by chemical and enzymatic degradations of the native or reduced and S-carboxymethylated protein. The polypeptide chain of protein HC contained 182 amino acid residues with a calculated molecular weight of 20,621. No amino acid sequence variability was found and such variability can therefore not explain the great charge heterogeneity of protein HC in a single individual. The amino acid sequence of protein HC was nearly identical to the one reported for human alpha 1-microglobulin in a research communication but contained 15 additional residues.
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| 22. |
- Löfberg, H, et al.
(författare)
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Occurrence of gamma-trace in the calcitonin-producing C-cells of simian thyroid gland and human medullary thyroid carcinoma
- 1983
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Ingår i: Acta Endocrinologica. - : Oxford University Press (OUP). - 0001-5598 .- 0804-4643 .- 1479-683X. ; 104:1, s. 69-76
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Tidskriftsartikel (refereegranskat)abstract
- gamma-Trace, a microprotein occurring in neuroendocrine cells, was demonstrated by immunohistochemical technique to be present in the calcitonin-producing C-cells of normal simian thyroid gland and of human medullary thyroid carcinoma. A comparatively high concentration of gamma-trace was demonstrated in tissue extract of neoplastic C-cells. The immunoreactive protein found in the extract had a molecular weight and electrophoretic mobility characteristic for gamma-trace.
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| 23. |
- Löfberg, H, et al.
(författare)
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The cerebrospinal fluid and plasma concentrations of gamma-trace and beta2-microglobulin at various ages and in neurological disorders
- 1980
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Ingår i: Journal of Neurology. - 0340-5354. ; 223:3, s. 70-159
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Tidskriftsartikel (refereegranskat)abstract
- The concentrations of gamma-trace and beta2-microglobulin in cerebrospinal fluid (CSF) and plasma were determined in 64 individuals of various ages without signs of organic disorder in the central nervous system (CNS). A strong connection was found between the CSF level of gamma-trace and the age of the individual, with the CSF level of newborns being 3--4 times that of adults. A similar, but less marked, connection was found for the CSF level of beta2-microglobulin and the age of the individual. The plasma levels of the two proteins also varied with the age of the individual, but the variations were not as great as those of the CSF levels. The results strongly emphasize the necessity of using age-matched reference values when CSF and plasma levels of the proteins are to be evaluated in different groups of patients. Thirteen children and 98 adults with various neurological disorders were also examined. Significantly increased CSF levels of gamma-trace and beta2-microglobulin as well as increased plasma concentration of gamma-trace and CSF/plasma gradient of beta2-microglobulin were found in infectious disorders. Increased gamma-trace concentration in plasma and beta2-microglobulin concentration in CSF were seen in cerebrovascular disorders. The mechanisms which regulate the turnover of proteins in CSF are discussed.
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| 24. |
- Mendez, E, et al.
(författare)
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Human complex-forming glycoprotein, heterogeneous in charge : the primary structure around the cysteine residues and characterization of a disulfide bridge
- 1982
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Ingår i: Archives of Biochemistry and Biophysics. - : Elsevier BV. - 0003-9861. ; 213:1, s. 50-240
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Tidskriftsartikel (refereegranskat)abstract
- The amino acid sequence of the cysteine-containing regions of human complex-forming glycoprotein, heterogeneous in charge (protein HC) was determined by studies of the tryptic peptides of the completely reduced and radioalkylated protein. One of the cysteines was located in the amino-terminal part of the molecule at position 34....Diagonal map electrophoresis showed that the cysteine residue in the carboxy-terminal region was bridged to the cysteine containing sequence in the middle of the molecule. The function of the cysteine residue at position 34 remains elusive since the residue was not found on the diagonal maps. The release of cysteic acid and a small cysteic acid containing peptide after oxidation of the native protein HC molecule suggests that this cysteine residue may be involved in disulfide bridges with cysteine and small cysteine containing peptides.
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| 25. |
- Palsdottir, A, et al.
(författare)
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Three RFLP's at the 3' end of the cystatin C gene, the disease gene in hereditary cystatin C amyloid angiopathy (HCCAA) in Iceland
- 1990
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 18:24, s. 7471-7471
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Tidskriftsartikel (refereegranskat)abstract
- Sputum samples from 25 patients with bronchiectasis were assayed enzymatically for myeloperoxidase, neutrophil elastase and cathepsin B, and immunologically for cystatin A, cystatin B, cystatin C, cystatin S and kininogen. High myeloperoxidase and neutrophil elastase levels were found in those sputum samples that were assessed visually to be purulent. These samples were also found to contain high levels of cathepsin B activity and cystatin A, but low levels of cystatin S and of the most effective cathepsin B inhibitor, cystatin C. In contrast, sputum samples that were low in myeloperoxidase and neutrophil elastase activities had low levels of cathepsin B and cystatin A, but high cystatin C and S levels. It is concluded that cathepsin B activity in sputum is positively correlated with the degree of inflammation and neutrophil recruitment. Although this may be due in part to reduced amounts of cathepsin B inhibitors, particularly cystatin C, theoretical considerations suggest that factors other than the gross level of inhibitors must be involved in the control of cathepsin B activity.
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