| 1. |
- Arnadottir, Margret, et al.
(författare)
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Hyperhomocysteinemia in cyclosporine-treated renal transplant recipients
- 1996
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Ingår i: Transplantation. - 1534-6080. ; 61:3, s. 509-512
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Tidskriftsartikel (refereegranskat)abstract
- Moderate hyperhomocysteinemia, an independent cardiovascular risk factor, has been reported in renal transplant recipients. In the present study, plasma concentrations of total homocysteine were significantly increased in 120 renal transplant recipients as compared with 60 healthy controls (19.0 +/- 6.9 vs. 11.6 +/- 2.8 mumol/L, P < 0.0001) and as compared with 53 patients without a transplant but with a comparable degree of renal failure (19.0 +/- 6.9 vs. 16.0 4.9 mumol/L, P < 0.01). There was a significant inverse correlation between glomerular filtration rates and plasma homocysteine concentrations in the renal transplant recipients (r = -0.52, P < 0.0001). Groups of renal transplant recipients, with and without cyclosporine, and renal patients without a transplant were studied; these groups were comparable regarding age, sex distribution, glomerular filtration rate, and folate and vitamin B12 concentrations. Renal transplant recipients on cyclosporine had significantly higher plasma homocysteine concentrations than those not on cyclosporine (19.5 +/- 7.6 vs. 16.2 +/- 4.8 mumol/L, P < 0.05), and the patients without a transplant (19.5 +/- 7.6 vs. 16.0 +/- 4.9 mumol/L, P < 0.01). Thus, the hyperhomocysteinemia of renal transplant recipients not treated with cyclosporine, and that of renal patients without a transplant probably is explained by the same mechanism: renal insufficiency. An additional mechanism seems to operate in renal transplant recipients treated with cyclosporine. The lack of correlation between the concentrations of plasma homocysteine and red cell folate in these patients suggests that cyclosporine interferes with folate-assisted remethylation of homocysteine. Plasma homocysteine concentrations were significantly increased in 24 patients with a history of atherosclerotic complications as compared with the remaining 96 renal transplant recipients (20.8 +/- 4.4 vs. 18.5 +/- 7.3 mumol/L, P < 0.01).
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| 2. |
- Arnadottir, M, et al.
(författare)
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The effect of reduced glomerular filtration rate on plasma total homocysteine concentration
- 1996
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 56:1, s. 41-46
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Tidskriftsartikel (refereegranskat)abstract
- The concentration of homocysteine in plasma has been shown to be increased in renal failure, possibly contributing to the accelerated atherosclerosis observed in uraemic patients. The aim of the present study was to document the relationship between plasma total homocysteine (tHcy) concentrations and glomerular filtration rates (GFR) in highly selected patients, with renal function ranging from normal to dialysis dependency. GFR was defined as the plasma clearance of iohexol; a more accurate method than the creatinine-based estimations applied in previous studies. Plasma tHcy concentrations were highly correlated to GFR (r = -0.70, p < 0.0001) and were significantly increased already in moderate renal failure. According to a multiple regression analysis, GFR and red cell folate concentrations independently predicted plasma tHcy concentrations, whereas those of serum creatinine, plasma pyridoxal-5-phosphate, urine albumin and urine alpha-1-microglobulin (a marker of tubular damage) did not. Thus, GFR seems to be a better determinant of plasma tHcy concentration than serum creatinine concentration. Plasma total cysteine and total cysteinylglycine concentrations followed the same pattern as those of tHcy.
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| 3. |
- Grubb, Anders, et al.
(författare)
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Production of an amino acid sequence-specific antiserum against human amyloid A (AA) and serum amyloid A (SAA) protein
- 1987
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - 0036-5513. ; 47:6, s. 619-626
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Tidskriftsartikel (refereegranskat)abstract
- The hydrophilic nonapeptide Ser-Asp-Ala-Arg-Glu-Asn-Ile-Gln-Arg, identical with residues 59-67 of human amyloid protein A (AA) and serum amyloid protein A (SAA), was covalently bound via its carboxyl-terminal end to the carrier-protein keyhole limpet haemocyanin. The complex was injected subcutaneously into ten rabbits. All rabbits produced antisera which, unabsorbed, were specific for AA and SAA. The antisera and their isolated peptide specific antibodies were performance-tested and found to be excellent for demonstration of AA and SAA in immunoblotting and immunohistochemical techniques but unsuitable for immunoprecipitation. Since it is difficult to produce AA- and SAA-specific antisera by procedures earlier described and commercial supplies of good such reagents are unavailable, the easy production of sequence-specific such antisera will facilitate more extended studies of the corresponding antigens for diagnostic and scientific purposes.
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| 4. |
- Hidestål, Joakim, et al.
(författare)
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Hypersensitivity to noradrenaline in human omental vein but not artery isolated from a patient with idiopathic orthostatic hypotension.
- 2002
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Ingår i: Autonomic Neuroscience: Basic & Clinical. - 1872-7484. ; 97:1, s. 55-58
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the smooth muscle contraction in response to noradrenaline (NA), endothelin-1 (ET) and 5-hydroxytryptamine (5-HT) in the omental artery and vein segments from a 67-year-old woman with idiopathic orthostatic hypotension. The blood vessels were obtained during the abdominal surgery and investigated in vitro. Noradrenaline, endothelin-1 and 5-hydroxytryptamine all induced a contraction in the artery and vein segments. Compared to the literature, the sensitivity to noradrenaline was 10 times higher than expected in the vein. In the artery, the sensitivity to noradrenaline and in both the artery and vein, the sensitivity to endothelin-1 and 5-hydroxytryptamine was similar to that reported in the literature. These results suggest that the patient had developed an isolated hypersensitivity to noradrenaline in the veins, probably due to an impairment of the sympathetic activity.
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| 5. |
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| 6. |
- Klein, Robert J., et al.
(författare)
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Prostate cancer polygenic risk score and prediction of lethal prostate cancer
- 2022
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Ingår i: npj Precision Oncology. - : Nature Publishing Group. - 2397-768X. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) for prostate cancer incidence have been proposed to optimize prostate cancer screening. Prediction of lethal prostate cancer is key to any stratified screening program to avoid excessive overdiagnosis. Herein, PRS for incident prostate cancer was evaluated in two population-based cohorts of unscreened middle-aged men linked to cancer and death registries: the Västerbotten Intervention Project (VIP) and the Malmö Diet and Cancer study (MDC). SNP genotypes were measured by genome-wide SNP genotyping by array followed by imputation or genotyping of selected SNPs using mass spectrometry. The ability of PRS to predict lethal prostate cancer was compared to PSA and a commercialized pre-specified model based on four kallikrein markers. The PRS was associated with incident prostate cancer, replicating previously reported relative risks, and was also associated with prostate cancer death. However, unlike PSA, the PRS did not show stronger association with lethal disease: the hazard ratio for prostate cancer incidence vs. prostate cancer metastasis and death was 1.69 vs. 1.65 in VIP and 1.25 vs. 1.25 in MDC. PSA was a much stronger predictor of prostate cancer metastasis or death with an area-under-the-curve of 0.78 versus 0.63 for the PRS. Importantly, addition of PRS to PSA did not contribute additional risk stratification for lethal prostate cancer. We have shown that a PRS that predicts prostate cancer incidence does not have utility above and beyond that of PSA measured at baseline when applied to the clinically relevant endpoint of prostate cancer death. These findings have implications for public health policies for delivery of prostate cancer screening. Focusing polygenic risk scores on clinically significant endpoints such as prostate cancer metastasis or death would likely improve clinical utility.
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| 7. |
- Köhler, Jan, et al.
(författare)
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Long-term effects of reflux nephropathy on blood pressure and renal function in adults.
- 2003
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Ingår i: Nephron Clinical Practice. - : S. Karger AG. - 1660-2110. ; 93:1, s. 35-46
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Tidskriftsartikel (refereegranskat)abstract
- <i>Aims:</i> We investigated whether the grade of renal damage assessed by urography in adult patients with vesicoureteral reflux can be used to identify patients at risk of developing hypertension and/or deterioration of renal function. In addition, maternal and fetal outcome of pregnancy was studied. <i>Methods:</i> Vesicoureteral reflux was diagnosed at a median age of 27 years (range 16–60) in 115 patients (98 women). Excluding patients subjected to nephrectomy or heminephrectomy after inclusion (n = 12), 88 patients had renal damage at inclusion urography and a median follow-up time of 16 years. The median follow-up time was 18 years in 15 patients without renal damage. Grading of renal damage was performed and blood pressure, serum creatinine concentration and albuminuria were measured. Hypertension was considered to be present if the systolic blood pressure was ≧140 mm Hg and/or the diastolic blood pressure was ≧90 mm Hg. It was classified as mild (<180 mm Hg systolic and <105 mm Hg diastolic), or moderate to severe (≧180 mm Hg systolic and/or ≧105 mm Hg diastolic). Renal function was classified as stable or deteriorating. <i>Results:</i> There was no significant difference in the frequency of hypertension among those with (52%) or without (33%) renal damage, but moderate to severe hypertension (16 patients) was only seen in patients with renal damage. Median systolic and diastolic blood pressure were higher in patients with than in those without renal damage. Malignant hypertension developed in 4 patients, all had extensive renal damage. Deterioration of renal function occurred in 25 patients, 1 with unilateral and 24 with extensive renal damage (bilateral or in a solitary kidney). This was associated with a high frequency of hypertension (92%) and albuminuria (88%). Sixteen patients developed end-stage renal disease. A total of 242 pregnancies occurred in 89 of the 98 women. Preeclampsia occurred in 16 (18%) women. <i>Conclusion:</i> Hypertension in adult patients with reflux nephropathy occurs with any grade of renal damage, whereas deterioration of renal function was strongly associated with extensive bilateral renal damage or damage in a solitary kidney.
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| 8. |
- Löfberg, Helge, et al.
(författare)
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Demonstration and classification of amyloidosis in needle biopsies of the kidneys, with special reference to amyloidosis of the AA-type
- 1987
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 0108-0164. ; 95A:1-6, s. 357-363
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Tidskriftsartikel (refereegranskat)abstract
- To examine whether sequence-specific antibodies directed against serum amyloid A were useful in the demonstration and classification of amyloidosis, needle biopsy specimens from the kidneys of 152 cases with renal disorders were investigated using the avidin-biotin-peroxidase complex technique of immunohistochemistry. A distinct immunoreactivity of protein AA was seen in biopsies from all 42 individuals who were clinically classified as having the AA-type of amyloidosis. The stained areas coincided with deposits stained by Congo red. Four of these cases demonstrated immunoreactivity of both protein AA and light immunoglobulin chains and all biopsies except one showed immunoreactivity for the amyloid P-component. After treatment with potassium permanganate, the amyloid deposits in the biopsies of all 42 cases lost their affinity for Congo red. Ten patients with clinical and laboratory findings compatible with the AL-type of amyloidosis were also investigated. All their biopsies demonstrated Congophilic amyloid deposits but none of them showed any immunoreactivity of protein AA. Amyloid deposits of lambda light immunoglobulin chains-but not kappa-were demonstrated in biopsies from four patients. The amyloid P-component was found in biopsies from six individuals and positive Congo red staining after treatment with potassium permanganate was seen in biopsies from four of the cases. Biopsies of 100 patients suffering from non-amyloid renal disorders were also examined. None of them displayed any immunoreactive deposits of protein AA. The investigation shows that amyloid deposits of the AA-type can be identified in needle biopsies when sequence-specific antibodies against serum amyloid A are used in the avidin-biotin-peroxidase complex technique. Both the diagnostic sensitivity (42 of 42) and specificity (110 of 110) of the assay were optimal (1.0). The method was found to be superior to other investigated techniques and useful for classifying amyloidosis in formalin-fixed renal biopsies.
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| 9. |
- Löfberg, Helge, et al.
(författare)
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The prevalence of renal amyloidosis of the AA-type in a series of 1,158 consecutive autopsies
- 1987
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 0108-0164. ; 95A:1-6, s. 297-302
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Tidskriftsartikel (refereegranskat)abstract
- To determine the prevalence of renal amyloidosis of the AA-type in a defined population, formalin-fixed specimens from the kidneys of all the cases autopsied in 1983 at The General Hospital of Malmö, Sweden, were investigated using immunohistochemical techniques. Amyloid deposits of protein AA were found in 10 of 1,158 investigated cases and the calculated prevalence was 0.86 per cent. The mean age at death of the individuals with the AA-type of amyloidosis was 79 years. Six of the cases with amyloidosis had rheumatoid arthritis. The avidin-biotin-peroxidase complex technique was found to be superior to the immunofluorescence method and a high sensitivity and specificity was achieved when sequence-specific antibodies against a synthetized nonapeptide corresponding to a hydrophilic segment of the polypeptide chain of protein AA were used in the assay. Nine cases with other types of amyloid deposits in the kidneys were also detected. None of these cases showed any AA immunoreactivity but all of them demonstrated Congophilic deposits which were immunohistochemically stained by antibodies against the amyloid P-component. The prevalence of renal amyloidosis comprising all types of amyloid protein deposits was 1.64 per cent.
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| 10. |
- Olsson, Inge, et al.
(författare)
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Isolation and characterization of a tumor necrosis factor binding protein from urine
- 1989
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 42:3, s. 270-275
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Tidskriftsartikel (refereegranskat)abstract
- Tumor necrosis factor (TNF)/cachectin can produce both beneficial and harmful manifestations. Mechanisms may operate to counteract potentially harmful effects such as shock and cachexia. The TNF binding protein (TNF-BP), which is found at increased levels in serum and urine of patients with chronic renal failure, may play such a role. TNF-BP was purified 1,000,000-fold to homogeneity from urine of patients with chronic renal failure by use of ion exchange chromatography, affinity chromatography on TNF-Sepharose and reverse phase chromatography. The purified protein contained only one chain with an apparent Mr on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of 30,000. The aminoterminal amino acid sequence D-S-V-X-P-Q-G-K-Y-I-H-P-Q-V-N-S-I-X-K-T revealed no significant homologies with previously described protein sequences. TNF-BP may act as a regulator of the bioactivities of TNF/cachectin.
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