| 1. |
- Jahnson, Staffan, et al.
(författare)
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Tumor mapping of regional immunostaining for p21, p53, and mdm2 in locally advanced bladder carcinoma
- 2000
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Ingår i: Cancer. - New York, USA : John Wiley & Sons. - 0008-543X .- 1097-0142. ; 89:3, s. 619-629
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to elucidate the associations among immunostaining for p53, p21, and mdm2; their respective expression within each tumor; and the value of these variables for predicting treatment outcome after cystectomy for patients with locally advanced bladder carcinoma.Methods: The hospital records from all 173 patients treated with cystectomy for locally advanced urothelial bladder carcinoma between 1967 and 1992 were retrospectively reviewed. Three consecutive sections from biopsies taken before any treatment were stained using the standard immunohistochemical technique for p53, p21, and mdm2, respectively. The cutoff limit was 20% or more for positive p53 expression and 10% or more for positive p21 and mdm2 expression.Results: Positive immunostaining was observed for p53 in 98 tumors (57%), for p21 in 89 tumors (51%), and for mdm2 in only 16 tumors (9%). The only association found between immunostaining for the three antibodies was that most mdm2-positive tumors had positive p21 expression. Tumor mapping of regional immunostaining showed no association between immunostaining for p53 and p21. In a proportional hazards analysis, no association was found between the results of immunostaining for the three antibodies and treatment outcome.Conclusions: Positive or negative expression of p53, p21, or mdm2, or combinations of these, was not associated with cancer specific mortality after cystectomy for bladder carcinoma. There was no association between immunostaining for p21 and p53, whereas positive immunostaining for mdm2 was observed in a minority of the tumors. These results indicate that, in addition to p21, p53, and mdm2, there are other oncoproteins and tumor suppressor proteins along the p53 pathway that are involved in tumor development and progression.
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| 2. |
- Lindvall, O, et al.
(författare)
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Cell therapy and transplantation in Parkinson's disease
- 2001
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : De Gruyter. - 1434-6621 .- 1437-4331. ; 39:4, s. 356-361
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Tidskriftsartikel (refereegranskat)abstract
- Transplanted human fetal dopamine neurons can reinnervate the striatum in patients with Parkinson's disease (PD). Recent findings using positron emission tomography indicate that the grafts are functionally integrated and restore dopamine release in the patient's striatum. The grafts can exhibit long-term survival without immunological rejection and despite an ongoing disease process and continuous antiparkinsonian drug treatment. In the most successful cases, patients have been able to withdraw L-dopa treatment after transplantation and resume an independent life. About two-thirds of grafted patients have shown clinically useful, partial recovery of motor function. The major obstacle for the further development of this cell replacement strategy is that large amounts of human fetal mesencephalic tissue are needed for therapeutic effects. Stem cells hold promise as a virtually unlimited source of self-renewing progenitors for transplantation. The possibility to generate dopamine neurons from such cells is now being explored using different approaches. However, so far the generated neurons have survived poorly after transplantation in animals.
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| 3. |
- Tisell, L E, et al.
(författare)
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The Ki67 index a prognostic marker in medullary thyroid carcinoma.
- 2003
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:11, s. 2093-7
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Tidskriftsartikel (refereegranskat)abstract
- Our objective was to examine the usefulness of the Ki67 proliferation index as a prognostic marker in patients with medullary thyroid carcinoma (MTC). It is difficult to predict the prognosis of MTC by using conventional prognostic factors. Immunocytochemical analysis of tumour proliferation has been used as a prognostic tool in some tumours, but only rarely in MTC. In all, 71 tumours from 36 patients were investigated, by using a semiautomatic image analysis programme. On average 10,000 nuclear profiles were counted per tumour, and the percentage of tumour cells expressing the proliferation marker, Ki67, was calculated. Primary tumours that had metastasised had higher Ki67 indices than primary tumours that had not metastasised. Recurrent lymph node metastasis had higher Ki67 indices than the primary tumours. By using a Poisson model, it was possible to estimate the median survival time for individual patients if the Ki67 index for the primary tumour and the age at surgery were known. The higher the Ki67 index and the age at operation were, the shorter was the survival. Estimating the median survival of individual patients will be of help for planning the patients' life and postoperative follow-up and treatment.
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| 4. |
- Axelson, Hans W, et al.
(författare)
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Microdialysis and electromyography of experimental muscle fatigue in healthy volunteers and patients with mitochondrial myopathy
- 2002
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Ingår i: Muscle and Nerve. - : Wiley. - 0148-639X .- 1097-4598. ; 26:4, s. 520-526
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Tidskriftsartikel (refereegranskat)abstract
- Consecutive 60-min microdialysis samples were taken from the tibial anterior muscle in 11 healthy subjects and 4 patients with mitochondrial myopathy before (2-3 samples) and after (3-4 samples, 2 controls and 1 patient excluded) sustained isometric foot dorsiflexions. Before exercise, mean concentrations of lactate, pyruvate, hypoxanthine, urate, aspartate, and glutamate did not significantly differ between controls and patients. After exercise, the controls showed significantly increased concentrations of lactate, pyruvate, and urate, decreased hypoxanthine, and no change in aspartate and glutamate. Similar findings were observed in the patients. Plasma lactate was unchanged. Exercise-induced increase in integrated electromyogram amplitude and rated subjective fatigue were correlated to increased post-exercise lactate concentrations, with no obvious difference between the groups. Microdialysis of skeletal muscle allows the detection and monitoring of biochemical changes in the interstitial space. With the exercise protocol used, however, it was not possible to demonstrate any biochemical difference between healthy controls and patients with mitochondrial myopathy.
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| 5. |
- Blennow, Kaj, 1958, et al.
(författare)
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No association between the alpha2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression.
- 2000
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Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 107:8-9, s. 1065-79
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Tidskriftsartikel (refereegranskat)abstract
- A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the alpha2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p < 0.0001) in ApoE epsilon4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE epsilon4 allele. No change in A2M exon 17-18 mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.
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| 6. |
- Emilsson, Kent, 1963-, et al.
(författare)
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The relation between mitral annulus motion and left ventricular ejection fraction in atrial fibrillation.
- 2000
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Ingår i: Clinical Physiology. - : Wiley. - 0144-5979 .- 1365-2281. ; 20:1, s. 44-9
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Tidskriftsartikel (refereegranskat)abstract
- Mitral annulus motion (MAM) has recently been introduced as an index of left ventricular function. Previous studies have shown a good agreement between MAM (mm) x 5 and ejection fraction in middle-aged and elderly patients. These studies only included patients with sinus rhythm, while patients with atrial fibrillation were excluded. In the present study, MAM was reduced in patients with atrial fibrillation while ejection fraction (EF) did not differ from age-matched control patients with sinus rhythm. The 'conversion factor' (EF/MAM) was 7.2 in the group with atrial fibrillation and 5. 1 in controls with sinus rhythm. This difference must be taken into account when MAM is used to estimate left ventricular function in patients with atrial fibrillation. Patients with atrial fibrillation had lower stroke volume and higher heart rate than patients with sinus rhythm. A decreased systolic long-axis shortening was found (P<0.005) compared to patients with sinus rhythm, but no difference in short-axis diameter shortening.
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| 7. |
- Johansson, Peter, 1958, et al.
(författare)
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Increased risk for vascular complications in PRV-1 positive patients with essential thrombocythaemia.
- 2003
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Ingår i: British journal of haematology. - 0007-1048. ; 123:3, s. 513-6
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Tidskriftsartikel (refereegranskat)abstract
- Essential thrombocythaemia (ET) is a heterogeneous disorder with respect to plasma erythropoietin concentration at diagnosis and clonality of haematopoiesis. Polycythaemia rubra vera-1 (PRV-1) positivity, i.e. PRV-1 mRNA overexpression, is known to be present in the vast majority of patients with polycythaemia vera and also in some patients with ET. In the present study, PRV-1 expression was quantified by real-time polymerase chain reaction in 70 ET patients; 17 of them (24%) were found to be PRV-1 positive. Ten of the 17 PRV-1 positive ET patients had experienced thromboembolic complications compared with 14 of 53 PRV-1 negative patients, the difference between the two groups being statistically significant (P=0.02). In addition, the frequency of total vascular complications, thromboembolic events and major bleedings, was significantly higher in the group of PRV-1 positive as compared with PRV-1 negative ET patients (P=0.03). The time from diagnosis of ET to the requirement of platelet-lowering therapy was significantly shorter in PRV-1 positive compared with PRV-1 negative ET patients (P=0.014). It can be concluded that PRV-1 positive patients appear to suffer from a more aggressive disorder with increased risk for vascular complications and a greater need for platelet-lowering therapy, compared with PRV-1 negative ET patients.
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| 8. |
- Johansson, Peter, 1958, et al.
(författare)
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The presence of a significant association between elevated PRV-1 mRNA expression and low plasma erythropoietin concentration in essential thrombocythaemia.
- 2003
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Ingår i: European journal of haematology. - 0902-4441. ; 70:6, s. 358-62
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 45% of newly diagnosed patients with essential thrombocythaemia (ET) demonstrate subnormal plasma erythropoietin (EPO) concentrations, which constitutes a risk factor for occlusive vascular events. In 58 ET patients, a possible association between polycythaemia rubra vera-1 (PRV-1) overexpression and subnormal plasma EPO was investigated, which was always measured prior to the institution of platelet lowering agents. At the time when PRV-1 expression was measured, 28 of 58 (48%) ET patients had received platelet lowering treatment. PRV-1 expression was measured by quantitative real-time reverse transcription-polymerase chain reaction assay of mRNA extracted from purified peripheral blood buffy coat. The cycle threshold (CT) value of PRV-1 was determined and was divided with the CT value for the housekeeping GAPDH gene transcript. A quotient <0.93 was defined as PRV-1 positive. Of the ET patients 12 of 58 (21%) were PRV-1 positive and 19 of 58 (33%) demonstrated subnormal plasma EPO. In the 58 ET patients there was a significant association between low plasma EPO and PRV-1 positive results (P = 0.001). The 30 ET patients who had not received any platelet lowering treatment showed a significant (P = 0.005) relation between PRV-1 positivity and subnormal plasma EPO. No such relationship was present in the 28 ET patients who had received prior treatment with the above drugs (P = 0.147).
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| 9. |
- Robinson, Yohan, 1977, et al.
(författare)
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An optimized method for the assay of the red blood cell--age-related enzyme aspartate aminotransferase.
- 2004
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Ingår i: Laboratory hematology : official publication of the International Society for Laboratory Hematology. - 1080-2924 .- 1523-6528. ; 10:3, s. 144-6
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Tidskriftsartikel (refereegranskat)abstract
- Three methods of preparation of red blood cell concentrate for erythrocyte aspartate aminotransferase measurement were compared: (1) filtration of whole blood through a cellulose column (n = 36); (2) washing of whole blood and aspiration of buffy coat after centrifugation (n = 48); (3) optimized method with washing without aspiration of buffy coat (n = 229).
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| 10. |
- Tsui, Janice C. S., et al.
(författare)
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Localization of nitric oxide synthase in saphenous vein grafts harvested with a novel "no-touch" technique : potential role of nitric oxide contribution to improved early graft patency rates.
- 2002
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Ingår i: Journal of Vascular Surgery. - New York, USA : Elsevier. - 0741-5214 .- 1097-6809. ; 35:2, s. 356-362
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The use of the saphenous vein in coronary artery bypass graft surgery is associated with high 1-year occlusion rates of as much as 30%. A new "no-touch" technique of saphenous vein harvesting in which the vein is harvested with a pedicle of surrounding tissue and not distended may result in improved early patency rates. We hypothesize that nitric oxide synthase is better preserved with the no-touch technique, and the aim of this study was the investigation of whether nitric oxide synthase distribution and quantity in saphenous veins harvested with the no-touch technique differ from those veins harvested with the conventional technique. The separate contribution of perivascular tissue removal and distension to alterations in nitric oxide synthase was also studied.Methods: Segments of 10 saphenous veins were harvested from 10 patients who underwent coronary artery bypass grafting surgery with the no-touch and conventional techniques. Samples were also taken from segments that were stripped of surrounding tissue but not distended. Nitric oxide synthase distribution was studied with reduced nicotinamide adenine dinucleotide phosphate--diaphorase histochemistry, and staining was quantified with image analysis. Immunohistochemistry was used for the identification of specific nitric oxide synthase isoforms, and immunomarkers were used for the identification of associated cell types.Results: Nitric oxide synthase content was higher in no-touch vessels as compared with conventionally harvested vessels (35.5%; P <.05, with analysis of variance). This content was associated with endothelial nitric oxide synthase on the lumen while all three isoforms were present in the media. In the intact adventitia of no-touch vessels, all three isoforms of nitric oxide synthase were also present, associated with microvessels and perivascular nerves. Perivascular tissue stripping and venous distension both contribute to the reduced nitric oxide synthase in conventionally harvested veins.Conclusion: The new no-touch technique of saphenous vein harvesting preserves nitric oxide synthase, which suggests that improved nitric oxide availability may be an important mechanism in the success of this technique.
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