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- Berggren de Verdier, P. J., et al.
(författare)
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Prognostic significance of homozygous deletions and multiple duplications at the CDKN2A (p16INK4a)/ARF (p14ARF) locus in urinary bladder cancer
- 2006
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Ingår i: Scand J Urol Nephrol. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 40:5, s. 363-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The 9p21 locus is a major target in the pathogenesis of human urinary bladder cancer. This locus harbours the CDKN2A/ARF tumour suppressor gene, which encodes two cell-cycle regulatory proteins: p16INK4a and p14ARF. We studied how homozygous deletions and multiple duplications at this locus affect prognosis and survival in patients with bladder cancer. MATERIAL AND METHODS: Real-time quantitative polymerase chain reaction (QPCR), based on simultaneous amplification of ARF and a reference gene, glyceraldehyde-3-phosphate dehydrogenase, was used to measure homozygous deletions and multiple duplications in a population-based material consisting of 478 patients with urinary bladder cancer. Results from real-time QPCR were compared with clinico-pathological parameters and survival curves were generated using the Kaplan-Meier method. RESULTS: Real-time QPCR analysis showed 71 (15%) homozygous deletions and 8 (2%) multiple duplications. We were unable to find any association between either stage or grade and urinary neoplasms with homozygous deletions. However, although there were only a limited number of patients with multiple duplications, 7/8 of them had highly malignant tumours (G2b-G4 or > or = T1; p = 0.02). CONCLUSIONS: Urinary bladder cancers constitute a spectrum of neoplasms with varying clinical manifestations. We were unable to establish a prognostic relevance for patients with tumours harbouring homozygous deletions at the CDKN2A/ARF locus. However, our data did indicate that patients with multiple duplications at the CDKN2A/ARF locus had poor survival. This suggests that multiple duplications, in combination with other genetic changes, have cooperative effects which have a negative outcome on urinary bladder cancer prognosis.
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- Adolfsson, L, et al.
(författare)
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Arthroscopically-assisted reduction of intra-articular fractures of the distal radius
- 1998
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Ingår i: Journal of Hand Surgery - British and European Volume. - 0266-7681 .- 1532-2211. ; 23B:3, s. 391-395
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Tidskriftsartikel (refereegranskat)abstract
- Twenty-seven patients with intraarticular fractures of the distal radius with a step of more than 1 mm in the joint surface after attempted closed reduction, were treated by reduction under arthroscopic control and percutaneous fixation. All fractures healed without measurable incongruity of the joint surface and at follow-up 3 to 38 months after surgery 19 patients had excellent and eight patients good results according to the Mayo modified wrist score.
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- Adolfsson, Per I., et al.
(författare)
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Characterization of EDG receptor expression and proliferative response in cultured human BPH smooth muscle cells
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The endogenous phospholipids, lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are both known to generate a Vvide variety of effects in various cell systems by the endothelial differentiation gene (Edg) receptor family, including 7 different G-protein coupled Edg receptors.In this study, expression of LPA- and SlP Edg receptors was examined, and so was the effect with respect to proliferation on cultured BPH smooth muscle cells smc. Mmeover, theresponse on cAMP levels was examined. Finally, a potential link between activation of the MAP kinase cascade and the LPA stimulated proliferation was investigated.First, the RT-PCR analysis of the Edg receptors in BPH smc, demonstrated a heterogeneous expression including all receptors except the Edg6 subtype. Further, in contrast to LPA, the mitogen effect of SIP, demonstrated a concentration-dependent biphasic response, including stimulation below 1μM, whereas inhibition was obtained at higher concentrations. Forskolin induced a rapid and transient cAMP response in LPA stimulated cells, with a peak-value after 3 minutes. After 15 minutes the cAMP level had retmned to base-line level. However a gradual increase to 15% of maximum value was obtained after additional 30 minutes, and thereafter a gradual reduction was observed. The mentioned antiproliferative response generated by SIP could not be conelated to an intracellular cAMP increase. Finally, when the LPA treated smc was co-incubated with the MAPK kinase inhibitor PD98059 (10 μM) the mitogen response was eliminated.The cAIVIP increase, which was induced by forskolin, corresponds with mentioned antiproliferative effect whereas a similar con-elation was not obtained regarding SIP. The intracellular signal mechanisms triggered by LPA and S1P in BPH smc remain to be further investigated.
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- Adolfsson, Per I., et al.
(författare)
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Characterization of α2-Adrenoceptor Subtypes in Pregnant Human Myometrium
- 1998
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Ingår i: Gynecologic and Obstetric Investigation. - : S. Karger AG. - 0378-7346 .- 1423-002X. ; 45:3, s. 145-150
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present investigation was to determine which subtypes of the α2-adrenoceptors are being expressed in the human pregnant myometrium at term pregnancy. In radioligand binding studies, the specific binding of [3H]rauwolscine to human myometrial membranes was specific and of high affinity with Kd of 2.8 ± 0.6 nM and Bmax of 95 ± 5 fmol/mg protein. Results from competition for the binding of [3H]rauwolscine using subtype-selective ligands, oxymetazoline (α2A-subptype), chlorpromazine (α2B-subtype) and prazosin (α2B-α2C-subtype), suggested that the α2A- and α2B-subtypes are being co-expressed. In order to examine if also the α2C-subtype is being expressed we used an optimal concentration of oxymetazoline or chlorpromazine which would block the high-affinity site, equivalent to the α2A- and α2B-subtype respectively. Competition curves of both oxymetazoline and chlorpromazine still showed a significantly better fit using a two-site model, suggesting that the α2C-subtype also is being expressed. The expression of α2C-subtype mRNA was confirmed using reverse transcription-polymerase chain reaction on mRNA isolated from myometrial biopsies.In conclusion, our results suggest that all three subtypes of α2-adrenoceptors are being coexpressed in the human myometrium at term pregnancy and that α2-expression is dominated by the α2A-subtype.
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- Adolfsson, Per I, et al.
(författare)
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Zinc Induces a Bell-shaped Proliferative Dose-response Effect in Cultured Smooth Muscle Cells From Benign Prostatic Hyperplasia.
- 2015
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Ingår i: Urology. - : Elsevier BV. - 0090-4295 .- 1527-9995. ; 85:3, s. 704.e15-704.e19
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the effects of zinc (Zn(2+)) concentrations on cultured benign prostatic hyperplasia (BPH) smooth muscle cell (SMC) proliferation.METHODS: The effects of Zn(2+) were studied in primary cultures of human BPH SMC, stimulated with either 10-μM lysophosphatidic acid (LPA) or LPA in combination with 100-nM testosterone. Deoxyribonucleic acid replication and protein synthesis using [(3)H]-thymidine and [(35)S]-methionine incorporation were measured. Furthermore, studies were performed to evaluate if Zn(2+) could potentiate the inhibitory effect of phosphodiesterase-5 blockers, on BPH SMC proliferation.RESULTS: Zn(2+) generated a bell-shaped concentration response, both regarding deoxyribonucleic acid replication and protein synthesis in cultured BPH SMC. Below a threshold value (approximately 200 μM), a significant mitogenic effect was seen, whereas higher concentrations inhibited SMC proliferation after stimulation with LPA. This effect was even more pronounced after stimulation of LPA in combination with testosterone. Moreover, phosphodiesterase-5 inhibitors, that is, sildenafil blocked LPA-stimulated BPH SMC proliferation. This antiproliferative effect, was significantly potentiated by coincubation with Zn(2+) in an additative manner.CONCLUSION: The bell-shaped concentration response of Zn(2+) on cultured BPH SMC proliferation suggests that changes in prostate Zn(2+) concentrations, during aging, diet, or inflammatory conditions, may be of importance in the pathogenesis of BPH.
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| 8. |
- Fattibene, P, et al.
(författare)
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The 4th international comparison on EPR dosimetry with tooth enamel Part 1: Report on the results
- 2011
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Ingår i: Radiation Measurements. - : Elsevier. - 1350-4487 .- 1879-0925. ; 46:9, s. 765-771
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents the results of the 4th International Comparison of in vitro electron paramagnetic resonance dosimetry with tooth enamel, where the performance parameters of tooth enamel dosimetry methods were compared among sixteen laboratories from all over the world. The participating laboratories were asked to determine a calibration curve with a set of tooth enamel powder samples provided by the organizers. Nine molar teeth extracted following medical indication from German donors and collected between 1997 and 2007 were prepared and irradiated at the Helmholtz Zentrum Munchen. Five out of six samples were irradiated at 0.1, 0.2, 0.5, 1.0 and 1.5 Gy air kerma; and one unirradiated sample was kept as control. The doses delivered to the individual samples were unknown to the participants, who were asked to measure each sample nine times, and to report the EPR signal response, the mass of aliquots measured, and the parameters of EPR signal acquisition and signal evaluation. Critical dose and detection limit were calculated by the organizers on the basis of the calibration-curve parameters obtained at every laboratory. For calibration curves obtained by measuring every calibration sample three times, the mean value of the detection limit was 205 mGy, ranging from 56 to 649 mGy. The participants were also invited to provide the signal response and the nominal dose of their current dose calibration curve (wherever available), the critical dose and detection limit of which were also calculated by the organizers.
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| 9. |
- Rantalaiho, Ida, et al.
(författare)
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Scandinavian Olecranon Research in the Elderly (SCORE) : protocol for a non- inferiority, randomised, controlled, multicentre trial comparing operative and conservative treatment of olecranon fractures in the elderly
- 2022
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Ingår i: BMJ Open. - : BMJ Publishing Group. - 2044-6055. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The incidence of olecranon fractures is growing in the elderly population. The traditional operative approach is giving way among the elderly to conservative treatment, which seems to provide a comparable functional outcome with a lower complication burden. However, there is still a lack of reliable evidence to support this shift. The objective of this trial is to investigate whether conservative treatment of displaced olecranon fractures in patients aged 75 or older yields comparable results to those of operative treatment in terms of pain and daily function. Methods and analysis Scandinavian Olecranon Research in the Elderly (SCORE) is a randomised, controlled, multicentre, non-inferiority trial. Eligible patients will be randomised to either conservative or operative treatment. The sample size will be 68 patients and allocation done at a 1:1 ratio (34 patients per group). The randomisation is stratified according to the participating hospital and patients sex. Both groups will receive the same postoperative physiotherapy and pain management. The primary outcome is Disabilities of the Arm, Shoulder and Hand at 1-year follow-up. Secondary outcomes are pain and satisfaction measured on visual analogue scales, Patient Reported Elbow Evaluation, range of motion of the elbow and extension strength of the elbow compared with the unaffected arm. Radiographs will be taken at each follow-up. Primary analysis of the results will be conducted on an intention-to-treat basis. Ethics and dissemination The study protocol for this clinical trial has been approved by the Ethics Committee of the Hospital District of Southwest Finland and will be submitted for approval to the Regional Ethics Committees in Linkoping, Sweden and Copenhagen, Denmark. Every recruiting centre will apply local research approvals. The results of this study will be submitted for publication in peer-reviewed journals.
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| 10. |
- Sakano, S., et al.
(författare)
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A single-nucleotide polymorphism in the XPG gene, and tumour stage, grade, and clinical course in patients with nonmuscle-invasive neoplasms of the urinary bladder
- 2006
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Ingår i: BJU Int. - 1464-4096 .- 1464-410X. ; 97:4, s. 847-51
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate whether the single nucleotide polymorphism (SNP), Asp1104His (G3507C), in the XPG gene affects malignant phenotypes of nonmuscle-invasive urinary bladder neoplasms (NIBN), by investigating associations between the SNP and clinicopathological variables in patients with NIBN. PATIENTS AND METHODS: The 233 patients constituted newly diagnosed cases of primary NIBN in the Stockholm area. The Asp1104His polymorphism in the XPG gene was genotyped using a polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: The GC + CC genotypes were more frequent in stage pT1 tumours at initial diagnosis than pTa (odds ratio 1.9, 95% confidence interval 1.0-3.5, P = 0.048). The difference was larger in the young group (4.6, 1.9-11.8, P = 0.001). In the young group, the GC + CC genotypes were significantly more frequent in high-grade than in low-grade tumours (3.1, 1.5-6.8, P = 0.004) whereas in the older group the genotypes were less frequent in high-grade tumours (0.3, 0.1-0.7, P = 0.007). The XPG genotypes were not associated with tumour recurrence, stage progression or survival. CONCLUSION: These results suggest that the SNP in the XPG gene might be related to tumour invasiveness in NIBN.
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