| 1. |
- Vertessy, Beata G., et al.
(författare)
-
The complete triphosphate moiety of non-hydrolyzable substrate analogues is required for a conformational shift of the flexible C-terminus in E. coli dUTP pyrophosphatase
- 1998
-
Ingår i: FEBS Letters. - 1873-3468. ; 421:1, s. 83-88
-
Tidskriftsartikel (refereegranskat)abstract
- The molecular mechanism of substrate analogue interaction with Escherichia coli dUTPase was investigated, using the non-hydrolyzable 2'-deoxyuridine 5'-(α,β-imido)triphosphate (α,β-imido-dUTP). Binding of this analogue induces a difference in the far UV circular dichroism (CD) spectrum arguing for a significant change in protein conformation. The spectral shift is strictly Mg2+-dependent, does not appear with dUDP instead of α,β-imido-dUTP and is not elicited if the flexible C-terminal arm is deleted from the protein by limited tryptic digestion. Involvement of the C-terminal arm in α,β-imido-dUTP binding is consistent with the finding that this analogue protects against tryptic hydrolysis at Arg-141. Near UV CD of ligand-enzyme complexes reveals a characteristic difference in the microenvironments of enzyme-bound dUDP and α,β-imido-dUTP, a difference not observable in C-terminally truncated dUTPase. The results suggest that (i) closing of the active site during the catalytic cycle, through the movement of the C-terminal arm, requires the presence of the complete triphosphate moiety of the substrate in complex with Mg2+, and (ii) after catalytic cleavage the active site pops open to facilitate product release.
|
|
| 2. |
- Cerantola, Yannick, et al.
(författare)
-
Guidelines for perioperative care after radical cystectomy for bladder cancer : enhanced Recovery After Surgery (ERAS(®)) society recommendations
- 2013
-
Ingår i: Clinical Nutrition. - Edinburgh, UK : Churchill-Livingstone. - 0261-5614 .- 1532-1983. ; 32:6, s. 879-887
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Enhanced recovery after surgery (ERAS) pathways have significantly reduced complications and length of hospital stay after colorectal procedures. This multimodal concept could probably be partially applied to major urological surgery.OBJECTIVES: The primary objective was to systematically assess the evidence of ERAS single items and protocols applied to cystectomy patients. The secondary objective was to address a grade of recommendation to each item, based on the evidence and, if lacking, on consensus opinion from our ERAS Society working group.EVIDENCE ACQUISITION: A systematic literature review was performed on ERAS for cystectomy by searching EMBASE and Medline. Relevant articles were selected and quality-assessed by two independent reviewers using the GRADE approach. If no study specific to cystectomy was available for any of the 22 given items, the authors evaluated whether colorectal guidelines could be extrapolated.EVIDENCE SYNTHESIS: Overall, 804 articles were retrieved from electronic databases. Fifteen articles were included in the present systematic review and 7 of 22 ERAS items were studied. Bowel preparation did not improve outcomes. Early nasogastric tube removal reduced morbidity, bowel recovery time and length of hospital stay. Doppler-guided fluid administration allowed for reduced morbidity. A quicker bowel recovery was observed with a multimodal prevention of ileus, including gum chewing, prevention of PONV and minimally invasive surgery.CONCLUSIONS: ERAS has not yet been widely implemented in urology and evidence for individual interventions is limited or unavailable. The experience in other surgical disciplines encourages the development of an ERAS protocol for cystectomy.
|
|
| 3. |
- Gottsäter, Anders, et al.
(författare)
-
Cardiovascular autonomic neuropathy associated with carotid atherosclerosis in Type 2 diabetic patients.
- 2003
-
Ingår i: Diabetic Medicine. - : Wiley. - 1464-5491 .- 0742-3071. ; 20:6, s. 495-499
-
Tidskriftsartikel (refereegranskat)abstract
- AimsTo clarify if cardiovascular autonomic neuropathy is associated with carotid artery atherosclerotic plaques in Type 2 diabetic patients. MethodsCardiovascular autonomic nerve function was related to carotid artery ultrasound in 61 Type 2 diabetic patients 5-6 years after diagnosis of diabetes. ResultsCardiovascular autonomic neuropathy [abnormal age corrected expiration/inspiration (E/I) ratio or acceleration index (AI)] was found in 13/61 (21%) patients. Patients with cardiovascular autonomic neuropathy showed increased degree of stenosis in the common carotid artery (24.6 ± 13.2% vs. 14.7 ± 9.2%; P = 0.014) and a tendency towards a higher plaque score (4.0 ± 1.7 vs. 3.2 ± 1.6; P = 0.064). Controlled for age, AI correlated inversely with degree of stenosis (r = -0.39; P = 0.005), plaque score (r = -0.39; P = 0.005), and mean (r = -0.33; P = 0.018) and maximum (r = -0.39; P = 0.004) intima-media thickness in the common carotid artery. In contrast, E/I ratio correlated only slightly with mean intima-media thickness in the common carotid artery (r = -0.28; P = 0.049). ConclusionsCardiovascular autonomic neuropathy was associated with carotid atherosclerosis in Type 2 diabetic patients. Abnormal E/I ratios reflect efferent structural damage to parasympathetic nerves whereas abnormal AI reflects afferent autonomic dysfunction possibly due to impaired baroreceptor sensitivity secondary to carotid atherosclerosis.
|
|
| 4. |
|
|
| 5. |
- Persson, Beata, et al.
(författare)
-
Initial experiences with the enhanced recovery after surgery (ERAS (R)) protocol in open radical cystectomy
- 2015
-
Ingår i: Scandinavian journal of urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 49:4, s. 302-307
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. This article describes the authors' experiences with the implementation of the Enhanced Recovery After Surgery (ERAS (R)) protocol for open radical cystectomy (ORC). Adherence to the ERAS cystectomy protocol was assessed; secondary outcome measures were impact on perioperative complication rate (Clavien-Dindo classification), time to first defecation, postoperative length of stay and hospital readmission rate. Materials and methods. This retrospective feasibility study compared outcomes with patients in a historical control group. The study group (ERAS) consisted of 31 consecutive patients undergoing ORC and urinary diversion during 1 year from 1 January to 31 December 2011. The control group (pre-ERAS) comprised 39 consecutive patients operated on during 2010. Follow-up was 30 days. Results. There were no significant demographic differences between the two groups, and no differences in complications graded Clavien III or above, or in total length of stay. The ERAS group had statistically significantly shorter mean time to first passage of stool and statistically significantly lower readmission frequency than the pre-ERAS group. The number of patients was small and the study was not randomized; moreover, the use of historical controls inevitably introduced different types of bias. Conclusions. Introduction of the ERAS protocol is clearly feasible in cystectomy, and may improve clinical outcomes in terms of faster return of bowel function and reduction of readmission within 30 days. However, more and larger studies are needed to prove the efficacy of ERAS for patients undergoing ORC.
|
|
| 6. |
- Persson, Beata, et al.
(författare)
-
The National Penile Cancer Register in Sweden 2000-2003
- 2007
-
Ingår i: Scandinavian Journal of Urology and Nephrology. - Oslo : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 41:4, s. 278-282
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. This article reviews the first 4 years of operation of the National Penile Cancer Register (NPECR) in Sweden. The register was set up to gain knowledge about the incidence and primary treatment of penile cancer, including the use of and the frequency of lymph node dissection. The register elicits treatment disparities between regions, and aims to determine the impact of clinical practice guidelines introduced in Sweden. Material and methods. All patients newly diagnosed with penile cancer after the year 2000 have been registered in the NPECR. A total of 454 patients were registered in the period 2000-2003. Results. Registrations in the NPECR were almost complete, with 98.7% of cases registered in the National Cancer Register also being registered in the NPECR. At least 145 clinicians reported to the register. The annual incidence of penile cancer is 2.2/100 000 men. Squamous cell carcinoma accounts for 95% of the cases. The mean age at diagnosis was 65.5 years. Most tumours were classified as Tis, T1 or T2, each class representing 25-30% of the total number of diagnosed cases. Penis-preserving treatment was performed in 58% of the patients (Table I). The number of patients classified as ≥T1/G2-G3 was 206, and 101 of these patients (49%) underwent inguinal lymphadenectomy. Conclusions. We have introduced a population-based register in Sweden with almost complete registration, and this offers unique possibilities for further studies of both epidemiological and clinical aspects of penile cancer. The results obtained to date indicate that the primary treatment is done in many settings and that guidelines, e.g. to dissect lymph nodes, are not always followed.
|
|
| 7. |
|
|
| 8. |
- Vertessy, Beata G, et al.
(författare)
-
Specific Derivatization of the Active Site Tyrosine in dUTPase Perturbs Ligand Binding to the Active Site
- 1996
-
Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 219:2, s. 294-300
-
Tidskriftsartikel (refereegranskat)abstract
- Selective modification of one (of three) tyrosine residue per enzyme monomer leads to inactivation of dUTPase of the retrovirus equine infectious anemia virus (EIAV). The substrate dUMP and the cofactor Mg2+protects against inactivation and modification, in agreement with the study onE. colidUTPase (Vertessyet al.(1994)Biochim. Biophys. Acta1205, 146-150). Amino acid analyses of nitrated dUTPases confirmed Tyr-selectivity of modification. The nitrated residue inE. colidUTPase was identified as the evolutionary highly conserved Tyr-93. The modifiable residue is shown to be the only Tyr exposed in bothE. coliand EIAV dUTPases. As a consequence of Tyr-93 derivatization, the Mg2+-dependent interaction between the substrate-analogue dUDP andE. colidUTPase becomes impaired as shown by circular dichroism spectroscopy, here presented as a tool for monitoring ligand binding to the active site.
|
|
| 9. |
- Zuntini, Alexandre R., et al.
(författare)
-
Phylogenomics and the rise of the angiosperms
- 2024
-
Ingår i: NATURE. - 0028-0836 .- 1476-4687. ; 629, s. 843-850
-
Tidskriftsartikel (refereegranskat)abstract
- Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods(1,2). A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome(3,4). Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins(5-7). However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes(8). This 15-fold increase in genus-level sampling relative to comparable nuclear studies(9) provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.
|
|
