bluuebunny/crossref_metadata_2025_split huggingface dataset:
Observation of intermediate states of the human prion protein by high pressure NMR spectroscopy
Authors: Kachel Norman , Kremer Werner , Zahn Ralph , Kalbitzer Hans Robert 
Published: July 2006

AbstractBackgroundPrions as causative agents of transmissible spongiform encephalopathies (TSEs) in humans and animals are composed of the infectious isomer, PrPSc, of the cellular prion protein, PrPC. The conversion and thus the propensity of PrPCto adopt alternative folds leads to the species-specific propagation of the disease. High pressure is a powerful tool to study the physico-chemical properties of proteins as well as the dynamics and structure of folding intermediates.ResultsConformational intermediates of the human prion proteinhuPrPCwere characterized by a combination of hydrostatic pressure (up to 200 MPa) with two-dimensional NMR spectroscopy. All pressure effects showed to be reversible and there is virtually no difference in the overall pressure response between the folded core of the N-terminal truncatedhuPrPC(121–230) and the full-lengthhuPrPC(23–230). The only significant differences in the pressure response of full-length and truncated PrP suggest that E168, H187, T192, E207, E211 and Y226 are involved in a transient interaction with the unfolded N-terminus. High-pressure NMR spectroscopy indicates that the folded core of the human prion protein occurs in two structural states N1and N2in solution associated with rather small differences in free enthalpies (3.0 kJ/mol). At atmospheric pressure approximately 29% of the protein are already in the pressure favored conformation N2. There is a second process representing two possible folding intermediates I1and I2with corresponding average free enthalpies of 10.8 and 18.6 kJ/mol. They could represent preaggregation states of the protein that coexist at ambient pressure with a very small population of approximately 1.2% and less than 0.1%. Further the pressure response of the N-terminus indicates that four different regions are in a fast equilibrium with non-random structural states whose populations are shifted by pressure.ConclusionWe identified pressure stabilized folding intermediates of the human prion protein. The regions reflecting most strongly the transition to the intermediate states are the β1/α1-loop and the solvent exposed side of α3. The most pressure-sensitive region (representing mainly intermediate I1) is the loop between β-strand 1 and α-helix 1 (residue 139–141), indicating that this region might be the first entry point for the infectious conformer to convert the cellular protein.
A general method for selection of riboflavin-overproducing food grade micro-organisms
Authors: Burgess Catherine M , Smid Eddy J , Rutten Ger , van Sinderen Douwe 
Published: July 2006

Abstract

Background
This study describes a strategy to select and isolate spontaneous riboflavin-overproducing strains of Lactobacillus (Lb.) plantarum, Leuconostoc (Lc.) mesenteroides and Propionibacterium (P.) freudenreichii.

Results
The toxic riboflavin analogue roseoflavin was used to isolate natural riboflavin-overproducing variants of the food grade micro-organisms Lb. plantarum, Lc. mesenteroides and P. freudenreichii strains. The method was successfully employed for strains of all three species. The mutation(s) responsible for the observed overproduction of riboflavin were identified for isolates of two species.

Conclusion
Selection for spontaneous roseoflavin-resistant mutants was found to be a reliable method to obtain natural riboflavin-overproducing strains of a number of species commonly used in the food industry. This study presents a convenient method for deriving riboflavin-overproducing strains of bacterial starter cultures, which are currently used in the food industry, by a non-recombinant methodology. Use of such starter strains can be exploited to increase the vitamin content in certain food products.
The positive impact of red palm oil in school meals on vitamin A status: study in Burkina Faso
Authors: Zeba Augustin N , Prével Yves Martin , Somé Issa T , Delisle Hélène F 
Published: July 2006

Abstract

Background
Vitamin A (VA) deficiency is widespread in sub-Saharan Africa and school-age children are a vulnerable group. In Burkina Faso, the production and consumption of red palm oil (RPO) is being promoted as a food supplement for VA. The objective of the study was to assess the impact on serum retinol of adding RPO to school lunch in two test zones of Burkina Faso.

Methods
Over one school year, 15 ml RPO was added to individual meals 3 times a week in selected primary schools in two sites. Serum retinol was measured with HPLC at baseline and exactly 12 months later to take account of seasonality. A simple pre-post test design was used in the Kaya area (north-central Burkina), where 239 pupils from 15 intervention schools were randomly selected for the evaluation. In Bogandé (eastern Burkina), 24 schools were randomised for the controlled intervention trial: 8 negative controls (G1) with only the regular school lunch; 8 positive controls (G2) where the pupils received a single VA capsule (60 mg) at the end of the school year; and 8 schools with RPO through the school year (G3). A random sample of 128 pupils in each school group took part in the evaluation.

Results
In Kaya, serum retinol went from 0.77 ± 0.37 μmol/L at baseline to 1.07 ± 0.40 μmol/L one year later (p < 0.001). The rate of low serum retinol (<0.7 μmol/L) declined from 47.2% to 13.1%. In Bogandé, serum retinol increased significantly (p < 0.001) only in the capsule and RPO groups, going from 0.77 ± 0.28 to 0.98 ± 0.33 μmol/L in the former, and from 0.82 ± 0.3 to 0.98 ± 0.33 μmol/L in the latter. The rate of low serum retinol went from 46.1 to 17.1% in the VA capsule group and from 40.4% to 14.9% in the RPO group. VA-deficient children benefited the most from the capsule or RPO. Female sex, age and height-for-age were positively associated with the response to VA capsules or RPO.

Conclusion
RPO given regularly in small amounts appears highly effective in the reduction of VA deficiency. RPO deserves more attention as a food supplement for VA and as a potential source of rural income in Sahelian countries.
Combining partial liver resection and local ablation of liver tumours: a preliminary Dutch experience
Authors: Fioole Bram , Jansen Maarten C , van Duijnhoven Frederieke H , van Hillegersberg Richard , van Gulik Thomas M , Borel Rinkes Inne H M 
Published: July 2006

Abstract

Background
The combination of partial liver resection and radiofrequency ablation (RFA) is a novel concept in the treatment of unresectable liver malignancies. The aim of this study is to evaluate the results of this combined strategy in the Netherlands.

Methods
Thirty-five patients treated with a combination of partial liver resection and RFA were identified from a prospectively registered pooled multicentre database. All patients were operated between June 1999 and November 2003 in 8 medical centres in the Netherlands. Main outcome parameters were morbidity, mortality, local success rate, and survival.

Results
Thirty-seven operations were performed in 35 patients. The group consisted of 20 male and 15 female patients with a median age of 59 years (range 41–76). Seventy-six lesions were resected and RFA was performed to ablate 82 unresectable liver tumours. Twelve patients developed a total of 24 complications, resulting in an overall perioperative morbidity rate of 32%. In two patients major complications resulted in postoperative death (postoperative mortality rate 5.4%). Local success rate after RFA was 88% and the estimated 1-, 2- and 3-year overall survival rates were 84%, 70% and 43%, respectively.

Conclusion
This strategy should only be performed following strict patient selection and within the context of prospective clinical trials.
A simplified method for power-law modelling of metabolic pathways from time-course data and steady-state flux profiles
Authors: Kitayama Tomoya , Kinoshita Ayako , Sugimoto Masahiro , Nakayama Yoichi , Tomita Masaru 
Published: July 2006

Abstract

Background
In order to improve understanding of metabolic systems there have been attempts to construct S-system models from time courses. Conventionally, non-linear curve-fitting algorithms have been used for modelling, because of the non-linear properties of parameter estimation from time series. However, the huge iterative calculations required have hindered the development of large-scale metabolic pathway models. To solve this problem we propose a novel method involving power-law modelling of metabolic pathways from the Jacobian of the targeted system and the steady-state flux profiles by linearization of S-systems.

Results
The results of two case studies modelling a straight and a branched pathway, respectively, showed that our method reduced the number of unknown parameters needing to be estimated. The time-courses simulated by conventional kinetic models and those described by our method behaved similarly under a wide range of perturbations of metabolite concentrations.

Conclusion
The proposed method reduces calculation complexity and facilitates the construction of large-scale S-system models of metabolic pathways, realizing a practical application of reverse engineering of dynamic simulation models from the Jacobian of the targeted system and steady-state flux profiles.
The prenatal ultrasonographic detection of myelomeningocele in patients referred to Children's Hospital Medical Center: a cross sectional study
Authors: Kazmi Syed Shuja , Nejat Farideh , Tajik Parvin , Roozbeh Hadi 
Published: July 2006

Abstract

Background
To find out about the prenatal diagnosis rate of myelomeningocele (MMC) by ultrasound scan in patients referred to the Children's Hospital Medical Center in Tehran, Iran from July 2004 to July 2005.

Methods
We included 140 children born with MMC and who were referred for management, surgery and treatment of complications associated with it. The ultrasound reports were examined. Data on sex, age, location of MMC, time of prenatal ultrasound and the trimester in which the diagnosis was made along with the results of the diagnosis (MMC, hydrocephalus, or both), were collected.

Results
Among the studied patients, 136 (97.1%) cases had prenatal ultrasound, amongst those, 58 (42.6%) sonographic evaluations were diagnostic for hydrocephalus and/or MMC. The prenatal ultrasound was positive for MMC in 16 (11.8%), hydrocephalus in 25 (18.4%) and both MMC and hydrocephalus in 17 (12.5%) cases. Among all cases with prenatal diagnosis of MMC, 3.4% were detected in the first, 31% in the second and 65.5% in the third trimester. Thoracic/thoracolumbar lesions were found prenatally in 40% of cases, which is significantly higher than the detection rate of other locations including cervical/cervicothoracic and lumbar/lumbosacral/sacral regions diagnosed only in 0% and 21% of cases respectively.

Conclusion
There is a large difference between the detection rate of our population (24.3%) compared to others (68%). Pregnant women should have an ultrasound at 20–22 week for detection of congenital anomalies including MMC.
Comparison of the effects of three different (-)-hydroxycitric acid preparations on food intake in rats: response
Authors: Preuss Harry G , Bagchi Manashi , Bagchi Debasis 
Published: July 2006

Abstract
A response to Louter-van de Haar J, Wielinga PY, Scheurink AJ, Nieuwenhuizen AG: Comparison of the effects of three different (-)-hydroxycitric acid preparations on food intake in rats. Nutr Metabol 2005, 2:23
Differential effects of curcumin on vasoactive factors in the diabetic rat heart
Authors: Farhangkhoee Hana , Khan Zia A , Chen Shali , Chakrabarti Subrata 
Published: July 2006

Abstract

Background
Increased oxidative stress has been associated with the pathogenesis of chronic diabetic complications, including cardiomyopathy. Recent studies indicate that curcumin, a potent antioxidant, may be beneficial in preventing diabetes-induced oxidative stress and subsequent secondary complications. We have investigated the effects of curcumin on the nitric oxide (NO) pathway in cardiac tissues and cultured cells.

Methods
Streptozotocin-induced diabetic rats were treated with curcumin for a period of one month. Heart tissues were then analyzed for endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) mRNA expression. Oxidative protein and DNA damage were assessed by immunohistochemical analysis of nitrotyrosine and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Heart tissues were further subjected to endothelin-1 (ET-1) mRNA expression. In order to further characterize the effects of curcumin, we assayed microvascular endothelial cells (MVECs). Cultured MVECs, exposed either to glucose or glucose and varying concentrations of curcumin, were assessed for alterations of NOS expression and activation of nuclear factor-κB (NF-κB) and activating protein-1 (AP-1). Oxidative stress and ET-1 expression levels were also assayed.

Results
Our results indicate that one month of diabetes causes an upregulation of both eNOS and iNOS mRNA levels, and nitrotyrosine and 8-OHdG immunoreactivity in the heart. Treatment of diabetic rats with curcumin reduced eNOS and iNOS levels in association with reduced oxidative DNA and protein damage. Interestingly, curcumin further increased vasoconstrictor ET-1 in the heart. Exposure of MVECs to high glucose increased both eNOS and iNOS levels and oxidative stress. Curcumin prevented NOS alteration and oxidative stress in a dose-dependent manner which was mediated by nuclear factor-κB and activating protein-1. Exposure to curcumin also increased ET-1 levels in the MVECs.

Conclusion
Our studies indicate the differential effects of curcumin in vasoactive factor expression in the heart and indicate the importance of tissue microenvironment in the treatment of diabetic complications.
The μ Opioid Agonist Morphine Modulates Potentiation of Capsaicin-Evoked TRPV1 Responses through a Cyclic AMP-Dependent Protein Kinase a Pathway
Authors: Vetter Irina , Wyse Bruce D , Monteith Gregory R , Roberts-Thomson Sarah J , Cabot Peter J 
Published: July 2006

Background The vanilloid receptor 1 (TRPV1) is critical in the development of inflammatory hyperalgesia. Several receptors including G-protein coupled prostaglandin receptors have been reported to functionally interact with the TRPV1 through a cAMP-dependent protein kinase A (PKA) pathway to potentiate TRPV1-mediated capsaicin responses. Such regulation may have significance in inflammatory pain. However, few functional receptor interactions that inhibit PKA-mediated potentiation of TRPV1 responses have been described. Results In the present studies we investigated the hypothesis that the μ opioid receptor (MOP) agonist morphine can modulate forskolin-potentiated capsaicin responses through a cAMP-dependent PKA pathway. HEK293 cells were stably transfected with TRPV1 and MOP, and calcium (Ca2+) responses to injection of the TRPV1 agonist capsaicin were monitored in Fluo-3-loaded cells. Pre-treatment with morphine did not inhibit unpotentiated capsaicin-induced Ca2+ responses but significantly altered capsaicin responses potentiated by forskolin. TRPV1-mediated Ca2+ responses potentiated by the direct PKA activator 8-Br-cAMP and the PKC activator Phorbol-12-myristate-13-acetatewere not modulated by morphine. Immunohistochemical studies confirmed that the TRPV1 and MOP are co-expressed on cultured Dorsal Root Ganglion neurones, pointing towards the existence of a functional relationship between the G-protein coupled MOP and nociceptive TRPV1. Conclusion The results presented here indicate that the opioid receptor agonist morphine acts via inhibition of adenylate cyclase to inhibit PKA-potentiated TRPV1 responses. Targeting of peripheral opioid receptors may therefore have therapeutic potential as an intervention to prevent potentiation of TRPV1 responses through the PKA pathway in inflammation.
Are bone erosions detected by magnetic resonance imaging and ultrasonography true erosions? A comparison with computed tomography in rheumatoid arthritis metacarpophalangeal joints
Authors: Døhn Uffe Møller , Ejbjerg Bo J , Court-Payen Michel , Hasselquist Maria , Narvestad Eva , Szkudlarek Marcin , Møller Jakob M , Thomsen Henrik S , Østergaard Mikkel 
Published: July 2006

AbstractThe objective of the study was, with multidetector computed tomography (CT) as the reference method, to determine whether bone erosions in rheumatoid arthritis (RA) metacarpophalangeal (MCP) joints detected with magnetic resonance imaging (MRI) and ultrasonography (US), but not with radiography, represent true erosive changes. We included 17 RA patients with at least one, previously detected, radiographically invisible MCP joint MRI erosion, and four healthy control individuals. They all underwent CT, MRI, US and radiography of the 2nd to 5th MCP joints of one hand on the same day. Each imaging modality was evaluated for the presence of bone erosions in each MCP joint quadrant. In total, 336 quadrants were examined. The sensitivity, specificity and accuracy, respectively, for detecting bone erosions (with CT as the reference method) were 19%, 100% and 81% for radiography; 68%, 96% and 89% for MRI; and 42%, 91% and 80% for US. When the 16 quadrants with radiographic erosions were excluded from the analysis, similar values for MRI (65%, 96% and 90%) and US (30%, 92% and 80%) were obtained. CT and MRI detected at least one erosion in all patients but none in control individuals. US detected at least one erosion in 15 patients, however, erosion-like changes were seen on US in all control individuals. Nine patients had no erosions on radiography. In conclusion, with CT as the reference method, MRI and US exhibited high specificities (96% and 91%, respectively) in detecting bone erosions in RA MCP joints, even in the radiographically non-erosive joints (96% and 92%). The moderate sensitivities indicate that even more erosions than are seen on MRI and, particularly, US are present. Radiography exhibited high specificity (100%) but low sensitivity (19%). The present study strongly indicates that bone erosions, detected with MRI and US in RA patients, represent a loss of calcified tissue with cortical destruction, and therefore can be considered true bone erosions.
A cell-cycle independent role for p21 in regulating synovial fibroblast migration in rheumatoid arthritis
Authors: Woods James M , Klosowska Karolina , Spoden Darrin J , Stumbo Nataliya G , Paige Douglas J , Scatizzi John C , Volin Michael V , Rao Malathi S , Perlman Harris 
Published: July 2006

AbstractRheumatoid arthritis (RA) is characterized by synovial hyperplasia and destruction of cartilage and bone. The fibroblast-like synoviocyte (FLS) population is central to the development of pannus by migrating into cartilage and bone. We demonstrated previously that expression of the cell cycle inhibitor p21 is significantly reduced in RA synovial lining, particularly in the FLS. The aim of this study was to determine whether reduced expression of p21 in FLS could alter the migratory behavior of these cells. FLS were isolated from mice deficient in p21 (p21(-/-)) and were examined with respect to growth and migration. p21(-/-) and wild-type (WT) FLS were compared with respect to migration towards chemoattractants found in RA synovial fluid in the presence and absence of cell cycle inhibitors. Restoration of p21 expression was accomplished using adenoviral infection. As anticipated from the loss of a cell cycle inhibitor, p21(-/-) FLS grow more rapidly than WT FLS. In examining migration towards biologically relevant RA synovial fluid, p21(-/-) FLS display a marked increase (3.1-fold; p < 0.05) in migration compared to WT cells. Moreover, this effect is independent of the cell cycle since chemical inhibitors that block the cell cycle have no effect on migration. In contrast, p21 is required to repress migration as restoration of p21 expression in p21(-/-) FLS reverses this effect. Taken together, these data suggest that p21 plays a novel role in normal FLS, namely to repress migration. Loss of p21 expression that occurs in RA FLS may contribute to excessive invasion and subsequent joint destruction.
Autoantibodies against the replication protein A complex in systemic lupus erythematosus and other autoimmune diseases
Authors: Yamasaki Yoshioki , Narain Sonali , Hernandez Liza , Barker Tolga , Ikeda Keigo , Segal Mark S , Richards Hanno B , Chan Edward KL , Reeves Westley H , Satoh Minoru 
Published: July 2006

AbstractReplication protein A (RPA), a heterotrimer with subunits of molecular masses 70, 32, and 14 kDa, is a single-stranded-DNA-binding factor involved in DNA replication, repair, and recombination. There have been only three reported cases of anti-RPA in systemic lupus erythematosus (SLE) and Sjögren syndrome (SjS). This study sought to clarify the clinical significance of autoantibodies against RPA. Sera from 1,119 patients enrolled during the period 2000 to 2005 were screened by immunoprecipitation (IP) of 35S-labeled K562 cell extract. Antigen-capture ELISA with anti-RPA32 mAb, immunofluorescent antinuclear antibodies (ANA) and western blot analysis with purified RPA were also performed. Our results show that nine sera immunoprecipitated the RPA70–RPA32–RPA14 complex and all were strongly positive by ELISA (titers 1:62,500 to 1:312,500). No additional sera were positive by ELISA and subsequently confirmed by IP or western blotting. All sera showed fine speckled/homogeneous nuclear staining. Anti-RPA was found in 1.4% (4/276) of SLE and 2.5% (1/40) of SjS sera, but not in rheumatoid arthritis (0/35), systemic sclerosis (0/47), or polymyositis/dermatomyositis (0/43). Eight of nine patients were female and there was no racial predilection. Other positive patients had interstitial lung disease, autoimmune thyroiditis/hepatitis C virus/pernicious anemia, or an unknown diagnosis. Autoantibody specificities found in up to 40% of SLE and other diseases, such as anti-nRNP, anti-Sm, anti-Ro, and anti-La, were unusual in anti-RPA-positive sera. Only one of nine had anti-Ro, and zero of nine had anti-nRNP, anti-Sm, anti-La, or anti-ribosomal P antibodies. In summary, high titers of anti-RPA antibodies were found in nine patients (1.4% of SLE and other diseases). Other autoantibodies found in SLE were rare in this subset, suggesting that patients with anti-RPA may form a unique clinical and immunological subset.