bluuebunny/crossref_metadata_2025_split huggingface dataset:
No Association of nineteen COX-2 gene variants to preclinical markers of atherosclerosis The Cardiovascular Risk in Young Finns Study
Authors: Lähteelä Kati , Kunnas Tarja , Lyytikäinen Leo-Pekka , Mononen Nina , Taittonen Leena , Laitinen Tomi , Kettunen Johannes , Juonala Markus , Hutri-Kähönen Nina , Kähönen Mika , Viikari Jorma S , Raitakari Olli T , Lehtimäki Terho , Nikkari Seppo T 
Published: May 2012

Abstract

Backgroud
The role of cyclooxygenase-2 (COX-2) single nucleotide polymorphisms has mostly been studied in relation to advanced atherosclerosis, but little is known how they contribute to preclinical disease. In the present study we analyzed whether COX-2 gene variants associate independently with the early subclinical markers of atherosclerosis, carotid intima-media thickness and carotid artery distensibility in a population of young healthy Caucasian adults.

Methods
SNPs for association analysis were collected from the COX-2 gene and 5 kb up- and downstream of it. There were 19 SNPs available for analysis, four genotyped and fifteen imputed. Genotype data was available for 2442 individuals participating in the Cardiovascular Risk in Young Finns Study. Genotype imputation was performed using MACH 1.0 and HapMap II CEU (release 22) samples as reference. Association analysis was performed using linear regression with an additive model. PLINK was used for true genotyped SNPs and ProbABEL for imputed genotype dosages. False discovery rate was used to take into account multiple testing bias.

Results
Two of the COX-2 variants (rs689470, rs689462) associated with distensibility (p = 0.005) under the linear regression additive model. After adjustment with gender, age, body mass index and smoking status, association between these SNPs and distensibility remained significant (p = 0.031). Subjects carrying the minor alleles had higher value of carotid artery distensibility compared to the major allele homozygotes. However, after correcting p-values for multiple testing bias using false discovery rate, association was lost. Another COX-2 variant rs4648261 associated with mean carotid intima-media thickness (p = 0.046) and maximal carotid intima-media thickness (p = 0.048) in the linear regression model. Subjects carrying the minor allele of rs4648261 had lower values of mean and maximal carotid intima-media thickness compared to subjects homozygote for major allele. After adjustments the associations were lost with both mean and maximal carotid intima-media thickness. Thus, no statistically significant associations of the studied COX-2 variants with carotid artery distensibility or carotid intima-media thickness were found.

Conclusions
Our results suggest that in a Finnish population, there are no significant associations between COX-2 variants and early atherosclerotic changes in young adulthood.
Serum C-reactive protein and thioredoxin levels in subjects with mildly reduced glomerular filtration rate
Authors: Tsuchikura Shoko , Shoji Tetsuo , Shimomura Naoko , Kakiya Ryusuke , Emoto Masanori , Koyama Hidenori , Ishimura Eiji , Inaba Masaaki , Nishizawa Yoshiki 
Published: May 2012

AbstractBackgroundChronic kidney disease (CKD) is a newly recognized high-risk condition for cardiovascular disease (CVD), and previous studies reported the changes in inflammation and oxidative stress in advanced stages of CKD. We compared the levels of serum biomarkers for inflammation and oxidative stress between subjects with normal and mildly reduced glomerular filtration rate (GFR).MethodsThe subjects were 182 participants of a health check-up program including those with normal (≥ 90 mL/min/1.73 m2, N = 79) and mildly reduced eGFR (60-89 mL/min/1.73 m2, N = 103) which was calculated based on serum creatinine, age and sex. We excluded those with reduced eGFR < 60 mL/min/1.73 m2. No one had proteinuria. We measured serum levels of C-reactive protein (CRP) and thioredoxin (TRX) as the markers of inflammation and oxidative stress, respectively.ResultsAs compared with subjects with normal eGFR, those with mildly reduced eGFR had increased levels of both CRP and TRX. Also, eGFR was inversely correlated with these biomarkers. The associations of eGFR with these biomarkers remained significant after adjustment for age and sex. When adjustment was done for eight possible confounders, CRP showed significant association with systolic blood pressure, high density lipoprotein cholesterol (HDL-C) and non-HDL-C, whereas TRX was associated with sex significantly, and with eGFR and systolic blood pressure at borderline significance.ConclusionsWe showed the increased levels of CRP and TRX in subjects with mildly reduced eGFR. The eGFR-CRP link and the eGFR-TRX link appeared to be mediated, at least partly, by the alterations in blood pressure and plasma lipids in these subjects.
Irradiation-induced telomerase activity and gastric cancer risk: a case-control analysis in a Chinese Han population
Authors: He Xianli , Qiao Qing , Ge Naijian , Nan Jing , Shen Shuqun , Wang Zizhong , Yang Yefa , Bao Guoqiang 
Published: May 2012

Abstract

Background
Telomerase expression is one of the characteristics of gastric cancer (GC) cells and telomerase activity is frequently up-regulated by a variety of mechanisms during GC development. Therefore, we hypothesized that elevated levels of activated telomerase might enhance GC risk due to increased propagation of cells with DNA damage, such as induced by γ-radiation.

Methods
To explore this hypothesis, 246 GC cases and 246 matched controls were recruited in our case-control study. TRAP-ELISA was used to assess the levels of telomerase activity at baseline and after γ-radiation and the γ-radiation-induced telomerase activity (defined as after γ-irradiation/baseline) in cultured peripheral blood lymphocytes (PBLs).

Results
Our data showed that there was no significant difference for the baseline telomerase activity between GC cases and controls (10.17 ± 7.21 vs. 11.02 ± 8.03, p = 0.168). However, after γ-radiation treatment, γ-radiation-induced telomerase activity was significantly higher in the cases than in the controls (1.51 ± 0.93 vs. 1.22 ± 0.66, p < 0.001). Using the median value of γ-radiation-induced telomerase activity in the controls as a cutoff point, we observed that high γ-radiation-induced telomerase activity was associated with a significantly increased GC risk (adjusted odds ratio, 2.45; 95% confidence interval, 1.83-3.18). Moreover, a dose response association was noted between γ-radiation-induced telomerase activity and GC risk. Age, but not sex, smoking and drinking status seem to have a modulating effect on the γ-radiation-induced telomerase activities in both cases and controls.

Conclusion
Overall, our findings for the first time suggest that the increased γ-radiation-induced telomerase activity in PBLs might be associated with elevated GC risk. Further confirmation of this association using a prospective study design is warranted.
Early assessment by FDG-PET/CT of patients with advanced renal cell carcinoma treated with tyrosine kinase inhibitors is predictive of disease course
Authors: Ueno Daiki , Yao Masahiro , Tateishi Ukihide , Minamimoto Ryogo , Makiyama Kazuhide , Hayashi Narihiko , Sano Futoshi , Murakami Takayuki , Kishida Takeshi , Miura Takeshi , Kobayashi Kazuki , Noguchi Sumio , Ikeda Ichiro , Ohgo Yoshiharu , Inoue Tomio , Kubota Yoshinobu , Nakaigawa Noboru 
Published: May 2012

Abstract

Background
We reported previously that 18F-2-fluoro-2-deoxyglucose positron emission tomography/ computed tomography (FDG PET/CT) had potential for evaluating early response to treatment by tyrosine kinase inhibitors (TKIs) in advanced renal cell carcinoma (RCC). This time we investigated the relation of the early assessment by FDG PET/CT to long-term prognosis with an expanded number of patients and period of observation.

Methods
Patients for whom TKI treatment for advanced RCC was planned were enrolled. FDG PET/CT was performed before TKI treatment and after one month of TKI treatment. The relations of the FDGPET/CT assessment to progression free survival (PFS) and overall survival (OS) were investigated.

Results
Thirty-five patients were enrolled (sunitinib 19 cases, sorafenib 16 cases). The patients with RCC showing high SUVmax in pretreatment FDG PET/CT demonstrated short PFS (P =0.024, hazard ratio 1.137, 95% CI 1.017-1.271) and short OS (P =0.004, hazard ratio 1.210 95% CI 1.062-1.379). Thirty patients (sunitinib 16 cases, sorafenib 14 cases) were evaluated again after 1 month. The PFS of the patients whose SUVmax decreased<20% was shorter than that of the patients whose SUVmax decreased<20% (P = 0.027, hazard ratio 3.043, 95% CI 1.134-8.167). The PFS of patients whose tumor diameter sum increased was shorter than that of the patient with tumors whose diameter sum did not (P =0.006, hazard ratio 4.555, 95% CI 1.543-13.448).
The patients were classified into three response groups: good responder (diameter sum did not increase, and SUVmax decreased ≥ 20%), intermediate responder (diameter sum did not increase, and SUVmax decreased<20%), and poor responder (diameter sum increased, or one or more new lesions appeared). The median PFS of good, intermediate, and poor responders were 458 ± 146 days, 131 ± 9 days, and 88 ± 26 days (good vs. intermediate P = 0.0366, intermediate vs. poor P = 0.0097, log-rank test). Additionally the mean OSs were 999 ± 70 days, 469 ± 34 days, and 374 ± 125 days, respectively (good vs. intermediate P = 0.0385, intermediate vs. poor P = 0.0305, log-rank test).

Conclusions
The evaluation of RCC response to TKI by tumor size and FDG uptake using FDG PET/CT after 1 month can predict PFS and OS.
Intraoperative fracture of phacoemulsification sleeve
Authors: Shum Jennifer WH , Chan Keith SK , Wong David , Li Kenneth KW 
Published: May 2012

Abstract

Background
We describe a case of intraoperative fracture of phacoemulsification sleeve during phacoemulsification surgery.

Case presentation
Phacoemulsification surgery was performed in the left eye of a 58-year-old lady with grade II nuclear sclerosis & grade I cortical cataract. Towards the end of quadrant removal, there was anterior chamber instability with impaired followability of nuclear fragments. The distal part of the fractured sleeve remained inside the anterior chamber upon removal of the phacoemulsification probe. The retained sleeve was retrieved with a pair of forceps through the corneal incision site, which did not require widening. There was no missing fragments retained intraocularly and the patient had an uneventful recovery with vision of 20/25 at three months post-operatively.

Conclusion
Phacoemulsification sleeve fracture is an uncommon complication. With early identification of this condition and proper management, major complications can be avoided.
The relationship between workers’ self-reported changes in health and their attitudes towards a workplace intervention: lessons from smoke-free legislation across the UK hospitality industry
Authors: MacCalman Laura , Semple Sean , Galea Karen S , Van Tongeren Martie , Dempsey Scott , Hilton Shona , Gee Ivan , Ayres Jon G 
Published: May 2012

Abstract

Background
The evaluation of smoke-free legislation (SFL) in the UK examined the impacts on exposure to second-hand smoke, workers’ attitudes and changes in respiratory health. Studies that investigate changes in the health of groups of people often use self-reported symptoms. Due to the subjective nature it is of interest to determine whether workers’ attitudes towards the change in their working conditions may be linked to the change in health they report.

Methods
Bar workers were recruited before the introduction of the SFL in Scotland and England with the aim of investigating their changes to health, attitudes and exposure as a result of the SFL. They were asked about their attitudes towards SFL and the presence of respiratory and sensory symptoms both before SFL and one year later. Here we examine the possibility of a relationship between initial attitudes and changes in reported symptoms, through the use of regression analyses.

Results
There was no difference in the initial attitudes towards SFL between those working in Scotland and England. Bar workers who were educated to a higher level tended to be more positive towards SFL. Attitude towards SFL was not found to be related to change in reported symptoms for bar workers in England (Respiratory, p = 0.755; Sensory, p = 0.910). In Scotland there was suggestion of a relationship with reporting of respiratory symptoms (p = 0.042), where those who were initially more negative to SFL experienced a greater improvement in self-reported health.

Conclusions
There was no evidence that workers who were more positive towards SFL reported greater improvements in respiratory and sensory symptoms. This may not be the case in all interventions and we recommend examining subjects’ attitudes towards the proposed intervention when evaluating possible health benefits using self-reported methods.
The crystal structure of the catalytic domain of a eukaryotic guanylate cyclase
Authors: Winger Jonathan A , Derbyshire Emily R , Lamers Meindert H , Marletta Michael A , Kuriyan John 
Published: May 2012

Abstract

Background
Soluble guanylate cyclases generate cyclic GMP when bound to nitric oxide, thereby linking nitric oxide levels to the control of processes such as vascular homeostasis and neurotransmission. The guanylate cyclase catalytic module, for which no structure has been determined at present, is a class III nucleotide cyclase domain that is also found in mammalian membrane-bound guanylate and adenylate cyclases.

Results
We have determined the crystal structure of the catalytic domain of a soluble guanylate cyclase from the green algae Chlamydomonas reinhardtii at 2.55 Å resolution, and show that it is a dimeric molecule.

Conclusion
Comparison of the structure of the guanylate cyclase domain with the known structures of adenylate cyclases confirms the close similarity in architecture between these two enzymes, as expected from their sequence similarity. The comparison also suggests that the crystallized guanylate cyclase is in an inactive conformation, and the structure provides indications as to how activation might occur. We demonstrate that the two active sites in the dimer exhibit positive cooperativity, with a Hill coefficient of ~1.5. Positive cooperativity has also been observed in the homodimeric mammalian membrane-bound guanylate cyclases. The structure described here provides a reliable model for functional analysis of mammalian guanylate cyclases, which are closely related in sequence.
Type II restriction endonuclease R.Hpy188I belongs to the GIY-YIG nuclease superfamily, but exhibits an unusual active site
Authors: Kaminska Katarzyna H , Kawai Mikihiko , Boniecki Michal , Kobayashi Ichizo , Bujnicki Janusz M 
Published: May 2012

Abstract

Background
Catalytic domains of Type II restriction endonucleases (REases) belong to a few unrelated three-dimensional folds. While the PD-(D/E)XK fold is most common among these enzymes, crystal structures have been also determined for single representatives of two other folds: PLD (R.BfiI) and half-pipe (R.PabI). Bioinformatics analyses supported by mutagenesis experiments suggested that some REases belong to the HNH fold (e.g. R.KpnI), and that a small group represented by R.Eco29kI belongs to the GIY-YIG fold. However, for a large fraction of REases with known sequences, the three-dimensional fold and the architecture of the active site remain unknown, mostly due to extreme sequence divergence that hampers detection of homology to enzymes with known folds.

Results
R.Hpy188I is a Type II REase with unknown structure. PSI-BLAST searches of the non-redundant protein sequence database reveal only 1 homolog (R.HpyF17I, with nearly identical amino acid sequence and the same DNA sequence specificity). Standard application of state-of-the-art protein fold-recognition methods failed to predict the relationship of R.Hpy188I to proteins with known structure or to other protein families. In order to increase the amount of evolutionary information in the multiple sequence alignment, we have expanded our sequence database searches to include sequences from metagenomics projects. This search resulted in identification of 23 further members of R.Hpy188I family, both from metagenomics and the non-redundant database. Moreover, fold-recognition analysis of the extended R.Hpy188I family revealed its relationship to the GIY-YIG domain and allowed for computational modeling of the R.Hpy188I structure. Analysis of the R.Hpy188I model in the light of sequence conservation among its homologs revealed an unusual variant of the active site, in which the typical Tyr residue of the YIG half-motif had been substituted by a Lys residue. Moreover, some of its homologs have the otherwise invariant Arg residue in a non-homologous position in sequence that nonetheless allows for spatial conservation of the guanidino group potentially involved in phosphate binding.

Conclusion
The present study eliminates a significant "white spot" on the structural map of REases. It also provides important insight into sequence-structure-function relationships in the GIY-YIG nuclease superfamily. Our results reveal that in the case of proteins with no or few detectable homologs in the standard "non-redundant" database, it is useful to expand this database by adding the metagenomic sequences, which may provide evolutionary linkage to detect more remote homologs.
Antipyretic, analgesic and anti-inflammatory activity of Viola betonicifolia whole plant
Authors: Muhammad Naveed , Saeed Muhammad , Khan Haroon 
Published: May 2012

Abstract

Background
Pyrexia, algesia and inflammation are associated with several pathological conditions. Synthetic drugs available for the treatment of these conditions cause multiple unwanted effects. Several studies are ongoing worldwide to find natural healing agents with better safety profile. The current study was thus aimed at evaluating antipyretic, analgesic and anti-inflammatory activities of the methanolic extract of whole plant of V. betonicifolia (VBME).

Methods
VBME was employed to assess antipyretic activity in yeast induced hyperthermia. Analgesic profile was ascertained in acetic acid induced writhing, hot plat and tail immersion test. Nevertheless, the anti-inflammatory activity was tested in carrageenan induced paw edema and histamine induced inflammatory tests. BALB/c mice were used at test doses of 100, 200 and 300mg/kg body weight intra peritoneally (i.p).

Results
In yeast induced pyrexia, VBME demonstrated dose dependently (78.23%) protection at 300mg/kg, similar to standard drug, paracetamol (90%) at 150mg/kg i.p. VBME showed a dose dependent analgesia in various pain models i.e. acetic acid, hot plat and tail immersion having 78.90%, 69.96% and 68.58% protection respectively at 300mg/kg. However, the analgesic action of VBME was completely antagonized by the injection of naloxone like opiate antagonists. Similarly carrageenan and histamine induces inflammation was significantly antagonized by VBME, 66.30% and 60.80% respectively at 300mg/kg.

Conclusions
It is concluded that VBME has marked antipyretic, analgesic and anti-inflammatory activities in various animal models and this strongly supports the ethnopharmacological uses of Viola betonicifolia as antipyretic, analgesic and anti-inflammatory plant.
Natural resistance to ascorbic acid induced oxidative stress is mainly mediated by catalase activity in human cancer cells and catalase-silencing sensitizes to oxidative stress
Authors: Klingelhoeffer Christoph , Kämmerer Ulrike , Koospal Monika , Mühling Bettina , Schneider Manuela , Kapp Michaela , Kübler Alexander , Germer Christoph-Thomas , Otto Christoph 
Published: May 2012

Abstract

Background
Ascorbic acid demonstrates a cytotoxic effect by generating hydrogen peroxide, a reactive oxygen species (ROS) involved in oxidative cell stress. A panel of eleven human cancer cell lines, glioblastoma and carcinoma, were exposed to serial dilutions of ascorbic acid (5-100 mmol/L). The purpose of this study was to analyse the impact of catalase, an important hydrogen peroxide-detoxifying enzyme, on the resistance of cancer cells to ascorbic acid mediated oxidative stress.

Methods
Effective concentration (EC50) values, which indicate the concentration of ascorbic acid that reduced the number of viable cells by 50%, were detected with the crystal violet assay. The level of intracellular catalase protein and enzyme activity was determined. Expression of catalase was silenced by catalase-specific short hairpin RNA (sh-RNA) in BT-20 breast carcinoma cells. Oxidative cell stress induced apoptosis was measured by a caspase luminescent assay.

Results
The tested human cancer cell lines demonstrated obvious differences in their resistance to ascorbic acid mediated oxidative cell stress. Forty-five percent of the cell lines had an EC50 > 20 mmol/L and fifty-five percent had an EC50 < 20 mmol/L. With an EC50 of 2.6–5.5 mmol/L, glioblastoma cells were the most susceptible cancer cell lines analysed in this study. A correlation between catalase activity and the susceptibility to ascorbic acid was observed. To study the possible protective role of catalase on the resistance of cancer cells to oxidative cell stress, the expression of catalase in the breast carcinoma cell line BT-20, which cells were highly resistant to the exposure to ascorbic acid (EC50: 94,9 mmol/L), was silenced with specific sh-RNA. The effect was that catalase-silenced BT-20 cells (BT-20 KD-CAT) became more susceptible to high concentrations of ascorbic acid (50 and 100 mmol/L).

Conclusions
Fifty-five percent of the human cancer cell lines tested were unable to protect themselves against oxidative stress mediated by ascorbic acid induced hydrogen peroxide production. The antioxidative enzyme catalase is important to protect cancer cells against cytotoxic hydrogen peroxide. Silenced catalase expression increased the susceptibility of the formerly resistant cancer cell line BT-20 to oxidative stress.
Assessing barriers to health insurance and threats to equity in comparative perspective: The Health Insurance Access Database
Authors: Quesnel-Vallée Amélie , Renahy Emilie , Jenkins Tania , Cerigo Helen 
Published: May 2012

Abstract

Background
Typologies traditionally used for international comparisons of health systems often conflate many system characteristics. To capture policy changes over time and by service in health systems regulation of public and private insurance, we propose a database containing explicit, standardized indicators of policy instruments.

Methods
The Health Insurance Access Database (HIAD) will collect policy information for ten OECD countries, over a range of eight health services, from 1990–2010. Policy indicators were selected through a comprehensive literature review which identified policy instruments most likely to constitute barriers to health insurance, thus potentially posing a threat to equity. As data collection is still underway, we present here the theoretical bases and methodology adopted, with a focus on the rationale underpinning the study instruments.

Results
These harmonized data will allow the capture of policy changes in health systems regulation of public and private insurance over time and by service. The standardization process will permit international comparisons of systems’ performance with regards to health insurance access and equity.

Conclusion
This research will inform and feed the current debate on the future of health care in developed countries and on the role of the private sector in these changes.