bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct clinical and biological features of de novo acute myeloid leukemia with additional sex comb-like 1 (ASXL1) mutations
Authors: Chou Wen-Chien , Huang Huai-Hsuan , Hou Hsin-An , Chen Chien-Yuan , Tang Jih-Luh , Yao Ming , Tsay Woei , Ko Bor-Sheng , Wu Shang-Ju , Huang Shang-Yi , Hsu Szu-Chun , Chen Yao-Chang , Huang Yen-Ning , Chang Yi-Chang , Lee Fen-Yu , Liu Min-Chih , Liu Chia-Wen , Tseng Mei-Hsuan , Huang Chi-Fei , Tien Hwei-Fang 
Published: August 2010

AbstractMutations in the additional sex comb-like 1 (ASXL1) gene were recently shown in various myeloid malignancies, but they have not been comprehensively investigated in acute myeloid leukemia (AML). In this study, we analyzed ASXL1 mutations in exon 12 in 501 adults with de novo AML. ASXL1 mutations were detected in 54 patients (10.8%), 8.9% among those with normal karyotype and 12.9% among those with abnormal cytogenetics. The mutation was closely associated with older age, male sex, isolated trisomy 8, RUNX1 mutation, and expression of human leukocyte antigen–DR and CD34, but inversely associated with t(15;17), complex cytogenetics, FLT3–internal tandem duplication, NPM1 mutations, WT1 mutations, and expression of CD33 and CD15. Patients with ASXL1 mutations had a shorter overall survival than patients without, but the mutation was not an independent adverse prognostic factor in multivariate analysis. Sequential analyses showed that the original ASXL1 mutations were lost at relapse and/or refractory status in 2 of the 6 relapsed ASXL1-mutated patients studied, whereas 2 of the 109 ASXL1-wild patients acquired a novel ASXL1 mutation at relapse. In conclusion, AML bearing ASXL1 mutations showed distinct clinical and biological features. The ASXL1 mutation status can change during disease evolution in a few patients.
Surfactant protein B polymorphisms, pulmonary function and COPD in 10,231 individuals
Authors: Bækvad-Hansen M. , Nordestgaard B.G. , Dahl M. 
Published: August 2010

Thesurfactant protein (SP)-Bgene may influence chronic obstructive pulmonary disease (COPD) and, thus, personalised medicine. We tested whether functional polymorphisms inSP-B(rs1130866 (1580T>C), rs2077079 (-18A>C) and rs3024791 (-384G>A)) associate with reduced lung function and risk of COPD in the general population.We genotyped 10,231 individuals from the general adult Danish population, and recorded spirometry and hospital admissions due to COPD. Because we previously found an association between the rareSP-B121ins2 mutation and COPD among smokers, we stratified the analyses for smoking status.None of the individualSP-Bgenotypes or genotype combinations were associated with reduced forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % pred and FEV1/FVC overall or among smokers (p = 0.25–0.99). The odds ratio for spirometrically defined COPD did not differ from 1.0 for any of theSP-Bgenotypes or genotype combinations overall or among smokers (p = 0.17–0.78). Similar results were obtained for hospitalisation due to COPD (p = 0.07–0.93); we could exclude overall hazard ratios for heterozygotes of 1.18–1.21 and for homozygotes of 1.25–1.57 or larger for all three polymorphisms.In conclusion, the functional rs1130866, rs2077079 and rs3024791 polymorphisms in theSP-Bgene are not associated with reduced lung function or risk of COPD, making it unlikely that these variants will be useful in personalised medicine.
The effect of dornase alfa on ventilation inhomogeneity in patients with cystic fibrosis
Authors: Amin R. , Subbarao P. , Lou W. , Jabar A. , Balkovec S. , Jensen R. , Kerrigan S. , Gustafsson P. , Ratjen F. 
Published: August 2010

Outcome measures to assess therapeutic interventions in cystic fibrosis (CF) patients with mild lung disease are lacking. Our aim was to determine if the lung clearance index (LCI) can detect a treatment response to dornase alfa in paediatric CF patients with normal spirometry.CF patients between 6–18 yrs of age with FEV1≥80% pred were eligible. In a crossover design, 17 patients received 4 weeks of dornase alfa and placebo in a randomised sequence separated by a 4-week washout period. The primary end-point was the change in LCI from dornase alfaversusplacebo. A mixed model approach incorporating period-dependent baselines was used.The mean±sdage was 10.32±3.35 yrs. Dornase alfa improved LCIversusplacebo (0.90±1.44; p = 0.022). Forced expiratory flow at 25–75% expired volume measured by % pred and z-scores also improved in subjects on dornase alfa (6.1%±10.34%; p = 0.03 and 0.28±0.46 z-score; p = 0.03).Dornase alfa significantly improved LCI. Therefore the LCI may be a suitable tool to assess early intervention strategies in this patient population.
Improving standards in flexible bronchoscopy for lung cancer
Authors: Slade M.G. , Rahman N.M. , Stanton A.E. , Curry L. , Slade G.C. , Clelland C.A. , Gleeson F.V. 
Published: August 2010

Can the detection rate of flexible bronchoscopy for lung cancer be increased by a series of simple quality improvement measures?Bronchoscopy-associated clinical parameters were prospectively recorded between 2001 and 2007 in patients with suspected lung malignancy. The detection rate of bronchoscopy, diagnostic yield of each biopsy modality and the possible impact of different service-improvement measures were assessed.746 bronchoscopies were performed in 704 patients. The detection rate of bronchoscopy for malignancy was 83.6%, and increased over time (67.3% detection rate in 2001 (95% CI 52.9–79.7), 89.7% detection rate in 2007 (95% CI 81.3–95.2); p<0.001). Detection rate increased for bronchoscopically visible (75.0% in 2001 to 94.5% in 2007) and non-visible tumours (41.7% in 2001 to 81.2% in 2007; p<0.001 for both analyses). Prior computed tomography availability was associated with a higher diagnostic yield that did not reach statistical significance. Logistic regression analysis identified tumour visibility, year of study, use of transbronchial needle aspiration and pathologist identity as independent predictors of a positive diagnosis.A significant increase in bronchoscopic detection rate for malignancy occurred in association with a number of simple improvement measures.
No increase in the prevalence of COPD in two decades
Authors: Vasankari T.M. , Impivaara O. , Heliövaara M. , Heistaro S. , Liippo K. , Puukka P. , Saarelainen S. , Kanervisto M. , Jousilahti P. 
Published: August 2010

Relevant information on the prevalence of chronic obstructive pulmonary disease (COPD) and its trends is scarce. In the present study, we compare the prevalence rates and potential determinants of COPD in two national population samples that were surveyed 20 yrs apart.In 1978–1980, a sample of 8,000 people was surveyed; subjects were representative of the Finnish population and were aged ≥30 yrs. Among those aged 30–74 yrs, acceptable spirometry was obtained from 6,364 (87%) subjects. In a similar survey conducted in 2000–2001, comparable spirometry was obtained from 5,495 (80%) participants. Airway obstruction was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity below the lower limit of normal and staged for severity on the basis of FEV1% predicted.The age-adjusted prevalence rates of obstruction (stages I–IV) were rather similar in both surveys in males (4.7versus4.3%; p = 0.25), but were almost significantly higher in females in the later survey (2.2versus3.1%; p = 0.06). The rates of COPD stage II or higher were 3.9% in 1978–1980, and 3.6% in 2000–2001 (p = 0.36) for males, and 1.4 and 1.5% (p = 0.93), respectively, for females.In conclusion, no significant difference was found in the prevalence of COPD stages II–IV between similar population based surveys performed 20 yrs apart. Since COPD is mostly mild or moderate there is a strong case for early prevention.
Possible use of ail and foxA polymorphisms for detecting pathogenic Yersinia enterocolitica
Authors: Huang Ying , Wang Xin , Cui Zhigang , Yang Yuhuan , Xiao Yuchun , Tang Liuying , Kan Biao , Xu Jianguo , Jing Huaiqi 
Published: August 2010

AbstractBackgroundYersinia enterocoliticais an enteric pathogen that invades the intestinal mucosa and proliferates within the lymphoid follicles (Peyer's patches). The attachment invasion locus (ail) mediates invasion byY. enterocoliticaand confers an invasive phenotype upon non-invasiveE. coli;ailis the primary virulence factor ofY. enterocolitica. The ferrioxamine receptor (foxA) located on theY. enterocoliticachromosome, together with its transport protein, transports a siderophore specific for ferric ion. Currently,ailis the primary target gene for nucleic acid detection of pathogenicY. enterocolitica.ResultsThe genesailandfoxAin 271 pathogenic and 27 non-pathogenicY. enterocoliticastrains isolated from China and 10 reference strains were sequenced, aligned, compared to theailandfoxAsequences ofYersinia enterocolitica subsp. enterocolitica8081 (Genbank: NC_008800), and analyzed for sequence polymorphism. Theailfrom the 282 strains showed 3 sequence patterns: 277 strains of serotypes O:3, O:9 and O:5, 27 with identical nucleic acid sequences formed pattern A1; 4 strains of serotype 1B/O:8 with identical nucleic acid sequences formed pattern A2; and one Chinese isolate 2/O:9 formed pattern A3. In the primary coding region of thefoxAORF (Genebank: X60447 nt 433-1866; nt 28 to 1,461 in the ORF), the sequences formed 3 groups and were further divided into 8 sequence patterns.ConclusionTheailandfoxAloci of pathogenicY. enterocoliticahave been analyzed. Theailsequence was highly conserved among the same serotype strains from different sources; andfoxAwas highly conserved among the pathogenic strains, although there was some sequence diversity. Fewer strains were used from outside China, which is a limitation of the study.
The ascorbic acid content of tomato fruits is associated with the expression of genes involved in pectin degradation
Authors: Di Matteo Antonio , Sacco Adriana , Anacleria Milena , Pezzotti Mario , Delledonne Massimo , Ferrarini Alberto , Frusciante Luigi , Barone Amalia 
Published: August 2010

Abstract

Background
High levels of ascorbic acid (AsA) in tomato fruits provide health benefits for humans and also play an important role in several aspects of plant life. Although AsA metabolism has been characterized in detail, the genetic mechanisms controlling AsA accumulation in tomatoes are poorly understood. The transcriptional control of AsA levels in fruits can be investigated by combining the advanced genetic and genomic resources currently available for tomato. A comparative transcriptomic analysis of fruit tissues was carried out on an introgression line containing a QTL promoting AsA accumulation in the fruit, using a parental cultivar with lower AsA levels as a reference.

Results
Introgression line IL 12-4 (S. pennellii in a S. lycopersicum background) was selected for transcriptomic analysis because it maintained differences in AsA levels compared to the parental genotypes M82 and S. pennellii over three consecutive trials. Comparative microarray analysis of IL 12-4 and M82 fruits over a 2-year period allowed 253 differentially-expressed genes to be identified, suggesting that AsA accumulation in IL 12-4 may be caused by a combination of increased metabolic flux and reduced utilization of AsA. In particular, the upregulation of a pectinesterase and two polygalacturonases suggests that AsA accumulation in IL12-4 fruit is mainly achieved by increasing flux through the L-galactonic acid pathway, which is driven by pectin degradation and may be triggered by ethylene.

Conclusions
Based on functional annotation, gene ontology classification and hierarchical clustering, a subset of the 253 differentially-expressed transcripts was used to develop a model to explain the higher AsA content in IL 12-4 fruits in terms of metabolic flux, precursor availability, demand for antioxidants, abundance of reactive oxygen species and ethylene signaling.
Chemical-genetic profile analysis of five inhibitory compounds in yeast
Authors: Alamgir Md , Erukova Veronika , Jessulat Matthew , Azizi Ali , Golshani Ashkan 
Published: August 2010

Abstract

Background
Chemical-genetic profiling of inhibitory compounds can lead to identification of their modes of action. These profiles can help elucidate the complex interactions between small bioactive compounds and the cell machinery, and explain putative gene function(s).

Results
Colony size reduction was used to investigate the chemical-genetic profile of cycloheximide, 3-amino-1,2,4-triazole, paromomycin, streptomycin and neomycin in the yeast Saccharomyces cerevisiae. These compounds target the process of protein biosynthesis. More than 70,000 strains were analyzed from the array of gene deletion mutant yeast strains. As expected, the overall profiles of the tested compounds were similar, with deletions for genes involved in protein biosynthesis being the major category followed by metabolism. This implies that novel genes involved in protein biosynthesis could be identified from these profiles. Further investigations were carried out to assess the activity of three profiled genes in the process of protein biosynthesis using relative fitness of double mutants and other genetic assays.

Conclusion
Chemical-genetic profiles provide insight into the molecular mechanism(s) of the examined compounds by elucidating their potential primary and secondary cellular target sites. Our follow-up investigations into the activity of three profiled genes in the process of protein biosynthesis provided further evidence concerning the usefulness of chemical-genetic analyses for annotating gene functions. We termed these genes TAE2, TAE3 and TAE4 for translation associated elements 2-4.
Intraoperative blood loss during different stages of scoliosis surgery: A prospective study
Authors: Modi Hitesh N , Suh Seung-Woo , Hong Jae-Young , Song Sang-Heon , Yang Jae-Hyuk 
Published: August 2010

Abstract

Background
There are a number of reasons for intraoperative blood loss during scoliosis surgery based on the type of approach, type of disease, osteopenia, and patient blood profile. However, no studies have investigated bleeding patterns according to the stage of the operation. The objective of this prospective study was to identify intraoperative bleeding patterns in different stages of scoliosis surgery.

Methods
We prospectively analyzed the estimated blood loss (EBL) and operation time over four stages of scoliosis surgery in 44 patients. The patients were divided into three groups: adolescent idiopathic (group 1), spastic neuromuscular (group 2) and paralytic neuromuscular (group 3). The per-level EBL and operation times of the groups were compared on a stage-by-stage basis. The bone marrow density (BMD) of each patient was also obtained, and the relationship between per-level EBL and BMD was compared using regression analysis.

Results
Per-level operation time was similar across all groups during surgical stage (p > 0.05). Per-level EBL was also similar during the dissection and bone-grafting states (p > 0.05). However, during the screw insertion stage, the per-level EBL was significantly higher in groups 2 and 3 compared to group 1 (p < 0.05). In the correction stage, per-level EBL was highest in group 3 (followed in order by groups 2 and 1) (p < 0.05). Preoperative BMD indicated that group 3 had the lowest bone quality, followed by groups 2 and 1 (in order), but the preoperative blood indices were similar in all groups. The differences in bleeding patterns in the screw insertion and correction stages were attributed to the poor bone quality of groups 2 and 3. Group 3 had the lowest bone quality, which caused loosening of the bone-screw interface during the correction stage and led to more bleeding. Patients with a T-score less than -2.5 showed a risk for high per-level EBL that was nine times higher than those with scores greater than -2.5 (p = 0.003).

Conclusions
We investigated the blood loss patterns during different stages of scoliosis surgery. Patients with poor BMD showed a risk of blood loss nine times higher than those with good BMD.
Expression of the apoptosis-related genes BCL-2 and BAD in human breast carcinoma and their associated relationship with chemosensitivity
Authors: Yu Bing , Sun Xin , Shen Hong-yan , Gao Feng , Fan Yuan-ming , Sun Zhi-jun 
Published: August 2010

Abstract

Objective
To evaluate the expression of BCL-2 and BAD genes in tissues of breast carcinoma and investigate the relationship between the expression of BCL-2 and BAD in breast cancer cells with chemosensitivity.

Methods
Immunohistochemical technique was used to detect the expression of BCL-2, BAD in 10 normal breast tissues, 10 breast fibroadenoma tissues, 40 youth human breast carcinoma tissues, 40 menopause human breast carcinoma tissues. And to detect the expression of ER, PR in 80 human breast carcinoma tissues. 20 Surgical samples of breast cancer, diagnosed by pathology, were obtained from The First Affiliated Hospital of Chongqing Medical University. The cancer sample cells were cultured separately in the incubator at 37°C, 5% CO2 in vitro. The rate of inhibition of cancer cells in 4 kinds of anticancer drugs-- Epirubicin Adriamycin (EADM),5-Fluorouracil (5-Fu), Navelbine(NVB) and Diaminedichloroplatinum (DDP), were assayed by MTT method.

Results
The expression of BCL-2, BAD genes in young human breast carcinoma tissues were lower than that in menopause human breast carcinoma tissues (
P

< 0.05). There was a negative correlation between the positive expression rate of BCL-2 and histologic grade or the lymph node metastasis (
P

< 0.05). There was a positive correlation between the expression rates of BCL-2 and of ER, PR (
P

< 0.05). The expression of BAD had no relationship with the expression of ER, PR, histologic grade and the lymph node metastasis(
P

=

NS
). Sensitivity rates of 20 breast cancer cells in 0.1 × PPC within 48 h in vitro were 30% EADM,20% 5-Fu,45% NVB and 25% DDP. Respectively, the rate of inhibition of EADM,5- Fu, NVB and DDP were significantly higher in the BCL-2 negative cancer cells than in the BCL-2 positive cancer cells. A negative correlation was found between expression of BCL-2 and chemosensitivity for all the 4 anticancer drugs. The inhibition rates of EADM and NVB were significantly lower in the BAD negative cancer cells than in the BAD positive cancer cells. A positive correlation was found between expression of BAD and chemosensitivity for Epirubicin.

Conclusion
The expression of BCL-2 and BAD can be used as prognosis factors of breast cancer. Detection of the BCL-2 protein expression level, particularly, combined with the detection of the expression of BCL-2 and BAD as well as ER and PR were helpful in confirming the prognosis of breast carcinoma. The combined detection of BCL-2 and BAD may be markers for predicting the responses to anticancer drugs.
Serum Bilirubin and Genes Controlling Bilirubin Concentrations as Biomarkers for Cardiovascular Disease
Authors: Lin Jing-Ping , Vitek Libor , Schwertner Harvey A 
Published: August 2010

BACKGROUNDSerum bilirubin has been consistently shown to be inversely related to cardiovascular disease (CVD). Recent studies showed serum bilirubin to be associated with CVD-related factors such as diabetes, metabolic syndrome, and body mass index. Although the association of serum bilirubin with CVD has been found in both retrospective and prospective studies, less information is available on the role of genes that control bilirubin concentrations and their association with CVD.CONTENTIn this review, we provide detailed information on the identity of the major genes that control bilirubin concentrations and their association with serum bilirubin concentrations and CVD risk. We also update the results of the major studies that have been performed on the association between serum bilirubin, CVD, and CVD-related diseases such as diabetes or metabolic syndrome. Studies consistently indicate that bilirubin concentrations are inversely associated with different types of CVD and CVD-related diseases. A conditional linkage study indicates that UGT1A1 is the major gene controlling serum bilirubin concentrations, and this finding has been confirmed in recent genomewide association studies. Studies also indicate that individuals homozygous for UGT1A1*28 have a significantly lower risk of developing CVD than carriers of the wild-type alleles.SUMMARYSerum bilirubin has a protective effect on CVD and CVD-related diseases, and UGT1A1 is the major gene controlling serum bilirubin concentrations. Pharmacologic, nonpharmacologic, or genetic interventions that increase serum bilirubin concentrations could provide more direct evidence on the role of bilirubin in CVD prevention.
Liver Fat Content in Type 2 Diabetes: Relationship With Hepatic Perfusion and Substrate Metabolism
Authors: Rijzewijk Luuk J. , van der Meer Rutger W. , Lubberink Mark , Lamb Hildo J. , Romijn Johannes A. , de Roos Albert , Twisk Jos W. , Heine Robert J. , Lammertsma Adriaan A. , Smit Johannes W.A. , Diamant Michaela 
Published: August 2010

OBJECTIVE
Hepatic steatosis is common in type 2 diabetes. It is causally linked to the features of the metabolic syndrome, liver cirrhosis, and cardiovascular disease. Experimental data have indicated that increased liver fat may impair hepatic perfusion and metabolism. The aim of the current study was to assess hepatic parenchymal perfusion, together with glucose and fatty acid metabolism, in relation to hepatic triglyceride content.

RESEARCH DESIGN AND METHODS
Fifty-nine men with well controlled type 2 diabetes and 18 age-matched healthy normoglycemic men were studied using positron emission tomography to assess hepatic tissue perfusion, insulin-stimulated glucose, and fasting fatty acid metabolism, respectively, in relation to hepatic triglyceride content, quantified by proton magnetic resonance spectroscopy. Patients were divided into two groups with hepatic triglyceride content below (type 2 diabetes-low) or above (type 2 diabetes-high) the median of 8.6%.

RESULTS
Type 2 diabetes-high patients had the highest BMI and A1C and lowest whole-body insulin sensitivity (ANOVA, all P &lt; 0.001). Compared with control subjects and type 2 diabetes-low patients, type 2 diabetes-high patients had the lowest hepatic parenchymal perfusion (P = 0.004) and insulin-stimulated hepatic glucose uptake (P = 0.013). The observed decrease in hepatic fatty acid influx rate constant, however, only reached borderline significance (P = 0.088). In type 2 diabetic patients, hepatic parenchymal perfusion (r = −0.360, P = 0.007) and hepatic fatty acid influx rate constant (r = −0.407, P = 0.007) correlated inversely with hepatic triglyceride content. In a pooled analysis, hepatic fat correlated with hepatic glucose uptake (r = −0.329, P = 0.004).

CONCLUSIONS
In conclusion, type 2 diabetic patients with increased hepatic triglyceride content showed decreased hepatic parenchymal perfusion and hepatic insulin mediated glucose uptake, suggesting a potential modulating effect of hepatic fat on hepatic physiology.