bluuebunny/crossref_metadata_2025 huggingface dataset:
CT‐guided percutaneous microwave ablation of adrenal malignant carcinoma
Authors: Li Xin , Fan Weijun , Zhang Liang , Zhao Ming , Huang Zilin , Li Wang , Gu Yangkui , Gao Fei , Huang Jinhua , Li Chuanxing , Zhang Fujun , Wu Peihong
Published: April 2011

BACKGROUND:

Microwave ablation has recently been developed as a safe and effective treatment for a variety of tumors. The authors evaluated the safety and efficacy of computed tomography (CT)‐guided percutaneous microwave ablation of adrenal malignant tumors.

METHODS:

Nine patients between 41 and 83 years of age (average age, 54 years) with adrenal carcinoma (a total of 10 lesions) received CT‐guided percutaneous water‐cooled microwave ablation. The 9 cases included 1 primary adrenocortical carcinoma and 8 metastatic carcinomas (4 from lung cancer, 2 from hepatocellular carcinoma, 1 from intrahepatic cholangiocarcinoma, and 1 from left tibial osteosarcoma). Of the 8 metastatic cases, 7 were unilateral, and 1 was bilateral. All cases were pathologically confirmed by aspiration biopsy or postsurgical biopsy. The tumor diameters ranged from 2.1 cm to 6.1 cm (average, 3.8 cm). The average number of ablation sites was 1.5 sites (1‐3 sites), and the average accumulated ablation time was 7.7 minutes (4‐15 minutes). The procedures were performed using a cooled‐shaft antenna.

RESULTS:

The patients were followed for 3‐37 months, with an average of 11.3 months. Nine of 10 lesions were completely necrotized after first treatment. The other lesion was completely necrotized after 2 treatments. One of the patients experienced hypertensive crisis during treatment. No patient experienced recurrent tumor at the treated site, and this lack of recurrence indicated effective local control. All patients had progression of metastatic disease at extra‐adrenal sites.

CONCLUSIONS:

CT‐guided percutaneous water‐cooled microwave ablation is a minimally invasive and effective method for the treatment of adrenal carcinoma. Cancer 2011;. © 2011 American Cancer Society.
Patterns of extralaryngeal spread of laryngeal cancer
Authors: Chen Susie A. , Muller Susan , Chen Amy Y. , Hudgins Patricia A. , Shin Dong M. , Khuri Fadlo , Saba Nabil F. , Beitler Jonathan J.
Published: April 2011

BACKGROUND:

Laryngeal preservation programs for patients with advanced laryngeal squamous cell carcinomas (SCC) have generally excluded patients with T4 disease. The accuracy of preoperative imaging in evaluating thyroid cartilage penetration and extralaryngeal spread (ELS) has previously been questioned. Clinically, SCC spread into noncartilaginous structures may have less of a functional impact when compared with thyroid cartilage penetration. The current study was designed to characterize and quantify the routes and frequency of ELS.

METHODS:

A total of 103 laryngectomy specimens with preoperative contrast‐enhanced neck computed tomography scans were coded according to the observed extent of disease by pathological and radiological data. Previously irradiated tumors or those of pyriform sinus origin were omitted. Routes of spread were categorized as anterior (thyroid cartilage penetration), posterior (arytenoid cartilage destruction and thyroarytenoid space widening), inferior (conus elasticus penetration), and superior (base of tongue, thyrohyoid membrane or thyroid notch penetration involvement).

RESULTS:

Sixty‐three cases of ELS were identified. Anterior spread by thyroid cartilage penetration occurred in 44% of all instances of ELS, followed by both inferior and posterior spread each representing 33% of ELS cases. Superior spread occurred with a frequency of 24%.

CONCLUSIONS:

Although thyroid cartilage penetration is a common route of ELS of glottic and supraglottic SCC, ELS into surrounding structures with thyroid cartilage penetration was found to occur in only 44% of the cases of ELS in the current study. As illustrated, advanced SCC spreads in a variety of pathways. Once these patterns are better understood and identified at the time of initial evaluation, subgroups of patients with ELS who may still be candidates for laryngeal preservation may be identified. Cancer 2011;. © 2011 American Cancer Society.
Colonoscopy screening rates among patients of colonoscopy‐trained African American primary care physicians
Authors: Xirasagar Sudha , Hurley Thomas G. , Burch James B. , Mansaray Ali , Hébert James R.
Published: April 2011

BACKGROUND:

When performed competently, colonoscopy screening can reduce colorectal cancer rates, especially in high‐risk groups such as African Americans. Training primary care physicians (PCPs) to perform colonoscopy may improve screening rates among underserved high‐risk populations.

METHODS:

The authors compared colonoscopy screening rates and computed adjusted odds ratios for colonoscopy‐eligible patients of trained African American PCPs (study group) versus untrained PCPs (comparison group), before and after initiating colonoscopy training. All colonoscopies were performed at a licensed ambulatory surgery center with specialist standby support. Retrospective chart review was conducted on 200 consecutive, established outpatients aged ≥50 years at each of 12 PCP offices (7 trained African American PCPs and 5 untrained PCPs, practicing in the same geographic region). There were a total of 1244 study group and 923 comparison group patients.

RESULTS:

Post‐training colonoscopy rates in both groups were higher than pretraining rates: 48.3% versus 9.3% in the study group, 29.6% versus 9.8% in the comparison group (both P < .001). African American patients in the study group showed a >5‐fold increase (8.9% pretraining vs 52.8% post‐training), with no change among whites (18.2% vs 25.0%). Corresponding pretraining and post‐training rates among comparison patients were 10.4%% and 38.7%, respectively, among African Americans (P < .001), and 13.3% versus 13.2%, respectively, among whites. After adjusting for demographics, duration since becoming the PCP's patient, and health insurance, the study group had a 66% higher likelihood of colonoscopy in the post‐training period (odds ratio, 1.66; 95% confidence interval, 1.30‐2.13), and African Americans had a 5‐fold increased likelihood of colonoscopy relative to whites.

CONCLUSIONS:

Colonoscopy‐trained PCPs may help reduce colorectal cancer disparities. Cancer 2011;. © 2011 American Cancer Society.
Retinoic acid induces REST degradation and neuronal differentiation by modulating the expression of SCFβ‐TRCP in neuroblastoma cells
Authors: Singh Akanksha , Rokes Christopher , Gireud Monica , Fletcher Stephen , Baumgartner James , Fuller Greg , Stewart John , Zage Peter , Gopalakrishnan Vidya
Published: April 2011

BACKGROUND:

The repressor element‐1 silencing transcription factor (REST) is a repressor of neuronal genes. Its expression is associated with poor neuronal differentiation in many neuroblastoma patient samples and cell lines. Because retinoic acid promotes neuronal differentiation, the authors postulated that it involves modulation of REST expression.

METHODS:

The expression of REST and of an S‐phase kinase‐associated protein 1/cullin 1/F‐box (SCF) protein complex that contains the F‐box protein β‐transducin repeat‐containing protein (β‐TRCP) (SCFβ‐TRCP) in neuroblastoma tumor samples and cell lines was analyzed by immunofluorescence and Western blot analysis. SK‐N‐SH and SK‐N‐AS cells were treated with retinoic acid and MG‐132 to measure proteasomal degradation of REST by Western blot and quantitative real‐time polymerase chain reaction analyses. Immunoprecipitation and coimmunoprecipitation assays were done in SK‐N‐AS cells that were transfected either with a control plasmid or with an enhanced green fluorescent protein‐SCFβ‐TRCP–expressing plasmid.

RESULTS:

Several neuroblastoma patient samples and cell lines displayed elevated REST expression. Although, REST transcription increased upon retinoic acid treatment in SK‐N‐SH and SK‐N‐AS cells, REST protein levels declined, concomitant with the induction of neuronal differentiation, in SK‐N‐SH cells but not in SK‐N‐AS cells. MG‐132 treatment countered the retinoic acid‐mediated decline in REST protein. SCFβ‐TRCP, a known REST‐specific E3‐ligase, was poorly expressed in many neuroblastoma samples, and its expression increased upon retinoic acid treatment in SK‐N‐SH cells but declined in SK‐N‐AS cells. Ectopic expression of SCFβ‐TRCP in SK‐N‐AS cells promoted REST ubiquitination and degradation and neuronal differentiation.

CONCLUSIONS:

The current results indicated that elevated transcription of REST compounded by its impaired degradation by SCFβ‐TRCP may contribute to the failure of these tumors to differentiate in response to retinoic acid. Cancer 2011;. © 2011 American Cancer Society.
Prognostic impact of deletions of derivative chromosome 9 in patients with chronic myelogenous leukemia treated with nilotinib or dasatinib
Authors: Quintás‐Cardama Alfonso , Kantarjian Hagop , Shan Jianqin , Jabbour Elias , Abruzzo Lynne V. , Verstovsek Srdan , Garcia‐Manero Guillermo , O'Brien Susan , Cortes Jorge
Published: April 2011

BACKGROUND:

Deletions of derivative chromosome 9 are a poor prognostic factor in patients with chronic myeloid leukemia (CML) treated with hydroxyurea, interferon, or stem cell transplantation. Imatinib may overcome the adverse prognostic impact of deletions of derivative chromosome 9.

METHODS:

A study was undertaken to investigate the prognostic impact of deletions of derivative chromosome 9 in 353 patients with CML receiving the second generation tyrosine kinase inhibitors (TKIs) nilotinib (n = 161) or dasatinib (n = 192).

RESULTS:

Deletion of derivative chromosome 9 status was determined in 245 (69%). Twenty‐eight (11%) patients, 22 in chronic phase, 4 in accelerated phase, and 2 in blast phase, carried deletions of derivative chromosome 9, including 17 receiving nilotinib and 11 receiving dasatinib (P = .47). Overall survival (OS) at 24 months was similar between patients with or without deletions of derivative chromosome 9 (70% vs 71%, P = .76). For patients in chronic phase, no significant differences in overall major cytogenetic response (77% vs 82%, P = .57) or complete cytogenetic response (77% vs 81%, P = .71) rates were observed between patients with or without deletions of derivative chromosome 9. At 24 months, patients with CML in chronic phase without deletions of derivative chromosome 9 had improved event‐free survival (EFS) (88% vs 66%, P = .07) and OS (96% vs 82%; P = .08) compared with those carrying deletions of derivative chromosome 9. However, multivariate analysis established second‐line versus frontline second generation TKI therapy as the only adverse prognostic factor for EFS and increased bone marrow blast burden and older age as independent adverse prognostic factors for OS.

CONCLUSIONS:

Deletions of derivative chromosome 9 do not appear to be an independent risk factor for survival among patients with CML in chronic phase receiving second generation TKIs. Cancer 2011;. © 2011 American Cancer Society.
Do multidisciplinary team meetings make a difference in the management of lung cancer?
Authors: Boxer Miriam M. , Vinod Shalini K. , Shafiq Jesmin , Duggan Kirsten J.
Published: April 2011

BACKGROUND:

There is limited evidence regarding the effectiveness of multidisciplinary team (MDT) meetings in lung cancer. The objective of this study was to compare the patterns of care for patients with newly diagnosed lung cancer who were presented at a lung cancer MDT meeting with the patterns of care for patients who were not presented.

METHODS:

All patients who had lung cancer newly diagnosed in South West Sydney (SWS) between December 1, 2005, and December 31, 2008, were identified from the local Clinical Cancer Registry. Patient and tumor characteristics and treatment receipt were compared between patients who were and were not presented at MDT meetings. A logistic regression model was constructed to determine predictors for receiving treatment and survival.

RESULTS:

In total, there were 988 patients, including 504 patients who were presented at MDT meetings and 484 who were not presented at MDT meetings. The median patient age was 69 years and 73 years in the MDT group and the non‐MDT group, respectively (P < .01). There was no pathologic diagnosis for 13% of non‐MDT patients compared with 4% of MDT patients (P < .01). Treatment receipt for MDT patients versus non‐MDT patients was 12% versus 13%, respectively, for surgery (P value nonsignificant); 66% versus 33%, respectively, for radiotherapy (P < .001); 46% versus 29%, respectively, for chemotherapy (P < .001); and 66% versus 53%, respectively, for palliative care (P < .001). In patients with good performance status, the MDT group had significantly better receipt of radiotherapy among patients with stage I through IV nonsmall cell lung cancer (NSCLC) and had significantly better receipt of chemotherapy among patients with stage IV NSCLC. MDT discussion was an independent predictor of receiving radiotherapy, chemotherapy, and referral to palliative care but did not influence survival.

CONCLUSIONS:

MDT discussion was associated with better treatment receipt, which potentially may improve quality of life for patients with lung cancer. However, it did not improve survival. Cancer 2011;. © 2011 American Cancer Society.
Expression and function role of DNA methyltransferase 1 in human bladder cancer
Authors: Wu Chun‐Te , Wu Ching‐Fang , Lu Chang‐Hsien , Lin Cheng‐Chia , Chen Wen‐Cheng , Lin Paul‐Yang , Chen Miao‐Fen
Published: April 2011

BACKGROUND:

The identification of potential tumor markers will help improve therapeutic planning and patient management. Therefore, the aim of this study was to highlight the role of DNA methyltransferase 1 (DNMT1) in bladder cancer.

METHODS:

A total of 50 samples of nonmalignant urothelium, 65 of muscle‐invasive bladder cancers, 15 of distant metastasis, and 50 of nonmuscle‐invasive bladder cancers were selected for immunohistochemical staining analysis. Furthermore, human bladder cancer cell lines HT1376 and HT1197 were selected for cell and animal experiments investigating changes in tumor behavior, treatment response, and related signaling in bladder cancer.

RESULTS:

The incidence of nuclear DNMT1 immunoreactivity in the bladder cancer specimens (45%) was significantly higher than in nonmalignant urothelium (15%, P = .0005), and the incidence in cancer was positively linked to clinical stage (24% in ≤T1 vs 55% in T2‐T4, P = .0007). The staining of DNMT1 was also significantly linked to lower complete response rates (P = .0014) and reduced survival rates (P = .000). By in vitro and in vivo experiments, DNMT1 silencing vector reduced tumor growth and attenuated treatment resistance in bladder cancer cells. Less epithelial‐mesenchymal transition, less invasion, and slower tumor growth were noted in cancer cells with inhibited DNMT1. Furthermore, the epidermal growth factor receptor‐mediated phosphatidylinositol 3′–kinase‐protein kinase B pathway might be the mechanism underlying the effects of DNMT1 on bladder cancer.

CONCLUSIONS:

DNMT1 could be a significant clinical predictor for stage and treatment response of bladder cancer. Moreover, targeting this enzyme could be a promising strategy for treating bladder cancer, as evidenced by inhibited tumor growth and enhanced radiosensitivity. Cancer 2011;. © 2011 American Cancer Society.
Prognostic influence of metformin as first‐line chemotherapy for advanced nonsmall cell lung cancer in patients with type 2 diabetes
Authors: Tan Ben‐Xu , Yao Wen‐Xiu , Ge Jun , Peng Xing‐Chen , Du Xiao‐Bo , Zhang Ru , Yao Bin , Xie Ke , Li Long‐Hao , Dong Hang , Gao Feng , Zhao Feng , Hou Jian‐Mei , Su Jing‐Mei , Liu Ji‐Yan
Published: April 2011

BACKGROUND:

It has been reported that antidiabetic drugs affect the risk of cancer and the prognosis of patients with diabetes, but few studies have demonstrated the influence of different antidiabetic agents on outcomes after anticancer therapy among patients with cancer. The objective of this study was to evaluate the influence of the antidiabetic drugs metformin and insulin on the prognosis of patients with advanced nonsmall cell lung cancer (NSCLC) plus type 2 diabetes who received first‐line chemotherapy.

METHODS:

Data on patients with NSCLC who had diabetes from 5 hospitals in China during January 2004 to March 2009 were reviewed retrospectively. Ninety‐nine patients were included in the final analysis. The influence of metformin and insulin on chemotherapy response rates and survival in these patients was evaluated.

RESULTS:

Chemotherapy with metformin (Group A) produced superior results compared with insulin (Group B) and compared with drugs other than metformin and insulin (Group C) in terms of both progression‐free survival (PFS) (8.4 months vs 4.7 months vs 6.4 months, respectively; P = .002) and overall survival (OS) (20.0 months vs 13.1 months vs 13.0 months, respectively; P = .007). Although no significant differences in the response rate (RR) were observed between these 3 groups, when groups B and C (ie, the nonmetformin group) were combined, there was a tendency for better disease control in Group A than that in nonmetformin group. No significant difference in survival was observed between chemotherapy with insulin (Group B) versus other drugs (Group C).

CONCLUSIONS:

The current data suggested that metformin may improve chemotherapy outcomes and survival for patients who have NSCLC with diabetes. Cancer 2011;. © 2011 American Cancer Society.
A functional polymorphism (−1607 1G→2G) in the matrix metalloproteinase‐1 promoter is associated with development and progression of lung cancer
Authors: Liu Li , Wu Jing , Wu Chen , Wang Ying , Zhong Rong , Zhang Xinyu , Tan Wen , Nie Shaofa , Miao Xiaoping , Lin Dongxin
Published: April 2011

BACKGROUND:

Matrix metalloproteinase‐1 (MMP‐1), an interstitial collagenase, plays an important role in the breakdown of extracellular matrix and mediates pathways of apoptosis, angiogenesis, and immunity. It has been demonstrated that the overexpression of this enzyme is associated with tumor initiation, invasion, and metastasis. The −1607 single guanine (1G)‐to‐2G polymorphism (reference single nucleotide polymorphism 1799750) in the MMP‐1 promoter region creates an E26 (Ets) binding site and results in transcriptional up‐regulation. The authors hypothesized that this MMP‐1 polymorphism may affect susceptibility to the development and progression of cancer.

METHODS:

The authors investigated their hypothesis in a lung cancer case‐control study. Genotypes were analyzed in 825 patients with lung cancer and in 825 controls. Odds ratios were estimated by multivariate logistic regression, and a meta‐analysis also was conducted to verify the findings.

RESULTS:

Patients who had the MMP‐1 2G/2G genotype had a 1.71‐fold increased risk of lung cancer (95% confidence interval, 1.22‐fold to 2.41‐fold increased risk) compared with patients who had the 1G/1G genotype. Moreover, when patients with stage I disease were considered as a reference group, patients who carried the 2G/2G genotype had a significantly increased risk of invasive disease (stage III‐IV: odds ratio, 2.02; 95% confidence interval, 1.09‐3.74) compared with patients who had the 1G/1G genotype. Pooled results from the meta‐analysis confirmed that those who had the 2G/2G genotype had a significantly increased risk of lung cancer compared with those who had the 1G/1G genotype, consistent with the case‐control findings.

CONCLUSIONS:

The current study demonstrated that the MMP‐1 −1607 1G‐to‐2G polymorphism is associated with susceptibility to both development and progression of lung cancer. Cancer 2011;. © 2011 American Cancer Society.
Increased genetic susceptibility to intestinal‐type gastric cancer is associated with increased activity of the RUNX3 distal promoter
Authors: Lim Byungho , Ju Hyoungseok , Kim Minjin , Kang Changwon
Published: April 2011

BACKGROUND:

The runt‐related transcription factor RUNX3 plays essential roles in various types of tumors, including gastric cancer. Epigenetic changes in the methylation of the RUNX3 proximal promoter, but not common genetic changes in RUNX3, have been associated with both changes in the gene expression and development of the cancer.

METHODS:

A case‐control association study was conducted by genotyping 865 unrelated Korean subjects. Subsequent functional studies were performed to reveal functional implication of genetic association.

RESULTS:

Several single‐nucleotide polymorphisms (SNPs) in RUNX3 were significantly associated with susceptibility to intestinal‐type gastric cancer (.0028 ≤ P ≤ .022) but not diffuse‐type gastric cancer (.70 ≤ P ≤ .96). The risk‐associated, minor variant of an intestinal‐type gastric cancer‐associated SNP in the RUNX3 distal promoter (rs7528484) significantly increased promoter activity in a CREB1‐dependent manner. The distal promoter‐derived, 33 kDa isoform of RUNX3 increased the activity of transcription factor nuclear factor kappa B (NF‐κB), which had been activated by Helicobacter pylori infection, a risk factor for intestinal‐type gastric cancer, and the expression of the interleukin‐1β gene (IL1B), an NF‐κB target genetically and functionally associated with gastric cancer. In contrast, the proximal promoter‐derived, 44 kDa isoform of RUNX3 decreased both NF‐κB activity and IL1B expression.

CONCLUSIONS:

In addition to epigenetic changes in the RUNX3 proximal promoter, genetic changes in the distal promoter may be associated with susceptibility to intestinal‐type gastric cancer by increasing promoter activity. Functionally, 2 RUNX3 isoforms may contribute differentially to intestinal‐type gastric cancer susceptibility, at least in part through regulating NF‐κB activity and IL1B expression Cancer 2011;. © 2011 American Cancer Society.
Prostacyclin synthase expression and epigenetic regulation in nonsmall cell lung cancer
Authors: Cathcart Mary‐Clare , Gray Steven G. , Baird Anne‐Marie , Boyle Elaine , Gately Kathy , Kay Elaine , Cummins Robert , Pidgeon Graham P. , O'Byrne Kenneth J.
Published: April 2011

BACKGROUND:

Prostacyclin synthase (PGIS) metabolizes prostaglandin H(2), into prostacyclin. This study aimed to determine the expression profile of PGIS in nonsmall cell lung cancer (NSCLC) and examine potential mechanisms involved in PGIS regulation.

METHODS:

PGIS expression was examined in human NSCLC and matched controls by reverse transcriptase polymerase chain reaction (RT‐PCR), Western analysis, and immunohistochemistry. A 204‐patient NSCLC tissue microarray was stained for PGIS and cyclooxygenase 2 (COX2) expression. Staining intensity was correlated with clinical parameters. Epigenetic mechanisms underpinning PGIS promoter expression were examined using RT‐PCR, methylation‐specific PCR, and chromatin immunoprecipitation analysis.

RESULTS:

PGIS expression was reduced/absent in human NSCLC protein samples (P < .0001), but not mRNA relative to matched controls. PGIS tissue expression was higher in squamous cell carcinoma (P = .004) and in male patients (P < .05). No significant correlation of PGIS or COX2 expression with overall patient survival was observed, although COX2 was prognostic for short‐term (2‐year) survival (P < .001). PGIS mRNA expression was regulated by DNA CpG methylation and histone acetylation in NSCLC cell lines, with chromatin remodeling taking place directly at the PGIS gene. PGIS mRNA expression was increased by both demethylation agents and histone deacetylase inhibitors. Protein levels were unaffected by demethylation agents, whereas PGIS protein stability was negatively affected by histone deacetylase inhibitors.

CONCLUSIONS:

PGIS protein expression is reduced in NSCLC, and does not correlate with overall patient survival. PGIS expression is regulated through epigenetic mechanisms. Differences in expression patterns between mRNA and protein levels suggest that PGIS expression and protein stability are regulated post‐translationally. PGIS protein stability may have an important therapeutic role in NSCLC. Cancer 2011;. © 2011 American Cancer Society.
Cytoarchitecture and ultrastructure of neural stem cell niches and neurogenic complexes maintaining adult neurogenesis in the olfactory midbrain of spiny lobsters, Panulirus argus
Authors: Schmidt Manfred , Derby Charles D.
Published: April 2011

New interneurons are continuously generated in small proliferation zones within neuronal somata clusters in the olfactory deutocerebrum of adult decapod crustaceans. Each proliferation zone is connected to a clump of cells containing one neural stem cell (i.e., adult neuroblast), thus forming a “neurogenic complex.” Here we provide a detailed analysis of the cytoarchitecture of neurogenic complexes in adult spiny lobsters, Panulirus argus, based on transmission electron microscopy and labeling with cell‐type‐selective markers. The clump of cells is composed of unique bipolar clump‐forming cells that collectively completely envelop the adult neuroblast and are themselves ensheathed by a layer of processes of multipolar cell body glia. An arteriole is attached to the clump of cells, but dye perfusion experiments show that hemolymph has no access to the interior of the clump of cells. Thus, the clump of cells fulfills morphological criteria of a protective stem cell niche, with clump‐forming cells constituting the adult neuroblast's microenvironment together with the cell body glia processes separating it from other tissue components. Bromodeoxyuridine pulse‐chase experiments with short survival times suggest that adult neuroblasts are not quiescent but rather cycle actively during daytime. We propose a cell lineage model in which an asymmetrically dividing adult neuroblast repopulates the pool of neuronal progenitor cells in the associated proliferation zone. In conclusion, as in mammalian brains, adult neurogenesis in crustacean brains is fueled by neural stem cells that are maintained by stem cell niches that preserve elements of the embryonic microenvironment and contain glial and vascular elements. J. Comp. Neurol. 519:2283–2319, 2011. © 2011 Wiley‐Liss, Inc.
Lgr4‐deficient mice showed premature differentiation of ureteric bud with reduced expression of Wnt effector Lef1 and Gata3
Authors: Mohri Yasuaki , Oyama Kazunori , Akamatsu Atsushi , Kato Shigeki , Nishimori Katsuhiko
Published: April 2011

We previously reported that Lgr4 has a critical role in the morphogenesis of kidney, but the detailed functions of Lgr4 in kidney development have not been elucidated. In contrast to Lgr4 null mice with 129Ola × C57BL/6J mixed background, C57BL/6J‐backcrossed Lgr4 null mice (Lgr4−/−) showed the severe phenotype of embryonic lethality and also had dilated tubules in kidneys at E16.5. Based on quantitative RT‐PCR and in situ hybridization, branching morphogenesis at E15.5 in the Lgr4−/− was arrested earlier, and both DBA‐lectin staining and immunohistochemical analysis using Aqp3 antibodies showed that the ureteric bud (UB) of Lgr4−/− kidneys underwent premature differentiation. Furthermore, quantitative RT‐PCR and histological analysis suggested that the impaired UB differentiation was caused by down‐regulation of the Wnt pathway and Gata3 in the Lgr4−/− kidneys. We demonstrate here that Lgr4 has a novel function for maintaining the UB in an undifferentiated state. Developmental Dynamics 240:1626–1634, 2011. © 2011 Wiley‐Liss, Inc.
A clinical perspective of IL‐1β as the gatekeeper of inflammation
Authors: Dinarello Charles A.
Published: April 2011

An expanding spectrum of acute and chronic non‐infectious inflammatory diseases is uniquely responsive to IL‐1β neutralization. IL‐1β‐mediated diseases are often called “auto‐inflammatory” and the dominant finding is the release of the active form of IL‐1β driven by endogenous molecules acting on the monocyte/macrophage. IL‐1β activity is tightly controlled and requires the conversion of the primary transcript, the inactive IL‐1β precursor, to the active cytokine by limited proteolysis. Limited proteolysis can take place extracellularly by serine proteases, released in particular by infiltrating neutrophils or intracellularly by the cysteine protease caspase‐1. Therefore, blocking IL‐1β resolves inflammation regardless of how the cytokine is released from the cell or how the precursor is cleaved. Endogenous stimulants such as oxidized fatty acids and lipoproteins, high glucose concentrations, uric acid crystals, activated complement, contents of necrotic cells, and cytokines, particularly IL‐1 itself, induce the synthesis of the inactive IL‐1β precursor, which awaits processing to the active form. Although bursts of IL‐1β precipitate acute attacks of systemic or local inflammation, IL‐1β also contributes to several chronic diseases. For example, ischemic injury, such as myocardial infarction or stroke, causes acute and extensive damage, and slowly progressive inflammatory processes take place in atherosclerosis, type 2 diabetes, osteoarthritis and smoldering myeloma. Evidence for the involvement of IL‐1β and the clinical results of reducing IL‐1β activity in this broad spectrum of inflammatory diseases are the focus of this review.
Molecular Diversity of Three‐Component Reactions of Aromatic Aldehydes, Arylamines, and Acetylenedicarboxylates
Authors: Sun Jing , Wu Qun , Xia Er‐Yan , Yan Chao‐Guo
Published: April 2011

The three‐component reactions of aromatic aldehydes, arylamines, and acetylenedicarboxylates show very interesting molecular diversity. In an aqueous ethanol solution the three‐component reaction gave polysubstituted 2‐hydroxyhydropyridines. In absolute ethanol 1,4‐dihydropyridines were produced in satisfactory yields. Finally, under acid catalysis, this three‐component reaction afforded polysubstituted 2‐pyrrolidinones. The reaction mechanism for the formation of the three products is briefly explained.
Salt (LiF) Regulated Fluorescence Switching
Authors: Sokkalingam Punidha , Yoo Jaeduk , Hwang Hyonseok , Lee Phil Ho , Jung Young Mee , Lee Chang‐Hee
Published: April 2011

A supramolecular host‐guest complex stimulated by lithium cation and fluoride anion, functioning as reliable fluorescence “Off‐On‐Off” switching system has been developed. Nonfluorescent, receptor‐bound fluorophore is exclusively displaced by second guest, fluoride anion to release thefluorophore that becomes highly fluorescent in guest concentration dependent way. Again, this process is completely reversed upon exposure to Li+. The entire process is an excellent model for fluorescence‐based logic system.
Determination of betaines in vegetable oils by capillary electrophoresis tandem mass spectrometry – application to the detection of olive oil adulteration with seed oils
Authors: Sánchez‐Hernández Laura , Castro‐Puyana María , Luisa Marina María , Crego Antonio L.
Published: April 2011

A CE–tandem mass spectrometry (MS2) methodology enabling the simultaneous determination of betaines (glycine betaine, trigonelline, proline betaine and total content of carnitines) in vegetable oils was developed. Betaines were derivatized with butanol previous to their baseline separation in 10 min using a 0.1 M formic acid buffer at pH 2.0. Ion trap conditions were optimized in order to maximize the selectivity and sensitivity. Analytical characteristics of the proposed method were established by evaluating its selectivity, linearity, precision (RSDs ranged from 4.8 to 10.7% for corrected peak areas) and accuracy by means of recovery studies (from 80 to 99%) and LODs and LOQs at 0.1 ppb level. The method was applied for the determination of the selected betaines in seed oils and extra virgin olive oils. MS2 experiments provided the fingerprint fragmentation for the betaines identified in vegetable oils. In extra virgin olive oils, carnitines were not detected, making it possible to propose them as a feasible novel marker for the detection of adulterations of olive oils. Application of the developed method for the analysis of different mixtures of extra virgin olive oil with seed oil (between 2 and 10%) enabled the detection and quantitation of the total content of carnitines. The results obtained show the high potential of the developed method for the authentication and quality control of olive oils.
Time‐of‐flight prediction for fermentation process monitoring
Authors: Hoche Sven , Hussein Walid B. , Hussein Mohamed A. , Becker Thomas
Published: April 2011

This work presents an ultrasound‐based inline sensor system, which is used to monitor the alcoholic yeast fermentation. The pulse‐echo method is used to determine ultrasound velocity (USV) of the sample medium. The major aim of the paper is to highlight the importance of an accurate time‐of‐flight (TOF) estimation for accurate concentration determination and to present method immanent strategies to fulfill the requirements. An algorithm aiming at a stable and highly accurate TOF estimation in time domain was developed. The basic methods of the algorithm are a frame‐wise signal analysis based on the sensor dimensions, cross‐correlation to find complementary impulses and root estimation via polynomial fit to calculate the TOF in time domain. The analysis results of laboratory‐scale validation trials (demineralized, vented water) and of real process data (yeast propagation) are presented. In spite of the stable algorithm performance in the lab scale, the algorithm fails in a few cases of real process signals. The relevant signals and corresponding causes for failure were analyzed and future strategies for algorithm enhancement are discussed. Reviewing the results, the aimed USV accuracy of 0.075 m/s can be achieved. The maximum USV error of the used principles and applied methods in the investigated temperature range is ±0.02%.
Time‐related element‐free Taylor–Galerkin method with non‐splitting decoupling process for incompressible steady flow
Authors: Wang Xiaodong , Ouyang Jie
Published: April 2011

The time‐related element‐free Taylor–Galerkin method with non‐splitting decoupling process (EFTG‐NSD) is proposed for the simulation of steady flows. The goal of the present paper is twofold. One is to raise the efficiency of the time‐related methods for solving steady flow problems, and the other is to obtain a good stability. The EFTG‐NSD method, which uses the time‐related Navier–Stokes equations to describe steady flows, does not care about the intermediate process and obtains solution of steady flows through time marching. Different from the classical time‐related fractional step methods, the EFTG‐NSD method decouples the Navier–Stokes equations without any operator‐splitting and correction. Because the elimination of correction at each iteration step reduces the computation cost, the EFTG‐NSD method possesses higher computation efficiency. In addition, the EFTG‐NSD method has a good stability due to the use of the Taylor–Galerkin formula in time and space discretization. Furthermore, the method combining element‐free Galerkin method with Taylor–Galerkin method is an important supplement of the element‐free Galerkin method for solving flow problems. Copyright © 2011 John Wiley & Sons, Ltd.
Reading skill is related to individual differences in brain structure in college students
Authors: Welcome Suzanne E. , Chiarello Christine , Thompson Paul M. , Sowell Elizabeth R.
Published: April 2011

We compared cortical anatomy, using 3D brain MRI scans, between three groups of university students: proficient readers (skilled at phonological decoding and text comprehension), poor readers (impaired at phonological decoding and text comprehension), and resilient readers (impaired at phonological decoding but skilled in text comprehension). This latter group provides a unique opportunity to investigate associations between cortical morphology and phonological decoding deficits in individuals without attendant reading comprehension deficits. We predicted widespread reductions in gray matter thickness and brain size in temporal and frontal regions in poor readers, and more focal differences in brain morphology in resilient readers. Typical asymmetry of gray matter thickness in the temporo‐parietal region was reduced in both poor and resilient readers. Poor readers also exhibited smaller brain sizes in the right inferior frontal region than both proficient and resilient readers. Altered asymmetry in the temporo‐parietal region may therefore be associated with poor phonological decoding and impaired text comprehension may be associated with altered frontal morphology. Resilient readers show relatively focal behavioral differences from typical readers, so it is interesting that they show reliable differences in brain morphology. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.
Osteonecrosis of the jaws associated with the use of yearly zoledronic acid: Report of 2 cases
Authors: Lee Jang‐Jaer , Cheng Shih‐Jung , Wang Yi‐Ping , Jeng Jiiang‐Huei , Chiang Chun‐Pin , Kok Sang‐Heng
Published: April 2011

Background

Once‐yearly zoledronic acid has been proven effective in the management of osteoporosis. Osteonecrosis of the jaws (ONJ) related to its use has not been reported since its approval in 2007.

Methods

Two women with osteoporosis/osteopenia developed ONJ after the second infusion of yearly zoledronic acid. They had no other systemic diseases and ONJ occurred after oral surgeries, which were performed about 2 months following drug administration.

Results

In 1 case osteonecrosis of the maxilla resolved after conservative therapy and sequestrectomy. In the other case bone necrosis developed on both sides of mandible, and the symptoms/signs of ONJ were partially responsive to conservative treatment.

Conclusions

ONJ related to yearly zoledronic acid is a severe complication that should not be ignored. To minimize the risk, we recommend preventive oral care before the start of therapy and avoiding dental invasive procedures within 3 months after drug administration. © 2011 Wiley Periodicals, Inc. Head Neck, 2013
Topographic anatomy of the internal laryngeal nerve: Surgical considerations
Authors: Paraskevas George K. , Raikos Athanasios , Ioannidis Orestis , Brand‐Saberi Beate
Published: April 2011

Background

This study is focused on the topographic features of the internal branch of the superior laryngeal nerve (ibSLN) at the thyrohyoid membrane area using as anatomic landmarks the posterior border of the thyrohyoid muscle and the superior border of the thyroid cartilage.

Methods

Thirty‐six fresh adult cadavers were dissected to determine the topography and branching pattern of the ibSLN and the superior laryngeal artery.

Results

The ibSLN prior to thyrohyoid membrane's penetration was divided into 3 or 2 branches, in 72.22% and 27.78% of cases. The trifurcated ibSLN was more common than the bifurcated in both sexes and in both sides of the neck. In over 80% of cases the ibSLN penetrated the thyrohyoid membrane 0.1 to 0.9 cm far from the posterior border of the thyrohyoid muscle and 0.1 to 1.2 cm far from the superior border of the thyroid cartilage.

Conclusions

We provide a schematic overview of the ibSLN penetration zone at the thyrohyoid membrane, the so‐called danger zone, to avoid ibSLN damage. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Some insights about the characteristics of communications observed from the off‐normal conditions of nuclear power plants
Authors: Kim Seunghwan , Park Jinkyun , Kim Yoon Joong
Published: April 2011

The result of existing research has revealed that maintaining good communication is one of the essential parts of securing the safety of a large and complex process system. Because the possibility of inappropriate communication would increase in proportion to the increase in workload, it is necessary to identify the characteristics of the communications of human operators who have to accomplish their required tasks under a high workload level. For this reason, the characteristics of communications observed under simulated off‐normal conditions of nuclear power plants (NPPs) are investigated. As a result, it is observed that the human operators working in NPPs show distinctive communication characteristics with respect to the nature of an off‐normal condition. Therefore, although additional data collections as well as research activities are indispensable, the results of this study would be a good starting point to take further steps toward reducing the possibility of inappropriate communications. © 2011 Wiley Periodicals, Inc.
Investigation of automation deployment in the main control room of nuclear power plants by using adaptive automation
Authors: Jou Yung‐Tsan , Yenn Tzu‐Chung , Yang Li‐Chen
Published: April 2011

Recently, with the progress of computer technology, the digitalization of human–system interface (HSI) in the main control room (MCR) of advanced nuclear power plants (NPPs) has become an important issue. A higher level of automation means that the computers execute the greater part of the task. The frequency, however, of automation‐induced system failures, including human errors, prompts us to more closely investigate the influences of automation. The objective of this study is to measure the effects of adaptive automation on the primary task performance, operator situation awareness (SA), and workload in an advanced MCR of an advanced NPP to reduce the number of failures and improve human performance. This study selects automatic mode and semi‐automatic mode to compose five different types of automation allocations. The experiment scenario is a reactor shutdown task. A personal computer transient analyzer (PCTran) is used to simulate the HSI of an MCR. Twelve participants are required to perform the experiment scenario on the automation allocation types. The dependent variables were the primary task performance; the subjective workload was measured using an NASA‐Task Load Index (NASA‐TLX) questionnaire; and three levels of SA were estimated by SA queries. Experimental results revealed that the automation allocations made up of higher ratio automatic modes led to superior primary task performance, lower operator workload, and lower frequency of human errors. In the high ratio automatic mode allocation, the operators have the lowest SA queries score. This study provides additional information for future digital HSI design in the MCRs of advanced NPPs. © 2011 Wiley Periodicals, Inc.
Superabsorbent polysaccharide hydrogels based on pullulan derivate as antibacterial release wound dressing
Authors: Li Huanan , Yang Jing , Hu Xiaona , Liang Jie , Fan Yujiang , Zhang Xingdong
Published: April 2011

To accomplish ideal wound dressing, hydrogels based on a natural polysaccharide, pullulan were synthesized by chemical cross‐linking. The tensile strengths of the hydrogel films (1 mm thick) were determined to range from 0.663 to 1.097 MPa in proportion to cross‐linking degrees and water contents. The swelling study of the hydrogels in water showed remarkable water absorption property with swelling ratio up to 4000%, which provided the hydrogel with quick hemostatic ability and prevent the wound bed from accumulation of exudates. The water vapor transmission rate and water retention of the hydrogels were found to be in the range of 2213–3498g/m2/day and 34.74–45.81% (after 6 days), indicating that the hydrogel can maintain a moist environment over wound bed, which could prevent the dehydration of the wound bed and prevent the scab formation. Biocompatibility test revealed that the hydrogels were not cytotoxic. The hydrogel could load antimicrobial agents and effectively suppress bacterial proliferation to protect the wound from bacterial invasion. These results suggest that the pullulan hydrogels prepared in this study may have high potential as new ideal wound‐dressing materials. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Understanding osteoblast responses to stiff nanotopographies through experiments and computational simulations
Authors: Yang Lei , Chinthapenta Viswanath , Li Qunyang , Stout David , Liang Amy , Sheldon Brian W. , Webster Thomas J.
Published: April 2011

An increasing number of studies have demonstrated the positive role nanotopographies can have toward promoting various cell functions. However, the relevant mechanism(s) behind this improvement in biological interactions at the cell–material interface is not well understood. For this reason, here, osteoblast (bone forming cell) functions (including adhesion, proliferation, and differentiation) on two carefully‐fabricated diamond films with dramatically‐different topographies were tested and modeled. The results over all the time periods tested revealed greater cell responses on nanocrystalline diamond (NCD, grain sizes <100 nm) compared to submicron crystalline diamond (SMCD, grain sizes 200–1000 nm). To understand this positive impact of cell responses per stiff nanotopographies, cell filopodia extension and cell spreading were studied through computational simulations and the results suggested that increasing the lateral dimensions or height of nanometer surface features could inhibit cell filopodia extension and, ultimately, decrease cell spreading. The computational simulation results were further verified by live cell imaging (LCI) experiments. This study, thus, describes a possible new approach to investigate (through experiments and computational simulation) the mechanisms behind nanotopography‐enhanced cell functions. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Laser‐modified nanostructures of PET films and cell behavior
Authors: Mirzadeh Hamid , Moghadam Ehsan Vahedi , Mivehchi Houri
Published: April 2011

The surface of polyethylene terephthalate (PET) films was irradiated using KrF excimer laser (λ = 248 nm) with different number of pulses at constant repetition rate. The adhesion behavior of L‐929 fibroblast cells on the irradiated surface was investigated. The changes in films' morphology were characterized by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The hydrophilicity and both polar and dispersion components of the surface tension of the treated films were evaluated by contact angle and surface tension measurement techniques. The films roughness was evaluated by atomic force microscopy. AFM and SEM observations showed that a specific nanostructure was created on the laser‐treated polyethylene terephthalate surface. Contact angle and surface energy measurements have indicated an increase in wettability of the laser treated samples up to 5 pulses as optimum result; while, by increasing the laser pulses beyond 5 pulses the hydrophilicity of laser treated samples dropped and the surface energy of the treated films was leveled off. Data from in vitro assays showed significant cell attachment and cell growth onto laser treated samples in comparison with the untreated films. Moreover, a number of fibroblast cells attached and proliferated onto treated PET films were achieved under optimum condition of 5 pulses which wassignificantly higher than the other treated samples. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.