bluuebunny/crossref_metadata_2025_split huggingface dataset:
SnoN expression is differently regulated in microsatellite unstable compared with microsatellite stable colorectal cancers
Authors: Chia June A , Simms Lisa A , Cozzi Sarah-Jane , Young Joanne , Jass Jeremy R , Walsh Michael D , Spring Kevin J , Leggett Barbara A , Whitehall Vicki LJ 
Published: October 2006

Abstract

Background

SnoN is an important regulator of the transforming growth factor beta (TGFβ) signalling pathway and has been shown to exhibit both tumour promotion and suppression activity.

Methods
To further explore the role of this complex molecule in colorectal tumorigenesis, we examined 52 paired normal and tumour colorectal specimens stratified by level of microsatellite instability; 18 with high-level microsatellite instability (MSI-H) and 34 microsatellite stable (MSS). SnoN transcript expression was quantitated by real-time PCR and analysed with respect to clinical indicators of prognosis.

Results
Within the MSI-H subgroup, SnoN was commonly either up-regulated (6/18, 33%) or down-regulated (7/18, 39%). A significantly different distribution of SnoN expression was observed in MSS cancers compared with MSI-H (P ≤ 0.001). Whilst 17/34 (50%) of MSS tumours demonstrated up-regulation, none showed down-regulated expression. Within the MSI-H subgroup, up-regulation was significantly correlated with lack of repeat tract mutation in the TGFβRII gene (P ≤ 0.025), suggesting that SnoN is more frequently up-regulated in the presence of functional TGFβ signalling.

Conclusion
Together these data support the notion that SnoN has both oncogenic and tumour suppressive properties depending on other genetic changes within the tumour, and that the MSI-H pathway of colorectal tumorigenesis presents an excellent model for the study of these opposing functions.
Frequent promoter hypermethylation of RASSF1A and CASP8 in neuroblastoma
Authors: Lázcoz Paula , Muñoz Jorge , Nistal Manuel , Pestaña Ángel , Encío Ignacio , Castresana Javier S 
Published: October 2006

AbstractBackgroundEpigenetic alterations and loss of heterozygosity are mechanisms of tumor suppressor gene inactivation. A new carcinogenic pathway, targeting the RAS effectors has recently been documented. RASSF1A, on 3p21.3, and NORE1A, on 1q32.1, are among the most important, representative RAS effectors.MethodsWe screened the 3p21 locus for the loss of heterozygosity and the hypermethylation status of RASSF1A, NORE1A and BLU (the latter located at 3p21.3) in 41 neuroblastic tumors. The statistical relationship of these data was correlated with CASP8 hypermethylation. The expression levels of these genes, in cell lines, were analyzed by RT-PCR.ResultsLoss of heterozygosity and microsatellite instability at 3p21 were detected in 14% of the analyzed tumors. Methylation was different for tumors and cell lines (tumors: 83% in RASSF1A, 3% in NORE1A, 8% in BLU and 60% in CASP8; cell lines: 100% in RASSF1A, 50% in NORE1A, 66% in BLU and 92% in CASP8). In cell lines, a correlation with lack of expression was evident for RASSF1A, but less clear for NORE1A, BLU and CASP8. We could only demonstrate a statistically significant association between hypermethylation of RASSF1A and hypermethylation of CASP8, while no association with MYCN amplification, 1p deletion, and/or aggressive histological pattern of the tumor was demonstrated.Conclusion1) LOH at 3p21 appears in a small percentage of neuroblastomas, indicating that a candidate tumor suppressor gene of neuroblastic tumors is not located in this region.2) Promoter hypermethylation of RASSF1A and CASP8 occurs at a high frequency in neuroblastomas.
Structure of vaccinia virus thymidine kinase in complex with dTTP: insights for drug design
Authors: El Omari Kamel , Solaroli Nicola , Karlsson Anna , Balzarini Jan , Stammers David K 
Published: October 2006

Abstract

Background
Development of countermeasures to bioterrorist threats such as those posed by the smallpox virus (variola), include vaccination and drug development. Selective activation of nucleoside analogues by virus-encoded thymidine (dThd) kinases (TK) represents one of the most successful strategies for antiviral chemotherapy as demonstrated for anti-herpes drugs. Vaccinia virus TK is a close orthologue of variola TK but also shares a relatively high sequence identity to human type 2 TK (hTK), thus achieving drug selectivity relative to the host enzyme is challenging.

Results
In order to identify any differences compared to hTK that may be exploitable in drug design, we have determined the crystal structure of VVTK, in complex with thymidine 5'-triphosphate (dTTP). Although most of the active site residues are conserved between hTK and VVTK, we observe a difference in conformation of residues Asp-43 and Arg-45. The equivalent residues in hTK hydrogen bond to dTTP, whereas in subunit D of VVTK, Asp-43 and Arg-45 adopt a different conformation preventing interaction with this nucleotide. Asp-43 and Arg-45 are present in a flexible loop, which is disordered in subunits A, B and C. The observed difference in conformation and flexibility may also explain the ability of VVTK to phosphorylate (South)-methanocarbathymine whereas, in contrast, no substrate activity with hTK is reported for this compound.

Conclusion
The difference in conformation for Asp-43 and Arg-45 could thus be used in drug design to generate VVTK/Variola TK-selective nucleoside analogue substrates and/or inhibitors that have lower affinity for hTK.
Too much data, but little inter-changeability: a lesson learned from mining public data on tissue specificity of gene expression
Authors: Li Shuyu , Li Yiqun Helen , Wei Tao , Su Eric Wen , Duffin Kevin , Liao Birong 
Published: October 2006

Abstract

Background
The tissue expression pattern of a gene often provides an important clue to its potential role in a biological process. A vast amount of gene expression data have been and are being accumulated in public repository through different technology platforms. However, exploitations of these rich data sources remain limited in part due to issues of technology standardization. Our objective is to test the data comparability between SAGE and microarray technologies, through examining the expression pattern of genes under normal physiological states across variety of tissues.

Results
There are 42–54% of genes showing significant correlations in tissue expression patterns between SAGE and GeneChip, with 30–40% of genes whose expression patterns are positively correlated and 10–15% of genes whose expression patterns are negatively correlated at a statistically significant level (p = 0.05). Our analysis suggests that the discrepancy on the expression patterns derived from technology platforms is not likely from the heterogeneity of tissues used in these technologies, or other spurious correlations resulting from microarray probe design, abundance of genes, or gene function. The discrepancy can be partially explained by errors in the original assignment of SAGE tags to genes due to the evolution of sequence databases. In addition, sequence analysis has indicated that many SAGE tags and Affymetrix array probe sets are mapped to different splice variants or different sequence regions although they represent the same gene, which also contributes to the observed discrepancies between SAGE and array expression data.

Conclusion
To our knowledge, this is the first report attempting to mine gene expression patterns across tissues using public data from different technology platforms. Unlike previous similar studies that only demonstrated the discrepancies between the two gene expression platforms, we carried out in-depth analysis to further investigate the cause for such discrepancies. Our study shows that the exploitation of rich public expression resource requires extensive knowledge about the technologies, and experiment. Informatic methodologies for better interoperability among platforms still remain a gap. One of the areas that can be improved practically is the accurate sequence mapping of SAGE tags and array probes to full-length genes.

Reviewers
This article was reviewed by Dr. I. King Jordan, Dr. Joel Bader, and Dr. Arcady Mushegian.
An enhanced RNA alignment benchmark for sequence alignment programs
Authors: Wilm Andreas , Mainz Indra , Steger Gerhard 
Published: October 2006

Abstract

Background
The performance of alignment programs is traditionally tested on sets of protein sequences, of which a reference alignment is known. Conclusions drawn from such protein benchmarks do not necessarily hold for the RNA alignment problem, as was demonstrated in the first RNA alignment benchmark published so far. For example, the twilight zone – the similarity range where alignment quality drops drastically – starts at 60 % for RNAs in comparison to 20 % for proteins. In this study we enhance the previous benchmark.

Results
The RNA sequence sets in the benchmark database are taken from an increased number of RNA families to avoid unintended impact by using only a few families. The size of sets varies from 2 to 15 sequences to assess the influence of the number of sequences on program performance. Alignment quality is scored by two measures: one takes into account only nucleotide matches, the other measures structural conservation. The performance order of parameters – like nucleotide substitution matrices and gap-costs – as well as of programs is rated by rank tests.

Conclusion
Most sequence alignment programs perform equally well on RNA sequence sets with high sequence identity, that is with an average pairwise sequence identity (APSI) above 75 %. Parameters for gap-open and gap-extension have a large influence on alignment quality lower than APSI ≤ 75 %; optimal parameter combinations are shown for several programs. The use of different 4 × 4 substitution matrices improved program performance only in some cases. The performance of iterative programs drastically increases with increasing sequence numbers and/or decreasing sequence identity, which makes them clearly superior to programs using a purely non-iterative, progressive approach. The best sequence alignment programs produce alignments of high quality down to APSI > 55 %; at lower APSI the use of sequence+structure alignment programs is recommended.
The generation and function of soluble apoE receptors in the CNS
Authors: Rebeck G William , LaDu Mary Jo , Estus Steven , Bu Guojun , Weeber Edwin J 
Published: October 2006

AbstractMore than a decade has passed since apolipoprotein E4 (APOE-ε4) was identified as a primary risk factor for Alzheimer 's disease (AD), yet researchers are even now struggling to understand how the apolipoprotein system integrates into the puzzle of AD etiology. The specific pathological actions of apoE4, methods of modulating apolipoprotein E4-associated risk, and possible roles of apoE in normal synaptic function are still being debated. These critical questions will never be fully answered without a complete understanding of the life cycle of the apolipoprotein receptors that mediate the uptake, signaling, and degradation of apoE. The present review will focus on apoE receptors as modulators of apoE actions and, in particular, explore the functions of soluble apoE receptors, a field almost entirely overlooked until now.
Association of the programmed cell death 1 (PDCD1) gene polymorphism with ankylosing spondylitis in the Korean population
Authors: Lee Sang-Hoon , Lee Yeon-Ah , Woo Doo-Hyun , Song Ran , Park Eun-Kyung , Ryu Mi-Hyun , Kim Young-Hoon , Kim Kyoung-Soo , Hong Seung-Jae , Yoo Myung Chul , Yang Hyung-In 
Published: October 2006

AbstractThe PD-1 (programmed death 1) molecule is a negative regulator of T cells.PDCD1(programmed cell death 1) has been reported to have a genetic association in systemic lupus erythematosus and rheumatoid arthritis in Caucasians. However, there are no reports on the association between this gene and ankylosing spondylitis (AS). The present study investigated the association of the PD-1 polymorphisms and the haplotypes with AS in a Korean population sample. In a case-control association study, two single-nucleotide polymorphisms, PD-1.5 C/T and PD-1.9 T/C, were genotyped in 95 AS patients and 130 healthy controls. The T allele of the PD-1.9 polymorphism was more frequent in the Korean male population with AS than in the Korean male controls (21.0% versus 6.9%, odds ratio 1.89, 95% confidence interval 1.483 to 2.408). The frequency of the CT haplotype (PD-1.5 C/T and PD-1.9 T/C) was higher in the AS patients (19%) than the controls (5.4%) (odds ratio 1.83, 95% confidence interval 1.559 to 2.521). The PD-1 polymorphism was demonstrated in Korean AS patients. The results suggest a genetic association between the PD-1 polymorphism and susceptibility to AS.
Prognostic Parameters of Metastatic Adrenocortical Carcinoma
Authors: Assié Guillaume , Antoni Guillemette , Tissier Frédérique , Caillou Bernard , Abiven Gwenaelle , Gicquel Christine , Leboulleux Sophie , Travagli Jean-Paul , Dromain Clarisse , Bertagna Xavier , Bertherat Jérôme , Schlumberger Martin , Baudin Eric 
Published: October 2006

AbstractContext: Prognostic parameters of metastatic adrenocortical carcinoma (ACC) are poorly characterized.Objective: The objective of the study was to describe the clinical presentation of metastatic ACC and determine prognostic factors for survival.Design: This was a retrospective cohort study (1988–2004).Setting: The study was conducted in an institutional practice.Patients: Participants included 124 consecutive patients with metastatic ACC, 70 from Gustave-Roussy Institute (main cohort) and 54 patients from the Cochin Hospital (validation cohort). Clinical data concerning all patients, histopathologic slides of primary tumors (44 in the main cohort and 40 in the validation cohort), and molecular biology data on 15 primary tumors (main cohort) were analyzed.Intervention: There was no intervention.Main Outcome: The main outcome was the specific survival after discovery of the first metastasis (Kaplan-Meier method). This included univariate analysis on the main cohort, confirmed on the validation cohort and then analyzed in a multivariate analysis.Results: In the main cohort, overall median survival was 20 months. In univariate analysis, the presence of hepatic and bone metastases, the number of metastatic lesions and the number of tumoral organs at the time of the first metastasis, a high mitotic rate (&gt;20 per 50 high-power field), and atypical mitoses in the primary tumor predicted survival (P = 0.05, 0.003, 0.046, 0.001, 0.01, and &lt; 0.001, respectively). The number of tumoral organs and a high mitotic rate were confirmed on the validation cohort (P = 0.009 and 0.03, respectively). These two parameters were confirmed in multivariate analysis (P = 0.0058 and 0.049).Conclusion: Metastatic ACC is a heterogeneous disease with poor outcome. The combination of the number of tumoral organs at the time of the first metastasis and the mitotic rate can predict different outcomes.
Atherogenic Lipoprotein Phenotype and Low-Density Lipoproteins Size and Subclasses in Women with Polycystic Ovary Syndrome
Authors: Berneis Kaspar , Rizzo Manfredi , Lazzaroni Veronica , Fruzzetti Franca , Carmina Enrico 
Published: October 2006

Abstract
Context: An altered lipid profile is common in polycystic ovary syndrome (PCOS) and is usually characterized by increased triglycerides and low high-density lipoprotein (HDL)-cholesterol levels. In the general population, these alterations are often associated with the increase of small low-density lipoproteins (LDLs) in the so-called “atherogenic lipoprotein phenotype” (ALP) that determines a further increase of cardiovascular risk. In this study, we evaluated the presence of ALP in the plasma of women with PCOS.
Setting: Measurements and analysis of LDL size were performed at the Clinic of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital, Zurich. PCOS patients were recruited at the Department of Clinical Medicine, University of Palermo, and the Department of Obstetrics and Gynecology, University of Pisa.
Patients: Thirty patients with PCOS (hyperandrogenism and chronic anovulation) and 24 matched controls were studied. Anthropometric data, blood glucose, serum insulin lipid profile, and LDL size and subclasses were evaluated.
Results: Compared with controls, patients with PCOS had higher plasma concentrations of insulin and triglycerides and lower HDL-cholesterol concentrations but no differences in LDL-cholesterol and total cholesterol. Patients with PCOS had smaller LDL size due to a reduction in LDL subclass I, with a concomitant increase in LDL subclasses III and IV. Fourteen PCOS patients had an increase of smaller LDL particles, and it represented the second most common lipid alteration after decrease in HDL-cholesterol. However, because in this PCOS population hypertriglyceridemia was only present in two patients, complete ALP was relatively uncommon.
Conclusions: Increase of type III or type IV LDL subclasses is a common finding in PCOS and represents the second most common lipid alteration after HDL-cholesterol decrease. However, in our PCOS patients, because of relatively low triglyceride levels, complete ALP is uncommon.
Brain radiation necrosis following treatment of an esthesioneuroblastoma (olfactory neurocytoma)
Authors: Baron Shirley Harold 
Published: October 2006

AbstractEsthesioneuroblastoma is an uncommon malignant nasal tumor which may be difficult to diagnose. Once diagnosed, selection of treatment may be a dilemma. Some advocate preoperative radiation and surgery; others, surgery and postoperative radiation if needed. A case that developed brain necrosis from postoperative radiation is presented. It is felt that the possibility exists that the patient might still be living with tumor had irradiation not been given. This is a plea for the conservative approach to treatment. The author agrees with John S. Lewis that it is unwise to use all modalities at once as there is no definite evidence that any one method of treatment or a combination of surgery and irradiation will alter the prognosis. The paper stresses the brain hazards of irradiation.
Prevention of major and minor fistulae after laryngectomy
Authors: Horgan Edwin C. , Dedo Herbert H. 
Published: October 2006

AbstractEvery Head and Neck surgeon has special techniques which he uses to get maximum rates of five‐year survival and minimum fistula formation, especially major fistula and carotid rupture. The literature reflects a wide variation in the rate of fistula formation. We reviewed the senior author's prior 78 total laryngectomies and noted a fistula rate of 10.3% (6.4% minor fistulae and 3.9% major fistulae). We also reviewed contributing factors and discuss surgical techniques designed to minimize fistula formation.
Stability of Vancomycin in Icodextrin Peritoneal Dialysis Solution
Authors: Nornoo Adwoa O , Elwell Rowland J 
Published: October 2006

Background: Icodextrin is a glucose polymer used as an alternative osmotic agent in peritoneal dialysis (PD) solutions. There are few data regarding the long-term stability of vancomycin in icodextrin PD solution. Objective: To determine the chemical stability of vancomycin in icodextrin PD solution in polyvinyl chloride containers over a 7 day period at 4, 24, and 37 °C. Methods: Study samples were prepared by adding 2000 mg vancomycin HCl to commercially available 2.0 L bags of icodextrin 7.5% PD solution. Nine bags were prepared and stored in the following conditions: 3 under refrigeration (5 °C), 3 at room temperature (24 °C), and 3 at body temperature (37 °C). Samples were withdrawn from each bag immediately after preparation and at predetermined intervals over the subsequent 7 days. Solutions were visually inspected for precipitation, cloudiness, or discoloration at each sampling interval. Total concentration of vancomycin in dialysate fluid was determined by high performance liquid chromatography. Results: Under refrigeration, a mean ± SD of 99.7% ± 0.5% of the initial vancomycin concentration remained at 168 hours (7 days). At room temperature, 97.5% ± 3.4% remained at 168 hours. At body temperature, 94.3% ± 3.9% remained at 24 hours. Stability was not assessed beyond these time points. Conclusions: Premixed vancomycin-icodextrin PD solutions, whether stored refrigerated or at room temperature, were found to be stable for up to 7 days. However, we recommend that these solutions be kept refrigerated whenever possible. Solutions stored at body temperature were stable for up to 24 hours, permitting the practice of prewarming solutions prior to administration.
Formulary Forum Doxercalciferol Treatment of Secondary Hyperparathyroidism
Authors: Dennis Vincent C , Albertson Guy L 
Published: October 2006

Objective: To review the pharmacology, pharmacokinetics, effectiveness, safety, and therapeutic considerations related to the use of doxercalciferol in the treatment of secondary hyperparathyroidism. Data Sources: A MEDLINE search (1966–June 2006) was conducted using the key words vitamin D, ergocalciferols, and secondary hyperparathyroidism. Text word searches were also performed for the terms 1-ά-hydroxy-vitamin D2,1-ά-hydroxyergocalciferol, Hectorol, and doxercalciferol. Searches were limited to studies published in English and conducted in human subjects. Study Selection and Data Extraction: All published clinical studies evaluating the safety and effectiveness of doxercalciferol in secondary hyperparathyroidism were reviewed, and anecdotal patient reports were also evaluated. Selected clinical studies involving the use of calcitriol and/or paricalcitol in the treatment of secondary hyperparathyroidism were also included. Data Synthesis: Doxercalciferol effectively reduces parathyroid hormone levels in patients with chronic kidney disease (CKD). Both oral and intravenous administration can significantly increase serum calcium and/or phosphorus levels as evidenced by placebo-controlled clinical trials. This agent has not been studied comparatively with calcitriol or paricalcitol to assess relative safety. Conclusions: Doxercalciferol is approved for and effective in the treatment of secondary hyperparathyroidism related to CKD, both before and during dialysis, but has not demonstrated a lower incidence of hypercalcemia and/or hyperphosphatemia in relation to other vitamin D therapies. The drug is available in both oral and intravenous dosage forms. Doxercalciferol should be maintained as a formulary alternative for patients unresponsive to or intolerant of other vitamin D therapies, but comparative randomized studies are needed to differentiate its place in therapy.