bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the genomic region containing the Shadow of Prion Protein (SPRN) gene in sheep
Authors: Lampo Evelyne , Van Poucke Mario , Hugot Karine , Hayes Hélène , Van Zeveren Alex , Peelman Luc J 
Published: May 2007

Abstract

Background
TSEs are a group of fatal neurodegenerative diseases occurring in man and animals. They are caused by prions, alternatively folded forms of the endogenous prion protein, encoded by PRNP. Since differences in the sequence of PRNP can not explain all variation in TSE susceptibility, there is growing interest in other genes that might have an influence on this susceptibility. One of these genes is SPRN, a gene coding for a protein showing remarkable similarities with the prion protein. Until now, SPRN has not been described in sheep, a highly relevant species in prion matters.

Results
In order to characterize the genomic region containing SPRN in sheep, a BAC mini-contig was built, covering approximately 200,000 bp and containing the genes ECHS1, PAOX, MTG1, SPRN, LOC619207, CYP2E1 and at least partially SYCE1. FISH mapping of the two most exterior BAC clones of the contig positioned this contig on Oari22q24. A fragment of 4,544 bp was also sequenced, covering the entire SPRN gene and 1206 bp of the promoter region. In addition, the transcription profile of SPRN in 21 tissues was determined by RT-PCR, showing high levels in cerebrum and cerebellum, and low levels in testis, lymph node, jejunum, ileum, colon and rectum.

Conclusion
Annotation of a mini-contig including SPRN suggests conserved linkage between Oari22q24 and Hsap10q26. The ovine SPRN sequence, described for the first time, shows a high level of homology with the bovine, and to a lesser extent with the human SPRN sequence. In addition, transcription profiling in sheep reveals main expression of SPRN in brain tissue, as in rat, cow, man and mouse.
Concurrent acute illness and comorbid conditions poorly predict antibiotic use in upper respiratory tract infections: a cross-sectional analysis
Authors: Zuckerman Ilene H , Perencevich Eli N , Harris Anthony D 
Published: May 2007

AbstractBackgroundInappropriate antibiotic use promotes resistance. Antibiotics are generally not indicated for upper respiratory infections (URIs). Our objectives were to describe patterns of URI treatment and to identify patient and provider factors associated with antibiotic use for URIs.MethodsThis study was a cross-sectional analysis of medical and pharmacy claims data from the Pennsylvania Medicaid fee-for-service program database. We identified Pennsylvania Medicaid recipients with a URI office visit over a one-year period. Our outcome variable was antibiotic use within seven days after the URI visit. Study variables included URI type and presence of concurrent acute illnesses and chronic conditions. We considered the associations of each study variable with antibiotic use in a logistic regression model, stratifying by age group and adjusting for confounders.ResultsAmong 69,936 recipients with URI, 35,786 (51.2%) received an antibiotic. In all age groups, acute sinusitis, chronic sinusitis, otitis, URI type and season were associated with antibiotic use. Except for the oldest group, physician specialty and streptococcal pharyngitis were associated with antibiotic use. History of chronic conditions was not associated with antibiotic use in any age group. In all age groups, concurrent acute illnesses and history of chronic conditions had only had fair to poor ability to distinguish patients who received an antibiotic from patients who did not.ConclusionAntibiotic prevalence for URIs was high, indicating that potentially inappropriate antibiotic utilization is occurring. Our data suggest that demographic and clinical factors are associated with antibiotic use, but additional reasons remain unexplained. Insight regarding reasons for antibiotic prescribing is needed to develop interventions to address the growing problem of antibiotic resistance.
Higher incidence of persistent chronic infection of Chlamydia pneumoniae among coronary artery disease patients in India is a cause of concern
Authors: Jha Hem C , Vardhan Harsh , Gupta Rishein , Varma Rakesh , Prasad Jagdish , Mittal Aruna 
Published: May 2007

Abstract

Background
There is growing evidence that Chlamydia pneumoniae may be involved in the pathogenesis of atherosclerosis, as several studies have demonstrated the presence of the organism in atherosclerotic lesions. C. pneumoniae infections, which are especially persistent infections, have been difficult to diagnose either by serological methods or isolation of the organism from the tissue. Nucleic Acid Amplification tests (NAATs) has emerged as an important method for detecting C. pneumoniae. Inspite of high prevalence of C. pneumoniae specific antibodies in coronary heart disease patients, direct detection of C. pneumoniae in circulating blood of coronary artery disease (CAD) patients by sensitive nucleic acid amplification tests nested PCR (nPCR), multiplex PCR (mPCR) has not been carried out is required. Further correlation of the presence of C. pneumoniae in blood of CAD patients with C. pneumoniae specific IgA and IgG antibodies, which may indicative of the status of infection with the progression of atherosclerosis. This will help in order to prepare strategies for the antibiotic intervention to avoid the progression towards CAD.

Methods
Venous blood was obtained from 91 CAD patients and 46 healthy controls. Nucleic acid amplification tests viz. nested -, semi-nested – and multiplex PCR were used for detection of C. pneumoniae. ELISA carried out prevalence of C. pneumoniae specific IgG and IgA antibodies.

Results
29.67% (27/91) patients were positive for C. pneumoniae using nested PCR. The sensitivity and specificity of semi-nested and multiplex PCR were 37.03%, 96.96% and 22.22%, 100% with respect to nested PCR. Positive nPCR patients were compared with presence of C. pneumoniae specific IgA, IgA+IgG and IgG antibodies. Among 27 (29.67%) nPCR C. pneumoniae positive CAD patients, 11(12%) were IgA positive, 13(14.2%) were IgA+IgG positive and only1 (1.1%) was IgG positive. A significant presence of C. pneumoniae was detected in heavy smokers, non-alcoholics and with family histories of diabetes and blood pressure group of CAD patients by nPCR.

Conclusion
The results indicate synergistic association of C. pneumoniae infection and development of CAD with other risk factors. We also detected increased positivity for C. pneumoniae IgA than IgG in nPCR positive CAD patients. Positive nPCR findings in conjunction with persisting high C. pneumoniae specific antibody strongly suggest an ongoing infection.
HTLV-1 Tax mutants that do not induce G1arrest are disabled in activating the anaphase promoting complex
Authors: Merling Randall , Chen Chunhua , Hong Sohee , Zhang Ling , Liu Meihong , Kuo Yu-Liang , Giam Chou-Zen 
Published: May 2007

Abstract
HTLV-1 Tax is a potent activator of viral transcription and NF-κB. Recent data indicate that Tax activates the anaphase promoting complex/cyclosome (APC/C) ahead of schedule, causing premature degradation of cyclin A, cyclin B1, securin, and Skp2. Premature loss of these mitotic regulators is accompanied by mitotic aberrations and leads to rapid senescence and cell cycle arrest in HeLa and S. cerevisiae cells. Tax-induced rapid senescence (tax-IRS) of HeLa cells is mediated primarily by a dramatic stabilization of p27
KIP
and is also accompanied by a great surge in the level of p21
CIP1
mRNA and protein. Deficiencies in p27
KIP
prevent Tax-IRS. A collection of tax point mutants that permit normal growth of S. cerevisiae have been isolated. Like wild-type tax, many of them (C23W, A108T, L159F, and L235F) transactivate both the HTLV-LTR and the NF-κB reporters. One of them, V19M, preferentially activates NF-κB, but is attenuated for LTR activation. None of the mutants significantly elevated the levels of p21
CIP1
and p27
KIP1
, indicating that the dramatic surge in p21
CIP1/WAF1
and p27
KIP 1
induced by Tax is brought about by a mechanism distinct from NF-κB or LTR activation. Importantly, the ability of these mutants to activate APC/C is attenuated or abrogated. These data indicate that Tax-induced rapid senescence is causally associated with APC/C activation.
GOGOT: a method for the identification of differentially expressed fragments from cDNA-AFLP data
Authors: Kadota Koji , Araki Ryoko , Nakai Yuji , Abe Masumi 
Published: May 2007

AbstractBackgroundOne-dimensional (1-D) electrophoretic data obtained using the cDNA-AFLP method have attracted great interest for the identification of differentially expressed transcript-derived fragments (TDFs). However, high-throughput analysis of the cDNA-AFLP data is currently limited by the need for labor-intensive visual evaluation of multiple electropherograms. We would like to have high-throughput ways of identifying such TDFs.ResultsWe describe a method, GOGOT, which automatically detects the differentially expressed TDFs in a set of time-course electropherograms. Analysis by GOGOT is conducted as follows: correction of fragment lengths of TDFs, alignment of identical TDFs across different electropherograms, normalization of peak heights, and identification of differentially expressed TDFs using a special statistic. The output of the analysis is a highly reduced list of differentially expressed TDFs. Visual evaluation confirmed that the peak alignment was performed perfectly for the TDFs by virtue of the correction of peak fragment lengths before alignment in step 1. The validity of the automated ranking of TDFs by the special statistic was confirmed by the visual evaluation of a third party.ConclusionGOGOT is useful for the automated detection of differentially expressed TDFs from cDNA-AFLP temporal electrophoretic data. The current algorithm may be applied to other electrophoretic data and temporal microarray data.
Unequal evolutionary conservation of human protein interactions in interologous networks
Authors: Brown Kevin R , Jurisica Igor 
Published: May 2007

Abstract
Background
Protein-protein interaction (PPI) networks have been transferred between organisms using interologs, allowing model organisms to supplement the interactomes of higher eukaryotes. However, the conservation of various network components has not been fully explored. Unequal conservation of certain network components may limit the ability to fully expand the target interactomes using interologs.

Results
In this study, we transfer high quality human interactions to lower eukaryotes, and examine the evolutionary conservation of individual network components. When human proteins are mapped to yeast, we find a strong positive correlation (r = 0.50, P = 3.9 × 10-4) between evolutionary conservation and the number of interacting proteins, which is also found when mapped to other model organisms. Examining overlapping PPI networks, Gene Ontology (GO) terms, and gene expression data, we are able to demonstrate that protein complexes are conserved preferentially, compared to transient interactions in the network. Despite the preferential conservation of complexes, and the fact that the human interactome comprises an abundance of transient interactions, we demonstrate how transferring human PPIs to yeast augments this well-studied protein interaction network, using the coatomer complex and replisome as examples.

Conclusion
Human proteins, like yeast proteins, show a correlation between the number of interacting partners and evolutionary conservation. The preferential conservation of proteins with higher degree leads to enrichment in protein complexes when interactions are transferred between organisms using interologs.
Crystal-induced neutrophil activation. IX. Syk-dependent activation of class Ia phosphatidylinositol 3-kinase
Authors: Popa-Nita Oana , Rollet-Labelle Emmanuelle , Thibault Nathalie , Gilbert Caroline , Bourgoin Sylvain G , Naccache Paul H 
Published: May 2007

AbstractThe deposition of monosodium urate (MSU) crystals in the joints of humans leads to an extremely acute, inflammatory reaction, commonly known as gout, characterized by a massive infiltration of neutrophils. Direct interactions of MSU crystals with human neutrophils and inflammatory mediators are crucial to the induction and perpetuation of gout attacks. The intracellular signaling events initiated by the physical interaction between MSU crystals and neutrophils depend on the activation of specific tyrosine kinases (Src and Syk, in particular). In addition, PI-3Ks may be involved. The present study investigates the involvement of the PI-3K family in the mediation of the responses of human neutrophils to MSU crystals. The results obtained indicate that the interaction of MSU crystals with human neutrophils leads to the stimulation of class Ia PI-3Ks by a mechanism that is dependent on the tyrosine kinase Syk. We also found an increase in the amount of p85 associated with the Nonidet P-40-insoluble fraction derived from MSU crystal-stimulated human neutrophils. Furthermore, MSU crystals induce the formation of a complex containing p85 and Syk, which is mediated by the Src family kinases. Finally, evidence is also obtained indicating that the activation of PI-3Ks by MSU crystals is a critical element regulating phospholipase D activation and degranulation of human neutrophils. The latter response is likely to be involved in the joint and tissue damage that occurs in gouty patients.
Open-Label, Uncontrolled, Multicenter Phase II Study to Evaluate the Efficacy and Toxicity of Cetuximab As a Single Agent in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Who Failed to Respond to Platinum-Based Therapy
Authors: Vermorken Jan B. , Trigo José , Hitt Ricardo , Koralewski Piotr , Diaz-Rubio Eduardo , Rolland Frédéric , Knecht Rainald , Amellal Nadia , Schueler Armin , Baselga José 
Published: May 2007

Purpose To evaluate the efficacy and safety of the epidermal growth factor receptor–directed monoclonal antibody cetuximab administered as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) who experience disease progression on platinum therapy. Patients and Methods An open-label multicenter study in which patients with disease progression on two to six cycles of platinum therapy received single-agent cetuximab (initial dose 400 mg/m2 followed by subsequent weekly doses of 250 mg/m2) for ≥ 6 weeks (single-agent phase). Patients who experienced disease progression could receive salvage therapy with cetuximab plus platinum (combination-therapy phase). From June 2001 to December 2002, 103 patients were enrolled and treated with cetuximab, 53 of whom subsequently received combination therapy. Results In the single-agent phase, response rate was 13%, disease control rate (complete response/partial response/stable disease) was 46%, and median time to progression (TTP) was 70 days. During the combination-therapy phase, the objective response rate was zero, disease control rate was 26%, and TTP was 50 days. Median overall survival was 178 days. Treatment was well tolerated. The most common cetuximab-related adverse events in the single-agent phase were skin reactions, particularly rash (49% of patients, mainly grade 1 or 2). There was one treatment-related death due to an infusion-related reaction. Conclusion Single-agent cetuximab was active and generally well tolerated in the treatment of recurrent and/or metastatic SCCHN that progressed on platinum therapy. Response was comparable to that seen with cetuximab plus platinum combination regimens in the same setting.
Gemcitabine Plus Capecitabine Compared With Gemcitabine Alone in Advanced Pancreatic Cancer: A Randomized, Multicenter, Phase III Trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group
Authors: Herrmann Richard , Bodoky György , Ruhstaller Thomas , Glimelius Bengt , Bajetta Emilio , Schüller Johannes , Saletti Piercarlo , Bauer Jean , Figer Arie , Pestalozzi Bernhard , Köhne Claus-Henning , Mingrone Walter , Stemmer Salomon M. , Tàmas Karin , Kornek Gabriela V. , Koeberle Dieter , Cina Susanne , Bernhard Jürg , Dietrich Daniel , Scheithauer Werner 
Published: May 2007

Purpose This phase III trial compared the efficacy and safety of gemcitabine (Gem) plus capecitabine (GemCap) versus single-agent Gem in advanced/metastatic pancreatic cancer. Patients and Methods Patients were randomly assigned to receive GemCap (oral capecitabine 650 mg/m2 twice daily on days 1 to 14 plus Gem 1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m2 by 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks). Patients were stratified according to center, Karnofsky performance score (KPS), presence of pain, and disease extent. Results A total of 319 patients were enrolled between June 2001 and June 2004. Median overall survival (OS) time, the primary end point, was 8.4 and 7.2 months in the GemCap and Gem arms, respectively (P = .234). Post hoc analysis in patients with good KPS (score of 90 to 100) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm (10.1 v 7.4 months, respectively; P = .014). The overall frequency of grade 3 or 4 adverse events was similar in each arm. Neutropenia was the most frequent grade 3 or 4 adverse event in both arms. Conclusion GemCap failed to improve OS at a statistically significant level compared with standard Gem treatment. The safety of GemCap and Gem was similar. In the subgroup of patients with good performance status, median OS was improved significantly. GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status.
Prospective Study of Gefitinib in Epidermal Growth Factor Receptor Fluorescence In Situ Hybridization–Positive/Phospho-Akt–Positive or Never Smoker Patients With Advanced Non–Small-Cell Lung Cancer: The ONCOBELL Trial
Authors: Cappuzzo Federico , Ligorio Claudia , Jänne Pasi A. , Toschi Luca , Rossi Elisa , Trisolini Rocco , Paioli Daniela , Holmes Alison J. , Magrini Elisabetta , Finocchiaro Giovanna , Bartolini Stefania , Cancellieri Alessandra , Ciardiello Fortunato , Patelli Marco , Crino Lucio , Varella-Garcia Marileila 
Published: May 2007

Purpose In non–small-cell lung cancer (NSCLC), clinical and biologic predictors for epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor sensitivity have been identified in retrospective studies, and there is urgent need to validate these results in prospective trials. The ONCOBELL trial is a prospective phase II study evaluating gefitinib sensitivity in NSCLC patients who never smoked or have increased EGFR gene copy number or activation of the antiapoptotic protein Akt. Patients and Methods EGFR gene copy number was evaluated using fluorescence in situ hybridization (FISH), and presence of phospho-Akt was evaluated using immunohistochemistry. Additional tests included immunohistochemistry analysis of EGFR, FISH analysis of HER2, and mutation analysis of EGFR, HER2, and K-ras. Results From November 2004 to February 2006, 183 patients were screened, and 42 patients were enrolled onto the trial. We observed one complete and 19 partial responses, for an overall response rate (RR) of 47.6% (95% CI, 32.5% to 62.7%). Median duration of response was 6.1 months, median time to progression (TTP) was 6.4 months, 1-year survival rate was 64.3%, and median survival time was not reached. EGFR FISH–positive patients, compared with negative patients, had higher RR (68.0% v 9.1%, respectively; P < .001), longer TTP (7.6 v 2.7 months, respectively; P = .02), and a trend for longer survival (median survival not reached v 7.4 months, respectively; P = .3). Therapy was well tolerated, and there were no drug-related deaths. Median follow-up time was too short for significance tests of differences in survival outcomes. Conclusion Gefitinib is active and well tolerated in patients with trial characteristics, and EGFR FISH analysis is an accurate predictor for such therapy.
Perspectives on Post-Treatment Cancer Care: Qualitative Research With Survivors, Nurses, and Physicians
Authors: Hewitt Maria E. , Bamundo Annette , Day Rebecca , Harvey Catherine 
Published: May 2007

Purpose Cancer survivors have many medical and psychosocial needs that are unaddressed in the post-treatment period. Qualitative research was carried out to assess how a survivorship care plan created by oncologists could improve the quality of survivorship care. Participants and Methods Focus groups and interviews conducted with cancer survivors, nurses, primary care physicians, and oncologists provide insights into post-treatment follow-up practices and the acceptability and feasibility of providing survivors and referring physicians with a cancer survivorship care plan. Results Cancer survivors reported satisfaction with post-treatment medical care, but felt that their psychosocial needs were not met. Survivors expressed enthusiastic support for receipt of a follow-up care plan. Primary care physicians viewed themselves as playing an important role during the post-treatment period and indicated that a written care plan for follow-up would help them improve their survivorship practices. Nurses recognized the need to improve the care of cancer survivors and suggested that they could play an active role in creating and implementing cancer survivorship plans. Physicians providing oncology care acknowledged the value of survivorship care plans, but were not inclined to complete them because such plans would not reduce other reporting and communication requirements and would be burdensome to complete given their busy schedules. Conclusion Survivorship care planning is viewed favorably by consumers, nurses, and physicians, however there are several barriers to its adoption. Barriers may be overcome with: electronic medical records, changes in reporting requirements of insurers, advocacy on the part of patients, and incorporation of care planning in education and training programs.
HLA Class II Expression by Hodgkin Reed-Sternberg Cells Is an Independent Prognostic Factor in Classical Hodgkin's Lymphoma
Authors: Diepstra Arjan , van Imhoff Gustaaf W. , Karim-Kos Henrike E. , van den Berg Anke , te Meerman Gerard J. , Niens Marijke , Nolte Ilja M. , Bastiaannet Esther , Schaapveld Michael , Vellenga Edo , Poppema Sibrand 
Published: May 2007

Purpose The neoplastic Hodgkin Reed-Sternberg (HRS) cells in classical Hodgkin's lymphoma (cHL) are derived from B cells. The frequency of HLA class II downregulation and its effect on prognosis are unknown. Patients and Methods Immunohistochemistry results for HLA class II were evaluated in 292 primary cHL patients in a population-based approach. Patients were diagnosed between 1989 and 2000 in the northern part of the Netherlands. Median age at diagnosis was 38 years (range, 8 to 88 years); 63% had Ann Arbor stage I or II, 24% stage III, and 13% stage IV disease. Median follow-up was 7.1 years. For 168 patients, HLA genotype data were available. Results Lack of HLA class II cell-surface expression on HRS cells was observed in 41.4% and was more common in patients with extranodal disease, patients with Epstein-Barr virus–negative disease, and patients with HLA class I–negative HRS cells. Alleles of three microsatellite markers in the HLA class II region were associated with presence or absence of protein expression. In univariate analyses, lack of HLA class II expression coincided with adverse outcome (5-years failure free survival [FFS], 67% v 85%; P = .001; 5-years age and sex matched relative survival (RS), 80% v 90%; P = .027). This effect remained in multivariate analyses for FFS with a hazard ratio of 2.40 (95% CI, 1.45 to 3.98) and RS with a relative excess risk of death of 2.55 (95% CI, 1.22 to 5.31). Conclusion Lack of membranous HLA class II expression by HRS cells in diagnostic lymph node specimens is an independent adverse prognostic factor in cHL.