bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Analysis of Regulatory and Effector T Cells in Progressively Growing versus Rejecting Tumors of Similar Origins
Authors: Bui Jack D. , Uppaluri Ravindra , Hsieh Chyi-Song , Schreiber Robert D. 
Published: July 2006

AbstractAlthough regulatory T cells (Tregs) have been detected in clinically apparent and experimentally induced tumors, the significance of their presence is obscured because past studies examined late-stage tumors that had formed in immunocompetent hosts and thus had evolved mechanisms to escape immunologic recognition and/or elimination. Herein, we report the first comparative analysis of the antitumor response to 3′-methylcholanthrene–induced tumors, which either grow progressively (progressor tumors) or are rejected by the immune system (regressor tumors). Surprisingly, we found that both progressor and regressor tumors harbored proliferating (i.e., activated) Foxp3+CD25+Tregs. However, progressor tumors contained a higher percentage of Tregs in the lymphocyte subset versus regressor tumors. The Tregs in progressor tumors were derived from peripheral CD25+ natural Tregs, accumulated early after tumor challenge and were actively proliferating, suggesting that progressor tumors recruited and/or activated endogenous Tregs as a mechanism of escaping immune destruction. To explore whether Tregs directly contributed to the progressive growth phenotype of progressor tumors, we monitored tumor outgrowth in naive wild-type recipients pretreated with either a control monoclonal antibody (mAb) or a depleting CD25-specific mAb. In mice predepleted of CD25+ cells, the tumors that subsequently developed displayed an increased accumulation of proliferating CD8+ T cells and were rejected. These results show that, although Tregs are activated in both regressor and progressor tumors, the ratio of regulatory to effector T cells is critical in determining whether the host successfully rejects the tumor or eventually succumbs to tumor outgrowth. (Cancer Res 2006; 66(14): 7301-9)
The Human Orthologue of Drosophila Ecdysoneless Protein Interacts with p53 and Regulates Its Function
Authors: Zhang Ying , Gurumurthy Channabasavaiah B. , Kim JunHyun , Bhat Ishfaq , Gao Qingshen , Dimri Goberdhan , Lee Sam W. , Band Hamid , Band Vimla 
Published: July 2006

Abstract
Biochemical mechanisms that control the levels and function of key tumor suppressor proteins are of great interest as their alterations can lead to oncogenic transformation. Here, we identify the human orthologue of Drosophila melanogaster ecdysoneless (hEcd) as a novel p53-interacting protein. Overexpression of hEcd increases the levels of p53 and enhances p53 target gene transcription whereas hEcd knockdown has the opposite effects on p53 levels and target gene expression. Furthermore, hEcd interacts with murine double minute-2 and stabilizes p53 by inhibiting murine double minute-2–mediated degradation of p53. Thus, hEcd protein represents a novel regulator of p53 stability and function. Our studies also represent the first demonstration of a biochemical function for hEcd protein and raise the possibility that altered hEcd levels and/or function may contribute to oncogenesis. (Cancer Res 2006; 66(14): 7167-75)
Papilloma Development Is Delayed in Osteopontin-Null Mice: Implicating an Antiapoptosis Role for Osteopontin
Authors: Hsieh Yu-Hua , Juliana M. Margaret , Hicks Patricia H. , Feng Gong , Elmets Craig , Liaw Lucy , Chang Pi-Ling 
Published: July 2006

Abstract
Osteopontin is a secreted, adhesive glycoprotein, whose expression is markedly elevated in several types of cancer and premalignant lesions, implicating its association with carcinogenesis. To test the hypothesis that induced osteopontin is involved in tumor promotion in vivo, osteopontin-null and wild-type (WT) mice were subjected to a two-stage skin chemical carcinogenesis protocol. Mice were initiated with 7,12-dimethylbenz(a)anthracene (DMBA) applied on to the dorsal skin followed by twice weekly application of 12-O-tetradecanoylphorbol-13-acetate (TPA) for 27 weeks. Osteopontin-null mice showed a marked decrease both in tumor/papilloma incidence and multiplicity compared with WT mice. Osteopontin is minimally expressed in normal epidermis, but on treatment with TPA its expression is highly induced. To determine the possible mechanism(s) by which osteopontin regulates tumor development, we examined cell proliferation and cell survival. Epidermis from osteopontin-null and WT mice treated with TPA thrice or with DMBA followed by TPA for 11 weeks showed a similar increase in epidermal hyperplasia, suggesting that osteopontin does not mediate TPA-induced cell proliferation. Bromodeoxyuridine staining of papillomas and adjacent epidermis showed no difference in cell proliferation between groups. However, terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling analyses indicated a greater number of apoptotic cells in DMBA-treated skin and papillomas from osteopontin-null versus WT mice. These studies are the first to show that induction of the matricellular protein osteopontin facilitates DMBA/TPA-induced cutaneous carcinogenesis most likely through prevention of apoptosis. (Cancer Res 2006; 66(14): 7119-27)
Prohibitin Is a Novel Target Gene of Vitamin D Involved in Its Antiproliferative Action in Breast Cancer Cells
Authors: Peng Xinjian , Mehta Rajeshwari , Wang Sheng , Chellappan Srikumar , Mehta Rajendra G. 
Published: July 2006

Abstract
Previously, we showed that N-methyl-N-nitrosourea–transformed MCF12F breast epithelial cells exhibited differential expression of several genes, including up-regulation of prohibitin and elevated sensitivity to a relatively noncalcemic vitamin D analogue, 1α-hydroxyvitamin D5 [1α(OH)D5]. In this report, we evaluated the functional significance of prohibitin in relation to the cellular response to vitamin D. The in silico screening for putative transcription factor binding sites identified two vitamin D receptor (VDR)/retinoid X receptor binding sites in the 1-kb promoter region of prohibitin. Prohibitin up-regulation by 1α(OH)D5 treatment at both transcriptional and translational levels was confirmed by real-time reverse transcription-PCR and Western blot analysis in breast cancer cells, identifying prohibitin as a vitamin D target gene. Confocal microscopic analysis showed that prohibitin was localized in the nuclei of MCF-7 cells and a portion of prohibitin was colocalized with VDR, but direct physical interaction between VDR and prohibitin in cell lysates was not detectable. In MCF-7 cells expressing tetracycline-inducible prohibitin (Tet-On model), the overexpression of prohibitin inhibited cell proliferation and enhanced vitamin D–induced antiproliferative activity. Knockdown of prohibitin was accompanied by increased number of cells incorporating bromodeoxyuridine in the whole population and increased cell distribution in the S phase of cell cycle. In addition, prohibitin level had no significant effect on the vitamin D–induced transactivation of CYP24, a VDR target gene. This is the first report to suggest that prohibitin serves as a novel vitamin D target gene, which is involved in the antiproliferative action of vitamin D without affecting CYP24 transactivation in breast cancer cells. (Cancer Res 2006; 66(14): 7361-9)
Association with HSP90 Inhibits Cbl-Mediated Down-regulation of Mutant Epidermal Growth Factor Receptors
Authors: Yang Seungchan , Qu Shimian , Perez-Tores Marianela , Sawai Ayana , Rosen Neal , Solit David B. , Arteaga Carlos L. 
Published: July 2006

Abstract
Activating mutations in the epidermal growth factor receptor (EGFR), localized in the activation loop within the kinase domain, have been discovered in non–small cell lung cancers (NSCLC). Most of these mutants are exquisitely sensitive to EGFR tyrosine kinase inhibitors, suggesting that they generate receptor dependence in the cancers that express them. 32D cells stably expressing EGFR-L861Q and EGFR-L858R but not wild-type EGFR exhibited ligand-independent receptor phosphorylation and viability. Ligand-induced receptor down-regulation (LIRD) was impaired in mutant-expressing cells. The EGFR mutants were constitutively associated with the E3 ubiquitin ligase Cbl but did not associate with the adaptor protein CIN85 on the addition of ligand. Inhibition of HSP90 activity with geldanamycin restored Cbl function as indicated by receptor ubiquitination and LIRD. These results suggest that EGFR mutants form defective endocytic complexes. In addition, HSP90 plays a role in maintaining the functional conformation of EGFR mutants and protecting activated receptors from LIRD. (Cancer Res 2006; 66(14): 6990-7)
"The Ministry of Reconciliation" (2 Cor 5:14–21): Paul's Key to the Problem of "the Other" in Corinth
Authors: Okure Teresa 
Published: July 2006

AbstractLocating the theme of reconciliation in the complex world of diversity, this article affirms and revisits reconciliation as a theological key to deal with the complex reality of our world. Recognizing the possibility of deep diversity of the first century Corinth, the author states that Paul's main purpose in writing to the Corinthians was to help them relate with "the other" within the Christian community and with him. The author then went on to draw what can be learned from Paul's plea to reconcile with God and with each other in 2 Corinthians 5:14–21. In his ministry of reconciliation, the former Pharisee of Pharisees crossed new boundaries as evident, for instance, in his affirmation of women as his co-ministers. Secondly, Paul tried to persuade others to join him in reflecting the meaning of their call to be ministers of reconciliation in concrete situations. Did Paul succeed in his ministry of reconciliation? It is clear from his letters that he was not successful. We will also encounter obstacles and difficulties, but we must hold on to God's reconciling ministry given to us as a gift, plead the author.
BBP: Brucella genome annotation with literature mining and curation
Authors: Xiang Zuoshuang , Zheng Wenjie , He Yongqun 
Published: July 2006

Abstract

Background

Brucella species are Gram-negative, facultative intracellular bacteria that cause brucellosis in humans and animals. Sequences of four Brucella genomes have been published, and various Brucella gene and genome data and analysis resources exist. A web gateway to integrate these resources will greatly facilitate Brucella research. Brucella genome data in current databases is largely derived from computational analysis without experimental validation typically found in peer-reviewed publications. It is partially due to the lack of a literature mining and curation system able to efficiently incorporate the large amount of literature data into genome annotation. It is further hypothesized that literature-based Brucella gene annotation would increase understanding of complicated Brucella pathogenesis mechanisms.

Results
The Brucella Bioinformatics Portal (BBP) is developed to integrate existing Brucella genome data and analysis tools with literature mining and curation. The BBP InterBru database and Brucella Genome Browser allow users to search and analyze genes of 4 currently available Brucella genomes and link to more than 20 existing databases and analysis programs. Brucella literature publications in PubMed are extracted and can be searched by a TextPresso-powered natural language processing method, a MeSH browser, a keywords search, and an automatic literature update service. To efficiently annotate Brucella genes using the large amount of literature publications, a literature mining and curation system coined Limix is developed to integrate computational literature mining methods with a PubSearch-powered manual curation and management system. The Limix system is used to quickly find and confirm 107 Brucella gene mutations including 75 genes shown to be essential for Brucella virulence. The 75 genes are further clustered using COG. In addition, 62 Brucella genetic interactions are extracted from literature publications. These results make possible more comprehensive investigation of Brucella pathogenesis. Other BBP features include publication email alert service, Brucella researchers' contact database, and discussion forum.

Conclusion
BBP is a gateway for Brucella researchers to search, analyze, and curate Brucella genome data originated from public databases and literature. Brucella gene mutations and genetic interactions are annotated using Limix leading to better understanding of Brucella pathogenesis.
Expression patterns of plexins and neuropilins are consistent with cooperative and separate functions during neural development
Authors: Mauti Olivier , Sadhu Rejina , Gemayel Joelle , Gesemann Matthias , Stoeckli Esther T 
Published: July 2006

Abstract

Background
Plexins are a family of transmembrane proteins that were shown to act as receptors for Semaphorins either alone or in a complex together with Neuropilins. Based on structural criteria Plexins were subdivided into 4 classes, A through D. PlexinAs are mainly thought to act as mediators of repulsive signals in cell migration and axon guidance. Their functional role in vertebrates has been studied almost exclusively in the context of Semaphorin signaling, i.e. as co-receptors for class 3 Semaphorins. Much less is known about Plexins of the other three classes. Despite the fact that Plexins are involved in the formation of neuronal circuits, the temporal changes of their expression patterns during development of the nervous system have not been analyzed in detail.

Results
Only seven plexins are found in the chicken genome in contrast to mammals, where nine plexins have been identified. Here, we describe the dynamic expression patterns of all known plexin family members in comparison to the neuropilins in the developing chicken spinal cord.

Conclusion
Our in situ hybridization study revealed that the expression patterns of plexins and neuropilins are only partially overlapping, especially during early and intermediate stages of spinal cord development, supporting both cooperative and separate functions of plexins and neuropilins in neural circuit formation.
The yfhQ gene of Escherichia coli encodes a tRNA:Cm32/Um32 methyltransferase
Authors: Purta Elzbieta , van Vliet Françoise , Tkaczuk Karolina L , Dunin-Horkawicz Stanislaw , Mori Hirotada , Droogmans Louis , Bujnicki Janusz M 
Published: July 2006

Abstract

Background
Naturally occurring tRNAs contain numerous modified nucleosides. They are formed by enzymatic modification of the primary transcripts during the complex RNA maturation process. In model organisms Escherichia coli and Saccharomyces cerevisiae most enzymes involved in this process have been identified. Interestingly, it was found that tRNA methylation, one of the most common modifications, can be introduced by S-adenosyl-L-methionine (AdoMet)-dependent methyltransferases (MTases) that belong to two structurally and phylogenetically unrelated protein superfamilies: RFM and SPOUT.

Results
As a part of a large-scale project aiming at characterization of a complete set of RNA modification enzymes of model organisms, we have studied the Escherichia coli proteins YibK, LasT, YfhQ, and YbeA for their ability to introduce the last unassigned methylations of ribose at positions 32 and 34 of the tRNA anticodon loop. We found that YfhQ catalyzes the AdoMet-dependent formation of Cm32 or Um32 in tRNASer1 and tRNAGln2 and that an E. coli strain with a disrupted yfhQ gene lacks the tRNA:Cm32/Um32 methyltransferase activity. Thus, we propose to rename YfhQ as TrMet(Xm32) according to the recently proposed, uniform nomenclature for all RNA modification enzymes, or TrmJ, according to the traditional nomenclature for bacterial tRNA MTases.

Conclusion
Our results reveal that methylation at position 32 is carried out by completely unrelated TrMet(Xm32) enzymes in eukaryota and prokaryota (RFM superfamily member Trm7 and SPOUT superfamily member TrmJ, respectively), mirroring the scenario observed in the case of the m1G37 modification (introduced by the RFM member Trm5 in eukaryota and archaea, and by the SPOUT member TrmD in bacteria).
Outcome of AIDS-associated cryptococcal meningitis initially treated with 200 mg/day or 400 mg/day of fluconazole
Authors: Schaars CF , Meintjes GA , Morroni C , Post FA , Maartens G 
Published: July 2006

Abstract

Background
AIDS-associated cryptococcal meningitis has a high mortality. Fluconazole was the only systemic antifungal therapy available in our centre. From 1999–2001 we used low-dose fluconazole (200 mg daily initially), and did not offer therapy to patients perceived to have poor prognoses. In 2001 donated fluconazole became available, allowing us to use standard doses (400 mg daily initially). Antiretroviral therapy was not available during the study period.

Methods
Retrospective chart review of adult patients before and after the fluconazole donation.

Results
205 patients fulfilled the inclusion criteria, 77 before and 128 after the donation. Following the donation fewer patients received no antifungal treatment (5% vs 19%, p = 0.002), and more patients received standard-dose fluconazole (90% vs 6%, p < 0.001). In-hospital mortality was 25%. Impaired consciousness, no antifungal treatment received and cerebrospinal fluid antigen titre > 1,000 were independent predictors of in-hospital mortality. Concomitant rifampicin did not affect in-hospital survival. Thirteen patients were referred to the tertiary referral hospital and received initial treatment with amphotericin B for a mean of 6 days – their in-hospital survival was not different from patients who received only fluconazole (p = 0.9). Kaplan-Meier analysis showed no differences in length of survival by initial treatment with standard or low doses of fluconazole (p = 0.27 log rank test); median survival was 76 and 82 days respectively.

Conclusion
Outcome of AIDS-associated cryptococcal meningitis is similar with low or standard doses of fluconazole. The early mortality is high. Initial therapy with amphotericin B and other measures may be needed to improve outcome.
Clustering of antibiotic resistance of E. coli in couples: suggestion for a major role of conjugal transmission
Authors: Lietzau Susanne , Raum Elke , von Baum Heike , Marre Reinhard , Brenner Hermann 
Published: July 2006

Abstract

Background
Spread of antibiotic resistance in hospitals is a well-known problem, but studies investigating the importance of factors potentially related to the spread of resistant bacteria in outpatients are sparse.

Methods
Stool samples were obtained from 206 healthy couples in a community setting in Southern Germany in 2002–2003. E. coli was cultured and minimal inhibition concentrations were tested. Prevalences of E. coli resistance to commonly prescribed antibiotics according to potential risk factors were ascertained.

Results
Prevalences of ampicillin resistance were 15.7% and 19.4% for women and men, respectively. About ten percent and 15% of all isolates were resistant to cotrimoxazole and doxycycline, respectively. A partner carrying resistance was the main risk factor for being colonized with resistant E. coli. Odds ratios (95% CI) for ampicillin and cotrimoxazole resistance given carriage of resistant isolates by the partner were 6.9 (3.1–15.5) and 3.3 (1.5–18.0), respectively.

Conclusion
Our data suggest that conjugal transmission may be more important for the spread of antibiotic resistance in the community setting than commonly suspected risk factors such as previous antibiotic intake or hospital contacts.
Changes in the incidence of occupational disability as a result of back and neck pain in the Netherlands
Authors: Steenstra Ivan A , Verbeek Jos H , Prinsze Femmeke J , Knol Dirk L 
Published: July 2006

Abstract

Background
Back pain (including neck pain) is one of the most prevalent health problems for which physicians are consulted. Back pain can decrease the quality of life considerably during a great part of the lives of those who suffer from it. At the same time it has an enormous economic impact, mainly through sickness absence and long-term disability. The objective of this paper is to compare the incidence of occupational disability as a result of back and neck pain in 1980–1985 to 1999–2000 and to explain the findings.

Methods
A descriptive study was performed at population level of changes in incidence of occupational disability as a result of back and neck pain. Statistics from the National Institute of Social Insurance in the Netherlands are used to calculate age and gender specific incidence rates for back pain diagnoses based on the ICD-classification. Incidence rate ratios stratified according to gender and adjusted for age were calculated to indicate changes over time.

Results
The incidence of occupational disability as a result of back pain decreased significantly by 37% (95% CI 37%–38%) in men and with 21% (95% CI 20%–24%) in women, after adjustment for age. For overall occupational disability as a result of all diagnoses this was 18% (95% CI 18%–19%) and 34% (95% CI 33%–35%) respectively. Changes were not homogeneous over diagnostic subcategories and age groups. Spondylosis decreased most in men by 59% (95% CI 57%–61%). The incidence of non-specific back pain and neck pain increased most by 196% (95% CI 164%–215%). Post-laminectomy syndrome increased over all age categories both for men (85%, 95% CI 61%–113%) and women (113%, 95% CI 65%–179%).

Conclusion
The decrease in occupational disability as a result of back pain was larger than the decrease in occupational disability over all diagnoses. However, time trends were not homogeneous over age-, nor over sex- nor back pain categories. Most of this decrease was due to general changes such as legal and economic changes. One of several additional explanations for a decrease is the changed view on management of back pain.
Using a conceptual framework during learning attenuates the loss of expert-type knowledge structure
Authors: Novak Kerry , Mandin Henry , Wilcox Elizabeth , McLaughlin Kevin 
Published: July 2006

Abstract

Background
During evolution from novice to expert, knowledge structure develops into an abridged network organized around pathophysiological concepts. The objectives of this study were to examine the change in knowledge structure in medical students in one year and to investigate the association between the use of a conceptual framework (diagnostic scheme) and long-term knowledge structure.

Methods
Medical students' knowledge structure of metabolic alkalosis was studied after instruction and one year later using concept-sorting. Knowledge structure was labeled 'expert-type' if students shared ≥ 2 concepts with experts and 'novice-type' if they shared < 2 concepts. Conditional logistic regression was used to study the association between short-term knowledge structure, the use of a diagnostic scheme and long-term knowledge structure.

Results
Thirty-four medical students completed the concept-sorting task on both occasions. Twenty-four used a diagnostic scheme for metabolic alkalosis. Short-term knowledge structure was not a correlate of long-term knowledge structure, whereas use of a diagnostic scheme was associated with increased odds of expert-type long-term knowledge structure (odds ratio 12.6 [1.4, 116.0], p = 0.02). There was an interaction between short-term knowledge structure and the use of a diagnostic scheme. In the group who did not use a diagnostic scheme the number of students changing from expert-type to novice-type was greater than vice versa (p = 0.046). There was no significant change in the group that used the diagnostic scheme (p = 0.6).

Conclusion
The use of a diagnostic scheme by students may attenuate the loss of expert-type knowledge structure.