bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asynchronous Growth of Prostate Cancer Is Reflected by Circulating Tumor Cells Delivered from Distinct, Even Small Foci, Harboring Loss of Heterozygosity of the PTEN Gene
Authors: Schmidt Hartmut , DeAngelis Gabriela , Eltze Elke , Gockel Iris , Semjonow Axel , Brandt Burkhard 
Published: September 2006

Abstract
The clinical value of prostate-specific antigen (PSA)–positive circulating tumor cells (CTCs) is still a matter of debate and it is also still unclear if these CTCs actually represent the primary tumor. Therefore, we isolated PSA-positive CTCs from the peripheral blood of patients suffering from multifocal cancers and did genetic profiling of each cancer focus by a multiplex PCR–based microsatellite analysis (D7S522, D8S522, NEFL, D10S541, D13S153, D16S400, D16S402, D16S422, and D17S855). In 17 of 20 prostate cancer cases, the loss of heterozygosity (LOH) pattern of the CTCs was identical with only one focus of the primary tumor. Moreover, in six cases, the LOH pattern suggested that smaller foci, down to 0.2 cm3, might deliver CTCs. Interestingly, the highest number of LOHs was observed at the marker D10S541 (85%), the PTEN gene, which was observed much less frequently in unifocal prostate cancer (48%). Furthermore, the infrequently occurring LOH in the BRCA1 gene (38%) was found in four of the five cases where a biochemical recurrence was seen within 3 years after prostatectomy. Therefore, the data might support the assumption that CTCs in prostate cancer are derived from distinct foci of a primary tumor. The size of the tumor focus is not related to the delivery of cells. Although the number of cases that were investigated in this study was small, it might be suggested that the LOH at distinct markers such as D10S541 and D17S855 represent the genes PTEN and BRCA1, which might be associated with the occurrence of CTCs in the peripheral blood of patients as well as an early biochemical recurrence. (Cancer Res 2006; 66(18): 8959-65)
β2-Microglobulin Is a Signaling and Growth-Promoting Factor for Human Prostate Cancer Bone Metastasis
Authors: Huang Wen-Chin , Wu Daqing , Xie Zhihui , Zhau Haiyen E. , Nomura Takeo , Zayzafoon Majd , Pohl Jan , Hsieh Chia-Ling , Weitzmann M. Neale , Farach-Carson Mary C. , Chung Leland W.K. 
Published: September 2006

AbstractThe protein factor β2-microglobulin (β2M), purified from the conditioned medium of human prostate cancer cell lines, stimulated growth and enhanced osteocalcin (OC) and bone sialoprotein (BSP) gene expression in human prostate cancer cells by activating a cyclic AMP (cAMP)–dependent protein kinase A signaling pathway. When β2M was overexpressed in prostate cancer cells, it induced explosive tumor growth in mouse bone through increased phosphorylated cAMP-responsive element binding protein (CREB) and activated CREB target gene expression, including OC, BSP, cyclin A, cyclin D1, and vascular endothelial growth factor. Interrupting the β2M downstream signaling pathway by injection of the β2M small interfering RNA liposome complex produced an effective regression of previously established prostate tumors in mouse bone through increased apoptosis as shown by immunohistochemistry and activation of caspase-9, caspase-3, and cleavage of poly(ADP-ribose) polymerase. These results suggest that β2M signaling is an attractive new therapeutic target for the treatment of lethal prostate cancer bone metastasis. (Cancer Res 2006; 66(18): 9108-16)
Inhibition of Hsp90 Compromises the DNA Damage Response to Radiation
Authors: Dote Hideaki , Burgan William E. , Camphausen Kevin , Tofilon Philip J. 
Published: September 2006

Abstract
Inhibitors of the molecular chaperone Hsp90 have been shown to enhance tumor cell radiosensitivity. To begin to address the mechanism responsible, we have determined the effect of the Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17DMAG) on the DNA damage response to radiation. Exposure of MiaPaCa tumor cells to 17DMAG, which results in radiosensitization, inhibited the repair of DNA double-strand breaks according to γH2AX foci dispersal and the neutral comet assay. This repair inhibition was associated with reduced DNA-PK catalytic subunit (DNA-PKcs) phosphorylation after irradiation and a disruption of DNA-PKcs/ErbB1 interaction. These data suggest that the previously established 17DMAG-mediated reduction in ErbB1 activity reduces its interaction with DNA-PKcs and thus accounts for the attenuation of radiation-induced DNA-PK activation. 17DMAG was also found to abrogate the activation of the G2- and S-phase cell cycle checkpoints. Associated with these events was a reduction in radiation-induced ataxia-telangiectasia mutated (ATM) activation and foci formation in 17DMAG-treated cells. Although no interaction between ATM and Hsp90 was detected, Hsp90 was found to interact with the MRE11/Rad50/NBS1 (MRN) complex. 17DMAG exposure reduced the ability of the MRN components to form nuclear foci after irradiation. Moreover, 17DMAG exposure reduced the interaction between NBS1 and ATM, although no degradation of the MRN complex was detected. These results suggest that the diminished radiation-induced activation of ATM in 17DMAG-treated cells was the result of a compromise in the function of the MRN complex. These data indicate that Hsp90 can contribute to the DNA damage response to radiation affecting both DNA repair and cell cycle checkpoint activation. (Cancer Res 2006; 66(18): 9211-20)
Physical activity and diet relative to socio-economic status and gender in British young people
Authors: Thomas Non-Eleri , Cooper Stephen-Mark , Baker Julien S , Davies Bruce 
Published: September 2006

Objective This study considers the physical activity (PA) and dietary habits of British young people according to socio-economic status (SES). Methods The PA and dietary habits of 98 boys and 101 girls (12.9 0.3 years) from two Welsh secondary schools (school 1 and school 2) were examined. Free school meal eligibility and Census 2001 data were used as indicators of SES. School 1 was designated high SES, while school 2 represented low SES. Participants were classified according to SES. Physical activity was estimated by seven-day recall and questionaire; dietary patterns were assessed using a seven-day food diary and questionnaire. Results Two-thirds of all participants had not taken part in vigorous activity over the last week. Furthermore, 83.8 per cent of participants did not meet the Health Education Authority's5 recommendation of one hour per day moderate activity. Boys were more active than girls, (P ≤ 0.05), but SES did not influence time spent in activity. Ninety-four percent of participants were taken to school via motorized transport. There were no significant differences in fat intake between the sexes or across SES. In addition, 93 per cent of the participants, irrespective of SES, exceeded the 10 per cent saturated fat cut off point recommended by the World Health Organization12 Conclusion Physical activity and dietary patterns are modifiable through suitable lifestyle changes. The present data support the notion that preventative strategies for combating chronic diseases should begin early in life and across socio-economic statuses.
To what extent are school drop-in clinics meeting pupils' self-identified health concerns?
Authors: Kay C M , Morgan D L , Tripp J H , Davies C , Sykes S 
Published: September 2006

Objective This paper explores young peoples' health concerns and their knowledge and views of school nurse drop-in clinics (drop-ins) held in their schools. Design Cross section survey of adolescents using questionnaires delivered in schools to 10 per cent of the population, and school drop-in monitoring data from the Primary Care Trust (PCT). Setting 11 secondary schools in a suburban south-east London borough. Method Data from 590 11-17 year olds were used to determine their health concerns, sources of advice for health concerns, views and peceptions of their school based drop-in clinics, and attendance at these clinics. Results Young people have a number of health concerns, notably in the area of inter-personal issues, emotional heath and well-being; however, few had sought help with these. Awareness of school based drop-ins was high but knowledge of times and locations was patchy. The droins were viewed positively, especially by users. Issues such as timing of drop-ins, their location and confidentiality were raised by students. Most consultations were dealt with by support or advice from the school nurse. Monitoring data suggested the service may be under-used but those who did attend often returned. Sixty-two per cent of students felt drop-ins were an important service in schools, this rose to 92 per cent among those who had accessed the service. Conclusion: School based drop-ins offer a valuable service but need planing and promotion to achieve good attendance figures. A school droin may be the first time a young person has accessed any health care setting by themselves and valuable transferable skills may be learnt.
Project MAINSTREAM's first fellowship cohort: Pilot test of a national dissemination model to enhance substance abuse curriculum at health professions schools
Authors: Brown Richard L , Marcus Marianne T , Lal S , Straussner A , Graham Antonette V , Madden Theresa , Schoener Eugene , Henry Rebecca 
Published: September 2006

Objective Generalist health professional training on substance abuse prevention is patchy. This study assessed the effects of Project MAINSTREAM, a national interdisciplinary faculty development fellowship program, whose principal objective was to enhance curriculum on basic substance abuse services at health professions training institutions. Five interdisciplinary teams of three health professions' faculty were selected as fellows. This study assessed changes in curriculum, training, fellows' knowledge, and fellows' academic productivity in substance abuse. Design Pre and post-program surveys and interviews were administered. Setting Fellows were located in five cities in the USA. Method The two-year, part-time training program featured training meetings, on-site and distance mentoring, and internet-based instructional materials. Principal learning activities consisted of developing independent projects in curriculum enhancement and prevention services delivery. Results Fellows implemented 45 distinct curricula, providing 19,000 hours of new instruction to over 5000 trainees. Over 80 per cent of the training occurred as required curricular experiences. Fellows' academic accomplishments included five peer-reviewed publications, seven additional submitted papers, 78 presentations, and 23 awards or appointments. Fellows' knowledge increased significantly. Conclusions Project MAINSTREAM shows promise as a national model for enhancing health professional training on substance abuse.
The experience of condom use and other sexual risk practices among male brewery employees who recently migrated in Nigeria
Authors: Sunmola Adegbenga M , Adebayo Dada , Olapegba Makinde , Alarape Aderemi 
Published: September 2006

Objective To identify factors that predict condom use and sexual practices of brewery employees who had recently been on short- and longterm migration in the course of their jobs in Nigeria. Design A cross-sectional survey design was adopted to investigate the relationship between sexual practices and condom use of migrant employees, and to determine the predictors of condom use at last intercourse during migration. Setting The study was conducted in a large multinational brewery in Nigeria with operational locations in various parts of the country. Method A sample of 936 male employees was selected consecutively in the brewery in 2002. They were independently invited to respond to a questionnaire consisting of items that covered background characteristics, condom use and sexual experiences. Results The findings showed that 40 per cent of participants reported they were using alcohol occasionally prior to sex and 54 per cent reported that they either received or paid money for sex. Forty-seven per cent of men indicated that they used condoms at their last intercourse during migration, while 62 per cent had had one to three sexual partners during their last migration. The odds of using a condom at last intercourse were significantly lower for married than for single participants (odds ratio, 0.57). Compared with participants without the intention to use a condom in next intercourse during migration, those with the intention were significantly more likely to report condom use (odds ratio, 9.7). The odds of condom use were significantly higher for participants who perceived that a condom prevents HIV transmission than those who either did not have the perception or were not sure (odds ratio, 0.30-1.80). Conclusion Steps are needed to promote condom use among brewery employees on migration. Intervention programmes aimed to enhance condom use among prospective migrant employees may be more effective if they provide opportunities for the employees to think about the advantages of condoms in sexual encounters under migration conditions.
Intravascular large B-cell lymphoma (IVLBCL): a clinicopathologic study of 96 cases with special reference to the immunophenotypic heterogeneity of CD5
Authors: Murase Takuhei , Yamaguchi Motoko , Suzuki Ritsuro , Okamoto Masataka , Sato Yumiko , Tamaru Jun-ichi , Kojima Masaru , Miura Ikuo , Mori Naoyoshi , Yoshino Tadashi , Nakamura Shigeo 
Published: September 2006

AbstractIntravascular large B-cell lymphoma (IVLBCL) is pathologically distinct with a broad clinical spectrum and immunophenotypic heterogeneity. A series of 96 patients with IVLBCL (median age, 67 years; range, 41-85 years; 50 men) was reviewed. Anemia/thrombocytopenia (84%), hepatosplenomegaly (77%), B symptoms (76%), bone marrow involvement (75%), and hemophagocytosis (61%) were frequently observed. The International Prognostic Index score was high or high-intermediate in 92%. For 62 patients receiving anthracycline-based chemotherapies, median survival was 13 months. CD5, CD10, Bcl-6, MUM1, and Bcl-2 were positive in 38%, 13%, 26%, 95%, and 91% of tumors, respectively. All 59 CD10− IVLBCL cases examined were nongerminal center B-cell type because they lacked the Bcl-6+MUM1− immunophenotype. CD5 positivity was associated with a higher prevalence of marrow/blood involvement and thrombocytopenia and a lower frequency of neurologic abnormalities among patients with CD10−IVLBCL. Compared with 97 cases of de novo CD5+CD10−diffuse LBCL, 31 cases of CD5+CD10−IVLBCL exhibited higher frequencies of poor prognostic parameters, except age. Multivariate analysis in IVLBCL revealed that a lack of anthracycline-based chemotherapies (P < .001, hazard ratio [HR]: 9.256), age older than 60 years (P = .012, HR: 2.459), and thrombocytopenia less than 100 × 109/L (P = .012, HR: 2.427) were independently unfavorable prognostic factors; CD5 positivity was not. Beyond immunophenotypic diversity, IVLBCL constitutes a unique group with aggressive behavior.
Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells
Authors: Sato Kazuya , Ozaki Katsutoshi , Oh Iekuni , Meguro Akiko , Hatanaka Keiko , Nagai Tadashi , Muroi Kazuo , Ozawa Keiya 
Published: September 2006

AbstractThe molecular mechanisms by which mesenchymal stem cells (MSCs) suppress T-cell proliferation are poorly understood, and whether a soluble factor plays a major role remains controversial. Here we demonstrate that the T-cell–receptor complex is not a target for the suppression, suggesting that downstream signals mediate the suppression. We found that Stat5 phosphorylation in T cells is suppressed in the presence of MSCs and that nitric oxide (NO) is involved in the suppression of Stat5 phosphorylation and T-cell proliferation. The induction of inducible NO synthase (NOS) was readily detected in MSCs but not T cells, and a specific inhibitor of NOS reversed the suppression of Stat5 phosphorylation and T-cell proliferation. This production of NO in the presence of MSCs was mediated by CD4 or CD8 T cells but not by CD19 B cells. Furthermore, inhibitors of prostaglandin synthase or NOS restored the proliferation of T cells, whereas an inhibitor of indoleamine 2,3-dioxygenase and a transforming growth factor–β–neutralizing antibody had no effect. Finally, MSCs from inducible NOS−/− mice had a reduced ability to suppress T-cell proliferation. Taken together, these results suggest that NO produced by MSCs is one of the major mediators of T-cell suppression by MSCs.
Distinct memory CD4+ T-cell subsets mediate immune recognition of Epstein Barr virus nuclear antigen 1 in healthy virus carriers
Authors: Heller Kevin N. , Upshaw Jenica , Seyoum Beza , Zebroski Henry , Münz Christian 
Published: September 2006

AbstractCD4+ T cells, specific for transforming latent infection with the Epstein Barr virus (EBV), consistently recognize the nuclear antigen 1 of EBV (EBNA1). EBNA1-specific effector CD4+ T cells are primarily T-helper 1 (TH1) polarized. Here we show that most healthy EBV carriers have such IFN-secreting EBNA1-specific CD4+ T cells at a frequency of 0.03% of circulating CD4+ T cells. In addition, healthy carriers have a large pool of CD4+ T cells that proliferated in response to EBNA1 and consisted of distinct memory-cell subsets. Despite continuous antigen presence due to persistent EBV infection, half of the proliferating EBNA1-specific CD4+ T cells belonged to the central-memory compartment (TCM). The remaining EBNA1-specific CD4+ T cells displayed an effector-memory phenotype (TEM), of which a minority rapidly secreted IFN upon stimulation with EBNA1. Based on chemokine receptor analysis, all EBNA1-specific TCM CD4+ T cells were TH1 committed. Our results suggest that protective immune control of chronic infections, like EBV, includes a substantial reservoir of TCM CD4+ TH1 precursors, which continuously fuels TH1-polarized effector cells.
Control of coronavirus infection through plasmacytoid dendritic-cell–derived type I interferon
Authors: Cervantes-Barragan Luisa , Züst Roland , Weber Friedemann , Spiegel Martin , Lang Karl S. , Akira Shizuo , Thiel Volker , Ludewig Burkhard 
Published: September 2006

AbstractThis study demonstrates a unique and crucial role of plasmacytoid dendritic cells (pDCs) and pDC-derived type I interferons (IFNs) in the pathogenesis of mouse coronavirus infection. pDCs controlled the fast replicating mouse hepatitis virus (MHV) through the immediate production of type I IFNs. Recognition of MHV by pDCs was mediated via TLR7 ensuring a swift IFN-α production following encounter with this cytopathic RNA virus. Furthermore, the particular type I IFN response pattern was not restricted to the murine coronavirus, but was also found in infection with the highly cytopathic human severe acute respiratory syndrome (SARS) coronavirus. Taken together, our results suggest that rapid production of type I IFNs by pDCs is essential for the control of potentially lethal coronavirus infections.
MicroArray Facility: a laboratory information management system with extended support for Nylon based technologies
Authors: Honoré Paul , Granjeaud Samuel , Tagett Rebecca , Deraco Stéphane , Beaudoing Emmanuel , Rougemont Jacques , Debono Stéphane , Hingamp Pascal 
Published: September 2006

Abstract

Background
High throughput gene expression profiling (GEP) is becoming a routine technique in life science laboratories. With experimental designs that repeatedly span thousands of genes and hundreds of samples, relying on a dedicated database infrastructure is no longer an option.
GEP technology is a fast moving target, with new approaches constantly broadening the field diversity. This technology heterogeneity, compounded by the informatics complexity of GEP databases, means that software developments have so far focused on mainstream techniques, leaving less typical yet established techniques such as Nylon microarrays at best partially supported.

Results
MAF (MicroArray Facility) is the laboratory database system we have developed for managing the design, production and hybridization of spotted microarrays. Although it can support the widely used glass microarrays and oligo-chips, MAF was designed with the specific idiosyncrasies of Nylon based microarrays in mind. Notably single channel radioactive probes, microarray stripping and reuse, vector control hybridizations and spike-in controls are all natively supported by the software suite. MicroArray Facility is MIAME supportive and dynamically provides feedback on missing annotations to help users estimate effective MIAME compliance. Genomic data such as clone identifiers and gene symbols are also directly annotated by MAF software using standard public resources. The MAGE-ML data format is implemented for full data export. Journalized database operations (audit tracking), data anonymization, material traceability and user/project level confidentiality policies are also managed by MAF.

Conclusion
MicroArray Facility is a complete data management system for microarray producers and end-users. Particular care has been devoted to adequately model Nylon based microarrays. The MAF system, developed and implemented in both private and academic environments, has proved a robust solution for shared facilities and industry service providers alike.
Detection of potentially valuable polymorphisms in four group I intron insertion sites at the 3'-end of the LSU rDNA genes in biocontrol isolates of Metarhizium anisopliae
Authors: Márquez Marcela , Iturriaga Enrique A , Quesada-Moraga Enrique , Santiago-Álvarez Cándido , Monte Enrique , Hermosa Rosa 
Published: September 2006

Abstract

Background
The entomopathogenic anamorphic fungus Metarhizum anisopliae is currently used as a biocontrol agent (BCA) of insects. In the present work, we analyzed the sequence data obtained from group I introns in the large subunit (LSU) of rDNA genes with a view to determining the genetic diversity present in an autochthonous collection of twenty-six M. anisopliae isolates selected as BCAs.

Results
DNA fragments corresponding to the 3'-end of the nuclear LSU rDNA genes of 26 M. anisopliae isolates were amplified by PCR. The amplicon sizes ranged from 0.8 to 3.4-kb. Four intron insertion sites, according to Escherichia coli J01695 numbering, were detected- Ec1921, Ec2066, Ec2449 and Ec2563- after sequencing and analysis of the PCR products. The presence/absence of introns allowed the 26 isolates to be distributed into seven genotypes. Nine of the isolates tested showed no introns, 4 had only one, 3 two, and 10 displayed three introns. The most frequent insertion sites were Ec1921 and Ec2449. Of the 26 isolates, 11 showed insertions at Ec2563 and a 1754-bp sequence was observed in ten of them. The most-parsimonious (MP) tree obtained from parsimony analysis of the introns revealed a main set containing four-groups that corresponded to the four insertion sites.

Conclusion
Four insertion sites of group I introns in the LSU rDNA genes allowed the establishment of seven genotypes among the twenty-six biocontrol isolates of M. anisopliae. Intron insertions at the Ec2563 site were observed for first time in this species.