bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expected Flow Parameters Within Hemodialysis Access and Selection for Remedial Intervention of Nonmaturing Conduits
Authors: Back Martin R. , Maynard Maureen , Winkler Adam , Bandyk Dennis F. 
Published: February 2008

Background Persistent poor patency rates of arteriovenous fistulae and bridge grafts for dialysis access prompted us to investigate whether flow parameters derived from an initial postconstruction, precannulation duplex study could predict access longevity or direct remedial procedures to salvage nonmaturing conduits. Methods We analyzed 125 consecutive dialysis access conduits (34 forearm fistulae, 53 arm fistulae, 38 prosthetic bridge grafts, 108 patients, 82 male/26 female, average age 58 years) over the past 5 years having early (2 to 8 weeks) duplex scanning done prior to attempted hemodialysis cannulation. Velocity waveforms were recorded in the arterial inflow, arterial and venous anastomoses, mid-conduit, and in the venous outflow with averaging of volume flow rate (product of average velocity and cross-sectional area) measured at 3 mid-conduit sites. Conduits were deemed “adequate” for dialysis cannulation or “nonmaturing” by the presence of detected high-grade stenoses (peak systolic velocity >400cm/s, velocity ratio >3, and minimal diameter <2 to 3 mm) and subjected to remedial interventions (endovascular or open). Subsequent access function for hemodialysis use and late patency were recorded and correlated with early duplex findings. Results Average flow rates (forearm fistula 784 ± 623 mL/min, arm fistula 1400 ± 850, bridge graft 1270 ± 604) and mid-conduit peak-systolic velocities (215 ± 214 cm/s forearm fistula vs 312 ± 194 arm fistula) differed between conduit type and location. Remedial interventions were needed in 10 (26%) bridge grafts and 18 (21%) fistulae “nonmaturing” due to occlusive lesions. Conduit flow rates differentiated “nonmaturing” (606 ± 769 mL/min) and “maturing” (1140 ± 857) fistulae ( P = .01). A threshold conduit flow rate of 800 mL/min better discriminated failing and functional fistulae and bridge grafts (accuracy 77%) than a flow rate greater or less than 500 mL/min (accuracy 67%). Remedial interventions doubled average flow rates of “nonmaturing” accesses (from 605 to 1159 mL/min) to values similar to “mature, functional” conduits (1374 mL/min) and facilitated a mean duration of patency (12.9 months) equivalent to conduits not needing remedial interventions (11.5 months). Conclusions Duplex-derived hemodynamic parameters characterized early dialysis access conduit function, prognosticated access patency, guided necessary remedial interventions, and facilitated favorable access longevity.
IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy
Authors: Hinrichs Christian S. , Spolski Rosanne , Paulos Chrystal M. , Gattinoni Luca , Kerstann Keith W. , Palmer Douglas C. , Klebanoff Christopher A. , Rosenberg Steven A. , Leonard Warren J. , Restifo Nicholas P. 
Published: February 2008

AbstractIL-2 and IL-21 are closely related cytokines that might have arisen by gene duplication. Both cytokines promote the function of effector CD8+ T cells, but their distinct effects on antigen-driven differentiation of naive CD8+ T cells into effector CD8+ T cells are not clearly understood. We found that antigen-induced expression of Eomesodermin (Eomes) and maturation of naive CD8+ T cells into granzyme B- and CD44-expressing effector CD8+ T cells was enhanced by IL-2, but, unexpectedly, suppressed by IL-21. Furthermore, IL-21 repressed expression of IL-2Ra and inhibited IL-2–mediated acquisition of a cytolytic CD8+ T-cell phenotype. Despite its inhibitory effects, IL-21 did not induce anergy, but instead potently enhanced the capacity of cells to mediate tumor regression upon adoptive transfer. In contrast, IL-2 impaired the subsequent antitumor function of transferred cells. Gene expression studies revealed a distinct IL-21 program that was characterized phenotypically by increased expression of L-selectin and functionally by enhanced antitumor immunity that was not reversed by secondary in vitro stimulation with antigen and IL-2. Thus, the efficacy of CD8+ T cells for adoptive immunotherapy can be influenced by opposing differentiation programs conferred by IL-2 and IL-21, a finding with important implications for the development of cellular cancer therapies.
Strong induction of 4-1BB, a growth and survival promoting costimulatory receptor, in HTLV-1–infected cultured and patients' T cells by the viral Tax oncoprotein
Authors: Pichler Klemens , Kattan Tarek , Gentzsch Juliane , Kress Andrea K. , Taylor Graham P. , Bangham Charles R. M. , Grassmann Ralph 
Published: February 2008

AbstractHuman T-cell leukemia virus type 1 (HTLV-1), the cause of adult T-cell leukemia, stimulates the growth of infected T cells in cultures and in nonleukemic patients. In the latter, HTLV-1 is found in long-term persisting T-cell clones. The persistence of normal T cells is controlled by the growth-stimulating and antiapoptotic functions of costimulatory receptors, while the growth-stimulating HTLV-1 functions are mediated by the viral oncoprotein Tax. Here we analyzed the impact of Tax on costimulatory receptors in T cells with repressible Tax and found that among these receptors 4-1BB (TNFRSF9/CD137/ILA) was induced most strongly. Up-regulated 4-1BB expression was a consistent feature of all HTLV-1–infected cell lines, whether patient-derived or in vitro transformed. Tax was sufficient to induce the expression of the endogenous 4-1BB gene in uninfected T cells, and it strongly activated (45-fold) the 4-1BB promoter via a single NF-κB site. The ligand of 4-1BB was also found on transformed T-cell lines, opening up the possibility of autostimulation. Moreover, 4-1BB expression in patients' lymphocytes ex vivo correlated with Tax expression, strongly suggesting Tax-mediated 4-1BB activation in vivo. Thus, 4-1BB up-regulation by Tax could contribute to growth, survival, and clonal expansion of the infected cells during persistence and disease.
Mutation analysis of the MDM4gene in German breast cancer patients
Authors: Reincke Scarlett , Govbakh Lina , Wilhelm Bettina , Jin Haiyan , Bogdanova Natalia , Bremer Michael , Karstens Johann H , Dörk Thilo 
Published: February 2008

Abstract

Background
MDM4 is a negative regulator of p53 and cooperates with MDM2 in the cellular response to DNA damage. It is unknown, however, whether MDM4 gene alterations play some role in the inherited component of breast cancer susceptibility.

Methods
We sequenced the whole MDM4 coding region and flanking untranslated regions in genomic DNA samples obtained from 40 German patients with familial breast cancer. Selected variants were subsequently screened by RFLP-based assays in an extended set of breast cancer cases and controls.

Results
Our resequencing study uncovered two MDM4 coding variants in 4/40 patients. Three patients carried a silent substitution at codon 74 that was linked with another rare variant in the 5'UTR. No association of this allele with breast cancer was found in a subsequent screening of 133 patients with bilateral breast cancer and 136 controls. The fourth patient was heterozygous for the missense substitution D153G which is located in a less conserved region of the MDM4 protein but may affect a predicted phosphorylation site. The D153G substitution only partially segregated with breast cancer in the family and was not identified on additional 680 chromosomes screened.

Conclusion
This study did not reveal clearly pathogenic mutations although it uncovered two new unclassified variants at a low frequency. We conclude that there is no evidence for a major role of MDM4 coding variants in the inherited susceptibility towards breast cancer in German patients.
Comparing a disease-specific and a generic health-related quality of life instrument in subjects with asthma from the general population
Authors: Puhan Milo A , Gaspoz Jean-Michel , Bridevaux Pierre-Olivier , Schindler Christian , Ackermann-Liebrich Ursula , Rochat Thierry , Gerbase Margaret W 
Published: February 2008

AbstractBackgroundFew epidemiologic studies have assessed health-related quality of life (HRQL) of asthma patients from a general population and it is unclear which instrument is best suitable for this purpose. We investigated the validity of the Asthma Quality of Life Questionnaire (AQLQ) and the SF-36 completed by individuals with asthma from the population-based SAPALDIA (Swiss study on air pollution and lung diseases in adults) cohort.MethodsThe study included 258 participants with a physician-diagnosed asthma who had completed the AQLQ and SF-36. We assessed floor and ceiling effects, internal consistency reliability and cross-sectional validity witha priorihypotheses that correlations between the specific HRQL domains (e.g. "symptoms" or "physical functioning") and the corresponding external validation measures (respiratory symptoms, need for doctor visits, limitation in activities due to asthma and lung function) would capture similar aspects and be correlated moderately (≥ 0.3) to strongly (≥ 0.5), whereas non-corresponding domains be correlated weakly with each other (<0.3).ResultsThe AQLQ showed pronounced ceiling effects with all median domain scores above 6 (scores varied from 1–7). For the SF-36, ceiling effects were present in 5 out of 8 domains. Cronbach's alpha was >0.7 for all AQLQ and SF-36 domains. Correlations between the AQLQ domains "respiratory symptoms", "activity limitation" and "environmental exposure", and the validation measures ranged from 0.29–0.57. Correlations between the "emotional function" domain and the validation measures were also in this range (0.31–0.55) and not as low as we hypothesized. For the SF-36, correlations between "physical functioning" and "role physical", and the validation measures ranged from 0.25–0.56, whereas "role emotional" and "mental health" correlated with these measures from 0.01–0.23.ConclusionThe AQLQ and the SF-36 showed fairly good internal consistency. Both instruments are limited by ceiling effects, but they appear less pronounced in the SF-36, which also shows a better discrimination between different aspects of HRQL. The SF-36 may therefore be a more valid measure of HRQL than the AQLQ when applied to individuals with asthma from the general population.
Epstein-Barr virus latent membrane protein-1 (LMP-1) 30-bp deletion and Xho I-loss is associated with type III nasopharyngeal carcinoma in Malaysia
Authors: See Hui Shien , Yap Yoke Yeow , Yip Wai Kien , Seow Heng Fong 
Published: February 2008

Abstract

Background
Nasopharyngeal carcinoma (NPC) is a human epithelial tumour with high prevalence amongst Chinese in Southern China and South East Asia and is associated with the Epstein-Barr virus (EBV). The viral genome harbours an oncogene, namely, the latent membrane protein 1 (LMP1) gene and known variants such as the 30-bp deletion and loss of Xho I restriction site have been found. Less is known about the relationship between these variants and the population characteristics and histological type.

Methods
In this study, the EBV LMP1 gene variants from 42 NPC and 10 non-malignant archived formalin fixed, paraffin-embedded tissues, as well as plasma from another 35 patients with nasopharyngeal carcinoma were determined by using Polymerase Chain Reaction (PCR). Statistical analysis was performed by using SPSS programme.

Results
LMP1 30-bp deletion was detected in 19/34 (55.9%) of NPC tissues, 7/29 (24.1%) of plasma but absent in non-malignant tissues (8/8). Coexistence of variants with and without 30bp deletion was found only in 5/29 (17.2%) plasma samples but not in NPC tissues. The loss of Xho I restriction site in LMP1 gene was found in 34/39 (87.2%) of the NPC tissues and 11/30 (36.7%) of plasma samples. None of the non-malignant nasopharyngeal tissues (8/8) harbour Xho I-loss variants. LMP1 30-bp deletion was detected in 16/18 Chinese versus 3/15 Malays and 13/16 type III (undifferentiated carcinoma) versus 1/6 type I (keratinizing squamous cell carcinoma). Xho I-loss was found in 19/19 Chinese versus 14/19 Malays and 18/18 type III (undifferentiated) versus 2/5 type I (keratinizing squamous cell carcinoma). Statistical analysis showed that these variants were associated with ethnic race (30-bp deletion, p < 0.05; Xho I-loss, p = 0.046) and histological type of NPC (30-bp deletion, p = 0.011; Xho I-loss, p = 0.006). Nineteen out of 32 NPC tissues (19/32; 59.4%) and 6/24 (25%) of plasma samples showed the coexistence of both the 30-bp deletion and the loss of Xho I restriction site. A significant relationship was found with the Chinese race but not histological type.

Conclusion
The incidence rate of 56% for LMP1 30-bp deletion was lower compared to previously reported rates of 75–100% in NPC tissues. Coexistence of variants with and without 30-bp deletion was found only in 5/29 plasma samples. The incidence rate of Xho I restriction site loss in NPC was comparable to other studies from endemic regions such as Southern China. For the first time, the presence of LMP1 30-bp deletion or Xho I-loss was associated with the Chinese race and type III NPC. Both these variants were not found in non-malignant tissues. The influence of these variants on disease progression and outcome in Chinese and type III NPC requires further investigation.
A case of virilization induced by a Krukenberg tumor from gastric cancer
Authors: Hornung Matthias , Vogel Peter , Schubert Thomas , Schlitt Hans-Jürgen , Bolder Ulrich 
Published: February 2008

Abstract

Background
The Krukenberg tumor represents ovarian metastases associated with gastric cancer or other gastrointestinal malignancies. Histology shows typical mucus-production and numerous signet-ring cells. Occasionally Krukenberg tumors have endocrine function and, as a consequence, some patients demonstrate hirsutism and virilization.

Case presentation
Here we report a case of virilization associated with an extensive gastric adenocarcinoma and Krukenberg tumor in a premenopausal woman. Virilization occurred three months after diagnosis of gastric cancer and the ovarian tumors. Palliative chemotherapy was initiated as primary therapy, but gastric outlet obstruction required a gastrojejunostomy. In addition, oopherectomy was performed to relieve abdominal tension and to abate hormonal effects. It is likely that virilization of the patient could have been prevented by earlier oopherectomy prior to development of hormone production.

Conclusion
Despite the limitation in survival time early oopherectomy should be considered to prevent the development of virilization even in palliative situations if a Krukenberg tumor is diagnosed with gastric cancer.
Prevention of airway inflammation with topical cream containing imiquimod and small interfering RNA for natriuretic peptide receptor
Authors: Wang Xiaoqin , Xu Weidong , Mohapatra Subhra , Kong Xiaoyuan , Li Xu , Lockey Richard F , Mohapatra Shyam S 
Published: February 2008

Abstract

Background
Asthma is a complex disease, characterized by reversible airway obstruction, hyperresponsiveness and chronic inflammation. Principle pharmacologic treatments for asthma include bronchodilating beta2-agonists and anti-inflammatory glucocorticosteroids; but these agents do not target the main cause of the disease, the generation of pathogenic Th2 cells. We previously reported reduction in allergic inflammation in mice deficient in the ANP receptor NPRA. Here we determined whether siRNA for natriuretic peptide receptor A (siNPRA) protected against asthma when administered transdermally.

Methods
Imiquimod cream mixed with chitosan nanoparticles containing either siRNA green indicator (siGLO) or siNPRA was applied to the skin of mice. Delivery of siGLO was confirmed by fluorescence microscopy. The anti-inflammatory activity of transdermal siNPRA was tested in OVA-sensitized mice by measuring airway hyperresponsiveness, eosinophilia, lung histopathology and pro-inflammatory cytokines.

Results
SiGLO appearing in the lung proved the feasibility of transdermal delivery. In a mouse asthma model, BALB/c mice treated with imiquimod cream containing siNPRA chitosan nanoparticles showed significantly reduced airway hyperresponsiveness, eosinophilia, lung histopathology and pro-inflammatory cytokines IL-4 and IL-5 in lung homogenates compared to controls.

Conclusion
These results demonstrate that topical cream containing imiquimod and siNPRA nanoparticles exerts an anti-inflammatory effect and may provide a new and simple therapy for asthma.
Prostate-specific antigen at or before age 50 as a predictor of advanced prostate cancer diagnosed up to 25 years later: A case-control study
Authors: Ulmert David , Cronin Angel M , Björk Thomas , O'Brien Matthew F , Scardino Peter T , Eastham James A , Becker Charlotte , Berglund Göran , Vickers Andrew J , Lilja Hans 
Published: February 2008

Abstract

Background
Based on a large, representative unscreened cohort from Malmö, Sweden, we have recently reported that a single prostate-specific antigen (PSA) measurement at or before age 50 is a strong predictor of prostate cancer occurring up to 25 years subsequently. We aimed to determine whether this association holds for advanced cancers, defined as clinical stage T3 or higher, or skeletal metastasis at the time of the cancer diagnosis.

Methods
In 1974–1986 blood samples were obtained from a cohort of 21,277 men aged up to 50. Through 1999, 498 men were diagnosed with prostate cancer, and of these 161 had locally advanced or metastatic prostate cancers. Three controls, matched for age and date of venipuncture, were selected for each case. Conditional logistic regression was used to test associations between molecular markers and advanced cancer.

Results
Median time from venipuncture to diagnosis was 17 years. Levels of all PSA forms and hK2 were associated with case status. Total PSA was a strong and statistically significant predictor of subsequent advanced cancer (area under the curve 0.791; p < 0.0005). Two-thirds of the advanced cancer cases occurred in men with the top 20% of PSA levels (0.9 ng/ml or higher).

Conclusion
A single PSA test taken at or before age 50 is a very strong predictor of advanced prostate cancer diagnosed up to 25 years later. This suggests the possibility of using an early PSA test to risk-stratify patients so that men at highest risk are the focus of the most intensive screening efforts.
Leiomyosarcoma of the skin with osteoclast-like giant cells: a case report
Authors: Sarma Deba P , Santos Eric E , Wang Bo 
Published: February 2008

Abstract

Introduction
Osteoclast-like giant cells have been noted in various malignant tumors, such as, carcinomas of pancreas and liver and leiomyosarcomas of non-cutaneous locations, such as, uterus and rectum. We were unable to find any reported case of a leiomyosarcoma of the skin where osteoclast-like giant cells were present in the tumor.

Case presentation
We report a case of a 59-year-old woman with a cutaneous leiomyosarcoma associated with osteoclast-like giant cells arising from the subcutaneous artery of the leg. The nature of the giant cells is discussed in light of the findings from the immunostaining as well as survey of the literature.

Conclusion
A rare case of cutaneous leiomyosarcoma with osteoclast-like giant cells is reported. The giant cells in the tumor appear to be reactive histiocytic cells.
Functional protein divergence in the evolution of Homo sapiens
Authors: Lopez-Bigas Nuria , De Subhajyoti , Teichmann Sarah A 
Published: February 2008

Abstract
Background
Protein-coding regions in a genome evolve by sequence divergence and gene gain and loss, altering the gene content of the organism. However, it is not well understood how this has given rise to the enormous diversity of metazoa present today.

Results
To obtain a global view of human genomic evolution, we quantify the divergence of proteins by functional category at different evolutionary distances from human.

Conclusion
This analysis highlights some general systems-level characteristics of human evolution: regulatory processes, such as signal transducers, transcription factors and receptors, have a high degree of plasticity, while core processes, such as metabolism, transport and protein synthesis, are largely conserved. Additionally, this study reveals a dynamic picture of selective forces at short, medium and long evolutionary timescales. Certain functional categories, such as 'development' and 'organogenesis', exhibit temporal patterns of sequence divergence in eukaryotes relative to human. This framework for a grammar of human evolution supports previously postulated theories of robustness and evolvability.
Ancora: a web resource for exploring highly conserved noncoding elements and their association with developmental regulatory genes
Authors: Engström Pär G , Fredman David , Lenhard Boris 
Published: February 2008

AbstractMetazoan genomes contain arrays of highly conserved noncoding elements (HCNEs) that span developmental regulatory genes and define regulatory domains. We describe Ancora http://ancora.genereg.net, a web resource that provides data and tools for exploring genomic organization of HCNEs for multiple genomes. Ancora includes a genome browser that shows HCNE locations and features novel HCNE density plots as a powerful tool to discover developmental regulatory genes and distinguish their regulatory elements and domains.
Multistep regulation of telomerase during differentiation of HL60 cells
Authors: Yamada Osamu , Ozaki Kohji , Nakatake Mayuka , Akiyama Masaharu , Kawauchi Kiyotaka , Matsuoka Rumiko 
Published: February 2008

AbstractUsing three different differentiation agents (1α, 25 dihydroxyvitamin D3, all-trans-retinoic acid, and Am80), down-regulation of telomerase activity was found to be a common response during the monocytic or granulocytic differentiation of human acute myeloblastic leukemia cell line 60 (HL60) cells. Rapid down-regulation of telomerase transcription occurred during early differentiation of HL60 cells prior to G1 arrest. Akt kinase activity was suppressed after 6 h of differentiation along with inhibition of telomerase activity, and the extent of the suppression that occurred while maintaining telomerase protein expression suggested the post-translational regulation of telomerase activity. Recombinant Akt dose-dependently increased telomerase activity, and telomerase was inhibited at the transcriptional and post-translational levels by LY294002, suggesting that PI-3K/Akt is one of the key signaling proteins involved in telomerase regulation. Each of the three differentiation agents caused a significant increase of signaling proteins (including Akt) at 3 days after the initiation of differentiation. Changes of acetyl-histone H4, which regulates transcription of the telomerase gene, were observed before the activation of Akt. This finding suggests that epigenetic control of telomerase transcription occurs before activation of Akt during the late stage of differentiation. These results indicate that telomerase activity is regulated by at least two mechanisms during granulocytic and monocytic differentiation, with one mechanism being transcriptional and the other being post-translational.