bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Analysis of H7 Avian Influenza Viruses from Australia and New Zealand: Genetic Diversity and Relationships from 1976 to 2007
Authors: Bulach Dieter , Halpin Rebecca , Spiro David , Pomeroy Laura , Janies Daniel , Boyle David B. 
Published: July 2010

ABSTRACT
Full-genome sequencing of 11 Australian and 1 New Zealand avian influenza A virus isolate (all subtype H7) has enabled comparison of the sequences of each of the genome segments to those of other subtype H7 avian influenza A viruses. The inference of phylogenetic relationships for each segment has been used to develop a model of the natural history of these viruses in Australia. Phylogenetic analysis of the hemagglutinin segment indicates that the Australian H7 isolates form a monophyletic clade. This pattern is consistent with the long-term, independent evolution that is, in this instance, associated with geographic regions. On the basis of the analysis of the other H7 hemagglutinin sequences, three other geographic regions for which similar monophyletic clades have been observed were confirmed. These regions are Eurasia plus Africa, North America, and South America. Analysis of the neuraminidase sequences from the H7N1, H7N3, and H7N7 genomes revealed the same region-based relationships. This pattern of independent evolution of Australian isolates is supported by the results of analysis of each of the six remaining genomic segments. These results, in conjunction with the occurrence of five different combinations of neuraminidase subtypes (H7N2, H7N3, H7N4, H7N6, H7N7) among the 11 Australian isolates, suggest that the maintenance host(s) is nearly exclusively associated with Australia. The single lineage of Australian H7 hemagglutinin sequences, despite the occurrence of multiple neuraminidase types, suggests the existence of a genetic pool from which a variety of reassortants arise rather than the presence of a small number of stable viral clones. This pattern of evolution is likely to occur in each of the regions mentioned above.
Interplay of Acute and Persistent Infections Caused by Venezuelan Equine Encephalitis Virus Encoding Mutated Capsid Protein
Authors: Atasheva Svetlana , Krendelchtchikova Valentina , Liopo Anton , Frolova Elena , Frolov Ilya 
Published: July 2010

ABSTRACT

Venezuelan equine encephalitis virus (VEEV) is a significant human and animal pathogen. The highlight of VEEV replication
in vitro
, in cells of vertebrate origin, is the rapid development of cytopathic effect (CPE), which is strongly dependent upon the expression of viral capsid protein. Besides being an integral part of virions, the latter protein is capable of (i) binding both the nuclear import and nuclear export receptors, (ii) accumulating in the nuclear pore complexes, (iii) inhibiting nucleocytoplasmic trafficking, and (iv) inhibiting transcription of cellular ribosomal and messenger RNAs. Using our knowledge of the mechanism of VEEV capsid protein function in these processes, we designed VEEV variants containing combinations of mutations in the capsid-coding sequences. These mutations made VEEV dramatically less cytopathic but had no effect on infectious virus production. In cell lines that have defects in type I interferon (IFN) signaling, the capsid mutants demonstrated very efficient persistent replication. In other cells, which have no defects in IFN production or signaling, the same mutants were capable of inducing a long-term antiviral state, downregulating virus replication to an almost undetectable level. However, ultimately, these cells also developed a persistent infection, characterized by continuous virus replication and beta IFN (IFN-β) release. The results of this study demonstrate that the long-term cellular antiviral state is determined by the synergistic effects of type I IFN signaling and the antiviral reaction induced by replicating viral RNA and/or the expression of VEEV-specific proteins. The designed mutants represent an important model for studying the mechanisms of cell interference with VEEV replication and development of persistent infection.
MET Receptor Sequence Variants R970C and T992I Lack Transforming Capacity
Authors: Tyner Jeffrey W. , Fletcher Luke B. , Wang Ellen Q. , Yang Wayne F. , Rutenberg-Schoenberg Michael L. , Beadling Carol , Mori Motomi , Heinrich Michael C. , Deininger Michael W. , Druker Brian J. , Loriaux Marc M. 
Published: July 2010

Abstract
High-throughput sequencing promises to accelerate the discovery of sequence variants, but distinguishing oncogenic mutations from irrelevant “passenger” mutations remains a major challenge. Here we present an analysis of two sequence variants of the MET receptor (hepatocyte growth factor receptor) R970C and T992I (also designated R988C and T1010I). Previous reports indicated that these sequence variants are transforming and contribute to oncogenesis. We screened patients with chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), colorectal cancer, endometrial cancer, thyroid cancer, or melanoma, as well as individuals without cancer, and found these variants at low frequencies in most cohorts, including normal individuals. No evidence of increased phosphorylation or transformative capacity by either sequence variant was found. Because small-molecule inhibitors for MET are currently in development, it will be important to distinguish between oncogenic sequence variants and rare single-nucleotide polymorphisms to avoid the use of unnecessary, and potentially toxic, cancer therapy agents. Cancer Res; 70(15); 6233–7. ©2010 AACR.
A Novel FRET-Based Biosensor for the Measurement of BCR-ABL Activity and Its Response to Drugs in Living Cells
Authors: Mizutani Tatsuaki , Kondo Takeshi , Darmanin Stephanie , Tsuda Masumi , Tanaka Shinya , Tobiume Minoru , Asaka Masahiro , Ohba Yusuke 
Published: July 2010

Abstract
Purpose: To develop a novel diagnostic method for the assessment of drug efficacy in chronic myeloid leukemia (CML) patients individually, we generated a biosensor that enables the evaluation of BCR-ABL kinase activity in living cells using the principle of fluorescence resonance energy transfer (FRET).
Experimental Design: To develop FRET-based biosensors, we used CrkL, the most characteristic substrate of BCR-ABL, and designed a protein in which CrkL is sandwiched between Venus, a variant of YFP, and enhanced cyan fluorescent protein, so that CrkL intramolecular binding of the SH2 domain to phosphorylated tyrosine (Y207) increases FRET efficiency. After evaluation of the properties of this biosensor by comparison with established methods including Western blotting and flow cytometry, BCR-ABL activity and its response to drugs were examined in CML patient cells.
Results: After optimization, we obtained a biosensor that possesses higher sensitivity than that of established techniques with respect to measuring BCR-ABL activity and its suppression by imatinib. Thanks to its high sensitivity, this biosensor accurately gauges BCR-ABL activity in relatively small cell numbers and can also detect &lt;1% minor drug-resistant populations within heterogeneous ones. We also noticed that this method enabled us to predict future onset of drug resistance as well as to monitor the disease status during imatinib therapy, using patient cells.
Conclusion: In consideration of its quick and practical nature, this method is potentially a promising tool for the prediction of both current and future therapeutic responses in individual CML patients, which will be surely beneficial for both patients and clinicians. Clin Cancer Res; 16(15); 3964–75. ©2010 AACR.
CD8+ Enriched “Young” Tumor Infiltrating Lymphocytes Can Mediate Regression of Metastatic Melanoma
Authors: Dudley Mark E. , Gross Colin A. , Langhan Michelle M. , Garcia Marcos R. , Sherry Richard M. , Yang James C. , Phan Giao Q. , Kammula Udai S. , Hughes Marybeth S. , Citrin Deborah E. , Restifo Nicholas P. , Wunderlich John R. , Prieto Peter A. , Hong Jenny J. , Langan Russell C. , Zlott Daniel A. , Morton Kathleen E. , White Donald E. , Laurencot Carolyn M. , Rosenberg Steven A. 
Published: July 2010

AbstractPurpose: Tumor-infiltrating lymphocytes (TIL) and interleukin (IL)-2 administered following lymphodepletion can cause the durable complete regression of bulky metastatic melanoma in patients refractory to approved treatments. However, the generation of a unique tumor-reactive TIL culture for each patient may be prohibitively difficult. We therefore investigated the clinical and immunologic impact of unscreened, CD8+ enriched “young” TIL.Experimental Design: Methods were developed for generating TIL that minimized the time in culture and eliminated the individualized tumor-reactivity screening step. Thirty-three patients were treated with these CD8+ enriched young TIL and IL-2 following nonmyeloablative lymphodepletion (NMA). Twenty-three additional patients were treated with CD8+ enriched young TIL and IL-2 after lymphodepletion with NMA and 6 Gy of total body irradiation.Results: Young TIL cultures for therapy were successfully established from 83% of 122 consecutive melanoma patients. Nineteen of 33 patients (58%) treated with CD8+ enriched young TIL and NMA had an objective response (Response Evaluation Criteria in Solid Tumors) including 3 complete responders. Eleven of 23 patients (48%) treated with TIL and 6 Gy total body irradiation had an objective response including 2 complete responders. At 1 month after TIL infusion the absolute CD8+ cell numbers in the periphery were highly correlated with response.Conclusions: This study shows that a rapid and simplified method can be used to reliably generate CD8+ enriched young TIL for administration as an individualized therapy for advanced melanoma, and may allow this potentially effective treatment to be applied at other institutions and to reach additional patients. Clin Cancer Res; 16(24); 6122–31. ©2010 AACR.
Fluorescence Resonance Energy Transfer Biosensors for Cancer Detection and Evaluation of Drug Efficacy
Authors: Lu Shaoying , Wang Yingxiao 
Published: July 2010

Abstract
A sensitive and specific fluorescence resonance energy transfer (FRET) biosensor was developed by Mizutani and colleagues and applied to detect the activity of BCR-ABL kinase in live cells. This biosensor allowed the detection of cancerous and drug-resistant cells, and the evaluation of kinase inhibitor efficacy. Future biosensor development and imaging can increasingly contribute to cancer diagnosis and therapeutics. Clin Cancer Res; 16(15); 3822–4. ©2010 AACR.
PIM Kinase Inhibitors Downregulate STAT3Tyr705 Phosphorylation
Authors: Chang Marisa , Kanwar Nisha , Feng Eric , Siu Allan , Liu Xiujie , Ma Dawei , Jongstra Jan 
Published: July 2010

Abstract
Using a cell-based high-throughput screen designed to detect small chemical compounds that inhibit cell growth and survival, we identified three structurally related compounds, 21A8, 21H7, and 65D4, with differential activity on cancer versus normal cells. Introduction of structural modifications yielded compound M-110, which inhibits the proliferation of prostate cancer cell lines with IC50s of 0.6 to 0.9 μmol/L, with no activity on normal human peripheral blood mononuclear cells up to 40 μmol/L. Screening of 261 recombinant kinases and subsequent analysis revealed that M-110 is a selective inhibitor of the PIM kinase family, with preference for PIM-3. The prostate cancer cell line DU-145 and the pancreatic cancer cell line MiaPaCa2 constitutively express activated STAT3 (pSTAT3Tyr705). Treatment of DU-145 cells with M-110 or with a structurally unrelated PIM inhibitor, SGI-1776, significantly reduces pSTAT3Tyr705 expression without affecting the expression of STAT3. Furthermore, treatment of DU-145 cells with M-110 attenuates the interleukin-6–induced increase in pSTAT3Tyr705. To determine which of the three PIM kinases is most likely to inhibit expression of pSTAT3Tyr705, we used PIM-1–, PIM-2–, or PIM-3–specific siRNA and showed that knockdown of PIM-3, but not of PIM-1 or PIM-2, in DU-145 cells results in a significant downregulation of pSTAT3Tyr705. The phosphorylation of STAT5 on Tyr694 in 22Rv1 cells is not affected by M-110 or SGI-1776, suggesting specificity for pSTAT3Tyr705. These results identify a novel role for PIM-3 kinase as a positive regulator of STAT3 signaling and suggest that PIM-3 inhibitors cause growth inhibition of cancer cells by downregulating the expression of pSTAT3Tyr705. Mol Cancer Ther; 9(9); 2478–87. ©2010 AACR.
Effect of TRMM Orbit Boost on Radar Reflectivity Distributions
Authors: Short David A. , Nakamura Kenji 
Published: July 2010

Abstract
Probability distributions of measured radar reflectivity from the precipitation radar (PR) on board the Tropical Rainfall Measuring Mission (TRMM) satellite show a small, counterintuitive increase in the midrange, 20–34 dBZ, when comparing data from periods before and after the orbit altitude was boosted in August 2001. Data from two 2-yr time periods, 1999–2000 (preboost) and 2002–03 (postboost), show statistically significant differences of 2%–3% at altitudes of 2, 4, and 10 km and for path-averaged reflectivity.
The bivariate Gaussian function, used to model idealized radar response functions, has mathematical properties that indicate an increase in field-of-view (FOV) size associated with an increase in satellite altitude can be expected to result in a narrowing of observed dBZ distributions, with a resulting increase in midrange values. Numerical simulations with echo areas much smaller and larger than the TRMM PR FOV before (4.3 km) and after (5.0 km) boost are used to demonstrate basic characteristics of the observed and expected distribution changes.
Improved cellular and humoral immune responses in vivo following targeting of HIV Gag to dendritic cells within human anti–human DEC205 monoclonal antibody
Authors: Cheong Cheolho , Choi Jae-Hoon , Vitale Laura , He Li-Zhen , Trumpfheller Christine , Bozzacco Leonia , Do Yoonkyung , Nchinda Godwin , Park Sung Ho , Dandamudi Durga Bhavani , Shrestha Elina , Pack Maggi , Lee Han-Woong , Keler Tibor , Steinman Ralph M. , Park Chae Gyu 
Published: July 2010

Abstract
Protein vaccines for T-cell immunity are not being prioritized because of poor immunogenicity. To overcome this hurdle, proteins are being targeted to maturing dendritic cells (DCs) within monoclonal antibodies (mAbs) to DC receptors. To extend the concept to humans, we immunized human immunoglobulin-expressing mice with human DEC205 (hDEC205) extracellular domain. 3D6 and 3G9 mAbs were selected for high-affinity binding to hDEC205. In addition, CD11c promoter hDEC205 transgenic mice were generated, and 3G9 was selectively targeted to DCs in these animals. When mAb heavy chain was engineered to express HIV Gag p24, the fusion mAb induced interferon-γ– and interleukin-2–producing CD4+ T cells in hDEC205 transgenic mice, if polynocinic polycytidylic acid was coadministered as an adjuvant. The T-cell response was broad, recognizing at least 3 Gag peptides, and high titers of anti-human immunoglobulin G antibody were made. Anti-hDEC205 also improved the cross-presentation of Gag to primed CD8+ T cells from HIV-infected individuals. In all tests, 3D6 and 3G9 targeting greatly enhanced immunization relative to nonbinding control mAb. These results provide preclinical evidence that in vivo hDEC205 targeting increases the efficiency with which proteins elicit specific immunity, setting the stage for proof-of-concept studies of these new protein vaccines in human subjects.
Life-threatening hemobilia caused by hepatic pseudoaneurysm after T-tube choledochostomy: report of a case
Authors: Lee Yueh-Tsung , Lin Ho , Chen Kuan-Yung , Wu Hurng-Sheng , Hwang Min-Ho , Yan Sheng-Lei 
Published: July 2010

Abstract

Background
Hemobilia is a rare but lethal biliary tract complication. There are several causes of hemobilia which might be classified as traumatic or nontraumatic. Hemobilia caused by pseudoaneurysm might result from hepatobiliary surgery or percutaneous interventional hepatobiliary procedures. However, to our knowledge, there are no previous reports pertaining to hemobilia caused by hepatic pseudoaneurysm after T-tube choledochostomy.

Case presentation
A 65-year-old male was admitted to our hospital because of acute calculous cholecystitis and cholangitis. He underwent cholecystectomy, choledocholithotomy via a right upper quadrant laparotomy and a temporary T-tube choledochostomy was created. However, on the 19th day after operation, he suffered from sudden onset of hematemesis and massive fresh blood drainage from the T-tube choledochostomy. Imaging studies confirmed the diagnosis of pseudoaneurysm associated hemobilia. The probable association of T-tube choledochostomy with pseudoaneurysm and hemobilia is also demonstrated. He underwent emergent selective microcoils emobolization to occlude the feeding artery of the pseudoaneurysm.

Conclusions
Pseudoaneurysm associated hemobilia may occur after T-tube choledochostomy. This case also highlights the importance that hemobilia should be highly suspected in a patient presenting with jaundice, right upper quadrant abdominal pain and upper gastrointestinal bleeding after liver or biliary surgery.
Regional variations in and correlates of disability-free life expectancy among older adults in China
Authors: Liu Jufen , Chen Gong , Chi Iris , Wu Jilei , Pei Lijun , Song Xinming , Zhang Lei , Pang Lihua , Han Youli , Zheng Xiaoying 
Published: July 2010

AbstractBackgroundConsiderable socioeconomic and health inequalities have been reported in China. However, because of a lack of appropriate data, limited research has been conducted on variations in disability-free life expectancy (DFLE) among older adults. This study aimed to use the most up-to-date disability survey data to explore geographical variations in DFLE at age 60 in China and to identify the socioeconomic and health care factors that partially account for these variations.MethodsThis study used 2006 mortality data extrapolated from the 1990 and 2000 Census and disability data from a national disability survey conducted in 2006. Disability was performance based and was diagnosed by trained physicians. DFLE was calculated by region using the Sullivan method. Multiple linear regression models by gender were conducted to explore correlates of DFLE.ResultsDFLE at age 60 varied widely by region, from 11.2 to 20.8 years in 2006. Per capita gross domestic product, proportion of urban residents, and access to health care were the primary factors associated with geographical variations in DFLE.ConclusionThe pattern of differences in DFLE by region mirrors the pattern of regional economic development in China. Countermeasures to decrease regional differences in DFLE include accelerating regional economic development and improving health care distribution.
PC-3 prostate carcinoma cells release signal substances that influence the migratory activity of cells in the tumor's microenvironment
Authors: Voss Melanie J , Niggemann Bernd , Zänker Kurt S , Entschladen Frank 
Published: July 2010

Abstract

Background
Tumor cells interact with the cells of the microenvironment not only by cell-cell-contacts but also by the release of signal substances. These substances are known to induce tumor vascularization, especially under hypoxic conditions, but are also supposed to provoke other processes such as tumor innervation and inflammatory conditions. Inflammation is mediated by two organ systems, the neuroendocrine system and the immune system. Therefore, we investigated the influence of substances released by PC-3 human prostate carcinoma cells on SH-SY5Y neuroblastoma cells as well as neutrophil granulocytes and cytotoxic T lymphocytes, especially with regard to their migratory activity.

Results
PC-3 cells express several cytokines and growth factors including vascular endothelial growth factors, fibroblast growth factors, interleukins and neurotrophic factors. SH-SY5Y cells are impaired in their migratory activity by PC-3 cell culture supernatant, but orientate chemotactically towards the source. Neutrophil granulocytes increase their locomotory activity only in response to cell culture supernantant of hypoxic but not of normoxic PC-3 cells. In contrast, cytotoxic T lymphocytes do not change their migratory activity in response to either culture supernatant, but increase their cytotoxicity, whereas supernatant of normoxic PC-3 cells leads to a stronger increase than that of hypoxic PC-3 cells.

Conclusions
PC-3 cells release several signal substances that influence the behavior of the cells in the tumor's microenvironment, whereas no clear pattern towards proinflammatory or immunosuppressive conditions can be seen.
Analysis of adenovirus trans-complementation-mediated gene expression controlled by melanoma-specific TETP promoter in vitro
Authors: Fontecedro Alessandra Curioni , Lutschg Verena , Eichhoff Ossia , Dummer Reinhard , Greber Urs F , Hemmi Silvio 
Published: July 2010

AbstractBackgroundHuman adenoviruses (Ads) have substantial potential for clinical applications in cancer patients. Conditionally replicating adenoviruses (CRAds) include oncolytic adenoviruses in which expression of the immediate early viral transactivator protein E1A is controlled by a cancer cell-selective promoter. To enhance efficacy, CRAds are further armed to contain therapeutic genes. Due to size constraints of the capsid geometry, the capacity for packaging transgenes into Ads is, however, limited. To overcome this limitation, the employment of E1A-deleted replication-deficient viruses carrying therapeutic genes in combination with replication-competent CRAd vectors expressing E1Ain transhas been proposed. Most trans-complementing studies involved transgene expressions from strong ubiquitous promoters, and thereby relied entirely on the cancer cell specificity of the CRAd vector.ResultsHere we tested the trans-complementation of a CRAd and a replication-deficient transgene vector containing the same cancer cell-selective promoter. Hereto, we generated two new vectors expressing IL-2 and CD40L from a bicistronic expression cassette under the control of the melanoma/melanocyte-specific tyrosinase enhancer tyrosinase promoter (TETP), which we previously described for the melanoma-specific CRAd vector AdΔEP-TETP. These vectors gave rise to tightly controlled melanoma-specific transgene expression levels, which were only 5 to 40-fold lower than those from vectors controlled by the nonselective CMV promoter. Reporter analyses using Ad-CMV-eGFP in combination with AdΔEP-TETP revealed a high level of trans-complementation in melanoma cells (up to about 30-fold), but not in non-melanoma cells, unlike the AdCMV-eGFP/wtAd5 binary vector system, which was equally efficient in melanoma and non-melanoma cells. Similar findings were obtained when replacing the transgene vector AdCMV-eGFP with AdCMV-IL-2 or AdCMV-CD40L. However, the combination of the novel AdTETP-CD40L/IL-2 vector with AdΔEP-TETP or wtAd5 gave reproducible moderate 3-fold enhancements of IL-2 by trans-complementation only.ConclusionsThe cancer cell-selective TETP tested here did not give the expected enforceable transgene expression typically achieved in the Ad trans-complementing system. Reasons for this could include virus-mediated down regulation of limiting transcription factors, and/or competition for such factors by different promoters. Whether this finding is unique to the particular promoter system tested here, or also occurs with other promoters warrants further investigations.