bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiotrophin-1 Promotes a High Survival Rate in Rabbits with Lethal Fulminant Hepatitis of Viral Origin
Authors: Tuñon Maria Jesus , San Miguel Beatriz , Crespo Irene , Riezu-Boj Jose Ignacio , Larrea Esther , Álvarez Marcelino , González Iranzu , Bustos Matilde , González-Gallego Javier , Prieto Jesus 
Published: October 2011

ABSTRACT

Rabbit hemorrhagic disease virus (RHDV) causes lethal fulminant hepatitis closely resembling acute liver failure (ALF) in humans. In this study, we investigated whether cardiotrophin-1 (CT-1), a cytokine with hepatoprotective properties, could attenuate liver damage and prolong survival in virus-induced ALF. Twenty-four rabbits were infected with 2 × 10
4
hemagglutination units of RHDV. Twelve received five doses of CT-1 (100 μg/kg) starting at 12 h postinfection (hpi) (the first three doses every 6 h and then two additional doses at 48 and 72 hpi), while the rest received saline. The animals were analyzed for survival, serum biochemistry, and viral load. Another cohort (
n
= 22) was infected and treated similarly, but animals were sacrificed at 30 and 36 hpi to analyze liver histology, viral load, and the expression of factors implicated in liver damage and repair. All infected rabbits that received saline died by 60 hpi, while 67% of the CT-1-treated animals survived until the end of the study. Treated animals showed improved liver function and histology, while the viral loads were similar. In the livers of CT-1-treated rabbits we observed reduction of oxidative stress, diminished PARP1/2 and JNK activation, and decreased inflammatory reaction, as reflected by reduced expression of tumor necrosis factor alpha,
interleukin-1β
, Toll-like receptor 4, VCAM-1, and MMP-9. In addition, CT-1-treated rabbits exhibited marked upregulation of TIMP-1 and increased expression of cytoprotective and proregenerative growth factors, including platelet-derived growth factor B, epidermal growth factor, platelet-derived growth factor receptor β, and c-Met. In conclusion, in a lethal form of acute viral hepatitis, CT-1 increases animal survival by attenuating inflammation and activating cytoprotective mechanisms, thus representing a promising therapy for ALF of viral origin.
Infection with Seasonal Influenza Virus Elicits CD4 T Cells Specific for Genetically Conserved Epitopes That Can Be Rapidly Mobilized for Protective Immunity to Pandemic H1N1 Influenza Virus
Authors: Alam Shabnam , Sant Andrea J. 
Published: October 2011

ABSTRACT
In recent years, influenza viruses with pandemic potential have been a major concern worldwide. One unresolved issue is how infection or vaccination with seasonal influenza virus strains influences the ability to mount a protective immune response to novel pandemic strains. In this study, we developed a mouse model of primary and secondary influenza infection by using a widely circulating seasonal H1N1 virus and the pandemic strain of H1N1 that emerged in Mexico in 2009, and we evaluated several key issues. First, using overlapping peptide libraries encompassing the entire translated sequences of 5 major influenza virus proteins, we assessed the specificity of CD4 T cell reactivity toward epitopes conserved among H1N1 viruses or unique to the seasonal or pandemic strain by enzyme-linked immunospot (ELISpot) assays. Our data show that CD4 T cells reactive to both virus-specific and genetically conserved epitopes are elicited, allowing separate tracking of these responses. Populations of cross-reactive CD4 T cells generated from seasonal influenza infection were found to expand earlier after secondary infection with the pandemic H1N1 virus than CD4 T cell populations specific for new epitopes. Coincident with this rapid CD4 T cell response was a potentiated neutralizing-antibody response to the pandemic strain and protection from the pathological effects of infection with the pandemic virus. This protection was not dependent on CD8 T cells. Together, our results indicate that exposure to seasonal vaccines and infection elicits CD4 T cells that promote the ability of the mammalian host to mount a protective immune response to pandemic strains of influenza virus.
Prediction of Hepatocellular Carcinoma Development by Plasma ADAMTS13 in Chronic Hepatitis B and C
Authors: Ikeda Hitoshi , Tateishi Ryosuke , Enooku Kenichiro , Yoshida Haruhiko , Nakagawa Hayato , Masuzaki Ryota , Kondo Yuji , Goto Tadashi , Shiina Shuichiro , Kume Yukio , Tomiya Tomoaki , Inoue Yukiko , Nishikawa Takako , Ohtomo Natsuko , Tanoue Yasushi , Ono Tomoko , Koike Kazuhiko , Yatomi Yutaka 
Published: October 2011

Abstract
Background: Chronic liver injury evokes a wound healing response, promoting fibrosis and finally hepatocellular carcinoma (HCC), in which hepatic stellate cells play an important role. Although a blood marker of hepatic stellate cells is not known, those cells importantly contribute to the regulation of plasma a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) activity, a defect of which causes thrombotic thrombocytopenic purpura.
Methods: Plasma ADAMTS13 was evaluated in chronic hepatitis B or C patients with or without HCC.
Results: Plasma ADAMTS13 activity significantly correlated with serum aspartate aminotransferase and alanine aminotransferase, liver stiffness value, and aspartate aminotransferase-to-platelet ratio index, irrespective of the presence of HCC, suggesting that it may reflect hepatocellular damage and subsequent wound healing and fibrosis as a result of hepatic stellate cell action. During the three-year follow-up period for patients without HCC, it developed in 10 among 81 patients. Plasma ADAMTS13 activity was significantly higher in patients with HCC development than in those without and was a significant risk for HCC development by univariate and multivariate analyses. Furthermore, during the one-year follow-up period for patients with HCC treated with radiofrequency ablation, HCC recurred in 55 among 107 patients. Plasma ADAMTS13 activity or antigen level was significantly higher in patients with HCC recurrence than in those without and was retained as a significant risk for HCC recurrence by multivariate analysis.
Conclusions: Higher plasma ADAMTS13 activity and antigen level was a risk of HCC development in chronic liver disease.
Impact: Plasma ADAMTS13 as a potential marker of hepatic stellate cells may be useful in the prediction of hepatocarcinogenesis. Cancer Epidemiol Biomarkers Prev; 20(10); 2204–11. ©2011 AACR.
The Retrovirus XMRV Is not Directly Involved in the Pathogenesis of Common Types of Lymphoid Malignancy
Authors: Waugh Elspeth M. , Jarrett Ruth F. , Shield Lesley , Montgomery Dorothy , Dean Robert T.G. , Mitchell Andrea , Greaves Mel F. , Gallagher Alice 
Published: October 2011

Abstract
Background: A novel retrovirus, xenotropic murine leukemia virus-related virus (XMRV), has been detected in prostate cancer samples and in peripheral blood mononuclear cells (PBMC) from patients with chronic fatigue syndrome. In addition, the virus has been identified in PBMCs from healthy controls. These data suggest that XMRV is circulating in the human population. XMRV is closely related to murine leukemia viruses, which cause lymphoid malignancies in mice. The aim of this study was to determine whether XMRV is directly associated with common forms of human lymphoma or leukemia.
Methods: DNA samples from 368 patients with lymphoid malignancies and 139 patients with benign lymphadenopathy or other malignant disease were screened for XMRV, using three specific and sensitive quantitative PCR assays.
Results: XMRV was not detected in any sample using any of the three assays.
Conclusions: The data suggest that this virus is not directly involved in the pathogenesis of common types of lymphoid malignancy and that XMRV is not a prevalent blood borne infection, at least in the United Kingdom.
Impact: There is no evidence that XMRV is associated with lymphoid malignancies, and further studies should resolve inconsistencies in results of studies examining XMRV prevalence. Cancer Epidemiol Biomarkers Prev. 20(10); 2232–6. ©2011 AACR.
Support for Caregivers of Cancer Patients: Transition After Active Treatment
Authors: Given Barbara A. , Sherwood Paula , Given Charles W. 
Published: October 2011

Abstract
Family caregivers provide uncompensated care and assistance to a family member who has cancer. When patients move through the care trajectory into the survivorship phase, roles and demands of caregivers change and caregivers assume responsibility to assist with coordination of ongoing care. The goal of this article is to describe aspects of caregiver experiences and the roles of caregivers as patients transition from active cancer treatment into the first and early phase of cancer care. Residual problems for patients and caregivers remain for some period of time. Cancer Epidemiol Biomarkers Prev; 20(10); 2015–21. ©2011 AACR.
A Framework for Cancer Survivorship Research and Translation to Policy
Authors: Grunfeld Eva , Earle Craig C. , Stovall Ellen 
Published: October 2011

Abstract
Awareness has grown over the past few years that needs specific to cancer survivors have long been neglected. Clinicians and policy makers continue to struggle, however, with exactly how to address these needs. We present a comprehensive framework for survivorship research and couple it with a model for translating research into policy, using two examples for illustration. Cancer Epidemiol Biomarkers Prev; 20(10); 2099–104. ©2011 AACR.
Methods to Assess Adverse Health-Related Outcomes in Cancer Survivors
Authors: Oeffinger Kevin C. , van Leeuwen Flora E. , Hodgson David C. 
Published: October 2011

AbstractDesigning a study focused on adverse health-related outcomes among cancer survivors is complex. Similarly, reading and interpreting the findings of a survivorship-focused study requires an appreciation of the complexities of study design, potential biases, confounding factors, and other limitations. The topic areas are broad—study design, comparison populations, measures of risk, key health outcomes of interest, potential modifying factors to consider. With brevity, this article includes basic information to consider within these areas as well as examples and concepts intended to advance the science of survivorship research and encourage further reading and exploration. Cancer Epidemiol Biomarkers Prev; 20(10); 2022–34. ©2011 AACR.
Pretargeted Radioimmunotherapy Using Genetically Engineered Antibody-Streptavidin Fusion Proteins for Treatment of Non-Hodgkin Lymphoma
Authors: Park Steven I. , Shenoi Jaideep , Frayo Shani M. , Hamlin Donald K. , Lin Yukang , Wilbur D. Scott , Stayton Patrick S. , Orgun Nural , Hylarides Mark , Buchegger Franz , Kenoyer Aimee L. , Axtman Amanda , Gopal Ajay K. , Green Damian J. , Pagel John M. , Press Oliver W. 
Published: October 2011

Abstract
Purpose: Pretargeted radioimmunotherapy (PRIT) using streptavidin (SAv)-biotin technology can deliver higher therapeutic doses of radioactivity to tumors than conventional RIT. However, “endogenous” biotin can interfere with the effectiveness of this approach by blocking binding of radiolabeled biotin to SAv. We engineered a series of SAv FPs that downmodulate the affinity of SAv for biotin, while retaining high avidity for divalent DOTA-bis-biotin to circumvent this problem.
Experimental Design: The single-chain variable region gene of the murine 1F5 anti-CD20 antibody was fused to the wild-type (WT) SAv gene and to mutant SAv genes, Y43A-SAv and S45A-SAv. FPs were expressed, purified, and compared in studies using athymic mice bearing Ramos lymphoma xenografts.
Results: Biodistribution studies showed delivery of more radioactivity to tumors of mice pretargeted with mutant SAv FPs followed by 111In-DOTA-bis-biotin [6.2 ± 1.7% of the injected dose per gram (%ID/gm) of tumor 24 hours after Y43A-SAv FP and 5.6 ± 2.2%ID/g with S45A-SAv FP] than in mice on normal diets pretargeted with WT-SAv FP (2.5 ± 1.6%ID/g; P = 0.01). These superior biodistributions translated into superior antitumor efficacy in mice treated with mutant FPs and 90Y-DOTA-bis-biotin [tumor volumes after 11 days: 237 ± 66 mm3 with Y43A-SAv, 543 ± 320 mm3 with S45A-SAv, 1129 ± 322 mm3 with WT-SAv, and 1435 ± 212 mm3 with control FP (P &lt; 0.0001)].
Conclusions: Genetically engineered mutant-SAv FPs and bis-biotin reagents provide an attractive alternative to current SAv-biotin PRIT methods in settings where endogenous biotin levels are high. Clin Cancer Res; 17(23); 7373–82. ©2011 AACR.
Quantifying Cardiac Hemodynamic Stress and Cardiomyocyte Damage in Ischemic and Nonischemic Acute Heart Failure
Authors: Drexler Beatrice , Heinisch Corinna , Balmelli Cathrin , Lassus Johan , Siirilä-Waris Krista , Arenja Nisha , Socrates Thenral , Noveanu Markus , Potocki Mihael , Meune Christophe , Haaf Philip , Degen Christian , Breidthardt Tobias , Reichlin Tobias , Nieminen Markku S. , Veli-Pekka Harjola , Osswald Stefan , Mueller Christian 
Published: October 2011

Background—
The early and noninvasive differentiation of ischemic and nonischemic acute heart failure (AHF) in the emergency department (ED) is an unmet clinical need.

Methods and Results—

We quantified cardiac hemodynamic stress using B-type natriuretic peptide (BNP) and cardiomyocyte damage using 2 different cardiac troponin assays in 718 consecutive patients presenting to the ED with AHF (derivation cohort). The diagnosis of ischemic AHF was adjudicated using all information, including coronary angiography. Findings were validated in a second independent multicenter cohort (326 AHF patients). Among the 718 patients, 400 (56%) were adjudicated to have ischemic AHF. BNP levels were significantly higher in ischemic compared with nonischemic AHF (1097 [604–1525] pg/mL versus 800 [427–1317] pg/mL;
P
<0.001). Cardiac troponin T (cTnT) and sensitive cardiac troponin I (s-cTnI) were also significantly higher in ischemic compared with nonischemic AHF patients (0.040 [0.010–0.306] μg/L versus 0.018 [0.010–0.060] μg/L [
P
<0.001]; 0.024 [0.008–0.106] μg/L versus 0.016 [0.004–0.044 ] μg/L [
P
=0.002]). The diagnostic accuracy of BNP, cTnT, and s-cTnI for the diagnosis of ischemic AHF, as quantified by the area under the receiver-operating characteristic curve, was low (0.58 [95% CI, 0.54–0.63], 0.61 [95% CI, 0.57–0.66], and 0.59 [95% CI,0.54–0.65], respectively). These findings were confirmed in the validation cohort.

Conclusions—
At presentation to the ED, patients with ischemic AHF exhibit more extensive hemodynamic cardiac stress and cardiomyocyte damage than patients with nonischemic AHF. However, the overlap is substantial, resulting in poor diagnostic accuracy.
The FARC and the Colombian Left
Authors: Lee Chris 
Published: October 2011

Is the FARC (Fuerzas Armadas Revolucionarias de Colombia–Ejército del Pueblo [Revolutionary Armed Forces of Colombia–People’s Army]) merely a terrorist organization involved in narcotrafficking and the predatory tactics of survival, or does it represent a legitimate political movement or alternative? Should the Colombian left sever any ties to the FARC, or should it attempt to integrate it into the political process? These questions are particularly salient now because the political left in Colombia is arguably emergent, whereas the FARC’s military strength has been eroded by the vigorous military and political attacks of the Uribe administration and its tactics have made it an unattractive political option. ¿Qué on las Fuerzas Armadas Revolucionarios de Colombia–Ejército del Pueblo (FARC), una organización terrorista involucrada con el narcotráfico y tácticas rapaces de supervivencia, o una alternativa o movimiento político legítimos? ¿Debería la izquierda colombiana deslindarse de ellas, o integrarlas al proceso político? Estas preguntas son de particular importancia hoy día ya que, mientras que la izquierda política es una fuerza emergente en Colombia, el poder militar de las FARC se ha erosionado a partir de los vigorosos ataques militares y políticos de la administración de Uribe. Además, sus tácticas les han convertido en una opción política poco atractiva.
Incidence and predictors of congestive heart failure after autologous hematopoietic cell transplantation
Authors: Armenian Saro H. , Sun Can-Lan , Shannon Tabitha , Mills George , Francisco Liton , Venkataraman Kalyanasundaram , Wong F. Lennie , Forman Stephen J. , Bhatia Smita 
Published: October 2011

Abstract
Advances in autologous hematopoietic cell transplantation (HCT) strategies have resulted in a growing number of long-term survivors. However, these survivors are at increased risk of developing cardiovascular complications due to pre-HCT therapeutic exposures and conditioning and post-HCT comorbidities. We examined the incidence and predictors of congestive heart failure (CHF) in 1244 patients undergoing autologous HCT for a hematologic malignancy between 1988 and 2002. The cumulative incidence of CHF was 4.8% at 5 years and increased to 9.1% at 15 years after transplantation; the CI for female lymphoma survivors was 14.5% at 15 years. The cohort was at a 4.5-fold increased risk of CHF (standardized incidence ratio = 4.5), compared with the general population. The risk of CHF increased substantially for patients receiving ≥ 250 mg/m2 of cumulative anthracycline exposure (odds ratio [OR]: 9.9, P < .01), creating a new and lower threshold for cardiac surveillance after HCT. The presence of hypertension among recipients of high-dose anthracycline (≥ 250 mg/m2) resulted in a 35-fold risk (OR: 35.3, P < .01) of CHF; the risk was nearly 27-fold (OR: 26.8, P < .01) for high-dose anthracycline recipients with diabetes, providing evidence that hypertension and diabetes may be critical modifiers of anthracycline-related myocardial injury after HCT and creating targeted populations for aggressive intervention.
Epigenetic inactivation of the MIR34B/C in multiple myeloma
Authors: Wong Kwan Yeung , Yim Rita Lok Hay , So Chi Chiu , Jin Dong-Yan , Liang Raymond , Chim Chor Sang 
Published: October 2011

Abstract
We postulated that MIR34B/C, a direct transcriptional target of TP53, might be inactivated by promoter hypermethylation in multiple myeloma (MM). MIR34B/C promoter methylation was studied in 8 normal marrow controls, 8 MM cell lines, 95 diagnostic, and 23 relapsed/progressed MM samples by methylation-specific PCR. MIR34B/C was methylated in 6 (75.0%) MM cell lines but not normal controls. 5-Aza-2′-deoxycytidine led to MIR34B/C promoter demethylation and MIR34B reexpression. Moreover, restoration of MIR34B led to reduced cellular proliferation and enhanced apoptosis of myeloma cells. In primary samples, methylation of MIR34B/C occurred in 5.3% at diagnosis and 52.2% at relapse/disease progression (P < .001). In 12 MM patients with paired samples at diagnosis and relapse/progression, MIR34B/C methylation was acquired in 6 at relapse/progression. In conclusion, MIR34B/C is a tumor suppressor in myeloma. Hypermethylation of MIR34B/C is tumor-specific. Frequent MIR34B/C hypermethylation during relapse/progression but not at diagnosis implicated a role of MIR34B/C hypermethylation in myeloma relapse/progression.
Transgenic mouse model for the formation of Hirano bodies
Authors: Ha Sangdeuk , Furukawa Ruth , Stramiello Michael , Wagner John J , Fechheimer Marcus 
Published: October 2011

AbstractBackgroundHirano bodies are actin-rich cytoplasmic inclusions found predominantly in the brain in association with a variety of conditions including aging and Alzheimer's disease. The function of Hirano bodies in normal aging and in progression of disease has not been extensively investigated due to a lack of experimental model systems. We have developed a transgenic mouse model by expression of a gain-of-function actin cross-linking protein mutant.ResultsWe used the Cre/loxP system to permit tissue specific expression of Hirano bodies, and employed the murine Thy 1 promoter to drive expression of Cre recombinase in the brain. Hirano bodies were observed in the cerebral cortex and hippocampus of homozygous double transgenic 6 month old mice containing Cre. The Hirano bodies were eosinophilic rods, and also exhibited the paracrystalline F-actin filament organization that is characteristic of these inclusions. Mice with Hirano bodies appear healthy and fertile, but exhibited some alterations in both short-term and long-term synaptic plasticity, including paired-pulse depression rather than facilitation, and decreased magnitude of early LTP.ConclusionsHirano bodies are not lethal and appear to have little or no effect on histology and tissue organization. Hirano bodies do modulate synaptic plasticity and exert clearly discernable effects on LTP and paired-pulse paradigms. This model system will allow us to investigate the impact of Hirano bodiesin vivo, the pathways for formation and degradation of Hirano bodies, and whether Hirano bodies promote or modulate development of pathology and disease progression.
In vivo imaging of lymphocytes in the CNS reveals different behaviour of naïve T cells in health and autoimmunity
Authors: Herz Josephine , Paterka Magdalena , Niesner Raluca A , Brandt Alexander U , Siffrin Volker , Leuenberger Tina , Birkenstock Jerome , Mossakowski Agata , Glumm Robert , Zipp Frauke , Radbruch Helena 
Published: October 2011

Abstract

Background
Two-photon laser scanning microscopy (TPLSM) has become a powerful tool in the visualization of immune cell dynamics and cellular communication within the complex biological networks of the inflamed central nervous system (CNS). Whereas many previous studies mainly focused on the role of effector or effector memory T cells, the role of naïve T cells as possible key players in immune regulation directly in the CNS is still highly debated.

Methods
We applied ex vivo and intravital TPLSM to investigate migratory pathways of naïve T cells in the inflamed and non-inflamed CNS. MACS-sorted naïve CD4+ T cells were either applied on healthy CNS slices or intravenously injected into RAG1 -/- mice, which were affected by experimental autoimmune encephalomyelitis (EAE). We further checked for the generation of second harmonic generation (SHG) signals produced by extracellular matrix (ECM) structures.

Results
By applying TPLSM on living brain slices we could show that the migratory capacity of activated CD4+ T cells is not strongly influenced by antigen specificity and is independent of regulatory or effector T cell phenotype. Naïve T cells, however, cannot find sufficient migratory signals in healthy, non-inflamed CNS parenchyma since they only showed stationary behaviour in this context. This is in contrast to the high motility of naïve CD4+ T cells in lymphoid organs. We observed a highly motile migration pattern for naïve T cells as compared to effector CD4+ T cells in inflamed brain tissue of living EAE-affected mice. Interestingly, in the inflamed CNS we could detect reticular structures by their SHG signal which partially co-localises with naïve CD4+ T cell tracks.

Conclusions
The activation status rather than antigen specificity or regulatory phenotype is the central requirement for CD4+ T cell migration within healthy CNS tissue. However, under inflammatory conditions naïve CD4+ T cells can get access to CNS parenchyma and partially migrate along inflammation-induced extracellular SHG structures, which are similar to those seen in lymphoid organs. These SHG structures apparently provide essential migratory signals for naïve CD4+ T cells within the diseased CNS.