bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of γ-chain cytokines on EBV-specific T cell cultures
Authors: Merlo Anna , Turrini Riccardo , Trento Cristina , Zanovello Paola , Dolcetti Riccardo , Rosato Antonio 
Published: November 2010

Abstract

Background
Recent preclinical adoptive immunotherapy studies in murine models prompt to employ "proper" rather than "as many as possible" antigen-specific T cells to gain better therapeutic results. Ideally, "proper" T cells are poorly differentiated in vitro, but retain the capacity to fully differentiate into effector cells in vivo, where they can undergo long-term survival and strong proliferation. Such requirements can be achieved by modifying culture conditions, namely using less "differentiating" cytokines than IL-2.

Methods
To evaluate this issue in human T cell cultures, we exploited a well characterized and clinical-grade protocol finalized at generating EBV-specific CTL for adoptive immunotherapy. In particular, we studied the impact of IL-7, IL-15 and IL-21 compared to IL-2 on different aspects of T cell functionality, namely growth kinetics, differentiation/activation marker expression, cytokine production, and short-term and long-term cytotoxicity.

Results
Results disclosed that the culture modifications we introduced in the standard protocol did not improve activity nor induce substantial changes in differentiation marker expression of EBV-specific CTL.

Conclusions
Our data indicated that the addition of γ-chain cytokines other than IL-2 for the generation of EBV-specific T cell cultures did not produce the improvements expected on the basis of recent published literature. This fact was likely due to the intrinsic differences between murine and human models and highlights the need to design ad hoc protocols rather than simply modify the cytokines added in culture.
Combining nitric oxide release with anti-inflammatory activity preserves nigrostriatal dopaminergic innervation and prevents motor impairment in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease
Authors: L'Episcopo Francesca , Tirolo Cataldo , Caniglia Salvatore , Testa Nunzio , Serra Pier A , Impagnatiello Francesco , Morale Maria C , Marchetti Bianca 
Published: November 2010

Abstract

Background
Current evidence suggests a role of neuroinflammation in the pathogenesis of Parkinson's disease (PD) and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of basal ganglia injury. Reportedly, nonsteroidal anti-inflammatory drugs (NSAIDs) mitigate DAergic neurotoxicity in rodent models of PD. Consistent with these findings, epidemiological analysis indicated that certain NSAIDs may prevent or delay the progression of PD. However, a serious impediment of chronic NSAID therapy, particularly in the elderly, is gastric, renal and cardiac toxicity. Nitric oxide (NO)-donating NSAIDs, have a safer profile while maintaining anti-inflammatory activity of parent compounds. We have investigated the oral activity of the NO-donating derivative of flurbiprofen, [2-fluoro-α-methyl (1,1'-biphenyl)-4-acetic-4-(nitrooxy)butyl ester], HCT1026 (30 mg kg-1 daily in rodent chow) in mice exposed to the parkinsonian neurotoxin MPTP.

Methods
Ageing mice were fed with a control, flurbiprofen, or HCT1026 diet starting ten days before MPTP administration and continuing for all the experimental period. Striatal high affinity synaptosomial dopamine up-take, motor coordination assessed with the rotarod, tyrosine hydroxylase (TH)- and dopamine transporter (DAT) fiber staining, stereological cell counts, immunoblotting and gene expression analyses were used to assess MPTP-induced nigrostriatal DAergic toxicity and glial activation 1-40 days post-MPTP.

Results
HCT1026 was well tolerated and did not cause any measurable toxic effect, whereas flurbiprofen fed mice showed severe gastrointestinal side-effects. HCT1026 efficiently counteracted motor impairment and reversed MPTP-induced decreased synaptosomal [3H]dopamine uptake, TH- and DAT-stained fibers in striatum and TH+ neuron loss in subtantia nigra pars compacta (SNpc), as opposed to age-matched mice fed with a control diet. These effects were associated to a significant decrease in reactive macrophage antigen-1 (Mac-1)-positive microglial cells within the striatum and ventral midbrain, decreased expression of iNOS, Mac-1 and NADPH oxidase (PHOX), and downregulation of 3-Nitrotyrosine, a peroxynitrite finger print, in SNpc DAergic neurons.

Conclusions
Oral treatment with HCT1026 has a safe profile and a significant efficacy in counteracting MPTP-induced dopaminergic (DAergic) neurotoxicity, motor impairment and microglia activation in ageing mice. HCT1026 provides a novel promising approach towards the development of effective pharmacological neuroprotective strategies against PD.
Role of oxidative stress on diesel-enhanced influenza infection in mice
Authors: Gowdy Kymberly M , Krantz Quentin T , King Charly , Boykin Elizabeth , Jaspers Ilona , Linak William P , Gilmour M Ian 
Published: November 2010

AbstractNumerous studies have shown that air pollutants, including diesel exhaust (DE), reduce host defenses, resulting in decreased resistance to respiratory infections. This study sought to determine if DE exposure could affect the severity of an ongoing influenza infection in mice, and examine if this could be modulated with antioxidants. BALB/c mice were treated by oropharyngeal aspiration with 50 plaque forming units of influenza A/HongKong/8/68 and immediately exposed to air or 0.5 mg/m3DE (4 hrs/day, 14 days). Mice were necropsied on days 1, 4, 8 and 14 post-infection and lungs were assessed for virus titers, lung inflammation, immune cytokine expression and pulmonary responsiveness (PR) to inhaled methacholine. Exposure to DE during the course of infection caused an increase in viral titers at days 4 and 8 post-infection, which was associated with increased neutrophils and protein in the BAL, and an early increase in PR. Increased virus load was not caused by decreased interferon levels, since IFN-β levels were enhanced in these mice. Expression and production of IL-4 was significantly increased on day 1 and 4 p.i. while expression of the Th1 cytokines, IFN-γ and IL-12p40 was decreased. Treatment with the antioxidant N-acetylcysteine did not affect diesel-enhanced virus titers but blocked the DE-induced changes in cytokine profiles and lung inflammation. We conclude that exposure to DE during an influenza infection polarizes the local immune responses to an IL-4 dominated profile in association with increased viral disease, and some aspects of this effect can be reversed with antioxidants.
Nociceptor-Expressed Ephrin-B2 Regulates Inflammatory and Neuropathic Pain
Authors: Zhao Jing , Yuan Guanglu , Cendan Cruz M , Nassar Mohammed A , Lagerström Malin C , Kullander Klas , Gavazzi Isabella , Wood John N 
Published: November 2010

Background: EphB receptors and their ephrin-B ligands play an important role in nervous system development, as well as synapse formation and plasticity in the adult brain. Recent studies show that intrathecal treatment with EphB-receptor activator ephrinB2-Fc induced thermal hyperalgesia and mechanical allodynia in rat, indicating that ephrin-B2 in small dorsal root ganglia (DRG) neurons and EphB receptors in the spinal cord modulate pain processing. To examine the role of ephrin-B2 in peripheral pain pathways, we deleted ephrin-B2 in Nav1.8+ nociceptive sensory neurons with the Cre-loxP system. Sensory neuron numbers and terminals were examined using neuronal makers. Pain behavior in acute, inflammatory and neuropathic pain models was assessed in the ephrin-B2 conditional knockout (CKO) mice. We also investigated the c-Fos expression and NMDA receptor NR2B phosphorylation in ephrin-B2 CKO mice and littermate controls. Results: The ephrin-B2 CKO mice were healthy with no sensory neuron loss. However, pain-related behavior was substantially altered. Although acute pain behavior and motor co-ordination were normal, inflammatory pain was attenuated in ephrin-B2 mutant mice. Complete Freund's adjuvant (CFA)-induced mechanical hyperalgesia was halved. Formalin-induced pain behavior was attenuated in the second phase, and this correlated with diminished tyrosine phosphorylation of N-methyl-D-aspartic acid (NMDA) receptor subunit NR2B in the dorsal horn. Thermal hyperalgesia and mechanical allodynia were significantly reduced in the Seltzer model of neuropathic pain. Conclusions: Presynaptic ephrin-B2 expression thus plays an important role in regulating inflammatory pain through the regulation of synaptic plasticity in the dorsal horn and is also involved in the pathogenesis of some types of neuropathic pain.
Development of a duodenal gallstone ileus with gastric outlet obstruction (Bouveret syndrome) four months after successful treatment of symptomatic gallstone disease with cholecystitis and cholangitis: a case report
Authors: Giese Arnd , Zieren Jürgen , Winnekendonk Guido , Henning Bernhard F 
Published: November 2010

Abstract

Introduction
Cases of gallstone ileus account for 1% to 4% of all instances of mechanical bowel obstruction. The majority of obstructing gallstones are located in the terminal ileum. Less than 10% of impacted gallstones are located in the duodenum. A gastric outlet obstruction secondary to a gallstone ileus is known as Bouveret syndrome. Gallstones usually enter the bowel through a biliary enteral fistula. Little is known about the formation of such fistulae in the course of gallstone disease.

Case presentation
We report the case of a 72-year-old Caucasian woman born in Germany with a gastric outlet obstruction due to a gallstone ileus (Bouveret syndrome), with a large gallstone impacted in the third part of the duodenum. Diagnostic investigations of our patient included plain abdominal films, gastroscopy and abdominal computed tomography, which showed a biliary enteric fistula between the gallbladder and the duodenal bulb. Our patient was successfully treated by laparotomy, duodenotomy, extraction of the stone, cholecystectomy, and resection of the fistula in a one-stage surgical approach. Histopathological examination showed chronic and acute cholecystitis, with perforated ulceration of the duodenal wall and acute purulent inflammation of the surrounding fatty tissue. Four months prior to developing a gallstone ileus our patient had been hospitalized for cholecystitis, a large gallstone in the gallbladder, cholangitis and a small obstructing gallstone in the common biliary duct. She had been treated with endoscopic retrograde cholangiopancreatography, endoscopic biliary sphincterotomy, balloon extraction of the common biliary duct gallstone, and intravenous antibiotics. At the time of her first presentation, abdominal ultrasound and endoscopic examination (including esophagogastroduodenoscopy and endoscopic retrograde cholangiopancreatography) had not shown any evidence of a biliary enteral fistula. In the four months preceding the gallstone ileus our patient had been asymptomatic.

Conclusion
In patients known to have gallstone disease presenting with symptoms of ileus, the differential diagnosis of a gallstone ileus should be considered even in the absence of preceding symptoms related to the gallbladder disease. Gallstones large enough to cause intestinal obstruction usually enter the bowel by a biliary enteral fistula. During the formation of such a fistula, patients can be asymptomatic.
Estrogen receptor α (ERα) mediates 17β-estradiol (E2)-activated expression of HBO1
Authors: Wang Wen-zhong , Liu Hai-ou , Wu Yi-hong , Hong Yi , Yang Jun-wu , Liu Ye-heng , Wu Wei-bin , Zhou Lei , Sun Lin-lin , Xu Jie-jie , Yun Xiao-jing , Gu Jian-xin 
Published: November 2010

AbstractBackgroundHBO1 (histone acetyltransferase binding to ORC1) is a histone acetyltransferase (HAT) which could exert oncogenic function in breast cancer. However, the biological role and underlying mechanism of HBO1 in breast cancer remains largely unknown. In the current study, we aimed to investigate the role of HBO1 in breast cancer and uncover the underlying molecular mechanism.MethodsImmunohistochemistry was applied to detect HBO1 protein expression in breast cancer specimens (n = 112). The expression of protein level was scored by integral optical density (IOD) for further statistical analyses using SPSS. Real-time PCR was used to simultaneously measure mRNA levels of HBO1. The HBO1 protein expression in breast cancer cells was confirmed by western blot.ResultsHBO1 was highly expressed in breast cancer tissues and significantly correlated with estrogen receptor α (ERα) (p < 0.001) and progestational hormone (PR) (p = 0.002). HBO1 protein level also correlated positively with histology grade in ERα positive tumors (p = 0.016) rather than ERα negative tumors. 17β-estradiol (E2) could upregulate HBO1 gene expression which was significantly inhibited by ICI 182,780 or ERα RNAi. E2-increased HBO1 protein expression was significantly suppressed by treatment with inhibitor of MEK1/2 (U0126) in T47 D and MCF-7 cells.ConclusionsHBO1 was an important downstream molecule of ERα, and ERK1/2 signaling pathway may involved in the expression of HBO1 increased by E2.
miRNA-145 inhibits non-small cell lung cancer cell proliferation by targeting c-Myc
Authors: Chen Zhe , Zeng Huazong , Guo Yong , Liu Pei , Pan Hui , Deng Anmei , Hu Jian 
Published: November 2010

Abstract
MicroRNAs are important gene regulators that potentially play a profound role in tumorigenesis. Increasing evidence indicates that miR-145 is a tumor suppressor capable of inhibiting breast and colon cancer cell growth both in vitro and in vivo. However, the biological function of miR-145 in non-small cell lung cancer (NSCLC) is largely unknown. In colon cancer cells, c-Myc is a confirmed direct target for miR-145. The aim of this work was to investigate the effect of miR-145 and c-Myc on proliferation of NSCLC cells, using the NSCLC cell lines A549 and H23 as models. We determined the expression level of miR-145 in tumor tissues relative to adjacent non-tumor tissues, and in NSCLC cell lines relative to non-malignant lung cells. Downregulation of miR-145 was seen in tumor tissues and the two NSCLC cell lines by real-time quantitative reverse transcription polymerase chain reaction. MTT and focus formation assays were conducted to measure cell proliferation rates. Cell growth was inhibited and the G1/S transition was blocked by miR-145 in transfection assays of A549 and H23 cells. We further showed that c-Myc was a direct target for miR-145. Introduction of miR-145 dramatically suppressed the c-Myc/eIF4E pathway, which was demonstrated to be crucial for cell proliferation in NSCLC cells. Furthermore, we found that CDK4 was regulated by miR-145 in cell cycle control. Taken together, our study results demonstrate that miR-145 inhibits proliferation of NSCLC cells through c-Myc. Increasing miR-145 expression may provide a novel approach for the treatment of NSCLC.
Regulators of ribonucleotide reductase inhibit Ty1 mobility in saccharomyces cerevisiae
Authors: O'Donnell John P , Gehman Marie , Keeney Jill B 
Published: November 2010

AbstractBackgroundTy1 is a long terminal repeat retrotransposon ofSaccharomyces cerevisiae, with a replication cycle similar to retrovirus replication. Structurally, Ty1 contains long terminal repeat (LTR) regions flanking thegagandpolgenes that encode for the proteins that enable Ty1 mobility. Reverse transcriptase produces Ty1 complementary (c)DNA that can either be integrated back into the genome by integrase or recombined into the yeast genome through homologous recombination. The frequency of Ty1 mobility is temperature sensitive, with optimum activity occurring at 24-26°C.ResultsIn this study, we identified two host genes that when deleted allow for high temperature Ty1 mobility:RFX1andSML1. The protein products of these genes are both negative regulators of the enzyme ribonucleotide reductase, a key enzyme in regulating deoxyribonucleotide triphosphate (dNTP) levels in the cell. Processing of Ty1 proteins is defective at high temperature, and processing is not improved in eitherrfx1orsml1deletion strains. Ty1 mobility at high temperature is mediated by homologous recombination of Ty1 cDNA to Ty1 elements within the yeast genome. We quantified cDNA levels in wild type,rfx1andsml1deletion background strains at different temperatures. Southern blot analysis demonstrated that cDNA levels were not markedly different between the wild type and mutant strains as temperatures increased, indicating that the increased Ty1 mobility is not a result of increased cDNA synthesis in the mutant strains. Homologous recombination efficiency was increased in bothrfx1andsml1deletion strains at high temperatures; therfx1deletion strain also had heightened homologous recombination efficiency at permissive temperatures. In the presence of the dNTP reducing agent hydroxyurea at permissive temperatures, Ty1 mobility was stimulated in the wild type andsml1deletion strains but not in therfx1deletion strain. Mobility frequency was greatly reduced in all strains at high temperature. Deletion of the S-phase checkpoint pathway Dun1 kinase, which inactivates Sml1 and Rfx1, reduced Ty1 mobility at a range of temperatures.ConclusionsLevels of cellular dNTPs, as regulated by components of the S-phase checkpoint pathway, are a limiting factor in homologous recombination-mediated Ty1 mobility.
Prospective comparison of switches in biomarker status between primary and recurrent breast cancer: the Breast Recurrence In Tissues Study (BRITS)
Authors: Thompson Alastair M , Jordan Lee B , Quinlan Philip , Anderson Elizabeth , Skene Anthony , Dewar John A , Purdie Colin A ,   the Breast Recurrence in Tissues Study Group
Published: November 2010

Abstract
Introduction
Immunohistochemistry of primary breast cancer is routinely used to guide changes in therapy at the time of relapse. Retrospective reviews suggest that the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor type 2 (HER2) receptor may differ between the primary and loco-regional recurrence or distant metastases. The Breast Recurrence In Tissues Study (BRITS) was a large, multicentre, prospective study to examine changes in ER, PR and HER2.

Methods
Matched primary and recurrent breast cancer tissue samples were prospectively collected from 205 women attending 20 institutions. Central laboratory immunohistochemical analysis of core biopsies and tissue microarrays of ER and PR using the Allred and Quickscore methods and HER2 (confirmed by fluorescence in situ hybridisation (FISH) for HER2 2+) were performed.

Results
From 205 consenting women, 18 (8.8%) did not have recurrent disease on biopsy, 35 were ineligible, 13 had insufficient paired tissue and 2 were excluded for safety reasons. Paired samples from 137 women, mean age 62.6 years (range 27-87 years), 83/137 (60.6%) postmenopausal with a median 92.2 months (range 5-327 months) from primary to recurrence and 88 (64.2%) as locoregional recurrence were successfully analysed. A switch in receptor status, in either direction, by Allred score, was identified for ER in 14 patients (10.2%; P = 0.983 Wilcoxon sign rank test), PR in 34 (24.8%; P = 0.003 Wilcoxon sign rank test) and HER2 in 4 (2.9%; P = 0.074 Wilcoxon sign rank test). There was no difference between locoregional or distant recurrence in the proportion who switched. The switch in receptor status led to a change in the subsequent treatment plan for 24 patients (17.5%).

Conclusions
This prospective study confirms retrospective evidence that the management of relapsed breast cancer should include confirmatory tissue sampling and identify switches of ER, PR or HER2 which change therapeutic management for one in six patients.
Cystatin M loss is associated with the losses of estrogen receptor, progesterone receptor, and HER4 in invasive breast cancer
Authors: Ko Eunkyung , Park Seong-Eun , Cho Eun Yoon , Kim Yujin , Hwang Jung-Ah , Lee Yeon-Su , Nam Seok Jin , Bang Saik , Park Joobae , Kim Duk-Hwan 
Published: November 2010

Abstract
Introduction
This study was aimed at understanding the clinicopathological significance of cystatin M loss, and investigating possible factors responsible for cystatin M loss in breast cancer.

Methods
The expression of estrogen receptor (ER), progesterone receptor (PR), HER2, HER4, and cystatin M was retrospectively analyzed using immunohistochemistry in 117 patients with ductal carcinoma in situ (DCIS) and in 175 patients with invasive breast cancer (IBC). The methylation status of CST6 gene encoding cystatin M was evaluated using methylation-specific polymerase chain reaction (PCR) in formalin-fixed paraffin-embedded tissues from 292 participants and using pyrosequencing in fresh-frozen tumor and matched normal tissues from 51 IBC patients.

Results
Cystatin M loss was found in 9 (8%) of 117 patients with DCIS and in 99 (57%) of 175 with invasive breast cancer (IBC) (P < 0.0001). Cystatin M loss was found in 58 (57%) of 101 HER2-negative IBCs and in 41 (55%) of 74 HER2-positive IBCs, and this difference was not statistically significant (P = 0.97). However, cystatin M loss was significantly associated with the loss of ER (P = 0.01), PR (P = 0.002), and HER4 (P = 0.003) in IBCs. Cystatin M loss occurred in 34 (76%) of the 45 HER4-negative IBCs and in 65 (50%) of the 130 HER4-positive IBCs. Multivariate analysis showed that cystatin M loss occurred at a 3.57 times (95% CI = 1.28 to 9.98; P = 0.01) higher prevalence in the triple-negative IBCs of ER, PR, and HER4 than in other subtypes, after adjusting for age. The quantity of CST6 methylation was associated with ER loss (P = 0.0002) in IBCs but not with the loss of PR (P = 0.64) or HER4 (P = 0.87).

Conclusions
The present study suggests that cystatin M loss may be associated with the losses of ER, PR, and HER4 in IBC.
Validation of a new transpulmonary thermodilution system to assess global end-diastolic volume and extravascular lung water
Authors: Bendjelid Karim , Giraud Raphael , Siegenthaler Nils , Michard Frederic 
Published: November 2010

Abstract
Introduction
A new system has been developed to assess global end-diastolic volume (GEDV), a volumetric marker of cardiac preload, and extravascular lung water (EVLW) from a transpulmonary thermodilution curve. Our goal was to compare this new system with the system currently in clinical use.

Methods
Eleven anesthetized and mechanically ventilated pigs were instrumented with a central venous catheter and a right (PulsioCath; Pulsion, Munich, Germany) and a left (VolumeView™; Edwards Lifesciences, Irvine, CA, USA) thermistor-tipped femoral arterial catheter. The right femoral catheter was used to measure GEDV and EVLW using the PiCCO2™ (Pulsion) method (GEDV1 and EVLW1, respectively). The left femoral catheter was used to measure the same parameters using the new VolumeView™ (Edwards Lifesciences) method (GEDV2 and EVLW2, respectively). Measurements were made during inotropic stimulation (dobutamine), during hypovolemia (bleeding), during hypervolemia (fluid overload), and after inducing acute lung injury (intravenous oleic acid).

Results
One hundred and thirty-seven paired measurements were analyzed. GEDV1 and GEDV2 ranged from 701 to 1,629 ml and from 774 to 1,645 ml, respectively. GEDV1 and GEDV2 were closely correlated (r2 = 0.79), with mean bias of -11 ± 80 ml and percentage error of 14%. EVLW1 and EVLW2 ranged from 507 to 2,379 ml and from 495 to 2,222 ml, respectively. EVLW1 and EVLW2 were closely correlated (r2 = 0.97), with mean bias of -5 ± 72 ml and percentage error of 15%.

Conclusions
In animals, and over a very wide range of values, a good agreement was found between the new VolumeView™ system and the PiCCO™ system to assess GEDV and EVLW.