tbuckley/cabot-search huggingface dataset:
Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-2 Fusion cDNA for Cancer Gene Immunotherapy
Authors: John Stagg, Jian Hui Wu, Nathaniel Bouganim, Jacques Galipeau
Journal: Cancer Research (2004)

Abstract Genetic engineering of tumor cells to express both granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-2 can induce synergistic immune antitumor effects. Paradoxically, the combination has also been reported to down-regulate certain immune functions, highlighting the unpredictability of dual cytokine use. We hypothesized that a GM-CSF and IL-2 fusion transgene (GIFT) could circumvent such limitations yet preserve synergistic features. We designed a fusion cDNA of murine GM-CSF and IL-2. Protein structure computer modeling of GIFT protein predicted for intact ligand binding domains for both cytokines. B16 mouse melanoma cells were gene modified to express GIFT (B16GIFT), and these cells were unable to form tumors in C57bl/6 mice. Irradiated B16GIFT whole-cell tumor vaccine could also induce absolute protective immunity against challenge by live B16 cells. In mice with established melanoma, B16GIFT therapeutic cellular vaccine significantly improved tumor-free survival when compared with B16 expressing both IL-2 and GM-CSF. We show that GIFT induced a significantly greater tumor site recruitment of macrophages than combined GM-CSF and IL-2 and that macrophage recruitment arises from novel chemotactic feature of GIFT. In contrast to suppression by GM-CSF of natural killer (NK) cell recruitment despite coexpression of IL-2, GIFT leads to significant functional NK cell infiltration as confirmed in NK-defective beige mice. In conclusion, we demonstrated that a fusion between GM-CSF and IL-2 can invoke greater antitumor effect than both cytokines in combination, and novel immunobiological properties can arise from such chimeric constructs.
Arrhythmias and cellular electrophysiological changes during myocardial "ischaemia" and reperfusion
Authors: W. J PENNY, D. J SHERIDAN
Journal: Cardiovascular Research (1983)

Journal Article Arrhythmias and cellular electrophysiological changes during myocardial "ischaemia" and reperfusion Get access WILLIAM J PENNY, WILLIAM J PENNY From the Department of Cardiology, Welsh National School of Medicine, Cardiff Reprint requests to: Dr D J Sheridan, Department of Cardiology, WNSM, Cardiff, CF4 4XN. Search for other works by this author on: Oxford Academic PubMed Google Scholar DESMOND J SHERIDAN DESMOND J SHERIDAN From the Department of Cardiology, Welsh National School of Medicine, Cardiff Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 17, Issue 6, June 1983, Pages 363–372, https://doi.org/10.1093/cvr/17.6.363 Published: 01 June 1983
Lung exposure to nanoparticles modulates an asthmatic response in a mouse model
Authors: S. Hussain, J.A.J. Vanoirbeek, K. Luyts, V. De Vooght, E. Verbeken, L.C.J. Thomassen, J.A. Martens, D. Dinsdale, S. Boland, F. Marano, B. Nemery, P.H.M. Hoet
Journal: European Respiratory Journal (2010)

The aim of this study was to investigate the modulation of an asthmatic response by titanium dioxide (TiO 2 ) or gold (Au) nanoparticles (NPs) in a murine model of diisocyanate-induced asthma. On days 1 and 8, BALB/c mice received 0.3% toluene diisocyanate (TDI) or the vehicle acetone–olive oil (AOO) on the dorsum of both ears (20 μL). On day 14, the mice were oropharyngeally dosed with 40 μL of a NP suspension (0.4 mg·mL −1 (∼0.8 mg·kg −1 ) TiO 2 or Au). 1 day later (day 15), the mice received an oropharyngeal challenge with 0.01% TDI (20 μL). On day 16, airway hyperreactivity (AHR), bronchoalveolar lavage (BAL) cell and cytokine analysis, lung histology, and total serum immunoglobulin E were assessed. NP exposure in sensitised mice led to a two- (TiO 2 ) or three-fold (Au) increase in AHR, and a three- (TiO 2 ) or five-fold (Au) increase in BAL total cell counts, mainly comprising neutrophils and macrophages. The NPs taken up by BAL macrophages were identified by energy dispersive X-ray spectroscopy. Histological analysis revealed increased oedema, epithelial damage and inflammation. In conclusion, these results show that a low, intrapulmonary doses of TiO 2 or Au NPs can aggravate pulmonary inflammation and AHR in a mouse model of diisocyanate-induced asthma.
Effects of Acute Volume Expansion and Altered Hemodynamics on Renal Tubular Function in Chronic Caval Dogs
Authors: Mortimer Levy
Journal: Journal of Clinical Investigation (1972)

It is well established that dogs with chronic partial constriction of the thoracic inferior vena cava develop sodium retention, ascites, and respond poorly to acute saline loading. A group of such chronic caval dogs, and a group of normal controls were studied during hydropenia, and again after acute saline loading by clearance and recollection micropuncture techniques. After volume expansion, the caval dogs excreted 52 muEq/min per kidney of sodium compared with 370 muEq/min per kidney for the normal controls. During hydropenia and after the saline infusions, single nephron filtration rates, fractional reabsorption of sodium within the proximal tubule, and proximal delivery of filtrate to the distal nephron were comparable in both groups of dogs. Micropuncture of distal tubular segments confirmed that the loop of Henle was the major site for salt and water retention in the expanded caval dogs. Alteration of intrarenal hemodynamics by vasodilating one kidney and elevating systemic arterial blood pressure induced a normal natriuretic response in the saline-loaded caval dogs. Proximal tubular function remained unchanged and the loop of Henle appeared to be the major site responsive to these hemodynamic maneuvers. These same experiments in saline-loaded control dogs had no effect on function of the proximal or distal nephron and did not increase urinary excretion of sodium or water. These experiments provide evidence that the loop of Henle is the major site for sodium retention in volume-expanded chronic caval dogs excreting minimal amounts of sodium.
Arterial stiffness in systemic scleroderma patients with restrictive lung disease
Authors: Nina Karoli, Andrey Rebrov
Journal: European Respiratory Journal (2011)

Systemic sclerosis (SSc) is a chronic disease of unknown etiology, characterized by enhanced fibrosis, and microvascular abnormalities.  To study the stiffness of large arteries in relation to the restrictive lung disease (RLD) aortic stiffness was examined in patients with systemic sclerosis (SSc).  27 non-smoking patients (52,48±7,18 yrs) with diagnosis of SS were included. 17 patient was with RLD (FVC  We noted significantly differences of arterial stiffness parameters between pts with RLD and healthy subjects.  Arterial stiffness infringement in patient without RLD was less experience. We noted decreased differentiation between central and peripheral blood pressure (BP) and increased differentiation between central and peripheral arterial stiffness (index AIxAo/AixB).
Steroids in Idiopathic Pulmonary Fibrosis Acute Exacerbation: Defenders or Killers?
Authors: Spyros A. Papiris, Effrosyni D. Manali, Likourgos Kolilekas, Christina Triantafillidou, Iraklis Tsangaris, Konstantinos Kagouridis
Journal: American Journal of Respiratory and Critical Care Medicine (2012)
Display of Fas Ligand Protein on Cardiac Vasculature as a Novel Means of Regulating Allograft Rejection
Authors: Nadir Askenasy, Esma S. Yolcu, Zhiliang Wang, Haval Shirwan
Journal: Circulation (2003)

Background— Fas ligand (FasL) is a potent death-inducing molecule with important functions in immune homeostasis and tolerance to self-antigens. The complex biological activities of FasL and its inefficient expression using conventional gene transfer approaches limit its use for immunomodulation to prevent allograft rejection. We have recently generated a chimeric FasL with core streptavidin (SA-FasL) with potent apoptotic activity and designed a novel approach to display it on the surface of several cell types via biotinylation. We herein tested whether SA-FasL can also be displayed on vascular endothelial cells in the heart and examined its effect on graft survival after transplantation into syngeneic and allogeneic hosts. Methods and Results— SA-FasL was efficiently displayed on the vasculature of BALB/c hearts with a half-life of 9 days in vivo. Transplantation of hearts displaying SA-FasL into syngeneic hosts resulted in indefinite graft survival without detectable toxicity to the grafts and hosts. In contrast, transplantation of allogeneic C57BL/10 hearts displaying SA-FasL into BALB/c recipients resulted in graft rejection, but in a delayed fashion as compared with control hearts (mean survival time=17.4±5 versus 9.6±1 days). Allograft survival was further extended to 21±2.6 and 24±3 days ( P &lt;0.05) by intravenous treatment of graft recipients with 1 dose of SA-FasL–decorated donor splenocytes on days 2 and 6 after transplantation, respectively. Conclusions— This study shows for the first time that exogenous proteins can be displayed on the endothelium of solid organs for therapeutic purposes. This approach provides a convenient and rapid means of displaying exogenous proteins on the surface of cells, tissues, and solid organs, with broad research and therapeutic implications.
Classification of Epstein–Barr Virus–Positive Gastric Cancers by Definition of DNA Methylation Epigenotypes
Authors: Keisuke Matsusaka, Atsushi Kaneda, Genta Nagae, Tetsuo Ushiku, Yasuko Kikuchi, Rumi Hino, Hiroshi Uozaki, Yasuyuki Seto, Kenzo Takada, Hiroyuki Aburatani, Masashi Fukayama
Journal: Cancer Research (2011)

Epstein-Barr virus (EBV) is associated with Burkitt lymphoma, nasopharyngeal carcinoma, opportunistic lymphomas in immunocompromised hosts, and a fraction of gastric cancers. Aberrant promoter methylation accompanies human gastric carcinogenesis, though the contribution of EBV to such somatic methylation changes has not been fully clarified. We analyzed promoter methylation in gastric cancer cases with Illumina's Infinium BeadArray and used hierarchical clustering analysis to classify gastric cancers into 3 subgroups: EBV(-)/low methylation, EBV(-)/high methylation, and EBV(+)/high methylation. The 3 epigenotypes were characterized by 3 groups of genes: genes methylated specifically in the EBV(+) tumors (e.g., CXXC4, TIMP2, and PLXND1), genes methylated both in EBV(+) and EBV(-)/high tumors (e.g., COL9A2, EYA1, and ZNF365), and genes methylated in all of the gastric cancers (e.g., AMPH, SORCS3, and AJAP1). Polycomb repressive complex (PRC) target genes in embryonic stem cells were significantly enriched among EBV(-)/high-methylation genes and commonly methylated gastric cancer genes (P = 2 × 10(-15) and 2 × 10(-34), respectively), but not among EBV(+) tumor-specific methylation genes (P = 0.2), suggesting a different cause for EBV(+)-associated de novo methylation. When recombinant EBV was introduced into the EBV(-)/low-methylation epigenotype gastric cancer cell, MKN7, 3 independently established subclones displayed increases in DNA methylation. The promoters targeted by methylation were mostly shared among the 3 subclones, and the new methylation changes caused gene repression. In summary, DNA methylation profiling classified gastric cancer into 3 epigenotypes, and EBV(+) gastric cancers showed distinct methylation patterns likely attributable to EBV infection.
Fibromyalgia and carpal tunnel syndrome
Authors: F PEREZ-RUIZ, M CALABOZO, A ALONSO-RUIZ, E RUIZ-LUCEA;, M. A CIMMINO, M. PARISI, G. MOGGIANA, S. ACCARDO
Journal: Annals of the Rheumatic Diseases (1997)

Recently, Cimmino et al 1 reported an epidemiological survey on the prevalence of carpal tunnel syndrome (CTS) in patients with fibromyalgia syndrome (FM). These authors found that 9.7% of 93 patients studied after mailing a questionaire had both CTS and FM, suggesting an association between them and that there were possible similarities in the aetiopathological mechanisms.

Cimmino et al referred to our previous report on CTS and FM2 in which we observed 33 patients with CTS in a group of 206 consecutive FM patients (16%), and they suggest that this 16% means that underlaying mechanisms may be common for CTS and FM.

We cannot agree with this suggestion. Our study was not controlled, but no statistically significant differences could be appreciated in the prevalence of CTS in FM women (29 of 191) from our series with that in general population women reported by de Krom et al (35 of 340).3 On the other hand, we noticed that CTS had been overlooked in 27 of 191 (14.1%) women with FM in our series despite mean duration of CTS symptoms of 8.1 years (range 6 months to 15 years)2 while only 23 of 340 (6.7%) women …
Expression of the T-cell regulatory marker FOXP3 in primary cutaneous large B-cell lymphoma tumour cells
Authors: M. Felcht, M. Heck, C. Weiss, J.C. Becker, E. Dippel, C.S.L. Müller, D. Nashan, M.M. Sachse, J.P. Nicolay, N. Booken, S. Goerdt, C.-D. Klemke
Journal: British Journal of Dermatology (2012)

Primary cutaneous B-cell lymphomas (PCBCL) are subdivided into the aggressive form, primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL, LT) and two subtypes of indolent behaviour (primary cutaneous follicle centre lymphoma and primary cutaneous marginal zone B-cell lymphoma). The difference in clinical behaviour can be explained by the tumour cell itself, or the lymphoma microenvironment including the antitumour immune response.To investigate the presence of regulatory T cells (Treg), CD4+CD25+FOXP3+, in the microenvironment of PCBCL in correlation with clinical outcome.Tumour specimens of 55 consecutive cases of PCBCL were blinded and analysed for FOXP3, CD4 and CD25 expression by immunohistochemistry. Confocal images were taken with a Leica SP5. Statistical analyses were performed to determine significance. The test was considered significant when P<0.05.The CD4 and FOXP3 expression as well as the CD4/FOXP3 ratio were significantly increased in PCBCL of indolent behaviour in contrast to PCLBCL, LT (P=0.0002 for CD4, P<0.0001 for FOXP3 and P=0.0345 for FOXP3/CD4 ratio). CD25 expression did not differ in the three groups (P=0.9414). Within the group of patients with PCLBCL, LT we identified a subgroup with FOXP3+ tumour cells as demonstrated by CD20/FOXP3 double stainings. Patients with FOXP3+ PCLBCL, LT tumour cells showed a better prognosis on Kaplan-Meier analysis.High numbers of Treg in the lymphoma microenvironment correlate with a better prognosis in PCBCL. In PCLBCL, LT the presence of FOXP3+ tumour cells is beneficial for prognosis suggesting that FOXP3 expression of PCLBCL, LT tumour cells might serve as a tumour suppressor.
A Clinical Experience With an Implanted Mechanical Auxiliary Ventricle
Authors: Adrian Kantrowitz
Journal: JAMA (1966)

A mechanical auxiliary ventricle for intermittent permanent assistance was implanted Feb 4, 1966, in a 33year-old man with intractable left ventricular failure due to idiopathic cardiomyopathy. When the ventricle began functioning, systemic pressure was returned to normal as was left auricular pressure. During the immediate postoperative period the patient maintained fair stability with arterial pressure remaining at physiologic levels. The patient's sensorium appeared normal postoperatively. His activity required sedation. No unusual sensations related to the implantation were reported. Despite a good clinical picture, a constantly increasing pulse rate rose to 160 to 180 beats per minute. Eleven hours postoperatively his left auricular and central venous pressure rose sharply while peripheral arterial pressure fell. The patient died 20 hours and 30 minutes following completion of the operation. Cause of death is not fully understood but may be related to prolonged uncontrollable tachycardia.
Epigenetic Modification of the Renin-Angiotensin System in the Fetal Programming of Hypertension
Authors: Irina Bogdarina, Simon Welham, Peter J. King, Shamus P. Burns, Adrian J.L. Clark
Journal: Circulation Research (2007)

Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Lifelong environmental factors (eg, salt intake, obesity, alcohol) and genetic factors clearly contribute to the development of hypertension, but it has also been established that stress in utero may program the later development of the disease. This phenomenon, known as fetal programming can be modeled in a range of experimental animal models. In maternal low protein diet rat models of programming, administration of angiotensin converting enzyme inhibitors or angiotensin receptor antagonists in early life can prevent development of hypertension, thus implicating the renin-angiotensin system in this process. Here we show that in this model, expression of the AT(1b) angiotensin receptor gene in the adrenal gland is upregulated by the first week of life resulting in increased receptor protein expression consistent with the increased adrenal angiotensin responsiveness observed by others. Furthermore, we show that the proximal promoter of the AT(1b) gene in the adrenal is significantly undermethylated, and that in vitro, AT(1b) gene expression is highly dependent on promoter methylation. These data suggest a link between fetal insults to epigenetic modification of genes and the resultant alteration of gene expression in adult life leading ultimately to the development of hypertension. It seems highly probable that similar influences may be involved in the development of human hypertension.
Antibodies From Preeclamptic Patients Stimulate Increased Intracellular Ca <sup>2+</sup> Mobilization Through Angiotensin Receptor Activation
Authors: Theingi M. Thway, Sergiy G. Shlykov, Mary-Clare Day, Barbara M. Sanborn, Larry C. Gilstrap, Yang Xia, Rodney E. Kellems
Journal: Circulation (2004)

Preeclampsia is a serious disorder of pregnancy characterized by hypertension, proteinuria, edema, and coagulation and vascular abnormalities. At the cellular level, abnormalities include increased calcium concentration in platelets, lymphocytes, and erythrocytes. Recent studies have shown that antibodies directed against angiotensin II type I (AT1) receptors are also highly associated with preeclampsia.We tested the hypothesis that AT1 receptor-agonistic antibodies (AT1-AAs) could activate AT1 receptors, leading to an increased intracellular concentration of free calcium and to downstream activation of Ca2+ signaling pathways. Sera of 30 pregnant patients, 16 diagnosed with severe preeclampsia and 14 normotensive, were examined for the presence of IgG capable of stimulating intracellular Ca2+ mobilization. IgG from all preeclamptic patients activated AT1 receptors and increased intracellular free calcium. In contrast, none of the normotensive individuals had IgG capable of activating AT1 receptors. The specific mobilization of intracellular Ca2+ by AT1-AAs was blocked by losartan, an AT1 receptor antagonist, and by a 7-amino-acid peptide that corresponds to a portion of the second extracellular loop of the AT1 receptor. In addition, we have shown that AT1-AA-stimulated mobilization of intracellular Ca2+ results in the activation of the transcription factor, nuclear factor of activated T cells.These results suggest that maternal antibodies capable of activating AT1 receptors are likely to account for increased intracellular free Ca2+ concentrations and changes in gene expression associated with preeclampsia.
Clinical Significance and Prognostic Value of microRNA Expression Signatures in Hepatocellular Carcinoma
Authors: Rongrong Wei, Guo-Liang Huang, Mei-Yin Zhang, Bin-Kui Li, Hui-Zhong Zhang, Ming Shi, Xiao-Qian Chen, Long Huang, Qing-Ming Zhou, Wei-Hua Jia, X.F. Steven Zheng, Yun-Fei Yuan, Hui-Yun Wang
Journal: Clinical Cancer Research (2013)

MicroRNAs (miRNAs) play important roles in the development and progression of cancer. The aim of this study is to identify miRNA expression signatures in hepatocellular carcinoma and delineate their clinical significance for hepatocellular carcinoma.Patients with hepatocellular carcinoma, undergoing hepatectomy were randomly divided into training set (60 patients) and test set (50 patients). Other 56 patients were used as an independent cohort. The miRNA expression levels were detected by microarray and verified by quantitative real-time reverse transcription-PCR (qRT-PCR).A 30-miRNA signature consisting of 10 downregulated and 20 upregulated miRNAs was established for distinguishing hepatocellular carcinoma from noncancerous liver tissues in the training set with 99.2% accuracy. The classification accuracies of this signature were 97% and 90% in the test set and independent cohort, respectively. The expression level of four miRNAs in the 30-miRNA signature was verified by qRT-PCR in the training set. Twenty miRNAs were then selected to construct prognostic signature in the training set. Of the 20 miRNAs, six were risk factors and 14 were protective factors. A formula based on the 20 miRNAs was built to compute prognostic index. Kaplan-Meier analysis showed that patients with a higher prognostic index had a significantly lower survival than those with a low index. This was verified in the test and independent sets. Multivariate analysis indicated that the 20-miRNA signature was an independent prognostic predictor.The 30- and 20-miRNA signatures identified in this study should provide new molecular approaches for diagnosis and prognosis of patients with hepatocellular carcinoma and clues for elucidating molecular mechanism of hepatocarcinogenesis.
Transformation of the education of health professionals in China: progress and challenges
Authors: Jianlin Hou, Catherine Michaud, Zhihui Li, Zhe Dong, Baozhi Sun, Junhua Zhang, Depin Cao, Xuehong Wan, Cheng Zeng, Bo Wei, Lijian Tao, Xiaosong Li, Weimin Wang, Yingqing Lu, Xiulong Xia, Guifang Guo, Zhiyong Zhang, Yunfei Cao, Yuanzhi Guan, Qingyue Meng, Qing Wang, Yuhong Zhao, Huaping Liu, Huiqing Lin, Yang Ke, Lincoln Chen
Journal: The Lancet (2014)
The Relationship between Serum Osteopontin Levels and Isolated Coronary Artery Ectasia
Authors: Abdulkadir Yıldız, Onder Bilge, Mehmet Zihni Bilik, Mehmet Ata Akil, Mustafa Oylumlu, Halil Akin, Bernas Altintas, Murat Yuksel, Halit Acet, Nihat Polat, Mesut Aydin, Hasan Kaya, Sait Alan
Journal: Journal of the American College of Cardiology (2013)
Phase II trial of pemetrexed-based induction chemotherapy followed by concomitant chemoradiotherapy in previously irradiated patients with squamous cell carcinoma of the head and neck
Authors: V.M. Villaflor, D. Haraf, J.K. Salama, M. Kocherginsky, A. Langerman, G. Gomez-Abuin, P. Beniwal, E.A. Blair, K.M. Stenson, L. Portugal, T. Seiwert, R.D. Williams, A.J. Dekker, M.E. Witt, E.E. Vokes, E.E.W. Cohen
Journal: Annals of Oncology (2011)