tbuckley/cabot-search huggingface dataset:
Selective enrichment of major histocompatibility complex class II-specific autoreactive T cells in the thymic Thy0 subset.
Authors: I Kariv, R R Hardy, K Hayakawa
Journal: The Journal of Experimental Medicine (1993)

We show here a unique enrichment of autoreactive T cells in the CD4+ mouse thymic subset, Thy0. A single- and 10-cell AMLR (autologous mixed leukocyte reaction) assay demonstrates that more than 30% (one cell per well) and almost all (10 cells per well) Thy0 cultures from normal mice exhibit reactivity specific to autologous cells, resulting in induction of interleukin 3 secretion. In contrast, no other mature thymic or splenic CD4+ T cell subsets showed such a high frequency. The majority of this AMLR reactivity in the Thy0 subset is accounted for by reactivity with self-major histocompatibility complex class II. Furthermore, antigenic selection in generating Thy0 subset is suggested by studies with T cell hybrids from a T cell receptor (TCR) V beta transgenic mouse line, 2B4 beta EH. TCR V-gene analysis of T cell hybrids revealed that those from Thy0, half of which responded to self-class II, consisted predominantly of cells that expressed endogenous TCR V beta s alone (without the transgene), unlike hybrids generated from peripheral naive T cells. Thus, we suggest that the presence of Thy0 results from selective stimulation of cells expressing TCR with sufficient affinity for autoantigens in the thymic CD4+ T cell repertoire.
An academy would be inappropriate
Authors: A H Grabham
Journal: BMJ (1996)

EDITOR,—Richard Smith discusses recent proposals to form an academy of medicine in Britain,1 which are set out in a consultation paper (a leaflet) included in the same issue of the BMJ. The matter is both complex and important. I am surprised that the two articles could contemplate such an exercise in the representation of the profession without making any reference to the possible role of the BMA. I do not, however, believe that pique should prevent the BMA …
Organ-specific selection of viral variants during chronic infection.
Authors: R Ahmed, M B Oldstone
Journal: The Journal of Experimental Medicine (1988)

This study demonstrates organ specific selection of viral variants during chronic lymphocytic choriomeningitis virus (LCMV) infection in its natural host. Isolates with different biological properties were present in the central nervous system (CNS) and lymphoid tissues of carrier mice infected at birth with the wt Armstrong strain of LCMV. Viral isolates from the CNS were similar to the wt Armstrong strain and induced potent virus-specific cytotoxic T lymphocyte (CTL) responses in adult mice and the infection was cleared within 2 wk. In contrast, LCMV isolates derived from the lymphoid tissues caused a chronic infection in adult mice associated with suppressed CTL responses. Revertants with wt Armstrong phenotype were present in the CNS of mice infected with a spleen isolate showing unequivocally the importance of host tissues in the selection of viral variants. These results provide a possible mechanism by which viral variants emerge in nature and suggest that tissue- and cell-specific selection is an important aspect of virus evolution.
WITHDRAWN: Comprehensive supercritical fluid chromatography combined with mass spectrometric detection for the analysis of related substances in polyene phosphatidylcholine extracted from soybean and its commercial capsule
Authors: Xiaohong Liu, Wanjun Liu, Qikun Jiang
Journal: Asian Journal of Pharmaceutical Sciences (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Causes for the premature interruption of psychotherapy by private practice patients
Authors: P Levinson, L McMurray, P Podell, H Weiner
Journal: American Journal of Psychiatry (1978)

Thirty patients who discontinued private psychotherapy prematurely were evaluated. Factors stemming from the dynamic interaction between the patient and the treatment process were the most common reasons for dropping out, followed by chronic character traits such as impulsivity and masochism. It is hoped that this assessment of variables in the premature termination of therapy will serve to alert the therapist to the probability that treatment will be aborted, suggest which mechanisms will cause interruption, and enable the therapist to use preventive measures sooner.
The CDK9 Inhibitor Dinaciclib Exerts Potent Apoptotic and Antitumor Effects in Preclinical Models of MLL-Rearranged Acute Myeloid Leukemia
Authors: Adele Baker, Gareth P. Gregory, Inge Verbrugge, Lev Kats, Joshua J. Hilton, Eva Vidacs, Erwin M. Lee, Richard B. Lock, Johannes Zuber, Jake Shortt, Ricky W. Johnstone
Journal: Cancer Research (2015)

Translocations of the mixed lineage leukemia (MLL) gene occur in 60% to 80% of all infant acute leukemias and are markers of poor prognosis. MLL-AF9 and other MLL fusion proteins aberrantly recruit epigenetic regulatory proteins, including histone deacetylases (HDAC), histone methyltransferases, bromodomain-containing proteins, and transcription elongation factors to mediate chromatin remodeling and regulate tumorigenic gene expression programs. We conducted a small-molecule inhibitor screen to test the ability of candidate pharmacologic agents targeting epigenetic and transcriptional regulatory proteins to induce apoptosis in leukemic cells derived from genetically engineered mouse models of MLL-AF9-driven acute myeloid leukemia (AML). We found that the CDK inhibitor dinaciclib and HDAC inhibitor panobinostat were the most potent inducers of apoptosis in short-term in vitro assays. Treatment of MLL-rearranged leukemic cells with dinaciclib resulted in rapidly decreased expression of the prosurvival protein Mcl-1, and accordingly, overexpression of Mcl-1 protected AML cells from dinaciclib-induced apoptosis. Administration of dinaciclib to mice bearing MLL-AF9-driven human and mouse leukemias elicited potent antitumor responses and significantly prolonged survival. Collectively, these studies highlight a new therapeutic approach to potentially overcome the resistance of MLL-rearranged AML to conventional chemotherapies and prompt further clinical evaluation of CDK inhibitors in AML patients harboring MLL fusion proteins.
Abstract 3241: Long-TermSurvival after Coronary Artery Bypass versus Percutaneous Coronary Intervention with Bare Metal Stent Implantation in Patients with Diabetic Retinopathy
Authors: Takayuki Ohno, Yoshihiro Suematsu, Noboru Motomura, Minoru Ono, Hideo Fujita, Jiro Ando, Toshihiro Morita, Yasunobu Hirata, Shinichi Takamoto
Journal: Circulation (2007)

Background : Coronary heart disease is the leading cause of death in diabetic population. Compared with diabetics without retinopathy, diabetics with retinopathy have an increased risk of myocardial infarction and death from coronary heart disease. Therefore, it is crucial to select an appropriate revascularization method in this considerable high-risk group. Methods: Between 1996 and 2004, a total of 149 patients with diabetic retinopathy underwent revascularization, either coronary artery bypass surgery (CABG) (n=56) or percutaneous coronary intervention with bare metal stents (BMS) (n=94). We compared overall survival rates of the two methods. Mortality was estimated according to Kaplan-Meier methods and was compared using the log-rank test. Results: The average follow-up from the time of the initial revascularization was 59.7 ± 33.3 months. During the entire follow-up, there was 8(14.5%)death in the CABG group and 27(28.7%) deaths in the BMS group. The average duration between death and revascularization was 81.3 ± 24.6 for the CABG group and 29.9 ± 23.8 for the BMS group (P&lt;0.001). The 6-year overall survival was 94.8% for the CABG group and 73.6% for the BMS group. Mortality curves differed significantly between the two groups (P=0.004) (Figure ). After adjustment for baseline characteristics including age, sex, HbA1c, insulin, serum creatinine, ejection fraction, and the extent of coronary disease, the hazard ratio of death afforded by CABG was 0.36 (95% confidence interval, 0.15–0.87; P=0.023). Conclusions: In patients with diabetic retinopathy, CABG conferred survival benefit over BMS implantation.
Development of Electrically Conductive Double‐Network Hydrogels via One‐Step Facile Strategy for Cardiac Tissue Engineering
Authors: Boguang Yang, Fanglian Yao, Tong Hao, Wancai Fang, Lei Ye, Yabin Zhang, Yan Wang, Junjie Li, Changyong Wang
Journal: Advanced Healthcare Materials (2015)

Cardiac tissue engineering is an effective method to treat the myocardial infarction. However, the lack of electrical conductivity of biomaterials limits their applications. In this work, a homogeneous electronically conductive double network (HEDN) hydrogel via one‐step facile strategy is developed, consisting of a rigid/hydrophobic/conductive network of chemical crosslinked poly(thiophene‐3‐acetic acid) (PTAA) and a flexible/hydrophilic/biocompatible network of photo‐crosslinking methacrylated aminated gelatin (MAAG). Results suggest that the swelling, mechanical, and conductive properties of HEDN hydrogel can be modulated via adjusting the ratio of PTAA network to MAAG network. HEDN hydrogel has Young's moduli ranging from 22.7 to 493.1 kPa, and its conductivity (≈10 −4 S cm −1 ) falls in the range of reported conductivities for native myocardium tissue. To assess their biological activity, the brown adipose‐derived stem cells (BADSCs) are seeded on the surface of HEDN hydrogel with or without electrical stimulation. Our data show that the HEDN hydrogel can support the survival and proliferation of BADSCs, and that it can improve the cardiac differentiation efficiency of BADSCs and upregulate the expression of connexin 43. Moreover, electrical stimulation can further improve this effect. Overall, it is concluded that the HEDN hydrogel may represent an ideal scaffold for cardiac tissue engineering.
Synergistic Effects of Combined Cell Therapy for Chronic Ischemic Cardiomyopathy
Authors: Vasileios Karantalis, Viky Y. Suncion-Loescher, Luiza Bagno, Samuel Golpanian, Ariel Wolf, Cristina Sanina, Courtney Premer, Anthony J. Kanelidis, Frederic McCall, Bo Wang, Wayne Balkan, Jose Rodriguez, Marcos Rosado, Azorides Morales, Konstantinos Hatzistergos, Makoto Natsumeda, Irene Margitich, Ivonne Hernandez Schulman, Samirah A. Gomes, Muzammil Mushtaq, Darcy L. DiFede, Joel E. Fishman, Pradip Pattany, Juan Pablo Zambrano, Alan W. Heldman, Joshua M. Hare
Journal: Journal of the American College of Cardiology (2015)
Discovery and characterization of an immunogenic neoantigen in a patient with metastatic triple negative breast cancer
Authors: Yasmine Assadipour, Stephanie Goff, Jessica S Crystal, Todd D Prickett, Jared J Gartner, Robert Somerville, Hui Xu, Mary Black, Isaac Kriley, Paul F Robbins, Steven A Rosenberg, Steven Feldman
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts A growing body of evidence suggests that successful clinical immunotherapy may depend on mutation-specific T cell responses. Using whole-exome and RNA sequencing of a resected metastatic deposit from a patient with triple-negative (ER-, PR-, Her2 non-amplified) breast cancer, we
New alliance of 19 health bodies adds voice to call for sugar tax
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

Nineteen UK organisations concerned with obesity are calling on the government to introduce a 20% tax on sugar sweetened beverages.

The Obesity Stakeholder Group has come together to urge the government to take action, such as new legislation to help families reduce their consumption of food and drink high in fat, salt, and sugar, in the light of the growing epidemic of obesity in the United Kingdom.

Around 30% of children in the UK are obese or overweight and at risk of growing into overweight or obese adults with an increased risk of cancer, type 2 diabetes, heart disease, and other life …
Determination of an optimal dosing schedule for combining Irinophore C™ and temozolomide in an orthotopic model of glioblastoma
Authors: M. Verreault, M. Wehbe, D. Strutt, D. Masin, M. Anantha, D. Walker, F. Chu, I. Backstrom, J. Kalra, D. Waterhouse, D.T. Yapp, M.B. Bally
Journal: Journal of Controlled Release (2015)
Efforts to improve US hospital safety stalled in 2014, report finds
Authors: Michael McCarthy
Journal: BMJ (2015)

After three years of steady decline in the numbers of patients harmed while receiving care in US hospitals, improvement stalled in 2014, says a report by the US Agency for Healthcare Research and Quality.1

The number of hospital acquired illnesses such as adverse drug events, catheter associated urinary tract infections, and surgical site infections fell from 145 per 1000 hospital discharges in 2010 to 121 per 1000 …
Eosinophilic airway inflammation is associated with increased TLR2 and TLR4 expression in adult asthmatics
Authors: Celeste Porsbjerg, Katherine Baines, Asger Sverrild, Vibeke Backer, Peter Gibson
Journal: European Respiratory Journal (2014)

Background:  It is increasingly recognised that innate immune pathways are involved in asthma: Toll like receptors (TLR) are up regulated in acute and fatal asthma, and in neutrophilic asthma. TLR activation may also induce a Th2 type response, but little evidence is available in humans.   Aim:  We hypothesized eosinophilic airway inflammation to be associated with increased TLR expression, independently of other causative factors such as neutrophilic inflammation or airflow obstruction.   Methods:  Asthma patients with at least one objective marker of asthma (Airway hyperresponsiveness ((AHR) to mannitol or methacholine), or reversibility to beta-2-agonist) were examined with induced sputum for differential cell count and TLR2 and TLR4 mRNA expression using real-time PCR.   Results : Induced sputum was obtained in 66 asthma patients (age 32 years (13.6), 56% females, median asthma duration: 1 year (range 0-56 years), FEV1% of predicted: 93.2% (±16.2) ACQ 1.4 (±1.0)). Airway eosinophilia (> 3%) was found in 29 % (n=19) and neutrophilia (> 61%) in 16 % (n=10).  In a regression analysis, eosinophilic and neutrophilic inflammation, as well as post bronchodilator FEV1%, were independently associated with the level of TLR2 expression (Eosinophils > 3%, Beta: 0.31, p= 0.007. Neutrophils > 61%: 0.31, p=0.007, FEV1% post SABA: -0.29, p=0.011), whereas TLR4 was only associated with eosinophilia (Beta: 0.29, p=0.018). Duration of asthma, asthma control, AHR and atopy were not predictors of an increased TLR expression.   Conclusion:  Airway eosinophilia was associated with increased airway TLR2 and TLR4 mRNA expression, independently of neutrophilic inflammation or chronic airflow obstruction.
Similarity, in molecular structure and function, between the plant toxin purothionin and the mammalian pore-forming proteins.
Authors: T Oka, Y Murata, T Nakanishi, H Yoshizumi, H Hayashida, Y Ohtsuki, K Toyoshima, A Hakura
Journal: Molecular Biology and Evolution (1992)

Many proteins containing domains of a cysteine-rich repeated motif, such as epidermal growth factor (EGF), have been reported. Here we report strong similarity between the amino acid sequence of a plant toxin--i.e., purothionin and its homologues--and with those of a domain found in mammalian pore-forming cytoplasmic proteins: components of complement and perforin of cytotoxic T-lymphocytes or natural killer-like cytotoxic cells. These similar sequences were found to be identical to the so-called EGF-like cysteine-rich repeated motif itself. Electron-microscopic observations indicated that, like complement and perforin, purothionin forms pores in the cytoplasmic membrane of target cells, resulting in their death within a few hours. On the basis of these sequence comparisons and physiological functions, we propose a scheme for the evolution of proteins containing modules of the cysteine-rich repeat motif.
Microarray and Proteomic Analysis of Brassinosteroid- and Gibberellin-Regulated Gene and Protein Expression in Rice
Authors: Guangxiao Yang, Setsuko Komatsu
Journal: Genomics Proteomics & Bioinformatics (2004)

Abstract Brassinosteroid (BR) and gibberellin (GA) are two groups of plant growth regulators essential for normal plant growth and development. To gain insight into the molecular mechanism by which BR and GA regulate the growth and development of plants, especially the monocot plant rice, it is necessary to identify and analyze more genes and proteins that are regulated by them. With the availability of draft sequences of two major types, japonica and indica rice, it has become possible to analyze expression changes of genes and proteins at genome scale. In this review, we summarize rice functional genomic research by using microarray and proteomic approaches and our recent research results focusing on the comparison of cDNA microarray and proteomic analyses of BR- and GA-regulated gene and protein expression in rice. We believe our findings have important implications for understanding the mechanism by which BR and GA regulate the growth and development of rice.
Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index
Authors: Jian Yang, Andrew Bakshi, Zhihong Zhu, Gibran Hemani, Anna A E Vinkhuyzen, Sang Hong Lee, Matthew R Robinson, John R B Perry, Ilja M Nolte, Jana V van Vliet-Ostaptchouk, Harold Snieder, Tonu Esko, Lili Milani, Reedik Mägi, Andres Metspalu, Anders Hamsten, Patrik K E Magnusson, Nancy L Pedersen, Erik Ingelsson, Nicole Soranzo, Matthew C Keller, Naomi R Wray, Michael E Goddard, Peter M Visscher
Journal: Nature Genetics (2015)
Modulation of Polycystic Kidney Disease Severity by Phosphodiesterase 1 and 3 Subfamilies
Authors: Hong Ye, Xiaofang Wang, Caroline R. Sussman, Katharina Hopp, Maria V. Irazabal, Jason L. Bakeberg, Wells B. LaRiviere, Vincent C. Manganiello, Charles V. Vorhees, Haiqing Zhao, Peter C. Harris, Jan van Deursen, Christopher J. Ward, Vicente E. Torres
Journal: Journal of the American Society of Nephrology (2015)

Aberrant intracellular calcium levels and increased cAMP signaling contribute to the development of polycystic kidney disease (PKD). cAMP can be hydrolyzed by various phosphodiesterases (PDEs). To examine the role of cAMP hydrolysis and the most relevant PDEs in the pathogenesis of PKD, we examined cyst development in Pde1 - or Pde3 -knockout mice on the Pkd2 −/WS25 background (WS25 is an unstable Pkd2 allele). These PDEs were selected because of their importance in cross-talk between calcium and cyclic nucleotide signaling ( PDE1 ), control of cell proliferation and cystic fibrosis transmembrane conductance regulator (CFTR) –driven fluid secretion (PDE3), and response to vasopressin V2 receptor activation (both). In Pkd2 −/WS25 mice, knockout of Pde1a , Pde1c , or Pde3a but not of Pde1b or Pde3b aggravated the development of PKD and was associated with higher levels of protein kinase A–phosphorylated (Ser133) cAMP–responsive binding protein (P-CREB), activating transcription factor-1, and CREB–induced CRE modulator proteins in kidney nuclear preparations. Immunostaining also revealed higher expression of P-CREB in Pkd2−/ WS25 ; Pde1a −/− , Pkd2− /WS25 ; Pde1c −/− , and Pkd2−/ WS25 ; Pde3a −/− kidneys. The cystogenic effect of desmopressin administration was markedly enhanced in Pkd2 −/WS25 ; Pde3a −/− mice, despite PDE3 accounting for only a small fraction of renal cAMP PDE activity. These observations show that calcium- and calmodulin-dependent PDEs ( PDE1A and PDE1C ) and PDE3A modulate the development of PKD, possibly through the regulation of compartmentalized cAMP pools that control cell proliferation and CFTR–driven fluid secretion. Treatments capable of increasing the expression or activity of these PDEs may, therefore, retard the development of PKD.
Increased Vegf-C Serum Levels are Predictive of a Poor Outcome in Patients with Resectable Gastric Cancer
Authors: M.M. Laterza, M. Orditura, A. Fabozzi, J. Ventriglia, B. Savastano, A. Petrillo, G. Giordano, E. Martinelli, V. Gambardella, F. Ciardiello, F. De Vita
Journal: Annals of Oncology (2014)
Single-cell motility and gene expression signature as predictors of the overall survival of act in melanoma patients
Authors: Melisa Martinez-Paniagua, Cara Haymaker, Jay R Adolacion, Laszlo Radvanyi, Patrick Hwu, Badrinath Roysam, Chantale Bernatchez, Navin Varadarajan
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Adoptive cell therapy (ACT) of tumor infiltrating lymphocytes (TIL) has shown the ability to induce complete regression of stage IV melanoma. Two challenges associated TIL ACT are that (i) T cells are capable of different anti-tumor effector functions including cytotoxicity,
Nanocomposite versus Mesocomposite for Osteogenic Differentiation of Tonsil‐Derived Mesenchymal Stem Cells
Authors: Hyo Jung Moon, Madhumita Patel, Heejung Chung, Byeongmoon Jeong
Journal: Advanced Healthcare Materials (2015)

Injectable inorganic/organic composite systems consisting of well‐defined mesocrystals (4–8 μm) of calcium phosphate and polypeptide thermogel significantly enhance the osteogenic differentiation of the tonsil derived mesenchymal stem cells (TMSCs). Compared to composite systems incorporating nanoparticles (10–100 nm) or pure hydrogel systems, osteogenic biomarkers including alkaline phosphatase (ALP), bone morphogenetic protein 2, and osteocalcin are highly expressed at both the mRNA level and the protein level in the mesocrystal composite systems. ALP activity of differentiated cells is also significantly higher in the mesocomposite systems compared to the nanocomposite systems or the pure hydrogel systems. The mesocomposite systems provide not only hard surfaces for binding the cells/proteins by the inorganic mesocrystals but also a soft matrix for holding the cells by the hydrogel. Through the current research, (1) a novel method of preparing mesocrystals is developed, (2) TMSCs are proved as a new resource of stem cells, and (3) the mesocomposite systems are proved to be a promising tool in controlling stem cell differentiation. (4) Finally, the research emphasizes the significance of mesoscience as a new perspective of science in controlling cell and material interfaces.
Oncolytic adenoviruses coated with MHC-I tumor epitopes for a new oncolytic vaccine platform
Authors: Cristian Capasso, Mari Hirvinen, Mariangela Garofalo, Dmitrii Romaniuk, Lukasz Kuryk, Teea Sarvela, Andrea Vitale, Maxim Antopolsky, Aniket Magarkar, Tapani Viitala, Teemu Suutari, Alex Bunker, Marjo Yliperttula, Arto Urtti, Vincenzo Cerullo
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Oncolytic adenoviruses (OAds) demonstrated great potential for the treatment of cancer in many pre-clinical studies. The pre-existing immunity and their immunodominance, however, still limit the success of oncolytic virotherapy in cancer patients. Thus, a transition from oncolytic
Folfiri Plus Cetuximab in Patients with Liver-Limited or Non-Liver-Limited Ras Wild-Type Metastatic Disease: a Sub-Group Analysis of the Crystal Study
Authors: C. Köhne, G. Folprecht, F. Ciardiello, P. Ronga, F. Beier, E. Van Cutsem
Journal: Annals of Oncology (2014)