tbuckley/cabot-search huggingface dataset:
Molecular analysis reveals heterogeneity of mouse mammary tumors conditionally mutant for Brca1
Authors: Mollie H Wright, Ana I Robles, Jason I Herschkowitz, Melinda G Hollingshead, Miriam R Anver, Charles M Perou, Lyuba Varticovski
Journal: Molecular Cancer (2008)

Abstract Background Development of therapies for patients with BRCA1 mutations has been hampered by lack of readily available in vitro and in vivo models. We recently showed that transplantation of transgenic mammary tumors as cell suspensions into naïve recipients generates reproducible tumors with remarkable stability of gene expression profile. We examined the expression profiles of original and serially transplanted mammary tumors from Brca1 deficient mice, and tumor derived cell lines to validate their use for preclinical testing and studies of tumor biology. Methods Original tumors, serially transplanted and multiple cell lines derived from Brca1 mammary tumors were characterized by morphology, gene and protein expression, and cell surface markers. Results Gene expression among Brca1 tumors showed more heterogeneity than among previously characterized tumors from MMTV- PyMT and - Wnt1 models. Gene expression data segregated Brca1 tumors into 3 distinct types: basal, mixed luminal, and tumors with epithelial-to-mesenchymal transition (EMT). Serial transplantation of individual tumors and multiple cell lines derived from the original tumors recapitulated the molecular characteristics of each tumor of origin. One tumor had distinct features of EMT and gave rise to cell lines that contained a distinct CD44 + /CD24 -/low population that may correlate with human breast cancer stem cells. Conclusion Although individual tumors expanded by transplantation maintain the genomic profile of the original tumors, the heterogeneity among Brca1 tumors limits the extent of their use for preclinical testing. However, cell lines offer a robust material for understanding tumor biology and response to therapies driven by BRCA1 deficiency.
Polymyositis in Rheumatoid Arthritis
Authors: D. A. Pitkeathly, E. N. Coomes
Journal: Annals of the Rheumatic Diseases (1966)

The family of conditions which comprise the polymyositis group have been clarified only in recent years and the syndrome has been extensively reviewed by Walton and Adams (1958), Pearson and Rose (1960), Barwick and Walton (1963), and Pearson (1964).There is now increasing awareness that many cases of polymyositis are to be found in association with diseases of connective tissue.However, the onset of the condition in patients with rheumatoid arthritis, if insidious, may be attributed to simple muscle weakness commonly found in such patients or to a myopathy induced by long-term steroid therapy.If the onset of polymyositis is acute with much systemic upset, the diagnosis may be difficult unless one is familiar with the presenting features of the condition.In order to draw further attention to the association of polymyositis and rheumatoid arthritis, three cases are described below.Methods The serum glutamate-oxaloacetate transaminase I copyright.
Effects of repeated hypoglycemia on cognitive function: a psychometrically validated reanalysis of the Diabetes Control and Complications Trial data.
Authors: E J Austin, I J Deary
Journal: Diabetes Care (1999)

To test the conclusion that there is no association between multiple episodes of severe hypoglycemia and cognitive decrements by reanalyzing the data from the Diabetes Control and Complications Trial (DCCT) with psychometrically validated cognitive factors and to conduct a novel analysis of the association between individual differences in baseline cognitive ability and episodes of severe hypoglycemia documented after baseline.The factor structure of cognitive ability in the neuropsychological data from the DCCT study was derived. Four cognitive factors (spatial ability, processing speed, memory, and verbal ability) were extracted. Changes in patients' cognitive scores for each year of follow-up were obtained, and paired comparisons of these change scores were performed between groups experiencing zero and five or more hypoglycemic episodes. The association between cognitive ability at baseline and number of subsequent episodes of severe hypoglycemia was also examined.Repeated episodes of hypoglycemia were found not to be associated with cognitive decline in any of the validated cognitive factors. No significant association was found between prospectively documented numbers of severe hypoglycemic episodes and baseline cognitive ability level.Repeated episodes of hypoglycemia were not related to cognitive decrement, and initial mental ability level was not associated with eventual numbers of hypoglycemic episodes in this group of patients.
Dr. Lieberman and Colleagues Reply
Authors: JEFFREY A. LIEBERMAN, T. SCOTT STROUP, JOSEPH P. McEVOY, MARVIN S. SWARTZ, ROBERT A. ROSENHECK, DIANA O. PERKINS, RICHARD S.E. KEEFE, SONIA M. DAVIS, CLARENCE E. DAVIS, JOHN HSIAO, JOANNE SEVERE, BARRY D. LEBOWITZ, None the CATIE Investigators
Journal: American Journal of Psychiatry (2006)
Functional Living Biointerphases
Authors: Anas Saadeddin, Aleixandre Rodrigo‐Navarro, Vicente Monedero, Patricia Rico, David Moratal, María Luisa González‐Martín, David Navarro, Andrés J. García, Manuel Salmerón‐Sánchez
Journal: Advanced Healthcare Materials (2013)

Lactococcus lactis is modified to express a fibronectin fragment (FNIII7-10) as a membrane protein. This interphase, based on a living system, can be further exploited to provide spatio-temporal factors to direct cell function at the material interface. This approach establishes a new paradigm in biomaterial surface functionalization for biomedical applications.
Phase II Trial of Temozolomide Plus O<sup>6</sup>-Benzylguanine in Adults With Recurrent, Temozolomide-Resistant Malignant Glioma
Authors: Jennifer A. Quinn, Sara Xiaoyin Jiang, David A. Reardon, Annick Desjardins, James J. Vredenburgh, Jeremy N. Rich, Sridharan Gururangan, Allan H. Friedman, Darell D. Bigner, John H. Sampson, Roger E. McLendon, James E. Herndon, Amy Walker, Henry S. Friedman
Journal: Journal of Clinical Oncology (2009)

Purpose This phase II trial was designed to define the role of O 6 -benzylguanine (O 6 -BG) in restoring temozolomide sensitivity in patients with recurrent or progressive, temozolomide-resistant malignant glioma and to evaluate the safety of administering O 6 -BG in combination with temozolomide. Patients and Methods Patients were accrued into two independent strata on the basis of histology: glioblastoma multiforme (GBM) and anaplastic glioma. Both temozolomide and O 6 -BG were administered on day 1 of a 28-day treatment cycle. Patients were administered a 1-hour O 6 -BG infusion at a dose of 120 mg/m 2 followed immediately by a 48-hour infusion at a dose of 30 mg/m 2 /d. Temozolomide was administered orally within 60 minutes of the end of the 1-hour O 6 -BG infusion at a dose of 472 mg/m 2 . The primary end point was objective response rate. Secondary end points included progression-free survival, overall survival, and safety. Results Sixty-six of 67 patients who enrolled were treated with temozolomide and O 6 -BG. One of 34 patients (3%) with GBM (95% CI, 0.1% to 15%) and five of 32 assessable patients (16%) with anaplastic glioma (95% CI, 5% to 33%) were responders. The most commonly reported adverse events were grade 4 hematologic events experienced in 48% of the patients. Conclusion O 6 -BG when added to a 1-day dosing regimen of temozolomide was able to restore temozolomide sensitivity in patients with temozolomide-resistant anaplastic glioma, but there seemed to be no significant restoration of temozolomide sensitivity in patients with temozolomide-resistant GBM.
Overexpression of endothelial nitric oxide synthase accelerates atherosclerotic lesion formation in apoE-deficient mice
Authors: Masanori Ozaki, Seinosuke Kawashima, Tomoya Yamashita, Tetsuaki Hirase, Masayuki Namiki, Nobutaka Inoue, Ken-ichi Hirata, Hiroyuki Yasui, Hiromu Sakurai, Yuichi Yoshida, Masahiro Masada, Mitsuhiro Yokoyama
Journal: Journal of Clinical Investigation (2002)

Nitric oxide (NO) derived from endothelial NO synthase (eNOS) is regarded as a protective factor against atherosclerosis. Therefore, augmentation of eNOS expression or NO production by pharmacological intervention is postulated to inhibit atherosclerosis. We crossed eNOS-overexpressing (eNOS-Tg) mice with atherogenic apoE-deficient (apoE-KO) mice to determine whether eNOS overexpression in the endothelium could inhibit the development of atherosclerosis. After 8 weeks on a high-cholesterol diet, the atherosclerotic lesion areas in the aortic sinus were unexpectedly increased by more than twofold in apoE-KO/eNOS-Tg mice compared with apoE-KO mice. Also, aortic tree lesion areas were approximately 50% larger in apoE-KO/eNOS-Tg mice after 12 weeks on a high-cholesterol diet. Expression of eNOS and NO production in aortas from apoE-KO/eNOS-Tg mice were significantly higher than those in apoE-KO mice. However, eNOS dysfunction, demonstrated by lower NO production relative to eNOS expression and enhanced superoxide production in the endothelium, was observed in apoE-KO/eNOS-Tg mice. Supplementation with tetrahydrobiopterin, an NOS cofactor, reduced the atherosclerotic lesion size in apoE-KO/eNOS-Tg mice to the level comparable to apoE-KO mice, possibly through the improvement of eNOS dysfunction. These data demonstrate that chronic overexpression of eNOS does not inhibit, but accelerates, atherosclerosis under hypercholesterolemia and that eNOS dysfunction appears to play important roles in the progression of atherosclerosis in apoE-KO/eNOS-Tg mice.
Frontostriatal Connectivity and Its Role in Cognitive Control in Parent-Child Dyads With ADHD
Authors: B.J. Casey, Jeffery N. Epstein, Jason Buhle, Conor Liston, Matthew C. Davidson, Simon T. Tonev, Julie Spicer, Sumit Niogi, Alexander J. Millner, Allan Reiss, Amy Garrett, Stephen P. Hinshaw, Laurence L. Greenhill, Keith M. Shafritz, Alan Vitolo, Lisa A. Kotler, Matthew A. Jarrett, Gary Glover
Journal: American Journal of Psychiatry (2007)

Objective: Many studies have linked the structure and function of frontostriatal circuitry to cognitive control deficits in attention deficit hyperactivity disorder (ADHD). Few studies have examined the role of white matter tracts between these structures or the extent to which white matter tract myelination and regularity correlate in family members with the disorder. Method: Functional imaging maps from a go/nogo task were used to identify portions of the ventral prefrontal cortex and striatum involved in suppressing an inappropriate action (i.e., cognitive control) in 30 parent-child dyads (N=60), including 20 dyads (N=40) with ADHD and 10 dyads (N=20) without ADHD. An automated fiber-tracking algorithm was used to delineate white matter fibers adjacent to these functionally defined regions based on diffusion tensor images. Fractional anisotropy, an index of white matter tract myelination and regularity derived from diffusion tensor images, was calculated to characterize the associations between white matter tracts and function. Results: Fractional anisotropy in right prefrontal fiber tracts correlated with both functional activity in the inferior frontal gyrus and caudate nucleus and performance of a go/nogo task in parent-child dyads with ADHD, even after controlling for age. Prefrontal fiber tract measures were tightly associated between ADHD parents and their children. Conclusions: Collectively, these findings support previous studies suggesting heritability of frontostriatal structures among individuals with ADHD and suggest disruption in frontostriatal white matter tracts as one possible pathway to the disorder.
The origin and evolution of Ebola and Marburg viruses
Authors: Y. Suzuki, T. Gojobori
Journal: Molecular Biology and Evolution (1997)

Molecular evolutionary analyses for Ebola and Marburg viruses were conducted with the aim of elucidating evolutionary features of these viruses. In particular, the rate of nonsynonymous substitutions for the glycoprotein gene of Ebola virus was estimated to be, on the average, 3.6 x 10(-5) per site per year. Marburg virus was also suggested to be evolving at a similar rate. Those rates were a hundred times slower than those of retroviruses and human influenza A virus, but were of the same order of magnitude as that of the hepatitis B virus. When these rates were applied to the degree of sequence divergence, the divergence time between Ebola and Marburg viruses was estimated to be more than several thousand years ago. Moreover, most of the nucleotide substitutions were transitions and synonymous for Marburg virus. This suggests that purifying selection has operated on Marburg virus during evolution.
Revisiting p53 and its effectors in ischemic heart injury
Authors: M CROW
Journal: Cardiovascular Research (2006)

See article by Matsusaka et al.  [4]  (pages 457–465) in this issue .

p53 is a tumor suppressor that enforces normal growth control and genomic stability. Its importance is reflected in the fact that acquired mutations in it or its upstream activators are found in all major human cancers [1]. p53 controls aberrant or inappropriate growth by acting as a transcription factor for a number of genes that promote apoptosis or growth arrest (Fig. 1). In addition, recent studies indicate that there are important non-transcriptional effects of p53 on apoptosis that involve its ability to suppress anti-apoptotic or activate pro-apoptotic Bcl-2 family members [2]. p53 expression or activity increases in cells in response to DNA damage and other forms of cell stress, including hypoxia [3], a major component of ischemic injury. Controversy over what role, if any, p53 plays in the response of the heart to ischemic injury dates back almost a decade. Three recent reports examine the role of p53 or well-characterized effectors of p53 in ischemia-induced injury to the heart. One, which is published in this issue of Cardiovascular Research , re-examines the role of p53 in ischemia-induced apoptosis, with a focus on the effects of p53 status on myocardial cell apoptosis and cardiac rupture [4].



Fig. 1 
Regulation of p53, p53-related proteins, and their effectors.



Following reports that p53 protein levels increase in non-myocyte cell lines in response to hypoxia [3] and that hypoxia could cause cell death of cultured cardiomyocytes [5], Long et al. [6] showed that hypoxia increases p53 expression in cardiomyocytes and that this increase occurs in connection with myocyte cell death. Although not all the data are in agreement regarding increased p53 expression in response to hypoxia [7], a recent study also reported increased p53 expression and cell death … 

* Tel.: +1 410 550 4148; fax: +1 410 550 2612. Email address: mcrow1{at}jhmi.edu
The role of the ICOS-B7h T cell costimulatory pathway in transplantation immunity
Authors: Hiroshi Harada, Alan D. Salama, Masayuki Sho, Atsushi Izawa, Sigrid E. Sandner, Toshiro Ito, Hisaya Akiba, Hideo Yagita, Arlene H. Sharpe, Gordon J. Freeman, Mohamed H. Sayegh
Journal: Journal of Clinical Investigation (2003)

Inducible costimulatory molecule (ICOS) plays a pivotal role in T cell activation and Th1/Th2 differentiation. ICOS blockade has disparate effects on immune responses depending on the timing of blockade. Its role in transplantation immunity, however, remains incompletely defined. We used a vascularized mouse cardiac allograft model to explore the role of ICOS signaling at different time points after transplantation, targeting immune initiation (early blockade) or the immune effector phase (delayed blockade). In major histocompatibility–mismatched recipients, ICOS blockade prolonged allograft survival using both protocols but did so more effectively in the delayed-treatment group. By contrast, in minor histocompatibility–mismatched recipients, early blockade accelerated rejection and delayed blockade prolonged graft survival. Alloreactive CD4+ T cell expansion and alloantibody production were suppressed in both treatment groups, whereas only delayed blockade resulted in suppression of effector CD8+ T cell generation. After delayed ICOS blockade, there was a diminished frequency of allospecific IL-10–producing cells and an increased frequency of both IFN-γ– and IL-4–producing cells. The beneficial effects of ICOS blockade in regulating allograft rejection were seen in the absence of CD28 costimulation but required CD8+ cells, cytotoxic T lymphocyte antigen-4, and an intact signal transducer and activator of transcription–6 pathway. These data define the complex functions of the ICOS-B7h pathway in regulating alloimmune responses in vivo.
Caval-Aortic Access to Allow Transcatheter Aortic Valve Replacement in Otherwise Ineligible Patients
Authors: Adam B. Greenbaum, William W. O'Neill, Gaetano Paone, Mayra E. Guerrero, Janet F. Wyman, R. Lebron Cooper, Robert J. Lederman
Journal: Journal of the American College of Cardiology (2014)
Guidelines of care for the management of psoriasis and psoriatic arthritis
Authors: Alan Menter, Neil J. Korman, Craig A. Elmets, Steven R. Feldman, Joel M. Gelfand, Kenneth B. Gordon, Alice B. Gottlieb, John Y.M. Koo, Mark Lebwohl, Henry W. Lim, Abby S. Van Voorhees, Karl R. Beutner, Reva Bhushan
Journal: Journal of the American Academy of Dermatology (2009)
P194Serum uric acid as independent predictor of decreased number of circulating proangiogenic progenitor cells in asymptomatic coronary artery disease patients
Authors: A Berezin, A Kremzer
Journal: Cardiovascular Research (2014)

Background: Serum uric acid (SUA) plays a pivotal role in the pathogenesis of cardiovascular diseases affecting xanthine oxidase pathway that contributes to the production of active oxygen species generation. Vascular oxidative stress and endothelial dysfunction contribute an injury of both cardiomyocytes and vascular endothelium that requires an activation of reparation processing. However, several types of circulating progenitor cells (CPCs) mediate an angiogenesis and tissue repair following injuries. Few studies have investigated the association of hyperuricemia with subclinical heart failure and atherosclerosis

The aim of this study was to determine whether serum uric acid (SUA) is an independent predictor of the decreased number of CPC of in asymptomatic CAD patients.

Design and Methods: 126 subjects (54 male), aged 48 to 62 years, and with asymptomatic CAD documented previously with angiography, and 25 healthy volunteers were enrolled in the study. Concentration of SUA was measured with enzymatic methods. The flow cytometric technique was used for predictably distinguishing cell subsets that depend on the expression of CD14, CD34, Tie-2, CD45, and CD309 (VEGFR2).

Results: The analysis of the outcome obtained shows a trend of decrease of circulating CD45-CD34+ CMCs and a reduction of number of CMCs defined as CD14+CD309+ and CD14+CD309+Tie2+ in known asymptomatic CAD patients in comparison with healthy volunteers. Substantial correlations between number of both CD14+CD309+ and CD14+CD309+Tie2+ and conventional cardiovascular risk factors (hs-CRP, T2DM, SUA and hypertension) were found in the patient cohort. Univariate regression analysis showed that T2DM (RR = 1.21; 95% CI = 1.10–1.40; P = 0.008), hs-CRP > 2.54 mg/L (RR = 1.29; 95% CI = 1.12–1.58; P = 0.006), Agatston score index (RR = 1.2095% CI = 1.15–1.27; P = 0.034), SUA > 459 mmol / L (RR = 1.31; 95% CI = 1.12–1.49; P = 0.008) were factors that associated with decreased both CD14+CD309+ and CD14+CD309+Tie2+ CPCs. In multivariate model SUA> 459 mmol / L had independent predicted value (RR = 1.18; 95% CI = 1.04–1.27; P = 0.001) for decreased CPCs defined as CD14+CD309+ and CD14+CD309+Tie2+.

Conclusion: Serum uric acid is independently associated with lowed circulating CD14+ CD309+ and CD14+CD309+Tei2+ cells in asymptomatic patients with known CAD.
Antigen- and receptor-driven regulatory mechanisms. II. Induction of suppressor T cells with idiotype-coupled syngeneic spleen cells.
Authors: M S Sy, B A Bach, A Brown, A Nisonoff, B Benacerraf, M I Greene
Journal: The Journal of Experimental Medicine (1979)

Anti-p-azobenzenearsonate (ABA) antibodies, coupled covalently to normal syngeneic spleen cells and then given intravenously to normal animals, were found to be potent tolerogens for delayed-type hypersensitivity (DTH) to ABA. The ability of the antibody-coupled cells to induce tolerance was determined to be a result of the cross-reactive idiotype (CRI+) fraction of the antibodies, because anti-ABA antibodies lacking the CRI+ components when coupled to spleen cells were unable to cause any significant inhibition. Furthermore, genetic analysis revealed that the ability of CRI-coupled cells to inhibit ABA-specific DTH is linked to Igh-1 heavy chain allotype, in as much animals which possess heavy chain allotypes similar to that of A/J were sensitive to this inhibition. Adoptive transfer experiments provided evidence that CRI-coupled cells induce suppressor cells, and spleen cells or thymocytes from animals received CRI-coupled cells were able to transfer suppression to naive recipients. In addition, treatment with anti-Thy1.2 serum plus complement completely abrogated their ability to transfer suppression. Thus, this active suppression is a T-cell-dependent phenomenon. In investigating the specificity of these suppressor T cells, it was found that they functioned in an antigen-specific manner and were unable to suppress the development of DTH to an unrelated hapten 2,4-dinitro-1-fluorobenzene.
Modulation of MAPK pathways and cell cycle by replicating hepatitis B virus: Factors contributing to hepatocarcinogenesis
Authors: Ruth Chin, Linda Earnest-Silveira, Bernd Koeberlein, Susanne Franz, Hanswalter Zentgraf, Xuebin Dong, Eric Gowans, C.-Thomas Bock, Joseph Torresi
Journal: Journal of Hepatology (2007)
Combination of IL-17 and TNFα induces a pro-inflammatory, pro-coagulant and pro-thrombotic phenotype in human endothelial cells
Authors: Arnaud Hot, Vanina Lenief, Pierre Miossec
Journal: Annals of the Rheumatic Diseases (2012)

Objective Cardiovascular events remain the leading cause of death in rheumatoid arthritis (RA). To study the role of cytokines in these observations, the effects of tumour necrosis factor α (TNFα) and interleukin (IL)-17, a classical and a new key player in RA, were assessed in endothelial cell (EC) dysfunction. Methods Primary human EC were treated with IL-17 alone or combined with TNFα. mRNA expression was quantified by qRT PCR and Affymetrix microarrays. The role of IL-17 was studied using functional assays of platelet aggregation, EC migration and invasion. Results IL-17 alone induced 248 pro-inflammatory genes and 9803, when combined with TNFα. IL-17 plus TNFα induced synergistically chemokine genes such as CCL5, IL-8 and cytokine genes such as IL-6. In contrast, IL-17 decreased genes involved in the regulation of inflammation such as IL-33. IL-17 induced EC migration and invasion in synergy with TNFα. Such invasion was inhibited with an antiCXCR4 antibody, indicating the contribution of the stromal cell-derived factor-1/C-X-C chemokine receptor type 4 axis. Supernatants of IL-17-treated EC induced strong platelet aggregation. IL-17 inhibited endothelial CD39/ATPDase expression, an inhibitor of platelet activation. Finally, IL-17 enhanced genes critical for coagulation such as tissue factor and decreased thrombomodulin, leading to a pro-thrombotic state. Conclusion These results indicate that IL-17 specifically when combined with TNFα has major pro-coagulant and pro-thrombotic effects on vessels.