tbuckley/cabot-search huggingface dataset:
The P2X7 Receptor Sustains the Growth of Human Neuroblastoma Cells through a Substance P–Dependent Mechanism
Authors: Lizzia Raffaghello, Paola Chiozzi, Simonetta Falzoni, Francesco Di Virgilio, Vito Pistoia
Journal: Cancer Research (2006)

P2X(7) is a receptor for extracellular nucleotides expressed by different normal cell types. P2X(7) triggering may result in stimulation of cell proliferation or induction of apoptosis depending on the level of activation. P2X(7) expression and function in B-cell chronic lymphocytic leukemia has been shown to correlate with disease severity. Here, we have asked the question of whether P2X(7) is expressed and functional in neuroblastoma, a pediatric tumor of neuroectodermal origin. P2X(7) was detected both in primary neuroblastoma tumors and in neuroblastoma cell lines. In the latter cells, P2X(7) stimulation by ATP was found to trigger (a) increased intracellular calcium fluxes, (b) plasma membrane depolarization, and (c) formation of a nonselective plasma membrane permeable pore. In contrast to the usual response typically observed in the majority of cell types, P2X(7) in vitro stimulation did not induce caspase-3 activation or apoptosis of neuroblastoma cells but rather supported their proliferation. Growth stimulation was partially due to substance P release from nucleotide-activated neuroblastoma cells. Therefore, neuroblastoma cells seem to have molded P2X(7) function to their advantage in two ways (i.e., by silencing P2X(7) proapoptotic activity and by coupling P2X(7) stimulation to release of locally acting trophic factors).
Mechanisms of Enhanced Radiation Response following Epidermal Growth Factor Receptor Signaling Inhibition by Erlotinib (Tarceva)
Authors: Prakash Chinnaiyan, Shyhmin Huang, Geetha Vallabhaneni, Eric Armstrong, Sooryanarayana Varambally, Scott A. Tomlins, Arul M. Chinnaiyan, Paul M. Harari
Journal: Cancer Research (2005)

Abstract Erlotinib (Tarceva) is an orally available HER1 (epidermal growth factor receptor, EGFR) tyrosine kinase inhibitor advancing through clinical trials for the treatment of a range of human malignancies. In this study, we examine the capacity of erlotinib to modulate radiation response and investigate specific mechanisms underlying these interactions in human tumor cell lines and xenografts. The impact of erlotinib on cell cycle kinetics was analyzed using flow cytometry, and the impact on apoptosis was evaluated via fluorescein-labeled pan-caspase inhibition and poly(ADP-ribose) polymerase cleavage. Radiation-induced EGFR autophosphorylation and Rad51 expression were examined by Western blot analysis. Radiation survival was analyzed using a clonogenic assay and assessment of in vivo tumor growth was done using a mouse xenograft model system. Microarray studies were carried out using 20 K human cDNA microarray and select genes were validated using quantitative reverse transcription-PCR (RT-PCR). Independently, erlotinib and radiation induce accumulation of tumor cells in G1 and G2-M phase, respectively, with a reduction of cells in S phase. When combined with radiation, erlotinib promotes a further reduction in S-phase fraction. Erlotinib enhances the induction of apoptosis, inhibits EGFR autophosphorylation and Rad51 expression following radiation exposure, and promotes an increase in radiosensitivity. Tumor xenograft studies confirm that systemic administration of erlotinib results in profound tumor growth inhibition when combined with radiation. cDNA microarray analysis assessing genes differentially regulated by erlotinib following radiation exposure identifies a diverse set of genes deriving from several functional classes. Validation is confirmed for several specific genes that may influence radiosensitization by erlotinib including Egr-1, CXCL1, and IL-1β. These results identify the capacity of erlotinib to enhance radiation response at several levels, including cell cycle arrest, apoptosis induction, accelerated cellular repopulation, and DNA damage repair. Preliminary microarray data suggests additional mechanisms underlying the complex interaction between EGFR signaling and radiation response. These data suggest that the erlotinib/radiation combination represents a strategy worthy of further examination in clinical trials.
NAEVUS SYRINOTOCYSTADKNOMATOSUS PAPILLTFERUS.
Authors: J. JANCAR
Journal: British Journal of Dermatology (1970)

Journal Article NAEVUS SYRINOTOCYSTADKNOMATOSUS PAPILLTFERUS: WITH SKULL AND BRAIN LESIONS, HEMIPARESIS, EPILEPSY AND MENTAL RETARDATION Get access J. JANCAR J. JANCAR Stoke Park Hospital Group, Bristol, England Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 82, Issue 4, 1 April 1970, Pages 402–405, https://doi.org/10.1111/j.1365-2133.1970.tb06840.x Published: 01 April 1970 Article history Accepted: 28 October 1969 Published: 01 April 1970
Reply to J. Moline et al
Authors: Daniel D. Buchanan, Yen Y. Tan, Michael D. Walsh, Mark Clendenning, Alexander M. Metcalf, Kaltin Ferguson, Sven T. Arnold, Bryony A. Thompson, Felicity A. Lose, Michael T. Parsons, Rhiannon J. Walters, Sally-Ann Pearson, Margaret Cummings, Martin K. Oehler, Penelope B. Blomfield, Michael A. Quinn, Judy A. Kirk, Colin J. Stewart, Andreas Obermair, Joanne P. Young, Penelope M. Webb, Amanda B. Spurdle
Journal: Journal of Clinical Oncology (2014)
Intestinal Malabsorption Syndromes
Authors: T A Brasitus, M D Sitrin
Journal: Annual Review of Medicine (1990)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Quantitative sacroiliac scintigraphy in ankylosing spondylitis and Crohn's disease: a single family study.
Authors: P Davis
Journal: Annals of the Rheumatic Diseases (1979)

A single family is presented in which 2 of the 3 sibs and 3 of 9 first degree relatives had Crohn's disease. Two subjects with Crohn's disease had classical ankylosing spondylitis (AS), and HLA typing revealed HLA B27 in all 5 members of the immediate family. The value of quantitative sacroiliac scintigraphy (QSS) in clinical practice is demonstrated. Both patients with AS had evidence of currently active sacroiliac disease in association with radiological change. One symptomatic sib had QSS evidence of sacroiliitis without radiological abnormality.
An ecological alternative to a “sad response”: Public language use transcends the boundaries of the skin
Authors: Carol A. Fowler
Journal: Behavioral and Brain Sciences (2013)

Abstract Embedding theories of language production and comprehension in theories of action-perception is realistic and highlights that production and comprehension processes are interleaved. However, layers of internal models that repeatedly predict future linguistic actions and perceptions are implausible. I sketch an ecological alternative whereby perceiver/actors are modeled as dynamical systems coupled to one another and to the environment.
Effect of sleep deprivation on overnight bronchoconstriction in nocturnal asthma.
Authors: J R Catterall, G B Rhind, I C Stewart, K F Whyte, C M Shapiro, N J Douglas
Journal: Thorax (1986)

Nocturnal cough and wheeze are common in asthma. The cause of nocturnal asthma is unknown and there is conflicting evidence on whether sleep is a factor. Twelve adult asthmatic subjects with nocturnal wheeze were studied on two occasions: on one night subjects were allowed to sleep and on the other they were kept awake all night, wakefulness being confirmed by electroencephalogram. Every patient developed bronchoconstriction overnight both on the asleep night, when peak expiratory flow (PEF) fell from a mean (SE) of 418 (40) 1 min-1 at 10 pm to 270 (46) 1 min-1 in the morning, and on the awake night (PEF 10 pm 465 (43), morning 371 (43) 1 min-1). The morning values of PEF were, however, higher (p less than 0.1) after the awake night and both the absolute and the percentage overnight falls in PEF were greater when the patients slept (asleep night 38% (6%), awake night 20% (4%); p less than 0.01). This study suggests that sleep is an important factor in determining overnight bronchoconstriction in patients with nocturnal asthma.
Phase II study of FOLFOX, bevacizumab and erlotinib as first-line therapy for patients with metastastic colorectal cancer
Authors: J.A. Meyerhardt, K. Stuart, C.S. Fuchs, A.X. Zhu, C.C. Earle, P. Bhargava, L. Blaszkowsky, P. Enzinger, R.J. Mayer, S. Battu, C. Lawrence, D.P. Ryan
Journal: Annals of Oncology (2007)
Urokinase in rheumatoid arthritis: causal or coincidental?
Authors: N. BUSSO, A. SO
Journal: Annals of the Rheumatic Diseases (1997)

The past 10 years have witnessed an increased interest in the plasminogen activation system and its potential role(s) in rheumatoid arthritis (RA). Two types of plasminogen activators (PAs), urokinase (uPA) and tissue type PA (tPA), which are structurally, immunologically, and genetically distinct, have been identified in mammals. Both PAs are secreted as a single chain protein, which in the case of uPA is essentially inactive (pro-uPA). Pro-uPA is then converted by a single enzymatic cleavage into two chain active enzyme. uPA and tPA are highly specific serine proteases catalysing the conversion of plasminogen into plasmin.1 2 Plasminogen, present in plasma and extracellular fluids, can bind to fibrin and also to cell surface plasminogen receptors (PlnR), via its lysine binding sites. The activity of PAs is controlled by natural inhibitors (PAls), which include PAI-1, the main PAI in the circulation, and PAI-2. In addition, uPA activity is blocked by protease nexin 1 (PN-1). Another important step in the regulation of PA activity involves binding of tPA to fibrin, leading to increased catalytic activity of the enzyme, and binding of pro-uPA and uPA through a growth factor domain contained in their amino terminal region, to a specific, high affinity cell surface receptor, uPAR. Binding of uPA to uPAR increases the rate of plasminogen activation and greatly increases extracellular matrix degradation and cell invasion in vitro and in vivo. In addition, upon binding to uPAR, uPA shows effects that are independent of its proteolytic activity.

Non-inflammatory synovial membranes from normal subjects or osteoarthritis patients expressed predominantly tPA, at the activity and antigenic level, which was associated to blood vessels.3 4 In contrast, in RA synovial tissues, tPA expression was reduced, while uPA activity was increased. Its corresponding antigen and mRNA were also increased, and mainly associated to the synovial lining layer. …
Electrophysiologic effects of ischemic preconditioning on QT dispersion during coronary angioplasty
Authors: Kaoru Okishige, Katsuhiro Yamashita, Haruhiko Yoshinaga, Kouji Azegami, Takako Satoh, Yoshenari Goseki, Satoki Fujii, Hiroshi Ohira, Shutarou Satake
Journal: Journal of the American College of Cardiology (1996)
Tumor Cell Loaded Type-1 Polarized Dendritic Cells Induce Th1-Mediated Tumor Immunity
Authors: David A. Hokey, Adriana T. Larregina, Geza Erdos, Simon C. Watkins, Louis D. Falo
Journal: Cancer Research (2005)

Abstract Dendritic cells are professional antigen-presenting cells capable of inducing and regulating innate and antigen-specific immune responses. Therapeutic cancer vaccines using ex vivo engineered or in vivo targeted dendritic cells are being evaluated in clinical trials. T-helper type-1 (Th1)–skewed immune responses are characterized by the preferential induction of antigen-specific IFN-γ–secreting CD4+ T cells and correlate with effector mechanisms important for tumor and viral immunity. Methods to “polarize” human monocyte-derived dendritic cells for the preferential induction of Th1-skewed immune responses have been developed, and polarized dendritic cells (DC1s) are being evaluated in preclinical and clinical studies. Here, we show that stimulation of bone marrow–derived murine dendritic cell populations with poly(I:C) and CpGs results in phenotypic maturation of dendritic cells and synergistic induction of durable, high-level IL-12p70 secretion characteristic of human type-1 polarized dendritic cells. Functionally, these dendritic cells induce antigen-specific Th1-type CD4+ T-cell activation in vitro and in vivo. Dendritic cell maturation and polarization are not inhibited by the presence of live B16 melanoma tumor cells, and tumor-loaded DC1s induce delayed-type hypersensitivity responses in vivo. DC1s loaded with B16 melanoma cells and injected into tumor-bearing mice induce Th1-skewed tumor-specific CD4+ T cells and a significant reduction in tumor growth. Tumor infiltrates in DC1-immunized animals are characterized by the presence of CD4+ T cells and activated macrophages. These results show a murine model of DC1 function and suggest an important role for CD4+ T cells and macrophages in DC1-induced antitumor immune responses. They have implications for the future development of DC1-based immunotherapies and strategies for clinical immune monitoring of their effectiveness.
Sudden Death from Haemorrhage into the Abdominal Cavity during Menstruation
Authors: E. J. Penny
Journal: BMJ (1886)

factory fibres, since it is found in animals devoid of smell.Like the optic chiasma, it is taken advantage of by crossing fibres of the great brain, its size varying inversely as that of the corpus callosum.By this root, the fibres of the olfactory nerve reach the extremity of the temporo-sphenoidal lobe, presenting, in their decussation, a close analogy to the optic nerves.The outer, larger, and more important root, lying on the under surface of the brain, passes backwards into the pyriform lobe.Here it divides into two parts, an outer thin expan- sion, which spreads over the surface of the lobe, and an inner thicker portion, which, passing to the inner side of the lobe, tucks itself in under the edge of the cortex-mantle.Omitting, for the moment, any account of the relation of these fibres to the hippocampus, the lecturer stated that the olfactory nervc was to be traced through the fimbria, posterior pillars, body, and anterior pillars of the fornix, into the corpus mammillare (corpora albicantia), in which it turns up as the bundle of Vicq d'Azyr, into the anterior end of the optic thala- mus.The anatomnical connections of this root were explained, and its functional coutinuity was prove(d by an appeal to what might be termed one of nature's experiments.In all aquatic mammalia, the sense of smell is either deficient or absent.In the porpois9, it is completely abrogated.The olfactory bulb is reduced to a mere cord, and all the other portions of the olfactory tract just indicated show a correspondinig want of development.The cross section of the body
The effect of antiarrhythmic drugs on depressed conduction and unidirectional block in sheep Purkinje fibers.
Authors: R W Wald, M B Waxman, E Downar
Journal: Circulation Research (1980)

We studied the effect of therapeutic concentrations of lidocaine, procainamide, quinidine, propranolol, and diphenylhydantoin on two models of depressed conduction and unidirectional block produced by asymmetric focal cooling and crushing in sheep Purkinje fibers. All drugs were shown to induce reversible deterioration of conduction. Unidirectional block was converted to bidirectional block with each drug. Improvement of conduction was rare and conversion of unidirectional block to bidirectional conduction never was observed. These experiments suggest that all five drugs may act by a uniform mechanism of action in some reentrant ventricular arrhythmias involving a zone of depressed conduction or unidirectional block within the Purkinje network.
DNA Methylation Changes after 5-Aza-2′-Deoxycytidine Therapy in Patients with Leukemia
Authors: Allen S. Yang, Ketan D. Doshi, Sang-Woon Choi, Joel B. Mason, Rajan K. Mannari, Vazganush Gharybian, Rene Luna, Asif Rashid, Lanlan Shen, Marcos R.H. Estecio, Hagop M. Kantarjian, Guillermo Garcia-Manero, Jean-Pierre J. Issa
Journal: Cancer Research (2006)

Abstract 5-Aza-2′-deoxycytidine (decitabine) is postulated to have clinical activity in myeloid leukemias via its ability to inhibit DNA methylation. To study this, we examined DNA methylation in patients with leukemia treated with decitabine. Five days after the treatment, total genomic 5-methylcytosine/cytosine decreased on average by 14% (from 4.3% to 3.7%), whereas methylation of repetitive DNA elements showed a mean decrease of 9% and 16% for Alu and long interspersed nucleotide elements, respectively. Methylation decreased linearly with increasing doses between 5 and 20 mg/m2/d (r = 0.88; P = 0.05) but showed a plateau above that. Hypomethylation correlated with response in patients with acute myelogenous leukemia treated with low doses (5-20 mg/m2/d), but patients with chronic myelogenous leukemia treated with high doses (100-180 mg/m2/d) showed no such correlation. Aberrant methylation of p15 (&amp;gt;10%) was found in 27% of patients, and 80% of these showed a decrease by at least one third, but this did not correlate with response. The imprinted gene H19 showed little change in methylation after decitabine. In conclusion, we show dose-dependent hypomethylation after decitabine at low doses. Increasing the dose, which has been shown previously to result in a reduced response rate, was not accompanied by further hypomethylation. (Cancer Res 2006; 66(10): 5495-503)
Focal adhesion kinase and angiogenesis. Where do we go from here?
Authors: M RIZZO
Journal: Cardiovascular Research (2004)

See article by Peng et al. (pages 421–430) in this issue. 

Processes involved in the generation of new blood vessels during embryonic development, wound healing, ischemia, inflammation and tumor growth have captured the imagination of investigators for many years. Numerous studies have led to the well-founded expectation that regulation of angiogenesis will soon be a therapeutically useful approach for a wide range of disorders, ranging from inflammation to neoplastic growth [1]. The angiogenic response is a multifaceted and highly orchestrated process initiated by the endothelial cells of preexisting capillaries. [2]. Responding to a wide array of external stimuli, endothelial cells engage in a series of events that lead to degradation of the extracellular matrix, apparently allowing the cells to proliferate, migrate freely into the perivascular space and differentiate into capillary-like structures [2,3]. The subsequent integration of mural cells and other perivascular cells on the surface of the developing endothelium results in the transformation of these immature tube-like structures into functionally mature blood vessels [2,4]. During neovascularization, the importance of the relationship of the endothelial cells with the microenvironment cannot be overemphasized [5]. In fact, the ability of the endothelial cells to adequately respond to angiogenic challenges is highly dependent on both their interactions with the extracellular matrix and agonists [5,6]. … 

*Signal Transduction Laboratory, Methodist Research Institute, 1701 N. Senate, Rm. E504, Indianapolis, IN 46202, USA. Tel.: +1 317 962 6891; fax: +1 317 962 9369. Email address: mrizzo{at}clarian.org
Association of Comorbidities With Overall Survival in Myelodysplastic Syndrome: Development of a Prognostic Model
Authors: Kiran Naqvi, Guillermo Garcia-Manero, Sagar Sardesai, Jeong Oh, Carlos E. Vigil, Sherry Pierce, Xiudong Lei, Jianqin Shan, Hagop M. Kantarjian, Maria E. Suarez-Almazor
Journal: Journal of Clinical Oncology (2011)

Patients with cancer often experience comorbidities that may affect their prognosis and outcome. The objective of this study was to determine the effect of comorbidities on the survival of patients with myelodysplastic syndrome (MDS).We conducted a retrospective cohort study of 600 consecutive patients with MDS who presented to MD Anderson Cancer Center from January 2002 to December 2004. The Adult Comorbidity Evaluation-27 (ACE-27) scale was used to assess comorbidities. Data on demographics, International Prognostic Scoring System (IPSS), treatment, and outcome (leukemic transformation and survival) were collected. Kaplan-Meier methods and Cox regression were used to assess survival. A prognostic model incorporating baseline comorbidities with age and IPSS was developed to predict survival.Overall median survival was 18.6 months. According to the ACE-27 categories, median survival was 31.8, 16.8, 15.2, and 9.7 months for those with none, mild, moderate, and severe comorbidities, respectively (P < .001). Adjusted hazard ratios were 1.3, 1.6, and 2.3 for mild, moderate, and severe comorbidities, respectively, compared with no comorbidities (P < .001). A final prognostic model including age, IPSS, and comorbidity score predicted median survival of 43.0, 23.0, and 9.0 months for lower-, intermediate-, and high-risk groups, respectively (P < .001).Comorbidities have a significant impact on the survival of patients with MDS. Patients with severe comorbidity had a 50% decrease in survival, independent of age and IPSS risk group. A comprehensive assessment of the severity of comorbidities helps predict survival in patients with MDS.
Immunophenotypic analysis of early mycotic lesions
Authors: D.N. Slater
Journal: British Journal of Dermatology (1987)

Journal Article Immunophenotypic analysis of early mycotic lesions Get access D.N. Slater D.N. Slater Department of Histopathology, Rotherham District General Hospital, Oakwood, Rotherham S60 2UD, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue 2, 1 August 1987, Pages 262–263, https://doi.org/10.1111/j.1365-2133.1987.tb04128.x Published: 01 August 1987