tbuckley/cabot-search huggingface dataset:
MAPS IN THE BRAIN: What Can We Learn from Them?
Authors: Dmitri B. Chklovskii, Alexei A. Koulakov
Journal: Annual Review of Neuroscience (2004)

In mammalian visual cortex, neurons are organized according to their functional properties into multiple maps such as retinotopic, ocular dominance, orientation preference, direction of motion, and others. What determines the organization of cortical maps? We argue that cortical maps reflect neuronal connectivity in intracortical circuits. Because connecting distant neurons requires costly wiring (i.e., axons and dendrites), there is an evolutionary pressure to place connected neurons as close to each other as possible. Then, cortical maps may be viewed as solutions that minimize wiring cost for given intracortical connectivity. These solutions can help us in inferring intracortical connectivity and, ultimately, in understanding the function of the visual system.
Molecular responses to hypoxia in tumor cells.
Authors: Manfred Kunz, Saleh M Ibrahim
Journal: Molecular Cancer (2003)

Highly aggressive, rapidly growing tumors are exposed to hypoxia or even anoxia which occurs as a consequence of inadequate blood supply. Both hypoxia and consecutive hypoxia/reoxygenation exert a variety of influences on tumor cell biology. Among these are activation of certain signal transduction pathways and gene regulatory mechanisms, induction of selection processes for gene mutations, tumor cell apoptosis and tumor angiogenesis. Most of these mechanisms contribute to tumor progression. Therefore, tissue hypoxia has been regarded as a central factor for tumor aggressiveness and metastasis. In this review, we summarize the current knowledge about the molecular mechanisms induced by tumor cell hypoxia with a special emphasis on intracellular signal transduction, gene regulation, angiogenesis and apoptosis. Interfering with these pathways might open perspectives for future innovative treatment of highly aggressive metastasizing tumors.
Fibroblast Expression of an IκB Dominant-Negative Transgene Attenuates Renal Fibrosis
Authors: Tsutomu Inoue, Tsuneo Takenaka, Matsuhiko Hayashi, Toshiaki Monkawa, Jun Yoshino, Kouji Shimoda, Eric G. Neilson, Hiromichi Suzuki, Hirokazu Okada
Journal: Journal of the American Society of Nephrology (2010)

It is not clear whether interstitial fibroblasts or tubular epithelial cells are primarily responsible for the profibrotic effects of NF-κB activation during renal fibrogenesis. Here, we crossed mice carrying a conditional IκB dominant-negative transgene (IκBdN) with mice transgenic for cell-specific FSP1.Cre (FSP1+ fibroblasts) or γGT.Cre (proximal tubular epithelia) and challenged all progeny with unilateral ureteral obstruction. We determined NF-κB activation by nuclear localization of phosphorylated p65 (pp65) in renal tissues after 7 days. We observed inhibition of NF-κB activation in interstitial cells and tubular epithelia in obstructed kidneys of FSP1.Cre;IκBdN and γGT.Cre;IκBdN mice, respectively, compared with IκBdN controls (P < 0.05). Deposition of extracellular matrix, however, was significantly lower in the obstructed kidneys of FSP1.Cre;IκBdN mice but not in γGT.Cre;IκBdN mice (P < 0.05). In addition, levels of mRNA encoding the profibrotic PAI-1, fibronectin-EIIIA, and type I (α1) procollagen were significantly lower in obstructed kidneys of FSP1.Cre;IκBdN mice compared with γGT.Cre;IκBdN mice (P < 0.05). Taken together, these data support a profibrotic role for fibroblasts, but not proximal tubular epithelial cells, in modulating NF-κB activation during renal fibrogenesis.
AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update
Authors: Sidney C. Smith, Emelia J. Benjamin, Robert O. Bonow, Lynne T. Braun, Mark A. Creager, Barry A. Franklin, Raymond J. Gibbons, Scott M. Grundy, Loren F. Hiratzka, Daniel W. Jones, Donald M. Lloyd-Jones, Margo Minissian, Lori Mosca, Eric D. Peterson, Ralph L. Sacco, John Spertus, James H. Stein, Kathryn A. Taubert
Journal: Circulation (2011)

The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship
Dietary Fat and Breast Cancer
Authors: Marion M. Lee, Scarlett S. Lin
Journal: Annual Review of Nutrition (2000)

One of the most often studied associations in epidemiology is dietary fat and breast cancer risk. That migrants from low-risk countries increase their risk on immigrating to higher-risk countries suggests that some modifiable lifestyle or environmental factor is responsible for the development of breast cancer. Although early international correlational studies and experimental animals studies support dietary fat as a risk factor for breast cancer, more recent data from case-control studies and cohort studies have been equivocal, thus the analytical data do not support a strong positive association. The conflicting results from analytic studies may be due to methodologic issues associated with study design, dietary assessment tools, measurement error, improper statistical analyses, and a lack of heterogeneity in fat intake among the study population. Moreover, current dietary questionnaires may be inadequate in capturing true dietary intakes or capturing the risk with exposure during earlier periods of a woman's life. Although two large clinical trials investigating the fat/breast cancer relationships issue are underway, researchers are generally skeptical at their ability to detect an independent association between fat and breast cancer risk. Further epidemiologic studies using current methodology may not prove to be fruitful in generating definitive answers to shed light on this controversial issue. In addition, rather than concentrating on dietary fat, researchers should focus on diets that are not only low in saturated fat, but also high in fruit and vegetable consumption. Researchers should take advantage of advances in molecular and genetic technology for a different perspective in examining the issue. For example, markers of susceptibility to breast cancer that can detect women at higher risk for breast cancer may be helpful in clarifying the role of dietary fat. More comprehensive and multiple approaches to studying dietary factors and breast cancer are recommended.
Endothelial Cell Production of Nitrogen Oxides in Response to Interferon in Combination With Tumor Necrosis Factor, Interleukin-1, or Endotoxin
Authors: R. G. Kilbourn, P. Belloni
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Endothelial Cell Production of Nitrogen Oxides in Response to Interferon γ in Combination With Tumor Necrosis Factor, Interleukin-1, or Endotoxin Get access Robert G. Kilbourn, Robert G. Kilbourn * Department of Medical Oncology, Genitourinary Section,The University of Texas M. D. Anderson Cancer CenterHouston, TX * Correspondence to: Robert G. Kilboum, Ph.D., Department of Medical Oncology, Genitourinary Section, The University of Texas M. D. Anderson Cancer Center, Box 13, 1515 Holcombe Blvd., Houston, TX 77030. Search for other works by this author on: Oxford Academic PubMed Google Scholar Paula Belloni Paula Belloni Department of Tumor Biology,The University of Texas M. D. Anderson Cancer CenterHouston, TX Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 9, 2 May 1990, Pages 772–776, https://doi.org/10.1093/jnci/82.9.772 Published: 02 May 1990 Article history Received: 16 January 1990 Accepted: 18 January 1990 Published: 02 May 1990
Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders
Authors: E Joanna Baxter, Linda M Scott, Peter J Campbell, Clare East, Nasios Fourouclas, Soheila Swanton, George S Vassiliou, Anthony J Bench, Elaine M Boyd, Natasha Curtin, Mike A Scott, Wendy N Erber, Anthony R Green
Journal: The Lancet (2005)
Effects of interferon gamma on cultured synovial cells from patients with rheumatoid arthritis: inhibition of cell growth, prostaglandin E2, and collagenase release.
Authors: H Nakajima, Y Hiyama, W Tsukada, H Warabi, S Uchida, S Hirose
Journal: Annals of the Rheumatic Diseases (1990)

The effects of recombinant interferon gamma (rIFN gamma) on the in vitro growth of adherent synovial fibroblast-like cells from patients with rheumatoid arthritis (RA) and also on the release of prostaglandin E2 and collagenase from these cells stimulated with recombinant interleukin-1 beta (rIL-1 beta) were investigated. The growth of adherent synovial cells from six of nine samples, determined by [3H]thymidine incorporation, was inhibited by rIFN gamma in a manner dependent on dose. The release of prostaglandin E2 and collagenase from adherent synovial cells stimulated with rIL-1 beta was also suppressed by rIFN gamma in all samples tested, though the basal release of these inflammatory mediators was little influenced. No apparent correlation between inhibition of proliferation by rIFN gamma and either inhibition by rIFN gamma of rIL-1 beta stimulated prostaglandin E2 release or the endogenous synthesis of prostaglandins was found.
Patients with Obstructive Sleep Apnea Exhibit Genioglossus Dysfunction that Is Normalized after Treatment with Continuous Positive Airway Pressure
Authors: MIGUEL CARRERA, FERRAN BARBÉ, JAUME SAULEDA, MANUEL TOMÁS, CRISTINA GÓMEZ, ALVAR GN. AGUSTÍ
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Obstructive sleep apnea syndrome (OSAS) is characterized by repetitive episodes of pharyngeal closure during sleep. The pathogenesis of OSAS is unclear. We hypothesized that the genioglossus (GG), the most important pharyngeal dilator muscle, would be abnormal in patients with OSAS. Further, because treatment with continuous positive airway pressure (CPAP) is very effective clinically in these patients, we investigated the effects of CPAP upon the structure and function of the GG. We studied 16 patients with OSAS (nine of them at diagnosis and seven after having been under treatment with CPAP for at least 1 yr) and 11 control subjects in whom OSAS was excluded clinically. A biopsy of the GG was obtained in each subject, mounted in a tissue bath, and stimulated through platinum electrodes. The following measurements were obtained: maximal twitch tension, contraction time, half-relaxation time, the force-frequency relationship, and the response to a fatiguing protocol. The percentage of type I (“slow twitch”) and type II (“fast twitch”) fibers was also quantified. Patients with OSAS showed a greater GG fatigability than did control subjects (ANOVA, p < 0.001). Interestingly, this abnormality was entirely corrected by CPAP. Likewise, the percentage of type II fibers was significantly higher in patients with OSAS (59 ± 4%) than in control subjects (39 ± 4%, p < 0.001) and, again, these structural changes were corrected by CPAP (40 ± 3%, p < 0.001). These results show that the function and structure of the GG is abnormal in patients with OSAS. Because these abnormalities are corrected by CPAP, we suggest that they are likely a consequence, not a cause, of the disease.
Effects of Sympathetic Nerve Stimulation on the Pulmonary Arterial Tree of the Isolated Lobe Perfused in Situ
Authors: ROLAND H. INGRAM, J. PETER SZIDON, RICHARD SKALAK, ALFRED P. FISHMAN
Journal: Circulation Research (1968)

The hemodynamic response to sympathetic nerve stimulation (SNS) was studied in canine lung lobes isolated in situ and perfused with a pulsatile pump. For the same input pulse, both the rate of rise and the rate of fall of pulmonary arterial pressure increased during SNS; the peak systolic pressure was also higher during SNS, whereas diastolic pressure levels were either at, or below, control levels. The increase in pulse pressure produced little or no change in mean pulmonary artery pressure and resistance. During SNS, compliance per unit length in large arteries fell, pulse wave velocity increased, and elastic modulus increased. Phenoxybenzamine produced opposite changes. Norepinephrine injections increased resistance and produced smaller compliance changes than SNS. Flow loads imposed by short bursts of rapid pump rate at constant stroke volume caused increments of vascular volume which returned to control levels after return to the slower rate. Volume increments were smaller and restoration rates faster during SNS than during control. After phenoxybenzamine, volume increments were larger and restoration rates slower than control. The results indicate that the distensibility of the large pulmonary arteries and the precapillary bed is decreased during sympathetic stimulation, while calculated resistance is not changed.
Sequential research-related biopsies in phase I trials: acceptance, feasibility and safety
Authors: C.A. Gomez-Roca, L. Lacroix, C. Massard, T. De Baere, F. Deschamps, R. Pramod, R. Bahleda, E. Deutsch, C. Bourgier, E. Angevin, V. Lazar, V. Ribrag, S. Koscielny, L. Chami, N. Lassau, C. Dromain, C. Robert, E. Routier, J.P. Armand, J.-C. Soria
Journal: Annals of Oncology (2011)
The Anti–Human Leukocyte Antigen-DR Monoclonal Antibody 1D09C3 Activates the Mitochondrial Cell Death Pathway and Exerts a Potent Antitumor Activity in Lymphoma-Bearing Nonobese Diabetic/Severe Combined Immunodeficient Mice
Authors: Carmelo Carlo-Stella, Massimo Di Nicola, Maria Caterina Turco, Loredana Cleris, Cristiana Lavazza, Paolo Longoni, Marco Milanesi, Michele Magni, Massimo Ammirante, Arturo Leone, Zoltan Nagy, Walter R. Gioffrè, Franca Formelli, Alessandro M. Gianni
Journal: Cancer Research (2006)

Abstract The fully human anti-HLA-DR antibody 1D09C3 has been shown to delay lymphoma cell growth in severe combined immunodeficient (SCID) mice. The present study was aimed at (a) investigating the mechanism(s) of 1D09C3-induced cell death and (b) further exploring the therapeutic efficacy of 1D09C3 in nonobese diabetic (NOD)/SCID mice. The chronic lymphocytic leukemia cell line JVM-2 and the mantle cell lymphoma cell line GRANTA-519 were used. Generation of reactive oxygen species (ROS) and mitochondrial membrane depolarization were measured by flow cytometry following cell incubation with dihydroethidium and TMRE, respectively. Western blot analysis was used to detect c-Jun-NH2-kinase (JNK) phosphorylation and apoptosis-inducing factor (AIF). NOD/SCID mice were used to investigate the activity of 1D09C3 in early- or advanced-stage tumor xenografts. In vitro, 1D09C3-induced cell death involves a cascade of events, including ROS increase, JNK activation, mitochondrial membrane depolarization, and AIF release from mitochondria. Inhibition of JNK activity significantly reduced 1D09C3-induced apoptosis, indicating that 1D09C3 activity involves activation of the kinase. In vivo, 1D09C3 induces long-term disease-free survival in a significant proportion of tumor-bearing mice treated at an early stage of disease. Treatment of mice bearing advanced-stage lymphoma results in a highly significant prolongation of survival. These data show that 1D09C3 (a) exerts a potent antitumor effect by activating ROS-dependent, JNK-driven cell death, (b) cures the great majority of mice treated at an early-stage of disease, and (c) significantly prolongs survival of mice with advanced-stage disease. (Cancer Res 2006; 66(3): 1799-808)
Peripheral T-Cell Tolerance Associated with Prostate Cancer Is Independent from CD4+CD25+ Regulatory T Cells
Authors: Elena Degl'Innocenti, Matteo Grioni, Giusy Capuano, Elena Jachetti, Massimo Freschi, Maria T.S. Bertilaccio, Rodrigo Hess-Michelini, Claudio Doglioni, Matteo Bellone
Journal: Cancer Research (2008)

Abstract CD4+CD25+Foxp3+ regulatory T cells (Treg) are thought to suppress the natural and vaccine-induced immune response against tumor-associated antigens (TAA). Here, we show that Treg accumulate in tumors and tumor-draining lymph nodes of aging transgenic adenocarcinoma of the mouse prostate (TRAMP) male mice, which spontaneously develop prostate cancer. TAA overexpression and disease progression associate also with induction of TAA-specific tolerance. TAA-specific T cells were found in the lymphoid organs of tumor-bearing mice. However, they had lost the ability to release IFN-γ and kill relevant targets. Neither in vivo depletion of Treg by PC61 monoclonal antibody followed by repeated vaccinations with antigen-pulsed dendritic cells nor the combined treatment with 1-methyl-l-tryptophan inhibitor of the enzyme indoleamine 2,3-dyoxigenase, PC61 antibody, and dendritic cell vaccination restored the TAA-specific immune response. Treg did not seem to control the early phases of tolerance induction, as well. Indeed, depletion of Treg, starting at week 6, the age at which TRAMP mice are not yet tolerant, and prolonged up to week 12, did not avoid tolerance induction. A similar accumulation of Treg was found in the lymph nodes draining the site of dendritic cell vaccination both in TRAMP and wild-type animals. Hence, we conclude that Treg accrual is a phenomenon common to the sites of an ongoing immune response, and in TRAMP mice in particular, Treg are dispensable for induction of tumor-specific tolerance. [Cancer Res 2008;68(1):292–300]
Clinical stability and switch therapy in hospitalised patients with community-acquired pneumonia: are we there yet?
Authors: Julio A. Ramirez
Journal: European Respiratory Journal (2012)

In this issue of the European Respiratory Journal , Engel et al. [1] studied barriers for early switch therapy in hospitalised patients with community-acquired pneumonia (CAP). The authors reference our initial work in the field of switch therapy, published in 1995 in Archives of Internal Medicine [2]. In hospitalised patients with CAP, the standard of practice before 1995 was to use intravenous antibiotics for the full duration of therapy. During our initial study, we obtained consent from patients to see if they were willing to participate in a trial using oral antibiotics once they reached clinical stability. Our Institutional Review Board requested a full evaluation of the initial 10 patients enrolled in the trial to be sure that a switch to oral antibiotics would not be associated with poor clinical outcomes. During the development of the protocol we decided to define clinical stability using two symptoms of CAP (cough and sputum production) and two signs of systemic response (fever and leukocytosis). Patients were defined as …
Urinary Human Chorionic Gonadotropin Free β-Subunit and β-Core Fragment: A New Marker of Gynecological Cancers
Authors: Laurence A. Cole, Yixun Wang, Margaret Elliott, Murshid Latif, Joseph T. Chambers, Setsuko K. Chambers, Peter E. Schwartz
Journal: Cancer Research (1988)

Many investigators have shown that a small proportion (13-36%) of subjects with nontrophoblastic gynecological cancers have elevated serum levels of human chorionic gonadotropin (hCG). The low proportion with detectable levels and the accompanying low titers have limited the use of hCG as a tumor marker. hCG is a glycoprotein composed of two noncovalently linked subunits (alpha and beta), which are the products of separate genes. With the intent of expanding the use of hCG as a tumor marker we investigated levels of hCG free beta-subunit and asialo free beta-subunit and its core glycopeptide (composed of beta-subunit residues 6-40 disulfide-linked to 55-92), collectively called urinary gonadotropin fragments (UGF), in healthy and cancer patients. An immunoradiometric assay was developed, using the core glycopeptide-directed antibody B204, that similarly measures the hCG free beta-subunit and the asialo free beta-subunit and its core glycopeptide. Parallel urine and serum samples were collected from 87 women with active gynecological cancer and hCG and UGF were measured. Just 18% of the women tested had detectable serum levels of hCG (greater than 0.2 ng/ml); none had elevated serum levels in the UGF assay (greater than 0.2 ng/ml). Of the same group, 32% had detectable urine hCG levels (mean titer, 0.50 ng/ml) and 74% exhibited elevated urinary levels in the UGF assay (mean titer, 2.0 ng/ml). In a control group (urines from 50 nonpregnant healthy women), 47 negative and three borderline positive results (0.30, 0.35, and 0.48 ng/ml) were observed in the UGF assay. These results suggested a sensitivity of 74% and specificity of 92% for the UGF test for gynecological cancers. By disease, 70% of those with cervical, 73% of those with ovarian, and 77% of those with endometrial cancers had detectable UGF levels (greater than 0.2 ng/ml). By stage, 50, 62, 75, 86, and 100% of those with stage 1, 2, 3, 4, or recurrent disease, respectively, had positive results. UGF is a promising new marker of gynecological malignancies.
High- and Low-Affinity Sites for [ <sup>3</sup> H]Dofetilide Binding to Guinea Pig Myocytes
Authors: Henry J. Duff, Zhong-Ping Feng, Robert S. Sheldon
Journal: Circulation Research (1995)

Abstract Dofetilide specifically blocks the rapid component of the delayed rectifier current (I Kr ) at nanomolar concentrations in a saturable manner, suggesting the presence of a receptor. We characterized two [ 3 H]dofetilide binding sites to ventricular myocytes from adult guinea pigs by using a conventional filter assay. Scatchard analysis revealed two binding sites with different affinities: a high-affinity site ( K d , 2.8±0.3×10 −8 mol/L; B max , 76±15 fmol/10 6 myocytes) and a low-affinity site ( K d , 1.64±0.4×10 −6 mol/L; B max , 1620±260 fmol/10 6 myocytes) (n=11). Kinetic studies showed that there were two dissociation rate constants for [ 3 H]dofetilide (0.02±0.005 min −1 [high-affinity site] and 0.22±0.064 min −1 [low-affinity site], n=4), although the observed association rate constant is equally well fit to a single- or two-site model. The ability of known I Kr blockers to compete with [ 3 H]dofetilide binding to both sites was assessed. E4031, clofilium, quinidine, and sotalol competed for binding at both sites. Disopyramide and NAPA only competed for a single binding site. The mean IC 50 values for inhibition of binding to both the high- and low-affinity binding sites correlated with their concentrations required to inhibit I Kr in electrophysiological studies. However, inhibition of [ 3 H]dofetilide binding to the high-affinity site by class III antiarrhythmic drugs occurred at pharmacological concentrations, whereas suprapharmacological concentrations were required to inhibit binding to the low-affinity site. To demonstrate that the low-affinity site was not associated with I Kr , [ 3 H]dofetilide binding was assessed in rat ventricular myocytes, which do not express I Kr electrophysiologically. In the rat, we observed specific binding of [ 3 H]dofetilide only to the low-affinity site ( K d , 2.9±0.8×10 −7 mol/L; B max , 248±75 fmol/10 6 myocytes; n=9). In addition, low concentrations of solatol (50 μmol/L) inhibit [ 3 H]dofetilide only at its high-affinity site without affecting its low-affinity site. Thus, it can be concluded that the high-affinity [ 3 H]dofetilide binding site is associated with I Kr in guinea pig ventricular myocytes.
Intratumoral Aromatase in Human Breast, Endometrial, and Ovarian Malignancies*
Authors: Hironobu Sasano, Nobuhiro Harada
Journal: Endocrine Reviews (1998)

In human estrogen-dependent neoplasms such as breast, endometrioid endometrial, and surface epithelial-stromal ovarian carcinomas, intratumoral aromatase is considered to play important roles in converting circulating androgens derived from adrenal cortex and/or ovary to estrogens, possibly in association with 17 beta-HSD type 1 and estrogen sulfatase. Analysis of intratumoral aromatase in these estrogen-dependent neoplasms is important not only in understanding the development and biological behavior of these tumors, but also in the clinical management of these patients, because suppression of intratumoral aromatase by newly developed aromatase inhibitors may provide new potentials in endocrine therapy of these patients.