tbuckley/cabot-search huggingface dataset:
A Specific Genetic Background Is Required for Acquisition and Expression of Virulence Factors in Escherichia coli
Authors: Patricia Escobar-Páramo, Olivier Clermont, Anne-Béatrice Blanc-Potard, Hung Bui, Chantal Le Bouguénec, Erick Denamur
Journal: Molecular Biology and Evolution (2004)

In bacteria, the evolution of pathogenicity seems to be the result of the constant arrival of virulence factors (VFs) into the bacterial genome. However, the integration, retention, and/or expression of these factors may be the result of the interaction between the new arriving genes and the bacterial genomic background. To test this hypothesis, a phylogenetic analysis was done on a collection of 98 Escherichia coli/Shigella strains representing the pathogenic and commensal diversity of the species. The distribution of 17 VFs associated to the different E. coli pathovars was superimposed on the phylogenetic tree. Three major types of VFs can be recognized: (1) VFs that arrive and are expressed in different genetic backgrounds (such as VFs associated with the pathovars of mild chronic diarrhea: enteroaggregative, enteropathogenic, and diffusely-adhering E. coli), (2) VFs that arrive in different genetic backgrounds but are preferentially found, associated with a specific pathology, in only one particular background (such as VFs associated with extraintestinal diseases), and (3) VFs that require a particular genetic background for the arrival and expression of their virulence potential (such as VFs associated with pathovars typical of severe acute diarrhea: enterohemorragic, enterotoxigenic, and enteroinvasive E. coli strains). The possibility of a single arrival of VFs by chance, followed by a vertical transmission, was ruled out by comparing the evolutionary histories of some of these VFs to the strain phylogeny. These evidences suggest that important changes in the genome of E. coli have occurred during the diversification of the species, allowing the virulence factors associated with severe acute diarrhea to arrive in the population. Thus, the E. coli genome seems to be formed by an "ancestral" and a "derived" background, each one responsible for the acquisition and expression of different virulence factors.
A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development
Authors: Jennifer M. Burns, Bretton C. Summers, Yu Wang, Anita Melikian, Rob Berahovich, Zhenhua Miao, Mark E. T. Penfold, Mary Jean Sunshine, Dan R. Littman, Calvin J. Kuo, Kevin Wei, Brian E. McMaster, Kim Wright, Maureen C. Howard, Thomas J. Schall
Journal: The Journal of Experimental Medicine (2006)

The chemokine stromal cell–derived factor (SDF-1; also known as chemokine ligand 12 [CXCL12]) regulates many essential biological processes, including cardiac and neuronal development, stem cell motility, neovascularization, angiogenesis, apoptosis, and tumorigenesis. It is generally believed that SDF-1 mediates these many disparate processes via a single cell surface receptor known as chemokine receptor 4 (CXCR4). This paper characterizes an alternate receptor, CXCR7, which binds with high affinity to SDF-1 and to a second chemokine, interferon-inducible T cell α chemoattractant (I-TAC; also known as CXCL11). Membrane-associated CXCR7 is expressed on many tumor cell lines, on activated endothelial cells, and on fetal liver cells, but on few other cell types. Unlike many other chemokine receptors, ligand activation of CXCR7 does not cause Ca2+ mobilization or cell migration. However, expression of CXCR7 provides cells with a growth and survival advantage and increased adhesion properties. Consistent with a role for CXCR7 in cell survival and adhesion, a specific, high affinity small molecule antagonist to CXCR7 impedes in vivo tumor growth in animal models, validating this new receptor as a target for development of novel cancer therapeutics.
MUCking about in IPF: identification of a novel goblet cell phenotype in pulmonary fibrosis
Authors: C. D. Bingle
Journal: Thorax (2011)

In the insect olfactory system the antennal lobe generates oscillatory synchronization of its output as a framework for coincidence detection by its target, the mushroom body (MB). The intrinsic neurons of the MB (Kenyon cells, KCs) are thus a good model system in which to investigate the functional relevance of oscillations and neural synchronization. We combine electrophysiological and modeling approaches to examine how intrinsic and circuit properties might contribute to the preference of KCs for coincident input and how their decoding of olfactory information is affected by the absence of oscillatory synchronization in their input. We show that voltage-dependent subthreshold properties of KCs bring about a supralinear summation of their inputs, favoring responses to coincident EPSPs. Abolishing oscillatory synchronization weakens the preference of KCs for coincident input and causes a large reduction in their odor specificity. Finally, we find that a decoding strategy that is based on coincidence detection enhances both noise tolerance and input discriminability by KCs.
Role of Uroguanylin, a Peptide with Natriuretic Activity, in Rats with Experimental Nephrotic Syndrome
Authors: Masao Kikuchi, Shouichi Fujimoto, Hiroko Fukae, Hiroshi Kinoshita, Toshihiro Kita, Masamitsu Nakazato, Tanenao Eto
Journal: Journal of the American Society of Nephrology (2004)

Uroguanylin induces natriuresis and diuresis in vivo as well as in vitro and is found mainly in the intestine and the kidney. However, the roles of uroguanylin in nephrotic syndrome, which is associated with sodium and water retention, have not been determined. Therefore, changes in the urine and plasma concentration of immunoreactive uroguanylin (ir-uroguanylin) and its mRNA expression in the kidney and intestine were examined using rats with puromycin aminonucleoside (PAN)-induced nephrosis. Male Sprague-Dawley rats were separated into control and nephrotic groups, and then the urinary excretion of sodium, protein, and ir-uroguanylin was examined over time. The plasma levels and renal and intestinal mRNA expression of uroguanylin at the periods of sodium retention and remarkable natriuresis also were evaluated. The sequential changes of urinary ir-uroguanylin excretion in the nephrotic group were similar to those of urinary sodium excretion. When the urinary excretion of ir-uroguanylin and sodium peaked, the plasma level of ir-uroguanylin also increased compared with that of the control group. Uroguanylin mRNA expression in the kidney increased during the period of sodium retention and then decreased during the period of remarkable natriuresis. Uroguanylin mRNA expression in the small intestines of control and nephrotic rats were identical. However, in a unilateral PAN-induced proteinuria, uroguanylin expression significantly increased in the PAN-perfused kidney compared with that in the opposite kidney. Considering the natriuretic effect of uroguanylin, these results suggested that uroguanylin plays an important role as a natriuretic factor in nephrotic syndrome via both the circulation and the kidney itself.
Implication of the Autologous Immune System in <i>BCR–ABL</i> Transcript Variations in Chronic Myelogenous Leukemia Patients Treated with Imatinib
Authors: Geoffrey D. Clapp, Thomas Lepoutre, Raouf El Cheikh, Samuel Bernard, Jérémy Ruby, Hélène Labussière-Wallet, Franck E. Nicolini, Doron Levy
Journal: Cancer Research (2015)

Imatinib and other tyrosine kinase inhibitors (TKI) have improved treatment of chronic myelogenous leukemia (CML); however, most patients are not cured. Deeper mechanistic understanding may improve TKI combination therapies to better control the residual leukemic cell population. In analyzing our patients' data, we found that many patients who otherwise responded well to imatinib therapy still showed variations in their BCR-ABL transcripts. To investigate this phenomenon, we applied a mathematical model that integrates CML and an autologous immune response to the patients' data. We define an immune window or a range of leukemic loads for which the autologous immune system induces an improved response. Our modeling results suggest that, at diagnosis, a patient's leukemic load is able to partially or fully suppress the autologous immune response developed in a majority of patients, toward the CML clone(s). Imatinib therapy drives the leukemic population into the "immune window," allowing the patient's autologous immune cells to expand and eventually mount an efficient recognition of the residual leukemic burden. This response drives the leukemic load below this immune window, allowing the leukemic population to partially recover until another weaker immune response is initiated. Thus, the autologous immune response may explain the oscillations in BCR-ABL transcripts regularly observed in patients on imatinib.
Activation of ErbB2 by Overexpression or by Transmembrane Neuregulin Results in Differential Signaling and Sensitivity to Herceptin
Authors: Laura Yuste, Juan C. Montero, Azucena Esparís-Ogando, Atanasio Pandiella
Journal: Cancer Research (2005)

Abstract The ligands of the epidermal growth factor family and their receptors, the ErbB proteins, have been linked to the development of different types of cancer. Particular attention has focused on ErbB2, whose activation may occur by receptor overexpression or by ligand-induced oligomerization with other ErbB receptors. Whether these two modes of ErbB2 activation cause the same biological responses is unknown. Here, we uncovered important differences in the signaling, proliferation rates, and the response to anti-ErbB2 antibodies when comparing MCF7 cells expressing the ligand neuregulin, to MCF7 cells overexpressing ErbB2. Expression of neuregulin caused higher proliferation than ErbB2 overexpression. Transmembrane neuregulin expression was accompanied by constitutive activation of ErbB2, ErbB3, and ErbB4 receptors. ErbB2 overexpression caused tyrosine phosphorylation of ErbB2, whereas ErbB3 and ErbB4 were only slightly tyrosine phosphorylated. Autocrine transmembrane neuregulin also caused constitutive activation of several signaling pathways, such as the Erk1/2, Erk5, and Akt routes, which have been linked to breast cancer cell proliferation. Interestingly, expression of neuregulin increased p21 levels and this was required for the proliferation of MCF7 cells. Treatment with the anti-ErbB2 receptor antibody Herceptin had an inhibitory effect on proliferation only in cells expressing neuregulin but not on cells overexpressing ErbB2, and its inhibitory activity was accompanied by a decrease in p21. These results suggest that Herceptin may also be of help in the treatment of tumors in which neuregulin feeds the tumoral tissue.
PUVA therapy prevents sensitization to mechlorethamine in patients with psoriasis
Authors: G. MAUDUIT, O. SILVESTRE, J. THIVOLET
Journal: British Journal of Dermatology (1985)

Two groups of 20 patients with psoriasis were treated with mechlorethamine applied topically (group A) or with PUVA combined with mechlorethamine (group B). In group B mechlorethamine was started after six PUVA treatments. Results showed a significant decrease of the incidence of contact dermatitis in group B (30%) compared with group A (75%). Allergic dermatitis, demonstrated by a positive patch test to mechlorethamine with an histology of eczema, was observed in 55% of patients in group A and 20% in group B. The incidence of irritant dermatitis was not significantly different in the two groups. Allergic dermatitis was observed later in group B: after an average of 32.2 applications of mechlorethamine compared with 25 applications in group A. Possible mechanisms responsible for these results are reduction of epidermal Langerhans cells by PUVA therapy and induction of antigen-specific suppressor T cells. Patients living far from a specialized centre might be treated initially with PUVA therapy then with mechlorethamine alone, at home. This schedule may reduce the incidence of contact dermatitis to mechlorethamine.
Loss of Oriented Cell Division Does not Initiate Cyst Formation
Authors: Saori Nishio, Xin Tian, Anna Rachel Gallagher, Zhiheng Yu, Vishal Patel, Peter Igarashi, Stefan Somlo
Journal: Journal of the American Society of Nephrology (2009)

Polycystic kidney disease (PKD) can arise from either developmental or postdevelopmental processes. Recessive PKD, caused by mutations in PKHD1, is a developmental defect, whereas dominant PKD, caused by mutations in PKD1 or PKD2, occurs by a cellular recessive mechanism in mature kidneys. Oriented cell division is a feature of planar cell polarity that describes the orientation of the mitotic axes of dividing cells during development with respect to the luminal vector of the elongating nephron. In polycystic mutant mice, the loss of oriented cell division may also contribute to the pathogenesis of PKD. Here, we examined the role of oriented cell division in mouse models based on mutations in Pkd1, Pkd2, and Pkhd1. Precystic tubules after kidney-selective inactivation of either Pkd1 or Pkd2 did not lose oriented division before cystic dilation but lost oriented division after tubular dilation began. In contrast, Pkhd1(del4/del4) mice lost oriented cell division but did not develop kidney cysts. Increased intercalation of cells into the plane of the tubular epithelium maintained the normal tubular morphology in Pkhd1(del4/del4) mice, which had more cells present in transverse tubular profiles. In conclusion, loss of oriented cell division is a feature of Pkhd1 mutation and cyst formation, but it is neither sufficient to produce kidney cysts nor required to initiate cyst formation after mutation in Pkd1 or Pkd2.
The expression of adhesion molecules in cigarette smoke-induced airways obstruction
Authors: S Gonzalez, J Hards, S van Eeden, JC Hogg
Journal: European Respiratory Journal (1996)

Cigarette smoking produces peripheral airway inflammation in all smokers, and chronic airways obstruction in approximately 20% of heavy smokers. The present study was designed to test the hypothesis that airways obstruction is related to changes in the expression of adhesion molecules involved in the recruitment of cells to sites of inflammation in the lung. Freshly resected lungs from heavy smokers with airways obstruction (n = 10) and from heavy smokers with normal lung function (n = 10) were collected in the operating room, inflated with optimal cutting temperature (OCT) medium and frozen over liquid nitrogen. Six micrometres thick cryostat sections cut from random samples of this tissue were stained, using immunohistochemistry, with monoclonal antibodies to the adhesion molecules on leucocytes: L-selectin, very late activation antigen-4 (VLA-4), CD11a/CD18, CD11b/CD18, CD11c/CD18; and on endothelial and epithelial surfaces: E-selectin, P-selectin, vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM)-1 and ICAM-2 using the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique. The slides were coded and the expression of each molecule scored by three observers using a semiquantitative grading system. Two inducible adhesion molecules, E-selectin on endothelium and CD11b on leucocytes, were also evaluated using quantitative morphometric analysis. The results showed a distribution of adhesion molecules that was consistent with the inflammatory response in the airways and parenchyma of all subjects but failed to show any differences between those with or without airways obstruction. We conclude that development of airways obstruction in heavy smokers cannot be explained by differences in the expression of adhesion molecules known to be involved in the control of cell traffic in the lung.
Protein losing enteropathy: an unusual presentation of intestinal schistosomiasis.
Authors: C F Kiire, N Gwavava
Journal: Gut (1987)

A patient presenting with features suggestive of malabsorption syndrome is described who had florid intestinal schistosomiasis on peroral biopsy of the jejunum. Liver biopsy and rectal biopsy also revealed schistosomal ova. Biochemical studies revealed severe hypoproteinaemia and hypoalbuminaemia, caused by a protein losing enteropathy. This is the first reported case of protein losing enteropathy caused by intestinal schistosomiasis.
Indicators of integration of oncology and palliative care programs: an international consensus
Authors: D. Hui, S. Bansal, F. Strasser, T. Morita, A. Caraceni, M. Davis, N. Cherny, S. Kaasa, D. Currow, A. Abernethy, C. Nekolaichuk, E. Bruera
Journal: Annals of Oncology (2015)
Rhinovirus Uses a Phosphatidylinositol 4-Phosphate/Cholesterol Counter-Current for the Formation of Replication Compartments at the ER-Golgi Interface
Authors: Pascal S. Roulin, Mark Lötzerich, Federico Torta, Lukas B. Tanner, Frank J.M. van Kuppeveld, Markus R. Wenk, Urs F. Greber
Journal: Cell Host & Microbe (2014)
AKR1C Isoforms Represent a Novel Cellular Target for Jasmonates alongside Their Mitochondrial-Mediated Effects
Authors: Nicholas J. Davies, Rachel E. Hayden, Paul J. Simpson, Jane Birtwistle, Katarina Mayer, Jonathan P. Ride, Chris M. Bunce
Journal: Cancer Research (2009)

Abstract Members of the aldo-keto reductase (AKR) superfamily, particularly the AKR1C subfamily, are emerging as important mediators of the pathology of cancer. Agents that inhibit these enzymes may provide novel agents for either the chemoprevention or treatment of diverse malignancies. Recently, jasmonates, a family of plant stress hormones that bear a structural resemblance to prostaglandins, have been shown to elicit anticancer activities both in vitro and in vivo. In this study, we show that jasmonic acid (JA) and methyl jasmonate (MeJ) are capable of inhibiting all four human AKR1C isoforms. Although JA is the more potent inhibitor of recombinant AKR1C proteins, including the in vitro prostaglandin F synthase activity of AKR1C3, MeJ displayed greater potency in cellular systems that was, at least in part, due to increased cellular uptake of MeJ. Moreover, using the acute myelogenous leukemia cell lines HL-60 and KG1a, we found that although both jasmonates were able to induce high levels of reactive oxygen species in a dose-dependent fashion, only MeJ was able to induce high levels of mitochondrial superoxide (MSO), possibly as an epiphenomenon of mitochondrial damage. There was a strong correlation observed between MSO formation at 24 hours and reduced cellularity at day 5. In conclusion, we have identified AKR1C isoforms as a novel target of jasmonates in cancer cells and provide further evidence of the promise of these compounds, or derivatives thereof, as adjunctive therapies in the treatment of cancer. [Cancer Res 2009;69(11):4769–75]
Phase Ib Study of Panobinostat and Bortezomib in Relapsed or Relapsed and Refractory Multiple Myeloma
Authors: Jesús F. San-Miguel, Paul G. Richardson, Andreas Günther, Orhan Sezer, David Siegel, Joan Bladé, Richard LeBlanc, Heather Sutherland, Monika Sopala, Kaushal K. Mishra, Song Mu, Priscille M. Bourquelot, María Victoria Mateos, Kenneth C. Anderson
Journal: Journal of Clinical Oncology (2013)

Despite advancements, prognosis for patients with relapsed/refractory multiple myeloma (MM) is poor, and novel therapies are needed. Panobinostat is a potent deacetylase inhibitor that elicits synergistic effects on MM cells in combination with bortezomib. This phase Ib study sought to determine the maximum-tolerated dose (MTD) of panobinostat plus bortezomib in patients with relapsed or relapsed and refractory MM.In the dose-escalation phase (n = 47), panobinostat was administered orally thrice weekly every week in combination with bortezomib (21-day cycles). After MTD determination, patients were evaluated in an expansion phase (n = 15) that incorporated a 1-week treatment holiday of panobinostat, with dexamethasone added in cycle 2. Additional assessments included safety, pharmacokinetics, and efficacy per International Myeloma Working Group criteria.The MTD was established at panobinostat 20 mg plus bortezomib 1.3 mg/m(2). Grade 3 or 4 adverse events (AEs) included thrombocytopenia (85.1%), neutropenia (63.8%), and asthenia (29.8%) in the escalation phase, and thrombocytopenia (66.7%), neutropenia (46.7%), and fatigue (20.0%) in the expansion phase. At MTD in the escalation phase, eight patients (47.1%) discontinued therapy as a result of AEs, whereas five patients (33.3%) discontinued treatment in the expansion phase. Expansion phase patients demonstrated greater median treatment duration. Overall response rate (ORR) was 73.3% in the expansion phase and 52.9% at the escalation phase MTD. Among bortezomib-refractory patients, the ORR was 26.3%, and 42.1% of patients had ≥ minimal response.The MTD of panobinostat plus bortezomib was determined and demonstrated activity in patients with relapsed or relapsed/refractory MM, including bortezomib-refractory patients. A phase II/III clinical trial program (Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma [PANORAMA]) has been initiated.
Effect of aerobic exercise programme on health related physical fitness components of middle aged women
Authors: A Shahana, Usha S Nair, S S Hasrani
Journal: British Journal of Sports Medicine (2010)

Fitness for living in the house or on the farm or at office or factory or in work places or in any service implies freedom from disease, enough strength, endurance and other abilities to meet the demands of daily living. Doing physical activity everyday contributes to optimum health and quality of life. Life styles can be changed to improve health and fitness through daily exercises. Aerobic exercise stimulates heart, lungs and all working group of muscles and produces beneficial changes in body and mind. Many physiological changes are determined by daily aerobic exercises. The purpose of the study was to determine the effect of a 12-week aerobic exercise programme on health-related physical fitness components, which are cardiorespiratory endurance, flexibility, abdominal strength endurance and body fat in middle-aged women. A total of 60 middle-aged women from Karyavattom panchayath of Trivandrum district in Kerala state between the age group of 35 and 45 years were selected as subjects for the study. They were tested to collect the data on selected variables. The cardiorespiratory endurance, flexibility, abdominal strength endurance and body fat percentage were selected variables. Further, 30 subjects were randomly assigned as experimental group and 30 as control group. The experimental group underwent aerobic exercise training thrice a week for 12 weeks. The control group did not attend any training programme. The post-tests were conducted on both groups to collect the data on the variables of the study. The data pertaining to health-related physical fitness components were analysed by paired ‘t’ test to determine the difference between initial and final mean for experimental and control groups. Significant difference seen at the 0.05 level with 29 degree of freedom is 2.045 and at 0.01 level with 29 degree of freedom is 2.756 in experimental group following 12 weeks of aerobic training programme for cardiorespiratory endurance, flexibility, muscular strength endurance and skin fold thickness (body fat %). In the case of control group no significant changes were seen in any of the selected variables. The conclusions of this study are improved cardiorespiratory endurance, flexibility, muscular strength endurance and decreased skin fold thickness (body fat %) among the experimental group of middle-aged women after 12 weeks of aerobic training.