tbuckley/cabot-search huggingface dataset:
Role of p38 and JNK MAPK signaling pathways and tumor suppressor p53 on induction of apoptosis in response to Ad-eIF5A1 in A549 lung cancer cells
Authors: Catherine A. Taylor, Qifa Zheng, Zhongda Liu, John E. Thompson
Journal: Molecular Cancer (2013)

Abstract Background The eukaryotic translation initiation factor 5A1 (eIF5A1) is a highly conserved protein involved in many cellular processes including cell division, translation, apoptosis, and inflammation. Induction of apoptosis is the only function of eIF5A1 that is known to be independent of post-translational hypusine modification. In the present study, we investigated the involvement of mitogen- and stress-activated protein kinases during apoptosis of A549 lung cancer cells infected with adenovirus expressing eIF5A1 or a mutant of eIF5A1 that cannot be hypusinated (eIF5A1 K50A ). Methods Using adenoviral-mediated transfection of human A549 lung cancer cells to over-express eIF5A1 and eIF5A1 K50A , the mechanism by which unhypusinated eIF5A1 induces apoptosis was investigated by Western blotting, flow cytometry, and use of MAPK and p53 inhibitors. Results Phosphorylation of ERK, p38 MAPK, and JNK was observed in response to adenovirus-mediated over-expression of eIF5A1 or eIF5A1 K50A , along with phosphorylation and stabilization of the p53 tumor suppressor protein. Synthetic inhibitors of p38 and JNK kinase activity, but not inhibitors of ERK1/2 or p53 activity, significantly inhibited apoptosis induced by Ad-eIF5A1. Importantly, normal lung cells were more resistant to apoptosis induced by eIF5A1 and eIF5A1 K50A than A549 lung cancer cells. Conclusions Collectively these data indicate that p38 and JNK MAP kinase signaling are important for eIF5A1-induced cell death and that induction of apoptosis was not dependent on p53 activity.
CUTANEOUS BASOPHIL HYPERSENSITIVITY
Authors: Hal B. Richerson, Harold F. Dvorak, Sidney Leskowitz
Journal: The Journal of Experimental Medicine (1970)

Jones-Mote reactivity, defined as a delayed-type skin reaction, occurs transiently early in the course of immunization with protein antigens or hapten conjugates with or without the adjuvant effect of tubercle bacilli. The skin reaction is typically a flat, well-circumscribed erythema with little induration beginning at about 6 hr, reaching a peak at 18-24 hr, and fading or gone at 48 hr. Immunogenic carrier requirements for hapten-specific Jones-Mote hypersitivity resemble those of antibody production rather than of classic delayed hypersensitivity. Skin test antigen requirements indicate that the Jones-Mote reaction involves an active stimulatory response rather than combination with preformed antibody, since ABA conjugates of nonimmunogenic D-polymers do not work. Studies with ALS and carrageenan suggest that the lymphocyte is an important contributor to the reaction, but the macrophage is not. Because the reactions studied here are operationally different from those described by Jones and Mote and because they have a characteristic histology, the term "cutaneous basophil hypersensitivity" is proposed.
Midwall Mechanics Are Improved After Regression of Hypertensive Left Ventricular Hypertrophy and Normalization of Chamber Geometry
Authors: Stefano Perlini, Maria Lorenza Muiesan, Cesare Cuspidi, Lorena Sampieri, Bruno Trimarco, Gerard P. Aurigemma, Enrico Agabiti-Rosei, Giuseppe Mancia
Journal: Circulation (2001)

It is still unclear whether substantial regression of hypertensive left ventricular hypertrophy (LVH) and normalization of chamber geometry are associated with improved left ventricular (LV) myocardial function.Midwall mechanics were evaluated in 152 patients undergoing 1 year of effective antihypertensive treatment. Two-dimensionally directed M-mode echocardiography was performed as follows: (1) after a 4-week placebo "run-in" period, (2) after 1 year of treatment with 20 mg/d lisinopril (alone or associated with 12.5 to 25 mg/d hydrochlorothiazide), and (3) after a final 1-month placebo period to allow blood pressure (24-hour average ambulatory monitoring) to return to pretreatment levels. Treatment-induced reductions in blood pressure (from 149+/-16/95+/-11 to 131+/-12/83+/-10 mm Hg, P:<0.05) and circumferential end-systolic wall stress (from 84+/-22 to 72+/-19 g/cm(2), P:<0.05) were associated with a marked reduction in LV mass index (from 159+/-30 to 133+/-26 g/m(2), P:<0.05). LVH regression was accompanied by an increase in midwall fractional shortening (from 19.7+/-2.7% to 20.9+/-2.7%, P:<0.05) and by a decrease in relative wall thickness (from 48.2+/-7.7% to 44.1+/-6.7%, P:<0.05). The improvement in midwall function associated with afterload reduction and substantial LVH regression persisted after antihypertensive therapy withdrawal and restoration of the hypertensive state. Despite a significant increase in end-systolic wall stress, further LV chamber remodeling did not occur. The preservation of relative wall thickness was associated with a persistent improvement in midwall systolic function.Regression of concentric LVH is associated with an improvement of midwall systolic function, which is more dependent on the normalization of LV geometry than on the reduction in LV systolic stress.
Senate Bills Target Employer Health Plan “Cadillac Tax”
Authors: Julie A. Jacob
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
NFATc1 Identifies a Population of Proximal Tubule Cell Progenitors
Authors: Melissa Langworthy, Bin Zhou, Mark de Caestecker, Gilbert Moeckel, H. Scott Baldwin
Journal: Journal of the American Society of Nephrology (2009)

Recovery from acute kidney injury requires regeneration of tubule cells. Because calcineurin induces nuclear transport of NFATc proteins, whose expression pattern correlates with the nephron segments injured by calcineurin inhibitors, we hypothesized that NFATc1 plays a role in modifying epithelial regeneration after injury. To test this, we induced proximal tubular cell (PTC) injury in Balb/c mice and Nfatc1+/− mice with mercuric chloride; the PTCs of Nfatc1+/− mice demonstrated increased apoptosis, sustained injury, and delayed regeneration. To attenuate NFATc1 activity further, we injected cyclosporin A daily. Cyclosporin A–treated Nfatc1+/− mice demonstrated rapid and severe injury after administration of mercuric chloride, with increased serum creatinine, increased apoptosis, decreased PTC proliferation, and increased mortality compared with similarly treated wild-type mice. Using a novel NFATc1 transgenic line that reports activation of an NFATc1 enhancer domain critical for NFATc1 autoamplification, we demonstrated accentuated NFATc1 expression in a PTC subpopulation after mercuric chloride–induced injury. In addition, NFATc1-labeled, apoptosis-resistant PTCs proliferated to repair the damaged proximal tubule segment. These data provide evidence for a resident progenitor PTC population and suggest a role for NFATc1 in the regeneration of injured proximal tubules.
Reduced Risk of Plasmodium vivax Malaria in Papua New Guinean Children with Southeast Asian Ovalocytosis in Two Cohorts and a Case-Control Study
Authors: Anna Rosanas-Urgell, Enmoore Lin, Laurens Manning, Patricia Rarau, Moses Laman, Nicolas Senn, Brian T. Grimberg, Livingstone Tavul, Danielle I. Stanisic, Leanne J. Robinson, John J. Aponte, Elijah Dabod, John C. Reeder, Peter Siba, Peter A. Zimmerman, Timothy M. E. Davis, Christopher L. King, Pascal Michon, Ivo Mueller
Journal: PLoS Medicine (2012)

Ivo Mueller and colleagues examined the association of Southeast Asian ovalocytosis with Plasmodium vivax infection by genotyping 1975 children enrolled in three independent epidemiological studies conducted in the Madang area of Papua New Guinea and assessing P. vivax infection and disease in the children.
Antigen-presenting cells and tolerance induction
Authors: D von Bubnoff, H de la Salle, J Wessendorf, S Koch, D Hanau, T Bieber
Journal: Allergy (2002)

T cell tolerance induction to foreign and self-antigens has occupied research since the beginning of the understanding of the immune system. Much controversy still exists on this question even though new methods became available to investigate immunoregulatory mechanisms. Antigen-presenting cells play a pivotal role in transferring information from the periphery of the organism to lymphoid organs. There, they initiate not only the activation of naive T cells but seem to deliver important signals which result in T cell unresponsiveness with antigen-specific tolerance induction.
Co-cultivation of rat pneumocytes and bovine endothelial cells on a liquid-air interface
Authors: N Gueven, B Glatthaar, HG Manke, H Haemmerle
Journal: European Respiratory Journal (1996)

The blood-air barrier is a most important functional element of the lung but little information is available about the cells constituting this barrier in vivo. The aim of the present study was to create an in vitro model of the blood-air barrier that would allow investigation of cellular interactions and alveolar metabolism, and would be suitable for in vitro drug screening. Rat pneumocytes and bovine microvascular endothelial cells were grown on opposite sides of microporous polycarbonate filters, as immersion, perfusion and liquid-air interface (LAI) cultures. The effects of culture conditions on cell morphology were examined by light and transmission electron microscopy. For immersion and perfusion co-cultures, both compartments were supplied with culture medium. In contrast, for liquid-air interface studies, only the endothelial cell compartment was continuously supplied with serum-free medium, whilst the type II pneumocytes were ventilated with air. The pneumocytes lost their morphological characteristics when using immersion or perfusion co-cultures. Under liquid-air interface conditions, they retained most of their characteristic morphological features when compared to the intact blood-air barrier. A subset of primary type II pneumocytes retained its differentiated phenotype, with cuboidal morphology, lamellar bodies and apical microvilli. These type II pneumocytes appeared to be connected by tight junctions to cells expressing morphological characteristics of type I pneumocytes. As shown herein, the liquid-air interface co-culture possesses many morphological characteristics of the intact blood-air barrier. In summary, this article describes the design of an artificial blood-air barrier, in which rat pneumocytes were cultivated with bovine microvascular endothelial lung cells on opposing sides of a microporous polycarbonate filter. We conclude that it might be a promising in vitro model for studies of molecular transport via the blood-air barrier, the investigation of repair mechanisms after alveolar injury, or as an in vitro screening system.
Peripheral Vasomotor Effects of Adrenaline and Noradrenaline Acting upon the Isolated Perfused Central Nervous System
Authors: ROBERT D. TAYLOR, IRVINE H. PAGE
Journal: Circulation (1951)

The problem of the participation of the nervous system in the control of blood pressure has received scant attention. Our purpose was to learn more of the nervous mechanisms which participate in its control. By means of a special technic which allows the brain to be perfused with blood from another animal and yet be connected with the body only by the nervous system, it was shown that pressor substances perfused through the brain cause a fall in pressure in the body. On the contrary, substances which are depressor in the donor's body cause a rise in pressure in the recipient's body when they act on the brain. We conclude that the brain contains hitherto unrecognized chemoreceptors independent of the carotid sinuses. Baroreceptors were not found in the blood vessels. This cerebral buffer mechanism must have important functions in determining the response to vasoactive substances, especially in hypertension and shock.
Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2–MyD88 signal pathway in dendritic cells and enhances Th2 immune responses
Authors: De Yang, Qian Chen, Shao Bo Su, Ping Zhang, Kahori Kurosaka, Rachel R. Caspi, Suzanne M. Michalek, Helene F. Rosenberg, Ning Zhang, Joost J. Oppenheim
Journal: The Journal of Experimental Medicine (2008)

Eosinophil-derived neurotoxin (EDN) is an eosinophil granule–derived secretory protein with ribonuclease and antiviral activity. We have previously shown that EDN can induce the migration and maturation of dendritic cells (DCs). Here, we report that EDN can activate myeloid DCs by triggering the Toll-like receptor (TLR)2–myeloid differentiation factor 88 signaling pathway, thus establishing EDN as an endogenous ligand of TLR2. EDN activates TLR2 independently of TLR1 or TLR6. When mice were immunized with ovalbumin (OVA) together with EDN or with EDN-treated OVA-loaded DCs, EDN enhanced OVA-specific T helper (Th)2-biased immune responses as indicated by predominant production of OVA-specific interleukin (IL)-5, IL-6, IL-10, and IL-13, as well as higher levels of immunoglobulin (Ig)G1 than IgG2a. Based on its ability to serve as a chemoattractant and activator of DCs, as well as the capacity to enhance antigen-specific immune responses, we consider EDN to have the properties of an endogenous alarmin that alerts the adaptive immune system for preferential enhancement of antigen-specific Th2 immune responses.
Community and occupational studies of lung cancer and polycyclic organic matter.
Authors: J Rantanen
Journal: Environmental Health Perspectives (1983)

Finland is used as a model in attempts to study the possible association of the incidence of lung cancer and exposure of population to fossil fuel combustion products. Unfortunately because of great geographical variation of unknown origin in the incidence of lung cancer in Finland, detailed studies of the possible role of an individual exposure in the lung cancer risk are not possible. This background variation in the incidence is much greater than variation carried by any known etiological factor and does not clearly correlate with the degree of urbanization, industrialization, regional use of fossil fuels, number of motor vehicles or smoking habits. To get more precise information on the possible association of lung cancer incidence with exposure to fossil fuel combustion products, occupational studies serve as powerful tools. The definition of population is more reliable and the measurement of exposures can be done more precisely; moreover the management of confounding and modifying factors is more effective than in community studies. So far the studies carried out among the Finnish working population exposed to PAH compounds reveal an association between the lung cancer risk and exposure to PAHs.
Respiratory medicines for children: current evidence, unlicensed use and research priorities
Authors: A. R. Smyth, A. Barbato, N. Beydon, H. Bisgaard, K. de Boeck, P. Brand, A. Bush, B. Fauroux, J. de Jongste, M. Korppi, C. O'Callaghan, M. Pijnenburg, F. Ratjen, K. Southern, D. Spencer, A. Thomson, H. Vyas, A. Warris, P. J. Merkus
Journal: European Respiratory Journal (2009)

This European Respiratory Society task force has reviewed the evidence for paediatric medicines in respiratory disease occurring in adults and children. We describe off-licence use, research priorities and ongoing studies. Off-licence and off-label prescribing in children is widespread and potentially harmful. Research areas in asthma include novel formulations and regimens, and individualised prescribing. In cystic fibrosis, future studies will focus on screened infants and robust outcome measures are needed. Other areas include new enzyme and antibiotic formulations and the basic defect. Research into pneumonia should include evaluation of new antibacterials and regimens, rapid diagnostic tests and, in pleural infection, antibiotic penetration, fibrinolytics and surveillance. In uncommon conditions, such as primary ciliary dyskinesia, congenital pulmonary abnormalities or neuromuscular disorders, drugs indicated for other conditions (e.g. dornase alfa) are commonly used and trials are needed. In neuromuscular disorders, the beta-agonists may enhance muscle strength and are in need of evaluation. Studies of antibiotic prophylaxis, immunoglobulin and antifungal drugs are needed in immune deficiency. We hope that this summary of the evidence for respiratory medicines in children, highlighting gaps and research priorities, will be useful for the pharmaceutical industry, the paediatric committee of the European Medicines Agency, academic investigators and the lay public.
T Cell Receptor αβ Diversity Inversely Correlates with Pathogen-Specific Antibody Levels in Human Cytomegalovirus Infection
Authors: George C. Wang, Pradyot Dash, Jonathan A. McCullers, Peter C. Doherty, Paul G. Thomas
Journal: Science Translational Medicine (2012)

CD8 + T cell diversity may be more important than T cell abundance in limiting the negative consequences of cytomegalovirus persistence.
Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECTION): a multicentre, randomised, double-blind extension trial
Authors: Gavin Giovannoni, Ralf Gold, Krzysztof Selmaj, Eva Havrdova, Xavier Montalban, Ernst-Wilhelm Radue, Dusan Stefoski, Manjit McNeill, Lakshmi Amaravadi, Marianne Sweetser, Jacob Elkins, Gilmore O'Neill
Journal: The Lancet Neurology (2014)
An inflammatory condition causing abdominal pain and weight loss: Emad El-Omar, Editor
Authors: A. Shah, J. Colby, J. Martin, C. Nwokolo
Journal: Gut (2010)

A 46-year-old female presented with a history of dysphagia, nausea and postprandial epigastric and right upper quadrant pain. Upper gastrointestinal endoscopy and biopsies were normal. Manometry revealed non-specific oesophageal dysmotility, while ultrasound imaging revealed gallstones. …
T cell-specific gamma genes in C57BL/10 mice. Sequence and expression of new constant and variable region genes.
Authors: A Iwamoto, F Rupp, P S Ohashi, C L Walker, H Pircher, R Joho, H Hengartner, T W Mak
Journal: The Journal of Experimental Medicine (1986)

The T cell-specific gamma genes in C57BL/10 (B10) mice have been analyzed. Based on the cDNA sequences of these genes from antigen-specific MHC-restricted cytotoxic T cells, we found that the repertoire of these genes is not as limited as previously postulated (8). T cells from the B10 mice express an identical copy of V gamma J gamma C gamma (V gamma 10.8A-JC gamma 10.5) transcript previously found in T cells of BALB/c mice. In addition, a potentially functional mRNA using V gamma 10.8B and newly identified J gamma and C gamma gene segments were found. The new J gamma C gamma (JC gamma 10.8) is located 5' to the inverted V gamma 10.8B in the germline DNA of both B10 and BALB/c mice. This new C gamma is only 77 and 66% homologous to the C gamma 10.5 at the nucleotide and deduced protein sequences, respectively, thus making it a potential isotype of the C gamma genes reported previously. The V gamma 5.7, J gamma 2.3 gene segments and pseudogene C gamma 7.5 found in the germline DNA of BALB/c mice are absent in B10 mice. The loss of this gamma chain pseudogene in the B10 mouse strain, and the retention of all potentially functional V gamma, J gamma, and C gamma genes with highly conserved coding sequences supports the importance of these genes.
Rectal cell proliferation and colon cancer risk in patients with hypergastrinaemia
Authors: M Renga, G Brandi, G M Paganelli, C Calabrese, S Papa, A Tosti, P Tomassetti, M Miglioli, G Biasco
Journal: Gut (1997)

Background —The influence of gastrin on the colonic mucosa is still uncertain. Some authors have suggested a stimulating effect on the growth of normal and malignant colonic epithelium, while others have shown no association between gastrin and neoplastic development. Aims —To evaluate the effect of gastrin on colorectal cell proliferation, patients with chronic endogenous hypergastrinaemia underwent proctoscopy. Biopsy specimens were taken in order to study rectal cell kinetics. Patients and controls —Ten patients with chronic autoimmune gastritis (CAG), six patients with Zollinger-Ellison syndrome (ZES), and 16 hospital controls took part in this study. Patients with CAG and ZES had basal serum gastrin concentrations significantly higher than controls (p&lt;0.001). Methods —Immunohistochemistry was performed on 3 μm sections of rectal biopsy specimens incubated with 5′-bromodeoxyuridine. Results —The percentage of proliferating cells in the entire crypts (overall labelling index) was similar in all the groups. However, the labelling frequency in the upper two fifths of the glands (φh value) was significantly higher in patients with CAG or ZES compared with controls (p&lt;0.01 in both patient groups versus controls). Conclusions —Endogenous hypergastrinaemia is associated with rectal cell proliferation defects, similar to those observed in conditions at high risk for colon cancer. The effect of the increased serum concentrations of gastrin on the colorectal mucosa after treatment with drugs inhibiting gastric acid secretion should be investigated.
Paralogous Radiations of PIN Proteins with Multiple Origins of Noncanonical PIN Structure
Authors: Tom Bennett, Samuel F. Brockington, Carl Rothfels, Sean W. Graham, Dennis Stevenson, Toni Kutchan, Megan Rolf, Philip Thomas, Gane Ka-Shu Wong, Ottoline Leyser, Beverley J. Glover, C. Jill Harrison
Journal: Molecular Biology and Evolution (2014)

The plant hormone auxin is a conserved regulator of development which has been implicated in the generation of morphological novelty. PIN-FORMED1 (PIN) auxin efflux carriers are central to auxin function by regulating its distribution. PIN family members have divergent structures and cellular localizations, but the origin and evolutionary significance of this variation is unresolved. To characterize PIN family evolution, we have undertaken phylogenetic and structural analyses with a massive increase in taxon sampling over previous studies. Our phylogeny shows that following the divergence of the bryophyte and lycophyte lineages, two deep duplication events gave rise to three distinct lineages of PIN proteins in euphyllophytes. Subsequent independent radiations within each of these lineages were taxonomically asymmetric, giving rise to at least 21 clades of PIN proteins, of which 15 are revealed here for the first time. Although most PIN protein clades share a conserved canonical structure with a modular central loop domain, a small number of noncanonical clades dispersed across the phylogeny have highly divergent protein structure. We propose that PIN proteins underwent sub- and neofunctionalization with substantial modification to protein structure throughout plant evolution. Our results have important implications for plant evolution as they suggest that structurally divergent PIN proteins that arose in paralogous radiations contributed to the convergent evolution of organ systems in different land plant lineages.