tbuckley/cabot-search huggingface dataset:
Electronic Cigarette Sales to Minors via the Internet
Authors: Rebecca S. Williams, Jason Derrick, Kurt M. Ribisl
Journal: JAMA Pediatrics (2015)

Electronic cigarettes (e-cigarettes) entered the US market in 2007 and, with little regulatory oversight, grew into a $2-billion-a-year industry by 2013. The Centers for Disease Control and Prevention has reported a trend of increasing e-cigarette use among teens, with use rates doubling from 2011 to 2012. While several studies have documented that teens can and do buy cigarettes online, to our knowledge, no studies have yet examined age verification among Internet tobacco vendors selling e-cigarettes.To estimate the extent to which minors can successfully purchase e-cigarettes online and assess compliance with North Carolina's 2013 e-cigarette age-verification law.In this cross-sectional study conducted from February 2014 to June 2014, 11 nonsmoking minors aged 14 to 17 years made supervised e-cigarette purchase attempts from 98 Internet e-cigarette vendors. Purchase attempts were made at the University of North Carolina Internet Tobacco Vendors Study project offices using credit cards.Rate at which minors can successfully purchase e-cigarettes on the Internet.Minors successfully received deliveries of e-cigarettes from 76.5% of purchase attempts, with no attempts by delivery companies to verify their ages at delivery and 95% of delivered orders simply left at the door. All delivered packages came from shipping companies that, according to company policy or federal regulation, do not ship cigarettes to consumers. Of the total orders, 18 failed for reasons unrelated to age verification. Only 5 of the remaining 80 youth purchase attempts were rejected owing to age verification, resulting in a youth buy rate of 93.7%. None of the vendors complied with North Carolina's e-cigarette age-verification law.Minors are easily able to purchase e-cigarettes from the Internet because of an absence of age-verification measures used by Internet e-cigarette vendors. Federal law should require and enforce rigorous age verification for all e-cigarette sales as with the federal PACT (Prevent All Cigarette Trafficking) Act's requirements for age verification in Internet cigarette sales.
T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial
Authors: Daniel W Lee, James N Kochenderfer, Maryalice Stetler-Stevenson, Yongzhi K Cui, Cindy Delbrook, Steven A Feldman, Terry J Fry, Rimas Orentas, Marianna Sabatino, Nirali N Shah, Seth M Steinberg, Dave Stroncek, Nick Tschernia, Constance Yuan, Hua Zhang, Ling Zhang, Steven A Rosenberg, Alan S Wayne, Crystal L Mackall
Journal: The Lancet (2014)
Bilateral nodular pulmonary infiltrates in an immunocompromised host
Authors: H A Ali, M Walkenstein
Journal: Thorax (2008)

A 74-year-old man of Jamaican origin residing in the USA for 20 years presented to the hospital with progressively increasing shortness of breath and low-grade fever for 3 weeks. He had been diagnosed with non-Hodgkin’s lymphoma 6 …
How can a causal role for small bacteria in chronic inflammatory arthritides be established or refuted?
Authors: D Taylor-Robinson
Journal: Annals of the Rheumatic Diseases (2001)

The concept of septic arthritis in which bacteria replicate in joint tissue and cause inflammation, joint destruction, and sometimes death is well established. Equally, the idea that some forms of aseptic inflammatory arthritis, such as rheumatoid arthritis, may well be provoked or sustained by the direct or indirect effects of microbial infection is familiar and attractive, though the notion is underpinned more by logic than by data. Between these extremes, reactive arthritis appears to offer a new understanding of microbial pathogenesis as joints, conventionally aseptic, have been found to contain small numbers of bacteria. These bacteria, principally chlamydiae and mycoplasmas, may well provoke and maintain the arthritis. Much evidence has accumulated that they have proinflammatory components, induce immune responses, and could interact with HLA-B27 in a manner consistent with current theories of disease pathogenesis.

The issue of searching for bacteria in joint tissue, however, has become complex. When conventional cultures are positive, the effect of eradication of the micro-organism can readily be gauged, so that the significance of finding the bacterium in the joint can be established. But, when a small number of intra-articular bacteria can only be detected by using ultrasensitive molecular techniques, mainly those based on the polymerase chain reaction (PCR), and there is no discernible benefit from antimicrobial treatment, at least so far as current data show, how can we tell whether these bacteria are part of the normal milieu, have spread from elsewhere into an already inflamed joint as innocent passengers, have spread from elsewhere and contribute to disease persistence or, in fact, are the cause of the disease? By comparison, identifying Mycobacterium tuberculosis in diseased lung by culture provides satisfactory evidence of specific infection and using a PCR or other nucleic acid amplification technique may reduce the time for diagnosis in acute cases by 40-fold. …
Interstitial lung disease in children: a multicentre survey on diagnostic approach
Authors: A. Barbato, C. Panizzolo, A. Cracco, J. de Blic, R. Dinwiddie, M Zach
Journal: European Respiratory Journal (2000)

Chronic interstitial lung disease (ILD) is a rare disorder in the paediatric age group, with a poor prognosis. The diagnostic approach to ILD is based on more or less invasive methods. This study was implemented to verify which methods are the most often used in children. Questionnaires (333) were sent to members of the European Respiratory Society Paediatric Assembly belonging to 187 European and non-European centres. Questions concerned the use of noninvasive diagnostic methods, e.g. history taking, physical examination, routine laboratory tests, respiratory function tests and radiology (chest radiography, high-resolution computed tomography (HRCT)), and the use of invasive techniques such as bronchoalveolar lavage (BAL), transbronchial biopsy (TBB), open lung biopsy (OLB), video-assisted thoracoscopic biopsy (VAT) and HRCT with fine-needle aspiration biopsy (FNAB). Thirty eight centres returned the questionnaires and 131 children with ILD were studied. A diagnosis of ILD was achieved in five (3.8%) patients using noninvasive techniques alone. Using the various biopsy methods, histological assessment was performed on a total of 98 (74.8%) children. The most frequently used invasive technique both alone and in combination was BAL (83, 63.3%), followed by OLB (64, 48.8%), TBB (26, 19.8%) and VAT (11, 8.4%); FNAB was used in one patient. In conclusion a diagnosis of interstitial lung disease was reached on the basis of aetiological and/or histological findings in 117 (89%) of the 131 patients studied.
Posttraumatic therapeutic vaccination with modified myelin self-antigen prevents complete paralysis while avoiding autoimmune disease
Authors: Ehud Hauben, Eugenia Agranov, Amalia Gothilf, Uri Nevo, Avi Cohen, Igor Smirnov, Lawrence Steinman, Michal Schwartz
Journal: Journal of Clinical Investigation (2001)

Spinal cord injury results in a massive loss of neurons, and thus of function. We recently reported that passive transfer of autoimmune T cells directed against myelin-associated antigens provides acutely damaged spinal cords with effective neuroprotection. The therapeutic time window for the passive transfer of T cells was found to be at least 1 week. Here we show that posttraumatic T cell–based active vaccination is also neuroprotective. Immunization with myelin-associated antigens such as myelin basic protein (MBP) significantly promoted recovery after spinal cord contusion injury in the rat model. To reduce the risk of autoimmune disease while retaining the benefit of the immunization, we vaccinated the rats immediately after severe incomplete spinal cord injury with MBP-derived altered peptide ligands. Immunization with these peptides resulted in significant protection from neuronal loss and thus in a reduced extent of paralysis, assessed by an open-field behavioral test. Retrograde labeling of the rubrospinal tracts and magnetic resonance imaging supported the behavioral results. Further optimization of nonpathogenic myelin-derived peptides can be expected to lead the way to the development of an effective therapeutic vaccination protocol as a strategy for the prevention of total paralysis after incomplete spinal cord injury.
Methylation and Inactivation of Estrogen, Progesterone, and Androgen Receptors in Prostate Cancer
Authors: M. Sasaki
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Prostate cancer development is initially steroid hormone dependent. Estrogen receptors (ERs), androgen receptors (ARs), and progesterone receptors (PRs) have been identified in normal and cancerous prostate tissues. We investigated whether the promoter regions of these steroid receptor genes are methylated and inactivated in prostate cancer cells and tissues. Methods: The expression and promoter methylation status of three ERα isoforms (ERα-A, ERα-B, and ERα-C), ERβ, two PR isoforms (PR-A and PR-B), and AR were investigated in five prostate cancer cell lines (ND1, DU145, PC3, LNCaP, and DUPro) and in pairs of normal and cancerous prostate tissues from 38 patients with prostate cancer. Methylation-specific polymerase chain reaction, reverse transcription–polymerase chain reaction, and 5` rapid amplification of complementary DNA ends were used. All statistical tests were two-sided. Results: ERα-C was expressed in all cell lines, but ERα-A and ERα-B were not expressed in any cell line. ERα-A and ERα-B promoters were methylated, but ERα-C was unmethylated. Promoters for ERβ, AR, PR-A, and PR-B were methylated and thus inactivated in some cell lines but not in others. Treating cells with the demethylating reagent 5-aza-2`-deoxycytidine restored expression of all steroid receptor genes with previously methylated promoters. All 38 pairs of cancer and normal tissues had unmethylated ERα-C promoters. Thirty-six (95%) of 38 cancers had methylated ERα-A, 35 (92%) of 38 cancers had methylated ERα-B, but all normal tissues had unmethylated ERα-A and ERα-B (both P<.001). ERβ was methylated in 30 (79%) of 38 cancers but unmethylated in all normal tissues. AR was methylated in three (8%) of 38 cancers but unmethylated in all normal tissues. PR-A and PR-B were unmethylated in all tissues. Conclusion: Certain steroid receptor genes appear to be inactivated by CpG methylation in prostate cancer tissue and cell lines.
Transmural Gradient of Retrograde Collateral Blood Flow in Acutely Ischemic Canine Myocardium
Authors: H. FRED DOWNEY, FOUAD A. BASHOUR, A. Jude STEPHENS, SARKIS J. KECHEJIAN, RONALD H. UNDERWOOD
Journal: Circulation Research (1974)

The contribution of retrograde coronary flow to total collateral flow was examined transmurally in anesthetized, open-chest dogs subjected to acute obstruction of the left anterior descending coronary artery. Regional coronary flow in normal and ischemic tissue was reflected by the tissue content of radioisotopes of potassium and rubidium and by radioactive microspheres. To measure total collateral flow, one isotope was administered when the retrograde cannula was clamped. The other isotope was administered when the cannula was opened to divert retrograde coronary flow away from acutely ischemic myocardium. Significant quantities of this isotope reached the ischemic region despite diversion of retrograde flow at an average rate of 3.5 ml/min. These results confirm earlier, but disputed, reports that total coronary collateral flow exceeds retrograde flow and are indicative of collateral pathways associated more closely with the microcirculation than with the larger epicardial arteries. Furthermore, the transmural distribution of myocardial blood flow in the ischemic tissue was altered nonuniformly by diversion of retrograde flow: 42 K or 86 Rb uptake was reduced to 25% of control in subepicardial tissue but only to 70% of control in subendocardial tissue. The transmural distribution of radioactive microspheres was similarly affected by diversion of retrograde flow. The results suggest that collateral pathways differ transmurally and may include significant luminal connections. Retrograde coronary flow is not a sensitive index of collateral flow to acutely ischemic subendocardial tissue.
BRAIN IMAGING IN SCHIZOPHRENIA
Authors: Kathyrn J. Kotrla, M.D, Daniel R. Weinberger, M.D
Journal: Annual Review of Medicine (1995)

Neuroimaging provides an unprecedented means by which to study psychiatric disorders. Structural imaging methods, i.e. computerized tomography (CT) and magnetic resonance imaging (MRI), have revealed subtle differences in the brains of schizophrenic patients that appear to be present before symptom onset. Radionuclide functional methods such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) have led to hypotheses about dysfunction in specific neuronal networks in schizophrenia. New advances in MRI allow functional data to be obtained noninvasively in a single individual using conventional MRI scanners. This chapter discusses the parallels between the historical technical developments in neuroimaging and the deepening understanding of the etiology and manifestations of schizophrenia.
Increased production of nitric oxide by neutrophils and monocytes from cirrhotic patients with ascites and hyperdynamic circulation
Authors: Giacomo Laffi, Marco Foschi, Emanuela Masini, Antonella Simoni, Laura Mugnai, Giorgio la Villa, Giuseppe Barletta, Pier Francesco Mannaioni, Paolo Gentilini
Journal: Hepatology (1995)

An increased release of nitric oxide (NO), a powerful vasodilating agent, has been proposed to play a role in the pathogenesis of vasodilation and hyperdynamic circulation associated with advanced cirrhosis. We evaluated NO synthase (NOS) activity in peripheral leukocytes of 12 cirrhotic patients and 9 healthy subjects together with plasma endotoxin levels and systemic hemodynamic (by a noninvasive echocardiographic method). NOS activity was evaluated by (1) measuring the capacity of isolated polymorphonuclear cells (PMNs) and monocytes to convert [3H]arginine to [3H]citrulline; (2) measuring the ability of neutrophils and monocytes to inhibit thrombin-induced platelet aggregation and to increase guanosine 3'-5'-cyclic monophosphate content in coincubated platelets, an expression of NO release from these cells. Both neutrophils and monocytes from cirrhotic patients produced significantly higher amounts of [3H]citrulline than cells obtained from healthy subjects (P < .001 and P < .02 for neutrophils and monocytes, respectively) and were more effective than control cells in inhibiting platelet aggregation (P < .05 and P < .001, respectively for 2 x 10(6) cells) and in increasing guanosine 3'-5'-cyclic monophosphate content in coincubated platelets (P < .05 and P < .001, respectively). The anti-aggregating activity expressed by leukocytes has a pharmacological profile similar to that described for NO, because it increased after addition of superoxide dismutase, a superoxide anion scavenger, and markedly decreased after inhibition of nitric oxide synthesis with NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine-methyl ester (L-NAME). Cirrhotic patients had significantly higher plasma endotoxin levels (P < .001) and cardiac index (P < .01) when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Induction cetuximab, paclitaxel, and carboplatin followed by chemoradiation with cetuximab, paclitaxel, and carboplatin for stage III/IV head and neck squamous cancer: a phase II ECOG-ACRIN trial (E2303)
Authors: H.J. Wanebo, J. Lee, B.A. Burtness, J.A. Ridge, M. Ghebremichael, S.A. Spencer, D. Psyrri, E. Pectasides, D. Rimm, F.R. Rosen, M.R. Hancock, K.A. Tolba, A.A. Forastiere
Journal: Annals of Oncology (2014)
Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus
Authors: Franck J. Barrat, Thea Meeker, Josh Gregorio, Jean H. Chan, Satoshi Uematsu, Shizuo Akira, Bonnie Chang, Omar Duramad, Robert L. Coffman
Journal: The Journal of Experimental Medicine (2005)

Raised serum levels of interferon (IFN)-α have been observed in systemic lupus erythematosus (SLE) patients, and these levels are correlated with both disease activity and severity. The origin of this IFN-α is still unclear, but increasing evidence suggests the critical involvement of activated plasmacytoid predendritic cells (PDCs). In SLE patients, DNA and RNA viruses, as well as immune complexes (ICs), that consist of autoantibodies specific to self-DNA and RNA protein particles can stimulate production of IFN-α. We have developed three series of oligonucleotide (ODN)-based inhibitors of Toll-like receptor (TLR) signaling. These ODNs include inhibitors of TLR9, inhibitors of TLR7 but not TLR9, and sequences that inhibit both TLR7 and TLR9. Specificity of these inhibitors is confirmed by inhibition of IFN-α production by PDCs in response to DNA or RNA viruses. We show that mammalian DNA and RNA, in the form of ICs, are potent self-antigens for TLR9 and TLR7, respectively, and induce IFN-α production by PDCs. This work suggests that TLRs may have a critical role in the promotion of lupus through the induction of IFN-α by PDCs. These inhibitors of TLR signaling thus represent novel therapeutic agents with potential for the treatment of lupus.
Multidrug Resistance-Associated Protein–Overexpressing Teniposide-Resistant Human Lymphomas Undergo Apoptosis by a Tubulin-Binding Agent
Authors: Ritu Aneja, Min Liu, Clayton Yates, Jinmin Gao, Xin Dong, Binfei Zhou, Surya N. Vangapandu, Jun Zhou, Harish C. Joshi
Journal: Cancer Research (2008)

Abstract Several DNA- and microtubule-binding agents are used to manage hematologic malignancies in the clinic. However, drug resistance has been a challenge, perhaps due to a few surviving cancer stem cells. Toxicity is another major impediment to successful chemotherapy, leading to an impoverished quality of life. Here, we show that a semisynthetic nontoxic tubulin-binding agent, 9-bromonoscapine (EM011), effectively inhibits growth and regresses multidrug resistance-associated protein (MRP)-overexpressing teniposide-resistant T-cell lymphoma xenografts and prolongs longevity. As expected, teniposide treatment failed to regress teniposide-resistant xenografts, rather, treated mice suffered tremendous body weight loss. Mechanistically, EM011 displays significant antiproliferative activity, perturbs cell cycle progression by arresting mitosis, and induces apoptosis in teniposide-resistant lymphoblastoid T cells both in vitro and in vivo. EM011-induced apoptosis has a mitochondrially-mediated component, which was attenuated by pretreatment with cyclosporin A. We also observed alterations of apoptosis-regulatory molecules such as inactivation of Bcl2, translocation of BAX to the mitochondrial membrane, cytochrome c release, and activation of downstream apoptotic signaling. EM011 caused DNA degradation as evident by terminal deoxynucleotidyl transferase–mediated dUTP-biotin end labeling staining of the increased concentration of 3′-DNA ends. Furthermore, the apoptotic induction was caspase dependent as shown by cleavage of the caspase substrate, poly(ADP)ribose polymerase. In addition, EM011 treatment caused a suppression of natural survival pathways such as the phosphatidylinositol-3′-kinase/Akt signaling. These preclinical findings suggest that EM011 is an excellent candidate for clinical evaluation. [Cancer Res 2008;68(5):1495–503]
The Effects of Malignant Transformation on Susceptibility of Human Urothelial Cells to CD40-Mediated Apoptosis
Authors: U. Bugajska
Journal: JNCI Journal of the National Cancer Institute (2002)

The tumor necrosis factor (TNF) superfamily of ligands and receptors mediates immune cell survival. Some members possess a death domain, a protein motif that functions to transmit apoptotic signals, whereas others, such as CD40, do not. CD40 is expressed by both normal and malignant epithelial cells. To investigate the functional significance of this expression, we studied the effects of ligation of CD40, Fas, and TNF receptors (TNFRs) on the proliferation and survival of normal and malignant human urothelial cells and urothelial cells with disabled p53 function.Normal and malignant human urothelial cells were cultured with soluble TNF family agonists (CD40 ligand [CD40L], TNF-alpha, anti-Fas antibody, or cocultured with mouse fibroblasts stably transfected with plasmids that caused the cells to constitutively express CD40L or CD32; cell proliferation was estimated by an [(3)H]thymidine incorporation assay, and apoptosis was determined by Annexin V staining and by a DNA fragmentation assay. Messenger RNA levels for CD40 and potential downstream effector molecules were quantified by polymerase chain reaction-based and ribonuclease protection assays, respectively, and nuclear factor (NF) kappaB nuclear translocation was detected by immunofluorescence. All statistical tests were two-sided.Soluble trimeric CD40L inhibited the growth of normal and malignant urothelial cells but did not induce apoptosis. Cell surface-presented CD40L induced massive apoptosis in CD40-positive transitional cell carcinoma cells but not in normal urothelial cells. Normal cells underwent CD40L-mediated apoptosis only in the presence of other TNFR agonists. An agonistic anti-CD40 antibody presented on the surface of CD32-transfected fibroblasts also induced apoptosis in transitional cell carcinoma cells and in normal urothelial cells. Apoptotic responses of tumor (but not normal) cells to soluble agonists were enhanced by blocking protein synthesis. Karyotypically normal urothelial cells with disabled p53 function underwent apoptosis during coculture with CD40L-expressing fibroblasts alone but were not additionally sensitive to additional TNFR agonists.Susceptibility to CD40 ligation-induced apoptosis may be a novel mechanism for eliminating neoplastically transformed urothelial cells. Loss of CD40 expression may be an important adaptive mechanism for transitional cell carcinoma development and progression.
Stress fracture of the tarsal navicular.
Authors: C G Moran, J A Fairclough, R C Evans
Journal: British Journal of Sports Medicine (1987)

<h3>ABSTRACT</h3> The highly charged RNA molecules, with each phosphate carrying a single negative charge, cannot fold into well-defined architectures with tertiary interactions, in the absence of ions. For ribozymes, divalent cations are known to be more effcient than monovalent ions in driving them to a compact state although Mg<sup>2+</sup>ions are needed for catalytic activities. Therefore, how ions interact with RNA is relevant in understanding RNA folding. It is often thought that most of the ions are territorially and non-specifically bound to the RNA, as predicted by the counterion condensation (CIC) theory. Here, we show using simulations of <i>Azoarcus</i> ribozyme, based on an accurate coarse-grained Three Site Interaction (TIS) model, with explicit divalent and monovalent cations, that ion condensation is highly specific and depends on the nucleotide position. The regions with high coordination between the phosphate groups and the divalent cations are discernible even at very low Mg<sup>2+</sup> concentrations when the ribozyme does not form tertiary interactions. Surprisingly, these regions also contain the secondary structural elements that nucleate subsequently in the self-assembly of RNA, implying that ion condensation is determined by the architecture of the folded state. These results are in sharp contrast to interactions of ions (monovalent and divalent) with rigid charged rods in which ion condensation is uniform and position independent. The differences are explained in terms of the dramatic non-monotonic shape fluctuations in the ribozyme as it folds with increasing Mg<sup>2+</sup> or Ca<sup>2+</sup> concentration.