tbuckley/cabot-search huggingface dataset:
Differential Effects of Airway Anesthesia on Ozone-induced Pulmonary Responses in Human Subjects
Authors: EDWARD S. SCHELEGLE, MARLOWE W. ELDRIDGE, CARROLL E. CROSS, WILLIAM F. WALBY, WILLIAM C. ADAMS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

We examined the effect of tetracaine aerosol inhalation, a local anesthetic, on lung volume decrements, rapid shallow breathing, and subjective symptoms of breathing discomfort induced by the acute inhalation of 0.30 ppm ozone for 65 min in 22 ozone-sensitive healthy human subjects. After 50 min of ozone inhalation FEV1 was reduced 24%, breathing frequency was increased 40%, tidal volume was decreased 31%, and total subjective symptom score was increased (71.2, compared with 3.8 for filtered air exposure). Inhalation of tetracaine aerosol resulted in marked reductions in ozone-induced subjective symptoms of throat tickle and/or irritation (92.1%), cough (78.5%), shortness of breath (72.5%), and pain on deep inspiration (69.4%). In contrast, inhalation of tetracaine aerosol (mass median aerodynamic diameter of 3.52 μ m with a geometric standard deviation of 1.92) resulted in only minor and inconsistent rectification of FEV1 decrements (5.0%) and breathing frequency ( − 3.8%) that was not significantly different from that produced by saline aerosol alone (FEV1, 5.1% and breathing frequency, − 2.7%). Our data are consistent with afferent endings located within the large conducting airways of the tracheobronchial tree being primarily responsible for ozone-induced subjective symptoms and provides strong evidence that ozone-induced inhibition of maximal inspiratory effort is not dependent on conscious sensations of inspiratory discomfort.
Iron lung<i>versus</i>conventional mechanical ventilation in acute exacerbation of COPD
Authors: A. Corrado, R. Ginanni, G. Villella, M. Gorini, A. Augustynen, D. Tozzi, A. Peris, S. Grifoni, A. Messori, C. Nozzoli, G. Berni
Journal: European Respiratory Journal (2004)

The aim of this randomised study was to compare the effects of iron lung ventilation (ILV) with invasive mechanical ventilation (IMV) in patients with acute respiratory failure (ARF) due to exacerbation of chronic obstructive pulmonary disease. Forty-four patients with ARF were assigned either to ILV (22 patients) or IMV (22 patients). Primary end-points were the improvement in gas exchange and complications related to mechanical ventilation. On admission ILV and IMV groups did not differ in age, simplified acute physiology score II, arterial oxygen tension ( P a,O 2 )/inspiratory oxygen fraction ( F I,O 2 ), arterial carbon dioxide tension ( P a,CO 2 ) and pH. Compared with baseline, ILV and IMV induced a similar and significant improvement in P a,O 2 / F I,O 2 , P a,CO 2 and pH after 1 h of treatment and at discontinuation of mechanical ventilation. Major complications tended to be more frequent in patients treated with IMV than in those treated with ILV (27.3% versus 4.5%), whereas mortality rate was similar (27.3% versus 18.2%). The ventilator-free days and the length of hospital stay were significantly lower in the ILV than in the IMV group. This study suggests that iron lung ventilation is as effective as invasive mechanical ventilation in improving gas exchange in chronic obstructive pulmonary disease patients with acute respiratory failure, and is associated with a tendency towards a lower rate of major complications.
A Recombinant Vesicular Stomatitis Virus Ebola Vaccine
Authors: Jason A. Regules, John H. Beigel, Kristopher M. Paolino, Jocelyn Voell, Amy R. Castellano, Zonghui Hu, Paula Muñoz, James E. Moon, Richard C. Ruck, Jason W. Bennett, Patrick S. Twomey, Ramiro L. Gutiérrez, Shon A. Remich, Holly R. Hack, Meagan L. Wisniewski, Matthew D. Josleyn, Steven A. Kwilas, Nicole Van Deusen, Olivier Tshiani Mbaya, Yan Zhou, Daphne A. Stanley, Wang Jing, Kirsten S. Smith, Meng Shi, Julie E. Ledgerwood, Barney S. Graham, Nancy J. Sullivan, Linda L. Jagodzinski, Sheila A. Peel, Judie B. Alimonti, Jay W. Hooper, Peter M. Silvera, Brian K. Martin, Thomas P. Monath, W. Jay Ramsey, Charles J. Link, H. Clifford Lane, Nelson L. Michael, Richard T. Davey, Stephen J. Thomas
Journal: New England Journal of Medicine (2015)

The worst Ebola virus disease (EVD) outbreak in history has resulted in more than 28,000 cases and 11,000 deaths. We present the final results of two phase 1 trials of an attenuated, replication-competent, recombinant vesicular stomatitis virus (rVSV)-based vaccine candidate designed to prevent EVD.
Oral 7, Cutaneous manifestations of disseminated BCG in a child with severe combined immunodeficiency
Authors: T. Brodie, H. Goodyear, S. Hackett
Journal: British Journal of Dermatology (2007)

Journal Article Oral 7, Cutaneous manifestations of disseminated BCG in a child with severe combined immunodeficiency Get access T. Brodie, T. Brodie Department of Paediatrics, Heart of England NHS Trust, Birmingham, U.K. Search for other works by this author on: Oxford Academic Google Scholar H. Goodyear, H. Goodyear Department of Paediatrics, Heart of England NHS Trust, Birmingham, U.K. Search for other works by this author on: Oxford Academic Google Scholar S. Hackett S. Hackett Department of Paediatrics, Heart of England NHS Trust, Birmingham, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 156, Issue 6, 1 June 2007, Page 1405, https://doi.org/10.1111/j.1365-2133.2007.07876_7.x Published: 01 June 2007
Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns
Authors: Karol Szafranski, Stefanie Schindler, Stefan Taudien, Michael Hiller, Klaus Huse, Niels Jahn, Stefan Schreiber, Rolf Backofen, Matthias Platzer
Journal: Genome biology (2007)

Abstract Background Despite some degeneracy of sequence signals that govern splicing of eukaryotic pre-mRNAs, it is an accepted rule that U2-dependent introns exhibit the 3' terminal dinucleotide AG. Intrigued by anecdotal evidence for functional non-AG 3' splice sites, we carried out a human genome-wide screen. Results We identified TG dinucleotides functioning as alternative 3' splice sites in 36 human genes. The TG-derived splice variants were experimentally validated with a success rate of 92%. Interestingly, ratios of alternative splice variants are tissue-specific for several introns. TG splice sites and their flanking intron sequences are substantially conserved between orthologous vertebrate genes, even between human and frog, indicating functional relevance. Remarkably, TG splice sites are exclusively found as alternative 3' splice sites, never as the sole 3' splice site for an intron, and we observed a distance constraint for TG-AG splice site tandems. Conclusion Since TGs splice sites are exclusively found as alternative 3' splice sites, the U2 spliceosome apparently accomplishes perfect specificity for 3' AGs at an early splicing step, but may choose 3' TGs during later steps. Given the tiny fraction of TG 3' splice sites compared to the vast amount of non-viable TGs, cis -acting sequence signals must significantly contribute to splice site definition. Thus, we consider TG-AG 3' splice site tandems as promising subjects for studies on the mechanisms of 3' splice site selection.
Gallstones and Laparoscopic Cholecystectomy
Authors: John L. Gollan
Journal: JAMA (1993)

The National Institutes of Health Consensus Development Conference on Gallstones and Laparoscopic Cholecystectomy brought together surgeons, endoscopists, hepatologists, gastroenterologists, internists, radiologists, and epidemiologists as well as other health care professionals and the public to address (1) the indications for treatment of patients with gallstones; (2) the role of laparoscopic cholecystectomy in treating patients with gallstones; (3) the role of alternative medical and surgical treatments for gallstones; (4) the comparative results of laparoscopic cholecystectomy with open cholecystectomy and other available treatments; (5) techniques for detecting and treating bile duct stones with or without laparoscopic cholecystectomy; and (6) future directions for research in prevention and management of gallstone disease and in laparoscopic cholecystectomy. Following 2 days of presentations by experts and extensive discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the panel concluded that (1) most patients who experience symptoms of gallstones should be treated; (2) in comparison with open cholecystectomy, laparoscopic cholecystectomy provides a safe and effective treatment for most patients with symptomatic gallstones and has become the treatment of choice for many patients; (3) patients who are not good candidates for laparoscopic cholecystectomy include those with generalized peritonitis, septic shock from cholangitis, severe acute pancreatitis, endstage cirrhosis, and gallbladder cancer; (4) laparoscopic cholecystectomy decreases pain and disability without increasing mortality and morbidity and can be performed at an equal or lower cost than open cholecystectomy; and (5) every effort should be made to ensure that surgeons performing laparoscopic cholecystectomy are properly trained and credentialed. The full text of the consensus panel's statement follows.
THE X-Y-Z SCHEME OF IMMUNOCYTE MATURATION
Authors: Vera S. Byers, Eli E. Sercarz
Journal: The Journal of Experimental Medicine (1968)

A set of conditions has been described under which primed rabbit lymph nodes produce a secondary antibody response upon in vivo stimulation with a large dose of antigen, but are subsequently "exhausted;" that is, lymph node cultures prepared at intervals following the booster injection cannot be re-stimulated to display tertiary responses. Rabbits given 100-fold less antigen in the booster inoculum were able to give a tertiary response upon in vitro challenge. The system used permits neither induction nor continuation of a primary response to BSA in vitro. Since it could be demonstrated that no memory cells were generated by the booster injection within the intervals between in vivo injection and culture, the tertiary response in nonexhausted nodes must have been due to residual memory cells which remained untriggered by the in vivo booster injection. The unresponsive state was not caused by antibody feedback. These results are interpreted to mean that a population of memory cells can be exhausted by a supraoptimal dose of antigen, rendering the node temporarily incapable of further response. This implies that long-lived memory is not due to asymmetric division of memory cells. The source and fate of memory cells is discussed with regard to this evidence.
Molecular Mechanism of Class Switch Recombination: Linkage with Somatic Hypermutation
Authors: Tasuku Honjo, Kazuo Kinoshita, Masamichi Muramatsu
Journal: Annual Review of Immunology (2002)

Class switch recombination (CSR) and somatic hypermutation (SHM) have been considered to be mediated by different molecular mechanisms because both target DNAs and DNA modification products are quite distinct. However, involvement of activation-induced cytidine deaminase (AID) in both CSR and SHM has revealed that the two genetic alteration mechanisms are surprisingly similar. Accumulating data led us to propose the following scenario: AID is likely to be an RNA editing enzyme that modifies an unknown pre-mRNA to generate mRNA encoding a nicking endonuclease specific to the stem-loop structure. Transcription of the S and V regions, which contain palindromic sequences, leads to transient denaturation, forming the stem-loop structure that is cleaved by the AID-regulated endonuclease. Cleaved single-strand tails will be processed by error-prone DNA polymerase-mediated gap-filling or exonuclease-mediated resection. Mismatched bases will be corrected or fixed by mismatch repair enzymes. CSR ends are then ligated by the NHEJ system while SHM nicks are repaired by another ligation system.
Colorectal screening guidelines in acromegaly
Authors: I Perry
Journal: Gut (2003)

We write with concern regarding the recent “Screening guidelines for colorectal cancer and polyps in patients with acromegaly” ( Gut2002;51(suppl V):V13–14. [OpenUrl][1][PubMed][2] ). While there is little doubt that patients with acromegaly have an increased risk of developing colorectal cancer, the exact nature of this risk is far from clear. The endocrine literature has witnessed a significant debate, polarising two separate views. Jenkins and Fairclough advocate screening while Renehan et al suggest that the risk of colorectal cancer formation does not warrant screening or surveillance.1,2 The recommendations by Jenkins and Fairclough for a national screening programme, endorsed by the BSG and ACPBG, are based largely on a series of 222 patients enrolled in a colonoscopy programme in one centre. The principal finding of this study was a 13–14-fold increase in the risk of colorectal cancer in acromegalics relative to the general population. This is at odds with larger studies (n=1362,3 n=1041,4 n=16345) which overall indicate an increased colorectal cancer risk of 2.5–3-fold. Jenkins and Fairclough advocate an intensive screening protocol beginning at … [1]: {openurl}?query=rft.jtitle%253DGut%26rft.volume%253D51%26rft.spage%253DV13%26rft_id%253Dinfo%253Apmid%252F12221033%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=12221033&link_type=MED&atom=%2Fgutjnl%2F52%2F9%2F1387.1.atom
Interleukin (IL)-1 promotes allogeneic T cell intimal infiltration and IL-17 production in a model of human artery rejection
Authors: Deepak A. Rao, Raymond E. Eid, Lingfeng Qin, Tai Yi, Nancy C. Kirkiles-Smith, George Tellides, Jordan S. Pober
Journal: The Journal of Experimental Medicine (2008)

Interleukin (IL) 1alpha produced by human endothelial cells (ECs), in response to tumor necrosis factor (TNF) or to co-culture with allogeneic T cells in a TNF-dependent manner, can augment the release of cytokines from alloreactive memory T cells in vitro. In a human-mouse chimeric model of artery allograft rejection, ECs lining the transplanted human arteries express IL-1alpha, and blocking IL-1 reduces the extent of human T cell infiltration into the artery intima and selectively inhibits IL-17 production by infiltrating T cells. In human skin grafts implanted on immunodeficient mice, administration of IL-17 is sufficient to induce mild inflammation. In cultured cells, IL-17 acts preferentially on vascular smooth muscle cells rather than ECs to enhance production of proinflammatory mediators, including IL-6, CXCL8, and CCL20. Neutralization of IL-17 does not reduce T cell infiltration into allogeneic human artery grafts, but markedly reduces IL-6, CXCL8, and CCL20 expression and selectively inhibits CCR6(+) T cell accumulation in rejecting arteries. We conclude that graft-derived IL-1 can promote T cell intimal recruitment and IL-17 production during human artery allograft rejection, and suggest that targeting IL-1 in the perioperative transplant period may modulate host alloreactivity.
Molecular cloning of a murine fibronectin receptor and its expression during inflammation. Expression of VLA-5 is increased in activated peritoneal macrophages in a manner discordant from major histocompatibility complex class II.
Authors: V M Holers, T G Ruff, D L Parks, J A McDonald, L L Ballard, E J Brown
Journal: The Journal of Experimental Medicine (1989)

Human fibronectin receptor (VLA-5) alpha and beta chain probes were used to identify their mouse homologues in a thioglycollate-elicited peritoneal exudate cell cDNA library. Sequence analysis of both alpha and beta chain-related murine clones revealed approximately 90% homology to their human counterparts by both nucleotide and derived amino acid sequence comparisons. Detectable alpha chain transcripts were seen predominantly in total RNA of peritoneal macrophages. beta chain expression, however, was detected at higher levels in lung, heart, brain, and kidney, suggesting the presence of a large murine VLA family similar to the human family. Analysis of levels of expression comparing resting peritoneal macrophages with macrophages elicited using inflammatory stimuli indicated that alpha chain message and surface VLA-5 expression were significantly increased using thioglycollate or Listeria monocytogenes as stimuli to elicit cells. Interestingly, beta chain message was unaffected by these inflammatory stimuli, suggesting that VLA-5 expression is regulated by VLA-5 alpha chain message levels. These results indicate that macrophage VLA-5 expression can be modulated in vivo and may provide an important mechanism by which macrophages are recruited to or adhere to fibronectin in inflammatory foci.
Case-control study of risk of cerebral sinus thrombosis in oral contraceptive users who are carriers of hereditary prothrombotic conditions
Authors: S F T M de Bruijn, J Stam, M M W Koopman, J P Vandenbroucke
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To investigate whether users of oral contraceptives who are carriers of a hereditary prothrombotic condition (factor V Leiden mutation, protein C, S, or antithrombin deficiency) have an increased risk of cerebral sinus thrombosis. <b>Design:</b> Comparison of a prospective series of cases of cerebral sinus thrombosis with population data. <b>Setting:</b> Neurological teaching hospitals from different regions in the Netherlands (cases) and a representative sample of the non-institutionalised Dutch population (controls). <b>Subjects:</b> 40 women aged 18-54 years with cerebral sinus thrombosis (cases) and 2248 women aged 18-49 years (controls). <b>Main outcome measure:</b> Current use of oral contraceptives at the time of the thrombosis (cases) or at the time of the questionnaire (controls). Prevalences of a hereditary prothrombotic condition in patients and in the population with odds ratios. <b>Results:</b> 34 of 40 (85%) women with cerebral sinus thrombosis used oral contraceptives, versus 1007 of 2248 (45%) of the control women; the age adjusted odds ratio was 13 (95% confidence interval 5 to 37). Seven of 36 patients (19%) had a prothrombotic deficiency, versus 7% expected in the population; this corresponds to a threefold to fourfold increase in risk. In women who used oral contraceptives and also carried a prothrombotic defect, the odds ratio for cerebral sinus thrombosis was about 30 relative to women who had neither risk factor. <b>Conclusion:</b> The use of oral contraceptives and being a carrier of a hereditary prothrombotic condition increase the risk of and interact in a multiplicative way in the development of cerebral sinus thrombosis. <h3>Key messages</h3> The use of oral contraceptives is associated with an increased risk of cerebral venous sinus thrombosis This risk of cerebral venous sinus thrombosis in women who use oral contraceptives is larger if there is an additional hereditary prothombotic factor (protein C, S, or antithrombin deficiency, factor V Leiden mutation) The association between oral contraceptives, thrombophilia, and deep vein thrombosis is also valid for cerebral sinus thrombosis Women do not need to stop using oral contraceptives as the absolute risk of cerebral sinus thrombosis is very small
Mapping and manipulating the Mycobacterium tuberculosis transcriptome using a transcription factor overexpression-derived regulatory network
Authors: Tige R Rustad, Kyle J Minch, Shuyi Ma, Jessica K Winkler, Samuel Hobbs, Mark Hickey, William Brabant, Serdar Turkarslan, Nathan D Price, Nitin S Baliga, David R Sherman
Journal: Genome biology (2014)

Abstract Background Mycobacterium tuberculosis senses and responds to the shifting and hostile landscape of the host. To characterize the underlying intertwined gene regulatory network governed by approximately 200 transcription factors of M. tuberculosis , we have assayed the global transcriptional consequences of overexpressing each transcription factor from an inducible promoter. Results We cloned and overexpressed 206 transcription factors in M. tuberculosis to identify the regulatory signature of each. We identified 9,335 regulatory consequences of overexpressing each of 183 transcription factors, providing evidence of regulation for 70% of the M. tuberculosis genome. These transcriptional signatures agree well with previously described M. tuberculosis regulons. The number of genes differentially regulated by transcription factor overexpression varied from hundreds of genes to none, with the majority of expression changes repressing basal transcription. Exploring the global transcriptional maps of transcription factor overexpressing (TFOE) strains, we predicted and validated the phenotype of a regulator that reduces susceptibility to a first line anti-tubercular drug, isoniazid. We also combined the TFOE data with an existing model of M. tuberculosis metabolism to predict the growth rates of individual TFOE strains with high fidelity. Conclusion This work has led to a systems-level framework describing the transcriptome of a devastating bacterial pathogen, characterized the transcriptional influence of nearly all individual transcription factors in M. tuberculosis , and demonstrated the utility of this resource. These results will stimulate additional systems-level and hypothesis-driven efforts to understand M. tuberculosis adaptations that promote disease.
ApoE Receptor 2 Mediation of Trophoblast Dysfunction and Pregnancy Complications Induced by Antiphospholipid Antibodies in Mice
Authors: Victoria Ulrich, Shari E. Gelber, Milena Vukelic, Anastasia Sacharidou, Joachim Herz, Rolf T. Urbanus, Philip G. de Groot, David R. Natale, Anirudha Harihara, Patricia Redecha, Vikki M. Abrahams, Philip W. Shaul, Jane E. Salmon, Chieko Mineo
Journal: Arthritis & Rheumatology (2015)

Objective Pregnancies in women with the antiphospholipid syndrome (APS) are frequently complicated by fetal loss and intrauterine growth restriction (IUGR). How circulating antiphospholipid antibodies (aPL) cause pregnancy complications in APS is poorly understood. We sought to determine whether the low‐density lipoprotein receptor family member apolipoprotein E receptor 2 (ApoER2) mediates trophoblast dysfunction and pregnancy complications induced by aPL. Methods Placental and trophoblast ApoER2 expression was evaluated by immunohistochemistry and immunoblotting. Normal human IgG and aPL were purified from healthy individuals and APS patients, respectively. The role of ApoER2 in aPL‐induced changes in trophoblast proliferation and migration and in kinase activation was assessed using RNA interference in HTR‐8/SVneo cells. The participation of ApoER2 in aPL‐induced pregnancy loss and IUGR was evaluated in pregnant ApoER2 +/+ and ApoER2 –/– mice injected with aPL or normal human IgG. Results We found that ApoER2 is abundant in human and mouse placental trophoblasts and in multiple trophoblast‐derived cell lines, including HTR‐8/SVneo cells. ApoER2 and its interaction with the cell surface protein β 2 ‐glycoprotein I were required for aPL‐induced inhibition of cultured trophoblast proliferation and migration. In parallel, aPL antagonism of Akt kinase activation by epidermal growth factor in trophoblasts was mediated by ApoER2. Furthermore, in a murine passive‐transfer model of pregnancy complications of APS, ApoER2 –/– mice were protected from both aPL‐induced fetal loss and aPL‐induced IUGR. Conclusion ApoER2 plays a major role in the attenuation of trophoblast function by aPL, and the receptor mediates aPL‐induced pregnancy complications in vivo in mice. ApoER2‐directed interventions can now potentially be developed to combat the pregnancy complications associated with APS.