tbuckley/cabot-search huggingface dataset:
Delineating the hierarchy of lung progenitor cells and their response to influenza
Authors: Jonathan L. McQualter, Geoffrey J. Laurent
Journal: European Respiratory Journal (2015)

Influenza viruses are significant human respiratory pathogens that cause acute inflammation and widespread epithelial cell death in the lungs [1]. Yet, patients can recover, even after widespread destruction of epithelial cells, implying that the lung has a tremendous capacity for regeneration after injury. The mechanism by which this wound-healing process occurs remains unclear. In the adult mouse lung, current models of lung repair have established that different cell types participate in the wound-healing response depending on the nature, anatomical region of the lung (tracheobronchial airways, bronchiolar airways or the alveoli) and extent of the injury. Basal cells are the main stem cell population in the tracheobronchial airways, club cells serve as abundant progenitors in the bronchiolar airways, and type II cells support the maintenance of the alveoli. There is also convincing evidence for the existence of a multipotent stem cell population(s) that can give rise to both airway and alveolar lineages, but the precise identity of these stem cells and their response to lung injury remains unclear [2, 3]. Thus, a key question remains: are rare stem cell populations aroused from their quiescent state to participate in de novo tissue regeneration after extensive epithelial injury? Regeneration of mouse alveoli after influenza infection involves rare stem cells in the bronchiolar airways <http://ow.ly/NUB7P>
A multicountry health partnership programme to establish sustainable trauma training in east, central, and southern African countries using a cascading trauma management course model
Authors: Noel Aaron Peter, Hermant Pandit, Grace Le, Mathenge Nduhiu, Emmanuel Moro, Christopher Lavy
Journal: The Lancet (2015)

Injury accounts for 267 000 deaths annually in the nine College of Surgeons of East, Central, and Southern Africa (COSECSA-ASESA) countries, and the introduction of a sustainable standardised trauma training programme across all cadres is essential. We have delivered a primary trauma care (PTC) programme that encompasses both a "provider" and "training the trainers" course using a "cascading training model" across nine COSECSA countries. The first "primary course" in each country is delivered by a team of UK instructors, followed by "cascading courses" to more rural regions led by newly qualified local instructors, with mentorship provided by UK instructors. This study examines the programme's effectiveness in terms of knowledge, clinical confidence, and cost-effectiveness.We collected pre-training and post-training data from 1030 candidates (119 clinical officers, 540 doctors, 260 nurses, and 111 medical students) trained over 28 courses (nine primary and 19 cascading courses) between Dec 5, 2012, and Dec 19, 2013. Knowledge was assessed with a validated PTC multiple choice questionnaire and clinical confidence ratings of eight trauma scenarios, measured against covariants of sex, age, clinical experience, job roles, country, and health institution's workload.Post-training, a significant improvement was noted across all cadres in knowledge (19% [95% CI 18·0-19·5]; p<0·05) and clinical confidence (22% [20·3-22·3]; p<0·05). Non-doctors showed a greater improvement in knowledge (22% vs 16%; p<0·05) and confidence (24% vs 20%; p<0·05) than doctors. Candidates attending cascading courses also showed larger improvements in knowledge (21% vs 15%; p<0·002) and clinical confidence (23% vs 19%; p<0·002) than their primary course counterparts. Multivariate regression analysis showed that attending cascading courses (Coef=4·83, p<0·05), being a nurse (Coef=3·89, p=0·007) or a clinical officer (Coef=4·11, p=0·015), and attending a course in Kenya (Coef=9·55, p<0·002) or Tanzania (Coef=9·40, p<0·002) were strong predictors to improvement in multiple choice questionnaire performance. However, improvement in clinical confidence was affected by the job-role of the clinical officer (Coef=6·49, p=0·002) and attending a course in Kenya (Coef=16·12, p<0·02) or Tanzania (Coef=7·01, p<0·05). Cascading courses were on average £2000 less expensive than primary care courses.To the best of our knowledge, this is the largest series in the literature on multicountry trauma management training in sub-Saharan Africa. Our study supports the concept of cascading courses as an educationally and cost-effective method in delivering vital trauma training in low-resource settings led by local clinicians.Health Partnership Scheme through the UK Department for International Development (DFID).
Lipid profile changes in patients undergoing bariatric surgery: A comparative study between sleeve gastrectomy and mini-gastric bypass
Authors: Marco Milone, Roberta Lupoli, Paola Maietta, Alessandro Di Minno, Paolo Bianco, Pasquale Ambrosino, Guido Coretti, Francesco Milone, Matteo Nicola Dario Di Minno, Mario Musella
Journal: International Journal of Surgery (2015)
Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hämato-Onkologie OSHO-53 phase II study
Authors: M. Montemurro, T. Kiefer, F. Schüler, H.K. Al-Ali, H-H. Wolf, R. Herbst, A. Haas, K. Helke, A. Theilig, C. Lotze, C. Hirt, D. Niederwieser, M. Schwenke, W.H. Krüger, G. Dölken
Journal: Annals of Oncology (2006)
Antiproliferative and Antitumor Activity of the 2-Cyanoaziridine Compound Imexon on Tumor Cell Lines and Fresh Tumor Cells In Vitro
Authors: E. M. Hersh, C. R. Gschwind, C. W. Taylor, R. T. Dorr, R. Taetle, S. E. Salmon
Journal: JNCI Journal of the National Cancer Institute (1992)

Background : Imexon, a 2-cyanoaziridine, is therapeutic and reverses lymphadenopathy and splenomegaly in the LP-BM5 murine retrovirus-induced immunodeficiency disease (murine AIDS). It can restore chemotherapy-induced immunosuppression. Imexon reduced the incidence of lym-phoma in severe combined immune deficient mice inoculated with human lymphocytes. Purpose : To determine its antitumor activity, we screened imexon against fresh human tumor cells and tumor cell lines. To determine the time-concentration relationships of its cytotoxicity, we studied the effects of imexon on macromolecular synthesis and on the cell cycle. Methods : Imexon was incubated at 1–200 xg/mL with various tumor cell lines, mitogen-stimulated peripheral blood lymphocytes, and fresh tumor cells. Cell survival, macromolecular synthesis, and cell cycle progression were studied. Results: The concentration of imexon that caused 50% inhibition of growth was under 10 (jLg/mL for lymphocytes stimulated with mitogens. It was about 3–10 xg/mL for B-cell lymphomas and both multi-drug-resistant and -sensitive myeloma cell lines. Imexon inhibited four of seven fresh lymphoma and 11 of 16 fresh myeloma biopsy specimens to less than 40% of the control. A 1-hour exposure of lymphoma cells to 50–100 (xg/mL followed by removal of drug by washing the cells and continuing culture resulted in greater than 95% inhibition during the next 48–72 hours. Imexon selectively inhibited protein synthesis during the first 24–48 hours of exposure of lymphoma and myeloma cells. Cells exposed to inhibitory concentrations of imexon were blocked in cell cycle progression. Conclusion: Imexon may be a potentially useful agent in the treatment of malignant disease, particularly lymphoid malignancies, and should be explored further. [J Natl Cancer Inst 84: 1238–1244, 1992]
Protein kinase C isozymes regulate matrix metalloproteinase-1 expression and cell invasion in<i>Helicobacter pylori</i>infection
Authors: Olga Sokolova, Michael Vieth, Michael Naumann
Journal: Gut (2012)

<h3>Background</h3> Protein kinase C (PKC) signalling is often dysregulated in gastric cancer and therefore represents a potential target in cancer therapy. The Gram-negative bacterium <i>Helicobacter pylori</i>, which colonises the human stomach, plays a major role in the development of gastritis, peptic ulcer and gastric adenocarcinoma. <h3>Objective</h3> To analyse the role of PKC isozymes as mediators of <i>H pylori</i>-induced pathogenesis. <h3>Methods</h3> PKC phosphorylation was evaluated by immunoblotting and immunohistochemistry. Gene reporter assays, RT-PCR and invasion assays were performed to assess the role of PKC in the regulation of activator protein-1 (AP-1), matrix metalloproteinase-1 (MMP-1) and the invasion of <i>H pylori</i>-infected epithelial cells. <h3>Results</h3> <i>H pylori</i> induced phosphorylation of PKC isozymes α, δ, θ in AGS cells, which was accompanied by the phosphorylation of PKC substrates, including PKCμ and myristoylated alanine-rich C kinase substrate (MARCKS), in a CagA-independent manner. Phospholipase C, phosphatidylinositol 3-kinase and Ca<sup>2+</sup> were crucial for PKC activation on infection; inhibition of PKC diminished AP-1 induction and, subsequently, MMP-1 expression. Invasion assays confirmed PKC involvement in <i>H pylori</i>-induced MMP-1 secretion. In addition, analysis of biopsies from human gastric mucosa showed increased phosphorylation of PKC in active <i>H pylori</i> gastritis and gastric adenocarcinoma. <h3>Conclusion</h3> The targeting of certain PKC isozymes might represent a suitable strategy to interfere with the MMP-1-dependent remodelling of infected tissue and to overcome the invasive behaviour of gastric cancer cells.
Human natural anti-alpha-galactosyl IgG. II. The specific recognition of alpha (1----3)-linked galactose residues.
Authors: U Galili, B A Macher, J Buehler, S B Shohet
Journal: The Journal of Experimental Medicine (1985)

A natural IgG antibody (anti-Gal) with alpha-galactosyl binding specificity has been found in large amounts (0.5 - 1.0% of serum IgG) in all individuals tested. It has been purified by affinity chromatography on a column of melibiose-Sepharose. In addition to its affinity for normal and pathological senescent human red cells, the antibody readily interacts with rabbit red blood cell (RRBC) glycolipids with alpha-galactosyl terminal residues. Two types (glycosidic linkages of 1----3 vs. 1----4) of rabbit red cells glycolipids with terminal alpha-galactosyl residues were tested for antibody binding. The antibody specifically bound to glycolipids with Gal alpha 1----3 terminal residues, and treatment of these glycolipids with alpha-galactosidase abolished binding. Hemagglutination inhibition studies with oligosaccharides of known structure also showed that the antibody binds specifically to glycoconjugates with an alpha 1----3 terminal galactose residue. Anti-Gal did not bind to a human B-active glycolipid, indicating that fucose-linked alpha 1----2 to the penultimate galactose prevents anti-Gal binding. The anti-Gal specificity for RRBC glycolipids also paralleled that of the alpha-galactosyl-specific Bandeiraea simplicifolia lectin. The possible reasons for the occurrence of this unique antibody in human serum are discussed.
Effect of VX-770 in Persons with Cystic Fibrosis and the G551D-<i>CFTR</i>Mutation
Authors: Frank J. Accurso, Steven M. Rowe, J.P. Clancy, Michael P. Boyle, Jordan M. Dunitz, Peter R. Durie, Scott D. Sagel, Douglas B. Hornick, Michael W. Konstan, Scott H. Donaldson, Richard B. Moss, Joseph M. Pilewski, Ronald C. Rubenstein, Ahmet Z. Uluer, Moira L. Aitken, Steven D. Freedman, Lynn M. Rose, Nicole Mayer-Hamblett, Qunming Dong, Jiuhong Zha, Anne J. Stone, Eric R. Olson, Claudia L. Ordoñez, Preston W. Campbell, Melissa A. Ashlock, Bonnie W. Ramsey
Journal: New England Journal of Medicine (2010)

A new approach in the treatment of cystic fibrosis involves improving the function of mutant cystic fibrosis transmembrane conductance regulator (CFTR). VX-770, a CFTR potentiator, has been shown to increase the activity of wild-type and defective cell-surface CFTR in vitro.We randomly assigned 39 adults with cystic fibrosis and at least one G551D-CFTR allele to receive oral VX-770 every 12 hours at a dose of 25, 75, or 150 mg or placebo for 14 days (in part 1 of the study) or VX-770 every 12 hours at a dose of 150 or 250 mg or placebo for 28 days (in part 2 of the study).At day 28, in the group of subjects who received 150 mg of VX-770, the median change in the nasal potential difference (in response to the administration of a chloride-free isoproterenol solution) from baseline was -3.5 mV (range, -8.3 to 0.5; P=0.02 for the within-subject comparison, P=0.13 vs. placebo), and the median change in the level of sweat chloride was -59.5 mmol per liter (range, -66.0 to -19.0; P=0.008 within-subject, P=0.02 vs. placebo). The median change from baseline in the percent of predicted forced expiratory volume in 1 second was 8.7% (range, 2.3 to 31.3; P=0.008 for the within-subject comparison, P=0.56 vs. placebo). None of the subjects withdrew from the study. Six severe adverse events occurred in two subjects (diffuse macular rash in one subject and five incidents of elevated blood and urine glucose levels in one subject with diabetes). All severe adverse events resolved without the discontinuation of VX-770.This study to evaluate the safety and adverse-event profile of VX-770 showed that VX-770 was associated with within-subject improvements in CFTR and lung function. These findings provide support for further studies of pharmacologic potentiation of CFTR as a means to treat cystic fibrosis. (Funded by Vertex Pharmaceuticals and others; ClinicalTrials.gov number, NCT00457821.).
Relationship between Free Fatty Acid Turnover and Total Body Oxygen Consumption in the Euthyroid and Hyperthyroid States*
Authors: R. Philip Eaton, Daniel Steinberg, Ronald H. Thompson
Journal: Journal of Clinical Investigation (1965)

Many of the signs and symptoms characteristic of the hyperthyroid state can be elicited in closely similar form by the administration of epinephrine or norepinephrine. Both in clinical and in experimental hyperthyroidism, some receptor systems are known to be more sensitive to catecholamines than they are in the euthyroid state (1). It has been frequently suggested, therefore, that the manifestations of hyperthyroidism are to some extent indirect effects, secondary to enhancement of effective sympathetic activity, rather than direct effects of the thyroid hormone itself. There is convincing evidence that at least some of the
Nitroxyl Activates SERCA in Cardiac Myocytes via Glutathiolation of Cysteine 674
Authors: Steve Lancel, Jingmei Zhang, Alicia Evangelista, Mario P. Trucillo, XiaoYong Tong, Deborah A. Siwik, Richard A. Cohen, Wilson S. Colucci
Journal: Circulation Research (2009)

Nitroxyl (HNO) exerts inotropic and lusitropic effects in myocardium, in part via activation of SERCA (sarcoplasmic reticulum calcium ATPase). To elucidate the molecular mechanism, adult rat ventricular myocytes were exposed to HNO derived from Angeli's salt. HNO increased the maximal rate of thapsigargin-sensitive Ca2+ uptake mediated by SERCA in sarcoplasmic vesicles and caused reversible oxidative modification of SERCA thiols. HNO increased the S-glutathiolation of SERCA, and adenoviral overexpression of glutaredoxin-1 prevented both the HNO-stimulated oxidative modification of SERCA and its activation, as did overexpression of a mutated SERCA in which cysteine 674 was replaced with serine. Thus, HNO increases the maximal activation of SERCA via S-glutathiolation at cysteine 674.
ILK mediates LPS-induced vascular adhesion receptor expression and subsequent leucocyte trans-endothelial migration†
Authors: Sonsoles Hortelano, Raquel López-Fontal, Paqui G. Través, Natividad Villa, Carsten Grashoff, Lisardo Boscá, Alfonso Luque
Journal: Cardiovascular Research (2010)

AimsThe inflammatory response to injurious agents is tightly regulated to avoid adverse consequences of inappropriate leucocyte accumulation or failed resolution. Lipopolysaccharide (LPS)-activated endothelium recruits leucocytes to the inflamed tissue through controlled expression of membrane-associated adhesion molecules. LPS responses in macrophages are known to be regulated by integrin-linked kinase (ILK); in this study, we investigated the role of ILK in the regulation of the LPS-elicited inflammatory response in endothelium.
Autogenous Vein Grafts for Femoropopliteal Occlusion
Authors: W. Andrew Dale
Journal: JAMA (1966)

Experience during the past decade has led to considerable agreement concerning the proper operative indications and optimal methods of surgical repair of peripheral arterial occlusions. Although some details remain unsettled, the body of accumulated experimental and clinical evidence has led to the concept that autogenous tissues are more suitable than are synthetic materials for vascular repair wherever possible. While synthetic-tube grafts are mandatory for certain vascular replacements, such as abdominal aneurysms, they should be avoided in favor of either thromboendarterectomy or autogenous vein grafts<sup>1</sup>or combinations for repairs of the femoropopliteal system. Acceptable experience has now been reported by a number of different surgeons and the continued longterm-patency rate of autogenous vein grafts has proved to be relatively good even in the face of slow continuation of degenerative disease of the peripheral artery which has been repaired.<sup>2</sup> <h3>Surgical Indications</h3> Recommendation for surgical repair of the femoropopliteal arterial system
Does This Adult Patient Have Acute Meningitis?
Authors: John Attia
Journal: JAMA (1999)

Early clinical recognition of meningitis is imperative to allow clinicians to efficiently complete further tests and initiate appropriate therapy.To review the accuracy and precision of the clinical examination in the diagnosis of adult meningitis.A comprehensive review of English- and French-language literature was conducted by searching MEDLINE for 1966 to July 1997, using a structured search strategy. Additional references were identified by reviewing reference lists of pertinent articles.The search yielded 139 potentially relevant studies, which were reviewed by the first author. Studies were included if they described the clinical examination in the diagnosis of objectively confirmed bacterial or viral meningitis. Studies were excluded if they enrolled predominantly children or immunocompromised adults or focused only on metastatic meningitis or meningitis of a single microbial origin. A total of 10 studies met the criteria and were included in the analysis.Validity of the studies was assessed by a critical appraisal of several components of the study design. These components included an assessment of the reference standard used to diagnose meningitis (lumbar puncture or autopsy), the completeness of patient ascertainment, and whether the clinical examination was described in sufficient detail to be reproducible.Individual items of the clinical history have low accuracy for the diagnosis of meningitis in adults (pooled sensitivity for headache, 50% [95% confidence interval [CI], 32%-68%]; for nausea/vomiting, 30% [95% CI, 22%-38%]). On physical examination, the absence of fever, neck stiffness, and altered mental status effectively eliminates meningitis (sensitivity, 99%-100% for the presence of 1 of these findings). Of the classic signs of meningeal irritation, only 1 study has assessed Kernig sign; no studies subsequent to the original report have evaluated Brudzinski sign. Among patients with fever and headache, jolt accentuation of headache is a useful adjunctive maneuver, with a sensitivity of 100%, specificity of 54%, positive likelihood ratio of 2.2, and negative likelihood ratio of 0 for the diagnosis of meningitis.Among adults with a clinical presentation that is low risk for meningitis, the clinical examination aids in excluding the diagnosis. However, given the seriousness of this infection, clinicians frequently need to proceed directly to lumbar puncture in high-risk patients. Many of the signs and symptoms of meningitis have been inadequately studied, and further prospective research is needed.
Serological responses to Cryptosporidium in human populations living in areas reporting high and low incidences of symptomatic cryptosporidiosis
Authors: K. Elwin, R.M. Chalmers, S.J. Hadfield, S. Hughes, L.M. Hesketh, M.M. Rothburn, T. Muller, P.R. Hunter
Journal: Clinical Microbiology and Infection (2007)
Systematic Review: Comparative Effectiveness and Harms of Disease-Modifying Medications for Rheumatoid Arthritis
Authors: Katrina E. Donahue, Gerald Gartlehner, Daniel E. Jonas, Linda J. Lux, Patricia Thieda, Beth L. Jonas, Richard A. Hansen, Laura C. Morgan, Kathleen N. Lohr
Journal: Annals of Internal Medicine (2008)

Background: The comparative effectiveness of rheumatoid arthritis therapies is uncertain. Purpose: To compare the benefits and harms of disease-modifying antirheumatic drugs (DMARDs) for adults with rheumatoid arthritis. Data Sources: Records limited to the English language and studies of adults were identified by using MEDLINE, EMBASE, The Cochrane Library, and International Pharmaceutical Abstracts from 1980 to September 2007. Study Selection: Two persons independently selected relevant head-to-head trials and prospective cohort studies with at least 100 participants and 12-week follow-up and relevant good- or fair-quality meta-analyses that compared benefits or harms of 11 drug therapies. For harms, they included retrospective cohort studies. Data Extraction: Information on study design, interventions, outcomes, and quality were extracted according to a standard protocol. Data Synthesis: Head-to-head trials (n = 23), mostly examining synthetic DMARDs, showed no clinically important differences in efficacy among synthetic DMARDs (limited to methotrexate, leflunomide, and sulfasalazine) or among anti–tumor necrosis factor drugs (adalimumab, etanercept, and infliximab). Monotherapy with anti–tumor necrosis factor drugs resulted in better radiographic outcomes than did methotrexate but no important differences in clinical outcomes (for example, 20%, 50%, or 70% improvement according to American College of Rheumatology response criteria). Various combinations of biological DMARDs plus methotrexate improved clinical response rates and functional outcomes more than monotherapy with either methotrexate or biological DMARDs. In patients whose monotherapy failed, combination therapy with synthetic DMARDs improved response rates. Numbers and types of short-term adverse events were similar for biological and synthetic DMARDs. The evidence was insufficient to draw conclusions about differences for rare but serious adverse events for biological DMARDs. Limitation: Most studies were short-term efficacy trials conducted in selected populations with few comorbid conditions. Conclusion: Limited available comparative evidence does not support one monotherapy over another for adults with rheumatoid arthritis. Although combination therapy is more effective for patients whose monotherapy fails, the evidence is insufficient to draw firm conclusions about whether one combination or treatment strategy is better than another or is the best treatment for early rheumatoid arthritis.
Pseudotumor of hemophilia in the orbit: The role of radiotherapy in management
Authors: Lee Meyers, Nasrollah Hakami
Journal: American Journal of Hematology (1985)

Abstract A case of pseudotumor of hemophilia is presented that occured in the right orbit of a boy with severe factor VIII deficiency and an inhibitor. After a period of observation and conservative management, low‐dose radiotherapy (750 rads) and Proples was used. Eighteen months after radiotherapy significant healing had occured. The role of radiotherapy in the treatment of hemophillic pseudotumor is reviewed.