tbuckley/cabot-search huggingface dataset:
S94 Two novel determinants of etoposide resistance in small cell lung cancer
Authors: M. H. Lawson, N. M. Cummings, D. M. Rassl, R. Russell, J. D. Brenton, R. C. Rintoul, G. Murphy
Journal: Thorax (2010)

<h3>Introduction</h3> Small Cell Lung Cancer (SCLC) typically responds well to initial chemotherapy with Etoposide and a platinum-containing agent. However survival is poor due to invariable relapse with chemoresistant disease. We used a unique series of SCLC cell lines (GLC-14, 16, 19), derived from a single patient at various time-points during her treatment, to identify genes involved in Etoposide resistance. We then attempted to determine their functional role and validate their importance using patient specimens. <h3>Methods</h3> The relationship of the cell lines to each other was confirmed using genomic methods. Genes whose expression pattern could explain the relative response of the cell lines to treatment with Etoposide were identified using cDNA microarray. These candidate Etoposide response genes were cloned from the cell line in which they were expressed at the highest level and transiently over-expressed in the cell line in which they were naturally expressed at the lowest level to determine whether this altered Etoposide resistance. Using immunohistochemistry, expression of the most promising candidates was examined using a tissue microarray (TMA). <h3>Results</h3> The two most promising candidate genes were identified as DNA Polymerase β, a DNA repair enzyme and NKX2.2, a neuroendocrine transcription factor. Specific inhibition of DNA Polymerase β with Pamoic Acid reduced the numbers of cells surviving treatment with Etoposide (p=0.029) and increased the amount of DNA damage in the cells (p&lt;0.001). Stable overexpression of NKX2.2 significantly increased cell survival in response to Etoposide in two different SCLC cell lines. In keeping with this, we found that absence of nuclear staining for NKX2.2 in the TMA was an independent predictor of improved outcome in chemotherapy treated SCLC patients (HR 0.52, 95% CI 0.33 to 0.82, p=0.005). <h3>Conclusion</h3> Using a biologically plausible model of in vivo acquired resistance to Etopoide we have identified two novel Etoposide resistance factors—DNA Polymerase β and NKX2.2. Our <i>in vitro</i> data, in conjunction with the TMA results, provide justification for further prospective work to confirm the roles of these molecules in chemotherapy resistance in SCLC.
Bowel perforation in intestinal lymphoma: incidence and clinical features
Authors: R. Vaidya, T.M. Habermann, J.H. Donohue, K.M. Ristow, M.J. Maurer, W.R. Macon, J.P. Colgan, D.J. Inwards, S.M. Ansell, L.F. Porrata, I.N. Micallef, P.B. Johnston, S.N. Markovic, C.A. Thompson, G.S. Nowakowski, T.E. Witzig
Journal: Annals of Oncology (2013)
On the Testing of Flour and Bread
Authors: J. A. Wanklyn
Journal: BMJ (1873)

it i quite obvious that the whole increase of inhabitants which the census demonstrates cannot thus be explained.Typhoid fever, under which head are included apparently more than one variety of continued fever, is neither more prevalent nor more fatal in Rome than in several of the larger capitals of Europe, such as Berlin and Vienna; but it is, unfortunately, impossible to compare the mortality from the disease in 1872 with that of the whole preceding year, as the necessary data for 187i have only been supplied for the sx months of that year, beginning with May.During those six months, the death-rate from typhoid fever in 1871 was materially higher than in the same period of last year.The water-supply of Rome is still good, though by no means so abundant as in the days of its great glory.All its chief sources are ancient and well known, though often cut off and renewed.The four principal waters are the A Vergine, or Trevi, so called from supplying the famed fountain of that name, the A Felice, the Acqua Paola, and the Acqua Marcia; the first and ast named being much the most pleasant to drink, and containing least orgic matter.In one litre of the water of Trevi there are fixed principles to the extent of gr.0.26381 ; in the same quantity of Acqua Felice, gr. 0.27045; and in the Acqua Paola, gr.0,14084, chiefly chloride of sodium, carbonates of lime and mag- nesia, and sulphate of soda.The Acqua Trevi contains more gaseous elements than the other two.Of the Acqua Marcia, re-introduced into the city onlr in i870, no good analysis has as yet been published.It is to be feared, however, that all the three waters, Acqua Trevi, Felice, and Paola, receive organic impurities; the Acqua Trevi from the aqueduct in which it runs, being open here and there in the Campagna;the Acqua Felice at its source, and the Acqua Paola on the Janiculum, as Pro essor Sca~zi points out, in an article on the subject in the Giornalo Medica di Roma for December, i869.There are besides several other sources of water-supply of minor importance, and many wells, unfortunately still in use, within the walls; but as regards the quantity, no city in the world is better off than Rome, as the four chief aqueducts alone provide 1,439 litres, or 317 gallons per day, for each inhabitant.The present article would not be complete without some reference to the chief meteorological features of the year; and those I have been able to obtain from the observatories of the Capitol and of the Col- legium Romanum, and now present in the following table.Ta3le showing the Temperature, Raifall, and Deaaths in each AMonth of the Year.LThe observations on the temperature were made at the Capitol at a height of nearly two hundred feet above the level of the sea; those on the rainfall at the Collegium Ronianum at a height of one hundred and sixty-two feet above thelevelof the sea.]TESII.ERATURE.
Antigenic variation in African trypanosomes
Authors: Lex H.T. Van der Ploeg, Keith Gottesdiener, Mary G-S. Lee
Journal: Trends in Genetics (1992)

African trypanosomes evade the humoral immune response by periodically changing the antigenic identity of their variant cell-surface glycoprotein (VSG) coat. Antigenic variation relies on DNA rearrangement events that can translocate a silent VSG gene to a telomerically located VSG gene expression site. Antigenic switches can also be brought about by the differential transcriptional control of the expression sites, only one of which is transcribed at any time.
Mechanisms of nutritional repletion during total parenteral nutrition.
Authors: E Pullicino, M Elia
Journal: Gut (1989)

Mechanisms of nutritional repletion during total parenteral nutritionE PULLICINO AND M ELIA Total parenteral nutrition (TPN) is a valuable form of treatment for patients with severe diffuse Crohns disease, or those with intestinal fistulae.In many cases TPN is used for nutrition rehabilitation as well as nutritional support.The mechanisms of intermediary metabolism during rehabilitation including the changes in fuel selection, energy expenditure, and mechanisms of nutrient deposition are poorly understood.Therefore the following study was undertaken to improve knowledge in this respect.Case history SS a 28 year old man with Crohn's disease of the small and large intestine presented in 1980 to his local hospital with diarrhoea, cramping abdominal pain, and weight loss.He was treated with salazopyrine
Effects of Acute Hypoglycemia on Working Memory and Language Processing in Adults With and Without Type 1 Diabetes
Authors: Kate V. Allen, Martin J. Pickering, Nicola N. Zammitt, Robert J. Hartsuiker, Matthew J. Traxler, Brian M. Frier, Ian J. Deary
Journal: Diabetes Care (2015)

OBJECTIVE To examine the effects of hypoglycemia on language processing in adults with and without type 1 diabetes. RESEARCH DESIGN AND METHODS Forty adults were studied (20 with type 1 diabetes and 20 healthy volunteers) using a hyperinsulinemic glucose clamp to lower blood glucose to 2.5 mmol/L (45 mg/dL) (hypoglycemia) for 60 min, or to maintain blood glucose at 4.5 mmol/L (81 mg/dL) (euglycemia), on separate occasions. Language tests were applied to assess the effects of hypoglycemia on the relationship between working memory and language (reading span), grammatical decoding (self-paced reading), and grammatical encoding (subject-verb agreement). RESULTS Hypoglycemia caused a significant deterioration in reading span (P &amp;lt; 0.001; η2 = 0.37; Cohen d = 0.65) and a fall in correct responses (P = 0.005; η2 = 0.19; Cohen d = 0.41). On the self-paced reading test, the reading time for the first sentence fragment increased during hypoglycemia (P = 0.039; η2 = 0.11; Cohen d = 0.25). For the reading of the next fragment, hypoglycemia affected the healthy volunteer group more than the adults with type 1 diabetes (P = 0.03; η2 = 0.12; Cohen d = 0.25). However, hypoglycemia did not significantly affect the number of errors in sentence comprehension or the time taken to answer questions. Hypoglycemia caused a deterioration of subject-verb agreement (correct responses: P = 0.011; η2 = 0.159; Cohen d = 0.31). CONCLUSIONS Hypoglycemia caused a significant deterioration in reading span and in the accuracy of subject-verb agreement, both of which are practical aspects of language involved in its everyday use. Language processing is therefore impaired during moderate hypoglycemia.
Molecular dissection of the murine antibody response to streptococcal group A carbohydrate.
Authors: C T Lutz, T L Bartholow, N S Greenspan, R J Fulton, W J Monafo, R M Perlmutter, H V Huang, J M Davie
Journal: The Journal of Experimental Medicine (1987)

Monoclonal antibodies (mAb) to streptococcal group A carbohydrate (GAC) are encoded by a minimum of two VH, four JH, four V kappa, three J kappa, one V lambda, and one J lambda gene segments. The IdX, IdI-1, and Id5 idiotypic determinants are expressed by anti-GAC mAb and are found on free kappa chains. Each pattern of these determinants is encoded by a distinct V kappa gene segment, apparently without the requirement for a particular J kappa, VH, or JH gene segment, or somatic mutation. In contrast, the binding site-associated idiotypic determinant IdI-3a does not correlate with any single V or J gene segment.
Tales from retirement: A senior's lecture tour
Authors: E J M Campbell
Journal: BMJ (1997)

Like others in academic medicine I have been to many places as a visiting lecturer. Latterly, however, I found these visits were unsatisfactory on two counts. Firstly, the places I visited tended to be rather privileged. Secondly, the visits were too short to have much impact. Since retirement I have made several visits designed to lessen these disadvantages. I would like to encourage other retired doctors to try similar ventures.

As a general rule I have avoided very rich and very poor countries because for different, but obvious, reasons they don't need me. I prefer a middle income country; one in which they may have the books and some equipment but lack experience and perspective. And, …
Side Effects and Cancer-Related Stress Determine Quality of Life in Long-Term Survivors of Testicular Cancer
Authors: Arnstein Mykletun, Alv A. Dahl, Carl Fredrik Haaland, Roy Bremnes, Olav Dahl, Olbjørn Klepp, Erik Wist, Sophie D. Fosså
Journal: Journal of Clinical Oncology (2005)

Purpose The prevalence of long-term survivors after treatment for testicular cancer (TC) is increasing, and most studies display normal or only slightly reduced quality of life (QOL) in TC survivors (TCSs). Impaired QOL is claimed to be associated with treatment modality and its side effects, although most studies in this field can be criticized for various methodologic shortcomings. We wanted to examine variation in long-term QOL in TCSs in relation to TC treatment modality, side effects, and TC-related stress in a large population. Patients and Methods QOL, side effects, and TC-related stress were self-rated by a questionnaire at a mean of 11 years of follow-up in 1,409 TCSs treated from 1980 to 1994. Norm data was obtained from 2,678 males who were representative of the general population. QOL was measured with the Short Form-36 (SF-36), and TC-related stress was measured with the Impact of Event Scale. Results There were no clinically relevant differences in QOL between TCSs and age-adjusted norm data, although there was a slightly lowered SF-36 Physical Component Summary Score in TCSs. Variation of QOL in TCSs was related to self-reported side effects and TC-related stress but not to TC treatment modality. A significant association was found between side effects and TC-related stress. Conclusion TCSs do not suffer long term from reduced QOL, and only minor differences in QOL were found between different treatment modalities. TCSs who report more side effects or TC-related stress have increased risk for reduced QOL, but these associations are not explained by TC treatment modalities. Further QOL research in this area should explore vulnerability factors for side effects and TC-related stress.
Rehabilitation for shoulder instability
Authors: A Jaggi, S Lambert
Journal: British Journal of Sports Medicine (2010)

Both structural and non-structural components can contribute to shoulder instability. Classification and therefore management must recognise these factors to achieve functional stability. This paper discusses a classification system proposing three types of shoulder instability recognising the structural and non-structural components and that a continuum exists between pathologies. Structural causes can be addressed with surgical intervention, but non-structural causes such as altered neuromuscular control within the rotator cuff should be addressed conservatively. The purpose of this article is to describe the types of instability and guide appropriate management, helping to avoid surgery in inappropriate cases and ensure that effective rehabilitation has been achieved.
Is addition of sodium fluoride to cyclical etidronate beneficial in the treatment of corticosteroid induced osteoporosis?
Authors: W. F Lems, J. W G Jacobs, J. W J Bijlsma, G. J M van Veen, H. H M L Houben, H. C M Haanen, M. I Gerrits, H. J M van Rijn
Journal: Annals of the Rheumatic Diseases (1997)

<h3>Objective</h3> To evaluate the clinical performance of two chlamydia point-of-care (POC) tests compared with a gold standard nucleic acid amplification testing (NAAT). <h3>Methods</h3> Tests evaluated were the Chlamydia Rapid Test (CRT), Diagnostics for the Real World and the ACON Chlamydia Rapid Test Device, ACON Laboratories (ACON). Overall 226 men and 225 women in Port Vila, Vanuatu, participated in this prospective study in 2010. NAAT and POC testing was performed on samples of male urine and female vaginal swabs for 156 men and 223 women (CRT), and 133 men and 75 women (ACON). <h3>Results</h3> The sensitivity and specificity of the CRT in men were 41.4% (95% CI 23.5% to 61.1%) and 89.0% (95% CI 82.2% to 93.8%), respectively, and in women 74.2% (95% CI 61.5% to 84.5%) and 95.7% (95% CI 91.3% to 98.2%), respectively; for ACON, they were 43.8% (95% CI 19.8% to 70.1%) and 98.3% (95% CI 93.9% to 99.8%) in men, and in women 66.7% (95% CI 22.3% to 95.7%) and 91.3% (95% CI 82.0% to 96.7%), respectively. Both tests were (absolutely) insensitive at organism loads less than 1000 (log=3) per mL or per swab; the CRT sensitivity was significantly lower at loads less than, compared with those greater than, 100 000 (log=5) per mL or per swab. <h3>Conclusions</h3> The performance of both CRT and ACON is well below the levels stated by the manufacturers. The evaluated tests are unlikely to be helpful in clinical settings due to the high proportion of false-negatives that will go untreated and false-positives that will result in overtreatment and potential adverse social consequences.
Lack of removal of calcitriol during hemodialysis procedures.
Authors: S R Ash, P J Gloeckner, S L Barnett
Journal: Journal of the American Society of Nephrology (1997)

In this study, an in vitro study with blood was performed to determine whether calcitriol (Calcijex) is either bound or removed from blood by dialyzer circuits. The study utilized five different dialyzers, each with a widely varying membrane type, and standard dialysate blood lines. One liter of fresh whole bovine blood was injected with 0.6 microg calcitriol and was dialyzed against 5 L of acetate-based dialysate for 180 min. By measurement of changes in blood and dialysate levels of calcitriol, there was no evidence of any calcitriol dialytic clearance and no evidence of calcitriol binding to the blood side components for any of the dialysis circuits. The results of this study indicate that calcitriol can be injected intravenously at any time during a dialysis procedure, without significant removal of the drug from the blood by dialyzer clearance or by binding to materials in the dialyzer circuit.
Clonal anergy blocks in vivo growth of mature T cells and can be reversed in the absence of antigen.
Authors: B Rocha, C Tanchot, H Von Boehmer
Journal: The Journal of Experimental Medicine (1993)

Experiments in various models have indicated that immunological tolerance can result from the physical elimination (deletion) of reactive lymphocytes as well as from anergy. We have previously reported that mature CD4-CD8+ T cells when confronted with their antigen can proliferate extensively but are finally eliminated or become intrinsically anergic such that remaining cells are refractory to stimulation by any T cell receptor ligands, even in the presence of exogenous interleukin 2. Here we show that in vivo the anergy can be reversed in the absence of antigen, such that the cells are then able to proliferate extensively in vivo to a new challenge with the antigen in question.
Topical Sodium Nitrite Is Effective In Reducing Leg Ulcer-Associated Pain In Patients With Sickle Cell Disease
Authors: Caterina P. Minniti, Caroline Cantilena, Dihua Xu, Anna K. Conrey, Marlene Peters-Lawrence, George Grimes, James Nichols, Karen Axelrod, Kathleen Rizzo, Gregory J. Kato
Journal: Blood (2013)
Engaging CD19 or target of an antiproliferative antibody 1 on human B lymphocytes induces binding of B cells to the interfollicular stroma of human tonsils via integrin alpha 4/beta 1 and fibronectin.
Authors: S Behr, F Schriever
Journal: The Journal of Experimental Medicine (1995)

Adhesion of B lymphocytes within the different compartments of secondary lymphoid organs is essential for the function of the humoral immune response. It is not currently known how the temporary immobilization of B cells in distinct areas of this complex microenvironment is regulated. The present study aimed at defining B cell antigens that initiate binding of B cells to human tonsil sections in situ. Engaging the B cell antigens CD19 and target of an antiproliferative antibody 1 (TAPA-1) with monoclonal antibodies induced adhesion of these B cells to the interfollicular stroma. This binding occurred through the integrin alpha 4 beta 1 on the B cell surface and via the extracellular matrix protein fibronectin expressed in the interfollicular compartment of the tonsil. Signaling through either antigen, CD19 or TAPA-1, depended on tyrosine kinases. Binding induced by engaging CD19 required an intact cytoskeleton, whereas TAPA-1-transmitted adhesion did not. We suggest that CD19 and TAPA-1 have a novel and unique function by regulating an alpha 4 beta 1/fibronectin-mediated binding of B cells to the interfollicular stroma of lymphoid tissues.
Randomized Trial of Decongestive Lymphatic Therapy for the Treatment of Lymphedema in Women With Breast Cancer
Authors: Ian S. Dayes, Tim J. Whelan, Jim A. Julian, Sameer Parpia, Kathleen I. Pritchard, David Paul D'Souza, Lyn Kligman, Donna Reise, Linda LeBlanc, Margaret L. McNeely, Lee Manchul, Jennifer Wiernikowski, Mark N. Levine
Journal: Journal of Clinical Oncology (2013)

Purpose Because of its morbidity and chronicity, arm lymphedema remains a concerning complication of breast cancer treatment. Although massage-based decongestive therapy is often recommended, randomized trials have not consistently demonstrated benefit over more conservative measures. Patients and Methods Women previously treated for breast cancer with lymphedema were enrolled from six institutions. Volumes were calculated from circumference measurements. Patients with a minimum of 10% volume difference between their arms were randomly assigned to either compression garments (control) or daily manual lymphatic drainage and bandaging followed by compression garments (experimental). The primary outcome was percent reduction in excess arm volume from baseline to 6 weeks. Results A total of 103 women were randomly assigned, and 95 were evaluable. Mean reduction of excess arm volume was 29.0% in the experimental group and 22.6% in the control group (difference, 6.4%; 95% CI, −6.8% to 20.5%; P = .34). Absolute volume loss was 250 mL and 143 mL in the experimental and control groups, respectively (difference, 107 mL; 95% CI, 13 to 203 mL; P = .03). There was no difference between groups in the proportion of patients losing 50% or greater excess arm volume. Quality of life (Short Form-36 Health Survey) and arm function were not different between groups. Conclusion This trial was unable to demonstrate a significant improvement in lymphedema with decongestive therapy compared with a more conservative approach. The failure to detect a difference may have been a result of the relatively small size of our trial.
UK survey confirms link between deprivation and smoking
Authors: J. Wise
Journal: BMJ (2014)

A new analysis from the Office for National Statistics confirms the strong association between the prevalence of smoking and levels of deprivation in England.

Men and women living in the most deprived areas of England were more than twice as likely to smoke as those living in the wealthiest areas, the analysis found.1

The analysis, which used data from …
Comparison of techniques for obtaining lower airway epithelial cells from children
Authors: P. S. McNamara, A. Kicic, E. N. Sutanto, P. T. Stevens, S. M. Stick
Journal: European Respiratory Journal (2008)

Airway epithelial cells (AECs) are important in asthma as they are the first cells to encounter pathogens/allergens. In children, AECs can be obtained using a “blind” nonbronchoscopic technique through an endotracheal tube. However, due to the increasing use of laryngeal masks the number of children in whom this technique is applicable has become limited. Recently, the present authors began to use a portable “bronchoscope-directed” technique to sample AECs. The current study compares both techniques in both asthmatic and nonasthmatic children. A total of 81 children undergoing elective surgery, were grouped according to atopic status and respiratory symptoms. Cellular yield of blind and bronchoscope-directed brushings were compared and immunocytochemistry performed. AECs were cultured and cytokine analysis of culture supernatant undertaken. Both techniques were equally well-tolerated, with the only adverse effect being a cough in 10% of the subjects. The mean± sd cell yield was higher in bronchoscope-directed than blind brushings (5.1±2.4 versus 3.1±1.4x10 6 cells). Immunocytochemistry confirmed an epithelial cell lineage. Culture supernatant cytokine concentrations were similar regardless of sampling technique with patterns preserved between asthmatic and healthy nonatopic phenotypes. Compared with blind brushing portable bronchoscope-directed brushing is well-tolerated, yields significantly more cells and is a potentially quick and useful technique for obtaining airway epithelial cells for research into childhood respiratory disease, specifically asthma.