tbuckley/cabot-search huggingface dataset:
Fbxw7 hotspot mutations and human colon cancer: mechanistic insights from new mouse models
Authors: Jonathan E Grim
Journal: Gut (2013)

The recent explosion in cancer genomics provides an unprecedented view of the genetic changes present in solid tumours. The characterisation of colorectal cancer samples via DNA sequencing has confirmed the importance of established oncogene and tumour suppressor pathways (including the ‘mountains’ of Apc, Tp53 and Ras) but has also identified novel cancer genes that are mutated in a small percentage of patient samples (hills).1 ,2 Furthermore, these studies give a new appreciation of the spectrum of gene mutations present in cancers, especially in candidate tumour suppressor genes (TSGs). While classic genetics teaches that two hits are required to inactivate TSGs, sequencing studies show that heterozygous mutations are also quite frequent. Some of these are loss of function alleles, while others are recurrent missense mutations known as ‘hotspots’. Now, researchers are charged with the task of understanding how these genetic changes contribute to cancer development, invasion and spread.

Why are heterozygous mutations in TSGs commonly found in cancer genomes? While many of these are passenger mutations, some single allele mutations can significantly alter tumour suppressor protein expression or function. This, in turn, leads to incremental changes in growth or to other hallmarks of cancer. The concept of haploinsufficiency refers to such situations where decreased dosage of certain gene products is sufficient to promote tumorigenesis.3 However, the impact of most heterozygous mutations is largely unknown, because they …
Reflex Inhibition of Renal Sympathetic Nerve Activity during Myocardial Ischemia Mediated by Left Ventricular Receptors with Vagal Afferents in Dogs
Authors: Marc D. Thames, Francois M. Abboud
Journal: Journal of Clinical Investigation (1979)

The major goal of this investigation was to determine if activation of cardiac receptors during coronary artery occlusion could inhibit efferent renal sympathetic nerve activity. In nine chloralose anesthetized dogs with only carotid (n = 3) or with sinoaortic (n = 6) baroreceptors operative, anterior descending coronary artery (LAD) occlusion resulted in a small decrease in mean arterial pressure (−9.8±5.1 mm Hg, NS) and in a significant (P < 0.05) increase in renal nerve activity (24.0±4.1%). In these dogs, circumflex coronary artery (Cx) occlusion resulted in greater hypotension (−18.4±4.0 mm Hg), and yet no change (1.1±9%) in renal nerve activity was noted. Changes in left atrial pressure during LAD and Cx occlusion were not different. In seven dogs with carotid sinus denervation, coronary occlusions resulted in decreases both in arterial pressure and in renal nerve activity which were consistently greater during Cx occlusion. The responses to coronary occlusion in six dogs after sinoaortic deafferentation were similar to those observed with only carotid sinuses denervated. In all experiments, vagotomy abolished the difference in the blood pressure responses and the decreases in renal sympathetic nerve activity during Cx occlusion. Vagotomy also abolished the decrease in nerve activity during LAD occlusion in dogs with carotid or sinoaortic denervation. These data show that Cx occlusion and, to a lesser degree, LAD occlusion resulted in reflex withdrawal of renal sympathetic nerve activity mediated by left ventricular receptors with vagal afferents. The reflex withdrawal of renal nerve activity during Cx occlusion occurred in spite of hypotension and the presence of functioning sinoaortic baroreceptors.
[181] MEASURING ACTUAL LIVER FUNCTION BY THE NEW INTRAVENOUS UMAX-TEST (MAXIMAL ENZYMATIC LIVER FUNCTION CAPACITY BASED ON 13C-METHACETIN KINETICS) BEFORE AND AFTER LIVER RESECTION
Authors: M. Stockmann, B. Riecke, M. Fricke, S. Niehues, A.R. Lemke, P. Neuhaus
Journal: Journal of Hepatology (2007)
B lymphocyte binding to E- and P-selectins is mediated through the de novo expression of carbohydrates on in vitro and in vivo activated human B cells.
Authors: A A Postigo, M Marazuela, F Sánchez-Madrid, M O de Landázuri
Journal: Journal of Clinical Investigation (1994)

Cell adhesion to endothelium regulates the trafficking and recruitment of leukocytes towards lymphoid organs and sites of inflammation. This phenomenon is mediated by the expression of a number of adhesion molecules on both the endothelium and circulating cells. Activation of endothelial cells (EC) with different stimuli induces the expression of several adhesion molecules (E- and P-selectins, ICAM-1, VCAM-1), involved in their interaction with circulating cells. In this report, we have studied the binding of nonactivated and activated B cells to purified E- and P-selectins. Activated but not resting B cells were able to interact with both selectins. This binding capacity of activated B cells paralleled the induction of different carbohydrate epitopes (Lewisx, sialyl-Lewisx, CD57 and CDw65) as well as other molecules bearing these or related epitopes in myeloid cells (L-selectin, alpha L beta 2 and alpha X beta 2 integrins, and CD35) involved in the interaction of different cell types with selectins. B cells infiltrating inflamed tissues like in Hashimoto's thyroiditis, also expressed these selectin-binding carbohydrates in parallel with the expression of E-selectin by surrounding follicular dendritic cells. Moreover, the crosslinking of these selectin-binding epitopes resulted in an increased binding of B cells to different integrin ligands. Thus, in addition to the involvement of integrins, E- and P-selectins could play an important role in the interaction of B lymphocytes with the endothelium during B cell extravasation into lymphoid tissues and inflammatory foci as well as in their organization into lymphoid organs.
Suppressor Cells in Mice With Murine Mammary Tumor Virus-Induced Mammary Tumors. I. Inhibition of Mitogen-Induced Lymphocyte Stimulation 2 3
Authors: Andrew B. Rudczynski, Richard F. Mortensen
Journal: JNCI Journal of the National Cancer Institute (1978)

Suppressor cell activity was present in the glass-adherent fraction of spleen cells from C3H mice bearing murine mammary tumor virus-induced mammary tumors. These cells effectively suppressed the blastogenic response of syngeneic normal lymphocytes to concanavalin A (Con A). Suppression by the spleen cells from mammary tumor-bearing mice was not dependent on DNA synthesis. Removal of the suppressor cells from spleen cell suspensions of tumor-bearing animals (TBA) by passage of the cells on glass wool columns increased the Con A response of the remaining cells by fourfold to eightfold. Characterization of the suppressor population indicated that the cells were also adherent to nylon wool but not to plastic and contained a significantly increased proportion of surface immunoglobulin-bearing and complement receptor-bearing lymphocytes. Depletion of macrophages and T-cells did not remove the suppressive activity from the spleens of the TBA. The results were consistent with the identification of the suppressor cell as a B-cell.
Prevention of lung infections associated with human immunodeficiency virus infection.
Authors: P C Hopewell
Journal: Thorax (1989)

Current evidence indicates that the length of survival for patients with the acquired immunodeficiency syndrome (AIDS) is increasing, thereby affording a greater opportunity for strategies designed to prevent the infectious diseases that mark the syndrome. Because these infections may occur at different stages of immunosuppression caused by the human immunodeficiency virus (HIV), effective application of preventive measures depends not only on detection of HIV infection but also on the use of staging indicators. The diseases that serve to define AIDS, such as Pneumocystis carinii pneumonia, tend to occur late in the course of HIV infection and often when the T helper lymphocyte (CD4+ cells) count is less than 0.2 x 10(9)/l. Other infections, such as tuberculosis and pyogenic bacterial pneumonia, may develop at any point after HIV infection has occurred. Given this relation between the degree of immunosuppression and the occurrence of particular pulmonary infections, different preventive interventions should be applied at different times. It is now known that the incidence of several of the pulmonary infections that are common in patients with HIV infection can be reduced by prophylactic measures. Pneumocystis pneumonia is decreased in frequency by any one of several prophylactic agents, the best established being pentamidine administered as an inhaled aerosol. The role of isoniazid in the chemoprophylaxis of tuberculosis in patients not infected with HIV is well established. Although there is little evidence of benefit so far from isoniazid in HIV infected patients with a positive tuberculin skin test response, it is logical to assume that there could be some effect. The use of pneumococcal polysaccharide vaccine may also be of some benefit in reducing the frequency of pneumococcal pneumonia in patients with AIDS. In addition to these specific measures, the antiretroviral agent zidovudine decreases both the frequency and the severity of opportunist infections, at least during the first few months of treatment. A comprehensive strategy for prevention of HIV associated lung infection first requires detection of HIV seropositivity, staging the immunosuppression by the CD4+ cell count, and determining whether tuberculous infection is present by a tuberculin skin test. All seropositive individuals should be given pneumococcal vaccine and those with evidence of tuberculosis infection should be treated with isoniazid for one year. Zidovudine should probably be started when CD4+ cell counts are in the range 0.4-0.5 x 10(9)/l and prophylaxis against pneumocystis infection when CD4+ cell counts are in the range 0.2-0.3 x 10(9)/l.
Comparison of inhaled salmeterol and individually dose-titrated slow-release theophylline in patients with reversible airway obstruction. European Study Group
Authors: PL Paggiaro, D Giannini, A Di Franco, R Testi
Journal: European Respiratory Journal (1996)

The aim of this study was to compare the clinical efficacy of salmeterol versus theophylline in the treatment of moderate-to-severe asthma. One hundred and eighty nine asthmatic patients (forced expiratory volume in one second (FEV1) or peak expiratory flow (PEF) >50% of predicted) were randomized to receive either salmeterol dry powder, 50 microg b.i.d. via a Diskhaler (n=92) or dose-titrated slow-release theophylline capsules ("Theo-Dur") b.i.d. (n=97), in a double-blind, double-dummy, parallel group study for 4 weeks. Patients had previously been titrated with theophylline to a serum theophylline level of 10-20 microg x mL-1. The median percentage of nights with no asthma symptoms rose from 14% in both groups at baseline to 71% with salmeterol and to 46% with theophylline (p=0.044). There was also a significant increase for salmeterol in the median percentage of nights with no rescue salbutamol use (from 36 to 86%) compared with theophylline (from 71 to 78%; p=0.002). The mean morning PEF increased from 337 L x min-1 in the salmeterol group and 332 L x min-1 in the theophylline group to 372 and 357 L x min-1, respectively. No significant difference between the two treatments was observed for PEF, symptoms or additional salbutamol medication during the day. The incidence of gastrointestinal symptoms (gastric irritation, nausea and vomiting) was greater among patients receiving theophylline (11%) than with salmeterol (3%). These findings suggest that inhaled salmeterol is more effective in relieving symptoms of asthma, and better tolerated than theophylline in patients with moderate-to-severe asthma.
John Bullough John Cramsie Camac Anne Kirkman Collins Elizabeth Mary Curry (nee Tuck) Christopher John Day Hubert Crayden Edmunds Stuart Crisp Farman Anthony Hargreaves Sidney Lee Charles Lennox Ogilvy Macalister Kenneth William Hand Browning McAlpine Ridley Scott Pronob Kumar Thakur Wilfred Robert Trotter
Authors: R. Bullough, S. H Goodacre, L. Cartner, C. Chapman, C. Oates, H. Enevoldson, E. K Gardner, E M Edmunds, O C Wetherell, J E O'Connor, F. Shear, K R Peel, G. Bigley, V. van Haga, V. Thakur, E J Ross, M. E Morgans
Journal: BMJ (1999)

Former consultant anaesthetist Dartford group of hospitals (b Essex 1921
Bacteroides causing osteomyelitis in rheumatoid arthritis.
Authors: P R Crook, J Gray
Journal: Annals of the Rheumatic Diseases (1982)

their faeces, when the preceding specimen had been nega- tive (-/+ sequence).Six (31-6%) of these occasions were associated with a deterioration in clinical state compared with a similar deterioration associated with only 17 (9.8%) of the remaining 174 faecal culture sequences (+/+, +l-, -I-).Using the chi-square method, the authors found a p value less than 0-02.The chi-square method, however, should only be applied to independent variables.2Bacteriological sequences from the same patient are not.Chi-square should in this case be calculated on one faecal sample or sequence per patient.Indeed, pooling related data artificially rein- forces the strength of an observation.Moreover, if there are seasonal variations in klebsiella prevalence-which we do not know-the comparison has to be done at the same month for all patients and controls.The same chi-square error is found in the first klebsiella paper,3 where 433 faecal samples from 163 patients are pooled and subdivided according to clinical activity.So it appears that, even if the klebsiella idea is an interesting one, the evidence thus far of a relationship between kleb- siella and activity of ankylosing spondylitis largely rests on unsound statistics.
Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life
Authors: N. Sigurs, F. Aljassim, B. Kjellman, P. D. Robinson, F. Sigurbergsson, R. Bjarnason, P. M. Gustafsson
Journal: Thorax (2010)

<h3>Background</h3> An increased prevalence of asthma/recurrent wheeze (RW), clinical allergy and allergic sensitisation up to age 13 years has previously been reported in subjects hospitalised with respiratory syncytial virus (RSV) bronchiolitis in their first year of life compared with matched controls. A study was undertaken to examine whether these features persist into early adulthood, to report longitudinal wheeze and allergy patterns, and to see how large and small airway function relates to RSV infection and asthma. <h3>Methods</h3> Follow-up at age 18 years was performed in 46 of 47 subjects with RSV and 92 of 93 controls. Assessments included questionnaire, clinical examination, skin prick tests, serum IgE antibodies to inhaled allergens, blood eosinophils, fraction of exhaled nitric oxide (FeNO), spirometry, multiple breath washout (lung clearance index, LCI) and dry air hyperventilation challenge. <h3>Results</h3> Increased prevalence of asthma/RW (39% vs 9%), clinical allergy (43% vs 17%) and sensitisation to perennial allergens (41% vs 14%) were present at age 18 in the RSV cohort compared with controls. Persistent/relapsing wheeze associated with early allergic sensitisation predominated in the RSV cohort compared with controls (30% vs 1%). Spirometric function was reduced in subjects with RSV with or without current asthma, but not in asthmatic controls. LCI was linked only to current asthma, airway hyperresponsiveness and FeNO. <h3>Conclusions</h3> Severe early RSV bronchiolitis is associated with an increased prevalence of allergic asthma persisting into early adulthood. Small airway dysfunction (LCI) is related to current asthma and airway inflammation but not to RSV bronchiolitis. Reduced spirometry after RSV may reflect airway remodelling.
Inverse relationship between ESR spin trapping of oxyradicals and degree of functional recovery during myocardial reperfusion in isolated working rat heart
Authors: I. E Blasig, B. Ebert, C. Hennig, T. Pali, A. Tosaki
Journal: Cardiovascular Research (1990)

Journal Article Inverse relationship between ESR spin trapping of oxyradicals and degree of functional recovery during myocardial reperfusion in isolated working rat heart Get access Ingolf E Blasig, Ingolf E Blasig Search for other works by this author on: Oxford Academic PubMed Google Scholar Bernd Ebert, Bernd Ebert Search for other works by this author on: Oxford Academic PubMed Google Scholar Carmen Hennig, Carmen Hennig Search for other works by this author on: Oxford Academic PubMed Google Scholar Tibor Pali, Tibor Pali Search for other works by this author on: Oxford Academic PubMed Google Scholar Arpad Tosaki Arpad Tosaki Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 24, Issue 4, April 1990, Pages 263–270, https://doi.org/10.1093/cvr/24.4.263 Published: 01 April 1990 Article history Received: 30 May 1989 Accepted: 22 November 1989 Published: 01 April 1990
miR-30c-2-3p and miR-30a-3p: New Pieces of the Jigsaw Puzzle in HIF2α Regulation
Authors: Holger Moch, Magdalena Lukamowicz-Rajska
Journal: Cancer Discovery (2014)

Abstract Summary: Clear cell renal cell carcinoma (ccRCC), the most frequent subtype of renal cell cancer, is characterized by mutation of the von Hippel–Lindau (VHL) tumor suppressor gene, which results in stabilization of hypoxia-inducible factor (HIF) α proteins. In this issue of Cancer Discovery, Mathew and colleagues report that miR-30c-2-3p and miR-30a-3p downregulation in ccRCC promotes increased expression of HIF2α.Cancer Discov; 4(1); 22–4. ©2014 AACR. See related article by Mathew et al., p. 53
Nitric oxide production by the alveolar compartment of the lungs in cirrhotic patients
Authors: B. Degano, M. Mittaine, P. Hervé, J. Rami, N. Kamar, B. Suc, D. Rivière, L. Rostaing
Journal: European Respiratory Journal (2009)

In cirrhotic patients, alveolar nitric oxide (NO) concentration is increased. This may be secondary to increased output of NO produced by the alveoli (V'(A,NO)) and/or to decreased lung transfer factor of NO. In advanced liver cirrhosis, NO produced by the alveoli may play a role in abnormalities of pulmonary haemodynamics and gas exchanges. In cirrhotic patients, we aimed to measure V'(A,NO) and to compare V'(A,NO) with pulmonary haemodynamics and gas exchange parameters. Measurements were performed in 22 healthy controls and in 29 cirrhotic patients, of whom eight had hepatopulmonary syndrome. Exhaled NO concentrations were measured at multiple expiratory flow rates to derive alveolar NO concentration. V'(A,NO) was the product of alveolar NO concentration by single breath lung transfer factor for NO. V'(A,NO) was increased in patients (median (range) 260 (177-341) nL x min(-1)) compared with controls (79 (60-90), p<0.0001). Alveolar-arterial oxygen tension difference failed to correlate with V'(A,NO). However, cardiac index correlated positively and systemic vascular resistance correlated negatively with V'(A,NO) (r = 0.56, p = 0.001 and r = -0.52, p = 0.004, respectively). In cirrhotic patients, NO was produced in excess by the alveolar compartment of the lungs. Alveolar NO production was associated with hyperdynamic circulatory syndrome but not with arterial oxygenation impairment.
Whole-Organ Tissue Engineering: Decellularization and Recellularization of Three-Dimensional Matrix Scaffolds
Authors: Stephen F. Badylak, Doris Taylor, Korkut Uygun
Journal: Annual Review of Biomedical Engineering (2011)

The definitive treatment for end-stage organ failure is orthotopic transplantation. However, the demand for transplantation far exceeds the number of available donor organs. A promising tissue-engineering/regenerative-medicine approach for functional organ replacement has emerged in recent years. Decellularization of donor organs such as heart, liver, and lung can provide an acellular, naturally occurring three-dimensional biologic scaffold material that can then be seeded with selected cell populations. Preliminary studies in animal models have provided encouraging results for the proof of concept. However, significant challenges for three-dimensional organ engineering approach remain. This manuscript describes the fundamental concepts of whole-organ engineering, including characterization of the extracellular matrix as a scaffold, methods for decellularization of vascular organs, potential cells to reseed such a scaffold, techniques for the recellularization process and important aspects regarding bioreactor design to support this approach. Critical challenges and future directions are also discussed.
Anti-GM-CSF antibodies in paediatric pulmonary alveolar proteinosis
Authors: P Latzin
Journal: Thorax (2004)

Auto-antibodies against granulocyte-macrophage colony stimulating factor (GM-CSF) may be central to the pathogenesis of adult sporadic pulmonary alveolar proteinosis (PAP). The role of anti-GM-CSF auto-antibodies in paediatric forms of PAP is as yet unclear.Anti-GM-CSF auto-antibodies were determined with the help of an antigen capture assay using serum and/or bronchoalveolar lavage (BAL) fluid from 27 patients with PAP (nine adults, 15 children, three neonates) and from 185 children with different diseases as disease controls (various pulmonary conditions and patients with malignancies).Anti-GM-CSF auto-antibodies were detected in the serum of five of seven adult PAP patients. They were not found in the serum of any of the children or neonates with PAP nor in any of the disease control patients. Raised anti-GM-CSF titres were found in BAL fluid from three of four adult patients with PAP. Anti-GM-CSF auto-antibodies were detected in BAL fluid of only one of the 15 children (age at diagnosis 11 years, age at BAL 24 years) and in none of the neonates with PAP, nor in any of the disease control patients.The presence of anti-GM-CSF auto-antibodies seems to define an autoimmune disease underlying most of the adult sporadic type of PAP, but age at diagnosis may cause an overlap with children in some rare instances. In most of the children and all of the neonates the anti-GM-CSF titres were not significantly increased, indicating that alternative explanations are needed for the pathogenesis of the disease in these patients.
Imprinting May Provide Cancer Prevention Tools
Authors: K. Hede
Journal: JNCI Journal of the National Cancer Institute (2007)

At a time when sequencing of can cer cell DNA is revealing the tremendous complexity of gene mutations, some researchers are propos ing an underlying theme that may precede and could unite all cancers: loss of imprinting (LOI). Now research from several laboratories is beginning to bear out the hypothesis, indicating that imprinting status may provide a powerful new tool in cancer pre vention and early de tection. Several companies are rush ing to create diagnostic tests for early cancer detection, even as other groups are con centrating on re versing the process to prevent cancer. Parent-of-origin gene imprinting is part