tbuckley/cabot-search huggingface dataset:
The brain to gut pathway: a possible route of prion transmission
Authors: Victoria A Lawson, John B Furness, Helen M Klemm, Louise Pontell, Ewan Chan, Andrew F Hill, Roberto Chiocchetti
Journal: Gut (2010)

<h3>Objective</h3> The intestine is recognised to play a key role in the transmission of prion diseases. These diseases are associated with pathological isoforms (PrP<sup>Sc</sup>) of the normal cellular prion protein (PrP<sup>C</sup>) and can be transmitted between individuals or arise spontaneously. The brain, as the primary site of prion replication, could provide infectious prions to peripheral tissues. Here, we examine whether the brain is a source of intestinal prion accumulation. <h3>Methods</h3> Following intracerebral inoculation with human origin prions the ileums of BalbC mice with clinical prion disease were assessed by Western immunoblot and immunohistochemical analysis for the presence of PrP<sup>Sc</sup> and the survival of enteric glial cells (EGCs) and specific neuronal subpopulations in the myenteric and submucosal plexus. <h3>Results</h3> PrP<sup>Sc</sup> was detected in the ileum of 13/13 mice following intracerebral inoculation with prions and 0/4 saline-inoculated mice. PrP<sup>Sc</sup> was localised at detectable levels in the Peyer9s patches of infected mice. Investigation of neuronal subpopulations revealed a significant decrease in neurofilament reactive neurons (11±8%, p&lt;0.05, <i>n=5</i>) compared with saline-inoculated mice (23±5%, <i>n</i>=3). Neuronal nitric oxide synthase (nNOS) and tyrosine hydroxylase reactive neurons were decreased in some (2 of 4 and 1 of 3, respectively) but not all prion-infected mice, whereas calretinin and vasoactive intestinal peptide reactive neurons were unaffected. EGCs were highly distorted in circumscribed ganglia of the myenteric plexus. In areas of glial derangement, the neurons showed undefined outlines and faint cytoplasmic immuoreactivity for the pan-neuronal marker Hu and loss of nNOS reactivity. <h3>Conclusions</h3> The present work shows that PrP<sup>Sc</sup> can be transmitted from the brain to the intestine. This causes pathological changes in enteric glia and neurons. We conclude that PrP<sup>Sc</sup> of brain origin finds a substrate in the naturally occurring PrP<sup>C</sup> of EGCs and neurons. This results in a reservoir of PrP<sup>Sc</sup> in the intestine, which may represent a source of prion disease transmission through surgical procedures and environmental contamination.
Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference
Authors: F. Roila, J. Herrstedt, M. Aapro, R.J. Gralla, L.H. Einhorn, E. Ballatori, E. Bria, R.A. Clark-Snow, B.T. Espersen, P. Feyer, S.M. Grunberg, P.J. Hesketh, K. Jordan, M.G. Kris, E. Maranzano, A. Molassiotis, G. Morrow, I. Olver, B.L. Rapoport, C. Rittenberg, M. Saito, M. Tonato, D. Warr
Journal: Annals of Oncology (2010)
Schizophrenia in the Offspring of Antenatally Depressed Mothers in the Northern Finland 1966 Birth Cohort: Relationship to Family History of Psychosis
Authors: Pirjo Mäki, Tiina Riekki, Jouko Miettunen, Matti Isohanni, Peter B. Jones, Graham K. Murray, Juha Veijola
Journal: American Journal of Psychiatry (2009)

Maternal depression is relatively common during pregnancy. The authors examined whether maternal antenatal depressed mood increased the risk of schizophrenia and other psychoses among offspring with and without a familial history of psychosis.In the Northern Finland 1966 birth cohort, mothers of 12,058 children were asked at mid-gestation at the antenatal clinic if they felt depressed. The offspring were followed for over 30 years, and subsequent schizophrenia and other psychoses were detected using the Finnish Hospital Discharge Register, which was also used for identifying psychosis in the parents. Familial risk for psychosis was considered as a genetic risk factor and mothers' depressed mood as an environmental or genetic risk factor.The risk for schizophrenia was higher in the offspring with both maternal depressed mood during pregnancy and parental psychosis (OR=9.4, 95% CI=4.2-20.9 adjusted for sex and perinatal complications) than in those with a depressed mother but without parental psychosis (OR=1.0, 95% CI=0.6-1.8) or those without maternal depression and with a psychotic parent (OR=2.6, 95% CI=1.2-5.4). The reference group was birth cohort members without maternal antenatal depression and without parental psychosis.Maternal depressed mood during pregnancy per se is unlikely to increase the risk for schizophrenia in the offspring but may affect subjects with a family history for psychosis. This finding could be an example of a gene-environment or possibly a gene-gene interaction in the development of schizophrenia. Mothers' antenatal depression may act as additive factor for subjects vulnerable to schizophrenia.
Combined donor specific transfusion and anti-CD154 therapy achieves airway allograft tolerance
Authors: W Chalermskulrat
Journal: Thorax (2005)

<b>Background:</b> The state of tolerance allows long term graft survival without immunosuppressants. Lung transplantation tolerance has not been consistently achieved in either small or large animal models. <b>Methods:</b> The mechanisms and effectiveness of a tolerance induction protocol consisting of donor specific transfusion (DST; day 0) and a short course of co-stimulatory blockade (anti-CD154 antibody; days −7, −4, 0 and +4) were studied in the mouse heterotopic tracheal transplant model of chronic lung rejection. C57BL/6 mice received BALB/c tracheal grafts (day 0) and were treated with DST alone, anti-CD154 alone, the combination (DST/anti-CD154), or no treatment. No non-specific immunosuppressants were used. <b>Results:</b> DST/anti-CD154 in combination, but neither treatment alone, markedly prolonged the lumen patency and survival (&gt;100 days) of fully histo-incompatible allografts (p&lt;0.05 versus control allografts at every time point studied up to 16 weeks) without immunosuppression. This protocol was donor antigen specific as third party grafts (C3H) were promptly rejected. In addition, DST/anti-CD154 did not result in mixed chimerism but induced transplantation tolerance via a peripheral mechanism(s), which included significantly reduced cytotoxic T cell activity (p&lt;0.001) and a significantly increased percentage of CD4+CD25+ cells (p = 0.03). <b>Conclusions:</b> The DST/anti-CD154 protocol successfully induced and maintained long term, donor specific tolerance in the mouse heterotopic airway graft model of chronic lung rejection. This finding may lead us closer to successful tolerance induction in lung transplantation.
Infliximab Therapy in Pulmonary Sarcoidosis
Authors: Christian M. Kähler, Peter Heininger, Judith Loeffler-Ragg, Helene Vogelsinger
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

In their article, Baughman and colleagues (1) reported that infliximab therapy in patients with chronic sarcoidosis was associated with a significant improvement in percent predicted FVC after 24 weeks of therapy in a cohort of 138 patients. However, no benefit was demonstrated on the endpoints of the six-minutewalk test (6MWT), St. George’s Respiratory Questionnaire (SGRQ), or Borg’s CR10 dyspnea score. Post hoc analyses further suggested a greater benefit in patients with more severe disease. The authors conclude that the clinical relevance of the observedFVC improvement remains unclear. Nevertheless, they suggest that their data support further evaluation of anti–TNFtherapy in severe chronic sarcoidosis. In our opinion, the conclusions are too optimistic. This may lead to an uncontrolled use of infliximab in patients with chronic pulmonary sarcoidosis outside new study protocols. First, there is a clear limitation of the study in using FVC percent predicted as primary endpoint. Pulmonary function tests characteristically reveal a restrictive pattern with a reduction in DlCO, although it is not unusual for lung function to be normal (2). Endobronchial sarcoidosis may lead to impairment of airflow and obstructive respiratory physiology. There might be several reasons for a decrease in FVC—for example, bad performance or obesity. Measurement of TLC, RV, and DlCO might be more powerful in reflecting improvement of lung function. In our opinion, measurement of dynamic lung volumes is insufficient to reflect the changes occurring in sarcoidosis with pulmonary involvement. An improvement of 2.8% FVC percent predicted corresponds to an absolute increase of only about 0.080 L. Furthermore, endobronchial disease exists in approximately 70% of patients with stage II or III disease. Thus, changes in FEV1 would also be of interest (not mentioned in the article). Even the improvement in radiological findings remains questionable. There is no indication of the severity of sarcoidosis in the study population investigated.A radiological classification of patients into stages II to IVmight be helpful. Furthermore, a computed tomography scan would be more helpful to observe changes in radiological findings concerning both pulmonary involvement and the status of hilar and mediastinal lymphadenopathy. The study protocol has shown that the use of infliximab in these patients seems to be safe. On the other hand, O’Shea and colleagues reported the development of pulmonary sarcoidosis occurring in the context of infliximab treatment for ankylosing spondylitis (3). Since the study design shows several limitations, the investigators cannot suggest a potential beneficial effect of this expensive drug or propose further evaluation.
Circulating endothelial stem cells are not decreased in pulmonary emphysema or COPD
Authors: G. Caramori, G. M. Rigolin, F. Mazzoni, S. Leprotti, P. Campioni, A. Papi
Journal: Thorax (2010)

Previous studies have suggested a role for an increased apoptosis of the endothelial cells in the pulmonary capillaries of the alveolar septa in the pathogenesis of human pulmonary emphysema.1 In animal models, circulating endothelial stem cells, characterised by the concomitant expression of CD34+, CD133 and vascular endothelial growth factor receptor 2 (VEGF-R2), may contribute to the repair of lung damage.2 However, it is unknown if a decrease in the blood of these stem cells contributes to the pathogenesis of pulmonary emphysema in humans. The aim of our study was to investigate by flow cytometry the number of total (CD34+) and endothelial stem (triple positive for CD34+/CD133/VEGF-R2) cells in the peripheral venous blood of current and …
Mechanical Ventilation Guided by Esophageal Pressure in Acute Lung Injury
Authors: Daniel Talmor, Todd Sarge, Atul Malhotra, Carl R. O'Donnell, Ray Ritz, Alan Lisbon, Victor Novack, Stephen H. Loring
Journal: New England Journal of Medicine (2008)

Survival of patients with acute lung injury or the acute respiratory distress syndrome (ARDS) has been improved by ventilation with small tidal volumes and the use of positive end-expiratory pressure (PEEP); however, the optimal level of PEEP has been difficult to determine. In this pilot study, we estimated transpulmonary pressure with the use of esophageal balloon catheters. We reasoned that the use of pleural-pressure measurements, despite the technical limitations to the accuracy of such measurements, would enable us to find a PEEP value that could maintain oxygenation while preventing lung injury due to repeated alveolar collapse or overdistention.We randomly assigned patients with acute lung injury or ARDS to undergo mechanical ventilation with PEEP adjusted according to measurements of esophageal pressure (the esophageal-pressure-guided group) or according to the Acute Respiratory Distress Syndrome Network standard-of-care recommendations (the control group). The primary end point was improvement in oxygenation. The secondary end points included respiratory-system compliance and patient outcomes.The study reached its stopping criterion and was terminated after 61 patients had been enrolled. The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen at 72 hours was 88 mm Hg higher in the esophageal-pressure-guided group than in the control group (95% confidence interval, 78.1 to 98.3; P=0.002). This effect was persistent over the entire follow-up time (at 24, 48, and 72 hours; P=0.001 by repeated-measures analysis of variance). Respiratory-system compliance was also significantly better at 24, 48, and 72 hours in the esophageal-pressure-guided group (P=0.01 by repeated-measures analysis of variance).As compared with the current standard of care, a ventilator strategy using esophageal pressures to estimate the transpulmonary pressure significantly improves oxygenation and compliance. Multicenter clinical trials are needed to determine whether this approach should be widely adopted. (ClinicalTrials.gov number, NCT00127491.)
Effect of sputum induction on arterial oxygen saturation and spirometry in HIV-infected patients
Authors: TR Leigh, K Kirby, BG Gazzard, JV Collins
Journal: European Respiratory Journal (1994)

We wanted to study the effect of sputum induction on forced expiratory volume in one second (FEV1) and on oxygen saturation in normal controls, asymptomatic human immunodeficiency virus (HIV)-seropositive individuals, and HIV-seropositive patients under investigation for suspected Pneumocystis carinii pneumonia (PCP). Over a five month period, sputum induction with ultrasonically nebulized 3% saline was performed on 110 HIV-seropositive patients with suspected PCP, 10 asymptomatic HIV-seropositive patients, and 15 normal controls. Oxygen saturation (peak, trough and change in oxygen saturation (delta O2)) was measured throughout the procedure using pulse oximetry, and these results compared with the chest radiograph and the final pulmonary diagnosis. In addition, the effect of sputum induction on FEV1 was measured in the 15 control subjects and 10 asymptomatic HIV-seropositive patients. Compared with bronchoalveolar lavage, sputum induction had a diagnostic sensitivity for PCP of 76%. Chest radiography was 79% sensitive, and had specificity of 83%. Patients with PCP had lower peak and trough oxygen saturation values compared with the non-PCP group (mean peak 95 vs 97%; mean trough 88 vs 91%), and greater falls in O2 saturation during the procedure (mean delta O2 7.6 vs 5.5%). One subject desaturated to 76%, requiring supplemental oxygen. Sputum induction caused significant but temporary falls in FEV1 both in control and HIV-seropositive groups (mean maximum fall in FEV1 10.4 vs 12.5%). We conclude that although sputum induction causes significant falls in oxygen saturation and FEV1, it remains sensitive and safe, and provides a useful alternative to bronchoscopy for the diagnosis of PCP.
The Bradshaw Lecture ON THE RESULTS OF BRONCHIAL OBSTRUCTION: Delivered before the Royal College of Physicians of London on November 1st, 1910
Authors: G. N. Pitt
Journal: BMJ (1910)

on such subjects as the use of cod-liver oil in -chronic rheumatism, on 4narcotics, on abdominal -abscess, and other non-.professional articles to ,the Miecellany and else- where.
Preparation of patient‐related allergens for hyposensitization
Authors: L. K. Poulsen, I. Søndergaard, B. Weeke
Journal: Allergy (1988)

An affinity chrormatography method for preparation of patient‐related antigens from commercially available allergen extracts has been investigated. IgC 1,2,4 from a patient previously hyposensitized with dog hair and dandruff allergen was bound to protein A‐sepharosc, Secondly, commercial allergen extract was applied to the immunosorbent, and patient‐related antigens were selectively absorbed by the specific antibodies from the patient serum. Finally, immune complexes containing antigen and IgG were eluted. Alternatively, the antigens alone were purified by retaining the IgG on the column by means of a covalent reinforcement of the protein A‐IgC‐binding. Purified, patient‐related antigens were investigated in crossed immunoelectrophoresis and identity to IgG‐and IgE‐binding antigens (as determined by the CRIE‐technique) was suggested. The affinity purified IgG was unaltered with regard to protein A‐binding, binding of antigen and affinity for monoclonal antibody to human IgG‐subclasses. Further, it was demonstrated that the antigen‐binding capacity of IgG in the immune complexes was intact as evidenced by strong affinity to antigens even at low pH. The antigens eluted together with IgG were predominantly found in immune complexes with a molecular weight of &gt; 300 kdalton equivalent to 2 or more molecules of IgG. The possibility of employing a similar method with IgE instead of IgG for preparation of patient‐related allergens instead of antigens, is discussed.
Hapten conjugation in the leucocyte migration inhibition test in allergic chromate eczema
Authors: M. RYTTER, U.-F. HAUSTEIN
Journal: British Journal of Dermatology (1982)

We studied the in vitro conjugation of chromium salts and found that trivalent chromium binds to protein 10 times more strongly than hexavalent chromium. We also investigated the use of two different lymphocyte migration inhibition tests for the diagnosis of chromium allergy. The capillary method proved superior to the Clausen technique, and potassium dichromate was shown to be a better antigen than chromium chloride. The test results correlated well with standard patch tests and we recommend the capillary method for the investigation of difficult cases of suspected chromium allergy.
Pulseless Electric Activity
Authors: Robert J. Myerburg, Henry Halperin, Debra A. Egan, Robin Boineau, Sumeet S. Chugh, Anne M. Gillis, Joshua I. Goldhaber, David A. Lathrop, Peter Liu, James T. Niemann, Joseph P. Ornato, George Sopko, Jennifer E. Van Eyk, Gregory P. Walcott, Myron L. Weisfeldt, Jacqueline D. Wright, Douglas P. Zipes
Journal: Circulation (2013)
ANIMAL MODELS TO STUDY ESCHERICHIA COLI 0157:H7 ISOLATED FROM PATIENTS WITH HAEMORRHAGIC COLITIS
Authors: J.J Farmer, LeeW Riley, PaulA Blake, MitchellL Cohen, GeorgeK Morris, BerniceM Thomason, MorrisE Potter, T.J Barrett, C.A Bopp, Arnold Kaufmann, RobertS Remis, JoyG Wells
Journal: The Lancet (1983)
Epstein-Barr Virus Infection and Expression of B-cell Oncogenic Markers in HIV-Related Diffuse Large B-cell Lymphoma
Authors: Chun Chao, Michael J. Silverberg, Otoniel Martínez-Maza, Margaret Chi, Donald I. Abrams, Reina Haque, Hongbin D. Zha, Michelle McGuire, Lanfang Xu, Jonathan Said
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Epstein-Barr virus (EBV)-mediated lymphomagenesis in the setting of HIV infection has been widely accepted. However, little is known about how EBV impacts prognosis. We investigated the hypothesis that EBV infection is associated with expression of specific B-cell oncogenic markers in HIV-related diffuse large B-cell lymphoma (DLBCL) and examined the prognostic use of detecting EBV infection. Experimental Design: HIV-related DLBCL cases diagnosed between 1996 and 2007 within Kaiser Permanente California were identified. Immunohistochemical staining was used to analyze the expression of selected markers that are cell-cycle regulators, B-cell activators, and antiapoptotic proteins among others. EBV infection was determined by in situ hybridization of EBV RNA. Correlations between EBV and marker expression were examined using Spearman correlation coefficient. The prognostic use of EBV status was examined in multivariable Cox model adjusting for International Prognostic Index (IPI). Receiver-operating characteristics (ROC) analysis was used to evaluate improvement in model discrimination. Results: Seventy HIV-related DLBCL cases were included (31% EBV±). EBV+ tumor was associated with increased expression of BLIMP1 and CD30 and reduced expression of BCL6 and LMO2. EBV+ tumor was independently associated with elevated 2-year overall mortality [HR, 3.3; 95% confidence interval (CI), 1.6–6.6]. Area under the ROC curve showed improved model discrimination when incorporating tumor EBV status with IPI in the prediction model [0.65 vs. 0.74 (IPI only)]. Conclusion: Our results suggest that EBV infection was associated with expression of several tumor markers that are involved in the NF-κB pathway and that detecting tumor EBV status may have prognostic use in HIV-related DLBCLs. Clin Cancer Res; 18(17); 4702–12. ©2012 AACR.
Inflammation is associated with progression of actinic keratoses to squamous cell carcinomas in humans
Authors: T. Berhane, G.M. Halliday, B. Cooke, R.st.c Barnetson
Journal: British Journal of Dermatology (2002)

Squamous cell carcinoma (SCC) is a common skin tumour that may metastasize and lead to death. We have observed that before actinic keratoses (AK) progress to SCCs they may become tender and inflamed. In some of these, histological examination shows that they are, in fact, SCCs.To study the progression of AK to SCCs.We studied skin tumours from 50 patients with either asymptomatic AK, inflamed AK or SCCs, using immunocytochemistry. The diagnosis of each tumour was confirmed by histological examination.Studies of differentiation using heat shock protein 27 showed a stepwise loss of differentiation as the tumours progressed from asymptomatic AK, through inflamed AK to SCCs. During the inflamed AK phase, there was a marked increase in T lymphocytes and Langerhans cells: the number of infiltrating cells diminished as progression to SCC occurred. There was an increase in immunoreactive p53 and the apoptosis inhibitor bcl-2 as tumours progressed from AK to SCCs, and a decrease in Fas and Fas ligand.These studies have shown that progression from benign to malignant tumours may be associated with an inflammatory response, which appears to drive malignant conversion, but subsides rapidly following this conversion.
Association between weight or body mass index and hand osteoarthritis: a systematic review
Authors: E. Yusuf, R. G. Nelissen, A. Ioan-Facsinay, V. Stojanovic-Susulic, J. DeGroot, G. van Osch, S. Middeldorp, T. W. J. Huizinga, M. Kloppenburg
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objective</h3> To investigate the association between weight or body mass index (BMI) and the development of hand osteoarthritis. <h3>Methods</h3> Systematic review of observational studies. Medical databases were searched up to April 2008. Articles that presented data on the association between weight and hand osteoarthritis were selected. The qualities of these studies were then assessed by two independent reviewers using a 19 criteria scoring system. Using the mean scores of all studies as a cut-off value, the studies were deemed as high or low quality. Study quality and study designs were combined to determine the level of evidence using best-evidence synthesis, which consisted of five levels of evidence. <h3>Results</h3> From the 25 studies included, two had cohort, three case–control and 20 cross-sectional study designs. Fifteen studies were considered high-quality studies. Of these high-quality studies, one cohort, two case–control and seven cross-sectional studies showed a positive association between weight or BMI and hand osteoarthritis. Based on three high-quality studies with preferred study designs (one cohort and two case–control) with a positive association, the level of evidence of the association between overweight and developing hand osteoarthritis is moderate. The approximate risk ratio of this association is 1.9. <h3>Conclusion</h3> Weight or BMI is associated with the development of hand osteoarthritis. The level of evidence of published studies is moderate according to best-evidence synthesis. Further high-quality cohort or case–control studies are needed to elucidate the role of weight in hand osteoarthritis.