tbuckley/cabot-search huggingface dataset:
Fluticasone propionate aqueous nasal spray compared with oral loratadine in patients with seasonal allergic rhinitis*
Authors: P. Géhanno, J.‐L. Desfougeres
Journal: Allergy (1997)

The effectiveness and safety of fluticasone propionate aqueous nasal spray (200 micrograms once daily for 4 weeks) were compared with those of loratadine (10 mg once daily for 4 weeks) in 114 adults and adolescents with seasonal allergic rhinitis in this multicenter, double-blind, double-dummy, randomized, parallel-group study. Patients recorded their nasal symptoms (nighttime and daytime obstruction, sneezing, itching, rhinorrhea, and overall discomfort) using a 4-point scale (0 = no symptoms, 3 = very frequent symptoms) in daily diaries. Clinicians assessed patients' nasal symptoms (nighttime and daytime obstruction, sneezing, itching, and rhinorrhea) using a 4-point scale at every scheduled visit. Clinicians and patients assessed the overall effectiveness of treatment at the end of the study. Fluticasone propionate improved clinician-rated total nasal symptom scores (defined as the sum of five nasal symptoms) more than loratadine at the 2-week and 4-week assessments (P < or = 0.008). Clinicians give fluticasone propionate better global ratings than loratadine (P = 0.04). After 4 weeks of treatment, between-group differences in clinician-rated individual nasal symptoms favored fluticasone propionate (P < 0.05), with the exception of nasal itching (P = 0.11). These findings were confirmed by between-group differences in the percentages of symptom-free days calculated from patient-recorded daily diary-card data. Both treatments were well tolerated. The incidence of adverse events between groups was similar. Fluticasone propionate aqueous nasal spray 200 micrograms administered once daily in the morning was more effective than loratadine 10 mg administered once daily for the treatment of seasonal allergic rhinitis.
Competition Between Two MHC Binding Registers in a Single Peptide Processed from Myelin Basic Protein Influences Tolerance and Susceptibility to Autoimmunity
Authors: Audrey Seamons, Jennifer Sutton, Dina Bai, Emily Baird, Nena Bonn, Björn F.C. Kafsack, Jeffrey Shabanowitz, Donald F. Hunt, Craig Beeson, Joan Goverman
Journal: The Journal of Experimental Medicine (2003)

Experimental allergic encephalomyelitis (EAE) is an animal model for multiple sclerosis induced by stimulating myelin basic protein (MBP)-specific T cells. The MBP-specific repertoire in B10.PL mice is shaped by tolerance mechanisms that eliminate MBP121–150–specific T cells. In contrast, MBPAc1–11–specific T cells escape tolerance and constitute the encephalitogenic repertoire. To determine if this differential tolerance is caused by differences in the abundance of MBP epitopes generated by processing, MBP peptides were eluted from I-Au complexes and analyzed by mass spectrometry. Peptides were identified from both the NH2-terminal and MBP121–150 regions. Unexpectedly, MBPAc1–18 and Ac1–17, which contain the MBPAc1–11 epitope, were much more abundant than MBP121–150 peptides. The results demonstrate that competition between two I-Au binding registers, a low affinity register defined by MBPAc1–11 and a high affinity register defined by MBP5–16, prevents most of the NH2-terminal naturally processed peptides from binding in the MBPAc1–11 register. The small fraction of MBPAc1–18 bound in the MBPAc1–11 register is not sufficient to induce tolerance but provides a ligand for MBPAc1–11–specific T cells during disease. These results provide a basis for both the lack of tolerance to MBPAc1–11 and the ability of this epitope to become a target during autoimmunity.
Profound duodenogastric reflux causes pancreatic growth in rats.
Authors: T Gasslander, H Mukaida, M K Herrington, R A Hinder, T E Adrian
Journal: Gut (1995)

Although duodenogastric reflux is a physiological event, excessive reflux may be a pathogenetic factor in several diseases of the foregut, including cancer. Long term profound duodenogastric reflux produces pancreatic and gastric tumours in rats. The trophic effect of surgically induced duodenogastric reflux on the pancreas was investigated and the mechanisms involved were examined. Rats with profound reflux from a split gastroenterostomy were compared with sham operated and unoperated controls after two and six weeks. In the six week experiment, one reflux and one sham group were given the cholecystokinin (CCK) receptor antagonist devazepide (25 nmol/kg/h). Duodenogastric reflux caused a significant increase in pancreatic weight, DNA, and plasma CCK and gastrin concentrations at both two and six weeks. Devazepide substantially reduced the pancreatic weight increase after six weeks but did not abolish it completely. CCK and gastrin were not affected by devazepide. These results suggest that CCK is largely responsible for the pancreatic growth induced by reflux but another factor may also be involved. The trophic effect of duodenogastric reflux may contribute to the increased incidence of pancreatic cancer reported after gastric surgery.
The unified theory of repression
Authors: Matthew Hugh Erdelyi
Journal: Behavioral and Brain Sciences (2006)

Repression has become an empirical fact that is at once obvious and problematic. Fragmented clinical and laboratory traditions and disputed terminology have resulted in a Babel of misunderstandings in which false distinctions are imposed (e.g., between repression and suppression) and necessary distinctions not drawn (e.g., between the mechanism and the use to which it is put, defense being just one). “Repression” was introduced by Herbart to designate the (nondefensive) inhibition of ideas by other ideas in their struggle for consciousness. Freud adapted repression to the defensive inhibition of “unbearable” mental contents. Substantial experimental literatures on attentional biases, thought avoidance, interference, and intentional forgetting exist, the oldest prototype being the work of Ebbinghaus, who showed that intentional avoidance of memories results in their progressive forgetting over time. It has now become clear, as clinicians had claimed, that the inaccessible materials are often available and emerge indirectly (e.g., procedurally, implicitly). It is also now established that the Ebbinghaus retention function can be partly reversed, with resulting increases of conscious memory over time ( hypermnesia ). Freud's clinical experience revealed early on that exclusion from consciousness was effected not just by simple repression (inhibition) but also by a variety of distorting techniques, some deployed to degrade latent contents ( denial ), all eventually subsumed under the rubric of defense mechanisms (“repression in the widest sense”). Freudian and Bartlettian distortions are essentially the same, even in name, except for motive (cognitive vs. emotional), and experimentally induced false memories and other “memory illusions” are laboratory analogs of self-induced distortions.
Podocyte Biology and Pathogenesis of Kidney Disease
Authors: Jochen Reiser, Sanja Sever
Journal: Annual Review of Medicine (2012)

Proteinuric chronic kidney disease (CKD), once a rare affliction believed to be mainly caused by genetic mutations, has become a global pandemic that severely diminishes the quality of life for millions. Despite the changing face of CKD, treatment options and resources remain woefully antiquated and have failed to arrest or reverse the effects of kidney-related diseases. Histological and genetic data strongly implicate one promising target: the podocyte. Podocytes are terminally differentiated cells of the kidney glomerulus that are essential for the integrity of the kidney filter. Their function is primarily based on their intricate structure, which includes foot processes. Loss of these actin-driven membrane extensions is tightly connected to the presence of protein in the urine, podocyte loss, development of CKD, and ultimately renal failure.
Identification of the Transferrin Receptor as a Novel Immunoglobulin (Ig)a1 Receptor and Its Enhanced Expression on Mesangial Cells in Iga Nephropathy
Authors: Ivan C. Moura, Miguel N. Centelles, Michelle Arcos-Fajardo, Denise M. Malheiros, James F. Collawn, Max D. Cooper, Renato C. Monteiro
Journal: The Journal of Experimental Medicine (2001)

The biological functions of immunoglobulin (Ig)A antibodies depend primarily on their interaction with cell surface receptors. Four IgA receptors are presently characterized. The FcαRI (CD89) expressed by myeloid cells selectively binds IgA1 and IgA2 antibodies, whereas the poly-IgR, Fcα/μR, and asialoglycoprotein receptors bind other ligands in addition to IgA. IgA binding by mesangial cells, epithelial cells, and proliferating lymphocytes is also well documented, but the nature of the IgA receptors on these cells remains elusive. A monoclonal antibody (A24) is described here that specifically blocks IgA binding to epithelial and B lymphocyte cell lines. Both the A24 antibody and IgA1 myelomas bind a cell surface protein that is identified as the transferrin receptor (CD71). The transferrin receptor selectively binds IgA1 antibodies, monomeric better than polymeric forms, and the IgA1 binding is inhibitable by transferrin. Transferrin receptor expression is upregulated on cultured mesangial cells as well as on glomerular mesangial cells in patients with IgA nephropathy. The characterization of transferrin receptor as a novel IgA1 receptor on renal mesangial cells suggests its potential involvement in the pathogenesis of IgA nephropathy.
The Protease Complex Consisting of Dipeptidyl Peptidase IV and Seprase Plays a Role in the Migration and Invasion of Human Endothelial Cells in Collagenous Matrices
Authors: Giulio Ghersi, Qiang Zhao, Monica Salamone, Yunyun Yeh, Stanley Zucker, Wen-Tien Chen
Journal: Cancer Research (2006)

Abstract Dipeptidyl peptidase IV (DPP4/CD26) and seprase/fibroblast activation protein α are homologous type II transmembrane, homodimeric glycoproteins that exhibit unique prolyl peptidase activities. Human DPP4 is ubiquitously expressed in epithelial and endothelial cells and serves multiple functions in cleaving the penultimate positioned prolyl bonds at the NH2 terminus of a variety of physiologically important peptides in the circulation. Recent studies showed a linkage between DPP4 and down-regulation of certain chemokines and mitogenic growth factors, and degradation of denatured collagens (gelatin), suggesting a role of DPP4 in the cell invasive phenotype. Here, we found the existence of a novel protease complex consisting of DPP4 and seprase in human endothelial cells that were activated to migrate and invade in the extracellular matrix in vitro. DPP4 and seprase were coexpressed with the three major protease systems (matrix metalloproteinase, plasminogen activator, and type II transmembrane serine protease) at the cell surface and organize as a complex at invadopodia-like protrusions. Both proteases were colocalized at the endothelial cells of capillaries, but not large blood vessels, in invasive breast ductal carcinoma in vivo. Importantly, monoclonal antibodies against the gelatin-binding domain of DPP4 blocked the local gelatin degradation by endothelial cells in the presence of the major metallo- and serine protease systems that modified pericellular collagenous matrices and subsequent cell migration and invasion. Thus, we have identified a novel mechanism involving the DPP4 gelatin-binding domain of the DPP4-seprase complex that facilitates the local degradation of the extracellular matrix and the invasion of the endothelial cells into collagenous matrices. (Cancer Res 2006; 66(9); 4652-61)
Response to Letter Regarding Article, “Dysregulation of Hydrogen Sulfide (H 2 S) Producing Enzyme Cystathionine γ-lyase (CSE) Contributes to Maternal Hypertension and Placental Abnormalities in Preeclampsia”
Authors: Keqing Wang, Shakil Ahmad, Meng Cai, Jillian Rennie, Takeshi Fujisawa, Fatima Crispi, James Baily, Mark R. Miller, Melissa Cudmore, Patrick W. F. Hadoke, Rui Wang, Eduard Gratacós, Irina A. Buhimschi, Catalin S. Buhimschi, Asif Ahmed
Journal: Circulation (2014)
Nondisruptive p53 Mutations Are Associated with Shorter Survival in Patients with Advanced Non–Small Cell Lung Cancer
Authors: Miguel A. Molina-Vila, Jordi Bertran-Alamillo, Amaya Gascó, Clara Mayo-de-las-Casas, María Sánchez-Ronco, Laia Pujantell-Pastor, Laura Bonanno, Adolfo G. Favaretto, Andrés F. Cardona, Alain Vergnenègre, Margarita Majem, Bartomeu Massuti, Teresa Morán, Enric Carcereny, Santiago Viteri, Rafael Rosell
Journal: Clinical Cancer Research (2014)

TP53 mutations in early-stage non-small cell lung cancer (NSCLC) may be associated with worse survival but their prognostic role in advanced NSCLC is controversial. In addition, it remains unclear whether mutated patients represent a clinically homogeneous group.We retrospectively examined TP53 mutations and outcome in a training cohort of 318 patients with stage IIIB-IV NSCLC: 125 epidermal growth factor receptor (EGFR) wild-type (wt) and 193 EGFR mutated (mut). An independent validation cohort of 64 EGFR-mut patients was subsequently analyzed. Mutations were classified as "disruptive" and "nondisruptive" according to their predicted degree of disturbance of the p53 protein structure and function.In the training cohort, TP53 mutations were found in 43 of the 125 EGFR-wt patients (34.4%). Of these, 28 had nondisruptive TP53 mutations and a median overall survival (OS) of 8.5 months, compared with 15.6 months for the remaining 97 patients (P=0.003). In the EGFR-mut group, TP53 mutations were found in 50 of the 193 patients (25.9%). The OS for the 26 patients with TP53 nondisruptive mutations was 17.8 months versus 28.4 months for the remaining 167 patients (P=0.04). In the validation cohort, the 11 patients with nondisruptive TP53 mutations had a median OS of 18.1 months compared with 37.8 months for the 53 remaining patients (P=0.006). In multivariate analyses, nondisruptive TP53 mutations had an independent, significant association with a shorter OS.Nondisruptive mutations in the TP53 gene are an independent prognostic factor of shorter survival in advanced NSCLC.
Treatment of exercise-induced asthma with beclomethasone dipropionate in children with asthma
Authors: R. Petersen, L. Agertoft, S. Pedersen
Journal: European Respiratory Journal (2004)

A new hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) aerosol markedly increases drug delivery to the airways. Therefore, even low doses of HFA-BDP should be effective, and the present study assesses this. A randomised, double-blind, crossover study was used to compare the effect of placebo, HFA-BDP 50 microg or 100 microg given q.d. (QVAR(TM) Autohaler(TM); 3M Pharmaceuticals, St. Paul, MN, USA) on exercise-induced bronchoconstriction and exhaled nitric oxide (eNO). After a 14-day run-in, 25 children (5-14 yrs old) entered three 4-week treatment periods, separated by a 1-week washout. After each period, the fall in forced expiratory volume in one second (FEV1), after an exercise test, and eNO were measured. Significant treatment effects with no carry-over or period effects were seen for both eNO and maximum fall in FEV1 after exercise. Differences were seen between placebo (fall in FEV1=27.9%; eNO=14.4 parts per billion (ppb)) and either dose of HFA-BDP, but not between the two active doses (50 microg: fall in FEV1=20.8%, eNO=9.3 ppb; 100 microg: fall in FEV1=20.9%, eNO=8.9 ppb). In conclusion, low q.d. doses of hydrofluoroalkane-beclomethasone dipropionate reduced exhaled nitric oxide and exercise-induced bronchoconstriction. Further studies are needed to assess whether q.d. administration of beclomethasone dipropionate is as effective as b.i.d. administration.
Morbidity After Sentinel Lymph Node Biopsy in Primary Breast Cancer: Results From a Randomized Controlled Trial
Authors: Anand David Purushotham, Sara Upponi, Manfred Borislav Klevesath, Lynda Bobrow, Keith Millar, Jonathan Peter Myles, Stephen William Duffy
Journal: Journal of Clinical Oncology (2005)

Purpose Axillary lymph node dissection (ALND) as part of surgical treatment for patients with breast cancer is associated with significant morbidity. Sentinel lymph node biopsy (SLNB) is a newly developed method of staging the axilla and has the potential to avoid an ALND in lymph node–negative patients, thereby minimizing morbidity. The aim of this study was to investigate physical and psychological morbidity after SLNB in the treatment of early breast cancer in a randomized controlled trial. Patients and Methods Between November 1999 and February 2003, 298 patients with early breast cancer (tumors 3 cm or less on ultrasound examination) who were clinically node negative were randomly allocated to undergo ALND (control group) or SLNB followed by ALND if subsequently found to be lymph node positive (study group). A detailed assessment of physical and psychological morbidity was performed during a 1-year period postoperatively. Results A significant reduction in postoperative arm swelling, rate of seroma formation, numbness, loss of sensitivity to light touch and pinprick was observed in the study group. Although shoulder mobility was less impaired on average in the study group, this was significant only for abduction at 1 month and flexion at 3 months. Scores reflecting quality of life and psychological morbidity were significantly better in the study group in the immediate postoperative period, with fewer long-term differences. Conclusion SLNB in patients undergoing surgery for breast cancer results in a significant reduction in physical and psychological morbidity.
System-based proteomic analysis of the interferon response in human liver cells
Authors: Wei Yan, Hookeun Lee, Eugene C Yi, David Reiss, Paul Shannon, Bartlomiej K Kwieciszewski, Carlos Coito, Xiao-jun Li, Andrew Keller, Jimmy Eng, Timothy Galitski, David R Goodlett, Ruedi Aebersold, Michael G Katze
Journal: Genome biology (2004)
U.K. Prospective Diabetes Study 22: Effect of age at diagnosis on diabetic tissue damage during the first 6 years of NIDDM
Authors: Timothy ME Davis, Irene M Stratton, Charles J Fox, Rury R Holman, Robert C Turner
Journal: Diabetes Care (1997)

OBJECTIVE To assess the effect of age at diagnosis on the initial prevalence and subsequent risk of the progression of diabetic tissue damage in patients with NIDDM. RESEARCH DESIGN AND METHODS The prevalence of Q-wave myocardial infarction, absent dorsalis pedis pulses, retinopathy, absent ankle jerks, hypertension, and microalbuminuria were determined at baseline and at 3 and 6 years of follow-up in five consecutive 6-year age-cohorts of 3,027 newly diagnosed white patients aged between 36 and 65 years recruited to the U.K. Prospective Diabetes Study. The effect of age at diagnosis on the initial prevalence and the risk of progression of these complications and associated conditions was analyzed using logistic regression and proportional odds methods, respectively. RESULTS Q-wave myocardial infarction and hypertension were more prevalent in older patients at presentation, but age at diagnosis did not have a significant effect on the increased risk of either after 6 years of NIDDM. Absent dorsalis pedis pulses and ankle jerks were also more prevalent in the older age-groups at presentation, but age at diagnosis was a significant predictor of the increasing prevalence of both during follow-up. The baseline prevalence of retinopathy and microalbuminuria was not related to age. The subsequent risk of retinopathy, but not microalbuminuria, increased significantly with age at diagnosis. CONCLUSIONS Age at diagnosis has a variable impact on different types of diabetic tissue damage and may thus be an important variable in epidemiological and intervention studies in NIDDM. Regular ophthalmologic surveillance and examination of the feet increase in importance with increasing age since the diagnosis of NIDDM.
Rare diseases bullet 7: Pleuropulmonary manifestations of systemic lupus erythematosus
Authors: M. P Keane
Journal: Thorax (2000)

Systemic lupus erythematosus (SLE), an autoimmune disorder which primarily affects women (10:1 female to male ratio), may affect virtually any organ.1 Predominant manifestations include non-deforming arthritis, serositis, photosensitivity, renal, haematological, and central nervous system involvement. Various laboratory abnormalities have been described in SLE, most commonly high titre antibodies directed against double stranded DNA,1nuclear ribonucleoprotein, Smith (Sm) antigen, Ro/SS-A, and La/SS-B/Ha.2 Pleuritis occurs in 17–60% of patients at some point in the course of the disease.1 3 Although severe parenchymal lung disease is uncommon, pulmonary complications of SLE are protean and include acute lupus pneumonitis, diaphragmatic dysfunction and shrinking lung syndrome, cavitating pulmonary nodules, pulmonary hypertension, pulmonary vasculitis, pulmonary embolism (often due to circulating anticardiolipin antibodies), alveolar haemorrhage (reflecting diffuse endothelial injury), chronic interstitial pneumonitis,3-7 bronchiolitis obliterans (with or without organising pneumonia),8 and opportunistic pulmonary infections or drug toxicity from immunosuppressive therapy.9 

The most common thoracic manifestation of SLE is pleuritis.3 10 Pleuritic pain is present in 45–60% of patients and may occur with or without a pleural effusion (fig1).3 Clinically apparent pleural effusions have been reported in up to 50% of patients with SLE3 and may be found in up to 93% of cases at necropsy.11 Effusions are usually bilateral but may be unilateral, equally distributed between the left and right hemithoraces. They are invariably exudative with higher glucose and lower lactate dehydrogenase levels than those found in rheumatoid arthritis.12 Antinuclear antibody (ANA), anti-DNA antibodies, and LE cells have been found in the pleural fluid.13 14 LE cells appear to be relatively specific.15 Pleural biopsies have rarely been performed in SLE and the findings are non-specific, revealing lymphocytic and plasma cell infiltration, fibrosis, and fibrinous pleuritis.16They are indicated primarily to exclude …
Population Density, Water Supply, and the Risk of Dengue Fever in Vietnam: Cohort Study and Spatial Analysis
Authors: Wolf-Peter Schmidt, Motoi Suzuki, Vu Dinh Thiem, Richard G. White, Ataru Tsuzuki, Lay-Myint Yoshida, Hideki Yanai, Ubydul Haque, Le Huu Tho, Dang Duc Anh, Koya Ariyoshi
Journal: PLoS Medicine (2011)

Aedes aegypti, the major vector of dengue viruses, often breeds in water storage containers used by households without tap water supply, and occurs in high numbers even in dense urban areas. We analysed the interaction between human population density and lack of tap water as a cause of dengue fever outbreaks with the aim of identifying geographic areas at highest risk.