tbuckley/cabot-search huggingface dataset:
Identification of amino acids at the junction of exons 3 and 7 that are used for the generation of glycosylation-related human CD45RO and CD45RO-like antigen specificities.
Authors: R Pulido, S F Schlossman, H Saito, M Streuli
Journal: The Journal of Experimental Medicine (1994)

The CD45 transmembrane protein tyrosine phosphatase plays an essential role in lymphocyte activation. In humans, CD45 is composed of five isoforms that are generated by alternative splicing of three exons of a common precursor mRNA. Expression of the smallest molecular mass 180-kD CD45 isoform (CD45-O) results from splicing out of exons 4(A), 5(B), and 6(C), which encode peptide regions near the NH2 terminus, and is regulated during T cell maturation and activation. Two monoclonal antibodies (mAb), UCHL1 (anti-CD45RO) and A6 (anti-CD45RO-like), were studied that selectively bind to murine transfectant cells expressing the human CD45-O isoform. The anti-CD45RO-like A6 mAb, but not the anti-CD45RO UCHL1 mAb, also weakly reacted with transfectant cells expressing the human CD45 isoforms that contained exons 4 and 5(AB), or exon 5(B) encoded sequences. The structural basis of the antigen specificities of these two different human anti-CD45RO mAbs was investigated at the molecular level by using potential glycosylation-defective CD45-O isoform variants containing amino acid substitutions at the junction of exons 3 and 7. Replacement of the threonine residue at position 8 (last amino acid encoded in exon 3 and a putative O-linked carbohydrate anchorage site) by an alanine, completely abrogated the reactivity of the UCHL1 mAb, but did not affect that of the A6 mAb. Conversely, replacement of either the asparagine at position 174 or the serine at position 176 (the first two putative carbohydrate anchorage sites in exon 7) by alanine, abrogated the reactivity of the A6 mAb, but not that of the UCHL1 mAb. Both the UCHL1 and A6 epitopes were dependent on the presence of O-linked carbohydrates; and the UCHL1, but not the A6 epitope, was dependent on the presence of sialic acid. These results demonstrate a pivotal role for the amino acids encoded at the junction of exons 3 and 7 for the generation of glycosylation-related CD45RO epitopes that are expressed in a cell lineage- and activation-regulated fashion.
Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial
Authors: David Sebag-Montefiore, Richard J Stephens, Robert Steele, John Monson, Robert Grieve, Subhash Khanna, Phil Quirke, Jean Couture, Catherine de Metz, Arthur Sun Myint, Eric Bessell, Gareth Griffiths, Lindsay C Thompson, Mahesh Parmar
Journal: The Lancet (2009)
Cardiac Rac1 overexpression in mice creates a substrate for atrial arrhythmias characterized by structural remodelling
Authors: Jan-Christian Reil, Mathias Hohl, Martin Oberhofer, Andrey Kazakov, Lars Kaestner, Patrick Mueller, Oliver Adam, Christoph Maack, Peter Lipp, Christian Mewis, Maurits Allessie, Ulrich Laufs, Michael Böhm, Hans-Ruprecht Neuberger
Journal: Cardiovascular Research (2010)

AimsThe small GTPase Rac1 seems to play a role in the pathogenesis of atrial fibrillation (AF). The aim of the present study was to characterize the effects of Rac1 overexpression on atrial electrophysiology.
Prevention and control of cystic echinococcosis
Authors: Philip S Craig, Donald P McManus, Marshall W Lightowlers, Jose A Chabalgoity, Hector H Garcia, Cesar M Gavidia, Robert H Gilman, Armando E Gonzalez, Myriam Lorca, Cesar Naquira, Alberto Nieto, Peter M Schantz
Journal: The Lancet Infectious Diseases (2007)
Expression of Interleukin-5 and Granulocyte-Macrophage Colony-stimulating Factor in Aspirin-sensitive and Non–Aspirin-sensitive Asthmatic Airways
Authors: ANA R. SOUSA, BORIS E. A. LAMS, RUDOLF PFISTER, PANDORA E. CHRISTIE, MICHAEL SCHMITZ, TAK H. LEE
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Increased numbers of eosinophils and mast cells in the bronchial mucosa are characteristic features in subjects with aspirin-sensitive asthma. Interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are involved in the activation, maturation, and perpetuation of survival of eosinophils. Immunohistochemical techniques were therefore used to study the expression of IL-5 and GM-CSF on frozen bronchial biopsies from 13 aspirin-sensitive asthmatic (ASA) and 8 non-ASA (NASA) subjects. Aspirin sensitivity was diagnosed by lysine-aspirin inhalation provocation. ASA airways demonstrated a significant 2-fold increase in the total number of submucosal inflammatory cells expressing IL-5 (p = 0.03) and approximate 4 - and 2-fold increases in the numbers of mast cells expressing IL-5 and GM-CSF (p = 0.02 and p = 0.04, respectively). There was also a 4-fold increase in the number of eosinophils expressing IL-5 (p = 0.004). These results suggest a central role for the mast cell and eosinophil in regulation of the inflammatory cell infiltrate of ASA airways by secretion of the hemopoietic cytokines IL-5 and GM-CSF.
Intrahepatic cholestasis of pregnancy: A randomized controlled trial comparing dexamethasone and ursodeoxycholic acid
Authors: Anna Glantz, Hanns‐Ulrich Marschall, Frank Lammert, Lars‐Åke Mattsson
Journal: Hepatology (2005)

Intrahepatic cholestasis of pregnancy (ICP) is characterized by troublesome maternal pruritus, elevated serum bile acids (> or =10 micromol/L) and increased fetal risk. Recently we determined a cutoff level of serum bile acids, > or =40 micromol/L, to be associated with impaired fetal outcome. We have now studied the effects of ursodeoxycholic acid (UDCA) and dexamethasone on pruritus, biochemical markers of cholestasis, and fetal complication rates in a double-blind, placebo-controlled trial. For this purpose, 130 women with ICP were randomly allocated to UDCA (1 g/day for three weeks), or dexamethasone (12 mg/day for 1 week and placebo during weeks 2 and 3), or placebo for 3 weeks. Pruritus and biochemical markers of cholestasis were analyzed at inclusion and after 3 weeks of treatment. Fetal complications (spontaneous preterm delivery; asphyxial events; and meconium staining of amniotic fluid, placenta, and membranes) were registered at delivery. An intention-to-treat analysis showed significant reduction of alanine aminotransferase (ALT) (P = .01) and bilirubin (P = .002) in the UDCA group only. In a subgroup analysis of ICP women with serum bile acids > or =40 micromol/L at inclusion (n = 34), UDCA had significant effects on pruritus (-75%), bile acids (-79%), ALT (-80%), and bilirubin (-50%) as well, but not on fetal complication rates. Dexamethasone yielded no alleviation of pruritus or reduction of ALT and was less effective than UDCA at reducing bile acids and bilirubin. In conclusion, 3 weeks of UDCA treatment improved some biochemical markers of ICP irrespective of disease severity, whereas significant relief from pruritus and marked reduction of serum bile acids were only found in patients with severe ICP.
Role of p75 Neurotrophin Receptor in the Neurotoxicity by β-amyloid Peptides and Synergistic Effect of Inflammatory Cytokines
Authors: Giovanni Perini, Vittorina Della-Bianca, Valeria Politi, Giuliano Della Valle, Ilaria Dal-Pra, Filippo Rossi, Ubaldo Armato
Journal: The Journal of Experimental Medicine (2002)

The neurodegenerative changes in Alzheimer's disease (AD) are elicited by the accumulation of β-amyloid peptides (Aβ), which damage neurons either directly by interacting with components of the cell surface to trigger cell death signaling or indirectly by activating astrocytes and microglia to produce inflammatory mediators. It has been recently proposed that the p75 neurotrophin receptor (p75NTR) is responsible for neuronal damage by interacting with Aβ. By using neuroblastoma cell clones lacking the expression of all neurotrophin receptors or engineered to express full-length or various truncated forms of p75NTR, we could show that p75NTR is involved in the direct signaling of cell death by Aβ via the function of its death domain. This signaling leads to the activation of caspases-8 and -3, the production of reactive oxygen intermediates and the induction of an oxidative stress. We also found that the direct and indirect (inflammatory) mechanisms of neuronal damage by Aβ could act synergistically. In fact, TNF-α and IL-1β, cytokines produced by Aβ-activated microglia, could potentiate the neurotoxic action of Aβ mediated by p75NTR signaling. Together, our results indicate that neurons expressing p75NTR, mostly if expressing also proinflammatory cytokine receptors, might be preferential targets of the cytotoxic action of Aβ in AD.
Subclinical Peripheral Neuropathy in Patients With Multiple Myeloma Before Chemotherapy Is Correlated With Decreased Fingertip Innervation Density
Authors: Alyssa K. Kosturakis, Zijing He, Yan Li, Jessica A. Boyette-Davis, Nina Shah, Sheeba K. Thomas, Haijun Zhang, Elisabeth G. Vichaya, Xin Shelley Wang, Gwen Wendelschafer-Crabb, William R. Kennedy, Donald A. Simone, Charles S. Cleeland, Patrick M. Dougherty
Journal: Journal of Clinical Oncology (2014)

The goal in this study was to determine the incidence of subclinical neuropathy in treatment-naive patients with multiple myeloma (MM) with no history of peripheral neuropathy using quantitative sensory tests (QSTs) and its correlation with innervation density of the extremities using noninvasive laser reflectance confocal microscopy.QST results were collected for 27 patients with a diagnosis of MM and compared with data collected from 30 age- and sex-matched healthy volunteers. Skin temperature, sensorimotor function (grooved pegboard test), and detection thresholds for temperature, sharpness, and low-threshold mechanical stimuli (von Frey monofilaments and bumps detection test) were measured. Meissner's corpuscle (MC) density in the fingertips was assessed using in vivo laser reflectance confocal microscopy.Patients showed a high incidence (> 80%) of ≥ one subclinical QST deficit. These included increased von Frey, bumps, and warmth detection thresholds as compared with healthy volunteers. Patients also showed increases in cold pain, sensorimotor deficits (grooved pegboard test), and higher overall neuropathy scores. MC density was significantly lower in patients than controls and showed significant inverse correlation with bumps detection threshold.Patients with MM commonly present with sensory and sensorimotor deficits before undergoing treatment, and these deficits seem to result from disease-related decreases in peripheral innervation density.
Non-invasive ventilation with neurally adjusted ventilatory assist improves patient-ventilator interaction
Authors: Martin Dres, Matthieu Schmidt, Matthieu Raux, Thomas Similowski, Alexandre Demoule
Journal: European Respiratory Journal (2011)

Neurally adjusted ventilatory assist (NAVA) is a mode of partial ventilatory support in which neural inspiratory activity is monitored and cycled through the continuous esophageal recording of the diaphragmatic electromyogram (EAdi). In non invasive ventilation (NIV), leaks can lead to patient-ventilator asynchronies which are source of failure. Then, using NAVA in NIV could, like in invasive ventilation, improve patient-ventilator interaction.  We analyzed whether, in comparison with pressure support (PS) with or without NIV algorithm (PS-NIV+ or PS-NIV0), NAVA with or without NIV algorithm (NAVA-NIV+ or NAVA-NIV0) could reduce inspiratory trigger delay, improve expiratory synchrony, and reduce the number of patient-ventilator asynchronies in NIV post-extubation patients. Randomly, the patients were ventilated during ten minutes in these four modes. Ventilatory breathing pattern and asynchronies (inspiratory and expiratory trigger delay, ineffective effort, autotriggering, double triggering, premature and late cycling) were compared between the four groups.  Seventeen patients were observed. Switching from PS-NIV+ to NAVA-NIV+ and from PS-NIV0 to NAVA-NIV0 did not appear to significantly modify the pattern of breathing. Leaks were significantly higher between NIV+ and NIV0. Inspiratory trigger delay was significantly shorter in NAVA-NIV+ than in PS-NIV+ (20 vs. 980ms, p   Compared to PS, NIV with NAVA improves patient-ventilator interaction which did not depend of the leaks level.
Birth and Death of Bone Cells: Basic Regulatory Mechanisms and Implications for the Pathogenesis and Treatment of Osteoporosis*
Authors: Stavros C. Manolagas
Journal: Endocrine Reviews (2000)

The adult skeleton regenerates by temporary cellular structures that comprise teams of juxtaposed osteoclasts and osteoblasts and replace periodically old bone with new. A considerable body of evidence accumulated during the last decade has shown that the rate of genesis of these two highly specialized cell types, as well as the prevalence of their apoptosis, is essential for the maintenance of bone homeostasis; and that common metabolic bone disorders such as osteoporosis result largely from a derangement in the birth or death of these cells. The purpose of this article is 3-fold: 1) to review the role and the molecular mechanism of action of regulatory molecules, such as cytokines and hormones, in osteoclast and osteoblast birth and apoptosis; 2) to review the evidence for the contribution of changes in bone cell birth or death to the pathogenesis of the most common forms of osteoporosis; and 3) to highlight the implications of bone cell birth and death for a better understanding of the mechanism of action and efficacy of present and future pharmacotherapeutic agents for osteoporosis.
Detection of Mutagenicity of the Colon Carcinogen 1,2-Dimethylhydrazine by the Host-Mediated Assay and Its Correlation to Carcinogenicity
Authors: Masaaki Moriya, Kimie Kato, Toshihiro Ohta, Kazuko Watanabe, Yoshiko Watanabe, Yasuhiko Shirasu
Journal: JNCI Journal of the National Cancer Institute (1978)

Mutagenic potential of 1,2-dimethylhydrazine (DMH) was investigated in the host-mediated assay with mice used as hosts. This assay revealed potent mutagenicity of this colon carcinogen for Salmonella typhimurium G46. The mutagenicity of DMH was inhibited by pretreatment of mice with disulfiram. In addition, mouse strain and sex differences influenced the mutation induction by DMH: Mutation induction was significantly lower in C57BL/6 mice than in outbred ICR mice of either sex and was generally higher in male than in females of either C57BL/6 or ICR mice.
Long-term macrolide therapy in chronic inflammatory airway diseases
Authors: P. A. J. Crosbie, M. A. Woodhead
Journal: European Respiratory Journal (2008)

In addition to direct antibacterial actions, 14- and 15-member-ring macrolides have immune modulating effects that appear to be the reason for clinical benefit in diffuse panbronchiolitis. A literature search was conducted for studies of the clinical effectiveness of macrolides in other chronic lung conditions. A number of studies were identified that showed short-term beneficial outcomes or the potential for such outcomes in cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease, asthma and post-transplant obliterative bronchiolitis. The studies were limited by small patient numbers, different outcome measures and short-term follow-up, and were not designed to assess potentially harmful effects. Further large prospective and long-term studies are required in order to identify potential benefit and harm before these agents can be recommended routinely for these conditions.
Effect of aclidinium bromide/formoterol fumarate fixed-dose combination (FDC) on night-time and early morning symptoms in COPD
Authors: Dave Singh, Kenneth Chapman, Barry Make, Michelle Mocarski, Cristina Serra, Esther Garcia Gil
Journal: European Respiratory Journal (2014)

Background 

Aclidinium/formoterol FDC is in clinical development for the treatment of COPD. We studied the effects of twice-daily aclidinium/formoterol FDC on night-time and early morning symptoms in patients with stable, moderate to severe COPD.

Methods 

ACLIFORM and AUGMENT were multinational, double-blind, placebo- and active-controlled, parallel-group studies. Patients were randomised to receive placebo, aclidinium 400 µg, formoterol 12 µg, FDC 400/6 µg or FDC 400/12 µg. Patients used an eDiary to report night-time and early morning symptoms, which also contained other questions related to symptom impacts.

Results 

The ITT population included 3394 patients (mean age 63.5 years; 60.5% male; moderate COPD 58.6%; baseline night-time symptom severity [mean±SD] 1.1±0.7, early morning symptom severity 1.3±0.7). Over 24 weeks, overall night-time symptom severity significantly improved with FDC vs placebo (FDC 400/12 µg: -0.11; 400/6 µg: -0.14), formoterol (FDC 400/12 µg: -0.05; 400/6 µg: -0.08) and aclidinium (FDC 400/12 µg: -0.09; 400/6 µg: -0.12) (all p<0.05). Overall, early morning symptom severity also improved with FDC vs placebo (FDC 400/12 µg: -0.12; 400/6 µg: -0.14), formoterol (FDC 400/12 µg: -0.06; 400/6 µg: -0.08) and aclidinium (FDC 400/12 µg: -0.09; 400/6 µg: -0.11) (all p<0.01). Night-time and early morning cough, wheezing, breathlessness and difficulty bringing up phlegm were significantly improved with FDC vs placebo (all p<0.05, both doses).

Conclusions 

These data suggest that aclidinium/formoterol FDC improves overall night-time and early morning symptom severity in patients with moderate to severe COPD compared with placebo and monotherapy.
The social and psychological impact of endometriosis on women's lives: a critical narrative review
Authors: Lorraine Culley, Caroline Law, Nicky Hudson, Elaine Denny, Helene Mitchell, Miriam Baumgarten, Nick Raine-Fenning
Journal: Human Reproduction Update (2013)

BACKGROUNDEndometriosis is a chronic condition affecting between 2 and 17% of women of reproductive age. Common symptoms are chronic pelvic pain, fatigue, congestive dysmenorrhoea, heavy menstrual bleeding and deep dyspareunia. Studies have demonstrated the considerable negative impact of this condition on women's quality of life (QoL), especially in the domains of pain and psychosocial functioning. The impact of endometriosis is likely to be exacerbated by the absence of an obvious cause and the likelihood of chronic, recurring symptoms. The aims of this paper are to review the current body of knowledge on the social and psychological impact of endometriosis on women's lives; to provide insights into women's experience of endometriosis; to provide a critical commentary on the current state of knowledge and to make recommendations for future psycho-social research.
Survival Associated with 5-Fluorouracil–Based Adjuvant Chemotherapy among Elderly Patients with Node-Positive Colon Cancer
Authors: Vijaya Sundararajan, Nandita Mitra, Judith S. Jacobson, Victor R. Grann, Daniel F. Heitjan, Alfred I. Neugut
Journal: Annals of Internal Medicine (2002)

Background: Randomized clinical trials have demonstrated the efficacy of adjuvant 5-fluorouracil (5-FU)-based chemotherapy after surgical resection of node-positive colon cancer. Although this treatment became the standard in 1990 following a National Institutes of Health Consensus Conference, among those at least 65 years of age it is less likely to be offered to older or nonwhite patients. Objective: To determine the association between 5-fu–based chemotherapy and survival in older patients. Design: Retrospective cohort study. Setting: Combined database of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program and Medicare. Patients: 4768 patients 65 years of age or older who received a diagnosis of node-positive colon cancer from 1992 to 1996, were covered by Medicare Parts A and B, and resided in the population covered by the SEER program. Measurements: Propensity scores to control for known predictors of receiving treatment, Cox proportional-hazards models to assess the association of 5-FU therapy with survival, and sensitivity analyses to estimate the possible effects of unknown confounders. Results: Fifty-two percent of patients received 5-FU therapy. For this sample, the hazard ratio for death associated with 5-FU therapy was 0.66 (95% CI, 0.60 to 0.73). Confounding could have accounted for this association only if an unmeasured confounder were extremely unequally distributed between the treated and untreated groups or increased mortality by at least 50%. Conclusions: 5-Fluorouracil adjuvant therapy is significantly associated with reduced mortality in older patients, similar to the association found in randomized, controlled trials among younger patients. More frequent use of 5-FU therapy in older patients would probably reduce death from colon cancer.
Magnification endoscopy, high resolution endoscopy, and chromoscopy; towards a better optical diagnosis
Authors: M J Bruno
Journal: Gut (2003)

In the past few years, optical magnification endoscopy and chromoscopy have gained renewed interest in the West as a means for the early detection of minute lesions in patients with Barrett’s oesophagus and in patients referred for colonic cancer screening. In Barrett’s oesophagus, the vast majority of data on the use of chromoscopy deals with the application of methylene blue. Conventional videoendoscopy in combination with methylene blue staining improves the detection of Barrett’s mucosa. A correlation has been shown between variation and intensity of staining and histologically verified stages of dysplasia or cancer. Magnification endoscopy and chromoscopy improve the detection of colonic non-polypoid lesions associated with neoplasia and carcinoma. Pitt pattern analysis enables the distinction of non-neoplastic non-polypoid lesions (type I and II) from neoplastic type non-polypoid lesions (type III-V) with great accuracy. It is certain that “old fashioned” chromoscopy combined with advanced endoscopic technology carry a great diagnostic potential and should be further put to the test for use in daily clinical practice.
Trimethoprim and tetracycline inhibit airway epithelial sodium absorption.
Authors: P G Middleton, D M Geddes, E W Alton
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Despite their frequent use in the treatment of chronic lung disease, the effect of antibiotics on the airway mucosa has not been defined. We have assessed the effect of a number of antibiotics on the ion transport processes of airway epithelia. Initial evaluation performed on sheep tracheal epithelium in vitro demonstrated that trimethoprim and tetracycline induced a rapid decrease in electrogenic ion transport. These responses were fully reversible, mediated through the mucosal surface, and reduced by amiloride pretreatment, suggesting inhibition of Na+ absorption. Serosal application of erythromycin produced a gradual decrease in short-circuit current, whereas other antibiotics (ampicillin, ceftazidime, colistin, chloramphenicol, gentamicin, and sulfamethoxazole) caused no significant change within 30 min of addition. In healthy human volunteers, trimethoprim and tetracycline induced a rapid decrease in nasal potential difference, which was attenuated by amiloride pretreatment. In subjects with cystic fibrosis, who exhibit increased Na+ absorption across respiratory epithelia, the responses to trimethoprim and tetracycline were enhanced, providing further evidence that these drugs inhibit Na+ absorption. In conclusion, this study has identified two antibacterial agents that also reduce the Na+ absorption found in CF. These drugs may offer combined effects for the treatment of CF.