tbuckley/cabot-search huggingface dataset:
Reversal of sinus arrest and atrioventricular conduction block in patients with sleep apnea during nasal continuous positive airway pressure.
Authors: H Becker, U Brandenburg, J H Peter, P Von Wichert
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Sinus arrest and atrioventricular (AV) block have been demonstrated in as much as 30% of patients with sleep apnea (SA). The reversal of heart block after tracheostomy has been shown. Nasal continuous positive airway pressure (nCPAP) now is widely used as the treatment of SA, but little data are available on the effect of nCPAP on heart block in patients with SA. During a 17-mo period 239 patients were found to have SA in an ambulatory study. Heart block was identified in 17 (16 male, one female) of these patients. Standard polysomnography and two-channel long-term ECG before and during nCPAP therapy were performed in order to assess the effect of nCPAP on SA and heart block. Mean age of the 17 patients was 50.7 yr (range, 27 to 78 yr), mean respiratory disturbance index (RDI) was 90/h (SD +/- 36.1) before nCPAP and 6/h (SD +/- 6.2) on the second treatment night. The number of episodes of heart block during sleep decreased significantly (p < 0.001) from 1,575 before therapy to 165 during nCPAP. In 12 patients (70.6%) heart block was totally prevented by nCPAP. In another three patients, there was a 71 to 97% reduction in the number of episodes of heart block on the second treatment night, and in two of them a complete reversal occurred thereafter. Two patients exhibited an increase in block frequency during nCPAP, which was reversed after 4 wk of nCPAP in one but persisted in the other.(ABSTRACT TRUNCATED AT 250 WORDS)
Determinants of gastro-oesophageal reflux perception in patients with persistent symptoms despite proton pump inhibitors
Authors: F Zerbib, A Duriez, S Roman, M Capdepont, F Mion
Journal: Gut (2007)

<h3>Background and aim:</h3> Approximately 20% of patients have persistent symptoms of gastro-oesophageal reflux despite proton pump inhibitor (PPI) therapy. The aim of this study was to assess the determinants of reflux perception in patients on PPI therapy. <h3>Patients and methods:</h3> 20 patients with typical gastro-oesophageal reflux symptoms (heartburn and/or regurgitation) despite double-dose PPIs (twice daily) were included in this study. Ambulatory 24 h pH–impedance studies were performed in all patients. The characteristics of symptomatic and asymptomatic reflux episodes were compared. Symptoms were considered globally and separately for heartburn and regurgitation. <h3>Results:</h3> A total of 1273 reflux episodes were detected including 243 (19.1%) acidic, 1018 (80.0%) weakly acidic and 12 (0.9%) weakly alkaline reflux episodes. Overall, 312 (24.5%) reflux episodes were symptomatic. The only factor associated with reflux perception was high proximal extent (p = 0.037). Compared with regurgitation, reflux episodes associated with heartburn were more frequently pure liquid (p = 0.009) and acidic (p = 0.027), had a lower nadir pH (p&lt;0.001), were more frequently preceded by acid reflux episodes (p&lt;0.001) and had a longer reflux bolus clearance time (p&lt;0.001). <h3>Conclusions:</h3> High proximal extent of the refluxate is the only factor associated with reflux perception in patients on double-dose PPI. However, compared with regurgitation, composition of the refluxate, sensitisation of the oesophagus by preceding acid exposure and delayed bolus clearance appear to play a role in heartburn perception.
Preneoplastic Markers of Hepatitis B Virus-Associated Hepatocellular Carcinoma
Authors: Hie-Won L. Hann, Jungmin Lee, Anne Bussard, Catherine Liu, Yongri R. Jin, Koel Guha, Marcia M. Clayton, Kristin Ardlie, Michael J. Pellini, Mark A. Feitelson
Journal: Cancer Research (2004)

Abstract Hepatitis B virus (HBV) carriers are at high risk for the development of hepatocellular carcinoma (HCC), but there are no reliable markers that will identify such high-risk carriers. The objective of this work is to identify serologic markers that may indicate the early presence of HCC. Since HBV-encoded X antigen (HBxAg) likely contributes to HCC by up- or down-regulation of host gene expression, X positive and negative HepG2 cells were made and subjected to cDNA subtraction. When specific ELISAs were constructed measuring differentially expressed antigens and corresponding antibodies, antibodies to several differentially expressed genes were detected. In cross-sectional and longitudinal studies, antibodies were predominantly present in patients with HBV-associated cirrhosis and HCC, but not in most carriers with hepatic inflammation alone or without active liver disease. Antibodies were also present in patients with hepatitis C virus (HCV)-related HCC, but rarely detected in sera from uninfected individuals, those with tumors other than HCC, or those with drug-induced hepatitis. Statistical analysis showed that HCC patients with four or more antibodies detectable before the appearance of HCC had decreased survival, suggesting that these markers may reflect stepwise hepatocarcinogenesis. Hence, these antibodies may serve as preneoplastic markers for HCC in HBV carriers with chronic liver disease, and may be identified by a simple blood test.
Heberden Oration, 1955: Research and the Rheumatic Diseases
Authors: W. Bauer
Journal: Annals of the Rheumatic Diseases (1957)

Iamparticularly pleased tobeprivileged todeliver theHeberden Oration this year.Lectureship before this Society constitutes anhonour ofwhich Iamvery proud.Thepreparation ofthislecture hasgiven meanopportunity toreview pastproblems, which wehaveundertaken withvarying degrees ofsuccess, todescribe workinprogress, andtotell offuture plans whichIbelieve holdunique opportunity and challenge.
Idiosyncratic Patterns of Learning and Word Association During Mania
Authors: GEORGE M. HENRY, HERBERT WEINGARTNER, DENNIS L. MURPHY
Journal: American Journal of Psychiatry (1971)

When compared to results from tests carried out when they were not manic, patients during mania showed changes in verbal learning and word association patterns. The findings support the hypothesis that a reversible learning disorder occurs during mania that is specific to this illness and is accounted for by different patterns of verbal association. The disorder may be related to states of hyperarousal and to alterations in central biogenic amine function.
Novel Cancer Therapeutics with Allosteric Modulation of the Mitochondrial C-Raf–DAPK Complex by Raf Inhibitor Combination Therapy
Authors: Yi-Ta Tsai, Mei-Jen Chuang, Shou-Hung Tang, Sheng-Tang Wu, Yu-Chi Chen, Guang-Huan Sun, Pei-Wen Hsiao, Shih-Ming Huang, Hwei-Jen Lee, Cheng-Ping Yu, Jar-Yi Ho, Hui-Kuan Lin, Ming-Rong Chen, Chung-Chih Lin, Sun-Yran Chang, Victor C. Lin, Dah-Shyong Yu, Tai-Lung Cha
Journal: Cancer Research (2015)

Mitochondria are the powerhouses of cells. Mitochondrial C-Raf is a potential cancer therapeutic target, as it regulates mitochondrial function and is localized to the mitochondria by its N-terminal domain. However, Raf inhibitor monotherapy can induce S338 phosphorylation of C-Raf (pC-Raf(S338)) and impede therapy. This study identified the interaction of C-Raf with S308 phosphorylated DAPK (pDAPK(S308)), which together became colocalized in the mitochondria to facilitate mitochondrial remodeling. Combined use of the Raf inhibitors sorafenib and GW5074 had synergistic anticancer effects in vitro and in vivo, but targeted mitochondrial function, rather than the canonical Raf signaling pathway. C-Raf depletion in knockout MEF(C-Raf-/-) or siRNA knockdown ACHN renal cancer cells abrogated the cytotoxicity of combination therapy. Crystal structure simulation showed that GW5074 bound to C-Raf and induced a C-Raf conformational change that enhanced sorafenib-binding affinity. In the presence of pDAPK(S308), this drug-target interaction compromised the mitochondrial targeting effect of the N-terminal domain of C-Raf, which induced two-hit damages to cancer cells. First, combination therapy facilitated pC-Raf(S338) and pDAPK(S308) translocation from mitochondria to cytoplasm, leading to mitochondrial dysfunction and reactive oxygen species (ROS) generation. Second, ROS facilitated PP2A-mediated dephosphorylation of pDAPK(S308) to DAPK. PP2A then dissociated from the C-Raf-DAPK complex and induced profound cancer cell death. Increased pDAPK(S308) modification was also observed in renal cancer tissues, which correlated with poor disease-free survival and poor overall survival in renal cancer patients. Besides mediating the anticancer effect, pDAPK(S308) may serve as a predictive biomarker for Raf inhibitors combination therapy, suggesting an ideal preclinical model that is worthy of clinical translation.
A Nodal-to-TGFβ Cascade Exerts Biphasic Control Over Cardiopoiesis
Authors: Wenqing Cai, Rosa M. Guzzo, Ke Wei, Erik Willems, Herman Davidovics, Mark Mercola
Journal: Circulation Research (2012)

The transforming growth factor-β (TGFβ) family member Nodal promotes cardiogenesis, but the mechanism is unclear despite the relevance of TGFβ family proteins for myocardial remodeling and regeneration.To determine the function(s) of TGFβ family members during stem cell cardiogenesis.Murine embryonic stem cells were engineered with a constitutively active human type I Nodal receptor (caACVR1b) to mimic activation by Nodal and found to secrete a paracrine signal that promotes cardiogenesis. Transcriptome and gain- and loss-of-function studies identified the factor as TGFβ2. Both Nodal and TGFβ induced early cardiogenic progenitors in embryonic stem cell cultures at day 0 to 2 of differentiation. However, Nodal expression declines by day 4 due to feedback inhibition, whereas TGFβ persists. At later stages (days 4-6), TGFβ suppresses the formation of cardiomyocytes from multipotent Kdr(+) progenitors while promoting the differentiation of vascular smooth muscle and endothelial cells.Nodal induces TGFβ, and both stimulate the formation of multipotent cardiovascular Kdr(+) progenitors. TGFβ, however, becomes uniquely responsible for controlling subsequent lineage segregation by stimulating vascular smooth muscle and endothelial lineages and simultaneously blocking cardiomyocyte differentiation.
Fc chimeric protein containing the cysteine-rich domain of the murine mannose receptor binds to macrophages from splenic marginal zone and lymph node subcapsular sinus and to germinal centers.
Authors: L Martínez-Pomares, M Kosco-Vilbois, E Darley, P Tree, S Herren, J Y Bonnefoy, S Gordon
Journal: The Journal of Experimental Medicine (1996)

Ligands for the cysteine-rich (CR) domain of the mannose receptor (MR) were detected by incubating murine tissues with a chimeric protein containing CR fused to the Fc region of human IgG1 (CR-Fc). In naive mice, CR-Fc bound to sialoadhesin+, F4/80low/-, macrosialin+ macrophages (M phi) in spleen marginal zone (metallophilic M phi) and lymph node subcapsular sinus. Labeling was also observed in B cell areas of splenic white pulp. Western blotting analysis of spleen and lymph nodes lysates revealed a restricted number of molecules that interacted specifically with CR-Fc. In immunized mice, labeling was upregulated on germinal centers in splenic white pulp and follicular areas of lymph nodes. Kinetic analysis of the pattern of CR-Fc labeling in lymph nodes during a secondary immune response to ovalbumin showed that CR ligand expression migrated towards B cell areas, associated with cells displaying distinctive dendritic morphology, and accumulated in developing germinal centers. These studies suggest that MR+ cells or MR-carbohydrate-containing antigen complexes could be directed towards areas where humoral immune responses take place, through the interaction of the MR CR domain with molecules expressed in specialized macrophage populations and antigen transporting cells.
Laminin γ2 fragments are increased in the circulation of patients with early phase acute lung injury
Authors: Masahiko Katayama, Akitoshi Ishizaka, Michiie Sakamoto, Seitaro Fujishima, Kiyotoshi Sekiguchi, Koichiro Asano, Tomoko Betsuyaku, Toru Kotani, Lorraine B. Ware, Michael A. Matthay, Satoru Hashimoto
Journal: Intensive Care Medicine (2009)

Laminin-5, a cell adhesive molecule expressed solely by epithelium, is known to enhance epithelial cell migration and repair of injured epithelium, after its essential component gamma2-chain is processed proteolytically. Our previous study revealed circulating levels of amino-terminal fragment of laminin gamma2-chain (G2F) reflect epithelial tumor invasiveness in carcinoma patients, but its physiological role in alveolar epithelial injury remains unknown.Sampling of epithelial lining fluids or pulmonary edema fluids from patients with acute lung injury (ALI) or related diseases was performed. Plasma samples were obtained from them at the time of disease onset or later. G2F concentrations were determined by immunoassay constructed by ourselves.We found a significantly higher amount of G2F in pulmonary edema and epithelial lining fluids of patients with ALI, as compared with those with the other respiratory diseases. Their plasma levels were also elevated significantly early at the onset of ALI (mean +/- SD; 147 +/- 82 ng/ml in non-surviving and 90 +/- 56 in surviving patients) as compared with those in the patients with cardiogenic pulmonary edema (59 +/- 36) or idiopathic pulmonary fibrosis (37 +/- 17), indicating alveolar epithelium rapidly secrete laminin-5 in ALI. At 5 days after onset, non-surviving patients maintained higher plasma concentrations (152 +/- 84), but in contrast, the levels in surviving patients declined (71 +/- 35), suggesting secretion of laminin-5 was suppressed, associated with recovery from ALI.Circulating G2F may be a biomarker for alveolar laminin-5 secreted early at disease onset in ALI, potentially regulating alveolar re-epithelialization.
Diagnosis of Ischemia-Causing Coronary Stenoses by Noninvasive Fractional Flow Reserve Computed From Coronary Computed Tomographic Angiograms
Authors: Bon-Kwon Koo, Andrejs Erglis, Joon-Hyung Doh, David V. Daniels, Sanda Jegere, Hyo-Soo Kim, Allison Dunning, Tony DeFrance, Alexandra Lansky, Jonathan Leipsic, James K. Min
Journal: Journal of the American College of Cardiology (2011)
Effect of the diaphragmatic contraction on lower oesophageal sphincter pressure in man.
Authors: R K Mittal, D F Rochester, R W McCallum
Journal: Gut (1987)

The effect of diaphragmatic contraction and relaxation on the lower oesophageal sphincter (LOS) pressure was studied in 10 healthy volunteers. Pressures in the oesophagus, LOS, and stomach were measured in three phases. Phase I, end tidal expiration; phase II, subjects inspired to total lung capacity (TLC) and kept the airway open (sustained diaphragmatic contraction); and phase III, at TLC subjects relaxed against a closed glottis (diaphragm relaxed). The LOS pressure in phase II was significantly higher than in phase I, while in phase III it was significantly lower compared with phase I. There was a net increase in LOS pressure of 32 mmHg in phase II as compared to phase I. After phase II, as subjects moved into phase III, there was a sudden drop in the LOS pressure. The LOS pressure in phase II correlated with the transdiaphragmatic pressure in a linear fashion. These observations suggest that diaphragmatic contraction in man enhances the LOS pressure and this augmentation of sphincter tone may be a vital component of the antireflux mechanism.
Simvastatin has an anti-inflammatory effect on macrophages via upregulation of an atheroprotective transcription factor, Kruppel-like factor 2
Authors: Tiina T. Tuomisto, Henri Lumivuori, Emilia Kansanen, Sanna-Kaisa Häkkinen, Mikko P. Turunen, Johannes V. van Thienen, Anton J. Horrevoets, Anna-Liisa Levonen, Seppo Ylä-Herttuala
Journal: Cardiovascular Research (2008)

AimsStatins have beneficial vascular effects beyond their cholesterol-lowering action. Since macrophages play a central role in atherogenesis, we characterized the effects of simvastatin on gene expression profile of human peripheral blood monocyte (HPBM)-macrophages.
THE RÔLE OF MICROBIC VIRULENCE, DOSAGE, AND HOST RESISTANCE IN DETERMINING THE SPREAD OF BACTERIAL INFECTIONS AMONG MICE
Authors: Leslie T. Webster
Journal: The Journal of Experimental Medicine (1930)

1. Three strains of Pasteurella native to rabbits, introduced into mouse communities failed to spread or survive. 2. One strain of fowl Pasteurella, so introduced, survived for 2 months without causing death, after which, it gave rise to a 5 day epidemic, fatal to 77 per cent of the population. Subsequently, no further deaths from this source occurred and the strain died out completely. 3. At the height of the epidemic, caused by the fowl strain of Pasteurella, 6 cultures were obtained which, on direct inoculation, proved to have a degree of virulence for mice and rabbits equal among themselves and the same as the strain originally employed.
Signaling Pathways Associated with Colonic Mucosa Hyperproliferation in Mice Overexpressing Gastrin Precursors
Authors: Audrey Ferrand, Claudine Bertrand, Ghislaine Portolan, Guanglin Cui, Jane Carlson, Lucien Pradayrol, Daniel Fourmy, Marlene Dufresne, Timothy C. Wang, Catherine Seva
Journal: Cancer Research (2005)

Abstract MTI/G-Gly mice and hGAS mice, overexpressing glycine-extended gastrin (G-Gly) and progastrin, respectively, display colonic mucosa hyperplasia, hyperproliferation, and an increased susceptibility to intestinal neoplasia. Here, we have used these transgenic mice to analyze in vivo the modulation of intracellular signaling pathways that may be responsible for the proliferative effects of gastrin precursors. The expression, activation, and localization of signaling and cell-to-cell adhesion molecules were studied using immunofluorescence and Western blot techniques on colonic tissues derived from MTI/G-Gly, hGAS, or wild-type FVB/N mice. These analyses revealed an up-regulation of Src tyrosine kinase and related signaling pathways [phosphatidyl inositol 3′-kinase (PI3K)/Akt, Janus-activated kinase (JAK) 2, signal transducer and activator of transcription (STAT) 3, and extracellular-signal regulated kinases (ERK)] in both MTI/G-Gly and hGAS mice compared with the wild-type control animals as well as an overexpression of transforming growth factor-α (TGF-α). In contrast, overexpression of the gastrin precursors did not affect the activation status of STAT1 nor the expression and the distribution of adhesion proteins (focal adhesion kinase, cadherins, and catenins). We report for the first time that the transition from a normal colonic epithelium to a hyperproliferative epithelium in MTI/G-Gly and hGAS mice may be a consequence of the up-regulation of Src, PI3K/Akt, JAK2, STAT3, ERKs, and TGF-α. Deregulation of cell adhesion, a late event in tumor progression, does not occur in these transgenic models.
Chemotherapy-Based Treatment for Castration-Resistant Prostate Cancer
Authors: Bostjan Seruga, Ian F. Tannock
Journal: Journal of Clinical Oncology (2011)

Most men with metastatic prostate cancer respond to various types of androgen ablation but progress to castration-resistant disease. The TAX 327 and Southwest Oncology Group (SWOG) 99-16 clinical trials established docetaxel-based chemotherapy as preferred first-line treatment for most men with symptomatic metastatic castration-resistant prostate cancer (mCRPC). However, only about half receive benefit from docetaxel, and those who respond initially progress and eventually die of (or with) mCRPC. Both cellular mechanisms and the tumor microenvironment are implicated in the development of resistance to docetaxel. New agents are being evaluated for men with mCRPC, either as first-line treatment in combination with docetaxel, or in men progressing during or after treatment with docetaxel. Thus far, agents evaluated in phase III trials in combination with docetaxel have not improved outcome, including the vaccine GVAX, high-dose vitamin D (DN-101), and the antiangiogenic agent bevacizumab. In contrast, cabazitaxel, a taxane that is not cross-resistant to docetaxel, substantially improved the outcome of men progressing during or after treatment with docetaxel-based chemotherapy when compared with mitoxantrone and prednisone. However, translation of benefit of cabazitaxel demonstrated in the TROPIC (Treatment of Hormone-Refractory Metastatic Prostate Cancer) trial into general oncologic practice will be challenging because this agent may cause serious toxicity. With the approval of less toxic hormonal agents (eg, abiraterone acetate) in the setting of docetaxel-resistant mCRPC, clinicians will have an opportunity to balance benefits and harms of new agents in an individual patient and may be able to use different agents in sequence.
IDENTIFICATION, CHARACTERIZATION AND MOLECULAR-CLONING OF A NOVEL HUMAN HEMATOPOIETIC-CELL ANTIGEN (HCA) EXPRESSED BY PRIMITIVE HEMATOPOIETIC PROGENITORS
Authors: N Uchida, Z Yang, O Pourquie, J Combs, M Nguyen, S Chen, L Humeau, R Ramanathan, S Craig, B Hill, K Leiby, K Wright, B Chen, G Weddell, A Sharma, R Hoffman, D Gearing, A Tsukamoto, B Peault
Journal: Blood (1994)
4sUDRB-seq: measuring genomewide transcriptional elongation rates and initiation frequencies within cells
Authors: Gilad Fuchs, Yoav Voichek, Sima Benjamin, Shlomit Gilad, Ido Amit, Moshe Oren
Journal: Genome biology (2014)

Abstract Although transcriptional elongation by RNA polymerase II is coupled with many RNA-related processes, genomewide elongation rates remain unknown. We describe a method, called 4sUDRB-seq, based on reversible inhibition of transcription elongation coupled with tagging newly transcribed RNA with 4-thiouridine and high throughput sequencing to measure simultaneously with high confidence genome-wide transcription elongation rates in cells. We find that most genes are transcribed at about 3.5 Kb/min, with elongation rates varying between 2 Kb/min and 6 Kb/min. 4sUDRB-seq can facilitate genomewide exploration of the involvement of specific elongation factors in transcription and the contribution of deregulated transcription elongation to various pathologies.
Determination of the kappa anti-alpha(1,3) dextran immune response difference by A gene(s) in the VKappa-locus of mice.
Authors: C de Preval, B Blomberg, M Cohn
Journal: The Journal of Experimental Medicine (1979)

Mice lacking the V(alpha(1,3) (h gamma1)-gene do not produce a gamma1 anti-alpha(1,3) dextran response. However, on hyperimmunization some strains mount a kappa-anti-alpha(1,3) dextran response, whereas other remain nonresponder. Responsiveness in dominant. The kappa-anti-alpha(1,3) response difference is linked to the Ly-3 locus on chromosone 6 and is likely the result of a structural Vkappa-gene(s). In conjunction with previous work, three Vkappa-allogroups can now be distinguished. At present, this is the only example of an immune responsiveness difference associated with the Vkappa-locus.
Child Murder by Mothers: A Critical Analysis of the Current State of Knowledge and a Research Agenda
Authors: Susan Hatters Friedman, Sarah McCue Horwitz, Phillip J. Resnick
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Maternal filicide, or child murder by mothers, occurs more frequently in the United States than in other developed nations. However, little is known about factors that confer risk to children. The authors review the literature to identify predictors of maternal filicide and identify gaps in knowledge about maternal filicide. METHOD: Databases were systematically searched for studies of maternal filicide and neonaticide (murder in the first day of life) that were conducted in industrialized countries and were published in peer-reviewed, English-language publications after 1980. RESULTS: Women who committed filicide varied greatly by the type of sample studied. Neonaticide was often committed by young, poor, unmarried women with little or no prenatal care. CONCLUSIONS: The results of the review suggest that little is known about the predictors of maternal filicide and that a systematic, focused program of research on reliable markers for maternal filicide is needed to better prevent these events.