tbuckley/cabot-search huggingface dataset:
Effect of Acute Volume Loading on Heart Rate in the Conscious Dog
Authors: LAWRENCE D. HORWITZ, VERNON S. BISHOP
Journal: Circulation Research (1972)

The effect on heart rate of rapid elevation of ventricular filling pressure by intravenous infusion of isotonic solution was studied in 31 conscious dogs with autonomic innervation intact and during vagal, beta-receptor, or combined vagal and beta-receptor blockade. When parasympathetic innervation was intact, heart rate always rose during infusion and there was a consistent relationship between mean left atrial pressure and heart rate described by f = f m - ( f m - f l ) e -kp where f is the heart rate at any left atrial pressure, p , f m the maximum heart rate, f l the initial heart rate, and k a rate constant. Sympathetic blockade reduced the magnitude of the response and parasympathetic blockade prevented the response. It is concluded that a steady rise in filling pressure during intravenous infusion in a normally innervated, conscious dog invariably results in a tachycardia, which is due to either reflex inhibition of the parasympathetic nervous system or direct mechanical stimulation of the sinoatrial node.
Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease
Authors: R Kiesslich, C A Duckworth, D Moussata, A Gloeckner, L G Lim, M Goetz, D M Pritchard, P R Galle, M F Neurath, A J M Watson
Journal: Gut (2011)

<h3>Objectives</h3> Loss of intestinal barrier function plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Shedding of intestinal epithelial cells is a potential cause of barrier loss during inflammation. The objectives of the study were (1) to determine whether cell shedding and barrier loss in humans can be detected by confocal endomicroscopy and (2) whether these parameters predict relapse of IBD. <h3>Methods</h3> Confocal endomicroscopy was performed in IBD and control patients using intravenous fluorescein to determine the relationship between cell shedding and local barrier dysfunction. A grading system based on appearances at confocal endomicroscopy in humans was devised and used to predict relapse in a prospective pilot study of 47 patients with ulcerative colitis and 11 patients with Crohn9s disease. <h3>Results</h3> Confocal endomicroscopy in humans detected shedding epithelial cells and local barrier defects as plumes of fluorescein effluxing through the epithelium. Mouse experiments demonstrated inward flow through some leakage-associated shedding events, which was increased when luminal osmolarity was decreased. In IBD patients in clinical remission, increased cell shedding with fluorescein leakage was associated with subsequent relapse within 12 months after endomicroscopic examination (p&lt;0.001). The sensitivity, specificity and accuracy for the grading system to predict a flare were 62.5% (95% CI 40.8% to 80.4%), 91.2% (95% CI 75.2 to 97.7) and 79% (95% CI 57.7 to 95.5), respectively. <h3>Conclusions</h3> Cell shedding and barrier loss detected by confocal endomicroscopy predicts relapse of IBD and has potential as a diagnostic tool for the management of the disease.
Protective effects of cholestyramine on liver cirrhosis induced by carbon tetrachloride in the rat.
Authors: K de Heer, H D Sauer, B Werner, G Kloeppel
Journal: Gut (1980)

The influence of cholestyramine and chenodeoxycholic acid on the induction of liver cirrhosis by carbon tetrachloride was investigated in the Wistar rat. The addition of 1.3% cholestyramine to the diet of the experimental animals inhibited to a large extent the induction of cirrhosis. While all the animals subjected to carbon tetrachloride exposure plus basal diet and those to carbon tetrachloride intoxication plus chenodeoxycholic acid diet developed cirrhosis, the morphological manifestation of cirrhosis occurred in the livers of only two out of 18 rats under carbon tetrachloride treatment plus cholestyramine diet. The administration of cholestryamine induces reactions which correspond to the physiological protective mechanisms of the liver. These are the bile acid binding, bacteriostatic, and microsomal enzymatic stimulating properties of cholestyramine.
S52 Clinical Effectiveness of Telemonitoring For Chronic Obstructive Pulmonary Disease (COPD): Randomised Controlled Trial
Authors: H Pinnock, L McCloughlan, A Todd, J Hanley, S Lewis, A Krishan, W MacNee, C Pagliari, A Sheikh, B McKinstry
Journal: Thorax (2012)

<h3>Introduction</h3> Previous trials of telehealthcare for COPD have included enhanced clinical care compared with controls. It is therefore unclear if telehealthcare alone improves clinical outcomes and reduces hospital admissions. <h3>Aim</h3> To determine if telemetrically supported self-monitoring of COPD postpones hospital admissions when both intervention and control groups receive optimised care. <h3>Trial design</h3> 1-year, researcher-blind RCT in UK primary care. <h3>Methods</h3> Patients with a COPD admission in the previous year were randomised centrally to telemetric or traditional modes of monitoring: both groups received the same clinical care. The primary outcome, assessed by a researcher blinded to allocation, was time to first hospital admission caused by a COPD exacerbation over the trial year. Other outcomes included number of admissions, bed days, deaths and health-related quality of life (St George's Respiratory Questionnaire (SGRQ)). <h3>Results</h3> We randomised 256 patients (128 telemonitoring): baseline characteristics were similar. Using an intention-to-treat analysis, there was no difference in time to admission between the groups (adjusted hazard ratio for admission (reference=tele-group) 1.03 (95%CI 0.70 to 1.50). 61 patients in each group had an admission. There was no significant difference in the mean number of admissions/person (tele-group: 1.2 (SD 1.9), control: 1.1 (SD 1.6) p=0.51); bed days (tele-group: 9.4 (SD 19.1) vs control 8.8 (SD 15.9) p=0.66); or deaths (tele-group: 16, control 21. p=0.38). Quality of life at 1 year was similar in both groups (SGRQ tele-group: 68.2 (16.3) vs usual: 67.3 (17.3), mean difference: 1.5 (95% CI –1.5 to 4.5)). <h3>Conclusion</h3> When both groups received optimised care, telemonitoring did not appear to reduce the time to a hospital admission, duration of hospital admissions or increase quality of life. The place of telemonitoring in clinical care may depend upon whether it offers efficiency savings by enabling professionals to monitor and support the care of more patients than using traditional means of communication. <h3>ISRCTN number</h3> 96634935 <h3>Funding</h3> Chief Scientist Office of Scottish Government.
Significance of anti-HBx antibodies in hepatitis B virus infection
Authors: Massimo Levrero, Marietta Stemler, Claudio Pasquinelli, Alfredo Alberti, Olivier Jean-Jean, Alessandra Franco, Clara Balsano, Dialo Diop, Christian Brechot, Margherita Melegari, Erica Villa, Vincenzo Barnaba, Michel Perricaudet, Hans Will
Journal: Hepatology (1991)

Serological responses to hepatitis B virus-X determinants have been noted in human sera, but conflicting findings concerning the correlation of anti-HBx antibodies with different stages of hepatitis B virus infection or pathological sequelae have been reported. Using an adenovirus-based eukaryotic vector, the 17 kD X protein was efficiently expressed in 293 cells. Cellular extracts containing the eukaryotic X protein have been used to screen for anti-HBx antibodies by immunoblot analysis in a large panel of sera from patients affected by hepatitis B virus chronic hepatitis, hepatocellular carcinoma and acute viral hepatitis. Sera from 32 of 171 (19%) chronic hepatitis B virus patients were positive for anti-HBx antibodies. Only one of thirty-two (3%) HBsAg-negative, anti-HBs/anti-HBc-positive chronic hepatitis serum was anti-HBx positive. Very few sera from primary hepatocellular carcinoma patients showed positivity for anti-HBx (8 of 149 or 5%). Anti-HBx were also detected in 8 of 48 (17%) acute viral hepatitis patients. In the four cases that were followed up weekly, anti-HBx antibodies appeared 3 to 4 wk after the onset of the clinical signs. To compare the X protein expressed in eukaryotic and prokaryotic cells as a substrate for anti-HBx antibody detection, 171 sera were screened with HBx fusion proteins expressed in Escherichia coli. The prokaryotic cell extract test seems to be more sensitive. During the chronic phase of hepatitis B virus infection, the presence of anti-HBx antibodies detected with the eukaryotic cell extract correlates with the presence of well-established markers of ongoing viral replication: serum hepatitis B virus-DNA (p less than 0.001) and intrahepatic HBcAg expression (p less than 0.001).
Parental brain and socioeconomic epigenetic effects in human development
Authors: James E. Swain, Suzanne C. Perkins, Carolyn J. Dayton, Eric D. Finegood, S. Shaun Ho
Journal: Behavioral and Brain Sciences (2012)

Abstract Critically significant parental effects in behavioral genetics may be partly understood as a consequence of maternal brain structure and function of caregiving systems recently studied in humans as well as rodents. Key parental brain areas regulate emotions, motivation/reward, and decision making, as well as more complex social-cognitive circuits. Additional key environmental factors must include socioeconomic status and paternal brain physiology. These have implications for developmental and evolutionary biology as well as public policy.
Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis
Authors: Despina Moshous, Christophe Pannetier, Régina de Chasseval, Françoise le Deist, Marina Cavazzana-Calvo, Serge Romana, Elizabeth Macintyre, Danielle Canioni, Nicole Brousse, Alain Fischer, Jean-Laurent Casanova, Jean-Pierre de Villartay
Journal: Journal of Clinical Investigation (2003)

We have previously described the identification of Artemis, a factor involved in the nonhomologous end joining (NHEJ) phase of V(D)J recombination of T and B cell receptor genes. Null mutations of the Artemis gene result in a complete absence of T and B lymphocytes that is associated with increased cell radiosensitivity, causing the radiosensitive T–B– SCID (RS-SCID) condition. We presently report the occurrence of hypomorphic mutations of the Artemis gene in four patients from two kindreds. Partially preserved in vivo activity of Artemis is associated with the presence of polyclonal T and B lymphocyte populations, albeit in reduced numbers, along with chromosomal instability and development of EBV-associated lymphoma in two of four patients. This syndrome emphasizes the role of Artemis in the NHEJ pathway of DNA repair and suggests that other, yet ill-defined, conditions associating immunodeficiency and lymphoma could be caused by mutations in genes encoding NHEJ factors.
Association of EGFR Expression Level and Cetuximab Activity in Patient-Derived Xenograft Models of Human Non–Small Cell Lung Cancer
Authors: Christiane Amendt, Eike Staub, Manja Friese-Hamim, Stephan Störkel, Christopher Stroh
Journal: Clinical Cancer Research (2014)

To explore in a panel of patient-derived xenograft models of human non-small cell lung cancer (NSCLC) whether high EGFR expression, was associated with cetuximab activity.NSCLC patient-derived xenograft models (n=45) were implanted subcutaneously into panels of nude mice and randomization cohorts were treated with either cetuximab, cisplatin, cisplatin plus cetuximab, vehicle control, or else were left untreated. Responses according to treatment were assessed at week 3 by analyzing the relative change in tumor volume and an experimental analogue of the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. An EGFR IHC score was calculated for each patient-derived xenograft model and response was assessed according to EGFR expression level.When tumors were stratified into high and low EGFR expression groups (IHC score threshold 200; scale 0-300), a stronger antitumor activity was seen in the high EGFR expression group compared with the low EGFR expression group in both the cetuximab monotherapy and cisplatin plus cetuximab combination therapy settings. For tumors treated with cisplatin plus cetuximab, the objective response rate was significantly higher in the high EGFR expression group compared with the low EGFR expression group (68% vs. 29%). Objective response rates were similar in high and low expression groups for tumors treated with cisplatin alone (27% vs. 24%, respectively).Cetuximab activity in NSCLC patient-derived xenograft models was demonstrated clearly only in tumors that expressed high levels of EGFR, as defined by an IHC score of ≥200.
Albumin stimulates interleukin-8 expression in proximal tubular epithelial cells in vitro and in vivo
Authors: Sydney Tang, Joseph C.K. Leung, Katsushige Abe, Kwok Wah Chan, Loretta Y.Y. Chan, Tak Mao Chan, Kar Neng Lai
Journal: Journal of Clinical Investigation (2003)

Renal tubulointerstitial injury is characterized by inflammatory cell infiltrate; however, the stimuli for leukocyte recruitment are not fully understood. IL-8 is a potent chemokine produced by proximal tubular epithelial cells (PTECs). Whether nephrotic proteins stimulate tubular IL-8 expression remains unknown. Acute exposure of human PTECs to albumin induced IL-8 gene and protein expression time- and dose-dependently. Apical albumin predominantly stimulated basolateral IL-8 secretion. Electrophoretic mobility shift assay demonstrated nuclear translocation of NF-κB, and the p65/p50 subunits were activated. NF-κB activation and IL-8 secretion were attenuated by the NF-κB inhibitors pyrrolidine dithiocarbamate and cell-permeable peptide. Albumin upregulated intracellular reactive oxygen species (ROS) generation, while exogenous H2O2 stimulated NF-κB translocation and IL-8 secretion. Albumin-induced ROS generation, NF-κB activation, and IL-8 secretion were endocytosis- and PKC-dependent as these downstream events were abrogated by the PI3K inhibitors LY294002 and wortmannin, and the PKC inhibitors GF109203X and staurosporin, respectively. In vivo, IL-8 mRNA expression was localized by in situ hybridization to the proximal tubules in nephrotic kidney tissues. The intensity of IL-8 immunostaining was higher in nephrotic than non-nephrotic subjects. In conclusion, albumin is a strong stimulus for tubular IL-8 expression, which occurs via NF-κB–dependent pathways through PKC activation and ROS generation.
The effect of gas standardisation on exhaled breath condensate pH and PCO2
Authors: S. Dodig, I. Čepelak, D. Plavec, Ž. Vlašić, B. Nogalo, M. Turkalj
Journal: European Respiratory Journal (2007)

To the Editors: 

We read with interest the recent article by Kullmann et al. 1 reporting the effect of gas standardisation on exhaled breath condensate (EBC) pH. pH can be determined immediately upon sampling, without gas standardisation 2, or following EBC gas standardisation in case of delayed analysis 3–5. The influence of ambient air and analytical sample preparation pose a major problem for pH and carbon dioxide tension ( P CO2) determination in EBC. In gas standardisation (argon bubbling or CO2-free gas), CO2 is removed from the sample, thus reducing the effect of CO2 on pH determination. Kullmann et al. 1 even proposed CO2 standardisation at a P CO2 of 5.33 kPa, physiological alveolar P CO2. Based on the experience with gas determination in blood, which should not be exposed to ambient air, the aim of our …
Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome
Authors: Jeroen K J Van Houdt, Beata Anna Nowakowska, Sérgio B Sousa, Barbera D C van Schaik, Eve Seuntjens, Nelson Avonce, Alejandro Sifrim, Omar A Abdul-Rahman, Marie-José H van den Boogaard, Armand Bottani, Marco Castori, Valérie Cormier-Daire, Matthew A Deardorff, Isabel Filges, Alan Fryer, Jean-Pierre Fryns, Simone Gana, Livia Garavelli, Gabriele Gillessen-Kaesbach, Bryan D Hall, Denise Horn, Danny Huylebroeck, Jakub Klapecki, Malgorzata Krajewska-Walasek, Alma Kuechler, Matthew A Lines, Saskia Maas, Kay D MacDermot, Shane McKee, Alex Magee, Stella A de Man, Yves Moreau, Fanny Morice-Picard, Ewa Obersztyn, Jacek Pilch, Elizabeth Rosser, Nora Shannon, Irene Stolte-Dijkstra, Patrick Van Dijck, Catheline Vilain, Annick Vogels, Emma Wakeling, Dagmar Wieczorek, Louise Wilson, Orsetta Zuffardi, Antoine H C van Kampen, Koenraad Devriendt, Raoul Hennekam, Joris Robert Vermeesch
Journal: Nature Genetics (2012)
Novel rat Alzheimer's disease models based on AAV-mediated gene transfer to selectively increase hippocampal Aβ levels
Authors: Patricia A Lawlor, Ross J Bland, Pritam Das, Robert W Price, Vallie Holloway, Lisa Smithson, Bridget L Dicker, Matthew J During, Deborah Young, Todd E Golde
Journal: Molecular Neurodegeneration (2007)

Alzheimer's disease (AD) is characterized by a decline in cognitive function and accumulation of amyloid-beta peptide (Abeta) in extracellular plaques. Mutations in amyloid precursor protein (APP) and presenilins alter APP metabolism resulting in accumulation of Abeta42, a peptide essential for the formation of amyloid deposits and proposed to initiate the cascade leading to AD. However, the role of Abeta40, the more prevalent Abeta peptide secreted by cells and a major component of cerebral Abeta deposits, is less clear. In this study, virally-mediated gene transfer was used to selectively increase hippocampal levels of human Abeta42 and Abeta40 in adult Wistar rats, allowing examination of the contribution of each to the cognitive deficits and pathology seen in AD.Adeno-associated viral (AAV) vectors encoding BRI-Abeta cDNAs were generated resulting in high-level hippocampal expression and secretion of the specific encoded Abeta peptide. As a comparison the effect of AAV-mediated overexpression of APPsw was also examined. Animals were tested for development of learning and memory deficits (open field, Morris water maze, passive avoidance, novel object recognition) three months after infusion of AAV. A range of impairments was found, with the most pronounced deficits observed in animals co-injected with both AAV-BRI-Abeta40 and AAV-BRI-Abeta42. Brain tissue was analyzed by ELISA and immunohistochemistry to quantify levels of detergent soluble and insoluble Abeta peptides. BRI-Abeta42 and the combination of BRI-Abeta40+42 overexpression resulted in elevated levels of detergent-insoluble Abeta. No significant increase in detergent-insoluble Abeta was seen in the rats expressing APPsw or BRI-Abeta40. No pathological features were noted in any rats, except the AAV-BRI-Abeta42 rats which showed focal, amorphous, Thioflavin-negative Abeta42 deposits.The results show that AAV-mediated gene transfer is a valuable tool to model aspects of AD pathology in vivo, and demonstrate that whilst expression of Abeta42 alone is sufficient to initiate Abeta deposition, both Abeta40 and Abeta42 may contribute to cognitive deficits.
Hepatoprotection via the IL-6/Stat3 pathway
Authors: Rebecca Taub
Journal: Journal of Clinical Investigation (2003)

Stat3 is a vital transcription factor that is activated downstream of the gp130 receptor, primarily via IL-6 signaling in adult liver. A new study demonstrates that Stat3 provides hepatoprotection against Fas-mediated apoptotic liver damage by two mechanisms: direct inactivation of caspases and reduction of reactive oxygen species.
THE REACTION MECHANISM OF ß1C-GLOBULIN (C'3) IN IMMUNE HEMOLYSIS
Authors: Hans J. Müller-Eberhard, Agustin P. Dalmasso, Mary Ann Calcott
Journal: The Journal of Experimental Medicine (1966)

During immune hemolysis by human complement, C'3 (beta(1C)-globulin) becomes physically attached to the erythrocyte membrane. Binding of C'3 was found to be mediated by cell-bound, activated C'2 and to have the characteristics of an enzymatic reaction. A single C'4,2a site on the cell surface effected the binding of several hundred molecules of C'3 if the latter was provided in excess. The accumulation of hemolytically inactive, physicochemically altered C'3 in the fluid phase was found to be an inherent feature of the process of C'3 binding. It is postulated that C'4,2a activates C'3 for its subsequent reaction with cell membrane receptors. Antierythrocyte antibody did not play an essential role in C'3 uptake; C'3 could be bound to erythrocyte-C'4,2a complexes which were entirely devoid of antibody. Cell-bound C'3 proved hemolytically active, the degree of hemolysis being proportional to the number of C'3 molecules per cell. Binding of a large number of C'3 molecules per cell was found to be a prerequisite for the production of the immune adherence phenomenon and for immune hemolysis.
Childhood Wheeze Phenotypes Show Less Than Expected Growth in FEV<sub>1</sub> across Adolescence
Authors: Caroline J. Lodge, Adrian J. Lowe, Katrina J. Allen, Sophie Zaloumis, Lyle C. Gurrin, Melanie C. Matheson, Christine Axelrad, Liam Welsh, Catherine M. Bennett, John Hopper, Paul S. Thomas, David J. Hill, Cliff S. Hosking, Cecilie Svanes, Michael J. Abramson, Shyamali C. Dharmage
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Better characterization of childhood wheeze phenotypes using newer statistical methods provides a basis for addressing the heterogeneity of childhood asthma. Outcomes of these phenotypes beyond childhood are unknown.To determine if adolescent respiratory symptoms, lung function, and changes in lung function over adolescence differ by childhood wheeze phenotypes defined through latent class analysis.A prospective birth cohort (Melbourne Atopy Cohort Study) followed 620 high allergy-risk children, recording respiratory symptoms and spirometry at 12 and 18 years. Regression analyses identified relationships between wheeze phenotypes (never/infrequent, early transient, early persistent, intermediate onset, and late onset) and lung function, change in lung function (12-18 yr), respiratory symptoms, and asthma. The baseline classification was never/infrequent wheeze.Deficits in expected growth of lung function, measured by change in prebronchodilator FEV1 between 12 and 18 years, were found for early persistent (reduced 290 ml; 95% confidence interval [CI], 82-498), intermediate-onset (reduced 210 ml; 95% CI, 62-359), and late-onset wheeze (reduced 255 ml; 95% CI, 69-442). Intermediate-onset wheezers had persistent FEV1 deficit after bronchodilator at 18 years (reduced 198 ml; 46,350). Current asthma risk was increased for all phenotypes except early transient, which was also not associated with lung function deficits at 12 or 18 years.Persistent wheeze phenotypes in childhood were associated with reduced growth in prebronchodilator FEV1 over adolescence. Intermediate-onset wheezers showed irreversible airflow limitation by 18 years. Conversely, early transient wheeze was a benign condition with no sequelae for respiratory health by age 18.