tbuckley/cabot-search huggingface dataset:
TRANSMISSION OF SWINE INFLUENZA VIRUS BY LUNGWORM MIGRATION
Authors: H. G. Sen, G. W. Kelley, N. R. Underdahl, G. A. Young
Journal: The Journal of Experimental Medicine (1961)

Experimental evidence is presented which confirms the reports by Shope (1, 2) that swine lungworms can serve as an intermediate host in transmitting swine influenza virus to pigs. The virus is present in a masked non-infective form as he showed and a provocative stimulus is necessary to initiate infection. Multiple injections of Ascaris extract or the migration of Ascaris larvae furnished the needed provocation. The virus could be elicited in the spring and summer as well as fall and winter, from the pathogen-free, colostrum-deprived pigs.
The plasma membrane sodium-hydrogen exchanger and its role in physiological and pathophysiological processes.
Authors: R L Mahnensmith, P S Aronson
Journal: Circulation Research (1985)

The plasma membranes of most if not all vertebrate cells contain a transport system that mediates the transmembrane exchange of sodium for hydrogen. The kinetic properties of this transport system include a 1:1 stoichiometry, affinity for lithium and ammonium ion in addition to sodium and hydrogen, the ability to function in multiple 1:1 exchange modes involving these four cations, sensitivity to inhibition by amiloride and its analogues, and allosteric regulation by intracellular protons. The plasma membrane sodium-hydrogen exchanger plays a physiological role in the regulation of intracellular pH, the control of cell growth and proliferation, stimulus-response coupling in white cells and platelets, the metabolic response to hormones such as insulin and glucocorticoids, the regulation of cell volume, and the transepithelial absorption and secretion of sodium, hydrogen, bicarbonate and chloride ions, and organic anions. Preliminary evidence raises the possibility that the sodium-hydrogen exchanger may play a pathophysiological role in such diverse conditions as renal acid-base disorders, essential hypertension, cancer, and tissue or organ hypertrophy. Thus, future research on cellular acid-base homeostasis in general, and on plasma membrane sodium-hydrogen exchange in particular, will enhance our understanding of a great variety of physiological and pathophysiological processes.
Dynamics analyses provide insight into the influence of precore mutations on the mechanisms of viral CL
Authors: E.J. Heathcote, Q. Thai, M. Margulies, M. Tsiang, J. Fry, C.S. Gibbs, C.E. Westland, S. Xiong, H. Yang, H. Namini, C. Brosgart
Journal: Journal of Hepatology (2001)
Predicting Epilepsy After Blunt Head Injury
Authors: W. B. Jennett
Journal: BMJ (1965)

Epilepsy occurs in rather less than 10% of patients admitted to hospital after a blunt head injury. The problem posed by a rather uncommon complication of a very common condition is to know which few patients, of the many at risk, are likely to develop it. If they could be recognized soon after injury, prophylactic anticonvulsants could be prescribed, different advice might be given about resettlement, and their lawyers could be advised to take the risk of epilepsy into account in assessing damages. The possibility of making a reliable prediction of epilepsy was explored by studying a series of head injuries prospectively and by investigating a number of patients with established traumatic epilepsy. The methods have been described in detail elsewhere with full statistical analysis (Jennett, 1962). The study was limited to non-missile head injuries admitted to hospital. While investigation of the influence of various factors on the incidence of epilepsy was based on a large series of cases from Oxford, Cardiff, and Manchester, estimation of the absolute overall incidence of epilepsy was based solely on 1,000 consecu tive admissions to the Accident Service of the Radcliffe Infirmary, Oxford. All patients with even brief amnesia after head injury were admitted to the service, which was the only one in the district. This series was therefore a relatively un selected one and included a high proportion of mild injuries compared with admissions to an average hospital ; the figure of 10% for the incidence of epilepsy is probably rather low on this account.
Differential Effects of β-Blockers in Patients With Heart Failure
Authors: Marco Metra, Raffaele Giubbini, Savina Nodari, Emiliano Boldi, Maria Grazia Modena, Livio Dei Cas
Journal: Circulation (2000)

Background —Both metoprolol and carvedilol produce hemodynamic and clinical benefits in patients with chronic heart failure; carvedilol exerts greater antiadrenergic effects than metoprolol, but it is unknown whether this pharmacological difference results in hemodynamic and clinical differences between the 2 drugs. Methods and Results —We randomized 150 patients with heart failure (left ventricular ejection fraction ≤0.35) to double-blind treatment with either metoprolol or carvedilol. When compared with metoprolol (124±55 mg/d), patients treated with carvedilol (49±18 mg/d) showed larger increases in left ventricular ejection fraction at rest (+10.9±11.0 versus +7.2±7.7 U, P =0.038) and in left ventricular stroke volume and stroke work during exercise (both P &lt;0.05) after 13 to 15 months of treatment. In addition, carvedilol produced greater decreases in mean pulmonary artery pressure and pulmonary wedge pressure, both at rest and during exercise, than metoprolol (all P &lt;0.05). In contrast, the metoprolol group showed greater increases in maximal exercise capacity than the carvedilol group ( P =0.035), but the 2 drugs improved symptoms, submaximal exercise tolerance, and quality of life to a similar degree. After a mean of 23±11 months of follow-up, 21 patients in the metoprolol group and 17 patients in the carvedilol group died or underwent urgent transplantation. Conclusions —The present study demonstrates that during long-term therapy, carvedilol improves cardiac performance to a greater extent than metoprolol when administered to patients with heart failure in the doses shown to be effective in clinical trials. These differences were likely related to a greater antiadrenergic activity of carvedilol.
Chest pain in patients with rheumatoid arthritis.
Authors: J C Martin, J Harvey, J Dixey
Journal: Annals of the Rheumatic Diseases (1996)

The transport of riboflavin and the relationship of riboflavin transport to the transport of the cyclic organic acids, aminohippurate and penicillin, were investigated in small renal slices in vitro. Riboflavin was accumulated by rabbit renal slices by a transport system that was inhibited by sugar-containing and sugarless flavins, cyclic organic acids including aminohippurate and penicillin, dinitrophenol and cold temperatures, but not by D-ribose or the weak base tolazoline. The transport of riboflavin into renal slices was not solely due to intracellular binding or metabolism of the riboflavin. Aminohippurate, penicillin and riboflavin inhibited the active accumulation of [14C] aminohippurate and [14C]penicillin by kidney slices. These studies support the notions that: 1) riboflavin is accumulated in kidney cortex slices by an energy-dependent saturable transport system; 2) riboflavin accumulation by kidney slices is inhibited by cyclic organic acids and sulfhydryl reagents, but not weak bases; and 3) riboflavin is a competitive inhibitor of aminohippurate as well as an inhibitor of penicillin G accumulation by kidney slices.
TI-CE High-Dose Chemotherapy for Patients With Previously Treated Germ Cell Tumors: Results and Prognostic Factor Analysis
Authors: Darren R. Feldman, Joel Sheinfeld, Dean F. Bajorin, Patricia Fischer, Stefan Turkula, Nicole Ishill, Sujata Patil, Manjit Bains, Lilian M. Reich, George J. Bosl, Robert J. Motzer
Journal: Journal of Clinical Oncology (2010)

We previously reported a dose-finding and phase II trial of the TI-CE regimen (paclitaxel [T] plus ifosfamide [I] followed by high-dose carboplatin [C] plus etoposide [E] with stem-cell support) in germ cell tumor (GCT) patients predicted to have a poor prognosis with conventional-dose salvage therapy. We now report the efficacy of TI-CE with prognostic factors for disease-free survival (DFS) and overall survival (OS) in our full data set of 107 patients.Eligible patients had advanced GCTs with progressive disease following chemotherapy and unfavorable prognostic features (extragonadal primary site, incomplete response [IR] to first-line therapy, or relapse/IR to ifosfamide-cisplatin-based conventional-dose salvage). Univariate and multivariate analyses (MVAs) of prognostic factors were performed. The predictive ability of the Einhorn and Beyer prognostic models was assessed.Most patients were platinum refractory and had an IR to first-line chemotherapy. There were 54 (5%) complete and eight (8%) partial responses with negative markers; 5-year DFS was 47% and OS was 52% (median follow-up, 61 months). No relapses occurred after 2 years. Five (24%) of 21 primary mediastinal nonseminomatous GCTs are continuously disease free. On MVA, primary mediastinal site (P < .001), two or more lines of prior therapy (P < .001), baseline human chorionic gonadotropin > or = 1,000 U/L (P = .01), and lung metastases (P = .02) significantly predicted adverse DFS. Poor-risk patients did worse than good- or intermediate-risk patients according to both Beyer (P < .002) and Einhorn (P < .05) models.TI-CE is effective salvage therapy for GCT patients with poor prognostic features. Mediastinal primary site and two or more lines of prior therapy were most predictive of adverse DFS. Beyer and Einhorn models can assist in predicting outcome.
IRF4 controls the positioning of mature B cells in the lymphoid microenvironments by regulating NOTCH2 expression and activity
Authors: Giorgia Simonetti, Amanda Carette, Kathryn Silva, Haowei Wang, Nilushi S. De Silva, Nicole Heise, Christian W. Siebel, Mark J. Shlomchik, Ulf Klein
Journal: The Journal of Experimental Medicine (2013)

The transcription factor interferon regulatory factor-4 (IRF4) is expressed in B cells at most developmental stages. In antigen-activated B cells, IRF4 controls germinal center formation, class-switch recombination, and the generation of plasma cells. Here we describe a novel function for IRF4 in the homeostasis of mature B cells. Inducible deletion of irf4 specifically in B cells in vivo led to the aberrant accumulation of irf4-deleted follicular B cells in the marginal zone (MZ) area. IRF4-deficient B cells showed elevated protein expression and activation of NOTCH2, a transmembrane receptor and transcriptional regulator known to be required for MZ B cell development. Administration of a NOTCH2-inhibitory antibody abolished nuclear translocation of NOTCH2 in B cells within 12 h and caused a rapid and progressive disintegration of the MZ that was virtually complete 48 h after injection. The disappearance of the MZ was accompanied by a transient increase of MZ-like B cells in the blood rather than increased B cell apoptosis, demonstrating that continued NOTCH2 activation is critical for the retention of B cells in the MZ. Our results suggest that IRF4 controls the positioning of mature B cells in the lymphoid microenvironments by regulating NOTCH2 expression. These findings may have implications for the understanding of B cell malignancies with dysregulated IRF4 and NOTCH2 activity.
Phase I/II trial of irinotecan plus high-dose 5-fluorouracil (TTD regimen) as first-line chemotherapy in advanced colorectal cancer
Authors: E. Aranda, A. Carrato, A. Cervantes, J. Sastre, M.A. Gómez, A. Abad, B. Masutti, F. Ribera, E. Marcuello, L. Pronk, M. Balcells, E. Díaz-Rubio
Journal: Annals of Oncology (2004)
Favorable Effects of Pioglitazone and Metformin Compared With Gliclazide on Lipoprotein Subfractions in Overweight Patients With Early Type 2 Diabetes
Authors: James M. Lawrence, Julia Reid, Gordon J. Taylor, Chris Stirling, John P.D. Reckless
Journal: Diabetes Care (2004)

OBJECTIVE—To compare effects of different oral hypoglycemic drugs as first-line therapy on lipoprotein subfractions in type 2 diabetes. RESEARCH DESIGN AND METHODS—Sixty overweight type 2 diabetic patients not on lipid-lowering therapy were randomized to metformin, pioglitazone, or gliclazide after a 3-month dietary run-in. Drug doses were uptitrated for 3 months to optimize glycemia and were kept fixed for a further 3 months. LDL subfractions (LDL1, LDL2, and LDL3) were prepared by density gradient ultracentrifugation at randomization and study end. Triglycerides, cholesterol, total protein, and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. The primary end point was change in proportion of LDL as LDL3. RESULTS—HbA1c, triglycerides, glucose, and cholesterol were comparable across groups at baseline and over time. LDL3 mass and the LDL3-to-LDL ratio fell with pioglitazone (LDL3 mass 36.2 to 28.0 mg/dl, P &amp;lt; 0.01; LDL3-to-LDL 19.2:13.3%, P &amp;lt; 0.01) and metformin (42.7 to 31.5 mg/dl, P &amp;lt; 0.01; 21.3:16.2%, P &amp;lt; 0.01, respectively) with no change on gliclazide. LDL3 reductions were associated with reciprocal LDL1 increases. Changes were independent of BMI, glycemic control, and triglycerides. Total HDL cholesterol increased on pioglitazone (1.28 to 1.36 mmol/l, P = 0.02) but not gliclazide (1.39 to 1.37 mmol/l, P = NS) or metformin (1.26 to 1.18 mmol/l, P = NS), largely due to an HDL2 increase (0.3 to 0.4 mmol/l, P &amp;lt; 0.05). HDL3 cholesterol fell on metformin (0.9 to 0.85 mmol/l, P &amp;lt; 0.01). On pioglitazone and metformin, the HDL2-to-HDL3 ratio increased compared with no change on gliclazide. CONCLUSIONS—For the same improvement in glycemic control, pioglitazone and metformin produce favorable changes in HDL and LDL subfractions compared with gliclazide in overweight type 2 diabetic patients. Such changes may be associated with reduced atherosclerosis risk and may inform the choice of initial oral hypoglycemic agent.
Decreasing Cellular Hydrogen Peroxide With Catalase Mimics the Effects of Hypoxia on the Sensitivity of the L-Type Ca <sup>2+</sup> Channel to β-Adrenergic Receptor Stimulation in Cardiac Myocytes
Authors: Livia C. Hool, Peter G. Arthur
Journal: Circulation Research (2002)

In cardiac myocytes, hypoxia inhibits the basal L-type Ca 2+ current ( I Ca-L ) and increases the sensitivity of I Ca-L to β-adrenergic receptor stimulation. We investigated whether hydrogen peroxide (H 2 O 2 ) is involved in the hypoxic response. Guinea pig ventricular myocytes were dialyzed with catalase, which specifically catalyzes the conversion of H 2 O 2 to H 2 O and oxygen, and then I Ca-L was recorded during exposure to isoproterenol (Iso). Catalase decreased the K 0.5 for activation of I Ca-L by Iso from 2.7±0.3 nmol/L (in cells dialyzed with heat-inactivated catalase) to 0.4±0.1 nmol/L. The increase in sensitivity to Iso by catalase may be attenuated when cells are preexposed to H 2 O 2 . A significant increase in sensitivity of I Ca-L to Iso was recorded when mitochondrial function was inhibited with myxothiazol or FCCP, suggesting that the source of H 2 O 2 was from the mitochondria. Prior exposure of cells to H 2 O 2 attenuated the inhibition of basal I Ca-L during hypoxia and the increase in sensitivity of I Ca-L to Iso during hypoxia. Additionally, extracellularly applied catalase mimicked the effect of hypoxia on basal I Ca-L . Measurement of the rate of production of hydrogen peroxide using 5- (and 6-)chloromethyl-2′, 7′-dichlorodihydrofluorescein diacetate acetyl ester indicated that hypoxia was associated with a significant decrease in the production of hydrogen peroxide in the cells. These data suggest that hypoxia mediates changes in channel activity through a lowering in H 2 O 2 levels and that H 2 O 2 is a key intermediate in modifying basal channel activity and the β-adrenergic responsiveness of the channel during hypoxia.
The Role of Rho in G Protein-Coupled Receptor Signal Transduction
Authors: Valerie P. Sah, Tammy M. Seasholtz, Sarah A. Sagi, Joan Heller Brown
Journal: The Annual Review of Pharmacology and Toxicology (2000)

Low molecular weight G proteins of the Rho subfamily are regulators of actin cytoskeletal organization. In contrast to the heterotrimeric G proteins, the small GTPases are not directly activated through ligand binding to G protein-coupled receptors (GPCRs). However, a subset of GPCRs, including those for lysophosphatidic acid and thrombin, induce stress fibers, focal adhesions, and cell rounding through Rho-dependent pathways. C3 exoenzyme has been a useful tool for demonstrating Rho involvement in these and other responses, including Ca2+ sensitization of smooth muscle contraction, cell migration, transformation, and serum response element-mediated gene expression. Most of the GPCRs that induce Rho-dependent responses can activate Gq, but this is not a sufficient signal. Recent data demonstrate that G alpha 12/13 can induce Rho-dependent responses. Furthermore, G alpha 12/13 can bind and activate Rho-specific guanine nucleotide exchange factors, providing a mechanism by which GPCRs that couple to G alpha 12/13 could activate Rho and its downstream responses.
Transforming Growth Factor α–Dependent Cancer Progression Is Modulated by Muc1
Authors: Mamata R. Pochampalli, Benjamin G. Bitler, Joyce A. Schroeder
Journal: Cancer Research (2007)

Abstract Transforming growth factor α (TGFα) is a potent inducer of cellular transformation, through its binding and activation of the epidermal growth factor receptor (EGFR). Previous studies in our laboratory showed that EGFR could also be affected by the glycoprotein MUC1, which inhibits ligand-stimulated degradation of EGFR in breast epithelial cell lines. To determine the effect of Muc1 expression on TGFα/EGFR-dependent breast transformation, we crossed the WAP-TGFα transgenic mouse model of breast cancer onto a Muc1-null background. We found that the loss of Muc1 expression dramatically affects mammary gland transformation and progression. Although 100% of WAP-TGFα/Muc1+/+ mice form mammary gland tumors by 1 year, only 37% of WAP-TGFα/Muc1−/− form tumors by this time. This difference is also associated with a delay in onset, with a doubling of onset time observed in the WAP-TGFα/Muc1−/− compared with the WAP-TGFα/Muc1+/+ mice. Analysis of signal transduction pathways revealed that activation of cyclin D1 expression is significantly suppressed in tumors derived from WAP-TGFα/Muc1−/− animals compared with those expressing Muc1. The loss of Muc1 expression also results in a significant inhibition in the formation of hyperplastic lesions during tumor progression. On the C57Bl/6 inbred background, pulmonary lesions were observed in 28 of 29 WAP-TGFα/Muc1+/+ animals (including one metastatic pulmonary adenocarcinoma and multiple perivascular lymphomas), although none were detected in the WAP-TGFα/Muc1−/− animals. Together, these data indicate that Muc1 is an important modulator of TGFα-dependent tumor progression. [Cancer Res 2007;67(14):6591–8]
P276 The Impact of the Optimum Patient Care Service on Outcomes for Adult Asthmatic Patients: Abstract P276 Table 1
Authors: D Ryan, F Ryan, L Mascarenhas, D Saralaya, M Britton, J von Ziegenweidt, A Burden, C Hutton, S Gould, P David
Journal: Thorax (2012)

<h3>Introduction and Objectives</h3> The Optimum Patient Care (OPC) service provides a comprehensive asthma assessment, analysing both GP-recorded and patient-reported outcomes to generate patient-specific management recommendations (based on British guidelines) for considerations by practise staff. This study evaluates the effect of the OPC asthma service evaluation on real-life asthma control outcomes in a UK primary care adult asthma population compared with a control population. <h3>Methods</h3> Routine and patient-reported questionnaire data were collected for 2952 patients with clinician-diagnosed asthma and 1 year outcome data managed in practises across Surrey and Leicester County and Rutland Primary Care Trusts. The effect of the OPC service was evaluated by assessing change in markers of asthma control between initiation and re-assessment: exacerbation frequency (Read code defined acute exacerbations and number of courses of acute oral steroids in previous 12 months) and risk status (high risk: ≥2 annual exacerbations). The number of OPC management suggestions implemented by each practise was also considered. Change in exacerbations over the 12 month period was compared with a control group of patients from UK practises who did not receive OPC management recommendations. Exacerbation rate ratios (RR) for treatment group were produced (relative to control), adjusted for baseline confounders (95%CI). <h3>Results</h3> There were 2952 patients in the study from 22 practises. At time of re-assessment 10% of OPC management suggestions had been implemented and 22% of patients managed at British Thoracic Society (BTS) steps 4/5 had improved their risk status. 17.1% of patients in the control group (n=22,952) suffered from ≥1 exacerbation during the baseline year, increasing to 17.3% of patients after 12 months. For patients receiving the OPC management review, 24.8% had ≥1 exacerbation during baseline, decreasing to 15.3% following review. <h3>Conclusions</h3> OPC’s combined patient-reported and practise data assessment allowed thorough patient assessment and the generation of tailored management recommendations. Although only 10% of recommendations were implemented at 12 months, the OPC service appeared to have a beneficial effect on risk status and exacerbation rates.
Incidence of Invasive Breast Cancer by Hormone Receptor Status From 1992 to 1998
Authors: Christopher I. Li, Janet R. Daling, Kathleen E. Malone
Journal: Journal of Clinical Oncology (2002)

Between 1987 and 1998, breast cancer incidence rates rose 0.5%/yr in the United States. A question of potential etiologic and clinical importance is whether the hormone receptor status of breast tumors is also changing over time. This is because hormone receptor status may reflect different etiologic pathways and is useful in predicting response to adjuvant therapy and prognosis.
Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1
Authors: Makoto Arita, Francesca Bianchini, Julio Aliberti, Alan Sher, Nan Chiang, Song Hong, Rong Yang, Nicos A. Petasis, Charles N. Serhan
Journal: The Journal of Experimental Medicine (2005)

The essential fatty acid eicosapentaenoic acid (EPA) present in fish oils displays beneficial effects in a range of human disorders associated with inflammation including cardiovascular disease. Resolvin E1 (RvE1), a new bioactive oxygenated product of EPA, was identified in human plasma and prepared by total organic synthesis. Results of bioaction and physical matching studies indicate that the complete structure of RvE1 is 5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-EPA. At nanomolar levels, RvE1 dramatically reduced dermal inflammation, peritonitis, dendritic cell (DC) migration, and interleukin (IL) 12 production. We screened receptors and identified one, denoted earlier as ChemR23, that mediates RvE1 signal to attenuate nuclear factor–κB. Specific binding of RvE1 to this receptor was confirmed using synthetic [3H]-labeled RvE1. Treatment of DCs with small interference RNA specific for ChemR23 sharply reduced RvE1 regulation of IL-12. These results demonstrate novel counterregulatory responses in inflammation initiated via RvE1 receptor activation that provide the first evidence for EPA-derived potent endogenous agonists of antiinflammation.