tbuckley/cabot-search huggingface dataset:
Certain beta-blockers can decrease beta-adrenergic receptor number: II. Down-regulation of receptor number by alprenolol and propranolol in cultured lymphoma and muscle cells.
Authors: R J Hughes, L C Mahan, P A Insel
Journal: Circulation Research (1988)

We have used two different cultured cell lines--S49 lymphoma cells and BC3H-1 muscle cells--to examine the regulation of beta-adrenergic receptors by receptor antagonists. Rather than an increase ("up-regulation") of receptor number that such antagonists often produce, we found that certain beta-blockers elicit a decrease ("down-regulation") of beta-adrenergic receptors. Alprenolol and propranolol, but not sotalol or ICI 118,551, at concentrations of 10-100 nM down-regulated beta-adrenergic receptors 20-70% following 16-20 hours of treatment of S49 or BC3H-1 cells. Several observations suggest that this phenomenon depends upon beta-receptor interaction, including stereoselectivity [(-)-enantiomers more potent than (+)-enantiomers], blockade of the effect by ICI 118,551, absence of down-regulation of alpha-adrenergic receptors in BC3H-1 cells, and lack of a decrease in beta-adrenergic receptor-independent (forskolin-stimulated) cyclic AMP accumulation in S49 cells. The possibility of retained antagonist interfering with receptor measurement was precluded by the fact that the antagonist-induced decrease in receptor number required several hours incubation and occurred without a prominent change in receptor affinity. The ability of the beta-blockers to elicit down-regulation did not correlate with hydrophobicity of the drugs. Antagonist-induced down regulation of beta-adrenergic receptors did not occur in S49 lymphoma cells that lack the alpha-subunit of Gs, the guanine nucleotide-binding regulatory protein, thus implying a requirement for receptor-alpha s interaction in eliciting beta-receptor down-regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Maintenance of Ectopic Chorionic Gonadotropin and Alpha Subunit Secretion by a Human Lung Cancer Cell Line (ChaGo) Transplanted Into Nude Mice
Authors: Jeffrey M. Lieblich, Saul W. Rosen, Bruce D. Weintraub, William F. Sindelar, Tommie Sue Tralka, Alan S. Rabson
Journal: JNCI Journal of the National Cancer Institute (1977)

ChaGo cells, derived from a human primary carcinoma of the lung, were successfully transplanted into nude mice without any change in morphologic characteristics over four generations and with continued ectopic secretion of human chorionic gonadotropin (HCG) and HCG alpha subunit (HCG-alpha). The concentration of free HCG-alpha was 1,100-fold higher than that of complete HCG in the original ChaGo culture medium but only 35-fold higher in nude mouse plasma, possibly due to slower metabolic clearance of complete HCG. Tumor weights correlated with plasma HCG-alpha but not with HCG. Tumor-bearing mice had significantly heavier uteri than did control mice.
The Cancer Paradigm of Severe Pulmonary Arterial Hypertension
Authors: Pradeep R. Rai, Carlyne D. Cool, Judy A. C. King, Troy Stevens, Nana Burns, Robert A. Winn, Michael Kasper, Norbert F. Voelkel
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

The plexiform lesions of severe pulmonary arterial hypertension (PAH) are similar in histologic appearance, whether the disease is idiopathic or secondary. Both forms of the disease show actively proliferating endothelial cells without evidence of apoptosis. Here, we discuss the pathobiology of the atypical, angioproliferative endothelial cells in severe PAH. The concept of the endothelial cell as a "quasi-malignant" cell provides a new framework for antiproliferative, antiangiogenic therapy in severe PAH.
Quality of Life Scores Predict Survival Among Patients With Head and Neck Cancer
Authors: Carrie A. Karvonen-Gutierrez, David L. Ronis, Karen E. Fowler, Jeffrey E. Terrell, Stephen B. Gruber, Sonia A. Duffy
Journal: Journal of Clinical Oncology (2008)

Purpose The purpose of this study was to examine whether quality of life (QOL) scores predict survival among patients with head and neck cancer, controlling for demographic, health behavior, and clinical variables. Patients and Methods A self-administered questionnaire was given to 495 patients being treated for head and neck cancer while they were waiting to be seen for a clinic appointment. Data collected from the survey included demographics, health behaviors, and QOL as measured by Short Form-36 (SF-36) physical and mental component scores and the Head and Neck QOL scores. Clinical measures were collected by chart abstraction. Kaplan-Meier plots and univariate and multivariate Cox proportional hazards models were used to determine the association between QOL scores and survival time. Results After controlling for age, time since diagnosis, marital status, education, tumor site and stage, comorbidities, and smoking, the SF-36 physical component score and three of the four Head and Neck QOL scales (pain, eating, and speech domains) were associated with survival. Controlling for the same variables, the SF-36 mental component score and the emotional domain of the Head and Neck QOL were not associated with survival. Conclusion QOL instruments may be valuable screening tools to identify patients who are at high risk for poor survival. Those with low QOL scores could be followed more closely, with the potential to identify recurrence earlier and perform salvage treatments, thereby possibly improving survival for this group of patients.
A rat model of esophageal varices
Authors: Kazuo Tanoue, Seigo Kitano, Makoto Hashizume, Hiroya Wada, Keizo Sugimachi
Journal: Hepatology (1991)

We have developed a new method for inducing portal hypertension and esophageal varices in rats--partial ligation of the portal vein after devascularization of the circumference of the left renal vein and complete ligation of the portal vein on the fifth day thereafter. Thirty rats were separated into groups of 10, control (sham operation), complete portal ligation only and complete portal ligation plus devascularization. Two weeks after the surgery, the presence of esophageal varices in rats with complete portal ligation plus devascularization was confirmed by portography and by the histological findings. The diameter (mean +/- SD) of the submucosal veins of the lower esophagus in the complete portal ligation plus devascularization group (219.4 +/- 86.6 microns) was significantly larger than that in the complete portal ligation group (99.8 +/- 53.4 microns) or in the control group (30.5 +/- 16.6 microns) (p less than 0.01). Vascular structures of the lower esophagus closely resembled those in humans with esophageal varices. This new technique is simple, rapid and reliable, and application can be made to various experimental studies on portal hypertension.
Aberrant Intracellular Calcium Signaling in Olfactory Neurons From Patients With Bipolar Disorder
Authors: Chang-Gyu Hahn, George Gomez, Diego Restrepo, Eitan Friedman, Richard Josiassen, Edmund A. Pribitkin, Louis D. Lowry, Robert J. Gallop, Nancy E. Rawson
Journal: American Journal of Psychiatry (2005)

The authors examined the feasibility of using olfactory receptor neurons from living patients to test whether calcium signaling is altered in a neuronal cell population in bipolar disorder.Ratiometric fluorescence photomicroscopy was used to assess basal and stimulus-induced changes in intracellular calcium levels in biopsy-derived olfactory receptor neurons from seven euthymic patients with bipolar disorder who were medication-free, 10 euthymic patients with bipolar disorder who were treated with mood stabilizers, and 17 age- and sex-matched comparison subjects without bipolar disorder.Olfactory receptor neurons from the seven medication-free patients responded to stimuli predominantly with decreases in intracellular calcium, unlike those from the seven matched healthy subjects. Olfactory receptor neurons from patients treated with mood stabilizers were less likely to respond to stimulation than olfactory receptor neurons from medication-free patients.This study demonstrates the feasibility of using olfactory receptor neurons to examine alterations in intracellular signaling in neuronal cells from living patients. Our results, although based on a small number of subjects, suggest that altered intracellular calcium signaling in olfactory receptor neurons may be a trait of bipolar disorder.
Vital capacities in acute and chronic airway obstruction: dependence on flow and volume histories
Authors: V Brusasco, R Pellegrino, None Rodarte
Journal: European Respiratory Journal (1997)

The aim of this study was to investigate whether measurements of vital capacity (VC) are affected by the direction of the manoeuvre (inspiratory vs expiratory) and by the rate of expiratory flow. The study was performed on 25 individuals with chronic airway obstruction (CAO) and a forced expiratory volume in one second (FEV1) (expressed in standardized residuals (SR)) of -2.0+/-1.4 SD (CAO group), and 10 asthmatic subjects with methacholine (MCh)-induced bronchoconstriction (FEV1 -23+/-1.02 SR) (MCh group). VCs were measured during fast inspiration following both slow (FIVCse) and forced (FIVCfe) expiration from end-tidal inspiration to residual volume (RV), and during slow (EVC) or forced (FVC) expiration from total lung capacity (TLC). In the CAO group, FVC was the smallest volume (3.75+/-1.03 L) and significantly different from the other three estimates of VC; FIVCse (4.03+/-0.91 L) was the largest volume and significantly different from FVC and FIVCfe (3.83+/-0.98 L). In the MCh group, FVC (4.16+/-0.94 L) and EVC (4.19+/-0.89 L) were the largest volumes, although only the difference between FVC and FIVCfe (3.76+/-0.81 L) reached statistical significance. These data suggest that both flow and volume histories contribute to decreased vital capacities during bronchoconstriction. However, whereas increasing expiratory flow always tends to decrease vital capacity, the volume history of full inflation has different effects in chronic and acute bronchoconstriction, probably due to different effects on airway calibre. These results stress the importance of using standardized manoeuvres in order to obtain comparable values of vital capacity.
Hemin and L-arginine regulation of blood pressure in spontaneous hypertensive rats.
Authors: P Martasek, M L Schwartzman, A I Goodman, K B Solangi, R D Levere, N G Abraham
Journal: Journal of the American Society of Nephrology (1991)

Perturbation in heme metabolism is known to affect the level and activity of hemoproteins, including cytochrome P450-dependent arachidonic acid metabolism. The latter has been associated with elevation in blood pressure seen in spontaneously hypertensive rats. The effect of heme arginate and its components, arginine and heme, on cytochrome P450 levels and blood pressure in spontaneously hypertensive rats were studied. Administration of heme arginate or heme alone at doses of 9 to 30 mg/kg body wt/day for 4 days resulted in a marked decrease of blood pressure in spontaneously hypertensive rats, whereas blood pressure in rats receiving the vehicle control was not affected. Similarly, L-arginine, but not D-arginine, in a dose-dependent manner decreased blood pressure in spontaneously hypertensive rats. The maximal change in blood pressure was achieved at 100 mg/kg body wt of arginine and was associated with a significant increase in heme oxygenase activity. A higher concentration (500 mg/kg) did not cause an additional decrease in blood pressure but further increased heme oxygenase activity. The arginine-induced heme oxygenase activity was suppressed by Sn-protoporphyrin. Administration of heme to spontaneously hypertensive rats resulted in an accumulation of heme oxygenase mRNA, which was accompanied by an increase in enzyme activity. The increase in heme oxygenase activity was also prevented by Sn-protoporphyrin. It is postulated that heme treatment resulted in an increase in heme oxygenase mRNA, which consequently led to a diminution of cellular heme and depletion of hemoproteins, such as the cytochrome P450 arachidonate metabolizing enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
Retinoic Acid and Retinoic Acid Receptors as Pleiotropic Modulators of the Immune System
Authors: Alexandre Larange, Hilde Cheroutre
Journal: Annual Review of Immunology (2016)

Vitamin A is a multifunctional vitamin implicated in a wide range of biological processes. Its control over the immune system and functions are perhaps the most pleiotropic not only for development but also for the functional fate of almost every cell involved in protective or regulatory adaptive or innate immunity. This is especially key at the intestinal border, where dietary vitamin A is first absorbed. Most effects of vitamin A are exerted by its metabolite, retinoic acid (RA), which through ligation of nuclear receptors controls transcriptional expression of RA target genes. In addition to this canonical function, RA and RA receptors (RARs), either as ligand-receptor or separately, play extranuclear, nongenomic roles that greatly expand the multiple mechanisms employed for their numerous and paradoxical functions that ultimately link environmental sensing with immune cell fate. This review discusses RA and RARs and their complex roles in innate and adaptive immunity.
Cell type–specific genetic and optogenetic tools reveal hippocampal CA2 circuits
Authors: Keigo Kohara, Michele Pignatelli, Alexander J Rivest, Hae-Yoon Jung, Takashi Kitamura, Junghyup Suh, Dominic Frank, Koichiro Kajikawa, Nathan Mise, Yuichi Obata, Ian R Wickersham, Susumu Tonegawa
Journal: Nature Neuroscience (2013)
Early Life Factors Contribute to the Decrease in Lung Function between Ages 18 and 40
Authors: George G. Apostol, David R. Jacobs, Albert W. Tsai, Richard S. Crow, O. Dale Williams, Mary C. Townsend, William S. Beckett
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Early life factors may influence pulmonary function. We measured forced expiratory volume in 1 second (FEV(1)) in 1985-1986 and 2, 5, and 10 years later in approximately 4,000 black and white men and women initially aged 18-30 years. We estimated the age pattern of FEV(1) according to family smoking status, early diagnosis of asthma, early smoking initiation, adult asthma, and cigarette smoking. FEV(1) followed a quadratic pattern from age of peak through age 40. The pattern varied by race and sex. Early smoking initiation was associated with a faster decrease in FEV(1). Smoking by family members was related to early life asthma and may have contributed to faster FEV(1) decrease by encouraging behaviors such as heavier smoking or earlier smoking initiation. Prevalence of smoking was 28% when no family member smoked, compared with 59% when four or more members smoked. The FEV(1) decline was 8.5% in never-smokers without asthma; 10.1% in nonsmoking individuals diagnosed with asthma; and 11.1% in baseline smokers who smoked 15 or more cigarettes per day. The combination of asthma and heavier smoking was synergistic (17.8% decline). This study delineates an increased rate of decline in those with asthma or in those who smoke cigarettes and implicates early life exposures as contributing to the faster rate of FEV(1) decline.
Psoriasis patients show signs of insulin resistance
Authors: S. Boehncke, D. Thaci, H. Beschmann, R.J. Ludwig, H. Ackermann, K. Badenhoop, W-H. Boehncke
Journal: British Journal of Dermatology (2007)

Recent observations suggest that psoriasis is a risk factor for the development of coronary artery calcification which in turn represents an indicator for atherosclerosis.To clarify a possible pathogenetic link between psoriasis and atherosclerosis, we studied the metabolic state of patients with psoriasis.Thirty-nine consecutive patients with moderate-to-severe plaque-type psoriasis were enrolled in the study. Detailed information was obtained on the patients' clinical picture and history of psoriasis, smoking habits and medication. The body mass index (BMI) of the patients was calculated. Laboratory investigations focused on values for inflammation, lipid profile and multiple cytokines. The intima-media thickness of the carotid artery was measured by ultrasound, and an oral glucose tolerance test was performed to calculate the homeostasis model assessment of insulin resistance (HOMA).Numerous well-recognized correlations such as between BMI and HOMA (P < 0.02) as well as BMI and vessel wall thickness (P < 0.05) were successfully reproduced, thus confirming consistency of our dataset. With regard to psoriasis, we observed a significant correlation between the Psoriasis Area and Severity Index (PASI) score and insulin secretion. Moreover, the PASI score was significantly correlated with serum resistin levels--a cytokine known to be increased in insulin resistance.Taken together, several measurements indicative of insulin resistance were found to be significantly correlated with the PASI score. The concept of insulin resistance as a consequence of chronic inflammation and possible pathogenetic cause for comorbidities known to be associated with psoriasis is supported by these data. Our findings validate further studies on larger cohorts as well as interventional studies.
Using Gene Expression Profiling to Differentiate Benign <b> <i>versus</i> </b> Malignant Thyroid Tumors
Authors: Chiara Mazzanti, Martha A. Zeiger, Nick Costourous, Christopher Umbricht, William H Westra, Danelle Smith, Helina Somervell, Generoso Bevilacqua, H. Richard Alexander, Steven K. Libutti
Journal: Cancer Research (2004)

Abstract DNA microarrays allow quick and complete evaluation of a cell’s transcriptional activity. Expression genomics is very powerful in that it can generate expression data for a large number of genes simultaneously across multiple samples. In cancer research, an intriguing application of expression arrays includes assessing the molecular components of the neoplastic process and utilizing the data for cancer classification (Miller LD, et al. Cancer Cell 2002;2:353–61). Classification of human cancers into distinct groups based on their molecular profile rather than their histological appearance may prove to be more relevant to specific cancer diagnoses and cancer treatment regimes. Several attempts to formulate a consensus about classification and treatment of thyroid carcinoma based on standard histopathological analysis have resulted in published guidelines for diagnosis and initial disease management (Sherman SI. Lancet 2003;361:501–11). In the past few decades, no improvement has been made in the differential diagnosis of thyroid tumors by fine needle aspiration biopsy, specifically suspicious or indeterminate thyroid lesions, suggesting that a new approach to this should be explored. Therefore, in this study, we developed a gene expression approach to diagnose benign versus malignant thyroid lesions in 73 patients with thyroid tumors. We successfully built a 10 and 6 gene model able to differentiate benign versus malignant thyroid tumors. Our results support the premise that a molecular classification system for thyroid tumors is possible, and this in turn may provide a more accurate diagnostic tool for the clinician managing patients with suspicious thyroid lesions.
Good and bad consequences of altered fatty acid metabolism in heart failure: evidence from mouse models
Authors: Desiree Abdurrachim, Joost J F P Luiken, Klaas Nicolay, Jan F C Glatz, Jeanine J Prompers, Miranda Nabben
Journal: Cardiovascular Research (2015)

The shift in substrate preference away from fatty acid oxidation (FAO) towards increased glucose utilization in heart failure has long been interpreted as an oxygen-sparing mechanism. Inhibition of FAO has therefore evolved as an accepted approach to treat heart failure. However, recent data indicate that increased reliance on glucose might be detrimental rather than beneficial for the failing heart. This review discusses new insights into metabolic adaptations in heart failure. A particular focus lies on data obtained from mouse models with modulations of cardiac FA metabolism at different levels of the FA metabolic pathway and how these differently affect cardiac function. Based on studies in which these mouse models were exposed to ischaemic and non-ischaemic heart failure, we discuss whether and when modulations in FA metabolism are protective against heart failure.
Postischemic Changes in Cardiac Sarcoplasmic Reticulum Ca <sup>2+</sup> Channels
Authors: Riccardo Zucchi, Simonetta Ronca-Testoni, Gongyuan Yu, Paola Galbani, Giovanni Ronca, Mario Mariani
Journal: Circulation Research (1995)

We investigated the modifications of cardiac ryanodine receptors/sarcoplasmic reticulum Ca2+ release channels occurring in ischemic preconditioning. In an isolated rat heart model, the injury produced by 30 minutes of global ischemia was reduced by preexposure to three 3-minute periods of global ischemia (preconditioning ischemia). The protection was still present 120 minutes after preconditioning ischemia but disappeared after 240 minutes. Three 1-minute periods of global ischemia did not provide any protection. In the crude homogenate obtained from ventricular myocardium, the density of [3H]ryanodine binding sites averaged 372 +/- 18 fmol/mg of protein in the control condition, decreased 5 minutes after preconditioning ischemia (290 +/- 15 fmol/mg, P < .01), was still significantly reduced after 120 minutes (298 +/- 17 fmol/mg, P < .05), and recovered after 240 minutes (341 +/- 21 fmol/mg). Three 1-minute periods of ischemia did not produce any change in ryanodine binding. The Kd for ryanodine (1.5 +/- 0.3 nmol/L) was unchanged in all cases. In parallel experiments, the crude homogenate or a microsomal fraction was passively loaded with 45Ca, and Ca(2+)-induced Ca2+ release was studied by the quick filtration technique. In both preparations, the rate constant of Ca(2+)-induced Ca2+ release decreased 5 and 120 minutes after preconditioning ischemia (homogenate values: 19.7 +/- 1.4 and 18.9 +/- 0.9 s-1 vs a control value of 25.4 +/- 1.7 s-1, P < .05 in both cases) and recovered after 240 minutes (23.0 +/- 1.9 s-1). The Ca2+ dependence of Ca(2+)-induced Ca2+ release was not affected by preconditioning ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Innate versus Adaptive Immunity: A Paradigm Past Its Prime?
Authors: Lisa Borghesi, Christine Milcarek
Journal: Cancer Research (2007)

Abstract Studies in tumor immunology have relied upon the classic paradigm of distinct innate and adaptive parts of the immune system. However, recent advances in immunology suggest that this division may be overly simplistic, with emerging evidence of a breakdown in conventional hallmarks of each system. Here, we provide an overview of this area and discuss how the concept of a continuum of immune cell populations suggests novel areas of investigation in cancer research. [Cancer Res 2007;67(9):3989–93]
Tracheostomy in a Thoracic Surgical Unit
Authors: D. B. Clarke
Journal: Thorax (1965)

Mast cells mediate inflammatory responses that promote hypersensitivity reactions and allergic disease. Mast cell activation can be induced by danger-associated molecular patterns such as IL-33 and ATP released by cell necrosis. IL-33 and ATP are elevated in the asthmatic lung, but how these factors act together is poorly understood. Using mouse bone marrow-derived mast cells, we show that IL-33 greatly sensitizes mast cells to ATP. Short term (30 minute) stimulation with IL-33 followed by its removal by washing, increased subsequent ATP-induced cytokine secretion up to 15-fold. This was consistent for ATP-induced IL-6, TNF, and IL-13. IL-33 did not significantly alter mast cell sensitivity to ATP as judged by IC<sub>50</sub> calculations, and had no effect on ATP-induced degranulation. We therefore propose IL-33 enhances ATP-induced transcription factor activation without altering calcium-mediated degranulation. We hypothesize that an IL-33-ATP cascade occurs during allergic inflammation and functions as an amplification loop promoting chronic disease.