tbuckley/cabot-search huggingface dataset:
Kava-induced dermopathy: a niacin deficiency?
Authors: P. Ruze
Journal: The Lancet (1990)

Heavy chronic consumption of kava (Piper methysticum) is associated with a pellagroid dermopathy that has been attributed to niacin deficiency. Over 200 male kava drinkers in the Tonga Islands were interviewed and examined regarding the characteristic skin changes. A scaly rash suggestive of ichthyosis and eye irritation were present in some heavy kava drinkers. 29 kava drinkers with prominent skin changes were randomised to receive either 100 mg oral nicotinamide or placebo daily for three weeks. Skin examinations and photographs showed clinical improvement in 5/15 of the nicotinamide group and 5/14 of the placebo group. These data, along with history and physical examination findings, suggest that niacin deficiency is not responsible for the rash, which is more characteristic of an acquired ichthyosis.
In Vitro Phospholipid Synthesis in Normal and Atheromatous Rabbit Aortas
Authors: H. A. I. NEWMAN, ALLEN J. DAY, D. B. ZILVERSMIT
Journal: Circulation Research (1966)

The incorporation of P 32 -phosphate and C 14 -choline into normal and atherosclerotic rabbit aortas was studied extensively in vitro . The same results as observed in vivo were found, namely an enhanced synthesis of phospholipids by the atheromatous aorta, localized primarily in the intima. Aortic intimal phospholipids incorporated more choline than phosphate. Tests with cyanide and fluoride showed that the higher incorporation of choline could not be attributed to exchange with preformed aortic phospholipid but presumably was due to differences in intermediate metabolic pools. The difference in distribution of P 32 between the two most active phospholipid classes, phosphatidyl choline and phosphatidyl inositol, of normal and atherosclerotic aortas was similar in vivo and in vitro . In the normal aorta, phosphatidyl inositol had a higher percentage of P 32 than phosphatidyl choline; in the atheromatous aorta, these percentages were reversed. The studies in vitro were used as evidence to show that the enhanced synthesis observed in vivo was probably not mediated by neural factors or stretch of the aorta, and that synthesis in situ could account for the higher amounts of phospholipid present in the atheromatous aorta.
The Na <sup>+</sup> -Ca <sup>2+</sup> Exchanger Is Essential for the Action of Cardiac Glycosides
Authors: Hannes Reuter, Scott A. Henderson, Tieyan Han, Robert S. Ross, Joshua I. Goldhaber, Kenneth D. Philipson
Journal: Circulation Research (2002)

The widely accepted model to explain the positive inotropic effect of cardiac glycosides invokes altered Na + -Ca 2+ exchange activity secondary to Na + pump inhibition. However, proof of this model is lacking and alternative mechanisms have been proposed. We directly tested the role of the Na + -Ca 2+ exchanger in the action of the glycoside ouabain using Na + -Ca 2+ exchanger knockout mice. Ablation of the exchanger is embryonic lethal, but contractility can be studied in embryonic heart tubes at day 9.5 postcoitum. Heart tubes isolated from homozygous Na + -Ca 2+ exchanger knockout mice (NCX −/− ) display surprisingly normal Ca 2+ transients. Removal of extracellular Na + induces Ca 2+ overload in wild-type heart tubes but does not alter the Ca 2+ transients of NCX −/− heart tubes. Similarly, ouabain, at levels causing Ca 2+ overload in wild-type heart tubes, has no effect on NCX −/− heart tubes. We conclude that in embryonic mouse myocytes the Na + -Ca 2+ exchanger is absolutely required for the effect of cardiac glycosides on Ca 2+ i .
Familial transmission rather than defective innate immunity shapes the distinct intestinal microbiota of TLR-deficient mice
Authors: Carles Ubeda, Lauren Lipuma, Asia Gobourne, Agnes Viale, Ingrid Leiner, Michele Equinda, Raya Khanin, Eric G. Pamer
Journal: The Journal of Experimental Medicine (2012)

The intestinal microbiota contributes to the development of the immune system, and conversely, the immune system influences the composition of the microbiota. Toll-like receptors (TLRs) in the gut recognize bacterial ligands. Although TLR signaling represents a major arm of the innate immune system, the extent to which TLRs influence the composition of the intestinal microbiota remains unclear. We performed deep 16S ribosomal RNA sequencing to characterize the complex bacterial populations inhabiting the ileum and cecum of TLR- and MyD88-deficient mice. The microbiota of MyD88- and TLR-deficient mouse colonies differed markedly, with each colony harboring distinct and distinguishable bacterial populations in the small and large intestine. Comparison of MyD88-, TLR2-, TLR4-, TLR5-, and TLR9-deficient mice and their respective wild-type (WT) littermates demonstrated that the impact of TLR deficiency on the composition of the intestinal microbiota is minimal under homeostatic conditions and after recovery from antibiotic treatment. Thus, differences between TLR-deficient mouse colonies reflected long-term divergence of the microbiota after extended husbandry in isolation from each other. Long-term breeding of isolated mouse colonies results in changes of the intestinal microbiota that are communicated to offspring by maternal transmission, which account for marked compositional differences between WT and mutant mouse strains.
Increased effects of C-type natriuretic peptide on cardiac ventricular contractility and relaxation in guanylyl cyclase A-deficient mice
Authors: M Pierkes
Journal: Cardiovascular Research (2002)

Objective: The natriuretic peptides (NPs), atrial (ANP), B-type (BNP), and C-type (CNP) natriuretic peptides as well as their respective receptor-guanylyl cyclases (GC-A for ANP and BNP, and GC-B for CNP) are expressed in the heart. However, the local role of NPs in the regulation of cardiac contractility and the mutual interactions of NPs remain controversial. In the present study we evaluated the effects of ANP and CNP on cardiac function of wild-type (GC-A +/+) and GC-A-deficient (GC-A −/−) mice. Methods: The effects of NPs and their molecular mechanisms were assessed in the isolated perfused mouse working heart preparation. Results: In GC-A +/+ hearts, CNP exerted a biphasic action: an immediate increase in inotropy and lusitropy, followed by a slowly developing negative inotropic effect. These effects were mimicked by the cGMP-analogue, 8-pCPT-cGMP. In contrast, ANP did not affect cardiac function. In GC-A −/− hearts, the immediate contractile responses to CNP and 8-pCPT-cGMP were significantly enhanced. CNP increased cardiac cGMP levels and stimulated phospholamban (PLB) phosphorylation; the effect on PLB, but not cGMP, was enhanced in GC-A −/− hearts. In addition, cardiac expression of cGMP-dependent protein kinase (cGK I) was significantly increased in GC-A −/− mice. Conclusion: CNP exerts a biphasic, initially positive inotropic and lusitropic, then negative inotropic effect in isolated working mouse hearts. A putative mechanism contributing to the immediate contractile responses is cGMP/cGK I-dependent phosphorylation of PLB and subsequent activation of the sarcoplasmic reticulum Ca2+-pump. ANP has no direct effects on cardiac contractility but chronic absence of its receptor, GC-A, results in increased responsiveness to CNP.
Infective respiratory exacerbations in young adults with cystic fibrosis: role of viruses and atypical microorganisms.
Authors: E L Ong, M E Ellis, A K Webb, K R Neal, M Dodd, E O Caul, S Burgess
Journal: Thorax (1989)

Thirty six adults with cystic fibrosis were studied over one year to determine the incidence of infection with respiratory viruses and atypical organisms. Nineteen patients entered the study during an acute exacerbation of respiratory symptoms with an increase in purulent sputum production, cough, or breathlessness accompanied by a fall in FEV1 (group 1); 17 patients entered when they were stable both clinically and in terms of lung function values (group 2). Group 1 patients had a mean of 2.6 (range 1-4) infective exacerbations during the year and group 2 patients a mean of 1.1 (0-2) exacerbations. Eleven patients developed serological evidence of viral (influenza virus A and B, cytomegalovirus, human rhinovirus 2, adenovirus) or Mycoplasma pneumoniae infection. There was no difference in seroconversion rates between group 1 (five patients) and group 2 (six patients). There was a weak association between viral seroconversion and the isolation of Pseudomonas aeruginosa from sputum, though this was not significant.
STUDIES ON THE TOTAL BILE
Authors: Philip D. McMaster, G. O. Broun, Peyton Rous
Journal: The Journal of Experimental Medicine (1923)

In bile that is secreted against an abnormally high pressure, as during partial obstruction, the pigment, cholate, and cholesterol outputs are all cut down, and so much more than is the fluid bulk that the concentration of the substances per cubic centimeter of bile is notably lessened. The fluid obtained at the greatest pressure compatible with secretion contains traces only of the typical biliary constituents. The bearing of these alterations in the bile on the consequences of partial biliary obstruction is discussed. An analysis of the liver changes following biliary obstruction brings out their essential likeness to the changes that occur under similar circumstances in glands in general and the kidney in particular. The major physiological factors concerned in the development of hydronephrosis and in the liver changes after biliary obstruction are identical. We would suggest that the term hydrohepatosis as applied to the liver condition would be useful not merely to designate it but to indicate the principles underlying its development. In clinical instances of biliary obstruction, the likeness to hydronephrosis is often hidden because of the activity of the gall bladder to render the stasis bile dark and thick. There is then a concealed hydrohepatosis, differing merely by the character of the duct content, from the manifest hydrohepatosis with "white bile," that is found when the gall bladder fails to act.
Exploration of the omics evidence landscape: adding qualitative labels to predicted protein-protein interactions
Authors: Vera van Noort, Berend Snel, Martijn A Huynen
Journal: Genome biology (2007)

In the post-genomic era various functional genomics, proteomics and computational techniques have been developed to elucidate the protein interaction network. While some of these techniques are specific for a certain type of interaction, most predict a mixture of interactions. Qualitative labels are essential for the molecular biologist to experimentally verify predicted interactions. Of the individual protein-protein interaction prediction methods, some can predict physical interactions without producing other types of interactions. None of the methods can specifically predict metabolic interactions. We have constructed an 'omics evidence landscape' that combines all sources of evidence for protein interactions from various types of omics data for Saccharomyces cerevisiae. We explore this evidence landscape to identify areas with either only metabolic or only physical interactions, allowing us to specifically predict the nature of new interactions in these areas. We combine the datasets in ways that examine the whole evidence landscape and not only the highest scoring protein pairs in both datasets and find specific predictions. The combination of evidence types in the form of the evidence landscape allows for qualitative labels to be inferred and placed on the predicted protein interaction network of S. cerevisiae. These qualitative labels will help in the biological interpretation of gene networks and will direct experimental verification of the predicted interactions.
Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans
Authors: Marielle Alders, Benjamin M Hogan, Evisa Gjini, Faranak Salehi, Lihadh Al-Gazali, Eric A Hennekam, Eva E Holmberg, Marcel M A M Mannens, Margot F Mulder, G Johan A Offerhaus, Trine E Prescott, Eelco J Schroor, Joke B G M Verheij, Merlijn Witte, Petra J Zwijnenburg, Mikka Vikkula, Stefan Schulte-Merker, Raoul C Hennekam
Journal: Nature Genetics (2009)
Effect of Arterial Hypoxia on Myocardial Oxygen Consumption
Authors: ERIC R. POWERS, WILLIAM John POWELL
Journal: Circulation Research (1973)

To evaluate the effect of arterial hypoxia on myocardial oxygen consumption (MVO 2 ) under controlled conditions of stable or decreased contractility and tension, 18 anesthetized, adrenergically blocked dogs on right heart bypass were studied. Heart rate, cardiac output, pH, and Pco 2 were constant. In 9 dogs, progressive decreases in arterial oxygen content were associated with progressive significant increases in MVO 2 to a peak of 1.5 ± 0.5 ml/min 100 g -1 left ventricle ( P &lt;0.005) above the control level at an arterial oxygen content of 7-9 ml/100 ml blood (Po 2 =30 mm Hg). This value represents a 19% increase from a control MVO 2 of 7.9 ml/min 100 g -1 left ventricle (arterial oxygen content 15-18 ml/100 ml blood, Po 2 &gt; 200 mm Hg). Progressive decreases occurred in mean aortic pressure ( P &lt; 0.001) and tension-time index ( P &lt; 0.001) with no significant change in mean ejection rate, left ventricular dP/dt, or left ventricular end-diastolic pressure. Quantitatively similar increases in MVO 2 with controlled hemodynamics were found when coronary flow was held constant (5 dogs), after catecholamine depletion with reserpine (2 dogs), and in the beating, empty ventricle (2 dogs). Thus, arterial hypoxia results in (1) an increase in MVO 2 despite no change or a decrease in the magnitude of the hemodynamic parameters correlated with MV 2 and (2) a decrease in myocardial efficiency.
Systematic Review: Transient Left Ventricular Apical Ballooning: A Syndrome That Mimics ST-Segment Elevation Myocardial Infarction
Authors: Kevin A. Bybee, Tomas Kara, Abhiram Prasad, Amir Lerman, Greg W. Barsness, R. Scott Wright, Charanjit S. Rihal
Journal: Annals of Internal Medicine (2004)

The transient left ventricular apical ballooning syndrome, also known as takotsubo cardiomyopathy, is characterized by transient wall-motion abnormalities involving the left ventricular apex and mid-ventricle in the absence of obstructive epicardial coronary disease. In this paper, we review case series that report on patients with the transient left ventricular apical ballooning syndrome to better characterize patients presenting with the syndrome. We identified 7 case series that reported on at least 5 consecutive patients with the transient left ventricular apical ballooning syndrome. The syndrome more often affects postmenopausal women (82% to 100%) (mean age, 62 to 75 years). Patients commonly present with ST-segment elevation in the precordial leads, chest pain, relatively minor elevation of cardiac enzyme and biomarker levels, and transient apical systolic left ventricular dysfunction despite the absence of obstructive epicardial coronary disease. An episode of emotional or physiologic stress frequently precedes presentation with the syndrome. The in-hospital mortality rate seems to be low, as does the risk for recurrence.
Ligand-dependent Inhibition of CD1d-restricted NKT Cell Development in Mice Transgenic for the Activating Receptor Ly49D
Authors: Roger B. Voyle, Friedrich Beermann, Rosemary K. Lees, Jens Schümann, Jacques Zimmer, Werner Held, H. Robson MacDonald
Journal: The Journal of Experimental Medicine (2003)

In addition to their CD1d-restricted T cell receptor (TCR), natural killer T (NKT) cells express various receptors normally associated with NK cells thought to act, in part, as modulators of TCR signaling. Immunoreceptor-tyrosine activation (ITAM) and inhibition (ITIM) motifs associated with NK receptors may augment or attenuate perceived TCR signals respectively, potentially influencing NKT cell development and function. ITIM-containing Ly49 family receptors expressed by NKT cells are proposed to play a role in their development and function. We have produced mice transgenic for the ITAM-associated Ly49D and ITIM-containing Ly49A receptors and their common ligand H2-Dd to determine the importance of these signaling interplays in NKT cell development. Ly49D/H2-Dd transgenic mice had selectively and severely reduced numbers of thymic and peripheral NKT cells, whereas both ligand and Ly49D transgenics had normal numbers of NKT cells. CD1d tetramer staining revealed a blockade of NKT cell development at an early precursor stage. Coexpression of a Ly49A transgene partially rescued NKT cell development in Ly49D/H2-Dd transgenics, presumably due to attenuation of ITAM signaling. Thus, Ly49D-induced ITAM signaling is incompatible with the early development of cells expressing semi-invariant CD1d-restricted TCRs and appropriately harmonized ITIM–ITAM signaling is likely to play an important role in the developmental program of NKT cells.
Effect of heparin on platelet count and platelet aggregation
Authors: A. Majid Shojania, Gail Turnbull
Journal: American Journal of Hematology (1987)

The in vitro effect of heparin on platelet aggregation was studied in three groups: in 26 subjects recently treated with heparin, in 18 subjects on maintenance hemodialysis, and in 20 normal controls. With the aid of Technicon H6000, platelet counts and platelet aggregations were compared in whole blood samples collected in ethylenediaminetetraacetic acid (EDTA) and in heparinized tubes. Although there was no significant difference between platelet count of heparinized and EDTA blood in the control group, the dialysis group and the group recently treated with heparin showed significantly lower platelet counts and more platelet aggregation in heparinized tubes than in EDTA tubes. We speculate that the majority of subjects exposed to heparin develop an antibody or a proaggregator which can aggregate or agglutinate platelets in the presence of heparin and causes destruction of platelets; but only in a small percentage of subjects receiving heparin is this reaction severe enough to cause thrombocytopenia.
967 PRECLINICAL CHARACTERIZATION OF SCH 900518, A NOVEL MECHANISM-BASED INHIBITOR OF HCV NS3 PROTEASE
Authors: X. Tong, A. Arasappan, F. Bennett, R. Chase, B. Feld, Z. Guo, A. Hart, V. Madison, B. Malcolm, J. Pichardo, A. Prongay, R. Ralston, A. Skelton, E. Xia, F.G. Njoroge
Journal: Journal of Hepatology (2009)
Effect of Self-Hypnosis on Hay Fever Symptoms – A Randomised Controlled Intervention Study
Authors: Wolf Langewitz, Jan Izakovic, Jane Wyler, Christian Schindler, Alexander Kiss, Andreas J. Bircher
Journal: Psychotherapy and Psychosomatics (2005)

&lt;i&gt;Background:&lt;/i&gt; Many people suffer from hay fever symptoms. Hypnosis has proved to be a useful adjunct in the treatment of conditions where allergic phenomena have an important role. &lt;i&gt;Methods:&lt;/i&gt; Randomised parallel group study over an observation period of two consecutive pollen seasons. Outcome data include nasal flow under hypnosis, pollinosis symptoms from diaries and retrospective assessments, restrictions in well-being and use of anti-allergic medication. We investigated 79 patients with a mean age of 34 years (range 19–54 years; 41 males), with moderate to severe allergic rhinitis to grass or birch pollen of at least 2 years duration and mild allergic asthma. The intervention consisted of teaching self-hypnosis during a mean of 2.4 sessions (SD 1.7; range 2–5 sessions) and continuation of standard anti-allergic pharmacological treatment. &lt;i&gt;Results:&lt;/i&gt; Of 79 randomised patients, 66 completed one, and 52 completed two seasons. Retrospective VAS scores yielded significant improvements in year 1 in patients who had learned self-hypnosis: pollinosis symptoms –29.2 (VAS score, range 0–100; SD 25.4; p &lt; 0.001), restriction of well-being –26.2 (VAS score, range 0–100; SD 28.7; p &lt; 0.001. In year 2, the control group improved significantly having learned self-hypnosis as well: pollinosis symptoms –24.8 (SD 29.1; p &lt; 0.001), restriction of well-being –23.7 (SD 30.0; p &lt; 0.001). Daily self-reports of subjects who learnt self-hypnosis do not show a significant improvement. The hazard ratio of reaching a critical flow of 70% in nasal provocation tests was 0.333 (95% CI 0.157–0.741) after having learnt and applied self-hypnosis.
Immunogenic HLA-B*0702-Restricted Epitopes Derived from Human Telomerase Reverse Transcriptase That Elicit Antitumor Cytotoxic T-Cell Responses
Authors: Olivier Adotévi, Karine Mollier, Christine Neuveut, Sylvain Cardinaud, Emmanuelle Boulanger, Blandine Mignen, Wolf-Hervé Fridman, Maurizio Zanetti, Pierre Charneau, Eric Tartour, François Lemonnier, Pierre Langlade-Demoyen
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The human telomerase reverse transcriptase (hTERT) is considered as a potential target for cancer immunotherapy because it is preferentially expressed in tumor cells. To increase the applicability of hTERT-based immunotherapy, we set out to identify CTL epitopes in hTERT restricted by HLA-B*0702 molecule, a common MHC class I allele. Experimental Design: HLA-B*0702-restricted peptides from hTERT were selected by using a method of epitope prediction and tested for their immunogenicity in human (in vitro) and HLA-B*0702 transgenic mice (in vivo). Results: All the six hTERT peptides that were predicted to bind to HLA-B*0702 molecule were found to induce primary human CTL responses in vitro. The peptide-specific CD8+ CTL lines were tested against various hTERT+ tumor cells. Although differences were observed according to the tumor origin, only three CTL lines specific for p277, p342, and p351 peptides exhibited cytotoxicity against tumor cells in a HLA-B*0702-restricted manner. In addition, this cytotoxicity was inhibited by the addition of peptide-loaded cold target cells and indicated that these epitopes are naturally processed and presented on the tumor cells. Further, in vivo studies using humanized HLA-B*0702 transgenic mice showed that all the candidate peptides were able to induce CTL responses after peptide immunization. Furthermore, vaccination with a plasmid DNA encoding full-length hTERT elicited peptide-specific CTL responses, indicating that these epitopes are efficiently processed in vivo. Conclusions: Together with previously reported hTERT epitopes, the identification of new CTL epitopes presented by HLA-B*0702 increases the applicability of hTERT-based immunotherapy to treating cancer.