tbuckley/cabot-search huggingface dataset:
CALCULATION OF INTRACELLULAR pH FROM THE DISTRIBUTION OF 5,5-DIMETHYL-2,4-OXAZOLIDINEDIONE (DMO). APPLICATION TO SKELETAL MUSCLE OF THE DOG*
Authors: William J. Waddell, Thomas C. Butler
Journal: Journal of Clinical Investigation (1959)

Estimations of hydrogen ion activities in the interior of cells have been attempted through a number of different experimental approaches. The methods that have been employed are of several general types: measurements on preparations of broken cells, measurements on fluid withdrawn from cells, observations with visible indicators, measurements with micro-electrodes introduced into cells, measurements of the intracellular and extracellular concentrations of weak organic acids and bases, and calculation of the balance of ionic charges. The last named method has been proposed by Conway (1). The other methods are discussed in the review of Caldwell (2), which contains a tabulation of the results of measurements on various types of cells with different experimental methods. Some of the methods that have been used are of quite limited applicability, and most of the values arrived at by any of the methods are subject to question. Potentially, the method utilizing the distribution of weak organic acids and bases has a wider range of applicability than the other methods, and it is not subject to some of the theoretical objections that can be raised to other methods. There is a great deal of evidence that membranes of animal and plant cells in general are characterized by free permeability to the undissociated forms of weak organic acids and bases and by impermea
HTLV-I provirus in seronegative healthy blood donors
Authors: Dorothea Zucker-Franklin, John G Gorman
Journal: The Lancet (1997)

There have been reports of patients with lymphotropic retrovirus (HTLV-I)-associated diseases who did not have antibodies to structural proteins of the virus (eg, 1 Nishimura M Minglioli E McFarlein DE Jacobson S Demonstration of human T-cell lymphotropic virus type I (HTLV-I) from an HTLV-I seronegative South Indian patient with chronic, progressive spastic paraparesis. Ann Neurol. 1993; 34: 867-870 Crossref PubMed Scopus (11) Google Scholar ). Most patients with mycosis fungoides, who are serologically negative have HTLV-I Tax sequence in their blood and skin-infiltrating lymphocytes. 2 Pancake BA Zucker-Franklin D Coutavas EE The cutaneous T cell lymphoma, mycosis fungoides, is a human T cell lymphotropic virus-associated disease. A study of 50 patients. J Clin Invest. 1995; 95: 545-554 Crossref Scopus (130) Google Scholar , 3 Khan ZM Sebenik M Zucker-Franklin D Localization of HTLV-I proviral sequences in skin biopsies of patients with mycosis fungoides by in-situ PCR. J Invest Dermatol. 1996; 106: 667-672 Crossref PubMed Scopus (38) Google Scholar Although patients with mycosis fungoides lack antibodies to the structural proteins of the virus, such as env and gag, more than 80% have antibodies to Tax protein when tested by western blot. 4 Pancake BA Wassef EH Zucker-Franklin D Demonstration of antibodies to human T-cell lymphotropic virus-I tax in patients with the cutaneous T-cell lymphoma, mycosis fungoides, who are seronegative for antibodies to the structural proteins of the virus. Blood. 1996; 88: 3004-3009 PubMed Google Scholar This condition of negative standard HTLV-I antibody tests, and positivity for Tax antibody and Tax sequence in lymphocytes, previously seen only in individuals with disease, was found in six of eight healthy relatives of our patients with mycosis fungoides tested to date.
Evidence for a subset of rheumatoid factors that cross-react with DNA-histone and have a distinct cross-idiotype.
Authors: V Agnello, A Arbetter, G Ibanez de Kasep, R Powell, E M Tan, F Joslin
Journal: The Journal of Experimental Medicine (1980)

Cross-reactivity of a monoclonal rheumatoid factor with an antigen present on IgG and DNA-nucleoprotein was demonstrated, and evidence presented that the combining site of the antibody was involved in the reaction. The antigen on the DNA-nucleoprotein was shown to involve both DNA and histone fraction H2A + H2B and was trypsin sensitive. The relative binding affinity of the antibody appeared to be greater for IgG than the DNA-histone antigen. Similar polyclonal cross-reactive rheumatoid factors were found in a variety of diseases. A high incidence was found among patients with rheumatoid arthritis and mixed connective tissue disease. None were detected in patients with systemic lupus erythematosus and idiopathic cryoglobulinemia. Studies on one representative isolated polyclonal rheumatoid factor demonstrated the same reactivity with DNA-histone H2A + H2B as the monoclonal antibody. Cross-idiotype studies using antigen-binding inhibition methods demonstrated the same cross-idiotype on the polyclonal and the monoclonal rheumatoid factor which reacted with DNA-histone. This cross-idiotype was shown to be distinct from the cross-idiotypes previously demonstrated on monoclonal IgM proteins with anti-gamma-globulin activity.
Treatment of hepatitis C virus-related cirrhosis: A randomized, controlled trial of interferon alfa-2b versus no treatment
Authors: Dominique-Charles Valla, Michele Chevallier, Patrick Marcellin, Jean-Louis Payen, Christian Trepo, Marianne Fonck, Marc Bourliere, Evelyne Boucher, Jean-Philippe Miguet, David Parlier, Catherine Lemonnier, Pierre Opolon
Journal: Hepatology (1999)

To examine the effects of interferon (IFN) therapy on clinical, biochemical, and histological features in patients with compensated hepatitis C virus (HCV)-related cirrhosis, we have conducted a randomized, controlled trial of IFN therapy versus observation. Eight centers included a total of 99 patients with biopsy-proven cirrhosis. IFN-alpha2b, 3 million units three times per week, or no antiviral therapy was given for 48 weeks. Twenty-three patients dropped out. End-of-treatment biochemical response was not observed in any of the 39 controls but was observed in 6 of the 47 treated patients (P <.02); sustained biochemical response was obtained in only 2 treated patients. Controls and treated patients did not significantly differ with regard to the changes in serum level of albumin, bilirubin, alpha-fetoprotein, in plasma prothrombin, in histological activity, or liver collagen content. During trial or follow-up (160 +/- 57 weeks), hepatocellular carcinoma developed in 9 controls and 5 treated patients (NS); decompensation of cirrhosis occurred in 5 controls and 7 treated patients. Seven controls and 10 treated patients died. In conclusion, in patients with compensated HCV-related cirrhosis, a 48-week course of IFN therapy is safe and is able to induce end-of-treatment biochemical response in a significant proportion of patients. However, a 48-week course of IFN therapy usually fails to achieve sustained response and, within the limit of this study, did not significantly improve the 3-year outcome. Therefore, a longer course of IFN therapy or combination therapy with ribavirin should be evaluated in patients with HCV-related cirrhosis.
Characteristics of a Human Cell Line Successively Transformed by Rous Sarcoma Virus and Simian Virus 402
Authors: T. Kuwata, T. Oda, S. Sekiya, Naoko Morinaga
Journal: JNCI Journal of the National Cancer Institute (1976)

Human enbryo cells were successively transformed by the Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV) and simian virus 40 (SV40) in vitro, and the double transformant HuE 13 RS was established. From this cell line the two clonal cell lines RSa and RSb were isolated. In both, presence of SV40 T antigens was demonstrated by the fluorescent antibody technique, and the presence of RSV genomes was verified in one RSb clone by focus formation after fusion with chick embryo cells. Growth of these cells was affected by dibutyryl cAMP without marked morphologic changes. Cells were extremely sensitive to the anticellular action of human leukocyte interferon.
Nitrogen dioxide induces apoptosis and proliferation but not emphysema in rat lungs
Authors: H. Fehrenbach, G. Zimmermann, E. Starke, V. A Bratu, D. Conrad, A. O Yildirim, A. Fehrenbach
Journal: Thorax (2007)

Apoptosis of alveolar septal cells has been linked to emphysema formation. Nitrogen dioxide, a component of cigarette smoke, has been shown to induce alveolar epithelial cell apoptosis in vitro. It is hypothesised that exposure of rats to nitrogen dioxide may result in increased alveolar septal cell apoptosis in vivo with ensuing emphysema-that is, airspace enlargement and loss of alveolar walls.Fischer 344 rats were exposed to 10 ppm nitrogen dioxide for 3, 7, 21 days or 21 days followed by 28 days at room air. Age-matched control rats were exposed to room air for 3, 21 or 49 days. Lungs fixed at 20 cm fluid column, embedded in paraffin wax, glycol methacrylate and araldite, were analysed by design-based stereology. Alveolar septal cell apoptosis (transferase dUTP nick end labelling assay, active caspase 3) and proliferation (Ki-67), airspace enlargement, total alveolar surface area, and absolute alveolar septal volume as well as the ultrastructural composition of the alveolar wall were quantified.Nitrogen dioxide resulted in an eightfold increase in alveolar septal cell apoptosis at day 3 and a 14-fold increase in proliferation compared with age-matched controls. Airspace enlargement, indicated by a 20% increase in mean airspace chord length, was evident by day 7 but was not associated with loss of alveolar walls. By contrast, nitrogen dioxide resulted in an increase in the total surface area and absolute volume of alveolar walls comprising all compartments. The ratio of collagen to elastin, however, was reduced at day 21. Lungs exposed to nitrogen dioxide for 21 days exhibited quantitative structural characteristics as seen in control lungs on day 49.Nitrogen dioxide exposure of rats results in increased alveolar septal cell turnover leading to accelerated lung growth, which is associated with an imbalance in the relative composition of the extracellular matrix, but fails to induce emphysema.
Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer
Authors: David Cunningham, Seppo Pyrhönen, Roger D James, Cornelis JA Punt, Tamas F Hickish, Reino Heikkila, Tom B Johannesen, Hans Starkhammar, Clare A Topham, Lucile Awad, Christian Jacques, Patrice Herait
Journal: The Lancet (1998)
Reliability and validity of the Advanced Basal Cell Carcinoma Index (aBCCdex)
Authors: S.D. Mathias, M.M. Chren, R.D. Crosby, H.H. Colwell, Y.M. Yim, C. Reyes, D.M. Chen, S.W. Fosko
Journal: British Journal of Dermatology (2015)

Patient-reported outcome (PRO) questionnaires were recently developed specifically for use with patients with advanced basal cell carcinoma (aBCC) and basal cell carcinoma naevus syndrome (BCCNS).To evaluate the measurement properties of PRO questionnaires for use in patients with aBCC or BCCNS.In total 129 patients from 10 clinical sites in the U.S.A. and the BCCNS Support Network completed the two newly developed questionnaires multiple times over 3 months. Patients also completed the Skindex-16 and the 12-Item Short-Form Health Survey as collateral measures. Psychometric properties of the questionnaires were evaluated, including internal consistency and test-retest reliability, construct and known-groups validity, and responsiveness.Based on the results of exploratory factor analysis and clinical input, the two newly developed questionnaires were combined into a single questionnaire, called the aBCCdex, which is relevant for patients with both aBCC and BCCNS. The internal consistency reliability was acceptable, and all aBCCdex scale scores correlated significantly with conceptually similar scales. When divided into groups that differed based on scores from collateral measures, aBCCdex scale scores differentiated between groups (known-groups validity) and were responsive to change.The aBCCdex is a brief and comprehensive questionnaire appropriate for use with patients with aBCC and BCCNS. Its reliability and validity have been confirmed. Further research is necessary to estimate the minimally important difference in a larger patient population.
Hypothalamic-Pituitary-Adrenal Axis in Psychiatric Disorders
Authors: Peter E. Stokes, Carolyn R. Sikes
Journal: Annual Review of Medicine (1991)

Hypothalamic-pituitary-adrenocortical (HPA) physiology is complex, and dysregulation of this neuroendocrine axis cannot be characterized adequately by isolated or unintegrated measures. Repeated assessments over time, involving multiple measures of axis activity (basal and dynamic tests), have furthered our understanding of the character of the HPA abnormalities reported in various psychiatric disorders. We review the nature and clinical significance of these HPA disturbances in the affective disorders and other psychiatric illnesses.
Tea polyphenols in preventing cardiovascular diseases
Authors: H YAMADA, H WATANABE
Journal: Cardiovascular Research (2006)

Epidemiological observations suggesting an inverse correlation between tea consumption and the incidence of cardiovascular diseases have been well established [1–4]. The review by Stangl et al. gives an overview of the effects of polyphenolic compounds in tea on the function of the cardiovascular system, especially on various signal transduction pathways in cardiovascular cells [5]. The underlying mechanisms of tea polyphenols in preventing cardiovascular disease, however, are yet to be well understood.

It is widely known, but still open to question, why the incidence of coronary events (death definitely or probably due to …
Electrophysiological and pharmacological correspondence between Kv4.2 current and rat cardiac transient outward current
Authors: S YEOLA, D SNYDERS
Journal: Cardiovascular Research (1997)

Objective: The transient outward current ( ITo) plays an important role in early repolarization and overall time course of the cardiac action potential.At least two K' channel a-subunits cloned from cardiac tissue (Kvl.4 and Kv4.2) encode rapidly inactivating channels.The goal of this study was to determine functional and pharmacological properties of Kv4.2 expressed in mammalian cells, especially those that would differentiate between both isoforms in comparison to native I,,.Methods: Both Kv4.2 and Kv 1.4 isoforms were stably expressed in mouse L-cell lines, and expressed currents were studied using whole-cell voltage clamp techniques.Results: The expressed Kv4.2 currents displayed fast inactivation with a half-inactivation potential of -41 mV.Recovery from inactivation was rapid (km" = 160 ms at -90 mV) and strongly voltage-dependent.Flecainide (10 PM) had minimal effects on Kv 1.4 currents, but reduced Kv4.2 peak current by 53% and increased the apparent rate of inactivation consistent with open channel block.Quinidine (IO-20 FM) reduced the peak current and accelerated the apparent rate of inactivation in both isoforms.The Kv4.2 current displayed use-dependent unblock in the presence of 4-AP.Conclusions: The functional properties of Kv4.2, especially the flecainide sensitivity, resemble those of ITo in rat (and human) myocytes better than those of Kv1.4.These results provide the necessary functional support for the hypothesis that Kv4.2 is a major isoform contributing to cardiac I,,, consistent with independent biochemical and molecular evidence that indicates that Kv4.2 is readily detected in rat myocytes.
Mediators of Glioblastoma Resistance and Invasion during Antivascular Endothelial Growth Factor Therapy
Authors: Agda K. Lucio-Eterovic, Yuji Piao, John F. de Groot
Journal: Clinical Cancer Research (2009)

Vascular endothelial growth factor (VEGF) has been identified as a critical regulator of angiogenesis. Currently, several different strategies are being used to target the VEGF-VEGF receptor signal transduction pathway in glioblastoma. Although anti-VEGF therapy seems be effective in normalizing abnormal tumor vasculature, leading to an enhanced response to radiation and chemotherapy, tumors eventually become resistant to the therapy and adopt a highly infiltrative and invasive phenotype.In the present study, we evaluated the effects of anti-VEGF therapy (bevacizumab) on glioblastoma invasion both in vitro and in vivo and evaluated the angiogenesis- and invasion-related mediators of developed resistance to this therapy.We found that glioblastoma tumors escaped from antiangiogenic treatment by (a) reactivating angiogenesis through up-regulation of other proangiogenic factors and (b) invading normal brain areas, which was seen in association with up-regulation of matrix metalloproteinase (MMP)-2, MMP-9, and MMP-12; secreted protein, acidic, cysteine-rich; and tissue inhibitor of metalloproteinase 1. In addition to the paracrine effects of VEGF on endothelial cells, autocrine VEGF signaling seemed to regulate glioblastoma invasion because anti-VEGF therapy increased tumor invasiveness in vitro.Collectively, these findings reinforce the importance of VEGF in regulating tumor invasion and identify potential mediators of resistance to targeted VEGF therapy. These results will be important for developing novel combination therapies to overcome this resistance phenotype.
Protein Kinase D Selectively Targets Cardiac Troponin I and Regulates Myofilament Ca <sup>2+</sup> Sensitivity in Ventricular Myocytes
Authors: Friederike Cuello, Sonya C. Bardswell, Robert S. Haworth, Xiaoke Yin, Susanne Lutz, Thomas Wieland, Manuel Mayr, Jonathan C. Kentish, Metin Avkiran
Journal: Circulation Research (2007)

Protein kinase D (PKD) is a serine/threonine kinase with emerging myocardial functions; in skinned adult rat ventricular myocytes (ARVMs), recombinant PKD catalytic domain phosphorylates cardiac troponin I at Ser22/Ser23 and reduces myofilament Ca(2+) sensitivity. We used adenoviral gene transfer to determine the effects of full-length PKD on protein phosphorylation, sarcomere shortening and [Ca(2+)](i) transients in intact ARVMs. In myocytes transduced to express wild-type PKD, the heterologously expressed enzyme was activated by endothelin 1 (ET1) (5 nmol/L), as reflected by PKD phosphorylation at Ser744/Ser748 (PKC phosphorylation sites) and Ser916 (autophosphorylation site). The ET1-induced increase in cellular PKD activity was accompanied by increased cardiac troponin I phosphorylation at Ser22/Ser23; this measured approximately 60% of that induced by isoproterenol (10 nmol/L), which activates cAMP-dependent protein kinase (PKA) but not PKD. Phosphorylation of other PKA targets, such as phospholamban at Ser16, phospholemman at Ser68 and cardiac myosin-binding protein C at Ser282, was unaltered. Furthermore, heterologous PKD expression had no effect on isoproterenol-induced phosphorylation of these proteins, or on isoproterenol-induced increases in sarcomere shortening and relaxation rate and [Ca(2+)](i) transient amplitude. In contrast, heterologous PKD expression suppressed the positive inotropic effect of ET1 seen in control cells, without altering ET1-induced increases in relaxation rate and [Ca(2+)](i) transient amplitude. Complementary experiments in "skinned" myocytes confirmed reduced myofilament Ca(2+) sensitivity by ET1-induced activation of heterologously expressed PKD. We conclude that increased myocardial PKD activity induces cardiac troponin I phosphorylation at Ser22/Ser23 and reduces myofilament Ca(2+) sensitivity, suggesting that altered PKD activity in disease may impact on contractile function.
Not Expecting the Unexpected: Diacylglycerol Kinase Alpha as a Cancer Target
Authors: Krishna P.L. Bhat, Kenneth Aldape
Journal: Cancer Discovery (2013)

In this issue of Cancer Discovery, Dominguez and colleagues identify diacylglycerol kinase alpha (DGKα), an enzyme that converts the membrane lipid diacylglycerol to phosphatidic acid, as a central node upstream of mTOR and other oncogenic pathways. Importantly, targeting DGKα causes apoptosis in cancer cells and tumor growth inhibition in mice with no overt toxicity, implicating DGKα as a novel cancer-specific target.
Cooperation, psychological game theory, and limitations of rationality in social interaction
Authors: Andrew M. Colman
Journal: Behavioral and Brain Sciences (2003)

Rational choice theory enjoys unprecedented popularity and influence in the behavioral and social sciences, but it generates intractable problems when applied to socially interactive decisions. In individual decisions, instrumental rationality is defined in terms of expected utility maximization. This becomes problematic in interactive decisions, when individuals have only partial control over the outcomes, because expected utility maximization is undefined in the absence of assumptions about how the other participants will behave. Game theory therefore incorporates not only rationality but also common knowledge assumptions, enabling players to anticipate their co-players' strategies. Under these assumptions, disparate anomalies emerge. Instrumental rationality, conventionally interpreted, fails to explain intuitively obvious features of human interaction, yields predictions starkly at variance with experimental findings, and breaks down completely in certain cases. In particular, focal point selection in pure coordination games is inexplicable, though it is easily achieved in practice; the intuitively compelling payoff-dominance principle lacks rational justification; rationality in social dilemmas is self-defeating; a key solution concept for cooperative coalition games is frequently inapplicable; and rational choice in certain sequential games generates contradictions. In experiments, human players behave more cooperatively and receive higher payoffs than strict rationality would permit. Orthodox conceptions of rationality are evidently internally deficient and inadequate for explaining human interaction. Psychological game theory, based on nonstandard assumptions, is required to solve these problems, and some suggestions along these lines have already been put forward.
A possible primary cause of cancer: deficient cellular interactions in endocrine pancreas
Authors: Maurice Israël
Journal: Molecular Cancer (2012)

Abstract Background Cancer is a devastating type of disease. New and innovative ways to tackle cancers that have so far proved refractive to conventional therapies is urgently needed. It is becoming increasingly clear that, in addition to conventional therapeutics targeting by small molecules, that tumor cell metabolism presents new opportunities to target selectively specific cancer cell populations. Metabolic defects in cancer cells can be manifested in many ways that might not be readily apparent, such as altering epigenetic gene regulation for example. The complex rewiring of metabolic pathways gives tumor cells a special advantage over differentiated cells, since they deplete body stores as fuel for their growth and proliferation. Tumor metabolism looks simpler when we consider that some enzymatic switches are in a neoglucogenic direction thereby depleting body stores. However, these pathways may be inadequately switched on by catabolic hormones (glucagon, epinephrine and cortisol) in a specific situation where anabolism is activated by, for example insulin released from beta pancreatic cells or IGF, inducing mitosis and synthesis that are powered by glucose catabolism. Such a hybrid metabolic situation would be reached if a pancreatic beta cell mechanism, mediated by GABA, failed to silence neighboring alpha cells and delta cells. The inhibitory transmitter GABA hyperpolarizes alpha and delta cells via their GABA A receptors, and blocks the release of glucagon and somatostatin. Alternatively, an anomaly of alpha cell channels, would lead to a similar situation. Whatever is the alteration, anabolism fails to silence catabolism and enzymatic switches controlled by kinases and phosphatases adopt an inadequate direction, leading to a hybrid metabolic rewiring found in cancer. It is daring to formulate such a hypothesis as this. However, it is quite possible that the starting point in cancer is an alteration of the endocrine pancreas, suppressing the mechanism by which beta cells silence the neighboring alpha and delta cells, with GABA and Zn 2+ .