tbuckley/cabot-search huggingface dataset:
Phorbol ester increases calcium current and simulates the effects of angiotensin II on cultured neonatal rat heart myocytes.
Authors: A Döşemeci, R S Dhallan, N M Cohen, W J Lederer, T B Rogers
Journal: Circulation Research (1988)

The effects of increased protein kinase C activity were studied in neonatal rat myocytes grown in primary culture. The changes in mechanical and electrical behavior, as well as protein phosphorylation, that followed the apparent activation of protein kinase C by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) were examined. As spontaneous beating frequency was increased minimally by 10 nM TPA and by 100% with 85 nM TPA, shortening amplitude, shortening velocity, and relaxation velocity decreased concomitantly. In contrast, 4-alpha-phorbol-12,13-didecanoate (alpha-PDD), which does not activate protein kinase C, had no effect on beating behavior at 800 nM. In voltage-clamped single myocytes, both steady-state and transient components of the cadmium-sensitive calcium current were increased by the addition of TPA (65 nM). Neither the time constant for the inactivation of the transient component of this calcium current nor the reversal potential was altered by TPA. The phosphorylation state of a discrete set of proteins, with apparent molecular weights of 32 and 83 kDa, was enhanced when TPA was added to intact myocytes. Angiotensin II enhances the phosphorylation state of the same set of proteins as observed with TPA. We conclude that activation of protein kinase C can modify mechanical behavior and increase L-type Ca2+ channel activity in cultured neonatal rat ventricular myocytes. The remarkable similarity in mechanical, electrical, and protein phosphorylation responses of cultured neonatal myocytes following TPA or angiotensin II application indicate that protein kinase C may mediate the action of angiotensin II.
Seroprevalence of hepatitis C virus nucleocapsid antibodies in patients with cryptogenic chronic liver disease
Authors: Jonathan Brown, Spyros Dourakis, Peter Karayiannis, Robert Goldin, Joe Chiba, Hiroyoshi Ohba, Tatsuo Miyamura, Howard C. Thomas
Journal: Hepatology (1992)

The serological responses to two different hepatitis C virus antigens were studied by enzyme-linked immunosorbent assay in a variety of chronic liver diseases and in healthy blood donors. The study population comprised 97 cases of cryptogenic chronic liver disease (40% with a history suggestive of parenterally transmitted non-A, non-B hepatitis and 60% without such a history), 87 cases of other well-characterized chronic liver diseases and 96 voluntary blood donors. The commercially available C100-3 assay and a new assay utilizing a 22 kD recombinant protein (c22) from the nucleocapsid region of the virus were used for antibody detection. Overall in the non-A, non-B hepatitis group, 77% were positive for anti-c22, 55% were positive for anti-C100-3 and 24% were negative by both tests. In the parenterally transmitted chronic liver disease group, 82% were positive for anti-C100-3 and 90% were positive for anti-c22 (not significant). In the cryptogenic chronic liver disease cases 36% were positive for anti-C100-3 and 67% were positive for anti-c22 (p less than 0.001). Only in one case (a patient with hepatitis B virus infection) was anti-C100-3 detected without concomitant anti-c22. None of the voluntary blood donors had detectable hepatitis C virus antibodies. The new enzyme-linked immunosorbent assay test for anti-c22 would appear to be a more sensitive indicator of chronic hepatitis C virus infection than the existing commercial test, suggesting a useful diagnostic role in both cases of cryptogenic chronic non-A, non-B hepatitis liver disease and for the screening of blood products for prevention of hepatitis after transfusion.
A Candidate Gene Study of Obstructive Sleep Apnea in European Americans and African Americans
Authors: Emma K. Larkin, Sanjay R. Patel, Robert J. Goodloe, Yali Li, Xiaofeng Zhu, Courtney Gray-McGuire, Mark D. Adams, Susan Redline
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Obstructive sleep apnea (OSA) is hypothesized to be influenced by genes within pathways involved with obesity, craniofacial development, inflammation, and ventilatory control.Objectives: We conducted the first candidate gene study of OSA using family data from European Americans and African Americans, selecting biologically plausible genes from within these pathways.Methods: A total of 1,080 single nucleotide polymorphisms (SNPs) were genotyped in 729 African Americans and 505 SNPs were genotyped in 694 European Americans. Coding for SNPs additively, association testing on the apnea-hypopnea index (AHI) as a continuous trait, and OSA as a dichotomous trait (AHI ≥15) was conducted using methods that account for familial correlations in models adjusted for age, age-squared, and sex, with and without body mass index.Measurements and Main Results: In European Americans, variants within C-reactive protein (CRP) and glial cell line–derived neurotrophic factor (GDNF) were associated with AHI (CRP: β = 4.6; SE = 1.1; P = 0.0000402) (GDNF: β = 4.3; SE = 1; P = 0.0000201) and with the dichotomous OSA trait (CRP: odds ratio = 2.4; 95% confidence interval, 1.5–3.9; P = 0.000170) (GDNF: odds ratio = 2; 95% confidence interval, 1.4–2.89; P = 0.0000433). In African Americans, rs9526240 within serotonin receptor 2a (HTR2A: odds ratio = 2.1; 95% confidence interval, 1.5–2.9; P = 0.00005233) was associated with OSA.Conclusions: This candidate gene analysis identified the potential role of genes operating through intermediate disease pathways to influence sleep apnea phenotypes, providing a framework for focusing future replication studies.
Radiosensitivity Enhancement by Combined Treatment of Celecoxib and Gefitinib on Human Lung Cancer Cells
Authors: Ji Sun Park, Hyun Jung Jun, Moon Jun Cho, Kwan Ho Cho, Jin Soo Lee, Jae Ill Zo, Hongryull Pyo
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To characterize the radiation-enhancing effects and underlying mechanisms of combined treatment with celecoxib, a cyclooxygenase-2 selective inhibitor, and gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in human lung cancer cells. Experimental Design: Clonogenic cytotoxicity assays and clonogenic radiation survival assays after treatments with celecoxib and gefitinib with or without radiation were done on three human lung cancer cell lines. Synergisms after combined treatment with celecoxib, gefitinib, and radiation were investigated using isobologram and statistical analyses according to an independent action model. Alterations in apoptosis and cell cycle were measured to identify the mechanisms underlying the cell killing or radiation-enhancing effects of celecoxib and gefitinib combination treatment. Western blots for phosphorylated EGFR, EGFR, cyclooxygenase-2, and G2 checkpoint molecules were conducted after treatment with celecoxib and/or gefitinib with or without radiation. Results: Combination celecoxib, gefitinib, and radiation treatments were shown to be synergistic in causing clonogenic cell deaths in all cell lines tested, but the nature of synergism was cell type specific. The combined drug treatments induced apoptosis in an additive manner in A549 cells and in a synergistic manner in NCI-H460 and VMRC-LCD cells. Celecoxib or gefitinib attenuated radiation-induced G2-M arrest, and combined drug treatment additively attenuated radiation-induced G2-M arrest in all cell lines. Radiation-induced checkpoint kinase (Chk) 1 and Chk2 phosphorylation were inhibited by celecoxib and gefitinib treatment, respectively. Conclusions: Combined celecoxib and gefitinib treatments were shown to synergistically enhance the effect of radiation on lung cancer cells. The mechanisms underlying these synergistic effects seem to involve the synergistic enhancement of apoptosis and cooperative attenuation of radiation-induced G2-M arrest, possibly via Chk1 and Chk2 inhibition, by the combined drug treatments.
Bootstrapping the mind
Authors: Julian Kiverstein, Andy Clark
Journal: Behavioral and Brain Sciences (2008)

Abstract After offering a brief account of how we understand the shared circuits model (SCM), we divide our response into four sections. First, in section R1, we assess to what extent SCM is committed to an account of the ontogeny and phylogeny of shared circuits. In section R2, we examine doubts raised by several commentators as to whether SCM might be expanded so as to accommodate the mirroring of emotions, sensations, and intransitive actions more generally. Section R3 responds to various criticisms that relate to the account of social-learning Hurley proposes in the target article. We conclude in section R4 by responding to a number of commentators who argued for the limitation of control theory as a framework for studying social cognition.
Developmental stage related patterns of codon usage and genomic GC content: searching for evolutionary fingerprints with models of stem cell differentiation
Authors: Lichen Ren, Ge Gao, Dongxin Zhao, Mingxiao Ding, Jingchu Luo, Hongkui Deng
Journal: Genome biology (2007)

Abstract Background The usage of synonymous codons shows considerable variation among mammalian genes. How and why this usage is non-random are fundamental biological questions and remain controversial. It is also important to explore whether mammalian genes that are selectively expressed at different developmental stages bear different molecular features. Results In two models of mouse stem cell differentiation, we established correlations between codon usage and the patterns of gene expression. We found that the optimal codons exhibited variation (AT- or GC-ending codons) in different cell types within the developmental hierarchy. We also found that genes that were enriched (developmental-pivotal genes) or specifically expressed (developmental-specific genes) at different developmental stages had different patterns of codon usage and local genomic GC (GCg) content. Moreover, at the same developmental stage, developmental-specific genes generally used more GC-ending codons and had higher GCg content compared with developmental-pivotal genes. Further analyses suggest that the model of translational selection might be consistent with the developmental stage-related patterns of codon usage, especially for the AT-ending optimal codons. In addition, our data show that after human-mouse divergence, the influence of selective constraints is still detectable. Conclusion Our findings suggest that developmental stage-related patterns of gene expression are correlated with codon usage (GC3) and GCg content in stem cell hierarchies. Moreover, this paper provides evidence for the influence of natural selection at synonymous sites in the mouse genome and novel clues for linking the molecular features of genes to their patterns of expression during mammalian ontogenesis.
American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer
Authors: M. Elizabeth H. Hammond, Daniel F. Hayes, Mitch Dowsett, D. Craig Allred, Karen L. Hagerty, Sunil Badve, Patrick L. Fitzgibbons, Glenn Francis, Neil S. Goldstein, Malcolm Hayes, David G. Hicks, Susan Lester, Richard Love, Pamela B. Mangu, Lisa McShane, Keith Miller, C. Kent Osborne, Soonmyung Paik, Jane Perlmutter, Anthony Rhodes, Hironobu Sasano, Jared N. Schwartz, Fred C.G. Sweep, Sheila Taube, Emina Emilia Torlakovic, Paul Valenstein, Giuseppe Viale, Daniel Visscher, Thomas Wheeler, R. Bruce Williams, James L. Wittliff, Antonio C. Wolff
Journal: Journal of Clinical Oncology (2010)

To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers.
PDGF Receptor Alpha Is an Alternative Mediator of Rapamycin-Induced Akt Activation: Implications for Combination Targeted Therapy of Synovial Sarcoma
Authors: Alan L. Ho, Shyamprasad Deraje Vasudeva, Marick Laé, Tsuyoshi Saito, Violetta Barbashina, Cristina R. Antonescu, Marc Ladanyi, Gary K. Schwartz
Journal: Cancer Research (2012)

Akt activation by the IGF-1 receptor (IGF-1R) has been posited to be a mechanism of intrinsic resistance to mTORC1 inhibitors (rapalogues) for sarcomas. Here we show that rapamycin-induced phosphorylation of Akt can occur in an IGF-1R-independent manner. Analysis of synovial sarcoma cell lines showed that either IGF-1R or the PDGF receptor alpha (PDGFRA) can mediate intrinsic resistance to rapamycin. Repressing expression of PDGFRA or inhibiting its kinase activity in synovial sarcoma cells blocked rapamycin-induced phosphorylation of Akt and decreased tumor cell viability. Expression profiling of clinical tumor samples revealed that PDGFRA was the most highly expressed kinase gene among several sarcoma disease subtypes, suggesting that PDGFRA may be uniquely significant for synovial sarcomas. Tumor biopsy analyses from a synovial sarcoma patient treated with the mTORC1 inhibitor everolimus and PDGFRA inhibitor imatinib mesylate confirmed that this drug combination can impact both mTORC1 and Akt signals in vivo. Together, our findings define mechanistic variations in the intrinsic resistance of synovial sarcomas to rapamycin and suggest therapeutic strategies to address them.
A reduction in training volume and intensity for 21 days does not impair performance in cyclists
Authors: G J W M Rietjens, H A Keizer, H Kuipers, W H M Saris
Journal: British Journal of Sports Medicine (2001)

(a) To investigate the effects of reduced training on physical condition and performance in well trained cyclists; (b) to study whether an intermittent exercise programme would maintain physiological training adaptations more effectively than a continuous exercise programme during a period of reduced training.Twelve male cyclists participated in a 21 day training programme and were divided into two training groups. One group (age 25.3 (7) years; weight 73.3 (5.7) kg; VO(2)MAX 58.6 (4.5) ml/kg/min; means (SD)) underwent a continuous endurance exercise training programme (CT) whereas the second group (age 22.8 (3.5) years; weight 74.1 (7.0) kg; VO(2)MAX 59.7 (6.7) ml/kg/min) followed an intermittent endurance exercise training programme (IT). During this reduced training period, both groups trained for two hours a day, three days a week.Neither group showed changes in maximal workload (WMAX) (4.6 (0.5) v 4.8 (0.5) W/kg and 4.6 (0.5) v 4.7 (0.6) W/kg for the CT and IT group respectively) and VO(2)MAX (58.6 (4.5) v 60.1 (5.8) ml/kg/min and 59.7 (6.7) v 58.8 (7.5) ml/kg/min for the CT and IT group respectively). During the submaximal steady state exercise test, substrate use and heart rate remained unchanged after reduced training.These results indicate that well trained cyclists who reduce training intensity and volume for 21 days can maintain physiological adaptations, as measured during submaximal and maximal exercise. An intermittent training regimen has no advantage over a continuous training regimen during a detraining period.
Deficiencies in Mouse <b> <i>Myh</i> </b> and <b> <i>Ogg1</i> </b> Result in Tumor Predisposition and G to T Mutations in Codon 12 of the <b> <i>K-Ras</i> </b> Oncogene in Lung Tumors
Authors: Yali Xie, Hanjing Yang, Cristina Cunanan, Kimberly Okamoto, Darryl Shibata, Janet Pan, Deborah E. Barnes, Tomas Lindahl, Michael McIlhatton, Richard Fishel, Jeffrey H. Miller
Journal: Cancer Research (2004)

Abstract Oxidative DNA damage is unavoidably and continuously generated by oxidant byproducts of normal cellular metabolism. The DNA damage repair genes, mutY and mutM, prevent G to T mutations caused by reactive oxygen species in Escherichia coli, but it has remained debatable whether deficiencies in their mammalian counterparts, Myh and Ogg1, are directly involved in tumorigenesis. Here, we demonstrate that deficiencies in Myh and Ogg1 predispose 65.7% of mice to tumors, predominantly lung and ovarian tumors, and lymphomas. Remarkably, subsequent analyses identified G to T mutations in 75% of the lung tumors at an activating hot spot, codon 12, of the K-ras oncogene, but none in their adjacent normal tissues. Moreover, malignant lung tumors were increased with combined heterozygosity of Msh2, a mismatch repair gene involved in oxidative DNA damage repair as well. Thus, oxidative DNA damage appears to play a causal role in tumorigenesis, and codon 12 of K-ras is likely to be an important downstream target in lung tumorigenesis. The multiple oxidative repair genes are required to prevent mutagenesis and tumor formation. The mice described here provide a valuable model for studying the mechanisms of oxidative DNA damage in tumorigenesis and investigating preventive or therapeutic approaches.
Circulating Long Noncoding RNA, LIPCAR, Predicts Survival in Patients With Heart Failure
Authors: Regalla Kumarswamy, Christophe Bauters, Ingo Volkmann, Fleur Maury, Jasmin Fetisch, Angelika Holzmann, Gilles Lemesle, Pascal de Groote, Florence Pinet, Thomas Thum
Journal: Circulation Research (2014)

Long noncoding RNAs represent a novel class of molecules regulating gene expression. Long noncoding RNAs are present in body fluids, but their potential as biomarkers was never investigated in cardiovascular disease.To study the role of long noncoding RNAs as potential biomarkers in heart disease.Global transcriptomic analyses were done in plasma RNA from patients with or without left ventricular remodeling after myocardial infarction. Regulated candidates were validated in 3 independent patient cohorts developing cardiac remodeling and heart failure (788 patients). The mitochondrial long noncoding RNA uc022bqs.1 (LIPCAR) was downregulated early after myocardial infarction but upregulated during later stages. LIPCAR levels identified patients developing cardiac remodeling and were independently to other risk markers associated with future cardiovascular deaths.LIPCAR is a novel biomarker of cardiac remodeling and predicts future death in patients with heart failure.
PHYSIOLOGICAL CONDITIONS EXISTING IN CONNECTIVE TISSUE
Authors: Philip D. McMaster, Robert J. Parsons
Journal: The Journal of Experimental Medicine (1939)

The escape of a vital dye from the lymphatics of the ears of living mice and its subsequent movement through normal and pathological connective tissue have been observed at high magnification. The dye first appears outside such channels as bristly, wavy lines of color, which can be bent and twisted by pressure with a micro probe and spring back to their original positions when the pressure is removed, as if the dye were fixed upon or between some tissue elements. Our findings indicate that this is the case, that the bristly lines of color are formed by dye moving between connective tissue fibers or along them. With the onset of mild edema, such as the dye induces secondarily, the bristles disappear, the coloration becoming diffuse and freely movable with the micro probe. When edema is induced before dye is introduced into the lymphatics, the character of its escape is wholly different. It first appears as a colored cloud, freely movable in the edema fluid, the manner of its passage into the tissues being completely changed. In the ears of mice partly dehydrated by bleeding, or in those of dead animals, the bristly or wavy lines were more evident than in normal individuals. It was plain that dehydration did not change the mode of transportation of the dye through the tissue but merely emphasized some of the characteristics of its passage. In animals injected intravenously with large amounts of physiological saline, with result in the presence of more tissue fluid than usual, the colored bristles were seldom seen. It is plain that connective tissue fibers serve indirectly as pathways for the transport of substances of large molecule. We have not been able by the dye method to demonstrate the presence of any free fluid in the normal tissues of the mouse ear.
Coding errors in NHS cause up to 1bn worth of inaccurate payments
Authors: A. O'Dowd
Journal: BMJ (2010)

Errors in clinical coding of patients’ treatments in NHS hospitals in England have meant that primary care trusts have made about £1bn worth of mistaken payments over the past three years, sometimes paying too little and sometimes too much. 

The mistakes were spotted by the spending watchdog the Audit Commission, which published a new report on the quality of use of data in the NHS on 26 August. The commission had audited the data that underpin England’s Payment by Results system, which generates a payment per patient, depending on the treatment given, and which hospitals use to charge primary care trusts.

The commission found that accuracy …
The influence of childhood traffic‐related air pollution exposure on asthma, allergy and sensitization
Authors: E. Fuertes, J. Heinrich, G. Bowatte, C. J. Lodge, A. J. Lowe, B. Erbas, J. Perret, M. J. Abramson, M. C. Matheson, S. C. Dharmage
Journal: Allergy (2015)
κ-Opioid System in Uremic Pruritus
Authors: Bjo[Combining Diaeresis]rn Wikstro[Combining Diaeresis]m, Ryszard Gellert, Søren D. Ladefoged, Yasuaki Danda, Masahiko Akai, Kaoru Ide, Midori Ogasawara, Yoshiharu Kawashima, Koki Ueno, Akio Mori, Yuji Ueno
Journal: Journal of the American Society of Nephrology (2005)

Uremic pruritus is a very common and frustrating condition for both patients and clinicians because no treatment has been demonstrated to be effective in relieving the itch. In this report, nalfurafine, a new kappa-opioid receptor agonist, was used to treat uremic pruritus in patients who were undergoing routine hemodialysis. Two multicenter, randomized, double-blind, placebo-controlled studies enrolled 144 patients with uremic pruritus to postdialysis intravenous treatment with either nalfurafine or placebo for 2 to 4 wk. A meta-analysis approach was used to assess the efficacy of nalfurafine. Statistically significant reductions in worst itching (P = 0.0212), itching intensity (P = 0.0410), and sleep disturbances (P = 0.0003) were noted in the nalfurafine group as compared with placebo. Improvements in itching (P = 0.0025) and excoriations (P = 0.0060) were noted for the nalfurafine-treated patients. Nalfurafine showed similar types and incidences of drug-related adverse events as did placebo. Nalfurafine was shown to be an effective and safe compound for use in this severely ill patient population.