tbuckley/cabot-search huggingface dataset:
Early loss of postextrasystolic potentiation in acutely ischemic myocardium: evaluation by contrast two-dimensional echocardiography.
Authors: T Force, A J Kemper, C Cohen, A F Parisi
Journal: Circulation (1985)

Studies in animals with acutely ischemic hearts have suggested that postextrasystolic potentiation (PESP) may predict the viability of dysfunctional myocardium. Most of these data have been obtained with sonomicrometers and therefore the presence and extent of PESP throughout the entire region at risk has not been defined. In this study we used contrast two-dimensional echocardiography (2DE) to define region at risk in vivo, and then with quantitative 2DE we examined the proportion of the region at risk that demonstrated PESP, the degree of the potentiation, and the time course of this response. The region at risk was divided into a central (inner 50%) and two peripheral (25% each) ischemic zones. Adjacent contrast-enhanced myocardium was divided into near and far border zones that were equal in size to the adjacent peripheral ischemic zone. Systolic thickening was analyzed within each zone along multiple radii at 5, 30, and 120 min after coronary occlusion. PESP was absent in the central ischemic zone at all three times. In the peripheral ischemic zone at 5 min, a small amount of PESP was detected (-4.1% vs + 3.1% for nonpotentiated and potentiated thickening, respectively; p less than .01). At 30 min after occlusion, no potentiation was seen in the region at risk and PESP was confined to the contrast-enhanced near and far border zones. These findings persisted at 120 min. These data indicate that the response to PESP is localized to perfused myocardium by 30 min after acute occlusion. PESP is therefore of limited value in predicting the presence of ischemic, potentially viable myocardium early in the course of acute infarction.
Calcification of glutaraldehyde-fixed porcine xenograft.
Authors: A G Rose, R Forman, R M Bowen
Journal: Thorax (1978)

The clinical and light and electron microscopic findings are reported in a 14-year-old patient who died 12 months after mitral valve replacement with a Hancock prosthesis. Severe cusp calcification had led to immobilisation of the valve and stenosis. Calcification involved the substance of the valve cusps. The cause of the calcification in this patient is unknown.
Of genes, environment, and destiny
Authors: Simona Cabib, Stefano Puglisi-Allegra
Journal: Behavioral and Brain Sciences (1999)

The target article approaches individual differences in terms of phenotypic differences developing through the interaction between a specific genetic make up and environmental variables. This interaction is proposed to be cooperative and oriented toward a progressive stabilisation of the trait. However, experimental data from animal studies indicate that environmental pressure promotes dramatic changes in phenotypic expression in mature organisms. Indeed, environmental constraint not only promotes the phenotypic expression of facilitated VTA-NAS DA transmission in genotype-resistant individuals; it also inhibits its expression in genetically prone individuals. This is in line with negative genotype-environment correlation revealed by behavior genetics.
CD28 costimulatory signal induces protein arginine methylation in T cells
Authors: Fabien Blanchet, Ana Cardona, Fabrice A. Letimier, Michael S. Hershfield, Oreste Acuto
Journal: The Journal of Experimental Medicine (2005)

Protein phosphorylation initiates signal transduction that triggers lymphocyte activation. However, other posttranslational modifications may contribute to this process. Here, we show that CD28 engagement induced protein arginine methyltransferase activity and methylation on arginine of several proteins, including Vav1. Methylation of Vav1 and IL-2 production were reduced by inhibiting S-adenosyl-L-homocysteine hydrolase, an enzyme that regulates cellular transmethylation. Methylated Vav1 was induced in human and mouse T cells and selectively localized in the nucleus, which suggested that this form marks a nuclear function of Vav1. Our findings uncover a signaling pathway that is controlled by CD28 that is likely to be important for T cell activation.
Activity-Dependent Synaptogenesis: Regulation by a CaM-Kinase Kinase/CaM-Kinase I/βPIX Signaling Complex
Authors: Takeo Saneyoshi, Gary Wayman, Dale Fortin, Monika Davare, Naoto Hoshi, Naohito Nozaki, Tohru Natsume, Thomas R. Soderling
Journal: Neuron (2008)
Synergistic Tumor Suppression by Coexpression of <i>FUS1</i> and <i>p53</i> Is Associated with Down-regulation of Murine Double Minute-2 and Activation of the Apoptotic Protease-Activating Factor 1–Dependent Apoptotic Pathway in Human Non–Small Cell Lung Cancer Cells
Authors: Wu-Guo Deng, Hiroyaki Kawashima, Guanglin Wu, Gitanjali Jayachandran, Kai Xu, John D. Minna, Jack A. Roth, Lin Ji
Journal: Cancer Research (2007)

Abstract FUS1 is a novel tumor suppressor gene identified in human chromosome 3p21.3 region. Loss of expression and deficiency of posttranslational modification of FUS1 protein have been found in a majority of human lung cancers. Restoration of wild-type FUS1 in 3p21.3-deficient human lung cancer cells exhibited a potent tumor suppression function in vitro and in vivo. In this study, we evaluated the combined effects of FUS1 and tumor suppressor p53 on antitumor activity and explored the molecular mechanisms of their mutual actions in human non–small cell lung cancer (NSCLC) cells. We found that coexpression of FUS1 and p53 by N-[1-(2,3-dioleoyloxyl)propyl]-NNN-trimethylammoniummethyl sulfate:cholesterol nanoparticle–mediated gene transfer significantly and synergistically inhibited NSCLC cell growth and induced apoptosis in vitro. We also found that a systemic treatment with a combination of FUS1 and p53 nanoparticles synergistically suppressed the development and growth of tumors in a human H322 lung cancer orthotopic mouse model. Furthermore, we showed that the observed synergistic tumor suppression by FUS1 and p53 concurred with the FUS1-mediated down-regulation of murine double minute-2 (MDM2) expression, the accumulation and stabilization of p53 protein, as well as the activation of the apoptotic protease-activating factor 1 (Apaf-1)–dependent apoptotic pathway in human NSCLC cells. Our results therefore provide new insights into the molecular mechanism of FUS1-mediated tumor suppression activity and imply that a molecular therapy combining two or more functionally synergistic tumor suppressors may constitute a novel and effective strategy for cancer treatment. [Cancer Res 2007;67(2):709–17]
In vivo cyclooxygenase expression in synovial tissues of patients with rheumatoid arthritis and osteoarthritis and rats with adjuvant and streptococcal cell wall arthritis.
Authors: H Sano, T Hla, J A Maier, L J Crofford, J P Case, T Maciag, R L Wilder
Journal: Journal of Clinical Investigation (1992)

Cyclooxygenase (COX), or prostaglandin (PG) H synthase, plays a role in inflammatory diseases, but very limited data exist on the regulation of COX in vivo. We, therefore, studied the in vivo expression of COX in synovia from patients with rheumatoid arthritis (RA) and osteoarthritis (OA), as well as joints of rats with streptococcal cell wall (SCW) and adjuvant arthritis. Extensive and intense intracellular COX immunostaining, which correlated with the extent and intensity of mononuclear cell infiltration, was observed in cells throughout RA synovia. Significantly less or equivocal staining was noted in OA and normal human synovia. Similarly, COX immunostaining was equivocal in the joints of normal and arthritis-resistant F344/N rats. In contrast, high level expression developed rapidly in euthymic female Lewis (LEW/N) rats throughout the hindlimb joints and overlying tissues including skin, preceding or paralleling clinically apparent experimental arthritis. COX was expressed in the joints of athymic LEW.rnu/rnu rats 2-4 d after injection of SCW or adjuvant but was not sustained. Physiological doses of antiinflammatory glucocorticoids, but not progesterone, suppressed both arthritis and COX expression in LEW/N rats. These observations suggest that, in vivo, (a) COX expression is upregulated in inflammatory joint diseases, (b) the level of expression is genetically controlled and is a biochemical correlate of disease severity, (c) sustained high level up-regulation is T cell dependent, and (d) expression is down-regulated by antiinflammatory glucocorticoids.
Risk Factors for Sleep-disordered Breathing in Children
Authors: SUSAN REDLINE, PETER V. TISHLER, MARK SCHLUCHTER, JOAN AYLOR, KATHRYN CLARK, GREGORY GRAHAM
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

This study examined risk factors for sleep-disordered breathing (SDB) in children and adolescents; specifically, quantifying risk associated with obesity, race, and upper and lower respiratory problems. Subjects were participants in a genetic-epidemiologic study of SDB and included 399 children and adolescents 2 to 18 yr of age, recruited as members of families with a member (a proband) with known sleep apnea (31 index families) or as members of neighborhood control families (30 families). SDB was assessed with home overnight multichannel monitoring and SDB was defined based on an apneahypopnea index ⩾ 10 (moderately affected) or < 5 (unaffected). SDB of moderate level was significantly associated with obesity (odds ratio, 4.59; 95% confidence interval [CI], 1.58 to 13.33) and African-American race (odds ratio, 3.49; 95% CI, 1.56 to 8.32) but not with sex or age. After adjusting for obesity, proband sampling, race and familial clustering, sinus problems and persistent wheeze each independently (of the other) predicted SDB. These data suggest the importance of upper and lower respiratory problems and obesity as risk factors for SDB in children and adolescents. Increased risk in African Americans appears to be independent of the effects of obesity or respiratory problems.
Cost of NHS and education grows faster than general economy
Authors: A. O'Dowd
Journal: BMJ (2009)

The cost of providing NHS services has risen faster in the past 10 years than costs throughout the whole economy, according to new figures from the Office for National Statistics (ONS).

The office has also confirmed its findings published in June that the NHS’s productivity has fallen in the past 10 years despite large cash injections.

The office regularly examines public sector productivity, but the Changing Costs of Public Services report contains a new measure called “relative unit cost of public service output.”

This wider measure takes into account productivity (how much input …
Hyperbaric Oxygen and Radiobiology of a C3H Mouse Mammary Carcinoma&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: H D Suit, M Maeda
Journal: JNCI Journal of the National Cancer Institute (1967)

A series of radiation dose-tumor control response assays was performed on the first-to-Fourth generation isotransplants of a C3H/J mouse mammary carcinoma For radiation administered under four different conditions: hypoxia, a damp across the root of the tumor-bearing part for 1 minute before treatmenti air, animal respiring air at one atmosphere of pressurei O2 30 or 44 psi, animal respiring pure oxygen at 30 or 44 psi for 15 minutes before and during local tumor irradiation. When radiation was administered as a single dose (v = 1) to 250 mm3 tumors, high pressure oxygen was only modestly effective in reducing the tumor control dose (TCDSO); TCD50 hypoxia/O2 30 psi and TCD50 hypoxia/O2 44 psi were only 1.2 and 1.3, respectively. However, for similar treatment of 0.6 mm3 tumors and of even smaller “microcolonies,” the ratios TCD50 hypoxia/O2 44 psi were 2.5 and 3.2, respectively. These results are discussed with respect to simple tumor models so as to estimate the proportion of hypoxic cells present in tumors under normal conditions and the influence of oxygen breathed at increased pressure on that proportion. High pressure oxygen was found much more effective when combined with fractionated irradiation (v = 10) than with single-dose therapy. Thus TCD50 hypoxia/O2 30 psi was 2.2 (v = 10) instead of 1.2 (v = 1). finally, the ratio TCD50 hypoxia v = 10/v = 1 was 2.15. These results are reviewed and inferences drawn as to the extent of tumor cell proliferation between treatments, repair of sublethal radiation injury by hypoxic cells, and the movement of cells from the hypoxic compartment to the aerobic compartment during fractionated irradiation (v = 10) under normal conditions.
Superiority of thalidomide and dexamethasone over vincristine-doxorubicindexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma
Authors: Michele Cavo, Elena Zamagni, Patrizia Tosi, Paola Tacchetti, Claudia Cellini, Delia Cangini, Antonio de Vivo, Nicoletta Testoni, Chiara Nicci, Carolina Terragna, Tiziana Grafone, Giulia Perrone, Michela Ceccolini, Sante Tura, Michele Baccarani
Journal: Blood (2005)
Notes of a Case of Porro's Operation
Authors: T. S. Wells
Journal: BMJ (1887)

the particular pabulum in the body suited for its growth may be very rapidly used up, and so spore-formation ensue.It has been endeavoured thus to find out, by a long course of careful investigations, embodying the results of several thousands of cultiva- tions, the specific cause of scarlet fever, and these, the records of such, are now placed before the medical fraternity.
Robustness of Coalescent Estimators to Between-Lineage Mutation Rate Variation
Authors: M. K. Kuhner
Journal: Molecular Biology and Evolution (2006)

Data from HIV and from human neoplastic cells can show substantial between-lineage mutation rate variation even within a single population. Such variation may affect estimators of population quantities such as Θ = 4Neμ. Using simulated DNA data, I measured the effect of rate variation on recovery of Θ by the summary-statistic estimator of Watterson (Watterson GA. 1975. On the number of segregating sites in genetical systems without recombination. Theor Popul Biol. 7:256–276) and the coalescent maximum likelihood algorithm LAMARC (Kuhner MK. 2006. LAMARC 2.0: maximum likelihood and Bayesian estimation of population parameters. Bioinformatics. Advance Access doi: 10.1093/bioinformatics/btk051). Watterson's estimator showed a downward bias, as expected, with high values of Θ. LAMARC's mean estimate was accurate for all tested values of Θ and rate variation except for a downward bias when rate variation was maximal (i.e., the slow rate was zero). LAMARC had consistently narrower confidence intervals (CIs) than Watterson's estimator. Both methods tended to reject the truth too often when rate variation was 8x or greater and independent among branches, as well as when variation was 4x or greater and correlated among branches. In the case of Watterson's estimate, this excess rejection was fully attributable to variation among genealogies in the amount of total branch length associated with the fast and slow rates. However, in the case of LAMARC, some excess rejection was still observed even when between-genealogy variation was taken into account. Both estimators are robust to modest rate variation; however, their use should be coupled with a statistical test to rule out extreme rate variation as the resulting CIs may not be reliable.
Induction of Nasal Tumors in Rats Exposed to Hexamethylphosphoramide by Inhalation
Authors: K P Lee, H J Trochimowicz
Journal: JNCI Journal of the National Cancer Institute (1982)

Charles River-CD Sprague-Dawley rats in 4 equal groups of 240 each were exposed to 4,000, 400, 50, and 0 ppb of hexamethylphosphoramide (HMPA) vapor for 9 to 24 months. In an additional study, 4 equal groups of 200 rats were similarly exposed to 100, 50, 10, and 0 ppb HMPA vapor. Nasal tumors were first detected after approximately 7 months exposure at 4,000 and 400 ppb, after 9 months at 100 ppb, and 12 months at 50 ppb. No HMPA-related lesions were found at 10 ppb. Tumor incidence was 83% at 4,000 ppb exposure, 82% at 400 ppb, 38% at 100 ppb, and 20% at 50 ppb after 24 months of exposure. Most tumors developed from the squamous, respiratory epithelium and nasal gland both of which showed squamous metaplasia or dysplasia in the anterior nasal cavity. Exposure concentrations correlated with tumor induction and latency but not with tumor types. Of a total of 473 nasal tumors, epidermoid carcinoma was predominant (71.9%) followed by adenoid squamous carcinoma (15%), papilloma (8.2%), transitional (respiratory epithelial) carcinoma (1.9%), adenocarcinoma (1.3%), and undifferentiated tumor (1.1%), (mixed) pleomorphic tumor (0.4%), and adenomatous polyp (0.2%). Most tumors developed in the anterior nasal cavity (59.1%), then progressed to the posterior nasal cavity (40.9%). Only 0.4% of the tumors involved the posterior nasal cavity alone. Tumors invaded the nasal bone (47.5%) and brain (1.1%), or metastasized to the lung (1.5%) and cervical lymph nodes (1.1%). Malignancy of the epidermoid carcinoma was correlated to the cellular differentiation and degree of keratinization.
ST-Segment Recovery Adds to the Assessment of TIMI 2 and 3 Flow in Predicting Infarct Wall Motion After Thrombolytic Therapy
Authors: Jacqueline Andrews, Ivan T. Straznicky, John K. French, Cindy L. Green, Arthur C. P. Maas, Mayanna Lund, Mitchell W. Krucoff, Harvey D. White
Journal: Circulation (2000)

Background —Early resolution of ST-segment elevation (ST-segment recovery) is associated with an improved outcome after infarction. Whether this relation is present in patients with Thrombolysis In Myocardial Infarction (TIMI) grade 2 or 3 flow (ie, patent) infarct-related arteries is not known. Methods and Results —To examine the associations between time to achieve stable 50% ST-segment recovery assessed by continuous ECG monitoring, infarct artery flow, and infarct zone wall motion (at 48 hours), we studied 134 patients who underwent angiography at 99 (interquartile range 92 to 110) minutes after commencing streptokinase, initiated within 12 hours of onset of symptoms of myocardial infarction. Patients with TIMI 2 or 3 flow who failed to achieve early stable ST-segment recovery (50% ST-segment recovery sustained for ≥4 hours with &lt;100 μV change in the peak lead) by 60 or 90 minutes had a higher fraction of chords in the infarct zone &gt;2 SD below normal wall motion (TIMI 2: 55.5% vs 15.3%, P =0.006; and 56.5% vs 26.8%, P =0.01, respectively; and TIMI 3: 48.8% vs 28.3%, P =0.07; and 51.8% vs 29.9%, P =0.03, respectively). Time to stable ST-segment recovery was a multivariate predictor of infarct zone wall motion ( P =0.04) independent of TIMI flow grade and the time from symptom onset to streptokinase therapy. Conclusions —In patients with TIMI 2 or 3 flow in infarct-related artery, early stable ST-segment recovery is associated with improved infarct zone wall motion at 48 hours. ST-segment recovery may provide additional information about the degree of myocyte reperfusion achieved in patients with a patent epicardial infarct-related artery after thrombolytic therapy.
Arteriovenous Malformations of the Brain
Authors: Robert M. Friedlander
Journal: New England Journal of Medicine (2007)

A 51-year-old woman presents with a generalized tonic–clonic seizure. After a brief postictal period, she recovers and reports no headache or other neurologic symptoms. She takes no medications and her medical history is unremarkable. Computed tomography of the head suggests a right occipital arteriovenous malformation, without evidence of hemorrhage. Imaging studies show a right occipital arteriovenous malformation as well as a feeding-artery aneurysm.
The CT-STAT (Coronary Computed Tomographic Angiography for Systematic Triage of Acute Chest Pain Patients to Treatment) Trial
Authors: James A. Goldstein, Kavitha M. Chinnaiyan, Aiden Abidov, Stephan Achenbach, Daniel S. Berman, Sean W. Hayes, Udo Hoffmann, John R. Lesser, Issam A. Mikati, Brian J. O'Neil, Leslee J. Shaw, Michael Y.H. Shen, Uma S. Valeti, Gilbert L. Raff
Journal: Journal of the American College of Cardiology (2011)
GABA receptor agonists: Pharmacological spectrum and therapeutic actions
Authors: G. Bartholini
Journal: Medicinal Research Reviews (1985)

From the data discussed in this review it appears that GABA receptor agonists exhibit a variety of actions in the central nervous system, some of which are therapeutically useful (Table V). GABA receptor agonists, by changing the firing rate of the corresponding neurons accelerate noradrenaline turnover without changes in postsynaptic receptor density and diminish serotonin liberation with an up-regulation of 5HT2 receptors. These effects differ from those of tricyclic antidepressants which primarily block monoamine re-uptake and cause down-regulation of beta-adrenergic and 5HT2 receptors. The GABA receptor agonist progabide has been shown to exert an antidepressant action which is indistinguishable from that of imipramine in patients with major affective disorders. The fact that: (a) GABA receptor agonists and tricyclic antidepressants affect noradrenergic and serotonergic transmission differently; and (b) tricyclic antidepressants alter GABA-related parameters challenges the classical monoamine hypothesis of depression and suggests that GABA-mediated mechanisms play a role in mood disorders. Decreases in cellular excitability produced by GABAergic stimulation leads to control of seizures in practically all animal models of epilepsy. GABA receptor agonists have a wide spectrum as they antagonize not only seizures which are dependent on decreased GABA synaptic activity but also convulsant states which are apparently independent of alterations in GABA-mediated events. These results in animals are confirmed in a wide range of human epileptic syndromes. GABA receptor agonists decrease dopamine turnover in the basal ganglia and antagonize neuroleptic-induced increase in dopamine release. On repeated treatment, progabide prevents or reverses the neuroleptic-induced up-regulation of dopamine receptors in the rat striatum and antagonizes the concomitant supersensitivity to dopaminomimetics. Behaviorally, GABA receptor agonists diminish the stereotypies induced by apomorphine or L-DOPA suggesting that GABAergic stimulation results also in an antidopaminergic action which is exerted beyond the dopamine synapse. These effects of GABA receptor agonists may represent the basis of the antidyskinetic action of these compounds which, however, remains to be fully confirmed. GABA receptor agonists reduce striatal acetylcholine turnover, an effect which occurs at doses much lower than those which affect dopamine neurons. Since hyperactivity of cholinergic neurons plays a determinant role in the pathogenesis of some parkinsonian symptoms, it is conceivable that GABAergic stimulation is effective in ameliorating Parkinson's disease.(ABSTRACT TRUNCATED AT 400 WORDS)
A phase III, randomized, open label study to evaluate the safety and efficacy of imiquimod 5% cream applied thrice weekly for 8 and 12 weeks in the treatment of low-risk nodular basal cell carcinoma
Authors: Thomas K. Eigentler, Anne Kamin, Benjamin M. Weide, Helmut Breuninger, Ulrich M. Caroli, Matthias Möhrle, Peter Radny, Claus Garbe
Journal: Journal of the American Academy of Dermatology (2007)