tbuckley/cabot-search huggingface dataset:
FURTHER EVIDENCE CONCERNING THE AUTOANTIGENIC STATUS OF THE TROPHOBLAST
Authors: Alan E. Beer, R. E. Billingham, S. L. Yang
Journal: The Journal of Experimental Medicine (1972)

Heterologous antisera were raised by inoculation of rabbits with fairly pure suspensions of trophoblast, lymphoid, fetal (excluding placental components), epidermal, decidual, and renal cells from Fischer rats. After absorption of hemagglutinins, these antisera were assayed for abortifacient activity by intramuscular inoculation into time-mated Fischer females. The anti-trophoblast serum aborted all the recipients, but had some nonspecific activity in that it caused the deaths of 12% of them. Anti-lymphocyte serum was more toxic and less potent as an abortifacient. None of the other sera harmed either the mothers or their fetuses. However, the anti-kidney cell serum caused kidney lesions. Absorption of the anti-trophoblast serum with lymphoid cells completely removed its toxicity for the pregnant females without perceptible impairment of its abortifacient activity. However, the latter could be removed by absorption with trophoblast cells. (a) The lymphocyte-absorbed anti-trophoblast serum was equally effective in aborting rats over the range 7-18 days postconception; (b) a single injection of 1 ml was sufficient in most cases, and (c) it was equally efficacious in terminating gestation in rats irrespective of their genetic constitution, and (d) its effect was highly species-specific. These findings support the premise that a unique antigen (or antigens), of possible clinical significance, is associated with trophoblast cells.
Decline in Incident Coronary Heart Disease
Authors: Russell V. Luepker
Journal: Circulation (2008)

I n the fall of 1979, the National Heart, Lung, and Blood Institute held a conference on the decline in coronary heart disease (CHD) death rates.It was apparent that in the previous 10 to 15 years, the epidemic crested and began to fall. 1 The reasons for this decline were unclear, but many hypotheses were offered.Explanations ranged from death classification artifact, new coronary care units, and coronary surgery to broad social change.Many were more than willing to take credit for this change, but few data were available.A search for explanations began.
New concepts of the pathogenesis of cystic fibrosis lung disease
Authors: R.C. Boucher
Journal: European Respiratory Journal (2003)

Although there has been impressive progress in the elucidation of the genetic and molecular basis of cystic fibrosis (CF), the pathogenesis of CF lung disease remains obscure. The elucidation of the pathogenesis of CF lung disease requires both a full description of normal innate airway defence and how absent function of the cystic fibrosis transmembrane regulator protein (CFTR) adversely perturbs this activity. Recent data have linked the abnormal ion transport properties of CF airway epithelia to depleted airway surface liquid (ASL) volume, reflecting the combined defects of accelerated Na+ transport and the failure to secrete Cl-. Depletion of a specific compartment of the ASL, i.e. the periciliary liquid (PCL), appears to abrogate both cilia-dependent and cough clearance. Subsequent to PCL depletion, mucus adheres to airway surfaces and persistent mucin secretion generates the formation of "thickened" mucus plaques and plugs, which become the nidus for bacterial infection. The paucity of liquid in these plaques/plugs, and the hypoxia in this environment, appear to promote biofilm bacterial infection. Therapeutic agents that restore airway surface liquid volume, i.e. blockers of Na+ transport, initiators of Cl- transport and osmolytes, are reviewed, as are strategies that may be required to use volume-restoring agents safely in patients with cystic fibrosis.
Isocitrate-to-SENP1 signaling amplifies insulin secretion and rescues dysfunctional β cells
Authors: Mourad Ferdaoussi, Xiaoqing Dai, Mette V. Jensen, Runsheng Wang, Brett S. Peterson, Chao Huang, Olga Ilkayeva, Nancy Smith, Nathanael Miller, Catherine Hajmrle, Aliya F. Spigelman, Robert C. Wright, Gregory Plummer, Kunimasa Suzuki, James P. Mackay, Martijn van de Bunt, Anna L. Gloyn, Terence E. Ryan, Lisa D. Norquay, M. Julia Brosnan, Jeff K. Trimmer, Timothy P. Rolph, Richard G. Kibbey, Jocelyn E. Manning Fox, William F. Colmers, Orian S. Shirihai, P. Darrell Neufer, Edward T.H. Yeh, Christopher B. Newgard, Patrick E. MacDonald
Journal: Journal of Clinical Investigation (2015)

Insulin secretion from β cells of the pancreatic islets of Langerhans controls metabolic homeostasis and is impaired in individuals with type 2 diabetes (T2D). Increases in blood glucose trigger insulin release by closing ATP-sensitive K+ channels, depolarizing β cells, and opening voltage-dependent Ca2+ channels to elicit insulin exocytosis. However, one or more additional pathway(s) amplify the secretory response, likely at the distal exocytotic site. The mitochondrial export of isocitrate and engagement with cytosolic isocitrate dehydrogenase (ICDc) may be one key pathway, but the mechanism linking this to insulin secretion and its role in T2D have not been defined. Here, we show that the ICDc-dependent generation of NADPH and subsequent glutathione (GSH) reduction contribute to the amplification of insulin exocytosis via sentrin/SUMO-specific protease-1 (SENP1). In human T2D and an in vitro model of human islet dysfunction, the glucose-dependent amplification of exocytosis was impaired and could be rescued by introduction of signaling intermediates from this pathway. Moreover, islet-specific Senp1 deletion in mice caused impaired glucose tolerance by reducing the amplification of insulin exocytosis. Together, our results identify a pathway that links glucose metabolism to the amplification of insulin secretion and demonstrate that restoration of this axis rescues β cell function in T2D.
MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1
Authors: Peixin Dong, Masanori Kaneuchi, Hidemichi Watari, Junichi Hamada, Satoko Sudo, Jingfang Ju, Noriaki Sakuragi
Journal: Molecular Cancer (2011)

Abstract Background Epithelial-mesenchymal transition (EMT) is the key process driving cancer metastasis. Oncogene/self renewal factor BMI-1 has been shown to induce EMT in cancer cells. Recent studies have implied that noncoding microRNAs (miRNAs) act as crucial modulators for EMT. The aims of this study was to determine the roles of BMI-1 in inducing EMT of endometrial cancer (EC) cells and the possible role of miRNA in controlling BMI-1 expression. Methods and results We evaluated the expression of BMI-1 gene in a panel of EC cell lines, and detected a strong association with invasive capability. Stable silencing of BMI-1 in invasive mesenchymal-type EC cells up-regulated the epithelial marker E-cadherin, down-regulated mesenchymal marker Vimentin, and significantly reduced cell invasion in vitro . Furthermore, we discovered that the expression of BMI-1 was suppressed by miR-194 via direct binding to the BMI-1 3'-untranslated region 3'-UTR). Ectopic expression of miR-194 in EC cells induced a mesenchymal to epithelial transition (MET) by restoring E-cadherin, reducing Vimentin expression, and inhibiting cell invasion in vitro . Moreover, BMI-1 knockdown inhibited in vitro EC cell proliferation and clone growth, correlated with either increased p16 expression or decreased expression of stem cell and chemoresistance markers (SOX-2, KLF4 and MRP-1). Conclusion These findings demonstrate the novel mechanism for BMI-1 in contributing to EC cell invasion and that repression of BMI-1 by miR-194 could have a therapeutic potential to suppress EC metastasis.
The Use of the P Wave for Control of a Pacemaker in Heart Block
Authors: C. K. Battye, F. E. Weale
Journal: Thorax (1960)

<h3>Objectives</h3> Postnatal thyroid dysfunction is common in preterm infants but the relationship between mild dysfunction and neurodevelopment is unclear. Our aim is to describe the relationship between thyroid function and neurodevelopment. <h3>Design</h3> Cohort analysis. <h3>Patients</h3> 1275 infants born under 31 weeks’ gestation; there were no exclusion criteria. <h3>Setting</h3> The infants were part of a UK daily iodine supplementation trial. <h3>Main outcomes</h3> Thyroid-stimulating hormone, thyroid-binding globulin and total thyroxine levels were measured in dried blood spots on postnatal days 7, 14, 28 and the equivalent of 34 weeks’ gestation. Neurodevelopment was measured using the Bayley-III Scales of infant development at 2 years of age. <h3>Results</h3> No infant was identified as hypothyroid through routine screening. The 3% of infants consistently in the top decile of gestationally age-adjusted thyroid-stimulating hormone levels had a reduction in cognitive score of 7 Bayley units when compared with those not in the top decile (95% CI –13 to –1). A reduction in motor composite score of 6 units (95% CI −12 to &lt;−0.1) and fine motor score of 1 unit (95% CI –2 to –0.1) was also identified. The 0.7% of infants consistently in the bottom decile of age-adjusted thyroxine levels had a reduction in motor composite score of 14 units (95% CI –25 to –2) and its two subset scores, fine and gross motor, of 2 units (95% CI respectively −4.5 to &lt;−0.1 and –4.3 to –0.3). <h3>Conclusions</h3> Preterm infants with consistent ‘mild’ thyroid dysfunction score less on neurodevelopmental tests at 2 years of age. Many of these infants will not be detected by current clinical protocols or screening programmes.
Prophylactic administration of parenteral steroids for preventing airway complications after extubation in adults: meta-analysis of randomised placebo controlled trials
Authors: T. Fan, G. Wang, B. Mao, Z. Xiong, Y. Zhang, X. Liu, L. Wang, S. Yang
Journal: BMJ (2008)

<b>Objective</b> To determine whether steroids are effective in preventing laryngeal oedema after extubation and reducing the need for subsequent reintubation in critically ill adults. <b>Design</b> Meta-analysis. <b>Data sources</b> PubMed, Cochrane Controlled Trials Register, Web of Science, and Embase with no limitation on language, study year, or publication status. <b>Selection criteria</b> Randomised placebo controlled trials in which parenteral steroids were compared with placebo for preventing complications after extubation in adults. <b>Review methods</b> Search, application of inclusion and exclusion criteria, data extraction, and assessment of methodological quality, independently performed in duplicate. Odds ratios with 95% confidence intervals, risk difference, and number needed to treat were calculated and pooled. <b>Main outcome measures</b> Primary outcome: laryngeal oedema after extubation. Secondary outcome: subsequent reintubation because of laryngeal oedema. <b>Results</b> Six trials (n=1923) were identified. Compared with placebo, steroids given before planned extubation decreased the odds ratio for laryngeal oedema (0.38, 95% confidence interval 0.17 to 0.85) and subsequent reintubation (0.29, 0.15 to 0.58), corresponding with a risk difference of −0.10 (−0.12 to −0.07; number needed to treat 10) and −0.02 (−0.04 to −0.01; 50), respectively. Subgroup analyses indicated that a multidose regimen of steroids had marked positive effects on the occurrence of laryngeal oedema (0.14; 0.08 to 0.23) and on the rate of subsequent reintubation (0.19; 0.07 to 0.50), with a risk difference of −0.19 (−0.24 to −0.15; 5) and −0.04 (−0.07 to −0.02; 25). In single doses there was only a trend towards benefit, with the confidence interval including 1. Side effects related to steroids were not found. <b>Conclusion</b> Prophylactic administration of steroids in multidose regimens before planned extubation reduces the incidence of laryngeal oedema after extubation and the consequent reintubation rate in adults, with few adverse events.
A time-released osmotic pump fabricated by compression-coated method: Formulation screen, mechanism research and pharmacokinetic study
Authors: Tiegang Xin, Yang Zhao, Hengpan Jing, Wenji Zhang, Yunyun Gao, Xinggang Yang, Xukai Qu, Weisan Pan
Journal: Asian Journal of Pharmaceutical Sciences (2014)

In this investigation, time-released monolithic osmotic pump (TMOP) tablets containing diltiazem hydrochloride (DIL) were prepared on the basis of osmotic pumping mechanism. The developed dosage forms were coated by Kollidon®SR-Polyethylene Glycol (PEG) mixtures via compression-coated technology instead of spray-coating method to form the outer membrane. For more efficient formulation screening, a three-factor five-level central composite design (CCD) was introduced to explore the optimal TMOP formulation during the experiments. The in vitro tests showed that the optimized formulation of DIL-loaded TMOP had a lag time of 4 h and a following 20-h drug release at an approximate zero-order rate. Moreover, the release mechanism was proven based on osmotic pressure and its profile could be well simulated by a dynamic equation. After oral administration by beagle dogs, the comparison of parameters with the TMOP tablets and reference preparations show no significant differences for Cmax (111.56 ± 20.42, 128.38 ± 29.46 ng/ml) and AUC0-48 h (1654.97 ± 283.77, 1625.10 ± 313.58 ng h/ml) but show significant differences for Tmax (13.00 ± 1.16, 4.00 ± 0.82 h). These pharmacokinetic parameters were consistent with the dissolution tests that the TMOP tablets had turned out to prolong the lag time of DIL release.
Abdominal muscle training in sport.
Authors: C M Norris
Journal: British Journal of Sports Medicine (1993)

This paper evaluates several abdominal exercises, and highlights factors which are important for their safe prescription and effective use. The function of the abdominal muscles and hip flexors is considered, and the importance of the infra-umbilical portion of the rectus abdominis is emphasized. The effects of flexion on the lumbar spine are outlined. The trunk curl, sit-up, and straight leg raise are analysed, together with modifications of these exercises. The effect of foot fixation and hip flexion during the performance of the sit-up is discussed. The sit-up performed with foot fixation, and the bilateral straight leg raise can compound hip muscle imbalance, and both hyperextend and hyperflex the lumbar spine and are therefore not recommended. The importance of muscular control of pelvic tilt is considered with reference to muscle imbalance around the pelvis. It is recommended that a musculoskeletal assessment should be performed before prescribing abdominal exercises. Exercise therapy to re-educate control of pelvic tilt is described. Intra-abdominal pressure, and the effects of abdominal exercise on this mechanism, and lumbar stabilization are examined. The importance of training specificity is stressed.
Fasting proinsulin concentrations predict the development of type 2 diabetes.
Authors: N J Wareham, C D Byrne, R Williams, N E Day, C N Hales
Journal: Diabetes Care (1999)

The development of specific assays allows the different molecules in the proinsulin processing pathway to be measured separately. 32,33 Split proinsulin is the predominant form of proinsulin and accounts for the disproportionate hyperproinsulinemia seen in individuals with prevalent type 2 diabetes. This study was established to examine whether the concentration of this molecule predicts diabetes.A population-based longitudinal cohort study was conducted in Ely, Cambridgeshire. At baseline, 1,122 individuals completed a 75-g oral glucose tolerance test (OGTT). At the 4.5-year follow-up study, repeat OGTTs were performed on 937 of the cohort of 1,071 individuals who had been nondiabetic at baseline.A total of 26 people progressed to diabetes as determined by the OGTTs. The risk of progression was strongly related to the fasting glucose concentration (relative risk [RR] comparing top with bottom quartile 17.6 [95% CI 2.4-130.4]) and fasting 32,33 split proinsulin (RR 16.4 [2.2-121.9]), but less strongly to the fasting insulin (RR 4.41 [1.5-12.9]) or intact proinsulin (RR 5.2 [1.5-17.3]). In multivariate analyses, these associations were independent of age, sex, BMI, and baseline glucose tolerance category. Subjects in the top quartile for fasting glucose and total proinsulin with a family history of diabetes were a high-risk subgroup (incidence 65.8 per 1,000 person-years of follow-up [pyfu]); 30% of them progressed to diabetes at follow-up.Fasting 32,33 split proinsulin independently predicts the development of diabetes. This prediction was better than that observed for either the insulin or intact proinsulin concentrations. The combination of family history, fasting glucose, and total proinsulin identified a subgroup of individuals at high risk of progression who might benefit from targeted interventions.
Regulation of Endothelial Nitric Oxide Synthase Expression in the Vascular Wall and in Mononuclear Cells From Hypercholesterolemic Rabbits
Authors: Ana Jiménez, María M. Arriero, Almudena López-Blaya, Fernando González-Fernandez, Rosa García, José Fortes, Inmaculada Millás, Sandra Velasco, Lourdes Sánchez de Miguel, Luis Rico, Jerónimo Farré, Santos Casado, Antonio López-Farré
Journal: Circulation (2001)

Background We recently obtained evidence demonstrating that cultured bovine endothelial cells contain cytosolic proteins that form complexes with the 3′-untranslated region of endothelial nitric oxide synthase (eNOS) mRNA and are associated with its destabilization. The aim of this study was to determine the presence of such proteins and eNOS expression in hypercholesterolemic rabbits as an in vivo model of endothelial dysfunction. Methods and Results Endothelium-dependent relaxation to acetylcholine and the calcium ionophore A23187 was reduced in aortic segments from hypercholesterolemic rabbits compared with controls. Treatment of hypercholesterolemic rabbits with cerivastatin (0.1 mg · kg body wt −1 · d −1 ) restored endothelium-dependent relaxation. Aortic eNOS expression was reduced in hypercholesterolemic rabbits and was accompanied by enhanced binding activity of a 60-kDa cytosolic protein and reduced stability of eNOS mRNA. Cerivastatin treatment upregulated eNOS expression and reduced the interaction of the cytosolic protein with the 3′-untranslated region of eNOS mRNA. Mononuclear cells from hypercholesterolemic rabbits also showed a marked reduction of eNOS expression and eNOS mRNA stability and an increase in binding activity of the cytosolic protein, which were also prevented by cerivastatin treatment. Conclusions These results demonstrate the presence of a 60-kDa protein that binds to eNOS mRNA and reductions in eNOS expression in both vascular wall and mononuclear cells that are prevented by cerivastatin.
Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice (COMPARE): a randomised trial
Authors: Elvin Kedhi, Kaiyum Sheik Joesoef, Eugene McFadden, Jochem Wassing, Carlos van Mieghem, Dick Goedhart, Pieter Cornelis Smits
Journal: The Lancet (2010)
Follicle dynamics and anovulation in polycystic ovary syndrome
Authors: S. Franks, J. Stark, K. Hardy
Journal: Human Reproduction Update (2008)

Polycystic ovary syndrome (PCOS) is the commonest cause of anovulatory infertility and menstrual cycle abnormalities, but the factors responsible for failure to select a dominant follicle remain unclear. Source is authors' own studies and search of the relevant literature. Arrest of antral follicle growth is associated with an abnormal endocrine environment involving hypersecretion of luteinizing hormone and insulin (and perhaps hyperandrogenism). The net effect is secondary suppression of FSH, which leads to inhibition of maturation of otherwise healthy follicles in the cohort. There is, however, emerging evidence for an intrinsic abnormality of folliculogenesis in PCOS that affects the very earliest, gonadotrophin independent, stages of follicle development. There is an increased density of small pre-antral follicles and an increased proportion of early growing follicles. These abnormalities in anovulatory PCOS are further defined by abnormal granulosa cell proliferation and disparate growth of oocyte and surrounding granulosa cells. This suggests that the normal 'dialogue' between oocyte and granulosa cells in these early growing follicles is altered. There is evidence that abnormal, local (follicle-to-follicle) signalling of anti-Müllerian hormone may play a part in disordered folliculogenesis, but it is plausible that other local regulators that have been implicated in normal and abnormal pre-antral follicle development—such as insulin-like growth factors and sex steroids—have a role in aberrant folliculogenesis in PCOS. Significant abnormalities in the very earliest stages of folliculogenesis may be the root cause of anovulation in PCOS.
Clinical highlights from the 2011 ERS Congress in Amsterdam
Authors: Martijn A. Spruit, Niels H. Chavannes, Felix J.F. Herth, Venerino Poletti, Sebastian Ley, Otto C. Burghuber, Enrico Clini, Vincent Cottin
Journal: European Respiratory Journal (2012)

This article reports on selected papers pertinent to the most important clinical problems in the field of respiratory medicine. Expert authors from the Clinical Assembly of the European Respiratory Society (ERS) have selected updated reports related to presentations given at the 2011 ERS Annual Congress, which was held in Amsterdam (the Netherlands) and attended by more than 20,000 participants. The hot topics and selected abstracts from the scientific groups of the Clinical Assembly are discussed here in the context of recent literature.
Identification and characterization of leukotriene C4 receptors in isolated rat renal glomeruli.
Authors: B J Ballermann, R A Lewis, E J Corey, K F Austen, B M Brenner
Journal: Circulation Research (1985)

The immediate reduction of renal blood flow and glomerular filtration rate in response to intravenous infusion of leukotriene C4 in the rat prompted an analysis of isolated rat renal glomeruli for the presence of specific receptors for leukotriene C4. Specific binding of [3H]leukotriene C4 to glomeruli increased in a time-dependent manner, reached equilibrium after 60 minutes of incubation at 4 degrees C, and was 80% reversible upon addition of excess unlabeled leukotriene C4 at equilibrium. Specific binding of [3H]leukotriene C4 to glomeruli increased in a dose-dependent manner, approaching saturation at concentrations of 40-60 nM. Inhibition of binding of [3H]leukotriene C4 with increasing concentrations of unlabeled leukotriene C4 was dose dependent. The equilibrium dissociation constant for [3H]leukotriene C4 binding to glomeruli, calculated from saturation and competitive binding-inhibition studies, was 25 +/- 7 nM and 35 +/- 16 nM (mean +/- SEM), respectively, and glomerular leukotriene C4 receptor density was 8.5 +/- 1.5 and 9.0 +/- 3.0 pmol/mg protein, respectively. The other natural vasoactive sulfidopeptide leukotrienes, leukotriene D4 and leukotriene E4, the chemotactic agent, leukotriene B4, and the sulfidopeptide leukotriene antagonist, FPL 55712, competed for the receptor at concentrations 2-3 orders of magnitude higher than the homoligand, leukotriene C4. The binding and specificity characteristics of the glomerular leukotriene C4 receptor are similar to those previously reported for the DDT1 nonvascular smooth muscle cell line derived from hamster vas deferens, for guinea pig ileum smooth muscle, and for a subcellular fraction of rat lung homogenate, and represent the first characterization of such a receptor in a vascular tissue.