tbuckley/cabot-search huggingface dataset:
Control of Von Willebrand Factor Multimer Size by Thrombospondin-1
Authors: Lijuan Xie, Colin N. Chesterman, Philip J. Hogg
Journal: The Journal of Experimental Medicine (2001)

Plasma von Willebrand factor (vWF) is a multimeric protein that mediates adhesion of platelets to sites of vascular injury. Only the very large vWF multimers are effective in promoting platelet adhesion in flowing blood. A protein disulfide bond reductase in plasma reduces the average multimer size of vWF secreted by endothelial cells. This activity has been isolated from human endothelial cell conditioned medium and shown to be the trimeric glycoprotein, thrombospondin-1 (TSP-1). Incubation of purified TSP-1 with vWF resulted in formation of thiol-dependent complexes of TSP-1 and vWF, generation of new thiols in vWF, and reduction in the average multimer size of vWF. The ratio of the concentrations of TSP-1 and vWF in plasma reflected with average multimer size of vWF. The higher the plasma TSP-1/vWF molar ratio, the smaller the average vWF multimer size. In addition, administration of TSP-1 to mice resulted in reduction in the average multimer size of plasma vWF. Interaction of TSP-1 with vWF is mediated by TSP-1 type 1 properdin domains and the vWF A3 domain. These results indicate that TSP-1 regulates the multimeric size and therefore hemostatic activity of vWF.
Effect of swimming intensity on subsequent cycling and overall triathlon performance
Authors: P D Peeling, D J Bishop, G J Landers
Journal: British Journal of Sports Medicine (2005)

To investigate the effects of different swimming intensities on subsequent cycling and overall triathlon performance.Nine highly trained, male triathletes completed five separate laboratory sessions comprising one graded exercise test, a swim time trial (STT), and three sprint distance triathlons (TRI). The swimming velocities of the three TRI sessions were 80-85% (S80), 90-95% (S90), and 98-102% (S100) of the STT velocity. Subsequent cycling and running were performed at a perceived maximal intensity. Swimming stroke mechanics were measured during the swim. Plasma lactate concentration and ratings of perceived exertion were recorded at the conclusion of the swim and over the course of subsequent cycling and running. Oxygen consumption was recorded during the cycle.The S80 and S90 cycle times were faster than the S100 cycle time (p<0.05). The overall triathlon time of S80 was faster than that of S100 (p<0.05). The S100 swim was characterised by a greater stroke rate than S80 and S90 (p<0.05) and a greater plasma lactate concentration than S80 (p<0.01).A swimming intensity below that of a time trial effort significantly improves subsequent cycling and overall triathlon performance.
A Randomized, Double-Blind, Phase 2 Trial of Veliparib (Abt-888) with Carboplatin and Paclitaxel in Previously Untreated Metastatic or Advanced Non-Small Cell Lung Cancer
Authors: S.S. Ramalingam, N. Blais, J. Mazieres, M. Reck, C.M. Jones, E. Juhasz, L. Urban, S. Orlov, F. Barlesi, E. Kio, U. Keilholz, Q. Qin, J. Qian, C. Nickner, J. Dziubinski, M.D. McKee, V.L. Giranda, V.A. Gorbunova
Journal: Annals of Oncology (2014)
CHANGES IN RENAL CONCENTRATING ABILITY PRODUCED BY PARATHYROID EXTRACT*
Authors: Franklin H. Epstein, David Beck, Frank A. Carone, Howard Levitin, Andrzej Manitius
Journal: Journal of Clinical Investigation (1959)

Polyuria is a frequent symptom of hyperparathyroidism.Impairment of renal concentrating ability, often out of proportion to other signs of renal insufficiency, has been noted in patients with hyperparathyroidism (1-3) as well as in patients and animals with hypercalcemia due to other causes (4-6).In many patients with hyperpara- thyroidism, extensive deposits of calcium in the renal parenchyma, secondary fibrosis, superim- posed pyelonephritis and vascular disease have combined to destroy considerable amounts of renal substance.The mechanism of the reported de- crease in renal concentrating ability in such pa- tients is not clear, since fixation of urinary spe- cific gravity is a well-known accompaniment of the simple ablation of renal tissue (7).In the present experiments, renal concentrating capacity was found to be depressed in dogs in which hypercalcemia had been induced for only 24 hours by injecting parathyroid extract.This functional defect was associated with morphologic changes in the distal portions of nephrons and the collecting ducts. MATERIALS AND METHODSMature female dogs weighing 8 to 22 Kg.were main- tained on Purina Chow® supplemented with horsemeat.All experiments were carried out under light pentobarbital anesthesia.Inulin was determined by the method of Walser, Davidson and Orloff (8), osmolality of serum and urine with a Fiske osmometer, serum calcium ac- cording to Kingsley and Robnett (9), and sodium in serum and urine by flame photometry.
Endotoxin-Induced Myocardial Tumor Necrosis Factor-α Synthesis Depresses Contractility of Isolated Rat Hearts
Authors: Ulrich Grandel, Ludger Fink, Andreas Blum, Martina Heep, Michael Buerke, Hans-Joachim Kraemer, Konstantin Mayer, Rainer M. Bohle, Werner Seeger, Friedrich Grimminger, Ulf Sibelius
Journal: Circulation (2000)

Background —Although endotoxin (lipopolysaccharides, LPS) is recognized as a mediator of septic cardiodepression, its cardiac effects are still not fully elucidated. Methods and Results —Perfusion of isolated rat hearts with LPS for 180 minutes resulted in a decline of left ventricular contractility after 90 minutes, whereas coronary perfusion pressure remained unaffected. This cardiodepression was paralleled by a release of tumor necrosis factor (TNF)-α into the perfusate and preceded by myocardial TNF-α mRNA upregulation as quantified by real-time polymerase chain reaction. The cardiodepression was abrogated when LPS was perfused with a TNF-α antiserum or the ceramidase inhibitor N -oleoylethanolamine. In contrast, the cardiac release of nitric oxide (NO) was not augmented by LPS. Immunohistochemical studies of LPS-perfused hearts revealed a positive staining for the constitutive (NOSIII) but not for the inducible NO synthase (NOSII). Accordingly, NOSII mRNA levels commenced to increase only at the very end of the LPS perfusion period. Progressive liberation of thromboxane (Tx) A 2 and prostacyclin was induced by LPS together with myocardial cyclooxygenase (Cox)-2 mRNA expression. Both nonselective inhibition of Cox by indomethacin and selective inhibition of the inducible Cox-2 by NS-398 abolished prostanoid release. Interestingly, the generation of TNF-α and the associated cardiodepression caused by LPS were reduced by indomethacin, NS-398 and the Tx-receptor antagonist daltroban. Conclusions —LPS depresses contractility of isolated rat hearts by inducing TNF-α synthesis and subsequently activating the sphingomyelinase pathway, whereas no evidence for a role of NOSII- or NOSIII-generated NO was found. Moreover, Cox-2–derived TxA 2 appears to facilitate TNF-α synthesis in response to LPS.
Transient downregulation of glomerular atrial natriuretic factor receptors in high output heart failure in the rat
Authors: G Gauquelin, M-C Bonhomme, R Garcia
Journal: Cardiovascular Research (1995)

The renal response to exogenous atrial natriuretic factor (ANF) is blunted in chronic heart failure. The aim of the present studies was to investigate whether renal ANF receptor regulation in chronic heart failure is a time related event.Glomerular ANF receptors were analysed in radioligand binding experiments at 0, 1, 2, 6, 12, 24, and 48 h, as well as at 1, 2, 4, and 8 weeks after the induction of an aortocaval shunt.Rats with aortocaval shunts had lower packed cell volume and body weight and higher relative heart weight than sham operated controls. Plasma ANF C and N terminal levels were increased in shunt rats as early as 5 min after establishment of the shunt. Right and left atrial ANF concentrations were decreased and ventricular ANF concentration was increased in shunt rats at 6 and 12 h respectively. Competitive inhibition of 125I-ANF binding showed that at 6 h the density (Bmax) of glomerular ANF receptors was significantly lower than in the controls [518(SEM 10) v 759(12) fmol.mg-1 protein] without differences in their affinity (Kd). The low Bmax in shunt animals persisted at 12, 24, and 48 h, even at 1 week [Bmax: 400(29) and 713(28) fmol.mg-1 protein; Kd: 80(2) and 70(4) pM, for AC rats and controls, respectively]. Bmax values were not significantly different at 2, 4, and 8 weeks. In 24 h animals, C-ANF displaced 65% of total binding, with both total and C ANF binding sites being 38% lower in shunt animals.Downregulation of glomerular ANF receptors is a transient event during the development of high output heart failure in the rat. Thus the blunted renal response to ANF during chronic heart failure is not likely to be due to a decrease in renal ANF receptor density or affinity.
AMH and AFC as predictors of excessive response in controlled ovarian hyperstimulation: a meta-analysis
Authors: S. L. Broer, M. Dolleman, B. C. Opmeer, B. C. Fauser, B. W. Mol, F. J. M. Broekmans
Journal: Human Reproduction Update (2010)

Anti-Mullerian hormone (AMH) is a marker of ovarian reserve status and represents a good predictor of ovarian response to ovarian hyperstimulation. The aim of this study was to assess the accuracy of AMH and antral follicle count (AFC) as predictors of an excessive response in IVF/ICSI treatment. A systematic review and meta-analysis of the existing literature was performed. Studies were included if 2 × 2 tables for the outcome excessive response in IVF patients in relation to AMH/AFC could be constructed. Using a bivariate meta-analytic model, both summary point estimates for sensitivity and specificity were calculated, as well as summary ROC curves. Clinical value was analysed by calculating post-test probabilities of excessive response at optimal cut-off levels, as well as the corresponding abnormal test rates. Nine studies reporting on AMH and five reporting on AFC were found. Summary estimates of sensitivity and specificity for AMH were 82 and 76%, respectively, and 82 and 80%, respectively, for AFC. Comparison of the summary estimates and ROC curves for AMH and AFC showed no statistical difference. Abnormal test rates for AMH and AFC amounted to ∼14 and 16%, respectively, at cut-off levels where test performance is optimal [likelihood ratio for a positive result (LR + )>8], with a post-test probability of ±70%. Both AMH and AFC are accurate predictors of excessive response to ovarian hyperstimulation. Moreover, both tests appear to have clinical value. This opens ways to explore the potential of individualized FSH dose regimens based on ovarian reserve testing.
Predictors of Successful Extubation in Neurosurgical Patients
Authors: ANDREW M. NAMEN, E. WESLEY ELY, STEPHEN B. TATTER, L. DOUGLAS CASE, MICHAEL A. LUCIA, ALLEN SMITH, SCOTT LANDRY, JOHN A. WILSON, STEVEN S. GLAZIER, CHARLES L. BRANCH, DAVID L. KELLY, DAVID L. BOWTON, EDWARD F. HAPONIK
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

A respiratory therapist-driven weaning protocol incorporating daily screens, spontaneous breathing trials (SBT), and prompts to caregivers has been associated with superior outcomes in mechanically ventilated medical patients. To determine the effectiveness of this approach in neurosurgical (NSY) patients, we conducted a randomized controlled trial involving 100 patients over a 14-mo period. All had daily screens of weaning parameters. If these were passed, a 2-h SBT was performed in the Intervention group. Study physicians communicated positive SBT results, and the decision to extubate was made by the primary NSY team. Patients in the Intervention (n = 49) and Control (n = 51) groups had similar demographic characteristics, illness severity, and neurologic injuries. Among all patients, 87 (45 in the Control and 42 in the Intervention group) passed at least one daily screen. Forty (82%) patients in the Intervention group passed SBT, but a median of 2 d passed before attempted extubation, primarily because of concerns about the patient's sensorium (84%). Of 167 successful SBT, 126 (75%) did not lead to attempted extubation on the same day. The median time of mechanical ventilation was 6 d in both study groups, and there were no differences in outcomes. Overall complications included death (36%), reintubation (16%), and pneumonia (9%). Tracheostomies were created in 29% of patients. Multivariate analysis showed that Glasgow Coma Scale (GCS) score (p < 0.0001) and partial pressure of arterial oxygen/fraction of inspired oxygen ratio (p < 0.0001) were associated with extubation success. The odds of successful extubation increased by 39% with each GCS score increment. A GCS score > or = 8 at extubation was associated with success in 75% of cases, versus 33% for a GCS score < 8 (p < 0.0001). Implementation of a weaning protocol based on traditional respiratory physiologic parameters had practical limitations in NSY patients, owing to concerns about neurologic impairment. Whether protocols combining respiratory parameters with neurologic measures lead to superior outcomes in this population requires further investigation.
Hypopyon
Authors: S Soloway, D Weissgold
Journal: New England Journal of Medicine (1996)

Figure 1. A 36-year-old man had painless, intermittent loss of vision. In this photograph, a hypopyon, or leukocytic exudate, is seen in the anterior chamber (arrow) of the eye, and the conjunctiva and the underlying episclera appear injected. These findings, with the accompanying severe retinopathy, were caused by Behcet's disease. Treatment with chlorambucil and prednisone eye drops, and later with cyclosporine, failed to improve the patient's vision.
Reviewing a patient with coeliac disease
Authors: J. W. Berrill, H. Ahmed, S. Butt, G. Swift
Journal: BMJ (2012)

A 44 year old woman diagnosed with coeliac disease 10 years ago presents to her general practitioner with symptoms of bloating and diarrhoea that have developed over the past two months. Coeliac disease is a common gastrointestinal disease, with international population studies reporting a prevalence of 0.5-1%. Inflammation of the small bowel mucosa occurs as a result of an immunological response to dietary gluten. The mainstay of treatment is a gluten-free diet. The most appropriate method of follow-up for patients with coeliac disease is still debated. Evidence suggests that regular follow-up improves compliance with a gluten-free diet. Survey data have shown that patients would prefer a model allowing regular follow-up with a dietitian, with specialist medical expertise available if needed. However, limited resources and the ability of patients to self manage means that many patients consult their general practitioner only when they have concerns. This consultation presents an opportunity to review their management. In patients with a relapse of symptoms:
Short term power output in relation to growth and maturation
Authors: N Armstrong, J R Welsman, M Y H Chia
Journal: British Journal of Sports Medicine (2001)

To examine short term power output during growth and maturation using a multilevel modelling approach.Body mass, stature, and triceps and subscapular skinfold thicknesses of boys and girls, aged 12.2 (0.4) years (mean (SD)) at the onset of the study, were measured at age 12, 13, and 17 years. Sexual maturation, classified according to Tanner's stage of pubic hair development, was assessed on the first two occasions and assumed to be stage 5 at 17 years. Peak power (PP) and mean power (MP) were assessed on each occasion using the Wingate anaerobic test.Initial models, founded on 417 determinations of short term power output, identified body mass, stature, and age as significant explanatory variables of both PP and MP. The values for girls were significantly lower than those for boys, and a significant age by sex interaction described a progressive divergence in the MP of boys and girls. The introduction of sum of two skinfold thicknesses produced a model with an improvement in fit as indicated by a significant change in log likelihood. The stature term was negated and the body mass term increased. The age and sex terms were reduced but remained significant. The age by sex interaction term remained a significant explanatory variable for MP. Maturity effects were non-significant additional explanatory variables in all models of power output.The values of PP and MP for boys are higher than those for girls, and, for MP, sex differences increase with age. Body mass and skinfold thicknesses are significant influences on both PP and MP, but age exerts a positive but non-linear effect on power output independent of body size and fatness.
Necrotizing Vasculitis Triggered by Gefitinib: An Unusual Clinical Presentation
Authors: Jui-Hung Ko, Yi-Chin Shih, Rosaline Chung-Yee Hui, Chih-Hsun Yang
Journal: Journal of Clinical Oncology (2010)

Case ReportA 47-year-old man with a history of T4N2M0 stage IIIB non-smallcell lung cancer over the right lower lobe had been experiencing dyspnea on exertion and malignant pleural effusion since October 2008.He received treatment gefitinib 250 mg daily.Multiple palpable painful purpuric and erythematous maculopapules appeared on his limbs after 4 months of treatment with gefitinib (Fig 1).The patient did not develop fever, symptoms of upper respiratory illness, or arthralgia before the appearance of the maculopapules.Laboratory tests showed a platelet count
Upregulation of Soluble Vascular Endothelial Growth Factor Receptor 1 Contributes to Angiogenesis Defects in the Placenta of α <sub>2B</sub> -Adrenoceptor–Deficient Mice
Authors: Verena Muthig, Ralf Gilsbach, Miriam Haubold, Melanie Philipp, Tomi Ivacevic, Manfred Gessler, Lutz Hein
Journal: Circulation Research (2007)

α 2 -adrenoceptors are essential presynaptic regulators of norepinephrine release from sympathetic nerves. Previous studies in mice with targeted deletions in the 3 α 2 -adrenoceptor genes have indicated that these receptors are essential for embryonic development. In the present study, we searched for the α 2 -adrenoceptor subtype(s) involved in placental development and its molecular mechanism using mice carrying targeted deletions in α 2 -adrenoceptor genes. Congenic α 2B -adrenoceptor–deficient mice ( Adra2b −/− ) developed a defect in fetal and maternal vessel formation in the placenta labyrinth at embryonic day 10.5. This defect was accompanied by reduced endothelial cell proliferation and decreased extracellular signal-regulated kinase 1/2 phosphorylation levels in Adra2b −/− as compared with Adra2b +/+ placentae. Microarray analysis of wild-type and mutant placentae (maternal genotype Adra2b +/− ) revealed 179 genes, which were significantly up- or downregulated &gt;1.5-fold in α 2B -deficient placentae. The type 1 receptor for vascular endothelial growth factor (Flt1), which is coexpressed with α 2B -adrenoceptors in spongiotrophoblast and giant cells of the placenta, was found to be 2.3-fold upregulated in α 2B -deficient placentae. Neutralization of Flt1 and its soluble splice variant sFlt1 by a specific antibody in vivo prevented the vascular defect in α 2B -deficient placentae at embryonic day 10.5. Thus, α 2B -adrenoceptors are essential to suppress antiangiogenic (s)Flt1 in spongiotrophoblasts to control the coordinated formation of a vascular labyrinth of fetal and maternal blood vessels in the murine placenta during development.
Abnormal vascular network complexity: a new phenotypic marker in hereditary non-polyposis colorectal cancer syndrome
Authors: C De Felice
Journal: Gut (2003)

Hereditary non-polyposis colorectal cancer (HNPCC) (Lynch cancer family syndrome I (LCFS1) and II (LCFS2)) is one of the most common hereditary cancer disorders. HNPCC results from dominantly inherited germline mutations in mismatch repair (MMR) genes, leading to genomic instability and cancer. No predictive physical signs of HNPCC are available to date.Increased complexity in tumour associated vascular growth has been reported. Here, we tested the hypothesis that an increased vascular network complexity is a phenotypic marker for LCFS2.Fourteen subjects from an LCFS2 kindred (gene carriers, n=5; non-carriers, n=9) and 30 controls were examined. Fractal dimension (D) at two scales (D (1-46), and D (1-15), tortuosity (minimum path dimension, Dmin), and relative Lempel-Ziev complexity (L-Z) of the vascular networks from the lower gingival and vestibular oral mucosa were measured.LCFS2 networks exhibited a significantly increased overall complexity at both larger (D (1-46): 1.82 (0.04) v 1.68 (0.08); p<0.0001) and smaller (D (1-15): 1.51 (0.11) v 1.20 (0.09); p<0.0001) scales, increased destructured randomness (L-Z: 0.77 (0.09) v 0.56 (0.03); p<0.0001), and decreased vessel tortuosity (DMIN: 1.02 (0.03) v 1.07 (0.04); p=0.0005) compared with control patterns. The vascular networks of LCFS2 gene carriers showed higher complexity at the smaller scale (D (1-15): 1.59 (0.12) v 1.47 (0.07); p=0.034), and higher destructured randomness (L-Z: 0.85 (0.11) v 0.73 (0.05); p=0.013) than those of non-carriers.Increased oral vascular network complexity is a previously unrecognised phenotypic marker for LCFS2, and is related to gene mutation carrier status.
Can recovery of ventricular function after elective early postinfarction revascularization of asymptomatic patients be predicted by perfusion/metabolism SPECT radionuclide imaging or dobutamine echocardiography?
Authors: G. Dangas, J. Machac, M.E. Goldman, M.J. Henzlova, R. Vidhun, J.H. Shao, J.A. Ambrose
Journal: Journal of the American College of Cardiology (1998)
Answering the endocrine test questions.
Authors: C W Schmidt
Journal: Environmental Health Perspectives (1999)

Evidence suggesting that certain chemicals may bind to endogenous hormone receptors and disturb normal endocrine functioning, thereby increasing the risk of reproductive problems and cancer in humans, has led to international efforts to screen chemicals for endocrine activity and potential health effects. The U.S. Environmental Protection Agency (EPA) has recommended that some 87,000 commercial chemicals for which there currently are inadequate toxicity data be evaluated. In December 1998, the EPA's Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) recommended the use of a tiered system of screening and testing assays to sequentially eliminate chemicals for which further testing is deemed unnecessary. The first step toward implementing such a system-validation of the tests to be used-is presenting some challenges, however, with stakeholders disagreeing over which tests to validate, how extensively to validate them, and how much it will cost.
Glucocorticoids upregulate CD40 ligand expression and induce CD40L-dependent immunoglobulin isotype switching
Authors: Haifa H. Jabara, Scott R. Brodeur, Raif S. Geha
Journal: Journal of Clinical Investigation (2001)

IL-4 and CD40 ligation are essential for IgE synthesis by B cells. We have shown previously that hydrocortisone (HC) induces IgE synthesis in IL-4–stimulated human B cells. In this study we demonstrate that HC fails to induce IgE synthesis in B cells from CD40 ligand–deficient (CD40L-deficient) patients. Disruption of CD40L-CD40 interactions by soluble CD40-Ig fusion protein or anti-CD40L mAb blocked the capacity of HC to induce IgE synthesis in normal B cells. HC upregulated CD40L mRNA expression in PBMCs and surface expression of CD40L in PBMCs as well as in purified populations of T and B cells. Upregulation of CD40L mRNA in PBMCs occurred 3 hours after stimulation with HC and was inhibited by actinomycin D. Upregulation of CD40L mRNA and induction of IgE synthesis by HC were inhibited by the steroid hormone receptor antagonist RU-486. These results indicate that ligand-mediated activation of the glucocorticoid receptor upregulates CD40L expression in human lymphocytes.