tbuckley/cabot-search huggingface dataset:
Combined endostatin/sFlt-1 antiangiogenic gene therapy is highly effective in a rat model of HCC
Authors: Florian Graepler, Barbara Verbeek, Tilmann Graeter, Irina Smirnow, Hwai Loong Kong, Detlef Schuppan, Michael Bauer, Reinhard Vonthein, Michael Gregor, Ulrich M. Lauer
Journal: Hepatology (2005)

Hepatocellular carcinoma (HCC) is regarded as a suitable target for antiangiogenic strategies. However, antiangiogenic agents aimed at single targets can be neutralized by upregulation of other proangiogenic factors. Therefore, combined approaches addressing at least two angiogenic targets should be more effective. Employing an appropriate rat hepatoma model, we examined the effects of sFlt-1 (soluble vascular endothelial growth factor [VEGF] receptor 1 as an indirect inhibitor of angiogenesis) and endostatin (a direct inhibitor of angiogenesis) in both single-agent as well as combined approaches under in vitro and in vivo conditions. Similar to human HCC, rat Morris hepatoma (MH) cells secreted high levels of VEGF, but no endogenous sFlt-1. Parental MH or MHES(r) cells, stably expressing rat endostatin, were adenovirally transduced either with AdsFlt-1 (encoding sFlt-1) or control vector Adnull (containing no transgene), followed by subcutaneous inoculation into syngeneic ACI rats. Compared with MH/Adnull cells, expressing no antiangiogenic factors at all, tumor weights were reduced fourfold in the MHES(r)/Adnull group, 19-fold in the MH/AdsFlt-1-group, and 77-fold in the MHES(r)/AdsFlt-1 combination therapy group. Analysis of variance did not show a significant interaction between the effects of the two factors ES(r) and sFlt-1; their effects multiplied. In conclusion, combined expression of sFlt-1 and endostatin effectively suppresses HCC growth under in vivo conditions. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2005.)
Abstract 1177: Pharmacological stimulation of DLL1-Notch signaling as an effective cancer immunotherapy
Authors: Asel K. Biktasova, Fred D. Dudimah, Roman Uzhachenko, Rajeswara Rao Arasada, Elena E. Tchekneva, David P. Carbone, Anil Shanker, Mikhail M. Dikov
Journal: Cancer Research (2014)

Abstract Our data demonstrated that in cancer, expression of Notch ligands is selectively altered and Notch signaling in the hematopoietic compartment is attenuated and associated with impaired anti-tumor immunity caused by the aberrant T cell differentiation and function. Our important and therapeutically relevant finding is that stimulation of DLL1-mediated Notch signaling by systemic administration of soluble multivalent (clustered) DLL1 efficiently restores Notch signaling in the hematopoietic compartment. Such therapy strongly activates Notch downstream signaling and variably modulates expression of Notch receptors and ligands. Clustered DLL1 treatment results in significant enhancement of tumor antigen-specific T cell immune responses and memory, decreased proportion of regulatory T cells, remarkably increased tumor infiltration by T cells, attenuated tumor vascularization, and suppression of tumor growth. In an inducible model of lung tumor expressing L858R mutant EGFR in lung epithelium, clustered DLL1 elicited robust anti-tumor immune responses in concert with EGFR inhibition by erlotinib and produced remarkably improved progression-free survival. It is also likely that more efficient tumor killing and induction of T cell memory would significantly delay tumor progression/recurrence. Activation of Notch signaling by multivalent DLL1 in a panel of lung cancer cells in vitro did not stimulate cells proliferative of colony-forming potential, but rather demonstrated inhibitory effect in several cases. Pharmacological stimulation of Notch by multivalent DLL1 might represent an efficient strategy for enhancement of anti-tumor immunity and targeting multiple mechanisms of tumor growth. Reagents based on the multivalent forms of Notch ligands can be efficiently utilized for the therapeutic modulation of Notch signaling. Citation Format: Asel K. Biktasova, Fred D. Dudimah, Roman Uzhachenko, Rajeswara Rao Arasada, Elena E. Tchekneva, David P. Carbone, Anil Shanker, Mikhail M. Dikov. Pharmacological stimulation of DLL1-Notch signaling as an effective cancer immunotherapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1177. doi:10.1158/1538-7445.AM2014-1177
Allergic Sensitization Demonstrable Between 3 to 5 Years of Age is Associated with the Development of Viral-induced Illnesses that Increasingly Require more Intensive Corticosteroid Treatment
Authors: T.E. Pappas, M.D. Evans, R.E. Gangnon, W.M. Lee, D.J. Jackson, J.E. Gern, R.F. Lemanske Jr.
Journal: Journal of Allergy and Clinical Immunology (2011)
Abstract 4660: Double combination array analysis detected A kinase anchor protein 12 (AKAP12) gene as a new tumor suppressor gene of hepatocellular carcinoma
Authors: Masamichi Hayashi, Syuji Nomoto, Mitsuro Kanda, Yukiyasu Okamura, Tsutomu Fujii, Hiroyuki Sugimoto, Shin Takeda, Akimasa Nakao
Journal: Cancer Research (2010)

Abstract Background Hepatocellular carcinoma (HCC) is the fifth most common malignancy and is caused environmental and genetic factors. However, little is known about the genetic characteristics of HCC cells. In this study, we investigated a novel tumor suppressor gene in HCC by double combination array method, consisting of both expression array analysis and karyotyping analysis of single-nucleotide polymorphism (SNP) array, using the same surgical specimen. Methods We performed double combination array analysis of the HCC sample from a 68-year-old woman with chronic hepatitis type C. The Affymetrix HGU133A and HGU133B was used for expression profiling and the Affymetrix GeneChip Mapping 500K array was used for SNP array. We verified the identified gene by using HCC cell lines and 48 primary HCC tissues of patients who had undergone hepatectomy at our hospital. Results AKAP12 gene expression was decreased in tumor tissue by the expression array analysis. This gene is said to produce a structurally diverse protein associated with protein kinase A, which blocks tumor cell growth and invasion. The copy number at locus 6q24-q25 did not show chromosomal deletion by the SNP array analysis. This gene was also revealed to have a CpG rich promoter region. We could recognize promoter hypermethylation by sequence analysis of the HCC cell lines. Furthermore, AKAP12 gene expression was reactivated after 5-aza-2′-deoxycytidine (5-aza-dC) treatment. As for the 48 HCC samples, 41 cases (85%) showed promoter hypermethylation by methylation specific PCR. In these cases, the values of AKAP12 gene expression in tumor tissues, which were examined by quantitative real-time PCR, were significantly lower (P = 0.0001) than those in adjacent non-cancerous tissues. Finally, we evaluated the downregulated status of AKAP12 and the clinico-pathological findings. The downregulated cases were correlated with poor overall survival rate, although the diffenrence was not significant (P = 0.115). Conclusion Our double combination array method successfully detected a tumor suppressor gene of HCC which has yet to be identified. The downregulation of AKAP12 gene occurred by promoter hypermethylation and correlated with poor prognosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4660.
Diet and Sleep Patterns in Newborn Infants
Authors: Michael W. Yogman, Steven H. Zeisel
Journal: New England Journal of Medicine (1983)

Sleep behavior is modulated by serotonergic neurons within the brain, and the synthesis and release of serotonin by such neurons is thought to be influenced by the availability of tryptophan, the amino acid precursor of serotonin. We investigated the effects on the sleep patterns of newborn infants of variations in diet designed to affect tryptophan availability. Twenty healthy newborns (two to three days of age) were randomly assigned to receive a feeding consisting either of tryptophan in 10 per cent glucose or valine in 5 per cent glucose (valine competes with tryptophan for entry into the brain). Sleep patterns during the three hours after this feeding were compared with those after a feeding of routine formula (Similac). The infants fed tryptophan entered active sleep 14.1 minutes sooner than they did after Similac, and entered quiet sleep 20 minutes sooner. Those fed valine entered active sleep 15.8 minutes later than they did after Similac, and entered quiet sleep 39 minutes later. The differences between the tryptophan and valine groups were significant (P less than 0.01 for active sleep and P less than 0.005 for quiet sleep). We conclude that variations in the composition of the diet may influence sleep behavior in newborns.
Paleontologist Offers Lessons From Other Eons
Authors: Beverly Merz
Journal: JAMA (1989)

WHY IS a paleontologist (whose credits include the first book on dinosaurs directed at scientists) teaching anatomy to first-year medical students? The question is one frequently directed at David Weishampel, PhD, assistant professor of cell biology and anatomy. The answer is, "Because we are very good comparative anatomists." Weishampel notes that, when it comes to extrapolating the anatomy of a hadrosaur or a parasaurolophus from a few bones, nothing is as valuable as experience in dissecting the composition of extant species. "One outlet is teaching human anatomy. The human structure has been very well studied, intensely scrutinized," he says. Dividing his professional time between human anatomy and paleontology gives Weishampel a particular perspective on the human's role in today's world. His studies of extinction and speciation more than 75 million years ago can be used as a case study of population behavior in the face of environmental crises. "We have
Opportunity for Intervention to Achieve American Heart Association Guidelines for Optimal Lipid Levels in High-Risk Women in a Managed Care Setting
Authors: Lori Mosca, Noel Bairey Merz, Roger S. Blumenthal, Mark J. Cziraky, Rosalind P. Fabunmi, Chaitanya Sarawate, Karol E. Watson, Vincent J. Willey, Eric J. Stanek
Journal: Circulation (2005)

Background— The American Heart Association (AHA) recently established evidence-based recommendations for cardiovascular disease (CVD) prevention in women, including lipid management. This study evaluated optimal lipid-level attainment and treatment patterns on the basis of these guidelines in high-risk women in a managed care setting. Methods and Results— We conducted a historical prospective cohort analysis of a 1.1-million-member, integrated, managed-care database. Eligible high-risk women were those with evidence of previous CVD or risk equivalent who had a full lipid panel available between October 1, 1999, and September 30, 2000; were naive to lipid therapy; and had a minimum of 12 months health plan eligibility preindex and postindex lipid panel. Optimal lipid levels were defined as LDL cholesterol (LDL-C) &lt;100 mg/dL, HDL cholesterol (HDL-C) &gt;50 mg/dL, non–HDL-C &lt;130 mg/dL, and triglycerides &lt;150 mg/dL. Laboratory values and lipid pharmacotherapy were assessed longitudinally over the postindex follow-up (up to 36 months). A total of 8353 high-risk women (mean age, 66±14 years) with a mean follow-up of 27±8 months were included. Only 7% attained optimal combined lipid levels initially, and this increased to 12% after 36 months. Lipid-modifying therapy was initiated in 32% of patients, including 35% of women with LDL-C ≥100 mg/dL and 15% with LDL-C &lt;100 mg/dL. Conclusions— Among high-risk women, few attained the AHA’s standards for all lipid fractions, and only one third received recommended drug therapy, highlighting significant opportunities to apply evidence-based recommendations to manage lipid abnormalities in high-risk women.
Paraneoplastic CNS and Renal Syndromes
Authors: Frederick M. Vincent
Journal: JAMA (1978)

THE TERM carcinomatous neuromyopathy was introduced by Brain and Henson<sup>1</sup>to describe the neurological syndromes that occur with malignant tumors in the absence of CNS metastases. These paraneoplastic effects of cancer on the CNS are largely manifested clinically as cerebellar degeneration, dementia, myelopathy, encephalopathy, or disorders of the motor unit. To my knowledge, cases of opsoclonus, a rare ocular dyskinesia characterized by rapid and arrhythmic conjugate oscillations of the eyes in all directions, have been reported twice in the past as a remote effect of lung cancer.<sup>2</sup> A patient had development of opsoclonus, dementia, and cerebellar dysfunction as the initial manifestation of an occult oat cell carcinoma of the lung. In addition, this patient suffered from the nephrotic syndrome secondary to an immune-complex glomerulonephritis, presumably of paraneoplastic origin. To my knowledge, this combination of a remote effect of carcinoma on both the CNS and the kidney has not
The role of the immune system in regulating the microbiota
Authors: Benjamin P. Willing, Navkiran Gill, B. Brett Finlay
Journal: Gut Microbes (2010)

A diverse population of bacteria, archaea, and fungi, collectively known as the microbiota, abounds within the gastrointestinal tract of the mammalian host. This microbial population makes many important contributions to host physiology through inter-kingdom signalling and by providing nutrients that have both local and systemic effects. In a healthy state the overall host-microbial interaction is symbiotic; however, a growing number of diseases have been associated with a dysregulated microbiota. To avoid these consequences, the host exerts substantial effort to maintain proper regulation of the microbiota with respect to localization and composition. Although important to maintaining microbial balance, the host immune response can also be the cause of a disrupted microbiota, contributing to disease severity. Here, we discuss the role of the host in both maintaining and disrupting a balanced gastrointestinal microbiota.
Optimum dose of olsalazine for maintaining remission in ulcerative colitis.
Authors: S P Travis, C Tysk, H J de Silva, H Sandberg-Gertzen, D P Jewell, G Jarnerot
Journal: Gut (1994)

To evaluate the optimum dose of olsalazine for maintaining remission in ulcerative colitis, 198 patients in remission for more than three months were randomly assigned to receive 0.5 g, 1.0 g, or 2.0 g/day for 12 months. A dose-ranging effect was detected in the per protocol analysis, with remission rates of 60% (0.5 g), 70% (1.0 g), and 78% (2.0 g) (p = 0.03, trend in proportions). The higher dose was most effective in patients with proctitis (90% remission on 2 g/day, p = 0.03) or those in remission for less than 12 months before the trial (88% remission on 2 g/day, p = 0.0006). There was little dose-ranging effect in patients with extensive colitis or those in remission for more than 12 months. Diarrhoea necessitated treatment withdrawal in 12%. The optimal dose of olsalazine for maintaining remission in ulcerative colitis is 1 g/day. For patients with proctitis or recent relapse, 2 g/day may be preferable, although the dose seems to be less important in patients with more extensive disease or those in long term remission.
Low-Temperature Mapping Predicts Site of Successful Ablation While Minimizing Myocardial Damage
Authors: Jean-Marc Cote, Michael R. Epstein, John K. Triedman, Edward P. Walsh, J. Philip Saul
Journal: Circulation (1996)

Background Temperatures near 50°C can cause reversible loss of excitability in myocardial cells. Methods and Results Low-temperature, short-duration applications of radiofrequency energy were used to determine the adequacy of electrophysiological mapping of accessory pathway (AP) locations in 15 patients at 27 target sites using a closed-loop, temperature-controlled generator set to 50°C. Energy was delivered until evidence of conduction block, or for a maximum of 10 seconds. If AP block occurred, a full 70°C set point radiofrequency application was delivered to the same site. In the absence of AP block, tests with higher temperature settings (60°C and 70°C) were delivered to determine if inadequate temperature or catheter position led to failure of the initial 50°C test. At 15 successful target sites where permanent AP block was achieved, the 50°C test resulted in AP block in 14 (93%). Conduction returned in 13 of 14 APs after radiofrequency power was turned off. The time to block for the 70°C applications was significantly shorter than for the 50°C tests, and the peak temperature achieved was significantly higher. At unsuccessful sites where permanent AP block was not achieved, no block was induced with 11 of 12 tests at 50°C, 6 of 6 tests at 60°C, and 1 of 2 tests at 70°C, suggesting that failure was due to incorrect catheter position. The sensitivity and positive predictive values of a 50°C test identifying a successful site were &gt;90%. Conclusions Low-temperature radiofrequency applications that cause transient AP block predict permanent success when a higher-temperature application is delivered at the same site. The time to achieve conduction block is a function of the temperature set point, and low-temperature tests produce reversible conduction block, suggesting minimal permanent injury.
Negative Inotropy of the Gastric Proton Pump Inhibitor Pantoprazole in Myocardium From Humans and Rabbits
Authors: Wolfgang Schillinger, Nils Teucher, Samuel Sossalla, Sarah Kettlewell, Carola Werner, Dirk Raddatz, Andreas Elgner, Gero Tenderich, Burkert Pieske, Giuliano Ramadori, Friedrich A. Schöndube, Harald Kögler, Jens Kockskämper, Lars S. Maier, Harald Schwörer, Godfrey L. Smith, Gerd Hasenfuss
Journal: Circulation (2007)

Background— Proton pump inhibitors are used extensively for acid-related gastrointestinal diseases. Their effect on cardiac contractility has not been assessed directly. Methods and Results— Under physiological conditions (37°C, pH 7.35, 1.25 mmol/L Ca 2+ ), there was a dose-dependent decrease in contractile force in ventricular trabeculae isolated from end-stage failing human hearts superfused with pantoprazole. The concentration leading to 50% maximal response was 17.3±1.3 μg/mL. Similar observations were made in trabeculae from human atria, normal rabbit ventricles, and isolated rabbit ventricular myocytes. Real-time polymerase chain reaction demonstrated the expression of gastric H + /K + –adenosine triphosphatase in human and rabbit myocardium. However, measurements with BCECF-loaded rabbit trabeculae did not reveal any significant pantoprazole-dependent changes of pH i . Ca 2+ transients recorded from field-stimulated fluo 3–loaded myocytes (F/F 0 ) were significantly depressed by 10.4±2.1% at 40 μg/mL. Intracellular Ca 2+ fluxes were assessed in fura 2–loaded, voltage-clamped rabbit ventricular myocytes. Pantoprazole (40 μg/mL) caused an increase in diastolic [Ca 2+ ] i by 33±12%, but peak systolic [Ca 2+ ] i was unchanged, resulting in a decreased Ca 2+ transient amplitude by 25±8%. The amplitude of the L-type Ca 2+ current ( I Ca,L ) was reduced by 35±5%, and sarcoplasmic reticulum Ca 2+ content was reduced by 18±6%. Measurements of oxalate-supported sarcoplasmic reticulum Ca 2+ uptake in permeabilized cardiomyocytes indicated that pantoprazole decreased Ca 2+ sensitivity (K d ) of sarcoplasmic reticulum Ca 2+ adenosine triphosphatase: control, K d =358±15 nmol/L; 40 μg/mL pantoprazole, K d =395±12 nmol/L ( P &lt;0.05). Pantoprazole also acted on cardiac myofilaments to reduced Ca 2+ -activated force. Conclusions— Pantoprazole depresses cardiac contractility in vitro by depression of Ca 2+ signaling and myofilament activity. In view of the extensive use of this agent, the effects should be evaluated in vivo.
Resection of Carotid Body Tumors reduces arterial blood pressure. An underestimated neuroendocrine syndrome
Authors: Stefano de Franciscis, Raffaele Grande, Lucia Butrico, Gianluca Buffone, Luca Gallelli, Edoardo Scarcello, Francesco Giuseppe Caliò, Domenico De Vito, Rita Compagna, Maurizio Amato, Francesco Fugetto, Vincenzo Gasbarro, Bruno Amato, Raffaele Serra
Journal: International Journal of Surgery (2014)
Accidental childhood poisoning with household products.
Authors: A W Craft, G R Lawson, H Williams, J R Sibert
Journal: BMJ (1984)

Revue de toutes les admissions d'enfants de moins de 5 ans, entre 1974 et 1982, pour intoxication par produits menagers. Produits le plus souvent impliques: terebenthine, White spirit ou succedanes, paraffine, alcool, dissolvant, soude caustique, essence de camphre etc. Ces produits devraient etre conserves dans des recipients a fermeture «resistant aux enfants» comme certains produits pharmaceutiques deja
Risk Factors for Persistent Middle-Ear Effusions
Authors: K. D. Rogers, J. L. Paradise, C. D. Bluestone
Journal: JAMA (1984)

<h3>To the Editor.—</h3> Kraemer et al<sup>1</sup>compared children with persistent middle-ear effusion (PMEE) admitted to a hospital for tympanostomy tube insertion with children admitted for other types of surgery and matched to patients with PMEE by age, sex, season, and surgical ward. Parents were interviewed about children's household exposure to cigarette smoke, frequency of nasal congestion, and frequency of defined atopic symptoms. The ratios of the proportions of children with PMEE to the proportions of children without PMEE in whom these factors were present were expressed as relative risks. When relative risks were calculated individually for nasal congestion, cigarettesmoke exposure (as measured by whether household residents reportedly smoked more than 0.5 packs per day), and atopy, nasal congestion was significantly different in children with and without PMEE, but cigarette smoke exposure and atopy were not. When risks were calculated for the three factors in pairs, exposure to
PROTOZOAL INFESTATIONS OF AMERICAN INDIAN CHILDREN
Authors: WILLIAM B. OWEN
Journal: JAMA (1934)

That amebiasis and other protozoal infections are conditions not peculiar to tropical countries, but are frequently encountered in all temperate climates, is a fact amply verified wherever careful observations have been made. Through the work of Boeck and Stiles,1Meleney, Riley,2Faust3and others, a large body of information has been accumulated relative to the prevalence of intestinal protozoa in the white race of the United States. Furthermore, Meleney, Bishop and Leathers4have obtained considerable data on these infections in the Negro population of Tennessee.  Notwithstanding the information made available by the aforementioned studies, little is known in regard to the prevalence of these infections in the North American Indians. Two principal reasons probably account for this fact. In the first place, most of the large Indian reservations are relatively isolated from centers of research in parasitology. And, secondly, amebic dysentery is either of rare occurrence