tbuckley/cabot-search huggingface dataset:
Abstract 3175: The splice variant of the human papillomavirus 16 E6 protein, E6*, displays anti-tumor properties <i>in vivo</i>
Authors: Whitney Evans, Maria Filippova, Robert Aragon, Valeri Filippov, Mark Reeves, Penelope Duerksen-Hughes
Journal: Cancer Research (2014)

Abstract High-risk types of the human papillomavirus (HPV) are the causative agents of nearly all cases of cervical cancer, as well as a significant number of head, neck, penile, vulvar, and anal cancers. Like many other viruses with small genomes, HPV (∼8 kb) utilizes numerous mechanisms to increase the capacity of its genome to encode the proteins necessary for successful completion of its infectious life cycle, including alternative splicing. Studies over the past few decades have focused intensively on the activities and roles of E6 proteins from high-risk types of HPV during the process of cellular transformation, clearly implicating E6 as a major transforming agent. In contrast, the role of the smaller splice isoform, E6*, in the carcinogenic process (if any) has not yet been established. In the present study, we examined the behavior of the E6* protein during tumor growth in an in vivo nude mouse xenograft model. We created E6*-expressing SiHa (HPV+) and C33A (HPV-) cells, then examined the ability of both the parental and E6*-expressing cells to form tumors in nude mice. The difference in tumor size observed in the presence and absence of E6*, when expressed in both HPV+ (SiHa) and HPV- (C33A) cells, was dramatic and consistent, strongly indicating an anti-oncogenic role for E6* in this context. Interestingly, we found that tumor growth inhibition by E6* was greater in tumors derived from SiHa cells, which are HPV16-positive, than in tumors produced by C33A, which are HPV-negative. This difference implies that E6* acts by interfering with the oncogenic activity of the full-length protein as well as through one or more HPV-independent mechanisms. Consistent with this idea, we found that E6* does indeed bind to the full-sized isoform and inhibits its ability to accelerate degradation of p53 and procaspase 8. These data represent the first demonstration of biologically-relevant E6* activities distinct from those of the full-length isoform in vivo. The significance of these findings in the context of human cancers is in the possibility of mimicking or replicating the anti-oncogenic activity of E6* in such a way as to provide therapeutic benefit. Citation Format: Whitney Evans, Maria Filippova, Robert Aragon, Valeri Filippov, Mark Reeves, Penelope Duerksen-Hughes. The splice variant of the human papillomavirus 16 E6 protein, E6*, displays anti-tumor properties in vivo. [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 3175. doi:10.1158/1538-7445.AM2014-3175
S-adenosyl-L-methionine prevents disruption of canalicular function and pericanalicular cytoskeleton integrity caused by cyclosporin A in isolated rat hepatocyte couplets
Authors: I D Roman, G D Johnson, R Coleman
Journal: Hepatology (1996)

Isolated rat hepatocyte couplets were used to study the effect of S–adenosyl–L methionine (SAMe) treatment on disruption of canalicular function caused by cyclosporin A (CyA). Canalicular function was assessed by counting the percentage of couplets that were able to accumulate the fluorescent cholephile choly–lysyl–fluorescein (CLF) into the canalicular vacuole between the two cells, i.e., canalicular vacuole accumulation (CVA). Cotreatment with 1 mmol/L SAMe prevented the inhibition of canalicular vacuole accumulation caused by CyA (75 nmol/L and 100 nmol/L), whereas treatment with it after CyA was unsuccessful. SAMe prevented the dose dependent reduction caused by CyA (5 nmol/L–1 mumol/L) both on CVA and on retention of CLF preaccumulated within the canaliculus, the effect on retention being complete. No difference in intracellular content of reduced glutathione (GSH) between the control and any dose level of the immunosuppressor, with or without SAMe treatment was observed, suggesting that changes in intracellular reduced GSH levels are not involved in the effects of SAMe. F–actin was stained with fluorescein–isothiocyanate phalloidin and fluorescence measurements were performed by confocal microscopy. The ratio of the percanalicular area fluorescence/total couplet fluorescence, indicative of F–actin distribution, significantly decreased with CyA. However, cotreatment of CyA with SAMe protected the integrity of the pericanalicular cytoskeleton, suggesting that this beneficial effect on canalicular function may maintain canalicular contractions and/or preserve tight junction function. Results are discussed in relation to possible involvement of the transmethylation pathway, modifications in membrane fluidity, effects on bile acid transport, and of inhibition of uptake of CyA. They suggest that SAMe could be a good candidate for protecting against CyA–induced membrane dysfunction.
1087-134 Improved calcium homeostasis and antiarrhythmic effects of a novel chimeric molecule that inhibits both type III phosphodiesterase and L-type calcium channel in failing hearts
Authors: Reza Mazhari, Katayoun Derakhchan, Gregory Hamilton, Marc-Antoine Gillis, Daniel Bednarik, Peter Suzdak, Stanley Nattel
Journal: Journal of the American College of Cardiology (2004)
Assessment of Commercial Laboratories Performing Hair Mineral Analysis
Authors: Sharon Seidel
Journal: JAMA (2001)

ContextHair mineral analysis is being used by health care practitioners and promoted by laboratories as a clinical assessment tool and to identify toxic exposures, despite a 1985 study that found poor reliability for this test.ObjectiveTo assess whether the reliability of data from commercial laboratories advertising multimineral hair analyses for nutritional or toxicity assessment has improved since the 1985 study.Design, Setting, and ParticipantsA split hair sample taken from near the scalp of a single healthy volunteer was submitted for analysis to 6 commercial US laboratories, which analyze 90% of samples submitted for mineral analysis in the United States.Main Outcome MeasuresAgreement of test results for each analyte, laboratory reference ranges, laboratory characteristics, and interpretation of health implications.ResultsLaboratory differences in highest and lowest reported mineral concentrations for the split sample exceeded 10-fold for 12 minerals, and statistically significant (P&lt;.05) extreme values were reported for 14 of the 31 minerals that were analyzed by 3 or more laboratories. Variations also were found in laboratory sample preparation methods and calibration standards. Laboratory designations of normal reference ranges varied greatly, resulting in conflicting classifications (high, normal, or low) of nearly all analyzed minerals. Laboratories also provided conflicting dietary and nutritional supplement recommendations based on their results.ConclusionsHair mineral analysis from these laboratories was unreliable, and we recommend that health care practitioners refrain from using such analyses to assess individual nutritional status or suspected environmental exposures. Problems with the regulation and certification of these laboratories also should be addressed.
Renal sodium handling in pre-ascitic cirrhosis
Authors: J CLARIA, J RODES
Journal: Gut (1999)

Editor,—We read with interest the commentary by Claria and Rodes (

(1999) Gut 45:639–639; 

[OpenUrl][1][Abstract/FREE Full Text][2]

) on our paper published in Gut which re-examined the mechanisms of renal sodium retention in patients with preascitic cirrhosis.1 In summary, in our patients we observed indirect evidence of expanded central vascular fluid volume compared with healthy controls and thought this physiopathological alteration was due to slightly reduced values of glomerular filtration rate (measured as creatinine clearance) and, mainly, to increased distal tubular retention of sodium when expressed as a fraction of the filtered sodium load that is reabsorbed by the distal nephron (26.9 (6.7)% v 12.5 (3.4)%, respectively; p<0.05).1 

Claria and Rodes advanced two criticisms and affirmed that our results, obtained by means of the lithium clearance and fractional excretion technique, may be influenced by two fundamental flaws. Firstly, the reliability of lithium clearance as a marker of distal fluid delivery in clinical conditions characterised by low fractional sodium excretion (below 0.40%) has not been proved due to possible lithium reabsorption in the distal nephron.2 Secondly, … 

Professor J Rodes, Liver Unit, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain.rodes{at}medicina.ub.es

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Calling on Europe to support operational research in low-income and middle-income countries
Authors: GianLuca Quaglio, Andy Ramsay, Anthony D Harries, Theodoros Karapiperis, Giovanni Putoto, Chris Dye, Ole F Olesen, Göran Tomson, Rony Zachariah
Journal: The Lancet Global Health (2014)

Calling on Europe to support operational research in low-income and middle-income countriesOperational research in public health is the investigation of strategies, interventions, instruments, or knowledge that can enhance the quality, coverage, eff ectiveness, or performance of health systems, health services, or disease control programmes. 1 By showing what works and what does not in various contexts, operational research can provide evidence to help policy makers to adapt health interventions and services for maximum public health benefi t. 2During a recent workshop organised by the Science and Technology Options Assessment body (STOA) of the European Parliament, experts in the fi eld of operational research concluded that the European Union (EU) should increase its support for this form of research.STOA, which provides independent assessments of scientifi c and technological options in various sectors including the life sciences, organised the workshop in collaboration with Médecins Sans Frontières, the International Union Against Tuberculosis and Lung Disease, and WHO/TDR.The participants discussed several overarching themes, concluding that research is too often separate from implementation.A crucial gap remains between the development of effi cacious health interventions and their optimum delivery in real-life settings.This gap is particularly true in many low-income and middleincome countries (LMICs).For example, two-thirds of childhood deaths are potentially avoidable with known technologies that are implemented to scale. 3Similarly, results of clinical trials have shown major benefi ts of parenteral artesunate compared with quinine to treat malaria, but quinine remains the standard treatment in most malaria-endemic countries. 4Operational research could show how to introduce and scale up such interventions, which could have a major eff ect on global health. 5any LMICs are rich in data, but have insuffi cient information.Massive amounts of routine data are collected within public health systems such as by ministries of health (MOH) and non-governmental organisations (NGOs), but are underused, reducing the potential eff ect of research on policy and practice.Compounding the problem, most data collected at
Some histological features of canine cardiac transplants
Authors: J. Leandri
Journal: Thorax (1967)

The cellular reaction in cardiac homografts was observed mainly in the perivascular areas and in the subepicardial and subendocardial layers. All the valvular structures were involved by the cellular infiltration, but the aortic and pulmonary cusp changes were less severe. Although the vascular changes seemed to be severe, yet, for unknown reasons, some vascular segments and consequently some myocardial areas were spared. The intermittent immunosuppressive therapy (azathioprine) seemed to have influenced the pathological changes; it did not completely prevent the rejection process, suggesting that better control of the host-versus-graft reaction could be obtained by continuous immunosuppression.
Impact of mild cognitive impairment on survival in very elderly people: cohort study
Authors: J Gussekloo, R G J Westendorp, E J Remarque, A M Lagaay, T J Heeren, D L Knook
Journal: BMJ (1997)

which successfully extended standard nursing practice to prevent falls in inpatients.A similar programme may be effective in Britain.STRATIFY may be applicable to many acute hospital elderly units.Further study is needed to determine whether the falls of inpatients identified as high risk can be prevented by a targeted intervention.
Structure of mammalian metallothionein.
Authors: J H Kägi, M Vasák, K Lerch, D E Gilg, P Hunziker, W R Bernhard, M Good
Journal: Environmental Health Perspectives (1984)

All mammalian metallothioneins characterized contain a single polypeptide chain of 61 amino acid residues, among them 20 cysteines providing the ligands for seven metal-binding sites. Native metallothioneins are usually heterogeneous in metal composition, with Zn, Cd, and Cu occurring in varying proportions. However, forms containing only a single metal species, i.e., Zn, Cd, Ni, Co, Hg, Pb, Bi, have now been prepared by in vitro reconstitution from the metal-free apoprotein. By spectroscopic analysis of such derivatives it was established that all cysteine residues participate in metal binding, that each metal ion is bound to four thiolate ligands, and that the symmetry of each complex is close to that of a tetrahedron. To satisfy the requirements of the overall Me7(Cys-)20 stoichiometry, the complexes must be combined to form metal-thiolate cluster structures. Experimental proof for the occurrence of such clusters comes from the demonstration of metal-metal interactions by spectroscopic and magnetic means. Thus, in Co(II)7-metallothionein, the Co(II)-specific ESR signals are effectively suppressed by antiferromagnetic coupling of juxtaposed paramagnetic metal ions. By monitoring changes in ESR signal size occurring on stepwise incorporation of Co(II) into the protein, it is possible to follow the building up of the clusters. This process is biphasic. Up to binding of four equivalents of Co(II), the ESR amplitude increases in proportion to the metal content, indicating generation of magnetically noninteracting high-spin complexes. However, upon addition of the remaining three equivalents of Co(II), these features are progressively suppressed, signaling the formation of clusters. The same mode of cluster formation has also been documented for Cd and Hg. The actual spatial organization of the clusters and the polypeptide chain remains to be established. An attractive possibility is the arrangement of the tetrahedral metal-thiolates in adamantane-like structures surrounded by properly folded segments of the chain providing the ligands. 1H-NMR data and infrared absorption measurements are consistent with a tightly folded structure rich in beta-type conformation.
FURTHER OBSERVATIONS ON THE INFLUENCE OF ALCOHOL ON THE METABOLISM OF HEPATIC GLYCOGEN.
Authors: WILLIAM SALANT
Journal: JAMA (1906)

The present report gives the results of a further study of the possible influence of alcohol on the metabolism of glycogen in the liver. It has recently been shown that, to a certain extent, alcohol can replace the carbohydrates of our daily diet. Consequently it would seem<i>a priori</i>that it might indirectly be a glycogen former, by sparing the carbohydrate radical of the tissue proteins, which may serve as a source of glycogen. The results of Nebelthan's<sup>1</sup>investigations, indeed, lend some support to this view. He found considerable quantities of glycogen in the liver of the hens to which large amounts of alcohol were fed after they had been starved for six days. In one of his experiments he found as much as 3.5 per cent. of glycogen in the liver after feeding 10 c.c. of 96 per cent. alcohol per kilo in twenty-four hours. To test the
Surface Charge: A Key Determinant of Protein Localization and Function
Authors: Neil M. Goldenberg, Benjamin E. Steinberg
Journal: Cancer Research (2010)

Electrostatic charge at the membrane surface has emerged as a crucial determinant of the localization and activation of many proteins containing polycationic domains in their amino acid sequence. The spatiotemporal regulation of surface charge, as well as the downstream effects of dysregulation of surface charge, may have a significant impact on many of the signaling molecules important to cancer biology such as K-ras. Cancer Res; 70(4); 1277-80.
Regulation of human endothelial progenitor cell maturation by polyurethane nanocomposites
Authors: Huey-Shan Hung, Yi-Chun Yang, Yu-Chun Lin, Shinn-Zong Lin, Wei-Chien Kao, Hsien-Hsu Hsieh, Mei-Yun Chu, Ru-Huei Fu, Shan-hui Hsu
Journal: Biomaterials (2014)
Stress and Coping in Time of War: Generalizations From the Israeli Experience
Authors: Norman R. Bernstein
Journal: JAMA (1987)

The purpose of this book is to examine the pattern of psychological and social stress in time of war as part of a general study of the consequences of catastrophic events, such as rape, war, cyclones, earthquakes, and incest. There are 34 authors, mostly Israeli, among whom are four Swedes and one American. They have made a profound effort to utilize the Israeli war experiences to understand war coping in an overall perspective. Much of their material also involves World Wars I and II and the Korean and Vietnam wars. There are sections on combat stress reaction and subsequent post-traumatic stress disorders, contrasting Americans in Vietnam and Israelis in Lebanon. Performance in highly stressful situations, such as combat, parachute jumping, solitary confinement, and climatic stress, is examined. Contributors discuss the psychological impact of terrorism on society in terms of what a country expects will happen and how it believes it
Surgical treatment of female infertility: value of paradoxical oophorectomy.
Authors: J S Scott, E M Lynch, J A Anderson
Journal: BMJ (1976)

The outcome of surgical treatment for infertility in 111 women has been reviewed. The procedures used, depending on the lesions present, were: myomectomy; tubal implantation, anastomosis, and salpingostomy; division of adhesions; ovarian wedge resection; and "paradoxical" oophorectomy. The results are analysed by comparing pregnancy rates after surgery with those for the total time of exposure. Only for division of adhesions and oophorectomy were statistically significant results obtained. Many of the pregnancies, however, occurred soon after operations that had been preceded by long periods of infertility. With single tube patency, which had been proved at laparotomy, contralateral oophorectomy appeared to be of value. In the light of these observations we suggest that in cases of tubal ectopic gestation salpingo-oophorectomy should be considered in preference to salpingectomy when the opposite tube and ovary are healthy. Wedge resection for the Stein-Leventhal syndrome effectively restored ovulatory activity.
Treat hypothyroidism—cure form of septal hypertrophy
Authors: Phil Gunby
Journal: JAMA (1979)

The prognosis is a gloomy one for patients with asymmetric septal hypertrophy (ASH). When the condition is severe enough to cause outflow tract obstruction, it is known as idiopathic hypertrophic subaortic stenosis (IHSS). Typically, patients with IHSS are asked to curtail their physical activity drastically and may be treated with β-adrenergic blocking agents or by surgical resection of the hypertrophied septum. Despite these interventions, they often experience progressive debility and live at risk of sudden death. Now a team in Rochester, NY, has discovered a form of the disease that is not only treatable but curable. Clinically indistinguishable from the familial form (which predominates in males and is transmitted as an autosomal dominant trait), the newly identified form of ASH is secondary to hypothyroidism (which predominates in women), rather than genetic in origin. It disappears completely with full thyroid replacement therapy. R. Paul Miller, MD, assistant professor of medicine at
Variability of fine particle deposition in healthy adults: effect of age and gender.
Authors: W D Bennett, K L Zeman, C Kim
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Recent epidemiologic studies suggest increased mortality among the elderly in association with particulate air pollution. We investigated the variability in fractional deposition (DF) of inhaled particles (2 microns mass median aerodynamic diameter [MMAD]) in 62 subjects with normal lung function, aged 18 to 80 yr. Each subject inhaled 2-microns monodisperse carnauba wax particles while following a breathing pattern previously determined by respiratory inductance plethysmography in that subject (i.e., particles inhaled) was determined by laser aerosol photometry and pneumotachometry at the mouth. DF (mean DF = 0.29 +/- 0.06 (ages 18 to 40 yr), 0.29 +/- 0.07 (ages 41 to 60 yr), and 0.26 +/- 0.06 (age over 60 yr) was independent of age. There was a tendency toward greater DF in female than in male subjects; DF = 0.30 +/- 0.07 (females) and 0.27 +/- 0.06 (males) (p = 0.06); however, because the males had 45% higher minute ventilations than the females, the deposition rate (Drate), or particles depositing per unit of time, was 30% greater in males than in females (p = 0.004). Multiple regression analysis showed that among all subjects, the variability in DF was best predicted by variability in the breathing period (T) associated with the pattern used to breathe the particles, and by the subject's specific airway resistance (sRAW). These results may prove useful in determining age- and gender-relative risks that may be associated with the inhalation of pollutant particles in ambient air.
Growth inhibition of the intestinal parasite Giardia lamblia by a dietary lectin is associated with arrest of the cell cycle.
Authors: E Ortega-Barria, H D Ward, G T Keusch, M E Pereira
Journal: Journal of Clinical Investigation (1994)

Giardia lamblia, a cause of diarrheal disease throughout the world, is a protozoan parasite that thrives in the small intestine. It is shown here that wheat germ agglutinin (WGA), a naturally occurring lectin widely consumed in normal human diets, reversibly inhibits the growth of G. lamblia trophozoites in vitro, and reduces infection by G. muris in the adult mouse model of giardiasis. The inhibitory effect was dose related, not associated with cytotoxicity and reversed by N-acetyl-D-glucosamine in accordance with the known specificity of the lectin and in agreement with the presence of GlcNAc residues on the surface membrane of G. lamblia trophozoites. Cell cycle analysis revealed that parasites grown in the presence of WGA are arrested in the G2/M phase, providing an explanation for the lectin-induced inhibition of cell proliferation. Comparison of electrophoretic profiles by lectin blot analysis revealed both glycoprotein induction and suppression in growth-arrested organisms. Our findings raise the possibility that blocking trophozoite growth with naturally occurring dietary lectins may influence the course of giardiasis. In addition, the study of cell cycle arrest by WGA may provide a model to study the regulation of cell division in lower eukaryotes.