tbuckley/cabot-search huggingface dataset:
Transcriptional profiling of MnSOD-mediated lifespan extension in Drosophila reveals a species-general network of aging and metabolic genes
Authors: Christina Curtis, Gary N Landis, Donna Folk, Nancy B Wehr, Nicholas Hoe, Morris Waskar, Diana Abdueva, Dmitriy Skvortsov, Daniel Ford, Allan Luu, Ananth Badrinath, Rodney L Levine, Timothy J Bradley, Simon Tavaré, John Tower
Journal: Genome biology (2007)

Abstract Background Several interventions increase lifespan in model organisms, including reduced insulin/insulin-like growth factor-like signaling (IIS), FOXO transcription factor activation, dietary restriction, and superoxide dismutase (SOD) over-expression. One question is whether these manipulations function through different mechanisms, or whether they intersect on common processes affecting aging. Results A doxycycline-regulated system was used to over-express manganese-SOD (MnSOD) in adult Drosophila , yielding increases in mean and maximal lifespan of 20%. Increased lifespan resulted from lowered initial mortality rate and required MnSOD over-expression in the adult. Transcriptional profiling indicated that the expression of specific genes was altered by MnSOD in a manner opposite to their pattern during normal aging, revealing a set of candidate biomarkers of aging enriched for carbohydrate metabolism and electron transport genes and suggesting a true delay in physiological aging, rather than a novel phenotype. Strikingly, cross-dataset comparisons indicated that the pattern of gene expression caused by MnSOD was similar to that observed in long-lived Caenorhabditis elegans insulin-like signaling mutants and to the xenobiotic stress response, thus exposing potential conserved longevity promoting genes and implicating detoxification in Drosophila longevity. Conclusion The data suggest that MnSOD up-regulation and a retrograde signal of reactive oxygen species from the mitochondria normally function as an intermediate step in the extension of lifespan caused by reduced insulin-like signaling in various species. The results implicate a species-conserved net of coordinated genes that affect the rate of senescence by modulating energetic efficiency, purine biosynthesis, apoptotic pathways, endocrine signals, and the detoxification and excretion of metabolites.
Contrasting levels of DNA polymorphism at the autosomal and X-linked visual color pigment loci in humans and squirrel monkeys
Authors: L. C. Shimmin, J. Miller, H. N. Tran, W. H. Li
Journal: Molecular Biology and Evolution (1998)

The X-linked color pigment (opsin) locus is known to be highly polymorphic in the squirrel monkey and other New World monkeys. To see whether this is also the case for the autosomal (blue) opsin locus, we obtained 32 squirrel monkey and 30 human blue opsin gene sequences. No amino acid polymorphism was found in either the squirrel monkey sample or the human sample, contrary to the situation at the X-linked opsin locus. This sharp contrast in the level of polymorphism might be due to differences in gene expression between the autosomal and the X-linked loci. At the X-linked locus, heterozygote advantage can occur because, owing to X-inactivation, the two alleles in a heterozygote are expressed in different cone cells, producing two types of cone cell, whereas at the autosomal locus, heterozygote advantage cannot occur because the two alleles in a heterozygote are expressed in the same cone cells, producing only one type of cone cell (i.e., phenotypically a homozygote). From the sequence data, the levels of nucleotide diversity (pi, i.e., the number of nucleotide differences per site) are estimated: for the human sample, pi = 0.00% per nondegenerate site, 0.00% per twofold degenerate site, and 0.04% per fourfold degenerate site in the coding regions and 0.01% per site in intron 4; for the squirrel monkey sample, pi = 0.00% per nondegenerate site, 0.00% per twofold degenerate site, and 0.15% per fourfold degenerate site in the coding regions and 0.17% per site in intron 4. The blue opsin genes from the common and pygmy chimpanzees, the gorilla, the capuchin, and the howler monkey were also sequenced. Features critical to the function of the opsin are well conserved in all known mammalian sequences. However, the interhelical loops are, on average, actually more conservative than the transmembrane helical regions. In addition, these sequence data and those from some other genes indicate that the common and pygmy chimpanzees are not closely related, their divergence data being from one third to one half the date of the human-chimpanzee divergence.
Sensitive Troponin I Assay in Early Diagnosis of Acute Myocardial Infarction
Authors: Till Keller, Tanja Zeller, Dirk Peetz, Stergios Tzikas, Alexander Roth, Ewa Czyz, Christoph Bickel, Stephan Baldus, Ascan Warnholtz, Meike Fröhlich, Christoph R. Sinning, Medea S. Eleftheriadis, Philipp S. Wild, Renate B. Schnabel, Edith Lubos, Nicole Jachmann, Sabine Genth-Zotz, Felix Post, Viviane Nicaud, Laurence Tiret, Karl J. Lackner, Thomas F. Münzel, Stefan Blankenberg
Journal: New England Journal of Medicine (2009)

Cardiac troponin testing is central to the diagnosis of acute myocardial infarction. We evaluated a sensitive troponin I assay for the early diagnosis and risk stratification of myocardial infarction.In a multicenter study, we determined levels of troponin I as assessed by a sensitive assay, troponin T, and traditional myocardial necrosis markers in 1818 consecutive patients with suspected acute myocardial infarction, on admission and 3 hours and 6 hours after admission.For samples obtained on admission, the diagnostic accuracy was highest with the sensitive troponin I assay (area under the receiver-operating-characteristic curve [AUC], 0.96), as compared with the troponin T assay (AUC, 0.85) and traditional myocardial necrosis markers. With the use of the sensitive troponin I assay (cutoff value, 0.04 ng per milliliter) on admission, the clinical sensitivity was 90.7%, and the specificity was 90.2%. The diagnostic accuracy was virtually identical in baseline and serial samples, regardless of the time of chest-pain onset. In patients presenting within 3 hours after chest-pain onset, a single sensitive troponin I assay had a negative predictive value of 84.1% and a positive predictive value of 86.7%; these findings predicted a 30% rise in the troponin I level within 6 hours. A troponin I level of more than 0.04 ng per milliliter was independently associated with an increased risk of an adverse outcome at 30 days (hazard ratio, 1.96; 95% confidence interval, 1.27 to 3.05; P=0.003).The use of a sensitive assay for troponin I improves early diagnosis of acute myocardial infarction and risk stratification, regardless of the time of chest-pain onset.
Utilization of Oral Hypoglycemic Agents in a Drug-Insured U.S. Population
Authors: Stephen J. Boccuzzi, Jenifer Wogen, James Fox, Jennifer C.Y. Sung, Amishi B. Shah, Jennifer Kim
Journal: Diabetes Care (2001)

OBJECTIVE—Clinical trials provide information regarding the safety and efficacy of medications used to manage type 2 diabetes but do not elucidate drug effectiveness in a typical managed care environment. The aim of this study was to characterize “real-world” drug utilization patterns from both a prescriber and a patient perspective. RESEARCH DESIGN AND METHODS—We conducted a retrospective analysis of a large administrative pharmacy claims database, using data on continuously pharmacy benefit–eligible members prescribed oral hypoglycemic agents (OHAs). RESULTS—The 12-month persistence rate for the OHA cohort was low, ranging from 31% for α-glucosidase inhibitors to 60% for metformin; compliance rates varied between 70 and 80%. During the first 12 months of therapy, 36% of the patients remaining on therapy at 12 months had one or more therapy modifications. The mean number of therapy changes increased with the length of patient follow-up, with more than half of all patients experiencing at least one therapy change over the duration of follow-up. CONCLUSIONS—These findings document the wide variation in utilization patterns associated with pharmacological management of type 2 diabetes, suggesting that opportunity exists to optimize its pharmacological management.
Blood and plasma 5-hydroxytryptamine levels in patients with cirrhosis
Authors: Patrice Beaudry, Antoine Hadengue, Jacques Callebert, Christophe Gaudin, Hany Soliman, Richard Moreau, Jean Marie Launay, Didier Lebrec
Journal: Hepatology (1994)

Serotoninergic mechanisms are thought to play a role in portal hypertension. Because this biomine is metabolized by the liver, peripheral blood and plasma levels of 5-hydroxytryptamine and 5-hydroxyindole acetic acid (the main metabolite of 5-hydroxytryptamine) were measured in 30 patients with cirrhosis. Whole-blood 5-hydroxytryptamine levels were significantly lower in patients with cirrhosis (158 +/- 28 nM) than in age-matched controls (332 +/- 19 nM), and no correlation was found between these levels and the severity of cirrhosis. Unconjugated plasma 5-hydroxytryptamine levels, an indication of the active form of 5-hydroxytryptamine, were significantly higher in patients with cirrhosis than in controls (6.8 +/- 1.7 nM and 3.4 +/- 0.5 nM, respectively), and in patients with cirrhosis these levels were higher in Pugh grade A than in Pugh grade C patients. Conjugated-plasma 5-hydroxytryptamine levels were not significantly different between patients with cirrhosis (32.2 +/- 8.1 nmol/L) and controls (16.4 +/- 1.4 nmol/L). Plasma 5-hydroxyindole acetic acid was significantly lower in patients with cirrhosis than in controls (1.5 +/- 0.1 nmol/L and 2.3 +/- 0.1 nmol/L, respectively). In conclusion, this study shows that serotoninergic mechanisms are altered in patients with cirrhosis.
Phase II Study of Abiraterone Acetate in Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer Displaying Bone Flare Discordant with Serologic Response
Authors: Charles J. Ryan, Shreya Shah, Eleni Efstathiou, Matthew R. Smith, Mary-Ellen Taplin, Glenn J. Bubley, Christopher J. Logothetis, Thian Kheoh, Christine Kilian, Christopher M. Haqq, Arturo Molina, Eric J. Small
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Abiraterone is an oral inhibitor of CYP17, which is essential for androgen biosynthesis. This multicenter study assessed its efficacy in patients with castration-resistant prostate cancer (CRPC), without prior chemotherapy or CYP17-targeted therapy, and frequency of bone scans discordant with prostate-specific antigen (PSA) and clinical response. Experimental Design: Thirty-three patients received abiraterone acetate 1,000 mg daily with prednisone 5 mg twice daily in continuous 28-day cycles. Patients were evaluated monthly for efficacy and safety. Bone scan flare was defined as the combination, after 3 months of therapy, of an interpreting radiologist's report indicating “disease progression” in context of a 50% or more decline in PSA level, with scan improvement or stability 3 months later. Results: A 50% or more decline in PSA level at week 12 was confirmed in 22 of 33 (67%) patients. Declines in PSA level of 50% or more were seen in 26 of 33 (79%) patients. Undetectable PSA levels (≤0.1 ng/mL) occurred in 2 patients. Median time on therapy and time to PSA progression were 63 weeks and 16.3 months, respectively. Twenty-three patients were evaluable for bone scan flare. Progression was indicated in radiologist's report in 12 of 23 (52%), and 11 of 12 subsequently showed improvement or stability. As prospectively defined, bone scan flare was observed in 11 of 23 (48%) evaluable patients or 11 of 33 (33%) enrolled patients. Adverse events were typically grade 1/2 and consistent with prior published abiraterone reports. Conclusion: Clinical responses to abiraterone plus prednisone were frequent and durable in men with metastatic CRPC. Further investigation is needed to clarify the confounding effect of bone scan flare on patient management and interpretation of results. Clin Cancer Res; 17(14); 4854–61. ©2011 AACR.
THE EFFECTS OF ENDOTOXIN ON VASCULAR ENDOTHELIUM
Authors: J. M. McGrath, G. J. Stewart
Journal: The Journal of Experimental Medicine (1969)

This study was undertaken to develop a technique for the preparation of sheets of endothelial cells and to investigate the effects of bacterial endotoxin on large numbers of cells from continuous sheets of vascular endothelium. Rabbits were divided into one control and two experimental groups. The experimental animals received intracardially an LD(50) dose of Escherichia coli endotoxin. 1 and 24 hr postinjection, the vessels of the animals were perfused with glutaraldehyde in Millonig's buffer with methylene blue as a marker. Pieces of mesentery containing arteries were postfixed in buffered glutaraldehyde, dehydrated, and placed in acetone (to remove fat deposits). The surrounding connective tissue was stripped from the mesenteric arteries, and segments of the vessels were slit longitudinally, flattened out, and firmly affixed to a sheet of cork with fine mounting pins. A 3% solution of Formvar in ethylene dichloride was pipetted onto the luminal surfaces of the vessels. The endothelial cells were impregnated with and adhered to the Formvar and, after soaking overnight in 10 N NaOH, could be stripped from the vessel walls as monolayers. Sheets of Formvar-impregnated cells were temporarily mounted on glass slides in aqueous methylene blue and examined by phase and bright-field microscopy. Methylene blue stained the nuclei a deep blue and the cytoplasm faintly, but cell outlines were indistinct. Endothelial sheets from control rabbits had smooth, elliptical nuclei oriented parallel to the longitudinal axis of the cells and irregularly distributed over a smooth background with faint longitudinal striations. Essentially every cell in endothelial sheets from endotoxin-injected animals appeared to be severely damaged. Cell sheets from 24 hr posttreatment animals exhibited the same type of, but more extensive, damage than that observed in 1 hr posttreatment animals. The most prominent features of the damaged endothelium were distorted nuclei, apparent nuclear vacuolization, and missing nuclei. Unstained platelets and plaques were present on the surfaces of the specimens from the experimental animals only. Stained and unstained red blood cells were also dispersed over the luminal surfaces of the endotoxin-treated vessels.
S9 Feasibility of establishing a Regional Weaning Unit in Scotland: modelling resource implications and costs
Authors: N. I. Lone, D. Sorensen, T. S. Walsh
Journal: Thorax (2010)

<h3>Introduction</h3> Intensive care (ICU) admission is usually mandatory for patients requiring mechanical ventilation (MV). A proportion of patients require prolonged MV (PMV). In other countries, specialised weaning units allow stable PMV patients to be discharged from the ICU. These units offer cost savings because of lower staff-to-patient ratios. A recent report of UK ICU services recommended that hospitals review the need for specialised weaning centres locally. <h3>Aims</h3> To assess the feasibility of establishing a weaning unit in a Scottish health board region and to model the potential impact on ICU services. <h3>Methods</h3> All admissions to the three adult ICUs in our health board requiring PMV (≥21 days MV) during a 2-year period (2005–2006) were extracted from the Scottish Intensive Care Audit Group database. Four hypothetical weaning units were modelled using different admission criteria, ranging from Unit-A, which required a prolonged period of stability prior to transfer from ICU to the weaning unit (7 days free of both cardiovascular support (CVS) and renal replacement therapy), to Unit-D (2 days free of CVS only). The date of eligibility for each PMV patient for each unit was determined. We used remaining length of stay (LOS) in ICU after eligibility to calculate occupancy rate, refusal rate and net cost saving, varying unit capacity from 1 to 8 beds. <h3>Results</h3> During 2005–2006, 126 patients required PMV. Of these, the number eligible for transfer to a weaning unit varied from 101 (Unit-A) to 117 (Unit-D). Mean ICU LOS after reaching eligibility varied from 14.9 to 15.3 days. Occupancy rates for Unit-A ranged from 90.8% to 25.5% (1-bed to 8-bed unit) and for Unit-D from 93.3% to 30.5%. Refusal rates for Unit-A ranged from 88.1% to 0%, and for Unit-D 92.3% to 0%. The greatest cost saving was for Unit-D with 3 beds (£344 025) (Abstract S9 Figure 1). <h3>Conclusion</h3> PMV patients use 25% of ICU bed-days in our region. Establishing a 3-bed weaning unit could lead to a reduction of 800 ICU bed-days, a net annual cost saving of £340 000, and acceptable occupancy (70%) and refusal (30%) rates. Establishing such a unit would be feasible in our health board region.
The Prognostic Value of MicroRNAs Varies with Patient Race/Ethnicity and Stage of Colorectal Cancer
Authors: Liselle C. Bovell, Chandrakumar Shanmugam, Balananda-Dhurjati K. Putcha, Venkat R. Katkoori, Bin Zhang, Sejong Bae, Karan P. Singh, William E. Grizzle, Upender Manne
Journal: Clinical Cancer Research (2013)

MicroRNAs (miRNA) have potential prognostic value for colorectal cancers; however, their value based on patient race/ethnicity and pathologic stage has not been determined. The goal was to ascertain the prognostic value of 5 miRNAs with increased expression in colorectal cancers of African American (black) and non-Hispanic Caucasian (white) patients.TaqMan quantitative real-time PCR was used to quantify expression of miR-20a, miR-21, miR-106a, miR-181b, and miR-203 in paired normal and tumor colorectal cancer archival tissues collected from 106 black and 239 white patients. The results were correlated with overall survival based on patient race/ethnicity and pathologic stage. Because decisions about adjuvant therapy are important for stage III colorectal cancers, and because miR-181b seemed to have prognostic value only for stage III black patients, we assessed its prognostic value in a separate cohort of 36 stage III colorectal cancers of blacks.All 5 miRNAs had higher expression in colorectal cancers (>1.0-fold) than in corresponding normal tissues. High expression of miR-203 was associated with poor survival of whites with stage IV colorectal cancers (HR = 3.00; 95% CI, 1.29-7.53), but in blacks it was an indicator of poor survival of patients with stages I and II colorectal cancers (HR = 5.63; 95% CI, 1.03-30.64). Increased miR-21 expression correlated with poor prognosis for white stage IV patients (HR = 2.50; 95% CI, 1.07-5.83). In both test and validation cohorts, high miR-181b expression correlated with poor survival of only black patients with stage III colorectal cancers (HR = 1.94; 95% CI, 1.03-3.67).These preliminary findings suggest that the prognostic value of miRNAs in colorectal cancers varies with patient race/ethnicity and stage of disease.
A CARRIER STATE OF MUMPS VIRUS IN HUMAN CONJUNCTIVA CELLS
Authors: Duard L. Walker, Harry C. Hinze
Journal: The Journal of Experimental Medicine (1962)

Mumps virus produced a carrier state in human conjunctiva cells that was maintained for more than 100 subcultures over a period of 3 years. Antiserum in the medium was not required. The virus had little apparent effect on the cells which grew at a rate similar to uninfected control cells. Mumps virus was regularly found in the culture medium at levels about 0.9 log higher than the cell-associated virus. When first tested after 30 subcultures, the virus was found to have lost its cytopathogenicity for cells ordinarily susceptible to mumps virus, but was identifiable as mumps virus by neutralization with specific antiserum. Use of fluorescein-labeled antiserum revealed that 80 to 95 per cent of cells in the carrier cultures contained mumps virus antigen. The antigen was concentrated in a few sharply circumscribed, discrete masses in the cell cytoplasm rather than in many granules throughout the cytoplasm as is characteristic of cell infection by cytopathogenic mumps virus. The carrier cultures were resistant to the destructive effect of a cytopathogenic line of mumps virus, but showed little resistance to the cytopathogenic effect of vesicular stomatitis, Sendai, or Newcastle disease viruses.
Experimental pain in the stomach: a model based on electrical stimulation guided by gastroscopy
Authors: A M Drewes, L Arendt-Nielsen, J H Jensen, J B Hansen, H B Krarup, U Tage-Jensen
Journal: Gut (1997)

Abdominal pain is often variable in intensity and difficult to characterise due to its referred pain pattern. Clinical pain is furthermore confounded by various emotional and cognitive factors.To develop and apply an experimental model to induce localised gastric pain.Twelve healthy male volunteers.Stimulating electrodes were mounted on a biopsy forceps and electric stimuli were delivered during gastroscopy. Single, five repeated, and continuous stimuli were given at four locations in the stomach. Pain detection thresholds and pain intensities were assessed together with localisation of the referred pain area.Pain detection thresholds were higher in the prepyloric region compared with those obtained at the lesser and greater curvature. Increasing stimulus intensity resulted in augmented pain perception and repeated stimuli elicited pain at a lower stimulus intensity than single stimuli. Continuous stimuli evoked constant (33%), increasing (33%), or decreasing (33%) pain. The localisation of referred pain varied considerably in the subjects.The model seems relevant to study basic pain mechanisms elicited by localised stimuli in the stomach. The experimental data support the premise that a gastric focus should always be suspected in patients referred with different kinds of abdominal pain.
Combined cetuximab and trastuzumab are superior to gemcitabine in the treatment of human pancreatic carcinoma xenografts
Authors: C. Larbouret, B. Robert, C. Bascoul-Mollevi, F. Penault-Llorca, A. Ho-Pun-Cheung, S. Morisseau, I. Navarro-Teulon, J.-P. Mach, A. Pèlegrin, D. Azria
Journal: Annals of Oncology (2009)