tbuckley/cabot-search huggingface dataset:
Enhanced expression of an exocrine pancreatic protein in Alzheimer's disease and the developing human brain.
Authors: S M de la Monte, M Ozturk, J R Wands
Journal: Journal of Clinical Investigation (1990)

Pancreatic thread protein (PTP) is a major exocrine secretory protein that in vitro forms filamentous bundles reminiscent of the paired helical filaments of Alzheimer's disease (AD). We previously described increased PTP immunoreactivity in AD brains and now report high levels in the developing human brain. Using a full-length cloned bovine PTP cDNA and synthetic oligonucleotides corresponding to human PTP cDNA, which is identical to human islet cell regeneration factor, we analyzed the expression of PTP in pancreas and brain. A major 0.9-kb as well as several minor transcripts were identified in human pancreas. In AD brain, the same size transcripts were detected by Northern analysis, primer extension assay, or polymerase chain reaction amplification of cDNAs generated by reverse transcriptase assay. There were significantly higher levels of PTP mRNA in brains with AD compared with aged controls, with increased amounts of 1.2-, 0.6-, and 0.4-kb transcripts by Northern analysis. In situ hybridization localized expression to pyramidal neurons in the cerebral cortex, the same population that contains neurofibrillary tangles and high levels of immunoreactive PTP. These findings suggest that AD is associated with enhanced expression of PTP-related transcripts with intraneuronal accumulation of PTP-like proteins.
Preoperative endoscopic sphincterotomy as an adjunct to cholecystectomy for common bile duct stones
Authors: Peter B. Cotton
Journal: Hepatology (1988)

One hundred and twenty patients with known common bile duct stones were entered into a prospective randomised study of preoperative endoscopic sphincterotomy and stone clearance (group 1) versus surgery alone (group 2). Five patients were incorrectly entered; the 55 patients randomised to group 1 and the 60 randomised to group 2 were well matched with respect to clinical features and biochemical and medical risk factors. In group 1 endoscopic stone clearance was successful in 50 patients (91%); five of these patients refused elective surgery, though this was subsequently necessary in one. In group 2 common bile duct stones were cleared surgically in 54 of 59 patients (91.5%); one patient was treated by endoscopic sphincterotomy alone because of a myocardial infarct. The overall major complication rate in group 1 was 16.4% and included two deaths; in group 2 this was 8.5% and included one death. The minor complication rate in group 1 was 16.4% and that in group 2, 13.6%. These differences in outcome were not significant. Despite a significant reduction in total hospital stay of patients in group 1, these results do not support the routine use of preoperative endoscopic sphincterotomy in patients having biliary surgery for stones in the common bile duct.
Mass screening for lung cancer with mobile spiral computed tomography scanner
Authors: Shusuke Sone, Shodayu Takashima, Feng Li, Zhigang Yang, Takayuki Honda, Yuichiro Maruyama, Minoru Hasegawa, Takeshi Yamanda, Keishi Kubo, Kazuhisa Hanamura, Kazuhiro Asakura
Journal: The Lancet (1998)
Abstract 5174: Involvement of COX-2 in p53 induction and Jnk activation following DNA damage.
Authors: Joohwee Kim, Hyunju Lee, Kawngil Park, Thomas E. Eling, Minsub Shim
Journal: Cancer Research (2013)

Abstract Cyclooxygenase (COX) is a rate-limiting enzyme in arachidonic acid cascade and exists as two related but unique isoforms, COX-1 and COX-2. While COX-1 is constitutively expressed in many tissues and is believed to play a role in tissue homeostasis, COX-2 is highly inducible by various stimuli including inflammatory cytokines, growth factors, and DNA damage. In addition, aberrant COX-2 expression is frequently observed in many types of cancer, suggesting the role of COX-2 in tumor development and progression. p53 is a well-known tumor suppressor and plays a key role in the control of normal cell's response to environmental or cellular stresses. Although p53 has been shown to regulate COX-2 expression, the modulation of p53 levels by COX-2 has not been determined. In the present study, we have examined the role of COX-2 as an upstream regulator of p53 levels using COX-2 knockout (KO) mouse embryonic fibroblasts (MEFs). DNA damage-induced increase in p53 protein levels were greatly reduced in COX-2 KO MEFs compared to wild type (WT) or COX-1 KO MEFs. Furthermore, a COX-2 specific inhibitor suppressed doxorubicin-induced p53 accumulation and cell death. However, initial induction of p53 accumulation in response to doxorubicin was not altered by deficiency or inhibition of COX-2, suggesting that COX-2 may be involved in maintenance of p53 stability. Doxorubicin-induced accumulation of p53 appeared to be mediated through the activation of Jun-N-terminal Kinase (Jnk). Activation of Jnk by doxorubicin was decreased in COX-2 KO MEFs or by COX-2 inhibition, suggesting that DNA damage induces activation of Jnk by a mechanism that involves COX-2. Our results suggest the existence of novel cross-talk between COX-2 and p53 and identify COX-2 as a potential target for reducing the side effects from chemotherapy. Citation Format: Joohwee Kim, Hyunju Lee, Kawngil Park, Thomas E. Eling, Minsub Shim. Involvement of COX-2 in p53 induction and Jnk activation following DNA damage. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5174. doi:10.1158/1538-7445.AM2013-5174
Are “exercise pills” the answer to the growing problem of physical inactivity?
Authors: Stuart J Warden, Robyn K Fuchs
Journal: British Journal of Sports Medicine (2008)

Physical inactivity is an important and growing major health concern and is defined as not engaging in any regular pattern of physical activity beyond that associated with daily functioning.1 The many consequences of inactivity include reductions in insulin sensitivity of skeletal muscle and expansion of fat storage, factors associated with the development of obesity, metabolic syndrome and type 2 diabetes.2 Exercise is often performed with the goal of counteracting these changes and enhancing health and life expectancy. Imagine if the health benefits of exercise could be produced simply by taking a so-called “exercise pill”. This would be every couch potato’s dream and may be a reality if a paper recently published in the prestigious journal Cell is any indication.

Narkar et al 3 investigated the benefits of two orally active compounds on exercise endurance in mice. The first compound, known simply as GW1516, did not enhance endurance when given to sedentary mice, but when combined with a progressive treadmill exercise programme, it enabled mice to run 60–75% further and longer than mice exposed to the exercise programme alone. Thus, there was synergy between exercise and GW1516, …
Novel Soy Germ Pasta Improves Endothelial Function, Blood Pressure, and Oxidative Stress in Patients With Type 2 Diabetes
Authors: Carlo Clerici, Elisabetta Nardi, Pier Maria Battezzati, Stefania Asciutti, Danilo Castellani, Nadia Corazzi, Vittorio Giuliano, Stefania Gizzi, Gabriele Perriello, Giorgio Di Matteo, Francesco Galli, Kenneth D.R. Setchell
Journal: Diabetes Care (2011)

To compare the effects of a novel soy germ-enriched pasta, containing isoflavone aglycons, with conventional pasta on endothelial function and cardiovascular risk markers in patients with type 2 diabetes (T2D).This randomized controlled double-blind crossover study compared one serving/day of soy germ pasta and conventional pasta for 8 weeks for effects on brachial artery flow-mediated vasodilation, blood pressure, plasma lipids, oxidized LDL cholesterol, 8-iso-PGF2α, total antioxidant capacity (TAC), glutathione (GSH), and homocysteine.Isoflavone-enriched pasta significantly improved arterial stiffness (P = 0.005) and reduced systolic (P = 0.026) and diastolic (P = 0.017) blood pressures. Plasma TAC increased (P = 0.0002), oxidized LDL cholesterol decreased (P = 0.009), 8-iso-PGF2α decreased (P = 0.001), GSH levels increased (P = 0.0003), and homocysteine decreased (P = 0.009) consistent with a reduction in oxidative stress. No significant changes were observed with conventional pasta.Pasta enriched with biologically active isoflavone aglycons improved endothelial function and had beneficial effects on cardiovascular risk markers in patients with T2D.
N-Propionylated Group B Meningococcal Polysaccharide Mimics a Unique Bactericidal Capsular Epitope in Group B Neisseria meningitidis
Authors: Robert A. Pon, Michele Lussier, Qing-Ling Yang, Harold J. Jennings
Journal: The Journal of Experimental Medicine (1997)

The N-propionylated group B meningococcal polysaccharide (NPrGBMP) mimics a unique protective epitope on the surface of group B meningococci (GBM) and Escherichia coli K1. Using a series of monoclonal antibodies (mAbs) induced by the NPrGBMP-monomeric tetanus toxoid (TT) conjugate vaccine it was demonstrated that mAbs having specificities for both extended and conventional short segments of the NPrGBMP were formed, but only the former were bactericidal, and/or gave passive protection against live challenge by GBM. The failure of mAbs specific for short epitopes to protect was further established when (NeuPr)4-TT was used as the vaccine. Of all the mAbs produced that were specific for short internal segments of the NPrGBMP, none were protective, despite the fact that most of them cross-react with the GBM capsular polysaccharide. In contrast, most of the protective mAbs produced by NPrGBMP- TT did not recognize the group B meningococcal polysaccharide (GBMP) unless it was present in its aggregated high molecular weight form. The bactericidal epitope mimicked by the NPrGBMP was shown to be ubiquitous in the capsule of both GBM and E. coli K1 using immunogold labeling techniques and, because of its unique properties, its identification could be significant in the development of a comprehensive conjugate vaccine against group B meningococcal meningitis. This is because most known human alpha(2-8)-polysialic acid self-antigens can be accommodated in 30-50 alpha(2-8)-linked sialic acid residues, which is roughly equivalent to an 11-kD length of the GBMP. It has been hypothesized that the formation of the protective epitope on the surface of GBM is due to the interaction of helical segments of the GBMP with another molecule and that the protective epitope is mimicked by the NPrGBMP. Support for the above hypothesis is provided by the fact that the protective NPrGBMP epitope has a similar unusual length dependency to that of the GBMP epitope.
Fentanyl buccal soluble film (FBSF) for breakthrough pain in patients with cancer: a randomized, double-blind, placebo-controlled study
Authors: R. Rauck, J. North, L.N. Gever, I. Tagarro, A.L. Finn
Journal: Annals of Oncology (2009)

Fentanyl buccal soluble film (FBSF) has been developed as a treatment of breakthrough pain in opioid-tolerant patients with cancer. The objective of this study was to evaluate the efficacy of FBSF at doses of 200-1200 microg in the management of breakthrough pain in patients with cancer receiving ongoing opioid therapy.This was a multicenter, randomized, double-blind, placebo-controlled, multiple-crossover study that included opioid-tolerant adult patients with chronic cancer pain who experienced one to four daily episodes of breakthrough pain. The primary efficacy assessment was the sum of pain intensity differences at 30 min (SPID30) postdose.The intent-to-treat population consisted of 80 patients with > or =1 post-baseline efficacy assessment. The least-squares mean (LSM +/- SEM) of the SPID30 was significantly greater for FBSF-treated episodes of breakthrough pain than for placebo-treated episodes (47.9 +/- 3.9 versus 38.1 +/- 4.3; P = 0.004). There was statistical separation from placebo starting at 15 min up through 60 min (last time point assessed). There were no unexpected adverse events (AEs) or clinically significant safety findings.FBSF is an effective option for control of breakthrough pain in patients receiving ongoing opioid therapy. In this study, FBSF was well tolerated in the oral cavity, with no reports of treatment-related oral AEs.
ECOG 3503: A pilot study to determine if downstream markers of EGFR linked signaling pathways predict response to erlotinib (OSI-774) in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC)
Authors: J. Kolesar, J. Brahmer, S. Li, P. Guaglianone, J. Patel, M. Keppen, M. Hidalgo, D. Carbone, J. Siegfried, J. Schiller
Journal: Journal of Clinical Oncology (2006)

7162 Background: Markers of response and survival in patients (pts) who benefit from erlotinib (Elb) remain controversial. In another study, pts who developed a rash on Elb survived longer. The primary objective of this study is to prospectively identify downstream markers of EGFR linked signaling pathways that are predictive of response. The secondary objectives are to estimate response rate (RR), disease control rate, time to progression, survival, and if a grade (gr) 2 rash is a predictor of response and survival. Methods: Pts with advanced NSCLC (Stage IIIB with pleural effusion and IV, no prior systemic treatment, performance status 0–2, no symptomatic CNS metastasis, and adequate renal, hepatic and hematologic function) were accrued to this single arm study. Elb was taken orally once a day until disease progression or unacceptable toxicity. Starting at 150 mg per day, the dose was escalated by 25 mg once every 2 weeks until a gr 2 rash developed, other toxicities precluded escalation, or a maximum dose of 250 mg reached. Response was evaluated by RECIST criteria. Paraffin-fixed tumor tissue was collected on all patients for correlative studies. Results: Over 8 months, 137 pts (58 M, 79 F) were recruited with a median age of 70 (41–92). Most pts were Caucasian (92%) and had adenocarcinoma (54%). Dose escalation occurred in 53/117 of pts, with 11 getting a dose of 250mg. Only 58 pts have been evaluated for response so far. The preliminary RR is 1% (1/58) with stable disease rate of 18% (32/58). Pts have received a median of 4 cycles of treatment (range 0–10). Most pts went off trial because of progression of disease (38%, 52/137) with only 8% (11/137) stopping because of toxicities (42% unknown). Of the 123 pts evaluated for toxicity, 44 (36%) and 10 (8%) had a grade 1 / 2 and 3 rash respectively. Grade 1 / 2 diarrhea occurred in 16% (20/123) and Grade 3 diarrhea in 10% (13/123). One pt died of pneumonitis of unclear cause. Conclusions: Mature toxicity, response, and survival data as well as laboratory studies which include IHC, EGFR mutation and FISH analysis, and genotype and allele frequency will be available at the meeting. [Table: see text]
Inhibition of CSF-1 Receptor Improves the Antitumor Efficacy of Adoptive Cell Transfer Immunotherapy
Authors: Stephen Mok, Richard C. Koya, Christopher Tsui, Jingying Xu, Lídia Robert, Lily Wu, Thomas G. Graeber, Brian L. West, Gideon Bollag, Antoni Ribas
Journal: Cancer Research (2013)

Colony stimulating factor 1 (CSF-1) recruits tumor-infiltrating myeloid cells (TIM) that suppress tumor immunity, including M2 macrophages and myeloid-derived suppressor cells (MDSC). The CSF-1 receptor (CSF-1R) is a tyrosine kinase that is targetable by small molecule inhibitors such as PLX3397. In this study, we used a syngeneic mouse model of BRAF(V600E)-driven melanoma to evaluate the ability of PLX3397 to improve the efficacy of adoptive cell therapy (ACT). In this model, we found that combined treatment produced superior antitumor responses compared with single treatments. In mice receiving the combined treatment, a dramatic reduction of TIMs and a skewing of MHCII(low) to MHCII(hi) macrophages were observed. Furthermore, mice receiving the combined treatment exhibited an increase in tumor-infiltrating lymphocytes (TIL) and T cells, as revealed by real-time imaging in vivo. In support of these observations, TILs from these mice released higher levels of IFN-γ. In conclusion, CSF-1R blockade with PLX3397 improved the efficacy of ACT immunotherapy by inhibiting the intratumoral accumulation of immunosuppressive macrophages.
IMMUNOLOGIC INCOMPETENCE OF IMMUNOLOGICALLY RUNTED ANIMALS
Authors: R. Michael Blaese, Carlos Martinez, Robert A. Good
Journal: The Journal of Experimental Medicine (1964)

1. Adult (A x C57Bl/1)F1 hybrids regularly show runt disease when injected with adult spleen cells from A strain donors. This also occurs when A strain spleen cells are administered to adult C3H mice made tolerant of A strain tissue in the neonatal period. 2. Mice undergoing the graft versus host reaction fail to form antibodies to an intraperitoneal challenge of T2 bacteriophage. This phenomenon was observed well before any of the other overt signs of runting had occurred. Further, inhibition of antibody production to T2 phage by graft versus host reaction initiated at an interval following antigenic stimulation is demonstrated. 3. The basis for the immunologic incompetence of the host with respect to T2 phage is presumed to be the attack of immunologically competent donor cells on the lymphoid cells of the recipient. 4. The failure of the injected parent strain cells to respond to the antigen used may imply immunologic commitment of these cells.
Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation
Authors: Christoph Schmid, Michael Schleuning, Rainer Schwerdtfeger, Bernd Hertenstein, Eva Mischak-Weissinger, Donald Bunjes, Stephanie v. Harsdorf, Christoph Scheid, Udo Holtick, Hildegard Greinix, Felix Keil, Barbara Schneider, Michael Sandherr, Gesine Bug, Johanna Tischer, Georg Ledderose, Michael Hallek, Wolfgang Hiddemann, Hans-Jochem Kolb
Journal: Blood (2006)
Preserved α-Adrenergic Tone in the Leg Vascular Bed of Spinal Cord–Injured Individuals
Authors: Miriam Kooijman, Gerard A. Rongen, Paul Smits, Maria T.E. Hopman
Journal: Circulation (2003)

Supraspinal sympathetic control of leg vascular tone is lost in spinal cord-injured individuals, but this does not result in a reduced leg vascular tone: Leg vascular resistance is even increased. The aim of this study was to assess the alpha-adrenergic contribution to the increased vascular tone in the lower extremity in patients without central sympathetic control of leg circulation.Upper-leg vascular resistance responses to local infusion of incremental doses of phentolamine (a competitive antagonist of the alpha-adrenoceptor) into the femoral artery were determined in 10 spinal cord-injured individuals (SCI) and 8 healthy age-matched control subjects during local beta-adrenergic receptor blockade with propranolol. Basal leg vascular resistance was higher in SCI than in control subjects (41+/-6 arbitrary units [AU] versus 24+/-4 AU; P=0.034). The same accounts for minimal leg vascular resistance, assessed during reactive hyperemia, which was higher in SCI compared with control subjects (6.9+/-1.0 AU versus 2.5+/-0.2 AU; P<0.01). The maximal phentolamine-induced reduction in leg vascular resistance normalized to each individual's minimal resistance did not differ between the groups (68+/-17% and 51+/-4% for SCI and control subjects, respectively; P>0.1). A decline in mean arterial pressure was observed in both groups with increasing dosage of phentolamine. In response, baroreceptor-mediated vasoconstriction was observed in the noninfused leg of the control subjects, whereas in SCI individuals this reaction was absent.These results indicate that the alpha-adrenoceptor-mediated vascular tone in the leg is preserved in spinal cord-injured individuals without sympathetic supraspinal control.
Characterizing the expression of the human olfactory receptor gene family using a novel DNA microarray
Authors: Xiaohong Zhang, Omar De la Cruz, Jayant M Pinto, Dan Nicolae, Stuart Firestein, Yoav Gilad
Journal: Genome biology (2007)

Abstract Background Olfactory receptor (OR) genes were discovered more than a decade ago, when Buck and Axel observed that, in rats, certain G-protein coupled receptors are expressed exclusively in the olfactory epithelium. Subsequently, protein sequence similarity was used to identify entire OR gene repertoires of a number of mammalian species, but only in mouse were these predictions followed up by expression studies in olfactory epithelium. To rectify this, we have developed a DNA microarray that contains probes for most predicted human OR loci and used that array to examine OR gene expression profiles in olfactory epithelium tissues from three individuals. Results We detected expression of 437 (76%) human OR genes in these olfactory epithelia. Interestingly, we detected widespread expression of OR pseudogenes, an observation that may shed light on the mechanism of OR gene choice in the olfactory sensory neurons. To address the hypothesis that OR genes may carry out additional functions, we also characterized the expression of OR genes in a number of non-olfactory tissues. Conclusion While our results corroborate the functional annotation of the majority of predicted human odorant receptors, we find that a large number of putative human OR genes are expressed in non-olfactory tissues, sometimes exclusively so. Our evolutionary analysis of ectopically expressed human OR genes does not lend support to the hypothesis that these genes have alternative functions.
Bungee running: a further report.
Authors: M E Lovell, V P Bradley
Journal: British Journal of Sports Medicine (1995)

Further to the report from Queen Mary's NHS Trust on bungee running affecting children, we present three cases of injury in adults. Two cases of injury presented to Noble's (Isle of Man) Hospital and one to Whiston Hospital, Merseyside. In all three cases, the competitors were trying to stretch the 'bungee' to grasp a pint of beer as a prize, much enthusiasm being shown by spectators. All injuries occurred when the competitors were catapulted backwards with some force.
Natural history of male psychological health. XI: Escape from the underclass
Authors: Jancis V.F. Long, George E. Vaillant
Journal: American Journal of Psychiatry (1984)

A long-term prospective study of 456 inner-city men tested the hypothesis that extreme poverty and chaotic family life produce a self-perpetuating underclass. Men from chronically dependent and multiproblem families were on average indistinguishable by midlife from the children of more stable working-class families in terms of mean income, years of employment, criminality, and mental health. Although attained social class was somewhat lower for the disadvantaged, given the opportunity for steady employment and occupational mobility, the children from multiproblem welfare families did not inevitably perpetuate their initial disadvantages.
Inhalation exposure methodology.
Authors: R F Phalen, R C Mannix, R T Drew
Journal: Environmental Health Perspectives (1984)

Modern man is being confronted with an ever-increasing inventory of potentially toxic airborne substances. Exposures to these atmospheric contaminants occur in residential and commercial settings, as well as in the workplace. In order to study the toxicity of such materials, a special technology relating to inhalation exposure systems has evolved. The purpose of this paper is to provide a description of the techniques which are used in exposing laboratory subjects to airborne particles and gases. The various modes of inhalation exposure (whole body, head only, nose or mouth only, etc.) are described at length, including the advantages and disadvantages inherent to each mode. Numerous literature citations are included for further reading. Among the topics briefly discussed are the selection of appropriate animal species for toxicological testing, and the types of inhalation studies performed (acute, chronic, etc.).