tbuckley/cabot-search huggingface dataset:
OBSEKVATIONS ON THE MECHANICS OF DIGESTION.
Authors: WALTER BRADFORD CANNON
Journal: JAMA (1903)

The results which are to be presented in outline in this paper have been obtained in researches carried on in 1897-98 and in 1901 in the Laboratory of Physiology of the Harvard Medical School, and they are part of an extensive investigation into the mechanical factors of digestion to be carried on during the next few years. The method thus far pursued has been that of mixing with the food subnitrate of bismuth, a harmless, almost inert, powder, opaque to the<i>x</i>-rays, and then with the fluorescent screen observing the changes in the shadows of the alimentary contents as they are worked on by the muscles of the digestive organs. The clearness with which masses of food can be seen is indicated in Figure 1, a radiograph of a cat. Observations have been made chiefly on cats, but many of these observations have been confirmed on dogs, rats and guinea-pigs,
Macrophage mannose receptor on lymphatics controls cell trafficking
Authors: Fumiko Marttila-Ichihara, Raisa Turja, Mari Miiluniemi, Marika Karikoski, Mikael Maksimow, Jussi Niemelä, Luisa Martinez-Pomares, Marko Salmi, Sirpa Jalkanen
Journal: Blood (2008)

Abstract Macrophage mannose receptor (MR) participates in pathogen recognition, clearance of endogenous serum glycoproteins, and antigen presentation. MR is also present on lymphatic vessels, where its function is unknown. Here we show that migration of lymphocytes from the skin into the draining lymph nodes through the afferent lymphatics is reduced in MR-deficient mice, while the structure of lymphatic vasculature remains normal in these animals. Moreover, in a tumor model the primary tumors grow significantly bigger in MR−/− mice than in the wild-type (WT) controls, whereas the regional lymph node metastases are markedly smaller. Adhesion of both normal lymphocytes and tumor cells to lymphatic vessels is significantly decreased in MR-deficient mice. The ability of macrophages to present tumor antigens is indistinguishable between the 2 genotypes. Thus, MR on lymphatic endothelial cells is involved in leukocyte trafficking and contributes to the metastatic behavior of cancer cells. Blocking of MR may provide a new approach to controlling inflammation and cancer metastasis by targeting the lymphatic vasculature.
Ischemic preconditioning is associated with a delay in ischemia-induced reduction of beta-adrenergic signal transduction in rabbit hearts.
Authors: T Iwase, T Murakami, T Tomita, S Miki, K Nagai, S Sasayama
Journal: Circulation (1993)

BACKGROUND It has been reported that the A1-adenosine receptor mediates the cardioprotective effect of ischemic preconditioning. This receptor couples inhibitory guanine nucleotide-binding protein (Gi) and inhibits adenylate cyclase activity. However, the role of adenylate cyclase in preconditioning is unknown. METHODS AND RESULTS We compared the effects of ischemia on the sarcolemmal beta-adrenergic receptor density (Bmax), the stimulatory guanine nucleotide-binding protein (Gs) activity as determined by reconstitution with S49 lymphoma cyc- membranes, and baseline and maximally stimulated adenylate cyclase activities (ACAs) in control and preconditioned rabbit hearts. The control population (n = 28) received 0, 10, 20, and 60 minutes of coronary occlusion (n = 6 to 8 per stage), and preconditioned rabbits (n = 24) received two cycles of alternating 5-minute occlusion and reperfusion before sustained ischemia (n = 6 per stage). In control hearts, occlusion induced rapid and progressive reductions in the Bmax, Gs, and ACAs after 10 to 60 minutes of ischemia. Preconditioning did not affect the reduction in Bmax, but it preserved reductions in Gs activity and ACAs after 10 to 20 but not 60 minutes of sustained ischemia. In another study, 18 rabbits were treated with pertussis toxin 48 hours before surgery to block Gi. During treatment, no significant difference was observed in the ischemia-induced reduction in ACAs in the ischemic region between control (n = 8) and preconditioned (n = 10) animals after 20 minutes of ischemia. CONCLUSIONS Preconditioning delays ischemia-induced reductions in beta-adrenergic signal transduction. Inhibition of ACA is not the target effect of the A1-adenosine receptor-Gi pathway responsible for the cardioprotective role of preconditioning.
Adjunctive Selectin Blockade Successfully Reduces Infarct Size Beyond Thrombolysis in the Electrolytic Canine Coronary Artery Model
Authors: Mitchell J. Silver, Joseph M. Sutton, Sharon Hook, Philmo Lee, Janis L. Malycky, M. Laurie Phillips, Stephen G. Ellis, Eric J. Topol, Francesca A. Nicolini
Journal: Circulation (1995)

An adjunctive pharmacological strategy to thrombolytic therapy that is tailored to limit reperfusion injury after thrombolysis could further maximize the unquestioned benefit of restoring flow to ischemic myocardium. Ischemia-reperfusion injury exhibits features characteristic of an acute inflammatory response, including the rapid activation and infiltration of neutrophils. The initial process of neutrophil migration from the circulation to injured tissue is modulated by a group of adhesion molecules called selectins. The purpose of the present study was to assess the efficacy of a selectin blocker (CY 1503) given as an adjunct to thrombolytic therapy to interfere with the inflammatory response after ischemia-reperfusion and subsequently reduce myocardial infarct size in the electrolytic canine model.A fully occlusive thrombus was formed in the left circumflex coronary artery by electrolytic injury in 20 anesthetized open-chest dogs. After occlusion, an infusion of 1 mg/kg recombinant tissue-type plasminogen activator (rTPA) was administered over 20 minutes with either a bolus of placebo or the selectin blocker CY 1503 (40 mg/kg). At the onset of reperfusion, 20 micrograms/kg per minute rTPA was administered for 1 hour to prevent reocclusion. After 1 hour of reperfusion, infarct size, myocardial myeloperoxidase activity, and reperfusion arrhythmias were measured. In CY 1503-treated dogs, there was a significant 69% reduction in infarct size when expressed as a percentage of the area at risk (6.7 +/- 8.4% versus 21.8 +/- 13.6%; P = .008) and a marked reduction in myeloperoxidase activity (0.014 +/- 0.009 versus 0.0370 +/- 0.025 U/min per gram; P = .02) compared with the placebo group. There was no difference between the groups in the occurrence of reperfusion arrhythmias.Selectin blockade as an adjunct to rTPA-mediated thrombolysis significantly reduces infarct size and myocardial neutrophil infiltration well beyond thrombolysis alone in the electrolytic canine model. These data suggest that selectin blockade is extremely effective at reducing ischemia-reperfusion injury and myocardial infarct size in this model and that the neutrophil is a potent mediator of ischemia-reperfusion injury.
Depression and mortality in nursing homes
Authors: Barry W. Rovner, Pearl S. German, Larry J. Brant, Rebecca Clark, Lynda Burton, Marshal F. Folstein
Journal: JAMA (1991)

To determine the prevalence rates of major depressive disorder and of depressive symptoms and their relationship to mortality in nursing homes, research psychiatrists examined 454 consecutive new admissions and followed them up longitudinally for 1 year. Major depressive disorder occurred in 12.6% and 18.1% had depressive symptoms; the majority of cases were unrecognized by nursing home physicians and were untreated. Major depressive disorder, but not depressive symptoms, was a risk factor for mortality over 1 year independent of selected physical health measures and increased the likelihood of death by 59%. Because depression is a prevalent and treatable condition associated with increased mortality, recognition and treatment in nursing homes is imperative.
The Year Book of Sports Medicine 1979
Authors: Bruno Balke
Journal: JAMA (1980)

The modern concept of sports medicine originated with the first international congress of sports medicine at the Olympic Games in 1928 in Amsterdam. The purpose of that congress was to exchange experiences and scientific observations on the treatment of injuries and the medical care of athletes. In the years to come, the field widened to include almost all biomedical sciences related to sports and physical activity. This wide-ranging interdisciplinary coverage of clinical knowledge and experimental research is embodied in the table of contents of<i>The Year Book of Sports Medicine 1979</i>. The editors screened 3,000 international journals and selected articles that had appeared in 1978 for brief review. These articles cover a great variety of subjects, such as diagnosis and treatment of sports trauma, preventive aspects of physical activity, exercise physiology and psychology, training for general fitness or competitive performance, selective criteria for special sports, exercise testing and prescription, the
Internalization of interleukin 2 is mediated by the beta chain of the high-affinity interleukin 2 receptor.
Authors: R J Robb, W C Greene
Journal: The Journal of Experimental Medicine (1987)

High-affinity IL-2-R correspond to a membrane receptor complex composed of two different IL-2-binding proteins, the Tac antigen (alpha chain) and a 70-75 kD beta chain. Using cell lines that express either the alpha or the beta protein, we demonstrate that IL-2 internalization occurs when ligand is bound to the isolated beta chain, but not when it is bound to the isolated alpha chain. The kinetics of IL-2 internalization mediated by the intermediate-affinity beta chain were nearly identical to those of the high-affinity alpha/beta heterodimer (t1/2 of 10-15 min), and each type of receptor targeted the bound IL-2 for intracellular degradation in lysosomes. The beta chain thus appeared to provide the essential element necessary for ligand internalization by both types of IL-2-R.
Leukotriene B4 amplifies NF-κB activation in mouse macrophages by reducing SOCS1 inhibition of MyD88 expression
Authors: Carlos H. Serezani, Casey Lewis, Sonia Jancar, Marc Peters-Golden
Journal: Journal of Clinical Investigation (2011)

Activation of NF-κB and 5-lipoxygenase-mediated (5-LO-mediated) biosynthesis of the lipid mediator leukotriene B4 (LTB4) are pivotal components of host defense and inflammatory responses. However, the role of LTB4 in mediating innate immune responses elicited by specific TLR ligands and cytokines is unknown. Here we have shown that responses dependent on MyD88 (an adaptor protein that mediates signaling through all of the known TLRs, except TLR3, as well as IL-1β and IL-18) are reduced in mice lacking either 5-LO or the LTB4 receptor BTL1, and that macrophages from these mice are impaired in MyD88-dependent activation of NF-κB. This macrophage defect was associated with lower basal and inducible expression of MyD88 and reflected impaired activation of STAT1 and overexpression of the STAT1 inhibitor SOCS1. Expression of MyD88 and responsiveness to the TLR4 ligand LPS were decreased by Stat1 siRNA silencing in WT macrophages and restored by Socs1 siRNA in 5-LO-deficient macrophages. These results uncover a pivotal role in macrophages for the GPCR BLT1 in regulating activation of NF-κB through Stat1-dependent expression of MyD88.
Adjuvant Therapy in the Elderly: Making the Right Decision
Authors: Hyman B. Muss, Laura Biganzoli, Daniel J. Sargent, Matti Aapro
Journal: Journal of Clinical Oncology (2007)

Adjuvant chemotherapy has led to improvements in relapse-free and overall survival in patients with breast, colon, and non-small-cell lung cancer, yet many older patients are not offered these potentially life-saving treatments. Moreover, older patients have been either excluded or under-represented in most adjuvant trials, limiting the generalizability of these treatments to older populations. Limited data in elders suggest that older patients derive significant benefits from adjuvant therapies provided they have life expectancies exceeding 5 years. Making treatment decisions in elders is challenging. Many have major comorbidities that may substantially limit life expectancy and minimize or negate the benefits of adjuvant chemotherapy. In this review, we discuss the potential benefits of adjuvant treatment in older patients with solid tumors with a focus on general principles involved in the selection of adjuvant therapy for patients with breast, colon, and non-small-cell lung cancer. In addition, we discuss the role of comorbidity and how it factors in treatment decisions. Finally, we discuss future research directions and funding for elders with cancer.
Abstract P4-12-18: BOLERO-3: Quality-of-life maintained in patients with metastatic breast cancer treated with everolimus plus trastuzumab plus vinorelbine
Authors: C Isaacs, M Ozguroglu, G Jerusalem, B Xu, I Láng, R O'Regan, M White, A Fasolo, J Litton, M Toi, K Shen, F Andre, P Vuylsteke, Y Zhang, J Zhang, T Taran, S Wilks
Journal: Cancer Research (2013)

Abstract Background: Activation of the PI3K/mTOR pathway is implicated in resistance to trastuzumab. Accordingly, the BOLERO-3 study evaluated the efficacy of adding everolimus (EVE), an mTOR inhibitor, to vinorelbine and trastuzumab. At the final progression-free survival (PFS) analysis, EVE significantly improved PFS vs PBO (hazard ratio [HR] = 0.78; log-rank P = .0067) but EVE-treated patients had higher rate of grade 3/4 toxicity. To further qualify the benefit:risk of adding EVE to trastuzumab-based therapy, per-protocol, patient-reported, health-related quality-of-life (HRQoL) data were analyzed. Methods: BOLERO-3 is a randomized phase 3, double-blind, placebo-controlled, international multicenter trial. Taxane-pretreated patients (N = 569) with trastuzumab-resistant, HER2+, advanced breast cancer were randomized (1:1) to treatment with EVE or placebo (PBO) plus vinorelbine and trastuzumab. The European Organisation for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire C30 (QLQ-C30) (including the breast cancer-specific BR23 module) was administered at baseline and every 6 weeks thereafter until progression. The QLQ-C30 consists of 30 items combined into 15 subscales, including Global Health Status and functional subscales, where higher scores (range, 0 to 100) indicate better HRQoL. Time to definitive deterioration (TTD) based on a 10% decrease from baseline for GHS and for the physical, emotional, and social function subscales was determined using the Kaplan-Meier method. Treatment arms were compared using a 2-sided log-rank test stratified by prior use of lapatinib. Results: Overall, there was no significant difference in median TDD of HRQoL between treatment arms. The median TTD in global health status score was 8.3 months for EVE (95% confidence interval [CI], 6.9-11.5) vs 7.3 months for PBO (95% CI, 5.6-10.4; P = .8386). The median TTD in the physical, emotional, and social function subscale scores showed no significant difference between arms. For example, median TTD in the physical function subscale score was 12.0 months (95% CI, 8.3-14.1) for EVE vs 12.5 months (95% CI, 8.3-20.9) for PBO (P = .4251), and median TTD in the emotional function subscale score was 15.2 months (95% CI, 9.2-17.3) for EVE vs 12.5 months (95% CI, 9.7-16.4) for PBO (P = .8140). Conclusions: These analyses demonstrate that, despite increased frequency of adverse events observed with the addition of EVE to the standard treatment of vinorelbine and trastuzumab, overall and functional HRQoL scores were not negatively impacted in patients with trastuzumab-resistant, HER2+, advanced breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-18.
Citizens juries vote to extend nurse roles
Authors: J. Bryan
Journal: BMJ (1997)

Expanding roles for pharmacists and nurse practitioners and practical improvements in gynaecological cancer services are among the latest recommendations to come from a programme of citizens juries, supported by the King's Fund.

The decisions come as a report from the Fabian Society out this week calls for wider use of citizens juries, saying that they can help health authorities improve their decisions and build public confidence.

The authors say: “In attempting to understand the public's perspective, too many elected representatives rely only on a self selected sample of people who come to …
Clinical Trial Evaluating DC/AML Fusion Cell Vaccination Alone and in Conjunction with PD-1 Blockade in AML Patients Who Achieve a Chemotherapy-Induced Remission
Authors: Jacalyn Rosenblatt, Richard M. Stone, Irit Avivi, Lynne Uhl, Donna Neuberg, Robin Joyce, Dimitrios Tzachanis, James D. Levine, Vassiliki A Boussiotis, Jeffrey Zwicker, Jon E. Arnason, Katarina Luptakova, David P. Steensma, Daniel J DeAngelo, Ilene Galinsky, Baldev Vasir, Poorvi Somaiya, Heidi Mills, Yan Emily Yuan, Jessica Bonhoff, Carol Delaney, Natalie Drummy, Lowell Nicholson, Dina Stroopinsky, Vicki Held, Tami Katz, Lina Bisharat, Jacob M. Rowe, Donald Kufe, David Avigan
Journal: Blood (2011)
Is Glycosylated Hemoglobin Clinically Useful?
Authors: David E. Goldstein
Journal: New England Journal of Medicine (1984)

The chemical reaction between glucose and hemoglobin is an example of a widespread biologic process called "nonenzymatic glycosylation" (more properly called "glucosylation," in reference to glucose–protein linkages, or adducts). In this instance, a protein, hemoglobin A, is modified postsynthetically by forming an adduct with glucose.1 The reaction is nonenzymatic, slow, and irreversible. The human erythrocyte is freely permeable to glucose, and within each erythrocyte, glycosylated hemoglobin is formed continuously from hemoglobin A at a rate dependent on the ambient glucose concentration.2 It is now widely accepted that measurement of glycosylated hemoglobin in a single blood sample provides an accurate index . . .
THE ASSOCIATION OF REDUCED DOOR TO BALLOON TIMES AND MORTALITY IN PATIENTS UNDERGOING PRIMARY PCI: A REPORT FROM THE NATIONAL CARDIOVASCULAR DATA REGISTRY (NCDR&amp;reg;)
Authors: Daniel S. Menees, Eric Peterson, Yongfei Wang, Jeptha Curtis, John Messenger, John Rumsfeld, Hitinder Gurm
Journal: Journal of the American College of Cardiology (2012)
Thrombolytic Therapy in Acute Myocardial Infarction
Authors: N U Bang, O G Wilhelm, M D Clayman
Journal: The Annual Review of Pharmacology and Toxicology (1989)

Since the spread of tobacco from the Americas hundreds of years ago, tobacco cigarettes and, more recently, alternative tobacco products have become global products of nicotine addiction. Within the evolving alternative tobacco product space, electronic ...Read More
Pathological glycogenesis through glycogen synthase 1 and suppression of excessive AMP kinase activity in myeloid leukemia cells
Authors: Haymanti Bhanot, Mamatha M Reddy, Atsushi Nonami, Ellen L Weisberg, Dennis Bonal, Paul T Kirschmeier, Sabrina Salgia, Klaus Podar, Ilene Galinsky, Tirumala K Chowdary, Donna Neuberg, Giovanni Tonon, Richard M Stone, John Asara, James D Griffin, Martin Sattler
Journal: Leukemia (2015)
Contempo '81. Neurosurgery
Authors: N. T. Zervas
Journal: JAMA (1981)

<h3>Cranial Artery Bypass</h3> Neurosurgeons today are involved in many areas of general concern. One of these, occlusive cerebrovascular disease, is a prevalent and potentially devastating problem, and a great effort is under way to prevent or treat this disorder. Extracranial-intracranial arterial bypass to circumvent obstruction of the carotid and vertebral arteries in the neck or base of the skull has received wide attention. It involves the anastomosis of vessels of 1 to 2 mm in diameter from the scalp to vessels of similar diameter on the surface of the brain. When performed by experienced neurosurgeons using microsurgical technique, the operative mortality and morbidity are low (less than 5%).<sup>1</sup>Typically, these small vessels can adequately perfuse brain areas made ischemic by proximal occlusive lesions. For example, proximal surgical occlusion of the middle cerebral artery to trap a distal giant aneurysm is often tolerated if a distal middle-cerebral arterial branch is
Mechanism of Effect of Prostaglandin E1 on Renal Water Excretion
Authors: T. Berl, R. W. Schrier
Journal: Journal of Clinical Investigation (1973)

The present study examined the effect of prostaglandin E(1) (PGE(1)) on renal water excretion in the anesthetized dog. Renal perfusion pressure was kept constant by adjustment of a suprarenal aortic clamp. In seven experiments the intravenous administration of PGE(1) (7 mug/min) significantly increased urinary osmolality from 76 to 381 mosmol (P < 0.001) and decreased free water clearance from 2.2 to - 0.02 ml/min (P < 0.001). These effects promptly were reversed with cessation of the infusion. This antidiuretic effect occurred both in innervated and denervated kidneys and was not associated with changes in glomerular filtration rate, renal vascular resistance, or solute excretion rate. In 10 experiments in hypophysectomized dogs no effect of intravenous PGE(1) on free water clearance and urinary osmolality was observed. The intrarenal administration of PGE(1) (1 mug/min) to six water-loaded and two hypophysectomized dogs caused no systemic vascular changes and increased rather than decreased free water clearance (2.83 to 4.08 ml/min, P < 0.001). No significant change in urinary osmolality occurred. Glomerular filtration rate was not altered by the intrarenal infusion, but reversible changes in solute excretion rate and renal vascular resistance occurred. These results thus indicate that the antidiuresis associated with intravenous PGE(1) is mediated primarily by the release of vasopressin rather than alterations in renal hemodynamics or solute excretion. The diuretic effect of intrarenal PGE(1) occurs in the absence of vasopressin and is most likely mediated primarily by increased distal delivery of tubular fluid to the diluting segment of the nephron rather than changes in water permeability of the renal tubular epithelium.
Report on the American Urologic Association/American Cancer Society scientific seminar on the detection and treatment of early-stage prostate cancer
Authors: G. P. Murphy
Journal: CA A Cancer Journal for Clinicians (1994)

In a recent AUA/ACS scientific seminar, experts on prostate cancer met to present and discuss information concerning the detection and treatment of early-stage prostate cancer. This article provides an overview of the major topics covered, including perspectives on the problem, proposed clinical studies, diagnosis and prognostic factors, treatment studies, cancer control, and future directions.
THE PROBLEM SOLDIER AND THE ARMY
Authors: JOHN M. CALDWELL
Journal: American Journal of Psychiatry (1948)

1. During World War II, neuropsychiatric disorders were the cause of rejections of 12% of all men examined for military service, the basis for 6 to 7% of total admissions to army hospitals, and the reason for 49% of all separations for mental or physical defects. 2. Over 126,000 men and women were separated administratively, with honorable discharges for inaptness, lack of adaptability, or enuresis. 3. Over 40,000 were separated for undesirable habits and traits of character with other than honorable discharges, and 25,000 more received similar administrative discharges for various reasons. 4. Some 74,000 officers and men were sentenced by a general court-martial to confinement and dishonorable discharge. 5. A War Department Review Board is currently considering all discharges other than honorable or dishonorable, with a view to changing, correcting, or modifying improper or inequitable discharges or dismissals. 6. A War Department Clemency Board is functioning to correct injustices and inconsistencies resulting from courts-martial sentences, and to enable qualified and deserving prisoners to be returned to duty. 7. Army Regulations are being modified to permit a greater variety and ease of administrative discharges, and courts-martial procedures are being changed and improved in the light of modern thought.