tbuckley/cabot-search huggingface dataset:
Immunoprotective behaviour of liposome entrapped cell wall subunit of Mycobacterium tuberculosis against experimental tuberculous infection in mice
Authors: IB Chugh, GK Khuller
Journal: European Respiratory Journal (1993)

We wanted to determine the immunoprotective behaviour of cell wall protein peptidoglycan complex (CW-PPC) of Mycobacterium tuberculosis H37Ra, using liposomes as adjuvant, in an experimental animal model. Immunization of mice with CW-PPC entrapped in liposomes induced both humoral response, as measured by enzyme-linked immunosorbent assay (ELISA), and cell-mediated immune responses, as seen by delayed type hypersensitivity (DTH) and leucocyte migration inhibition (LMI) techniques. Ten days after complete immunization, the animals were challenged with median lethal dose (LD50) of M. tuberculosis H37Rv. The animals exhibited significant protection, as evident by 72% survival after 30 days of infection, compared to 38% survival in control animals. Protective effect of immunization with liposome entrapped CW-PPC was further substantiated by significant decrease in the number of viable bacilli in lungs, liver and spleen of immunized animals, as compared to control animals. These results indicate that immunization with liposome-entrapped mycobacterial cell wall protein peptidoglycan complex induces protection against experimental tuberculosis.
Inhibitory Effect of Glucocorticosteroids on Anti‐IgE‐Induced Histamine Release from Human Basophilic Leukocytes: Evidence for a Dual Mechanism of Action
Authors: Hårkan Bergstrand, Anette Björnsson, Britta Lundquist, Annika Nilsson, Ralph Brattsand
Journal: Allergy (1984)

Anti-IgE-induced histamine release from human leukocytes is inhibited when the cells before challenge are cultured overnight in the presence of glucocorticoids (GCSs). The present report suggests that the GCSs might exert their effect by at least a dual mechanism of action. Histamine release was induced by a suboptimum concentration of anti-IgE. When the release recorded in the presence of the steroid is plotted against the release recorded in its absence, the data points of several experiments fit a regression line characterized by two parameters: its slope and its intercept with the abscissa. Structure-activity examination with selected GCSs indicates that the orders of potency for affecting these two parameters are not identical. Furthermore, pulse experiments suggest that the cells require different times of contact with the steroid to express inhibition according to the two parameters. The removal of adherent cells or platelets did not markedly affect the degree of leukocyte histamine release or its inhibition by a given GCS, suggesting that the steroid interacts directly with the basophil. Finally, steroid-induced inhibition was not affected by the putative phospholipase A2-inhibitor p-bromophenacylbromide (BPB) or the 5-lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA).
Induction of a CD8+ Cytotoxic T Lymphocyte Response by Cross-priming Requires Cognate CD4+ T Cell Help
Authors: Sally R.M. Bennett, Francis R. Carbone, Freda Karamalis, Jacques F.A.P. Miller, William R. Heath
Journal: The Journal of Experimental Medicine (1997)

Class I–restricted presentation is usually associated with cytoplasmic degradation of cellular proteins and is often considered inaccessible to exogenous antigens. Nonetheless, certain exogenous elements can gain entry into this so-called endogenous pathway by a mechanism termed cross-presentation. This is known to be effective for class I–restricted cytotoxic T lymphocyte (CTL) cross-priming directed against a variety of exogenous tumor, viral, and minor transplantation antigens. The related effect of cross-tolerance can also effectively eliminate responses to selected self components. In both cases, this presentation appears to require the active involvement of a bone marrow–derived antigen presenting cell (APC). Here, we show that CTL induction by cross-priming with cell-associated ovalbumin requires the active involvement of CD4+ helper T cells. Importantly, this CD4+ population is only effective when both the helper and CTL determinants are recognized on the same APC. Moreover, we would argue that the cognitive nature of this event suggests that the CD4+ T cell actively modifies the APC, converting it into an effective stimulator for the successful priming of the CTL precursor.
A STUDY OF THE EFFECTS OF L.S.D.: PHYSIOLOGIC AND PSYCHOLOGICAL CHANGES AND THEIR INTERRELATIONS
Authors: ALBERTO DIMASCIO, MILTON GREENBLATT, ROBERT W. HYDE
Journal: American Journal of Psychiatry (1957)

The physiological and psychological changes throughout the day subsequent to the administration of Lysergic Acid Diethyl-amide were recorded and analyses made of their interrelations. The Harvard Polygraph was used to simultaneously and continuously record heart rate, respiration, skin temperature, blood pressure, and muscle tension. Recordings were made under resting conditions immediately before and 1½, 2½, 4½, and 7½ hours subsequent to L. S. D. administration. Physiologically, a general sympathetic excitation resulted, which reached a peak of tension in 3 to 4 hours and then gradually returned to the pre-L. S. D. level by the eighth hour. Heart rate increased and became more stable, systolic and diastolic blood pressures were elevated, pulse pressure rose, muscle tension mounted, skin temperature tended to drop, breathing became faster and more variable, the inspiration/respiration ratio decreased and became more variable, and pupillary dilation occurred. No such drastic changes were noted in the control (placebo) days. Changes occurred psychologically that paralleled the physiological changes. Deviation from "normality" both behaviorally and subjectively was most pronounced, in number of symptoms expressed and intensity of expression, about 3 to 4 hours after L. S. D. administration and gradually diminished until the eighth hour. Some of the implications of this study are mentioned and the similarity between the sequences of events post-L. S. D. with the changes pre-post lobotomy are discussed.
P55 Is Prescription Uptake And Medication Adherence Rating Scale (mars) A Useful Tool In Assessing Asthma Control In Children With Problematic Severe Asthma (psa)?
Authors: P. Nagakumar, P. Hall, M. Bracken, S. Saglani, A. Bush, L. Fleming
Journal: Thorax (2014)

<h3>Introduction</h3> Sub-optimal adherence to medications results in poor asthma control, however objective measurement of adherence is challenging. <h3>Aim</h3> To assess adherence to inhaled corticosteroids (ICS) in children with problematic severe asthma (PSA) using prescription uptake and the Medicines Adherence Rating Scale (MARS) (self-reported adherence) and relate them to measures of asthma control. <h3>Methods</h3> 160 patients assessed as part of the established RBH difficult asthma protocol (2008–2013) were included [[Arch Dis Child 2009;94:780–4]. Adherence was assessed using prescription uptake data (GP and local hospital) and MARS. Sub-optimal adherence was defined as a prescription uptake of &lt;80%. Spirometry (FEV<sub>1 </sub>pre bronchodilator), bronchodilator reversibility (BDR), and exhaled nitric oxide (FENO) were measured. The Asthma Control Test (ACT), Paediatric Asthma Quality of Life Questionnaire (PAQLQ) was used to evaluate control. Number of courses of oral steroids and hospital admissions in the previous 12 months were recorded. <h3>Results</h3> Median age was 11.6 yr (5–16). 66% were male. 52% had prescription uptake of &lt;80%. MARS score showed only a weak correlation with prescription uptake (n = 48, r<sup>2</sup> =0.03, p = 0.29), even in patients with prescription uptake of &lt;50% (n = 23, r<sup>2</sup>=0.09, p = 0.32). No relationship was found between prescription uptake and ACT, MARS, FEV<sub>1</sub>, rescue courses of OCS, FeNO or BDR (Table 1). <h3>Conclusion</h3> Poor prescription uptake was not related to any measure of asthma control, meaning that we could not differentiate the genuine therapy resistant from the non-adherent. But it is not possible to assess how much ICS was actually inhaled. Patterns of ICS use may be a more important determinant of control. Self-reported adherence, as measured by MARS was high even in those with very poor &lt;50%) prescription uptake highlighting the limitations of this questionnaire. More objective means of assessing adherence should be incorporated into protocols for assessing severe asthma.
Incidence and follow-up of inflammatory cardiac complications after smallpox vaccination11The views expressed in this study are those of the authors and do not reflect the official policy or position of the U.S. government.
Authors: Robert E Eckart, Suzanne S Love, J.Edwin Atwood, Mark K Arness, Dimitri C Cassimatis, Charles L Campbell, Sheri Y Boyd, Joseph G Murphy, David L Swerdlow, Limone C Collins, James R Riddle, David N Tornberg, John D Grabenstein, Renata J.M Engler
Journal: Journal of the American College of Cardiology (2004)
Endothelium-Dependent Relaxation of Collateral Microvessels After Intramuscular Gene Transfer of Vascular Endothelial Growth Factor in a Rat Model of Hindlimb Ischemia
Authors: Satoshi Takeshita, Takaaki Isshiki, Masahiko Ochiai, Koji Eto, Hidezo Mori, Etsuro Tanaka, Keiji Umetani, Tomohide Sato
Journal: Circulation (1998)

Background —Recent investigations have demonstrated the ability of vascular endothelial growth factor (VEGF) to augment the development of collateral arteries in vivo. In vitro studies have suggested that the use of VEGF also improves the endothelium-dependent relaxation of collaterals at the microvascular level. The purpose of this study was to determine in vivo the extent to which vasomotor responses of collateral microvessels are altered after VEGF treatment. Methods and Results —Ischemia was induced in the hindlimb of 35 rats by excision of the femoral artery. Immediately thereafter, 400 μg of a plasmid encoding VEGF or β-galactosidase (control) was transfected into limb muscles. Four weeks later, synchrotron radiation microangiography, with a spatial resolution of 30 μm, was performed to document the reactivity of collateral microvessels. Administration of the endothelium-dependent vasodilator acetylcholine failed to induce dilation of collateral microvessels in control animals. By contrast, profound dilation of collaterals was observed after acetylcholine in VEGF-treated animals. This response was evident in vessels with a linear appearance but not in those with an undulating appearance. The resulting blood flow in the ischemic limb after administration of acetylcholine in the control animals was only 64.6±17.0% of that of the contralateral normal limb, whereas blood flow was augmented to 106.1±8.4% in VEGF-treated animals ( P &lt;0.05). Conclusions —These results demonstrate in vivo that the use of VEGF restores impaired vasomotor responses in some types of collateral microvessels, which may help to provide a basis for understanding the microcirculation after therapeutic angiogenesis with VEGF.
Comparative analysis of detection of Mycobacterium tuberculosis and rifampin resistance determination through microbiological and molecular genetics methods for pulmonary tuberculosis patients with presence or absence of sputum
Authors: Maria Alvarez Figueroa, Ekaterina Dolgova, Maria Gordukova, Dmitry Belov
Journal: European Respiratory Journal (2012)

The majority of studies on diagnostics of pulmonary tuberculosis (PTB) used only sputum that appears at later stages of disease and don9t use bronchoalveolar lavage (BAL) fluid obtained by bronchoscopes. At the same time these patients are epidemiologically dangerous even at the early stages of disease. The aim of our study was to compare the possibilities of microbiological and molecular genetics methods for Mycobacterium tuberculosis (MTB) detection and rifampin resistance identification (RIF-R) in new cases of PTB through sputum or BAL fluid examination. We conducted a double-blind randomized retrospective investigation. The aetiology of PTB has been proven by receiving the culture growth or histological examination of lung tissue with Ziehl-Neelsen staining. A total of 134 specimens (32 sputum and 102 BAL fluid) from 133 patients gave positive results by Real-Time PCR (kit “AmpliSenceMTB-FL”) and by sequencing of rpoB gene (kit “AmpliSenceMTB-Rif-seq”). We received growing of MTB culture in only 23 (74.2%) sputum and 56 (54.9%) BAL fluid compared to the molecular genetics investigations. We found RIF-R in 12 (38.7%) sputum and 37 (36.3%) BAL fluid by all methods. In addition to the culture method we managed to detect RIF-R in 5 sputum and 25 BAL fluid samples (plus one insignificant mutation). Due to the higher sensitivity of molecular genetics methods we not only found out MTB in proven cases of PTB more likely than culture method, but also higher level of RIF-R that did not demonstrate a difference between patients with presence or absence of sputum.
An Epigenetic Pathway Regulates Sensitivity of Breast Cancer Cells to HER2 Inhibition via FOXO/c-Myc Axis
Authors: Smita Matkar, Paras Sharma, Shubin Gao, Buddha Gurung, Bryson W. Katona, Jennifer Liao, Abdul Bari Muhammad, Xiang-Cheng Kong, Lei Wang, Guanghui Jin, Chi V. Dang, Xianxin Hua
Journal: Cancer Cell (2015)
Nicotine-induced survival signaling in lung cancer cells is dependent on their p53 status while its down-regulation by curcumin is independent
Authors: Vineshkumar T Puliyappadamba, Vino T Cheriyan, Arun Kumar T Thulasidasan, Smitha V Bava, Balachandran S Vinod, Priya R Prabhu, Ranji Varghese, Arathy Bevin, Shalini Venugopal, Ruby John Anto
Journal: Molecular Cancer (2010)

Lung cancer is the most lethal cancer and almost 90% of lung cancer is due to cigarette smoking. Even though nicotine, one of the major ingredients of cigarette smoke and the causative agent for addiction, is not a carcinogen by itself, several investigators have shown that nicotine can induce cell proliferation and angiogenesis. We observed that the proliferative index of nicotine is different in the lung cancer cell lines H1299 (p53-/-) and A549 (p53+/+) which indicates that the mode of up-regulation of survival signals by nicotine might be different in cells with and without p53.While low concentrations of nicotine induced activation of NF-κB, Akt, Bcl2, MAPKs, AP1 and IAPs in H1299, it failed to induce NF-κB in A549, and compared to H1299, almost 100 times higher concentration of nicotine was required to induce all other survival signals in A549. Transfection of WT-p53 and DN-p53 in H1299 and A549 respectively, reversed the mode of activation of survival signals. Curcumin down-regulated all the survival signals induced by nicotine in both the cells, irrespective of their p53 status. The hypothesis was confirmed when lower concentrations of nicotine induced NF-κB in two more lung cancer cells, Hop-92 and NCI-H522 with mutant p53 status. Silencing of p53 in A549 using siRNA made the cells susceptible to nicotine-induced NF-κB nuclear translocation as in A549 DN-p53 cells.The present study reveals a detrimental role of nicotine especially in lung cancer patients with impaired p53 status and identifies curcumin as a potential chemopreventive.
The physical therapist’s role in physical activity promotion
Authors: E Verhagen, L Engbers
Journal: British Journal of Sports Medicine (2008)

Clinicians are increasingly confronted with the diseases of physical inactivity. Paradoxically, a promising strategy to motivate sedentary individuals to become more active is the opportunity to encourage physical activity related behavioural change when individuals encounter health professionals. Although health care professionals trained in exercise prescription are recognised as having the potential to play an important role in promoting regular physical activity, their role has been minimal in multidisciplinary approaches to date. Even so, the role of physical therapists has gone largely unrecognised. Nevertheless, because of their training and experience, physical therapists are ideally placed to promote the health and well being of individuals and the general public through physical activity and exercise prescription. Therefore, physical therapists, general practitioners and other caregivers alike should become aware of the physical therapist’s potential in promoting safe and healthy physical activity.
Evidence for Cardiovascular Autonomic Dysfunction in Neonates With Coarctation of the Aorta
Authors: Jaimie W. Polson, Naomi McCallion, Hidefumi Waki, Gareth Thorne, Mark A. Tooley, Julian F.R. Paton, Andrew R. Wolf
Journal: Circulation (2006)

Coarctation of the aorta (CoA) is associated with hypertension and abnormalities of blood pressure control, which persist after late repair. Assumptions that neonatal repair would prevent development of blood pressure abnormalities have not been supported by recent data. We hypothesized that early pathological adjustment of autonomic cardiovascular function may already be established in the neonate with coarctation.We studied 8 otherwise well neonates with simple CoA and compared measures of spontaneous baroreflex sensitivity, heart rate variability, and blood pressure variability with 13 healthy newborn babies. Spontaneous baroreflex sensitivity was calculated with sequence methodology from an ECG, and noninvasive blood pressure was recorded with a Portapres. Heart rate variability was determined with time- and frequency-domain measures. Blood pressure variability was measured in the frequency domain. In comparison with normal controls, neonates with CoA had raised blood pressure (78.9+/-3.8 versus 67.1+/-2.1 mm Hg), depressed baroreflex sensitivity (8.7+/-1.5 versus 13.8+/-1.1 ms/mm Hg), reduced heart rate variability (total power 16.5+/-3.1 versus 31.5+/-2.2 ms2), and an increase in the high-frequency component of blood pressure variability (3.1+/-0.3 versus 2.2+/-0. 2 mm Hg2). This is not the pattern expected if neonates with CoA simply had subclinical cardiac failure.These data suggest that infants with CoA already show signs of pathological adjustment of autonomic cardiovascular homeostasis. Further longitudinal studies are required to determine whether these alterations play a role in the increased risk of late hypertension in these patients.
Cysteamine Modulates Oxidative Stress and Blocks Myofibroblast Activity in CKD
Authors: Daryl M. Okamura, Nadia M. Bahrami, Shuyu Ren, Katie Pasichnyk, Juliana M. Williams, Jon A. Gangoiti, Jesus M. Lopez-Guisa, Ikuyo Yamaguchi, Bruce A. Barshop, Jeremy S. Duffield, Allison A. Eddy
Journal: Journal of the American Society of Nephrology (2013)

Therapy to slow the relentless expansion of interstitial extracellular matrix that leads to renal functional decline in patients with CKD is currently lacking. Because chronic kidney injury increases tissue oxidative stress, we evaluated the antifibrotic efficacy of cysteamine bitartrate, an antioxidant therapy for patients with nephropathic cystinosis, in a mouse model of unilateral ureteral obstruction. Fresh cysteamine (600 mg/kg) was added to drinking water daily beginning on the day of surgery, and outcomes were assessed on days 7, 14, and 21 after surgery. Plasma cysteamine levels showed diurnal variation, with peak levels similar to those observed in patients with cystinosis. In cysteamine-treated mice, fibrosis severity decreased significantly at 14 and 21 days after unilateral ureteral obstruction, and renal oxidized protein levels decreased at each time point, suggesting reduced oxidative stress. Consistent with these results, treatment of cultured macrophages with cysteamine reduced cellular generation of reactive oxygen species. Furthermore, treatment with cysteamine reduced α-smooth muscle actin-positive interstitial myofibroblast proliferation and mRNA levels of extracellular matrix proteins in mice and attenuated myofibroblast differentiation and proliferation in vitro, but did not augment TGF-β signaling. In a study of renal ischemia reperfusion, cysteamine therapy initiated 10 days after injury and continued for 14 days decreased renal fibrosis by 40%. Taken together, these data suggest previously unrecognized antifibrotic actions of cysteamine via TGF-β-independent mechanisms that include oxidative stress reduction and attenuation of the myofibroblast response to kidney injury and support further investigation into the potential benefit of cysteamine therapy in the treatment of CKD.
Management of anticancer treatment in patients under chronic dialysis: results of the multicentric CANDY (CANcer and DialYsis) study
Authors: N. Janus, V. Launay-Vacher, A. Thyss, H. Boulanger, O. Moranne, M.S. Islam, J.-P. Durande, M. Ducret, L. Juillard, Z. Soltani, G. Motte, J. Rottembourg, G. Deray, J. Thariat
Journal: Annals of Oncology (2012)
Malpractice Reform Must Include Steps To Prevent Medical Injury
Authors: Stephen C. Schoenbaum, Randall R. Bovbjerg
Journal: Annals of Internal Medicine (2004)

In the current malpractice insurance crisis, physicians have focused their advocacy and energy primarily on rapidly increasing liability premiums; problems in access to care; and demands for legal reform, especially caps on damages. An even more important focus, however, is prevention of injury and improvement of patient safety. Physicians largely control patient care and can play a critical role in systematically reducing injury. Reforms should go beyond liability issues; they should also harness and enhance physicians' ability to act. More visible efforts by physicians to reduce harm, better communication with patients and others, and true evidence of improved patient safety should reduce patient anger and litigiousness. Individually and collectively, physicians can and should ensure that "doing no harm" comes first in the malpractice debate.
Endocrinology of Aging
Authors: David M. Grossman
Journal: Annals of Internal Medicine (2000)

Medical Writings: Book Notes4 July 2000Endocrinology of AgingDavid M. Grossman, MDDavid M. Grossman, MDTulane University School of Medicine, New Orleans, Louisiana. (Grossman)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-133-1-200007040-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Morley JE, van den Berg L, eds. 280 pages. Totowa, NJ: Humana; 2000. $99.50. ISBN 0896034568. Order phone 973-256-1699.Field of medicine: Geriatrics and endocrinology.Format: Hardcover book.Audience: Geriatricians, endocrinologists, and general internists.Purpose: To discuss aspects of endocrinology in relation to the aging process.Content: The book describes aging-related changes in endocrine histology, function, and presentation of endocrine disorders. Topics include the growth hormone, thyroid, adrenal, and gonadal axes; bone metabolism; water balance; hypertension; nutrition; and the sympathetic nervous system. Endocrine changes affecting body composition, bone density, reproductive function, and the response to stress and exercise that accompany ... Author, Article, and Disclosure InformationAffiliations: Tulane University School of Medicine, New Orleans, Louisiana. (Grossman) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 July 2000Volume 133, Issue 1Page: 80KeywordsAgingElderlyEndocrinologyNutritionObesityOsteoporosisProstate cancerSoftware toolsSympathetic nervous systemThyroid hormones ePublished: 15 August 2000 Issue Published: 4 July 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...