tbuckley/cabot-search huggingface dataset:
Research Policy: Peering into the bowels of the MRC I: setting priorities
Authors: R. Smith
Journal: BMJ (1988)

The Medical Research Council does not set the priorities for British medical research.Nobody does.Many bodies fund health research, and few set priorities even within their own programmes.Most are "bottom up" rather than "top down" organisations, which means that they choose between competing grant applications rather than set priorities and then propose or commission research.The logic of this approach is that scientists-particularly clinical researchers who also treat patients-know what needs to be done and, importantly, know what can be done; they also have the skills needed to determine the relative scientific excellence of different proposed projects.But, critics argue, scientists and doctors have priorities that often do not match those of the public'-3 and vested interests in awarding grants to friends in their own coterie rather than to those with genuinely new ideas.2-9The current British government is impressed with some of these arguments and is encouraging the organisations that spend government money on research to be much more "top down" in their approach.The government, borrowing its thinking from the commercial sector, wants objectives set, guidelines issued, and criteria of success and failure determined.A Priorities Board for Research and Development in Agriculture and Food has already been established and has produced two reports.'0The board uses "criteria related to output value, competitive position, social and political influences and scientific potential""J (note the order) to reach its recommendations on priorities, and the Agriculture and Food Research Council and the relevant ministries commissioning research dance to its tune.How long will it be before we have something similar for health research?Here I look at how priorities might be set in general for scientific research and then consider in more detail the MRC's priorities and how it sets them.The next article will examine the mechanisms that the MRC uses for determining who will be supported: in effect these mechanisms set the priorities-haphazardly.Although the council funds less than half of British biomedical research, its mechanisms merit such close attention not only because they are more accessible and are used to spend public money but also because something similar is used by many of the other funding organisations.
The effect of enoxacin on osteoclastogenesis and reduction of titanium particle-induced osteolysis via suppression of JNK signaling pathway
Authors: Xuqiang Liu, Xinhua Qu, Chuanlong Wu, Zanjing Zhai, Bo Tian, Haowei Li, Zhengxiao Ouyang, Xinchen Xu, Wengang Wang, Qiming Fan, Tingting Tang, An Qin, Kerong Dai
Journal: Biomaterials (2014)
Long-term beneficial effects of neonatal cardiomyocytes on left ventricular ejection fraction, regional wall motion, and scar thickness after transplantation into infarcted rat hearts
Authors: Jochen Muller-Ehmsen, Kirk L. Peterson, Larry Kedes, Peter Whittaker, Joan S. Dow, Robert A. Kloner
Journal: Journal of the American College of Cardiology (2002)
LEGAL REGULATION OF THE PRACTICE OF MEDICINE.
Authors: Jas. F. Hibberd
Journal: JAMA (1884)

<h3>Editor Journal of the American Medical Association.</h3> In 1849, at the Boston meeting of the American Medical Association, that body had a report from an able committee on the subject, among other things, of regulating the practice of medicine by law, the conclusion reached being that it was not at that time expedient to seek the aid of State legislatures in that direction, and this has probably been the dominant sentiment of that organization since, as no further agitation of the matter has occurred. But many things have happened in the thirty-five years since that first Boston meeting of the Association, and it is quite probable that the present members of that body may hold views differing from those of the members of that day. At least, for years thoughtful physicians have been filled with regret to observe so many persons engaged in the practice of medicine, who possessed no
Fatal Pulmonary and Cerebral Fat Embolism in Systemic Lupus Erythematosus
Authors: David A. Katz
Journal: JAMA (1983)

A patient with an eight-year history of systemic lupus erythematosus (SLE) and recent onset of recurrent psychosis died after acute deterioration of cardiopulmonary status and level of consciousness. Autopsy disclosed massive pulmonary hemorrhage and unsuspected fat emboli in the lungs, kidney, and brain. This article discusses the significance of systemic fat embolism in SLE, with reference to corticosteroid therapy, fatal pulmonary hemorrhage, and lupus psychosis. (<i>JAMA</i>1983;250:2666-2669)
Documented Rocky Mountain spotted fever in Wintertime
Authors: James V. Lange, David H. Walker, Thad B. Wester
Journal: JAMA (1982)

ROCKY Mountain spotted fever (RMSF) is the most severe rickettsial disease of man in North America and is generally considered to be a seasonal disease.1-3The overwhelming majority of cases occur between the months of April and October.4,5This mostly warm-weather period also happens to be the time of maximum activity of the ixodid ticks that serve as both reservoir and vector for the disease.  We report a case of RMSF during a prolonged cold winter period in February 1981 in North Carolina. This case is interesting not only because of its temporal occurrence but also because the etiologic agent was isolated and there was no tick bite history associated with it.  Report of a Case  In early February 1981, a 6-year-old boy, a resident of rural eastern North Carolina who resides in a single-family dwelling on a partially cleared 3-acre wooded tract with his parents, two siblings
Endoproteolytic Activation of α <sub>v</sub> Integrin by Proprotein Convertase PC5 Is Required for Vascular Smooth Muscle Cell Adhesion to Vitronectin and Integrin-Dependent Signaling
Authors: Philipp Stawowy, Heike Kallisch, John P. Veinot, Adam Kilimnik, Wendy Prichett, Stephan Goetze, Nabil G. Seidah, Michel Chrétien, Eckart Fleck, Kristof Graf
Journal: Circulation (2004)

Background— Integrins play an important role for vascular smooth muscle cell (VSMC) migration during the development of atherosclerosis and restenosis. Integrin α v -subunit consists of disulphide-bound 125-kDa heavy and 25-kDa light chains, which are generated by endoproteolytic cleavage. This type of activation requires the presence of suitable proprotein convertases (PCs). Based on ex vivo and in vitro data, the PC5 isozyme has been suggested to be the major integrin convertase. We have recently demonstrated that PC5 is upregulated during vascular remodeling in rodents, colocalizing with α v in VSMCs. The aim of this study was to investigate the activation of α v by PCs in VSMCs and its consequences for α v -dependent cell functions. Methods and Results— Immunoblotting demonstrated that inhibition of PC activity by the specific pharmacological inhibitor dec-CMK inhibits α v cleavage in VSMCs. These results were confirmed using PC5-specific antisense oligonucleotides. PC5-antisense oligonucleotides and dec-CMK inhibited VSMC adhesion to the α v β 3 /β 5 ligand vitronectin (both P &lt;0.05). Furthermore, PC5-asODNs inhibited VSMC migration on vitronectin-coated wells ( P &lt;0.05). Inhibition of PC activity and consequently α v cleavage inhibited the adhesion-dependent focal adhesion kinase Y397 -autophosphorylation and subsequent Akt activation, whereas phosphorylation of extracellular signal-regulated kinase 1/2 was not affected. In human endarterectomy lesions, PC5 colocalized with α v integrin in VSMCs in the atherosclerotic plaques. Conclusions— The present study demonstrates that α v endoproteolytic activation is necessary for integrin-mediated adhesion and migration as well as signaling and requires PC5 in VSMCs. The colocalization of PC5 and α v in human carotid plaques indicates that PC5 might play a key role for α v activation in vivo.
Defective Spermatogenesis: Martin et al. Respond
Authors: Olwenn V. Martin, Tassos Shialis, Alan R. Boobis, Nikolaos Voulvoulis, John N. Lester, Mark D. Scrimshaw
Journal: Environmental Health Perspectives (2008)

BACKGROUND: Male reproductive tract abnormalities such as hypospadias and cryptorchidism, and testicular cancer have been proposed to comprise a common syndrome together with impaired spermatogenesis with a common etiology resulting from the disruption of gonadal development during fetal life, the testicular dysgenesis syndrome (TDS).The hypothesis that in utero exposure to estrogenic agents could induce these disorders was first proposed in 1993.The only quantitative summary estimate of the association between prenatal exposure to estrogenic agents and testicular cancer was published over 10 years ago, and other systematic reviews of the association between estrogenic compounds, other than the potent pharmaceutical estrogen diethylstilbestrol (DES), and TDS end points have remained inconclusive.OBJECTIVES: We conducted a quantitative meta-analysis of the association between the end points related to TDS and prenatal exposure to estrogenic agents.Inclusion in this analysis was based on mechanistic criteria, and the plausibility of an estrogen receptor (ER)-α-mediated mode of action was specifically explored.RESULTS: We included in this meta-analysis eight studies investigating the etiology of hypospadias and/or cryptorchidism that had not been identified in previous systematic reviews.Four additional studies of pharmaceutical estrogens yielded a statistically significant updated summary estimate for testicular cancer.CONCLUSIONS: The doubling of the risk ratios for all three end points investigated after DES exposure is consistent with a shared etiology and the TDS hypothesis but does not constitute evidence of an estrogenic mode of action.Results of the subset analyses point to the existence of unidentified sources of heterogeneity between studies or within the study population.
756 SONAZOID CONTRAST ENHANCED ULTRASONOGRAPHY COULD BE USED FOR MONITORING OF SORAFENIB'S EARLY RESPONSE AND FOR FOLLOW UP OF ADVANCED HEPATOCELLULAR CARCINOMA?
Authors: H. Tanaka, H. Iijima, Y. Shibata, R. Takata, T. Iwai, T. Takashima, Y. Sakai, N. Aizawa, K. Iwata, N. Ikeda, Y. Iwata, H. Enomoto, M. Saito, H. Imanishi, S. Nishiguchi
Journal: Journal of Hepatology (2012)
Determination of no-observed-adverse-effect levels and eliciting doses in a representative group of peanut-sensitized children
Authors: Annebeth E. Flinterman, Suzanne G. Pasmans, Maarten O. Hoekstra, Yolanda Meijer, Els van Hoffen, Edward F. Knol, Susan L. Hefle, Carla A. Bruijnzeel-Koomen, André C. Knulst
Journal: Journal of Allergy and Clinical Immunology (2006)
Immunologic Aspects of Renal Diseases
Authors: Curtis B. Wilson
Journal: JAMA (1992)

SINCE the turn of the century, animal models have provided an understanding of the many possible ways in which the immune system can cause human renal injury. These models have refined and expanded our knowledge of how nephritogenic antigen and antibody interactions lead to phlogogenic immune deposit formation, immune mediator activation, and induction of damage to surrounding renal structures, which in turn produce histological and pathophysiological changes. 1,2   In addition, antibody reactions that are capable of inducing selective glomerular (or tubular) cell damage have been defined. Cellular immune reactions clearly are important in tubulointerstitial injury, and studies continue to define cellular immune contributions to glomerular injury. Knowledge of the humoral and cellular mediation pathways that magnify antibody-induced injury has expanded with the appreciation, at the molecular level, of proinflammatory cytokines, growth factors, adhesion molecules, and extracellular matrix interactions responsible for inflammation and subsequent sclerosis. The cells of the glomerulus (and
CELL INTERACTIONS BETWEEN HISTOINCOMPATIBLE T AND B LYMPHOCYTES
Authors: David H. Katz, Toshiyuki Hamaoka, Martin E. Dorf, Paul H. Maurer, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1973)

In the present study we have asked the question of whether F(1) carrier-primed T cells can serve as helper cells for either or both parental B cells when (a) the carrier molecule employed is under genetic control such that one parental strain is a responder and the other is a nonresponder, and (b) the determinant specificity of the parental B cells being assessed is not under genetic control and bears no relationship to the specificity of the carrier molecule. Utilizing the system of immune response gene control of responses to the terpolymer L-glutamic acid-L-lysine-L-tyrosine (GLT) to which A strain mice (H-2(a)) are nonresponders, whereas BALB/c (H-2(d)) and (BALB/c x A)F(1) hybrids (CAF(1)) are responders, these studies demonstrate that GLT-primed T cells of CAF(1) donors can provide for responder BALB/c, but not for nonresponder A/J, the required stimulus for the anti-DNP responses of DNP-specific B cells of these respective parental strains to the DNP conjugate of GLT. The implications of these findings for Ir gene function in physiologic T-B cell interactions are discussed in detail.
Review: In renal impairment, apixaban reduces, or does not increase, bleeding compared with other anticoagulants
Authors: Christine M. Ribic, Catherine M. Clase
Journal: Annals of Internal Medicine (2015)

ACP Journal Club21 April 2015Review: In renal impairment, apixaban reduces, or does not increase, bleeding compared with other anticoagulantsChristine M. Ribic, MD, MSc, FRCPC, Catherine M. Clase, MB, BChir, MSc, FRCPCChristine M. Ribic, MD, MSc, FRCPCMcMaster University, Hamilton, Ontario, Canada (C.M.R., C.M.C.)Search for more papers by this author, Catherine M. Clase, MB, BChir, MSc, FRCPCMcMaster University, Hamilton, Ontario, Canada (C.M.R., C.M.C.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2015-162-8-003 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationPathak R, Pandit A, Karmacharya P, et al. Meta-analysis on risk of bleeding with apixaban in patients with renal impairment. Am J Cardiol. 2015;115:323-7. https://pubmed.ncbi.nlm.nih.gov/25527282Clinical Impact RatingsGIM/FP/GP: Cardiology: Hematology: Nephrology: References1. Connolly SJ, Ezekowitz MD, Yusuf S, et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139-51. [PMID: 19717844] Google Scholar2. Hernandez I, Baik SH, Piñera A, Zhang Y. Risk of bleeding with dabigatran in atrial fibrillation. JAMA Intern Med. 2015;175:18-24. [PMID: 25365537] Google Scholar3. Jun M, James MT, Manns BJ, et al; Alberta Kidney Disease Network. The association between kidney function and major bleeding in older adults with atrial fibrillation starting warfarin treatment: population based observational study. BMJ. 2015;350:h246. [PMID: 25647223] Google Scholar4. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney International Supplements. 2013;3:1−150. Google Scholar Author, Article, and Disclosure InformationAffiliations: McMaster University, Hamilton, Ontario, Canada (C.M.R., C.M.C.)This article was published at Annals.org on 7 April 2015. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByClinical Application and Pharmacodynamic Monitoring of Apixaban in a Patient with End-Stage Renal Disease Requiring Chronic Hemodialysis 21 April 2015Volume 162, Issue 8Page: JC3KeywordsAcute renal failureAnticoagulantsCreatinineDrugsHemorrhageKidneysResearch designSafety ePublished: 21 April 2015 Issue Published: 21 April 2015 CopyrightCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Combination in a Single Hospital Service of Gynecologic and Obstetric Patients
Authors: Herman W. Rannels
Journal: JAMA (1962)

The purpose of this 5-year pilot study was to seek a safe and practical way to utilize empty obstetrical beds by the admission of clean gynecologic cases in an otherwise overcrowded general hospital. During this period there were 3,398 deliveries and 1,472 gynecologic cases cared for on the combined service. The 5-year obstetric morbidity rate was 2.2%. There were no infection outbreaks of epidemic proportions. The same nursing personnel cared for both types of patients. The average number of hours of nursing care per person per day was not substantially increased. Utilization of beds was increased by almost 25%. To insure success, intensive around-the-clock indoctrination and orientation of all personnel, including physicians, was essential. The responsibility for the program, including admissions and transfers, must rest solely with the director of the service.
Expression ofβ2−microglobulin on hepatocytes in acute and chronic type B hepatitis
Authors: Yukihisa Nagafuchi, Peter J. Scheuer
Journal: Hepatology (1986)

beta 2-Microglobulin display was examined in 131 liver biopsies from patients with acute and chronic type B hepatitis, using an indirect immunoperoxidase method. Enhanced expression of beta 2-microglobulin on hepatocyte membranes was observed in patients with acute hepatitis, chronic active hepatitis with moderate to severe activity and cirrhosis, when compared with normal liver. In acute hepatitis, beta 2-microglobulin-positive hepatocytes were mainly observed in perivenular areas in association with bridging necrosis. In chronic hepatitis, beta 2-microglobulin-positive hepatocytes were observed mainly in periportal zones and in some areas of lobular activity. Diffuse-enhanced display of beta 2-microglobulin on hepatocytes was observed in 5 of 6 patients treated with lymphoblastoid interferon as part of a trial of antiviral therapy. The mechanism by which beta 2-microglobulin display is enhanced on hepatocytes in patients not treated with interferon is uncertain. However, display of beta 2-microglobulin on hepatocytes probably reflects display of HLA-A, B and C antigens and may influence the course of hepatitis B virus infection by increasing susceptibility of the affected cells to T cell-mediated immune attack.
Osteopathy and Legislation.
Authors: Robert T. Morris
Journal: JAMA (1903)

New York, April 10, 1903. <h3>To the Editor:</h3> —My recent letter toThe Journalon this subject has brought a number of letters from physicians who have been interested in the matter, and I have received voluminous literature in the way of arguments. Right here lies the weak point in our opposition. Arguments on both sides have been so extensive that they have sometimes become top heavy and have fallen by their own weight, toppling occasionally in the wrong direction. A very able lawyer who presented the interests of the osteopaths before one legislative committee told me afterward that he had no fear of the physicians or of their lawyers, but when he saw the osteopaths slip up on making a demonstration when opportunity was given them to move a few bones, he at once lost faith in his clients and would have nothing more to do with them. He
Medical manpower and the career structure: a new approach.
Authors: M D Vickers
Journal: BMJ (1981)

A change in the ratio of trainees to consultants is necessary: despite being the agreed policy of the profession and DHSS, existing central planning machinery has failed to bring about its implementation. There is no reason to suppose that central methods can ever achieve the desired ends without intolerable constraints on the liberty of doctors. Freedom for individual groups of consultants to negotiate local changes in manpower coupled with inducements to both them and the authorities would seem to provide a promising approach that has not yet been adequately debated for explored. In the nature of it such an idea is unlikely to be attractive to central bureaucratic organisations, whether governmental or professional.
Glutamine transport in isolated human hepatocytes and transformed liver cells
Authors: Barrie P. Bode, Donald L. Kaminski, Wiley W. Souba, Al P. Li
Journal: Hepatology (1995)

The transport of L-glutamine was examined in isolated adult and fetal human hepatocytes as well as in the human hepatoma cell lines HepG2 and SK-Hep. In all cells studied, glutamine uptake was at least 85% Na(+)-dependent. Kinetic analysis of the Na(+)-dependent component indicated mediation by a single transporter in three human hepatocyte preparations and in SK-Hep cells, whereas two transporters appeared to be responsible for glutamine uptake in HepG2 cells and in hepatocytes from the liver of one male patient. Amino acid inhibition analysis showed primary mediation by System N in fetal and adult hepatocytes, whereas System ASC was principally responsible for glutamine uptake in transformed cells. Similar to the rat transporter, human System N was pH-sensitive, stereospecific, and responsive to treatment with steroid hormones. Although the human carrier was less tolerant of Li(+)- for Na+ substitution, glutamine transport in primary human hepatocytes was stimulated by treatment with hypotonic buffer (cell swelling), as reported in rat parenchymal cells. In contrast, glutamine transport in hepatoma cells was relatively insensitive to changes in extracellular pH and failed to show enhanced activity in response to hypoosmotic challenge. Collectively, the data suggest that markedly distinct plasma membrane transporters mediate the concentrative uptake of glutamine in normal and transformed human hepatocytes, and that the salient properties of System N have been largely conserved from rat to man.
Comparative hybridization reveals extensive genome variation in the AIDS-associated pathogen Cryptococcus neoformans
Authors: Guanggan Hu, Iris Liu, Anita Sham, Jason E Stajich, Fred S Dietrich, James W Kronstad
Journal: Genome biology (2008)

Genome variability can have a profound influence on the virulence of pathogenic microbes. The availability of genome sequences for two strains of the AIDS-associated fungal pathogen Cryptococcus neoformans presented an opportunity to use comparative genome hybridization (CGH) to examine genome variability between strains of different mating type, molecular subtype, and ploidy.Initially, CGH was used to compare the approximately 100 kilobase MATa and MATalpha mating-type regions in serotype A and D strains to establish the relationship between the Log2 ratios of hybridization signals and sequence identity. Subsequently, we compared the genomes of the environmental isolate NIH433 (MATa) and the clinical isolate NIH12 (MATalpha) with a tiling array of the genome of the laboratory strain JEC21 derived from these strains. In this case, CGH identified putative recombination sites and the origins of specific segments of the JEC21 genome. Similarly, CGH analysis revealed marked variability in the genomes of strains representing the VNI, VNII, and VNB molecular subtypes of the A serotype, including disomy for chromosome 13 in two strains. Additionally, CGH identified differences in chromosome content between three strains with the hybrid AD serotype and revealed that chromosome 1 from the serotype A genome is preferentially retained in all three strains.The genomes of serotypes A, D, and AD strains exhibit extensive variation that spans the range from small differences (such as regions of divergence, deletion, or amplification) to the unexpected disomy for chromosome 13 in haploid strains and preferential retention of specific chromosomes in naturally occurring diploids.