tbuckley/cabot-search huggingface dataset:
319. Comparison of Serum-Free Media for Optimal Ex Vivo Transduction of Human CD34+ Cells
Authors: Joanna L. Ireland, Greg M. Podsakoff, Donald B. Kohn, Barbara C. Engel
Journal: Molecular Therapy (2006)

Current studies involving the clinical application of genetically modified hematopoietic stem cells (HSC) require an ex vivo culture period during which the cells must maintain their ability to self- renew, repopulate the bone marrow, and produce the genetically corrected progeny cells. Recent advances in the formulation of optimized serum-free HSC tissue culture media led us to compare several recently commercially available culture media with the medium used in our current clinical gene therapy protocols for the transduction of HSC. We compared expansion, transduction efficiency, and differentiation of both cord blood (CB) and bone marrow (BM) derived CD34+ cells using X-Vivo15 (BioWhittaker, supplemented with 1% HSA), Cellgro® SCGM (Cellgenix), StemSpan™ H300 (Stemline Technologies), Stemline™ I (Sigma- Aldrich), and Stemline™ II (Sigma-Aldrich). We observed comparable cell viability among the various media when using BM and CB derived CD34+ cells after 4 days of culture. Both BM and CB CD34+ cells cultured in X-Vivo 15, Cellgro® SCGM, and Stemline™ II expanded to a greater extent than cells cultured in StemSpan™ H3000 or Stemline™. Higher transduction efficiency using a retrovirus containing the eGFP gene was also observed in X- Vivo 15, Cellgro® SCGM, and Stemline™ II media. A direct comparison between BM and CB CD34+ cells cultured in X-Vivo 15 or Stemline™ II resulted in 23% (BM) and 27% (CB) more transduced cells in the Stemline™ II medium. We then examined the clonogenicity of the transduced BM CD34+ cells in a Colony Forming Unit (CFU) assay. BM CD34+ cells cultured in Stemline™ II medium displayed a two-fold higher (16%) plating efficiency in the CFU assay compared to BM CD34+ cells cultured in X-Vivo 15 (8-9.5%). The number of colonies that were transduced (eGFP+) was higher in the BM CD34+ cells cultured in Stemline™ II medium compared to those cultured in X-Vivo 15 (29.9% and 10.3% respectively). From these results it is evident that BM CD34+ cells cultured in Stemline™ II medium have both a higher percentage of transduced cells and a higher percentage of these transduced cells remain capable of producing colonies in a CFU assay when compared with X-Vivo 15. From these data, Stemline™ II appears to be a more suitable medium for the ex vivo culturing and transduction of HSC for use in clinical therapies.
Severe and progressive encephalitis as a presenting manifestation of a novel missense perforin mutation and impaired cytolytic activity
Authors: Jérôme Feldmann, Gaël Ménasché, Isabelle Callebaut, Véronique Minard-Colin, Brigitte Bader-Meunier, Laurence Le Clainche, Alain Fischer, Françoise Le Deist, Marc Tardieu, Geneviève de Saint Basile
Journal: Blood (2004)

Mutations in the perforin gene cause familial hemophagocytic lymphohistiocytosis (FHL). The first symptoms of FHL are usually intractable fever, hepatosplenomegaly, and pancytopenia. Most FHL patients subsequently develop central nervous system (CNS) manifestations due to infiltration of tissues by activated lymphocytes and macrophages. We report 2 FHL patients with an atypical phenotype characterized by isolated severe neurologic symptoms mimicking chronic encephalitis and leading to an early death. Functional and molecular analyses revealed the same novel missense mutation in the perforin gene in both patients; this mutation affected the calcium-binding domain of the protein. This missense mutation did not affect perforin maturation or expression in cytotoxic cells but impaired in vitro cytotoxic activity. Diagnosis was delayed in both patients because of the initial neurologic expression and the normal expression of perforin in circulating lymphocytes. This emphasizes the importance of early diagnosis of this atypical form of FHL, as CNS involvement causes severe, irreversible encephalopathy. This observation also raises the question of the role of some mutations in the neurologic expression of FHL.
Normal Macular Thickness Measurements Using Optical Coherence Tomography in Healthy Eyes of Adult Chinese Persons: The Handan Eye Study
Authors: Xin Rong Duan, Yuan Bo Liang, David S. Friedman, Lan Ping Sun, Tien Yin Wong, Qiu shan Tao, Lingzhi Bao, Ning Li Wang, Jie Jin Wang
Journal: Ophthalmology (2010)
Blair trumpets Labour's investment in NHS—and stands by his reforms of the past decade
Authors: Lynn Eaton
Journal: BMJ (2007)

The government has admitted that it will have to wait years before it discovers whether there are real productivity gains from the new consultants' contract.NHS leaders also told the House of Commons Committee of Public Accounts last week that lessons had been learnt from mistakes made when the contract was introduced, such as not piloting it before implementation.They were giving evidence as part of the committee's inquiry into the consultants' contract.The session was prompted by the publication earlier this month of a report from the government's
Rod Vision Is Controlled by Dopamine-Dependent Sensitization of Rod Bipolar Cells by GABA
Authors: Rolf Herrmann, Stephanie J. Heflin, Timothy Hammond, Bowa Lee, Jing Wang, Raul R. Gainetdinov, Marc G. Caron, Erika D. Eggers, Laura J. Frishman, Maureen A. McCall, Vadim Y. Arshavsky
Journal: Neuron (2011)
CONCEALED ALCOHOL IN DRUGS.
Authors: T. D. CROTHERS
Journal: JAMA (1897)

The fact is well known that nearly all proprietary drugs contain large quantities of spirits, particularly the bitters and tonics that are advertised so widely Several authorities have made extensive examinations of drugs advertised as temperance drinks and free from alcohol, and in every instance have found spirits from 3 to 50 per cent. of volume, literally ranging all the way from the lighter beers up to the strongest alcoholic drinks in common use. Dr. Bradner has published tables of these drugs compiled from the reports of the Massachusetts Health Board and the examination of State chemists in different parts of the country. His paper appeared in the<i>Journal of Inebriety</i>for January, 1890, and the second paper on this subject will be found in the July issue of that journal. These papers bring out the fact, not well known, that nearly all the more prominent proprietary drugs on the
Radiation Therapy in Cancer of the Larynx
Authors: M. Lederman
Journal: JAMA (1972)

Unlike bronchial cancer, which has assumed almost epidemic proportions in many countries, cancer of the trachea is rare, and cancer of the larynx is uncommon. Laryngeal cancer, nevertheless, resembles bronchial cancer in being essentially a disease of men who smoke. Because of its accessibility to investigation, laryngeal cancer has been studied in detail; three regional and very different varieties of cancer have been recognized as occurring within this limited and specialized part of the upper respiratory tract.<sup>9</sup>The glottis, formed by the vocal cords, is the seat of 70% of these cancers; in 20% of cases, the supraglottis, ie, the region between the margins of the laryngeal opening and the epiglottis, is affected; the rarest laryngeal cancer site is the subglottic region, between the vocal cords and the lower border of the cricoid cartilage, where the incidence is 10%. The favorable features of laryngeal cancer are its relatively slow
GSK makes structures of potential antimalarials freely available
Authors: J. Wise
Journal: BMJ (2010)

GlaxoSmithKline has announced that it will make the chemical structures of 13 500 compounds with potential antimalarial activity freely available on scientific websites to encourage research into new drugs for malaria.

The company says it has screened its pharmaceutical compound library of more than two million molecules for any that inhibit the malaria parasite Plasmodium falciparum . The company says this process took five scientists a year to complete.

Andrew Witty, chief executive of GSK, announced his “Open Innovation” strategy in a speech given at the Council on Foreign Relations in New York on 20 January. As well as opening up access to these potential antimalarial compounds, the company has set up an “open lab,” which will be part of its research centre in Tres Cantos, near Madrid. The laboratory will have capacity for up to 60 independent researchers to pursue their own projects as part of a drug discovery …
Elderly Licensure Laws and Motor Vehicle Fatalities
Authors: David C. Grabowski
Journal: JAMA (2004)

ContextLittle is known about how state-level driver licensure laws, such as inperson renewal, vision tests, road tests, and the frequency of license renewal relate to the older driver traffic fatality rate.Objective To determine whether state driver's license renewal policies are associated with the fatality rate among elderly drivers. Design, Setting, and PopulationRetrospective, longitudinal study conducted January 1990 through December 2000 of all fatal crashes in the contiguous United States identified in the Fatality Analysis Reporting System, which involved either an older (ages 65-74 years, 75-84 years, and Ն85 years) or middle-aged (ages 25-64 years) driver.Two regression approaches were used to study the effect of state laws mandating inperson renewal, vision tests, road tests, and frequency of license renewal on driver fatalities, controlling for state-level factors including the number of licensed elderly drivers, primary and secondary seatbelt laws, maximum speed limit laws, blood alcohol level of 0.08, and administrative license revocation drinking and driving laws, per capita income, and unemployment rate.The first regression approach examined only elderly driver fatalities and the second approach examined daytime elderly driver fatalities and used daytime fatalities among middle-aged drivers as a general control for unobserved variation across states and over time. Main Outcome MeasuresOlder driver fatalities and older and middle-aged daytime driver fatalities. ResultsAmong individuals aged 85 years or older, there were a total of 4605 driver fatalities and 4179 daytime driver fatalities during the study period.For this age cohort, after controlling for middle-aged daytime driver deaths, states with in-person license renewal were associated with a lower driver fatality rate (incident rate ratio [RR], 0.83; 95% confidence interval [CI], 0.72-0.96).This was the only policy related to older drivers that was significantly associated with a lower fatality risk across both regression models.Thus, state-mandated vision tests, road tests, more frequent license renewal, and in-person renewal (for individuals aged 65-74 years and 75-84 years) were not found to be independently associated with the fatality rate among older drivers in the 2 models. ConclusionsIn-person license renewal was related to a significantly lower fatality rate among the oldest old drivers.More stringent state licensure policies such as vision tests, road tests, and more frequent license renewal cycles were not independently associated with additional benefits.
EFFECTS OF MAINTAINED INTENSE EXERCISE THROUGHOUT THE LIFE ON THE ADAPTIVE IMMUNE RESPONSE IN ELDERLY AND YOUNG ATHLETES
Authors: Antonio Moro-García Marco, Benjamin Fernández-García, Rebeca Alonso-Arias, Manuel Rodriguez-Alonso, Manuel Suárez García Francisco, Carlos López- Larrea
Journal: British Journal of Sports Medicine (2013)

Background Exercise induces a series of changes on the immune system depending on their intensity and duration. 1 2 In fact, transient states of immunosuppression are induced after intense physical activity 3 and yet beneficial exercise anti-inflammatory effects have been described over many diseases and longevity. 1 Methods To study the impact of intense exercise for long periods of life on adaptive immunity at different ages we compared phenotypical and functional features of T lymphocytes of young (n=27) and elderly athletes (n=15) with young (n=30) and elderly non-athletes (n=30). We characterized leukocyte and lymphocyte subpopulations by flow cytometry and measured the T cell proliferation and activation response (CD69) against anti-CD3. We also studied the percentage of recent thymic emigrants (RTEs) by quantification of TREC by real-time PCR. Specific antibody titers against CMV were determined by ELISA. Results Leucopenia was found in both groups of athletes, mainly explained by low levels of neutrophils and lymphocytes. Exercise induced higher frequencies of NK, B lymphocytes and CD8+ T cells, whereas CD4+ T lymphocytes showed significant lower levels in the elderly athletes. Moreover, young athletes showed significant differences in all parameters that define the immune risk profile (IRP), with characteristics of an aging immune system, but we did not find differences between elderly groups. Less differentiated subsets of T lymphocytes were more frequents in non-athletes, with the exception of CD8+ T lymphocytes in young individuals. The analysis of TREC content in the elderly groups showed no significant difference in either the CD4+ or CD8+ T lymphocytes. In the young non-athletes group we observe an increase in the content of TREC in CD8+ T cells, but not in CD4+ T cells. Moreover, functional response of CD4+ and CD8+ T lymphocytes was significantly impaired only in young but no in elderly athletes. Conclusions Intensive training for long periods throughout life induces important phenotypical and functional changes on the adaptive immune response. These changes are most striking in young individuals and they damped with physiologic immune aging.
We want raw data, now
Authors: F. Godlee
Journal: BMJ (2009)

This week’s BMJ is dominated by a cluster of articles on oseltamivir (Tamiflu) (doi:10.1136/bmj.b5351, doi:10.1136/bmj.b5387, doi:10.1136/bmj.b5106, doi:10.1136/bmj.b5164, doi:10.1136/bmj.b5248, doi:10.1136/bmj.b5364). Between them the articles conclude that the evidence that oseltamivir reduces complications in otherwise healthy people with pandemic influenza is now uncertain and that we need a radical change in the rules on access to trial data.

Briefly, in updating their Cochrane review, published this week (doi:10.1136/bmj.b5106), Tom Jefferson and colleagues failed to verify claims, based on an analysis of 10 drug company trials, that oseltamivir reduced the risk of complications in healthy adults with influenza. These …
A Phase II First-Line Study of Gemcitabine, Carboplatin, and Bevacizumab in Advanced Stage Nonsquamous Non-small Cell Lung Cancer
Authors: Christelle Clément-Duchêne, Yelena Krupitskaya, Kristen Ganjoo, Philip Lavori, Alex McMillan, Atul Kumar, Gary Zhao, Sukhmani Padda, Lisa Zhou, Melanie San Pedro-Salcedo, A. Dimitrios Colevas, Heather A. Wakelee
Journal: Journal of Thoracic Oncology (2010)
Addressing the “Fas Counterattack” Controversy: Blocking Fas Ligand Expression Suppresses Tumor Immune Evasion of Colon Cancer<i>In vivo</i>
Authors: Aideen E. Ryan, Fergus Shanahan, Joe O'Connell, Aileen M. Houston
Journal: Cancer Research (2005)

Abstract Fas ligand (FasL/CD95L) is a transmembrane protein belonging to the tumor necrosis factor superfamily that can trigger apoptotic cell death following ligation to its receptor, Fas (CD95/APO-1). Expression of FasL may help to maintain tumor cells in a state of immune privilege by inducing apoptosis of antitumor immune effector cells—the “Fas counterattack.” However, the ability of FasL to mediate tumor immune privilege is controversial due to studies that indicate FasL has both pro- and anti-inflammatory activities. To resolve this controversy and functionally define the role of FasL in tumor immune evasion, we investigated if suppression of endogenously expressed FasL in colon tumor cells resulted in reduced tumor development and improved antitumor immune challenge in vivo. Specifically, FasL expression in CMT93 colon carcinoma cells was down-regulated following stable transfection with a plasmid encoding antisense FasL cDNA. Down-regulation of FasL expression had no effect on tumor growth in vitro but significantly reduced tumor development in syngeneic immunocompetent mice in vivo. Tumor size was also significantly decreased. Reduced FasL expression by tumor cells led to increased lymphocyte infiltration. The overall level of neutrophils present in all of the tumors examined was low, with no difference between the tumors, irrespective of FasL expression. Thus, down-regulation of FasL expression by colon tumor cells results in an improved antitumor immune challenge in vivo, providing functional evidence in favor of the “Fas counterattack” as a mechanism of tumor immune evasion.
Correctional Health Care
Authors: Linda Johnson White
Journal: Annals of Internal Medicine (1993)

Letters15 January 1993Correctional Health CareLinda Johnson White, MDLinda Johnson White, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-2-199301150-00027 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We thank Dr. Cunningham for his insightful comments. We hope that continuing dialogue within the medical community about correctional health care will foster the steps needed to assure the quality of health care delivered in prisons and jails in this country. Author, Article, and Disclosure InformationAuthors: Linda Johnson White, MD PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 January 1993Volume 118, Issue 2Page: 158KeywordsHealth careHealth care qualityPrevention, policy, and public health ePublished: 15 August 2000 Issue Published: 15 January 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Clonal analysis of primary B cells responsive to the pathogenic bacterium Salmonella typhimurium.
Authors: L W Duran, E S Metcalf
Journal: The Journal of Experimental Medicine (1987)

In the present study, a modification of the splenic focus system is used to analyze the S. typhimurium strain TML (TML)-specific B cell repertoire. The results show that the frequency of primary TML-specific splenic B cells in CBA/Ca mice is approximately 1 per 10(5) B cells and less than 30% of these B cells are specific for LPS. In contrast, the frequency of memory TML-specific cells is approximately 1 per 5-8 X 10(3) splenic B cells and greater than 95% of these B cells are specific for LPS. These results suggest that the frequency of primary TML-specific B cells is extremely low and that it expands 15-20-fold after antigen exposure. It is interesting that less than 30% of the primary B cells are specific for the LPS molecule since it is considered to be the major antigenic determinant on Salmonella organisms. Furthermore, the majority of the LPS-specific anti-TML antibody-producing clones are directed against the LPS O antigen region. Conversely, more than half to two-thirds of the memory LPS-specific anti-TML B cell clones are directed against the KDO or lipid A region of the LPS molecule. These results indicate that the preferential expansion of LPS-specific B cell clones observed after immunization resides primarily in the B cell subsets responsive to the KDO/lipid A moieties on the LPS molecule. Finally, unlike B cell responses to chemically defined antigens, TML stimulates very little IgG1 antibody. IgG2 and IgA isotypes appear to play a predominant role in anti-TML antibody responses, although all H chain classes are produced to some extent. Collectively, these findings are consistent with the responses reported for two other natural antigens, HA and PC. Hence, the pattern of stimulation by infectious agents, such as S. typhimurium, appears to be distinct from that of synthetic antigens. Thus, the studies presented herein have begun to provide insights into those subsets of B cells responsive to S. typhimurium and other infectious disease organisms.
FACTORS GOVERNING CORRECTION OF THE ALKALOSIS ASSOCIATED WITH POTASSIUM DEFICIENCY; THE CRITICAL ROLE OF CHLORIDE IN THE RECOVERY PROCESS*
Authors: E. Laurence Atkins, William B. Schwartz
Journal: Journal of Clinical Investigation (1962)

Recent observations on the dog indicate that during recovery from chronic hypercapnia the chloride ion plays a critical role in permitting full restoration of plasma composition to normal (1).Plasma bicarbonate concentration remains sig- nificantly elevated, and plasma chloride concen- tration markedly depressed unless chloride is provided in the diet.It was tentatively proposed that when the quantity of chloride available for reabsorption is reduced, the transtubular potential difference generated by active transport of sodium is greater than normal and that this, in turn, is responsible for a higher than normal rate of dif- fusion of hydrogen ions into the glomerular fil- trate and for the sustained elevation of plasma bi- carbonate concentration.The present study was undertaken to deter- mine whether chloride may play a significant role in the correction of the metabolic alkalosis associated with potassium deficiency.For this purpose, studies have been performed in dogs made potassium deficient, alkalotic, and hypochloremic by the administration of deoxycorticosterone acetate (DCA)' and sodium bicarbonate.Subsequently, three consecutive maneuvers were carried out while the animals were maintained on a diet low in potassium and chloride: 1) DCA was withdrawn, 2) potassium bicarbonate was sub- stituted for sodium bicarbonate in the daily elec- trolyte supplement, and 3) chloride was adminis- tered in various forms.
Preliminary experience with the POSSIS coronary AngioJet rheolytic thrombectomy catheter in the VeGAS I pilot study
Authors: Stephen R. Ramee, Richard E. Kuntz, Richard A. Schatz, Joseph P. Carrozza, Jeffrey J. Popma, Alyce S. Lanoue, Cynthia Senerchia, Robert C. Stoler, Kalon K.L. Ho, Donald S. Baim
Journal: Journal of the American College of Cardiology (1996)
Academic medicine: who is it for?
Authors: Jacqueline M Atkinson
Journal: BMJ (2005)

Wright and Wedge contend that the academic freedom of clinical academics is constrained by the primacy of patients' welfare, putting them in a different position to non-clinical academics. 1However, they may be more similar to other academics than they think.Academic freedom has two aspects: the freedom to research whatever the academic wishes, and the freedom to interpret data free from outside influence.The first freedom was lost by all academics because of the research assessment exercise.The second freedom is arguably more important.Patients' safety may be compromised by inappropriate conclusions being drawn, but this is part of the scientific debate central to all research.Patients' safety can be compromised by non-academic clinicians whose practice is affected by other interests-for example, links with the drug industry.All researchers have a duty not to harm research participants or place the public at risk while carrying out their research.As universities move to require ethical approval for all research, including that on humans, this becomes ever more clear.A different issue is the use to which some research is put.Finally, the authors raise issues of competence and unacceptable behaviour.All researchers, in any discipline, can carry out research ethically and safely only if they have the appropriate skills so to do.Unacceptable behaviour, to research participants or members of the department, can lead to complaints and disciplinary action, which might have an impact on research.Medicine's particular role has meant that ethical guidelines for research have led other disciplines.Rather than seek to see itself as apart it would be more helpful to engage in the wider discussions on ethical research, public safety, and the use of research.
546 DAY OF SURGERY REJECTION OF DONORS IN LIVING DONOR LIVER TRANSPLANTATION: IS IT ACCEPTABLE?
Authors: B. Hegab, A. Azzam, H. Mohamed, Y. Kamel, H. Al Bahili, H. Khalaf, F. Abal Khail, W. AL-Hamoudi, M. Al Sofayan, M. Al Sebayel
Journal: Journal of Hepatology (2011)