tbuckley/cabot-search huggingface dataset:
Caetano Reis e Sousa: harnessing DC power
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2008)

DCs can either magnify or mute immunity by sampling antigens throughout body and presenting them to lymphocytes in combination with secondary signals that either activate or tolerize the responding cell. This quality, which makes DCs a handy weapon against both cancer and autoimmune disease, spurred Caetano Reis e Sousa to dissect the pathways that control different DC functions.




Figure 1





Caetano Reis e Sousa




Reis e Sousa first encountered DCs as a graduate student in Jonathan Austyn's laboratory at Oxford University. At the time, these cells were thought to lack the ability to phagocytose antigens—a troubling deficiency in cells known as the initiators of immune responses to microbes. Using DCs found in the skin, Reis e Sousa showed that the inability to pick up antigen was limited to mature cells; freshly isolated (immature) DCs could engulf particulate antigens with ease (1).

Determined that his DC expertise become more than skin-deep, Reis e Sousa accepted a post-doctoral position with Ron Germain at the NIH, where he studied antigen processing and cross-presentation by DCs and other cells (2). While at the NIH, he also collaborated with Alan Sher to investigate how microbe-activated DCs induce a T helper (Th)-1 cell response (3).

Since starting his own laboratory at the London Research Institute in 1998, Reis e Sousa has defined several pathways of DC activation that involve Toll-like receptors (TLRs) and non-TLRs such as RIG-I and C-type lectins (4–7). His group recently discovered a marker for a DC subset adept at cross-presentation, which might help bring DCs further into the realm of translational medicine (8).
Glucocorticoid Receptor Regulates Expression of L-Selectin and CD11/CD18 on Human Neutrophils
Authors: János G. Filep, Aline Delalandre, Yves Payette, Éva Földes-Filep
Journal: Circulation (1997)

Background Recent studies have raised the hypothesis that glucocorticoids could diminish the ability of endothelial cells to direct leukocyte traffic into inflamed tissues by inhibiting expression of the adhesion molecules endothelial-leukocyte adhesion molecule-1 and intercellular adhesion molecule-1. The aim of the present study was to investigate whether glucocorticoids also regulate the expression of L-selectin and CD11/CD18 integrins on human neutrophil granulocytes. Methods and Results Incubation of human whole blood with platelet-activating factor (PAF, 1 μmol/L) evoked downregulation of L-selectin and upregulation of CD11/CD18 adhesion receptors on neutrophils as measured by flow cytometry. While dexamethasone (0.1 nmol/L to 100 μmol/L) did not affect expression of adhesion molecules on resting neutrophils, it attenuated the PAF-induced changes in L-selectin and CD18 expression in a time- and concentration-dependent fashion with IC 50 values of 31 and 13 nmol/L, respectively. These effects of dexamethasone were completely aborted by RU-486 (10 μmol/L), which blocks transcriptional activation of the glucocorticoid receptor, and by the protein synthesis inhibitor cycloheximide (35.5 μmol/L). Dexamethasone, up to a concentration of 1 μmol/L, neither affected significantly the release of granule enzymes nor interfered with PAF binding to its membrane receptors. Conclusions Our results show that glucocorticoids at clinically relevant concentrations exert specific actions on expression of adhesion molecules on activated neutrophils, which are mediated through ligation of glucocorticoid receptors and induction of protein synthesis, and suggest a novel mechanism by which anti-inflammatory corticosteroids may inhibit leukocyte accumulation.
BCR-ABL1 compound mutations in tyrosine kinase inhibitor–resistant CML: frequency and clonal relationships
Authors: Jamshid S. Khorashad, Todd W. Kelley, Philippe Szankasi, Clinton C. Mason, Simona Soverini, Lauren T. Adrian, Christopher A. Eide, Matthew S. Zabriskie, Thoralf Lange, Johanna C. Estrada, Anthony D. Pomicter, Anna M. Eiring, Ira L. Kraft, David J. Anderson, Zhimin Gu, Mary Alikian, Alistair G. Reid, Letizia Foroni, David Marin, Brian J. Druker, Thomas O'Hare, Michael W. Deininger
Journal: Blood (2012)
Kinship, optimality, and typology
Authors: Simon Musgrave, David L. Dowe
Journal: Behavioral and Brain Sciences (2010)

Abstract Jones uses a mechanism from the linguistic theory, Optimality Theory, to generate the range of kin systems observed in human cultures and human languages. The observed distribution of kinship systems across human societies suggests that some possibilities are preferred over others, a result that would indicate Jones' model needs to be refined, especially in its treatment of markedness.
The Premarital Medical Examination and the Carolina Population Center
Authors: Ethel M. Nash
Journal: JAMA (1969)

This study, based on a sample of 3,592 young people in North Carolina, has produced data concerning (1) widespread ignorance of the purpose of the premarital medical examination; (2) hopes held by patients that the physician will give the extended type of premarital examination and especially that he offer, unasked, contraceptive and sexual counsel during conferences with the pair who are to be married; (3) the need to extend sex education to younger age groups; and (4) the distinction made by youth about the respective roles of the physician and the clergyman. The premarital medical examination provides an initial opportunity to give sexual and contraceptive counseling to individuals as well as couples. Physicians could probably be of great service to patients if at this time they would suggest that the couple return to a physician after one to three months of marriage, to talk over problems or questions that have arisen during the initial stage of their relationship.
KANGRI-BURN CANCER
Authors: E. F. Neve
Journal: BMJ (1923)

Similarly large mononuclear increase in malaria means tissue response to the malaria parasite.Absence of a large mono- nuclear increase is not a sign that malaria is not present; it is simply a sign that the patient is not reacting Both large mononuclear increase in malaria and eosinophilia in bilharzia are indications of the response of the tissues- both are signs of good omen, but neither is a specific sign.Absence is in neither case a reliable sign that either malaria in the one case or bilharzia in the other is abseint.
Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy
Authors: Mark J. Millan, Yves Agid, Martin Brüne, Edward T. Bullmore, Cameron S. Carter, Nicola S. Clayton, Richard Connor, Sabrina Davis, Bill Deakin, Robert J. DeRubeis, Bruno Dubois, Mark A. Geyer, Guy M. Goodwin, Philip Gorwood, Thérèse M. Jay, Marian Joëls, Isabelle M. Mansuy, Andreas Meyer-Lindenberg, Declan Murphy, Edmund Rolls, Bernd Saletu, Michael Spedding, John Sweeney, Miles Whittington, Larry J. Young
Journal: Nature Reviews Drug Discovery (2012)
Giemsa Stain for Legionella pneumophila and TATLOCK Bacterium
Authors: Werner A. Janssen, Kenneth W. Hedlund
Journal: Annals of Internal Medicine (1981)

Letters and Corrections1 March 1981Giemsa Stain for Legionella pneumophila and TATLOCK BacteriumWERNER A. JANSSEN, S.M., KENNETH W. HEDLUND, M.D.WERNER A. JANSSEN, S.M.Search for more papers by this author, KENNETH W. HEDLUND, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-94-3-413_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The causative organisms in Legionnaires' disease, Pontiac fever, and Pittsburgh pneumonia are rod-shaped bacteria that are refractory to most bacteriologic and histologic stains. They are considered to be gram-negative, although they usually stain very weakly even after prolonged exposure to safranin in the Gram staining procedure. The initial successful demonstration ofLegionella pneumophilain culture smears was made by McDade and colleagues (1) using the Giménez stain and in human lung tissue sections by Chandler and associates (2) using a modified Dieterle silver impregnation procedure. These staining procedures are still the most widely used in studies of...References1. MCDADESHEPARDFRASER JCD. Legionnaires' disease: isolation of a bacterium and demonstration of its role in other respiratory diseases. N Engl J Med. 1977;297:1197-1203. CrossrefMedlineGoogle Scholar2. CHANDLERHIKLINBLACKMON FMJ. Demonstration of the agent of Legionnaires' disease in tissue. N Engl J Med. 1977;297:1218-20. CrossrefMedlineGoogle Scholar3. FRENKELBAKERCHONKO JLA. Autopsy diagnosis of Legionnaires' disease in immunosuppressed patients: a paleodiagnosis using Giemsa stain (Wohlbach modification). Ann Intern Med. 1979;90:559-62. LinkGoogle Scholar4. CHERRYPITTMANHARRIS WBP. Detection of Legionnaires' disease bacteria by direct immunofluorescent staining. J Clin Microbiol. 1978;8:329-38. CrossrefMedlineGoogle Scholar5. HEBERTTHOMASONHARRISHICKLINMCKINNEY GBPMR. "Pittsburgh pneumonia agent": a bacterium phenotypically similar to Legionella pnuemophila and identical to the TATLOCK bacterium. Ann Intern Med. 1980;92:53-4. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: WERNER A. JANSSEN, S.M.; KENNETH W. HEDLUND, M.D.Affiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byLegionella and Legionnaires' Disease: A Review with Emphasis on Environmental Studies and Laboratory DiagnosisLaboratory Diagnosis of Infections Caused by Legionella Species 1 March 1981Volume 94, Issue 3Page: 413-414KeywordsBacteriaFeversGram stainingLegionella pneumophilaLegionellosisLungsPneumoniaStaining ePublished: 1 December 2008 Issue Published: 1 March 1981 PDF downloadLoading ...
AGGLUTINATION PHENOMENA IN LOBAR PNEUMONIA
Authors: Henry T. Chickering
Journal: The Journal of Experimental Medicine (1914)

1. Agglutinins are present in the blood of patients suffering from lobar pneumonia during some stage of the disease in a large percentage (73.8 per cent.) of the cases due to pneumococci belonging in groups I, II, and IV. 2. In most very severe and fatal cases agglutinins cannot be demonstrated, and it is probable that their absence during the later days of the disease may have unfavorable prognostic significance. 3. No agglutinins are demonstrable by the technique employed in the blood of patients suffering from infection with Pneumococcus mucosus (group III). 4. In certain cases agglutinins may be demonstrable for only one day, and in other cases they may persist for several weeks. 5. When agglutinins are demonstrable they usually appear at about the time of the crisis. 6. It has not been possible to demonstrate that treatment with immune serum has any effect on the appearance of agglutinins. 7. The agglutinins present in cases due to organisms of types I and II are always specific for the type of organism causing the infection. In certain cases the agglutination reaction may be more active or appear earlier when the homologous organism is employed than when other organisms of the group are used in the test. In cases due to organisms of type IV, the serum never causes agglutination of any organism except the homologous one.
The Use and Abuse of Physical Therapeutics
Authors: FRANK GRANGER
Journal: New England Journal of Medicine (1928)

Prior to the World War, physical measures of treatment were in rather general disrepute. It is true that through the efforts of Peter Hunter Ling, Metzger, Weir Mitchell, and Douglas Graham, massage had been placed on a sound basis. It was also recognized that it could be scientifically applied:   As a means of passive exercise.  For its local and general circulatory effects.  For the promotion of the lymphatic circulation.  For its direct stimulation or its sedation of the nervous system.  For the general improvement it might secure in nutrition, and, to a more limited degree, in muscular development.  For its value in certain types of ankylosis.   The works of Fraenkel, Franz, and Robert W. Lovett had proved that muscle training or reeducation had a field not only in anterior poliomyelitis and peripheral nerve paralyses, but also in organic nerve lesions, such as tabes dorsalis, the spinal scleroses and some of
Adaptive Evolution of <i>Cry</i> Genes in <i>Bacillus Thuringiensis</i>: Implications for Their Specificity Determination
Authors: Jin-Yu Wu, Fang-Qing Zhao, Jie Bai, Gang Deng, Song Qin, Qi-Yu Bao
Journal: Genomics Proteomics & Bioinformatics (2007)

The cry gene family, produced during the late exponential phase of growth in Bacillus thuringiensis, is a large, still-growing family of homologous genes, in which each gene encodes a protein with strong specific activity against only one or a few insect species. Extensive studies are mostly focusing on the structural and functional relationships of Cry proteins, and have revealed several residues or domains that are important for the target recognition and receptor attachment. In this study, we have employed a maximum likelihood method to detect evidence of adaptive evolution in Cry proteins, and have identified 24 positively selected residues, which are all located in Domain II or III. Combined with known data from mutagenesis studies, the majority of these residues, at the molecular level, contribute much to the insect specificity determination. We postulate that the potential pressures driving the diversification of Cry proteins may be in an attempt to adapt for the "arm race" between delta-endotoxins and the targeted insects, or to enlarge their target spectra, hence result in the functional divergence. The sites identified to be under positive selection would provide targets for further structural and functional analyses on Cry proteins.
Aerosolized Pentamidine: Effect on Diagnosis and Presentation of Pneumocystis carinii Pneumonia
Authors: Kethy M. Jules-Elysee
Journal: Annals of Internal Medicine (1990)

Study Objective: To determine the effect of previous aerosolized pentamidine therapy on diagnosis and presentation of Pneumocystis carinii pneumonia. Design: A retrospective study. Setting: A tertiary care hospital. Patients: Fifty-two consecutive patients with P. carinii pneumonia and underlying infection with the human immunodeficiency virus (HIV) who had bronchoscopy. Twenty-one patients who were on aerosolized pentamidine therapy served as the study group. Thirty-one patients who had not received the drug served as the control group. Measurements and Main Results: The yield of bronchoalveolar lavage for P. carinii pneumonia was 62% for the study group and 100% for the control group (P < 0.05). This lower yield was significant for the subset of patients having their first episode of P. carinii pneumonia. The yield of transbronchial biopsy was similar for both groups of patients (81% compared with 84%). The yield of bronchoscopy was not influenced by use of zidovudine. Review of lavage specimen slides suggested that there may be fewer organisms present in patients receiving aerosolized pentamidine. An atypical roentgenographic presentation of upper lobe predominant infiltrates was seen in 38% of the study patients and 7% of the control patients. In addition, pneumothoraces and cystic changes were also frequently seen in the study patients. Gallium scans, when done, were also atypical in the study group. Markers of the severity of disease, however, were similar in both groups. Conclusion: The yield of bronchoalveolar lavage for P. carinii pneumonia in HIV-infected patients is lower in patients receiving aerosolized pentamidine. Unusual roentgenographic presentations and atypical gallium scans are also found in this setting.
Being the Ghost in the Machine: A Medical Ghostwriter's Personal View
Authors: Linda Logdberg
Journal: PLoS Medicine (2011)

Ethical concerns about medical ghostwriting have been directed primarily at “guest” authors and the pharmaceutical companies that pay them. One voice that is largely missing is that of the ghostwriters themselves who, after all, create the documents that are in the ethical and legal crosshairs. Without them, one could argue, there can be no fraud, because it is they who create the fraudulent product.

For almost 11 years, I worked as a medical writer, creating a variety of pieces including the occasional ghostwritten article. For the most part, I never saw the finished paper, nor did I care to. This article describes what I did, why I did it, why I stopped doing it, and what I think might be done about the problem of fraud in authorship.
Tumor necrosis factor-alpha- and hyperglycemia-induced insulin resistance. Evidence for different mechanisms and different effects on insulin signaling.
Authors: G Kroder, B Bossenmaier, M Kellerer, E Capp, B Stoyanov, A Mühlhöfer, L Berti, H Horikoshi, A Ullrich, H Häring
Journal: Journal of Clinical Investigation (1996)

Inhibition of insulin receptor signaling by high glucose levels and by TNF-alpha was recently observed in different cell systems. The aim of the present study was to characterize the mechanism of TNF-alpha-induced insulin receptor inhibition and to compare the consequences of TNF-alpha- and hyperglycemia-induced insulin receptor inhibition for signal transduction downstream from the IR. TNF-alpha (0.5-10 nM) and high glucose (25 mM) showed similar rapid kinetics of inhibition (5-10 min, > 50%) of insulin receptor autophosphorylation in NIH3T3 cells overexpressing the human insulin receptor. TNF-alpha effects were completely prevented by the phosphotyrosine phosphatase (PTPase) inhibitors orthovanadate (40 microM) and phenylarsenoxide (35 microM), but they were unaffected by the protein kinase C (PKC) inhibitor H7 (0.1 mM), the phosphatidylinositol-3 kinase inhibitor wortmannin (5 microM), and the thiazolidindione troglitazone (CS045) (2 microgram/ml). In contrast, glucose effects were prevented by PKC inhibitors and CS045 but unaffected by PTPase inhibitors and wortmannin. To assess effects on downstream signaling, tyrosine phosphorylation of the following substrate proteins of the insulin receptor was determined: insulin receptor substrate-1, the coupling protein Shc, focal adhesion kinase (FAK125), and unidentified proteins of 130 kD, 60 kD. Hyperglycemia (25 mM glucose) and TNF-alpha showed analogous (> 50% inhibition) effects on tyrosine phosphorylation of insulin receptor substrate-1, Shc, p60, and p44, whereas opposite effects were observed for tyrosine phosphorylation of FAK125, which is dephosphorylated after insulin stimulation. Whereas TNF-alpha did not prevent insulin-induced dephosphorylation of FAK125, 25 mM glucose blocked this insulin effect completely. In summary, the data suggest that TNF-alpha and high glucose modulate insulin receptor-signaling through different mechanisms: (a) TNF-alpha modulates insulin receptor signals by PTPase activation, whereas glucose acts through activation of PKC. (b) Differences in modulation of the insulin receptor signaling cascade are found with TNF-alpha and high glucose: Hyperglycemia-induced insulin receptor inhibition blocks both insulin receptor-dependent tyrosine phosphorylation and dephosphorylation of insulin receptor substrate proteins. In contrast, TNF-alpha blocks only substrate phosphorylation, and it does not block insulin-induced substrate dephosphorylation. The different effects on FAK125 regulation allow the speculation that long-term cell effects related to FAK125 activity might develop in a different way in hyperglycemia- and TNF-alpha-dependent insulin resistance.
Occurrence of late gadolinium enhancement is associated with increased left ventricular wall stress and mass in patients with non‐ischaemic dilated cardiomyopathy
Authors: Peter Alter, Heinz Rupp, Philipp Adams, Florian Stoll, Jens H. Figiel, Klaus J. Klose, Marga B. Rominger, Bernhard Maisch
Journal: European Journal of Heart Failure (2011)
A COMPARATIVE STUDY OF THE RATE OF PROTEOLYSIS OF TISSUES OBTAINED FROM RABBITS INFECTED WITH PNEUMOCOCCI AND OF TISSUES FROM NORMAL RABBITS
Authors: Florentin Medigreceanu
Journal: The Journal of Experimental Medicine (1914)

Liver.-The amount of filterable nitrogen in the samples before autolysis is too variable, both in the normal livers and in the livers from pneumococcus infections in the rabbit, for a constant difference to be obtained. The amino nitrogen before autolysis is generally slightly increased in the livers of the infected animals, especially in the perfused specimens. Most of the experiments show an increased disintegration of the livers of the infected animals during the first stages of proteolysis (twenty to thirty hours), both in the non-perfused and the perfused specimens. This increased disintegration is generally more evident for the complex proteins (filterable nitrogen) than for the lower products (amino nitrogen). In the later stages the proteolysis of the blood-containing livers of the normal and the infected rabbits tends to an equalization, or the relations reverse, the proteolysis of the normal samples becoming more advanced. In the perfused specimens the differences in the rate of proteolysis are the same as in the earlier stages. Kidney.-The rate of proteolysis shows no constant differences in the normal and infected tissues.
Clinical trials of Ebola therapies to begin in December
Authors: A. Gulland
Journal: BMJ (2014)

The first clinical trials of therapies for Ebola virus disease will begin next month in the treatment centres run by Medecins Sans Frontieres in Guinea.

At a press conference in Geneva the principal investigators of the trials announced that three therapies would be tested at three separate sites. They said that the trials would begin in December, and 100-200 patients at each treatment centre would undergo testing.

A team led by the French National Institute of Health and Medical Research will test the antiviral drug favipiravir in Gueckedou, the antiviral brincidofovir will be tested by a consortium led by the University of Oxford at a site yet to be announced, and convalescent whole blood and plasma therapy will be tested by a group led by the Antwerp Institute of …
Antioxidative Effects of Exercise Training in Patients With Chronic Heart Failure
Authors: Axel Linke, Volker Adams, Paul Christian Schulze, Sandra Erbs, Stephan Gielen, Eduard Fiehn, Sven Möbius-Winkler, Andreas Schubert, Gerhard Schuler, Rainer Hambrecht
Journal: Circulation (2005)

In chronic heart failure (CHF), cross-talk between inflammatory activation and oxidative stress has been anticipated in skeletal muscle (SM). The role of the radical scavenger enzymes superoxide dismutase (SOD), catalase (Cat), and glutathione peroxidase (GPX), which remove oxygen radicals, has never been assessed in the SM in this context. Moreover, it remains unknown whether exercise training augments the activity of these enzymes in CHF.Twenty-three patients with CHF were randomized to either 6 months of exercise training (T) or a sedentary lifestyle (C); 12 age-matched healthy subjects (HS) were studied in parallel. Activity of Cat, SOD, and GPX was assessed in SM biopsies before and after 6 months (6 months). Oxidative stress was determined by measuring nitrotyrosine formation. SOD, Cat, and GPX activity was reduced by 31%, 57%, and 51%, respectively, whereas nitrotyrosine formation was increased by 107% in SM in CHF (P<0.05 versus HS). In CHF, exercise training augmented GPX and Cat activity in SM by 41% (P<0.05 versus before and group C) and 42% (P<0.05 versus before and group C), respectively, and decreased nitrotyrosine production by 35% (from 3.8+/-0.4% tissue area before to 2.5+/-0.3% after 6 months; P<0.05 versus before).The reduced activity of major antioxidative enzymes in the SM of CHF patients is associated with increased local oxidative stress. Exercise training exerts antioxidative effects in the SM in CHF, in particular, due to an augmentation in activity of radical scavenger enzymes.