tbuckley/cabot-search huggingface dataset:
The Role of Somatic Mutation in the Generation of the Protective Humoral Immune Response against Vesicular Stomatitis Virus
Authors: Ulrich Kalinke, Etienne M. Bucher, Bettina Ernst, Annette Oxenius, Hans-Peter Roost, Stephan Geley, Reinhard Kofler, Rolf M. Zinkernagel, Hans Hengartner
Journal: Immunity (1996)
Vaccines in the 21st century
Authors: M. A Liu
Journal: BMJ (1999)

Vaccination against infectious diseases has literally transformed the planet. It has succeeded in the elimination of smallpox and the near elimination of polio as scourges of humankind. This kind of success, as well as the great increase in understanding of immunology and the development of new technologies, has increased the hope that new vaccines will target other diseases. Indeed, expectations have been raised so much that vaccines are now being developed not just to prevent infectious diseases but to cure them. In addition, some conditions have now been shown to be related to infectious diseases—for example, human papillomavirus infection has been implicated in cervical cancer and Helicobacter pylori in gastritis, peptic ulcer disease, and stomach cancer—and vaccines should help to prevent or treat these diseases. Other clinical diseases or conditions are also now considered within the purview of vaccines. These include cancers (even those without a known infectious aetiological component), allergies, autoimmune diseases such as diabetes, metabolic diseases such as hyperlipidaemias that lead to atherosclerosis and coronary artery disease, and even addictions such as cocaine and nicotine dependencies. 

An examination of the recent advances in immunology and vaccinology provides insights into future vaccine developments. Great strides have been made in understanding how the body distinguishes self from non-self—that is, how the immune system recognises a pathogen as being foreign and hence a target for killing. This is likewise important for understanding why the immune response sometimes becomes too active, resulting in allergies or autoimmune disease. By understanding which cells become activated and knowing what the triggers are, we can try intentionally to stimulate, alter, or suppress the responses.

#### Summary points

New vaccines are being developed for treatment as well as prophylaxis

Elucidation of how immune system cells process and then recognise and respond to antigens has prompted the development of new technologies …
Abstract ES04-2: Understanding nuclear receptor in breast cancer
Authors: SAW Fuqua
Journal: Cancer Research (2013)

Abstract Breast cancer cells have receptors on the surface, in the cytoplasm and in the nucleus. Chemical messengers such as steroid hormones bind to receptors, and this causes changes in the transcriptional program of the cells. Breast cancer cells may express two important steroid receptors: estrogen receptor s alpha and beta (ERs a and b, respectively), and/or progesterone receptor (PR). ER-positive cancer cells depend on estrogen for their growth, so they can be treated with drugs to block estrogen effects (e.g. tamoxifen), or which block estrogen synthesis (Cyp19 [aromatase] inhibitors or Cyp19 inhibitors which block both androgen and estrogen synthesis. Cells which express more of these receptors generally respond better to hormonal therapies. The ERs are from a large family of nuclear receptor transcription factors (TFs). When bound by hormone (they bind to DNA directly or they can interact with other transcription factors bound to DNA to regulate gene expression. ER and PR acts by recruiting a complex of coactivator or corepressor proteins that modulate ER functions. These coactivators are important regulatory molecules, and evidence suggests that some are oncogenes, capable of causing breast cancer and showing gene amplification and/or over-expression in a ER-psositiv breast cancers, thus affecting tumor growth and treatment. Many mechanisms for resistance to endocrine therapies have been postulated and the loss of ER over time although not common can happen. The evolution of receptor mutations over time perhaps in tumor subpopulations has also been postulated, and recent evidence suggests that they occur more frequently than once thought in ER-positive metastatic gtumors. In addition, the PR is frequently lost or altered, which can result from its activation from upstream growth factor receptors. Coactivators that are overexpressed can also modulate ER function so that tumors fail to respond to blocking ER therapies. The basic biology, function, and altered mechanism of action of ER/PR which occur during tumor evolution will be discussed in this educational session. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr ES04-2.
Acute hepatitis and exfoliative dermatitis associated with minocycline.
Authors: M. G. Davies, P. J. Kersey
Journal: BMJ (1989)

that this has been seen as a regional responsibility.Instead it should be viewed as a duty of the health district or short stay hospital to provide the service.Every district general hospital in Britain should have a computed tomography scanner in the 1990s if it is to practise effective medicine.
Contribution of alcohol to deaths in road traffic accidents in Tayside 1982-6
Authors: G. R Foster, J. A Dunbar, D. Whittet, G. C A Fernando
Journal: BMJ (1988)

In Britain the precise number and relative proportions of deaths among drivers, passengers, and pedestrians in road traffic accidents related to alcohol are not known. These data were obtained in Tayside by cross matching police accident records with blood alcohol concentrations at necropsy. Of 71 alcohol-related deaths 30 were the drivers (or motorcyclists) themselves, nine were their passengers, 23 were pedestrians with raised blood alcohol concentrations, and nine were innocent victims. The high blood alcohol concentrations of the intoxicated drivers, passengers, and pedestrians, which may point to alcoholism, suggest that publicity campaigns will be of little value in reducing the number of deaths in road traffic accidents related to alcohol. The time at which these accidents occurred was related to licensing hours, and this should be taken into account when considering changes in licensing laws.
Pancreatic cancer cells overexpress gelsolin family-capping proteins, which contribute to their cell motility
Authors: C C Thompson, F J Ashcroft, S Patel, G Saraga, D Vimalachandran, W Prime, F Campbell, A Dodson, R E Jenkins, N R Lemoine, T Crnogorac-Jurcevic, H L Yin, E Costello
Journal: Gut (2006)

Previously, proteomic methods were applied to characterise differentially expressed proteins in microdissected pancreatic ductal adenocarcinoma cells.To report that CapG and a related protein, gelsolin, which have established roles in cell motility, are overexpressed in metastatic pancreatic cancer; and to describe their pattern of expression in pancreatic cancer tissue and their effect on cell motility in pancreatic cancer cell lines.CapG was identified by mass spectrometry and immunoblotting. CapG and gelsolin expression was assessed by immunohistochemical analysis on a pancreatic cancer tissue microarray and correlated with clinical and pathological parameters. CapG and gelsolin levels were reduced using RNA interface in Suit-2, Panc-1 and MiaPaCa-2 cells. Cell motility was assessed using modified Boyden chamber or wound-healing assays.Multiple isoforms of CapG were detected in pancreatic cancer tissue and cell lines. Immunohistochemical analysis of benign (n = 44 patients) and malignant (n = 69) pancreatic ductal cells showed significantly higher CapG staining intensity in nuclear (p<0.001) and cytoplasmic (p<0.001) compartments of malignant cells. Similarly, gelsolin immunostaining of benign (n = 24 patients) and malignant (n = 68 patients) pancreatic ductal cells showed higher expression in both compartments (both p<0.001). High nuclear CapG was associated with increased tumour size (p = 0.001). High nuclear gelsolin was associated with reduced survival (p = 0.01). Reduction of CapG or gelsolin expression in cell lines by RNAi was accompanied by significantly impaired motility.Up regulation of these actin-capping proteins in pancreatic cancer and their ability to modulate cell motility in vitro suggest their potentially important role in pancreatic cancer cell motility and consequently dissemination.
Intolerance of the dirty intestine
Authors: A J S MACPHERSON, K J MALOY, I BJARNASON
Journal: Gut (1999)

An apparatus is described which uses the principle of the ballistic pendulum to measure the tensile strength of blood clots formed in special cuvettes. The method appears to have a reproducibility which would allow a study to be made of the factors influencing clot strength. A brief survey of the findings with normal blood and with blood from cases of thrombosis and haemophilia shows significant differences between the mean values for each group.
Preload Induces Troponin I Degradation Independently of Myocardial Ischemia
Authors: Jun Feng, Benjamin J. Schaus, James A. Fallavollita, Te-Chung Lee, John M. Canty
Journal: Circulation (2001)

Background —Although global ischemia induces troponin I (TnI) degradation, regional ischemia does not. We hypothesized that this disparity is related to preload-induced proteolysis, which varies as a function of the amount of myocardium at risk of ischemia. Methods and Results —Isolated rat hearts were buffer-perfused at controlled levels of preload. Increasing preload to 25 mm Hg in the absence of ischemia produced pronounced TnI degradation (27 kDa versus 31 kDa bands: 16.4±3.6% versus 4.7±1.9% in immediately excised controls, P &lt;0.05). TnI degradation could be blocked by preventing the activation of endogenous calpains with 25 μmol/L calpeptin (4.3±0.6%). This improved function, with left ventricular systolic pressure increasing from 103±4 mm Hg to 137±7 mm Hg ( P &lt;0.05). Eliminating elevations in preload after global ischemia-induced stunning also prevented TnI degradation. Conclusions —Calpain-mediated TnI proteolysis can be dissociated from stunning and arises from elevations in preload rather than ischemia. This raises the possibility that ongoing preload-induced TnI degradation could impair myocardial function long-term.
Rats and the Urban Scene
Authors: JAMES M. CLINTON
Journal: Annals of Internal Medicine (1968)

Editorials1 October 1968Rats and the Urban SceneJAMES M. CLINTON, V.M.D.JAMES M. CLINTON, V.M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-69-4-839 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptRats are among our most refractory and costly pests. In the early days of the Virginia Colony more than 150 years before the birth of our nation, Captain John Smith recorded (1) that:In searching our casked corne, wee found it halfe rotten, and the reste so consumed with the many thousand rats, increased first from the ships, that wee knewe not how to keepe that little wee had. This did drive us all to our wits end; for there was nothing in the countrie but what nature afforded.Nature still affords us a good living, but our 90 million...References1. ARBER E (editor): Travels and Works of Capt. John Smith, volume 1, John Grant, Edinburgh, 1910, pp. 154-155. Google Scholar2. Grain Sanitation Program, Food and Drug Administration, U. S. Government Printing Office, Washington, D. C., 1957, pp. 2-6. Google Scholar3. DRUMMOND D: Rats resistant to warfarin. New Scientist 30: 771, 1966. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Training & Consultation Section Aedes Aegypti Eradication Program National Communicable Disease Center Atlanta, Ga. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1968Volume 69, Issue 4Page: 839-841KeywordsBirth Issue Published: 1 October 1968 PDF DownloadLoading ...
Cardioprotection Through <i>S</i> -Nitros(yl)ation of Macrophage Migration Inhibitory Factor
Authors: Peter Luedike, Ulrike B. Hendgen-Cotta, Julia Sobierajski, Matthias Totzeck, Marcel Reeh, Manfred Dewor, Hongqi Lue, Christoph Krisp, Dirk Wolters, Malte Kelm, Jürgen Bernhagen, Tienush Rassaf
Journal: Circulation (2012)

Background— Macrophage migration inhibitory factor (MIF) is a structurally unique inflammatory cytokine that controls cellular signaling in human physiology and disease through extra- and intracellular processes. Macrophage migration inhibitory factor has been shown to mediate both disease-exacerbating and beneficial effects, but the underlying mechanism(s) controlling these diverse functions are poorly understood. Methods and Results— Here, we have identified an S -nitros(yl)ation modification of MIF that regulates the protective functional phenotype of MIF in myocardial reperfusion injury. Macrophage migration inhibitory factor contains 3 cysteine (Cys) residues; using recombinant wtMIF and site-specific MIF mutants, we have identified that Cys-81 is modified by S -nitros(yl)ation whereas the CXXC-derived Cys residues of MIF remained unaffected. The selective S -nitrosothiol formation at Cys-81 led to a doubling of the oxidoreductase activity of MIF. Importantly, S -nitrosothiol-MIF formation was measured both in vitro and in vivo and led to a decrease in cardiomyocyte apoptosis in the reperfused heart. This decrease was paralleled by a S -nitrosothiol-MIF– but not Cys81 serine (Ser)–MIF mutant–dependent reduction of infarct size in an in vivo model of myocardial ischemia/reperfusion injury. Conclusions— S -nitros(yl)ation of MIF is a pivotal novel regulatory mechanism, providing enhanced activity resulting in increased cytoprotection in myocardial reperfusion injury.
HAIR I.
Authors: Arthur Rook
Journal: British Journal of Dermatology (1975)

Journal Article HAIR I: The clinical significance of abnormal hair‐slope patterns—Trichoglyphics Get access Arthur Rook Arthur Rook Addenbrooke's Hospital, Cambridge, England Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 92, Issue 2, 1 February 1975, Pages 239–240, https://doi.org/10.1111/j.1365-2133.1975.tb03071.x Published: 01 February 1975
Clogged renal, femoral arteries yield to balloon catheter technique
Authors: B. J. Montgomery
Journal: JAMA (1980)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Hormone-fuel concentrations in anephric subjects. Effect of hemodialysis (with special reference to amino acids).
Authors: O P Ganda, T T Aoki, J S Soeldner, R S Morrison, G F Cahill
Journal: Journal of Clinical Investigation (1976)

Arterial blood concentrations of insulin, glucagon, and various substrates were determined in six anephric subjects in the postabsorptive state and immediately after hemodialysis. Plasma glucose and serum insulin concentrations were normal, and declined during dialysis. Plasma glucagon was elevated and remained unchanged. There was moderate hypertriglyceridemia before dialysis, but this decreased significantly after administration of heparin just before the start of dialysis, and at the end of dialysis was lowered further into the normal range. Comparison of postabsorptive whole blood concentrations of amino acids with those in normal, healthy adults revealed striking differences. Glutamine, proline, citrulline, glycine and both 1- and 3-methyl-histidines were increased, while serine, glutamate, tyrosine, lysine, and branched-chain amino acids were decreased. The glycine/serine ratio was elevated to 300% and tyrosine/phenylalanine ratio was lowered to 60% of normal. To investigate the potential role of blood cells in amino acid transport, the distribution of individual amino acids in plasma and blood cell compartments was studied. Despite a markedly diminished blood cell mass (mean hematocrit, 20.6 +/- 1.4%), there was no significant decrease in the fraction of most amino acids present in the cell compartment, and this was explained by increases of several amino acids in cellular water. None were decreased. Furthermore, during dialysis, whole blood and plasma amino acids declined by approximately 30% and 40%, respectively, whereas no significant change was observed in the cell compartment. Alanine was the only amino acid whose concentration declined in the cells as well as in plasma. The results indicate (a) significant alterations in the concentrations of hormones and substrates in patients on chronic, intermittent hemodialysis; (b) removal of amino acids during hemodialysis, predominantly from the plasma compartment, with no significant change in cell content; and (c) a redistribution of amino acids in plasma and blood cell compartments with increased gradients of most of the amino acids per unit cell water, by mechanism(s) as yet undetermined.
Epidemiological Characteristics of 2009 (H1N1) Pandemic Influenza Based on Paired Sera from a Longitudinal Community Cohort Study
Authors: Steven Riley, Kin O. Kwok, Kendra M. Wu, Danny Y. Ning, Benjamin J. Cowling, Joseph T. Wu, Lai-Ming Ho, Thomas Tsang, Su-Vui Lo, Daniel K. W. Chu, Edward S. K. Ma, J. S. Malik Peiris
Journal: PLoS Medicine (2011)

Steven Riley and colleagues analyze a community cohort study from the 2009 (H1N1) influenza pandemic in Hong Kong, and found that more children than adults were infected with H1N1, but children were less likely to progress to severe disease than adults.
The Fluent State of Cyclamate
Authors: G. G. Liddle
Journal: JAMA (1970)

<h3>To the Editor.—</h3> My business has increased voluminously, now that I wave the magic prescription pad for cyclamates. A whole new coterie of patients knocks upon my door. Indeed, yesterday morning on arriving at the office I found the following note tacked over my sign saying the doctor is out: Oh cyclamate! your dismal fate Leaves all your friends Disconsolate. Oh solid state of cyclamate! Your turn is come To abdicate. Du grünst no more Im rootbeerate Im toothy paste Or carbonate Oh cyclamate! Oh, cyclamate! You're just a mean old Reprobate. The note was signed by one of my more heavy users of cyclamate. Do you think I should refer him to a psychiatrist?
Dofetilide, a new class III antiarrhythmic agent, reduces pacing induced heterogeneity of repolarisation in vivo
Authors: M. Gwilt, R. C King, A. A Milne, A. M Solca
Journal: Cardiovascular Research (1992)

The aim was to determine whether dofetilide, a new class III antiarrhythmic agent, could reduce the heterogeneity of repolarisation produced by rapid cardiac pacing and to compare it with quinidine. Increased heterogeneity of repolarisation times may be causally linked to malignant cardiac re-entrant arrhythmias.Studies were performed in open chest, artificially ventilated, pentobarbitone anaesthetised beagle dogs of 13 to 15 kg body weight. Myocardial electrocardiograms were simultaneously recorded from 31 electrodes located on the left and right ventricular surfaces of the in situ canine heart. Recordings were obtained over a single cardiac cycle during rapid ventricular pacing at the maximum following frequency. Computer assisted measurements of activation time, activation-repolarisation interval, and repolarisation time were performed and the heterogeneity of these measurements calculated. Measurements were performed before treatment and after each incremental intravenous dose of dofetilide (3, 10, 30, and 100 micrograms.kg-1), quinidine (1, 3, and 10 mg.kg-1), or saline vehicle.Dofetilide increased repolarisation time via a selective prolongation of activation-repolarisation interval, activation time being unchanged. It reduced the heterogeneity of repolarisation time and activation-repolarisation interval, heterogeneity of activation time being unchanged. Quinidine increased repolarisation time by a non-selective increase of both activation-repolarisation interval and activation time. It increased the heterogeneity of activation times which offset a decrease in heterogeneity of activation-repolarisation intervals to produce no change in heterogeneity of repolarisation times.Dofetilide, but not quinidine, reduces pacing induced asynchrony of repolarisation in the canine heart and this effect may contribute to its antiarrhythmic activity.
The human CD40 agonistic antibody ADC-1013 generates immune mediated anti-tumor effects in syngeneic tumor models in hCD40 transgenic mice
Authors: Sara M Mangsbo, Niina Veitonmäki, Erika Gustfson, Karin Smith, Christina Furebring, Per Norlén, Malin Lindstedt, Thomas H Tötterman, Peter Ellmark
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Local activation of costimulatory pathways by e.g. CD40 activation has been shown to generate powerful systemic anti-tumor responses. Here we report significant anti-tumor effects obtained with an optimized fully human agonistic CD40 antibody, ADC-1013, in two syngeneic tumor
Increase in Hepatocyte and Nuclear Volume and Decrease in the Population of Binucleated Cells in Preneoplastic Foci of Rat Liver: A Stereological Study Using the Nucleator Method
Authors: Elspeth M. Jack, Philip Bentley, Francoise Bieri, Samar F. Muakkassah-Kelly, Willy Stäubli, Joseph Suter, Felix Waechter, Luis M. Cruz-Orive
Journal: Hepatology (1990)

Gamma-glutamyltranspeptidase-positive hepatocyte foci were produced in female rats given a single dose of diethylnitrosamine neonatally after birth and, after weaning, a diet containing phenobarbitone for 30 wk. The nucleator method, a new stereological approach, provided an efficient, unbiased estimate of mean cell volume in focal lesions and extrafocal areas. It also provided an unbiased sample of cells to estimate hepatocyte nuclear volume and the percentage of binucleated cells. The results showed an increase in the mean volume of mononucleated cells--from 4,700 micron3 in extrafocal areas to 12,700 micron2 in foci--and of binucleated cells--from 6,900 micron3 to 25,000 micron3. This demonstrated the hypertrophic effect of the carcinogenic treatment in focal lesions. A striking reduction in the proportion of binucleated cells was also observed in the preneoplastic lesions. Nuclear volume measurements from mononucleated and binucleated hepatocytes were used to assess ploidy. An apparent increase in nuclear ploidy, with no change in cellular ploidy, was noted in focal tissue when compared with nonfocal tissue. This appeared to be caused by an increase in mononucleated tetraploid cells and a reduction in binucleated cells with two diploid nuclei, indicating an altered mitotic mechanism in focal lesions. The significance of these changes in cell volume, apparent ploidy levels and binuclearity in preneoplastic foci is discussed in relation to the hepatocarcinogenic process.