tbuckley/cabot-search huggingface dataset:
The major histocompatibility complex-restricted response of recombinant inbred strains of mice to natural tick transmission of Borrelia burgdorferi.
Authors: W T Golde, T R Burkot, S Sviat, M G Keen, L W Mayer, B J Johnson, J Piesman
Journal: The Journal of Experimental Medicine (1993)

The causative agent of Lyme disease, Borrelia burgdorferi, is transmitted by ticks of the Ixodes ricinus complex. In this study, we report the antibody response of recombinant inbred strains of mice of the H-2, b, d, and k haplotypes, infected with B. burgdorferi as a result of exposure to infected I. dammini. The patterns of antibody response assayed by Western blot analysis indicate significant major histocompatibility complex (MHC) restriction to bacterial antigens within the first 2 mo of infection in mice. Other bacterial antigens induce a significant response across the MHC haplotypes tested when assayed on the same bacterial strain used to transmit the infection, but do not crossreact with the same proteins derived from heterologous strains of B. burgdorferi. No response to outer surface protein A was detected at any time during the 60-d period we analyzed this infection. A third group of bacterial antigens appear to generate a MHC-nonrestricted response, and this lack of restriction is maintained when assaying the crossreactivity of the response with other strains of B. burgdorferi. These proteins may provide more accurate diagnostic probes than those currently in use. Finally, there appears to be a significant difference in the expression of most bacterial antigens when the spirochete is cultured for many passages since the same strain of bacterium isolated from low-passage and high-passage preparations exhibit different banding patterns in Western blots when assayed with the same sera.
Compression of the coronary arteries by the fibrillating canine heart.
Authors: J Downey
Journal: Circulation Research (1976)

We performed experiments to test whether the subendocardial ischemia which reportedly accompanies elective ventricular fibrillation (VF) during cardiopulmonary bypass might be the result of mechanical compression of the coronary vessels. The left coronary artery of the open-chest, anesthetized dog was cannulated and perfused with arterial blood through an extracorporeal circuit. Coronary inflow rate was held constant with a pump and the coronary vessels were dilated maximally by infusing adenosine. Any change in perfusion pressure or the transmural distribution of flow in these hearts would have been due to changes in compression. When the hearts were stopped in diastole by vagal stimulation, infusion of microspheres 15 mum in diameter revealed a subendocardial to subepicardial (inner to outer) flow ratio (I/O) of 1.2. When the same hearts were caused to fibrillate spontaneously (not electrically maintained) the I/O fell to 0.9. Little change in coronary perfusion pressure occurred between arrest and VF. When the contractile activity during VF was attenuated by intracoronary sodium pentobarbital (120 mg) the I/O rose toward that seen during arrest. However, augmentation of muscle activity by infusion of isoproterenol during VF failed to change the I/O. Finally the I/O fell in proportion to the degree of distention in the fibrillating ventricle. The results that we observed indicate that muscular contraction during VF preferentially inhibits subendocardial flow through vascular compression.
Baseline Selenium Status and Effects of Selenium and Vitamin E Supplementation on Prostate Cancer Risk
Authors: Alan R. Kristal, Amy K. Darke, J. Steven Morris, Catherine M. Tangen, Phyllis J. Goodman, Ian M. Thompson, Frank L. Meyskens, Gary E. Goodman, Lori M. Minasian, Howard L. Parnes, Scott M. Lippman, Eric A. Klein
Journal: JNCI Journal of the National Cancer Institute (2014)

The Selenium and Vitamin E Cancer Prevention Trial found no effect of selenium supplementation on prostate cancer (PCa) risk but a 17% increased risk from vitamin E supplementation. This case–cohort study investigates effects of selenium and vitamin E supplementation conditional upon baseline selenium status. There were 1739 total and 489 high-grade (Gleason 7–10) PCa cases and 3117 men in the randomly selected cohort. Proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for effects of supplementation within quintiles of baseline toenail selenium. Cox proportional hazards models were used to estimate hazard ratios, and all statistical tests are two-sided. Toenail selenium, in the absence of supplementation, was not associated with PCa risk. Selenium supplementation (combined selenium only and selenium + vitamin E arms) had no effect among men with low selenium status (<60th percentile of toenail selenium) but increased the risk of high-grade PCa among men with higher selenium status by 91% (P = .007). Vitamin E supplementation (alone) had no effect among men with high selenium status (≥40th percentile of toenail selenium) but increased the risks of total, low-grade, and high-grade PCa among men with lower selenium status (63%, P = .02; 46%, P = .09; 111%, P = .008, respectively). Selenium supplementation did not benefit men with low selenium status but increased the risk of high-grade PCa among men with high selenium status. Vitamin E increased the risk of PCa among men with low selenium status. Men should avoid selenium or vitamin E supplementation at doses that exceed recommended dietary intakes.
Immune deviation of 2C transgenic intraepithelial lymphocytes in antigen-bearing hosts.
Authors: S R Guehler, J A Bluestone, T A Barrett
Journal: The Journal of Experimental Medicine (1996)

The present study examined self-tolerance for T cell receptor (TCR) alpha beta intestinal intraepithelial lymphocytes (iIELs) using the 2C transgenic (Tg) mouse model specific for a peptide antigen (Ag) presented by the class I major histocompatibility complex H-2Ld. Although Tg+ T cells were largely deleted from the periphery of Ag+ mice, equivalent numbers of Tg iIELs were present in Ag+ compared to Ag- mice. Tg iIELs in Ag- mice contained CD8 alpha beta, CD8 alpha alpha, and CD4-CD8- subsets, whereas only CD8 alpha alpha and CD4-CD8- Tg iIEL subsets were detected in Ag+ mice. Analysis of surface markers revealed that Tg iIELs in Ag+ mice expressed decreased levels of Thy-1 and increased CD45R/B220 as compared to Ag- Tg iIELs. In response to activation with exogenous peptide or immobilized anti-TCR mAB, iIELs from Ag- mice proliferated at high levels and produced interleukin (IL)-2 and interferon (IFN)-gamma, while Tg+ iIELs from Ag+ mice proliferated at low levels and failed to produce detectable IL-2 or IFN-gamma. Activation of sorted iIEL subsets from Ag- mice revealed that CD8 alpha alpha and CD4-CD8- subsets produced low levels of IL-2 and IFN-gamma in response to activation with antigen-presenting cells and added peptide or immobilized anti-TCR mAb, while CD8 alpha beta + iIELs responded to endogenous levels of peptide. In response to APC and exogenous peptide, sorted iIEL subsets from Ag+ mice produced IL-2 and IFN-gamma, and proliferated at greatly reduced levels compared to corresponding subsets from Ag- mice. Analysis of cytokine mRNA levels revealed that activation in vitro induced IL-2 mRNA only in Ag-, but not Ag+ iIELs, whereas a high level of IL-4 mRNA induction was detected in Tg+ iIELs from Ag+ mice, and to a lesser degree, from Ag- mice. These data suggest that tolerance for Tg+ iIELs resulted in the deletion of CD8 alpha beta + subsets and the persistence of Tg+ iIEL subsets with decreased sensitivity to endogenous levels of self-peptide. A comparison of the cytokine profiles expressed by Tg+ iIEL subsets in Ag- and Ag+ mice suggested that tolerance induction had involved the functional deviation of cells from TC1 (T helper-1-like) to a less inflammatory TC2 (T helper-2-like) phenotype capable of mediating humoral immune responses in the mucosa.
A Functional Cancer Genomics Screen Identifies a Druggable Synthetic Lethal Interaction between <i>MSH3</i> and <i>PRKDC</i>
Authors: Felix Dietlein, Lisa Thelen, Mladen Jokic, Ron D. Jachimowicz, Laura Ivan, Gero Knittel, Uschi Leeser, Johanna van Oers, Winfried Edelmann, Lukas C. Heukamp, H. Christian Reinhardt
Journal: Cancer Discovery (2014)

Abstract Here, we use a large-scale cell line–based approach to identify cancer cell–specific mutations that are associated with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) dependence. For this purpose, we profiled the mutational landscape across 1,319 cancer-associated genes of 67 distinct cell lines and identified numerous genes involved in homologous recombination–mediated DNA repair, including BRCA1, BRCA2, ATM, PAXIP, and RAD50, as being associated with non-oncogene addiction to DNA-PKcs. Mutations in the mismatch repair gene MSH3, which have been reported to occur recurrently in numerous human cancer entities, emerged as the most significant predictors of DNA-PKcs addiction. Concordantly, DNA-PKcs inhibition robustly induced apoptosis in MSH3-mutant cell lines in vitro and displayed remarkable single-agent efficacy against MSH3-mutant tumors in vivo. Thus, we here identify a therapeutically actionable synthetic lethal interaction between MSH3 and the non-homologous end joining kinase DNA-PKcs. Our observations recommend DNA-PKcs inhibition as a therapeutic concept for the treatment of human cancers displaying homologous recombination defects. Significance: We associate mutations in the MSH3 gene, which are frequently detected in microsatellite-instable colon cancer (∼40%), with a therapeutic response to specific DNA-PKcs inhibitors. Because potent DNA-PKcs inhibitors are currently entering early clinical trials, we offer a novel opportunity to genetically stratify patients who may benefit from a DNA-PKcs–inhibitory therapy. Cancer Discov; 4(5); 592–605. ©2014 AACR. See related commentary by Hemann, p. 516 This article is highlighted in the In This Issue feature, p. 495
Mechanism suppressing glycogen synthesis in neurons and its demise in progressive myoclonus epilepsy
Authors: David Vilchez, Susana Ros, Daniel Cifuentes, Lluís Pujadas, Jordi Vallès, Belén García-Fojeda, Olga Criado-García, Elena Fernández-Sánchez, Iria Medraño-Fernández, Jorge Domínguez, Mar García-Rocha, Eduardo Soriano, Santiago Rodríguez de Córdoba, Joan J Guinovart
Journal: Nature Neuroscience (2007)
Forced Migration
Authors: Lawrence O. Gostin, Anna E. Roberts
Journal: JAMA (2015)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Development of an integrated model for analysis of the kinetics of apolipoprotein B in plasma very low density lipoproteins, intermediate density lipoproteins, and low density lipoproteins.
Authors: W F Beltz, Y A Kesäniemi, B V Howard, S M Grundy
Journal: Journal of Clinical Investigation (1985)

To quantify more precisely the metabolism of apolipoprotein B (apo B) in human beings, an integrated model was developed for the analysis of the isotope kinetics of apo B in very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low density lipoproteins (LDL). The experimental basis for model development was a series of 30 triple-isotope studies in which patients received autologous 131I-VLDL, 125I-IDL, and [3H]glycerol as a precursor of VLDL triglycerides. The currently proposed model contains the following components: (a) a VLDL delipidation cascade that has a variable number of subcompartments, (b) a slowly catabolized pool of VLDL, (c) an IDL compartment consisting of two closely connected subcompartments, one of which is outside the immediate circulation, and (d) a two-compartment subsystem for LDL. Because mass data indicate that not all VLDL were converted to LDL, the model allows for irreversible removal of apo B from VLDL (or IDL) subsystems. It accounts for apparent "direct" input of LDL by postulating an early, rapidly metabolized compartment of VLDL that is converted directly to IDL. The model appears to be consistent with specific activity curves from the current triple-isotope studies and with present concepts of lipoprotein physiology; it also can be used to quantify pathways of lipoprotein apo B transport in normal and abnormal states.
The Growth of Medical Information Systems in the United States
Authors: George D. Lundberg
Journal: JAMA (1981)

It often has been said that 25% to 40% of a hospital's total costs are expended in the development, documentation, and transfer of information. Dealing with these tasks effectively and efficiently is both the greatest burden and the greatest challenge to health services administrators. This book represents an attempt by a highly knowledgeable author to describe the effort of dealing with the information glut in hospitals by automated means. This modern and up-to-date book is divided into nine chapters: Introduction," "Definition and Means of Comparing Medical Information Systems (MISs)," "State of the Art of MISs," "Description of MISs," "Evaluating the Worth of MISs," "Barriers to the Development and Diffusion of MIS Technology," "Effects of Changes in Technology on Future MISs," "Impact of Public Policy on the Development, Adoption, and Diffusion of MIS Technology," and "Conclusions." The book grew out of a background paper, "The Development and Diffusion of a Medical
Early contact with animals is linked to reduced asthma risk, study shows
Authors: Susan Mayor
Journal: BMJ (2015)

Contact with dogs or farm animals during the first year of a child’s life is associated with reduced risk for childhood asthma, a study published in JAMA Pediatrics has shown.1

Childhood asthma is increasing, and this is blamed on environmental factors, including tobacco smoke exposure, domestic cat and dog exposure, microbial exposure, and socioeconomic factors. Several studies have shown that early childhood exposure to pets is actually associated with reduced risk of asthma, but results have been conflicting.

To investigate this further, researchers looked at the association between asthma …
Stricture of the Sigmoid Flexure of the Colon: Death
Authors: M. M. de Bartolome
Journal: BMJ (1886)

B='RITIfit JRDCAL JOURMAL.(Jam 3Oi 1886.the sheet-anchor in violent cases.Do not add digitalis.Calabar bean is indicated in the early stages of general paralysis.Iodide of potassium and mercury often allay excitement, when the mental sym- ptoms are due to some syphilitic taint.Hydrocyanic acids with or without the bromides, is nseful in robust cases of mania.Henbane, in my han(ls, has proved a disappointing remedy.It is feeble as a sedative, and only valuable as such in large doses, such as half an ounce of the tincture ; andl even in small doses it often pro- duces headache.Combinations of drugs are invaluable, such as chloral with bromide of potassium, chloral with the liquor morphiia bimeconatis, bromide with cannabis Indica, in acuite imiania; broniide with ergot, in re- cmrrent insanity; iiorphia with assaftutida, in hysteria.Conium is useful where there is murh motility ; quinine in inter- mittent insanity; and sumbul or chloral in the status epilepticus.Aperients are almost always required in the early stages.The Milder purges are, as a rtle, indicated.These are: Esculap and Hunyadi Jtanos waters; granular effervescing citrate of magnesia; stewed prunies, oranges, andi similar domestic remedies.In extreme cases, enemata are inece;sary, which must sonietimes be a(lministered daily, and, if there be no obstruction, croton-oil.Avoid pills, as the patient, if suticidal, w-ill hoard them up, and then take a poisonouis quantity.Should melicine be refused, a subcuxtaneous injection is occasionally useful, but I prefer disguising my remiiedies.Chloral in beer or port- wine, tincture of opium in coffee, antimony in any liquid (as it is tasteless) ; and, as regards aperients, calomel between thin slices of bread and butter ; syrup of senna in a cup of tea, in lieu of sugar;and other similar harmless modes of deception are now allowable.3. The 7iwral treatbrei, must con1sist of a mixture of kindness and firmness; and, above all things, we must remember that each case requires different treatment.4. The hygienic treatcwnt is obvious.Let the patient walk out daily till he nearly drops from fatigue, and soon all complaints of loss of sleep and want of appetite will cease; and, although the disease may yet have to ruin its course, the symptoms will be mnilder, and the outlook more hopefuil, than would have been the case if the patient had been allowed to have his own way.I must apolopse for the concentrated form in which I have been obliged to put ttiese remarks.Let us not think that, by treating the premonitory symptoms of insanity, medical men will want for work.As long as human nature, sexual intercourse, and alcohol exist, so long will there be excess; and, in consequence, plenty of work for our profession-whether we endeavour to sound a note of warning to the foolish, or to alleviate the distress of those who now undeservedly suffer for the sins of their forefathers.
Human Papillomavirus Testing and Liquid-Based Cytology: Results at Recruitment From the New Technologies for Cervical Cancer Randomized Controlled Trial
Authors: Guglielmo Ronco, Nereo Segnan, Paolo Giorgi-Rossi, Marco Zappa, Gian Piero Casadei, Francesca Carozzi, Paolo Dalla Palma, Annarosa Del Mistro, Stefania Folicaldi, Anna Gillio-Tos, Gaetano Nardo, Carlo Naldoni, Patrizia Schincaglia, Manuel Zorzi, Massimo Confortini, Jack Cuzick
Journal: JNCI Journal of the National Cancer Institute (2006)

Although testing for human papillomavirus (HPV) has higher sensitivity and lower specificity than cytology alone for detecting cervical intraepithelial neoplasia (CIN), studies comparing conventional and liquid-based cytology have had conflicting results.In the first phase of a two-phase multicenter randomized controlled trial, women aged 35-60 years in the conventional arm (n = 16,658) were screened using conventional cytology, and women in the experimental arm (n = 16,706) had liquid-based cytology and were tested for high-risk HPV types using the Hybrid Capture 2 assay. Women in the conventional arm were referred to colposcopy with atypical cells of undetermined significance (ASCUS) or higher and those in the experimental arm were referred with ASCUS or higher cytology or with a positive (> or = 1 pg/mL) HPV test. Sensitivity and positive predictive value (PPV) for detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) were calculated.The screening methods and referral criterion applied in the experimental arm had higher sensitivity than that in the conventional arm (relative sensitivity = 1.47; 95% confidence interval [CI] = 1.03 to 2.09) but a lower PPV (relative PPV = 0.40; 95% CI = 0.23 to 0.66). With HPV testing alone at > or = 1 pg/mL and at > or = 2 pg/mL, the gain in sensitivity compared with the conventional arm remained similar (relative sensitivity = 1.43, 95% CI = 1.00 to 2.04 and relative sensitivity = 1.41, 95% CI = 0.98 to 2.01, respectively) but PPV progressively improved (relative PPV = 0.58, 95% CI = 0.33 to 0.98 and relative PPV = 0.75, 95% CI = 0.45 and 1.27, respectively). Referral based on liquid-based cytology alone did not increase sensitivity compared with conventional cytology (relative sensitivity = 1.06; 95% CI = 0.72 to 1.55) but reduced PPV (relative PPV = 0.57; 95% CI = 0.39 to 0.82).HPV testing alone was more sensitive than conventional cytology among women 35-60 years old. Adding liquid-based cytology improved sensitivity only marginally but increased false-positives. HPV testing using Hybrid Capture 2 with a 2 pg/mL cutoff may be more appropriate than a 1 pg/mL cutoff for primary cervical cancer screening.
Glomerular deposition of properdin in acute and chronic glomerulonephritis with hypocomplementemia
Authors: N. Gunnar Westberg, George B. Naff, John T. Boyer, Alfred F. Michael
Journal: Journal of Clinical Investigation (1971)

Kidney tissue from 97 patients was studied by immunofluorescent techniques using antiserum to purified properdin. All patients with acute poststreptococcal glomerulonephritis showed deposition of properdin and the third component of complement (C3), either as "humps" on the basement membrane, or in the mesangium. In all cases of chronic membranoproliferative glomerulonephritis, properdin and C3 were localized in the glomeruli, most commonly in a lobular pattern on the basement membrane. Activation of C3 by the properdin system may explain the depressed serum levels of C3 and terminal complement components even though levels of earlier components are normal, and the deposition of C3, often without immunoglobulins, in the kidneys of patients with acute glomerulonephritis or chronic membranoproliferative glomerulonephritis.
Role of the basophil activation test in the diagnosis of local allergic rhinitis
Authors: Enrique Gómez, Paloma Campo, Carmen Rondón, Esther Barrionuevo, Natalia Blanca-López, María José Torres, Rocío Herrera, Luisa Galindo, Cristobalina Mayorga, Miguel Blanca
Journal: Journal of Allergy and Clinical Immunology (2013)