tbuckley/cabot-search huggingface dataset:
Anti-A2/RA33 autoantibodies are directed to the RNA binding region of the A2 protein of the heterogeneous nuclear ribonucleoprotein complex. Differential epitope recognition in rheumatoid arthritis, systemic lupus erythematosus, and mixed connective tissue disease.
Authors: K Skriner, W H Sommergruber, V Tremmel, I Fischer, A Barta, J S Smolen, G Steiner
Journal: Journal of Clinical Investigation (1997)

The recently described anti-A2/RA33 autoantibodies occur in 20-40% of patients with RA, SLE, and mixed connective tissue disease (MCTD). They are directed to the A2 protein of the heterogeneous nuclear ribonucleoprotein complex (hnRNP-A2), an abundant nuclear protein associated with the spliceosome. The NH2-terminal half of the antigen contains two conserved RNA binding domains whereas its COOH-terminal part is extremely glycine-rich. The aim of this study was to characterize the autoepitopes of hnRNP-A2 and to investigate the effects of anti-A2/RA33 autoantibodies on possible functions of the antigen. Using bacterially expressed fragments, two major discontinuous epitopes were identified. One containing the complete second RNA binding domain was recognized by the majority of patients with RA and SLE but not by patients with MCTD. The second epitope contained sequences of both RNA binding domains and was preferentially targeted by patients with MCTD. When the RNA binding properties of the antigen were investigated, oligoribonucleotides containing the sequence motif r(UUAG) were found to bind to a site closely adjacent or overlapping with the epitope targeted by autoantibodies from patients with RA and SLE. Moreover, anti-A2/RA33 autoantibodies from patients with RA or SLE, but not from patients with MCTD, inhibited binding of RNA. Thus, anti-A2/RA33 autoantibodies recognize conformation-dependent epitopes located in a functionally important region of the antigen. Furthermore, the specific recognition of an epitope by MCTD patients may be used as another argument in favor of considering MCTD a distinct connective tissue disease.
[99mTcOAADT]-(CH2)2-NEt2: A Potential Small-Molecule Single-Photon Emission Computed Tomography Probe for Imaging Metastatic Melanoma
Authors: Zhen Cheng, Ashfaq Mahmood, Huazhi Li, Alan Davison, Alun G. Jones
Journal: Cancer Research (2005)

Abstract Evaluation of [99mTc]oxotechnetium(V) complexes of the amine-amide-dithiol (AADT) chelates containing tertiary amine substituents as small-molecule probes for the diagnostic imaging of metastatic melanoma has shown that technetium-99m–labeled AADT-(CH2)2-NEt2 (99mTc-1) has the highest tumor uptake and other favorable biological properties. We have, therefore, assessed this agent in a more realistic metastatic melanoma model in which, after i.v. tail injection, a highly invasive melanoma cell line, B16F10, forms pulmonary tumor nodules in normal C57BL6 mice. Small melanotic lesions develop in the lungs and, on histologic examination, appear as small black melanoma colonies, increasing in size and number with time after tumor cell injection. Groups of mice received tumor cell inocula of 2 × 105, 4 × 105, or 8 × 105 B16F10 cells; 14 days later, 2 hours after 99mTc-1 administration, lung uptake of 2.83 ± 0.21%, 3.63 ± 1.07%, and 4.92 ± 1.61% injected dose per gram of tissue (% ID/g), respectively, was observed, compared with normal lung uptake of 2.13 ± 0.2% ID/g (P &amp;lt; 0.05). Additionally, a higher level of 99mTc-1 accumulation was seen 17 days after tumor cell inoculation as the lung lesions grew. These in vivo studies coupled with additional in vitro and ex vivo assessment show that 99mTc-1 has high and specific uptake in melanoma metastases in lungs and can potentially follow the temporal growth of these tumors.
The spinal cord as an alternative model for nerve tissue graft
Authors: A. Privat, M. Giménez y Ribotta
Journal: Behavioral and Brain Sciences (1995)

Abstract The spinal cord provides an alternative model for nerve tissue grafting experiments. Anatomo-functional correlations are easier to make here than in any other region of the CNS because of a direct implication of spinal cord neurons in sensorimotor activities. Lesions can be easily performed to isolate spinal cord neurons from descending inputs. The anatomy of descending monoaminergic systems is well defined and these systems offer a favourable paradigm for lesion-graft experiments.
Dual use of amphiphilic macromolecules as cholesterol efflux triggers and inhibitors of macrophage athero-inflammation
Authors: Nicole M. Iverson, Nicole M. Plourde, Sarah M. Sparks, Jinzhong Wang, Ekta N. Patel, Pratik S. Shah, Daniel R. Lewis, Kyle R. Zablocki, Gary B. Nackman, Kathryn E. Uhrich, Prabhas V. Moghe
Journal: Biomaterials (2011)
Up-regulation of Tissue Factor in Human Pulmonary Artery Endothelial Cells after Ultrafine Particle Exposure
Authors: Edward D. Karoly, Zhuowei Li, Lisa A. Dailey, Xhevahire Hyseni, Yuh-Chin T. Huang
Journal: Environmental Health Perspectives (2007)

Epidemiology studies have linked exposure to pollutant particles to increased cardiovascular mortality and morbidity, but the mechanisms remain unknown.We tested the hypothesis that the ultrafine fraction of ambient pollutant particles would cause endothelial cell dysfunction.We profiled gene expression of human pulmonary artery endothelial cells (HPAEC) exposed to ultrafine particles (UFPs; 100 microg/mL) from Chapel Hill, North Carolina, or vehicle for 4 hr with Affymetrix HG U133 Plus 2.0 chips (n = 4 each).We found 320 up-regulated genes and 106 down-regulated genes (p < 0.01, 5% false discovery rate). We noted up-regulation of genes related to coagulation [tissue factor (F3) and coagulation factor II receptor-like 2 (F2RL2)] and differential regulation of genes related to F3 signaling (FOS, JUN, and NFKBIA). Results of quantitative polymerase chain reaction show a significant up-regulation of F3 after 10 and 100 microg/mLUFP exposures. Additionally, the water-soluble fractions of UFPs were sufficient to induce the expression of F3, F2RL2, and heme oxygenase 1 (HMOX1). Treatment of HPAEC with UFPs for 16 hr increased the release of interleukin (IL)-6 and IL-8. Pretreatment of HPAEC with a blocking antibody against F3 attenuated IL-6 and IL-8 release by 30 and 70%, respectively.Using gene profiling, we discovered that UFPs may induce vascular endothelial cells to express genes related to clotting. These results indicate that PM may cause adverse cardiovascular health effects by activating coagulation-inflammation circuitry.
Immunizations, Seizures, and Subsequent Evaluation
Authors: J. T. Jabhour
Journal: JAMA (1987)

<h3>To the Editor.—</h3> The recent article by Funkhouser et al<sup>1</sup>focuses on one alternative to the present immunization schedule recommended in the United States for diphtheria and tetanus toxoids and pertussis vaccine (DTP). The analysis utilizes a host of assumptions and extrapolations that require substantiation and clarification. Incidence data on pertussis and adverse reactions to vaccine need further study. It is imperative at this juncture that we develop criteria for the evaluation of children with alleged temporal associations between immunizations and sequelae to develop reliable data on severe adverse reactions to DTP in the United States. A uniform system of evaluation will facilitate our understanding of true reactions to DTP. The diagnostic evaluation of such patients must recognize that many of the patients have preexisting or concurrent infections or neurological conditions that surface following the administration of the vaccine, eg, an enterovirus or<i>Haemophilus influenzae</i>meningitis infection. Such an
Apes in the Anthropocene: flexibility and survival
Authors: Kimberley J. Hockings, Matthew R. McLennan, Susana Carvalho, Marc Ancrenaz, René Bobe, Richard W. Byrne, Robin I.M. Dunbar, Tetsuro Matsuzawa, William C. McGrew, Elizabeth A. Williamson, Michael L. Wilson, Bernard Wood, Richard W. Wrangham, Catherine M. Hill
Journal: Trends in Ecology & Evolution (2015)
Molecular pathogenesis of alpha-1-antitrypsin deficiency-associated liver disease: A meeting review
Authors: David H. Perlmutter, Jeffrey L. Brodsky, William F. Balistreri, Bruce C. Trapnell
Journal: Hepatology (2007)

In recent years, we have witnessed several important paradigm shifts in understanding the molecular basis of liver disease in alpha-1-antitrypsin (AT) deficiency. These shifts have become possible as a result of a number of advances in research on the cell biology of aggregation-prone mutant proteins and in research on the pathobiological mechanisms of liver disease in general. Late-breaking research in these areas was the subject of an AASLD/Alpha-1 Foundation Single Topic Conference in Atlanta, Georgia, on January 26 to 28, 2006. The conference was titled "Alpha-1-Antitrypsin Deficiency and Other Liver Diseases Caused by Aggregated Proteins." Investigators from all over the world, representing a broad array of scientific disciplines and perspectives, discussed the pathobiology of AT deficiency, mechanisms of cell injury in diseases associated with aggregation-prone proteins, pathways by which cells respond to protein aggregation and mislocalization, and mechanisms of liver injury in general and in diseases related to AT deficiency. A session of the meeting was devoted to novel therapeutic strategies being developed for AT deficiency as well as to strategies either in development or already being applied to the class of diseases associated with mutant proteins.
Observations ON SPLENIC ANAEMIA: BANTI'S DISEASE: Part of the Bradshaw Lecture on the Surgery of the Spleen
Authors: B. Moynihan
Journal: BMJ (1921)

_UDICAL _J____ patient move the joint spontaneously and vigorously, to cause the effusion to be forced out.Passive movements do barm.Under this treatment many even severely affected joints have recovered witih free movement.To encourage movement of any sort wlhile inflammation is still prsenit in a joint, or indeed in any part, is contrary to all previoutIs teaching, yet tlhe reconmmendation is juatfied by results, as I liave been able to prove to my satisfacLion on several occasions duriig thle war anid since my return to civil prac- tice.I wishi to point out thlat the same factor as is involved in the use of active movements in joint sepsis is revealed at work in cases wihichi recover after operation for peritonitis or pleuritis.In thiese, normal inovements of bowel.or Ilung speedily occur, and, niark you, it is better to dispense with drainage.1f, in peritoniitis, the bowel is so badly affected that peristalsis is paraIysed, or if, afier operation for pleurisy, the lung-does not expand, recovery is, to say the least, a doubtful issue, even when dr-ainage is estab- lished.In some cas-s of peritonitis, when thie bowel is paralysed, temporary drainage of the bowel to remove its
TCT-283 Intimal Hyperplasia and Vascular Remodeling after Everolimus-eluting and Sirolimus-eluting Stent Implantation in Diabetic Patients. The Randomized Diabetes and Drug-Eluting Stent (DiabeDES) IV Intravascular Ultrasound Trial
Authors: Lisbeth Antonsen, Lisette Okkels Jensen, Michael Maeng, Per Thayssen, Evald Høj Christiansen, Knud Nørregaard Hansen, Anne Kaltoft, Henrik Steen Hansen, Leif Thuesen, Jens Flensted Lassen
Journal: Journal of the American College of Cardiology (2012)
Sex Distribution of<i>Staphylococcus aureus</i>Colonization and Disease in Newborn Infants
Authors: Donovan J. Thompson, Horace M. Gezon, Theodore F. Hatch, Russell R. Rycheck, Kenneth D. Rogers
Journal: New England Journal of Medicine (1963)

AS part of an extensive study of the epidemiology of staphylococcal colonization and resultant disease in newborn infants in four hospitals** in Pittsburgh, Pennsylvania, home visits at approximately three weeks of life have recently been completed on a sufficient sample of infants to warrant investigation of the possible role of a number of factors, including the sex of the infant, in staphylococcal infection and disease. Contrary to an impression gained from examination of data from earlier studies limited to the period preceding discharge from the hospital, there appears to be a marked and highly consistent difference in the staphylococcal-disease experience . . .
The Examination of the Cornea and Lens by Means of the Ophthalmoscope, Having behind it a Strong Convex Lens
Authors: G. Hartridge
Journal: BMJ (1885)

<h3>Objective</h3> To investigate the relationship between cognitive reserve (CR) and clinical progression across the Alzheimer disease (AD) spectrum. <h3>Methods</h3> We selected 839 β-amyloid (Aβ)–positive participants with normal cognition (NC, n = 175), mild cognitive impairment (MCI, n = 437), or AD dementia (n = 227) from the Alzheimer9s Disease Neuroimaging Initiative (ADNI). CR was quantified using standardized residuals (W scores) from a (covariate-adjusted) linear regression with global cognition (13-item Alzheimer9s Disease Assessment Scale–cognitive subscale) as an independent variable of interest, and either gray matter volumes or white matter hyperintensity volume as dependent variables. These W scores, reflecting whether an individual9s degree of cerebral damage is lower or higher than clinically expected, were tested as predictors of diagnostic conversion (i.e., NC to MCI/AD dementia, or MCI to AD dementia) and longitudinal changes in memory (ADNI-MEM) and executive functions (ADNI-EF). <h3>Results</h3> The median follow-up period was 24 months (interquartile range 6–42). Corrected for age, sex, <i>APOE4</i> status, and baseline cerebral damage, higher gray matter volume-based W scores (i.e., greater CR) were associated with a lower diagnostic conversion risk (hazard ratio [HR] 0.22, <i>p</i> &lt; 0.001) and slower decline in memory (β = 0.48, <i>p</i> &lt; 0.001) and executive function (β = 0.67, <i>p</i> &lt; 0.001). Stratified by disease stage, we found similar results for NC (diagnostic conversion: HR 0.30, <i>p</i> = 0.038; ADNI-MEM: β = 0.52, <i>p</i> = 0.028; ADNI-EF: β = 0.42, <i>p</i> = 0.077) and MCI (diagnostic conversion: HR 0.21, <i>p</i> &lt; 0.001; ADNI-MEM: β = 0.43, <i>p</i> = 0.003; ADNI-EF: β = 0.59, <i>p</i> &lt; 0.001), but opposite findings (i.e., more rapid decline) for AD dementia (ADNI-MEM: β = −0.91, <i>p</i> = 0.002; ADNI-EF: β = −0.77, <i>p</i> = 0.081). <h3>Conclusions</h3> Among Aβ-positive individuals, greater CR related to attenuated clinical progression in predementia stages of AD, but accelerated cognitive decline after the onset of dementia.
Central Pontine Myelinolysis
Authors: Khosrow Afsari, Jonathan P. Posin
Journal: Annals of Internal Medicine (2002)

Letters17 September 2002Central Pontine MyelinolysisKhosrow Afsari, MD and Jonathan P. Posin, MDKhosrow Afsari, MDTouro University College of Osteopathic Medicine; San Pablo, CA 94806University of California, San Francisco; Pinole, CA 94564Search for more papers by this author and Jonathan P. Posin, MDTouro University College of Osteopathic Medicine; San Pablo, CA 94806University of California, San Francisco; Pinole, CA 94564Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-137-6-200209170-00036 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:A 42-year-old woman receiving hydrochlorothiazide for hypertension presented with nausea, vomiting, diarrhea, shock, and dehydration after binge drinking of vodka and mixed hard liquor. Serum sodium level at admission was 97 mmol/L; the patient required 4 L of intravenous normal saline infusion to achieve hemodynamic stability. Serum sodium level gradually normalized within the next 4 days (<1 L of sodium correction per hour), but the patient's course was complicated over the next 7 days by dysarthria, mutism, facial and neck weakness, and profound quadriparesis with spastic flexion of the lower limbs and Babinski signs.On magnetic resonance ... Author, Article, and Disclosure InformationAffiliations: Touro University College of Osteopathic Medicine; San Pablo, CA 94806University of California, San Francisco; Pinole, CA 94564 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoCorrection: Central Pontine Myelinolysis Metrics Cited byCorrection: Central Pontine Myelinolysis 17 September 2002Volume 137, Issue 6Page: 553KeywordsDiarrheaEdemaHemodynamicsHypertensionMagnetic resonance imagingNauseaSaline solutionsShockSodiumVomiting ePublished: 17 September 2002 Issue Published: 17 September 2002 Copyright & PermissionsCopyright © 2002 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Doctors in poll position
Authors: Imre Loefler
Journal: BMJ (2005)

Doctors have the opportunity to turn the gears of medicalisation a notch further: the electorate ought to be medically certified before being allowed to vote.

There is a staggering number of voters with dementia. Their ranks are growing. It is estimated that by 2015 there will be 15 million people with dementia in the United States alone.

Not only are people with dementia incompetent to vote, but they are also easily manipulated. The exploitation of such …
IgE‐binding epitopes of the American cockroach Per a 3 allergen
Authors: C. H. Wu, M. F. Lee, C. Y. Tseng
Journal: Allergy (2003)

Background: The Per a 3 is a species‐specific allergen of the American cockroach ( Periplaneta americana ) related to insect hemolymph proteins and includes four known isoallergens. This study aimed to identify Per a 3 linear IgE‐binding epitopes. Methods: Per a 3 recombinant fragments were generated from the recombinant Per a 3.01 allergen (685 amino acid residues) by using existing restriction sites or by using polymerase chain reaction products, and expressed in Escherichia coli . Antigenicities were assessed by immunoblotting, enzyme‐linked immunosorbent assay (ELISA), and binding inhibition with human IgE. Results: Human IgE recognized recombinant fragments 340–425, 466–579, 502–595, and 595–636 as revealed by immunoblotting and ELISA. On the other hand, the N‐terminal fragment 1–399, recombinants 410–443, 472–551, 502–579, 606–636, and the C‐terminal fragment 636–685 were unable to bind human IgE. Amino acid sequences 400–409, 466–471, 580–595, and 595–605 were shown to be required for IgE binding to the Per a 3.01 allergen, suggesting that the C‐terminus contains most of the IgE‐binding sites. Four peptides corresponding to these IgE‐binding amino acid sequences were synthesized. These peptides reacted with most sera (62.5–87.5%) tested as revealed by ELISA, demonstrating a heterogeneous IgE‐binding response. Moreover, preincubation of IgE‐positive recombinant proteins and synthetic peptides with atopic IgE resulted in marked inhibition of the IgE binding to Per a 3.01 allergen. Amino acid sequences 400 TVLRDPVFYQ 409 , 466 NNVDQI 471 , 580 VDKGHNYCGYPENLLI 595 , and 595 IPKGKKGGQAY 605 of the major recombinant American cockroach Per a 3.01 allergen were involved in IgE binding. Conclusion: These findings will advance our understanding of the antigenic structures responsible for allergenicity to the American cockroach, thereby providing strategies for the development of immunotherapies.
The role of the host defence response in the progression and outcome of ARDS: pathophysiological correlations and response to glucocorticoid treatment
Authors: GU Meduri
Journal: European Respiratory Journal (1996)

The host defence response (HDR) to insults is similar regardless of the tissue involved and consists of an interactive network of simultaneously activated pathways that act in synergy to increase the host's chance of survival. Among this cascade of integrated pathways, three aspects of the HDR, inflammation, coagulation and tissue repair, are analysed separately to explain the histological and physiological changes occurring at the tissue level in unresolving acute respiratory distress syndrome (ARDS). Cellular responses in HDR are regulated by a complex interaction among cytokines, and cytokines have concentration-dependent biological effects. The degree of initial HDR may determine the progression of ARDS. On Day 1 of mechanical ventilation and over time, nonsurvivors of ARDS have significantly higher plasma and bronchoalveolar lavage inflammatory cytokine levels than survivors. In the absence of inhibitory signals, the continued production of HDR mediators prevents effective restoration of lung anatomy and function by sustaining inflammation with tissue injury, intra- and extravascular coagulation and proliferation of mesenchymal cells (fibroproliferation) with deposition of extracellular matrix resulting in fibrosis. Glucocorticoids inhibit the HDR cascade at virtually all levels; their gradual and generalized suppressive influence protects the host from overshooting. In patients with exaggerated HDR, however, cytokine elevation may cause a concentration-dependent resistance to glucocorticoids by reducing glucocorticoid receptor binding affinity. Recent clinical and experimental studies have shown that effective containment of the HDR in unresolving ARDS may be achieved only if glucocorticoid administration is prolonged. A double-blind randomized study is in progress to evaluate the role of prolonged glucocorticoid treatment in unresolving ARDS.
Naturally processed and presented epitopes of the islet cell autoantigen IA-2 eluted from HLA-DR4
Authors: Mark Peakman, Elizabeth J. Stevens, Tobias Lohmann, Parth Narendran, James Dromey, Angela Alexander, Andrew J. Tomlinson, Massimo Trucco, Joan C. Gorga, Roman M. Chicz
Journal: Journal of Clinical Investigation (1999)

During immune responses, antigen-presenting cells (APCs) process antigens and present peptide epitopes complexed with human leukocyte antigen (HLA) molecules. CD4 cells recognize these naturally processed and presented epitopes (NPPEs) bound to HLA class II molecules. Epitope identification is important for developing diagnostic and therapeutic tools for immune-mediated diseases and providing insight into their etiology, but current approaches overlook effects of natural processing on epitope selection. We have developed a technique to identify NPPEs using mass spectrometry (MS) after antigen is targeted onto APCs using a lectin-based antigen delivery system (ADS). We applied the technique to identify NPPEs of the intracellular domain of the type 1 diabetes mellitus–associated (type 1 DM-associated) autoantigen insulinoma-associated-2 (IA-2ic), presented by HLA-DR4 (0401). IA-2ic–derived NPPEs eluted from HLA-DR4 constitute 6 sets of peptides nested around distinct core regions. Synthetic peptides based on these regions bind HLA-DR4 and elicit primary T-cell proliferation frequently in HLA-DR4–positive type 1 DM patients, but rarely in non–HLA-DR4 patients, and in none of the HLA-DR4 nondiabetic controls we tested. This flexible, direct approach identifies an HLA allele-specific map of NPPEs for any antigen, presented by any HLA class II molecule. This method should enable a greater understanding of epitope selection and lead to the generation of sensitive and specific reagents for detecting autoreactive T cells.
LETTER FROM BERMUDA.Winter Days in Summer Islands—Notes from the Land of the Lily and the Rose.
Authors: J. B. Mattison
Journal: JAMA (1894)

Hamilton, Bermuda, Feb. 28, 1894. <h3>To the Editor:</h3> —Out of the gray and the gloom of a foggy February morning steamed the<i>Trinidad</i>to a summery land at sea, bearing the biggest boatload of tourists ever bound from New York to Bermuda. The early advent of Lent doubtless had much to do with this unusual tide of travel, though the fashion still obtains of waiting till nearly the end of winter before coming here. From the snow and the slush, the hail and the cold of New York and Brooklyn to the warm sunshine and balmy breezes of Bermuda—when life out of doors is a perennial pleasure—is a change so great that many fail to realize it, and nothing less than a personal experience will convince a doubting searcher for health or pleasure that here is a charming country, where the real rivals the ideal, and where fact touches fancy,