tbuckley/cabot-search huggingface dataset:
Anti-phospholipid human monoclonal antibodies inhibit CCR5-tropic HIV-1 and induce β-chemokines
Authors: M. Anthony Moody, Hua-Xin Liao, S. Munir Alam, Richard M. Scearce, M. Kelly Plonk, Daniel M. Kozink, Mark S. Drinker, Ruijun Zhang, Shi-Mao Xia, Laura L. Sutherland, Georgia D. Tomaras, Ian P. Giles, John C. Kappes, Christina Ochsenbauer-Jambor, Tara G. Edmonds, Melina Soares, Gustavo Barbero, Donald N. Forthal, Gary Landucci, Connie Chang, Steven W. King, Anita Kavlie, Thomas N. Denny, Kwan-Ki Hwang, Pojen P. Chen, Philip E. Thorpe, David C. Montefiori, Barton F. Haynes
Journal: The Journal of Experimental Medicine (2010)

Traditional antibody-mediated neutralization of HIV-1 infection is thought to result from the binding of antibodies to virions, thus preventing virus entry. However, antibodies that broadly neutralize HIV-1 are rare and are not induced by current vaccines. We report that four human anti-phospholipid monoclonal antibodies (mAbs) (PGN632, P1, IS4, and CL1) inhibit HIV-1 CCR5-tropic (R5) primary isolate infection of peripheral blood mononuclear cells (PBMCs) with 80% inhibitory concentrations of &amp;lt;0.02 to ∼10 µg/ml. Anti-phospholipid mAbs inhibited PBMC HIV-1 infection in vitro by mechanisms involving binding to monocytes and triggering the release of MIP-1α and MIP-1β. The release of these β-chemokines explains both the specificity for R5 HIV-1 and the activity of these mAbs in PBMC cultures containing both primary lymphocytes and monocytes.
p63RhoGEF Couples G <sub>αq/11</sub> -Mediated Signaling to Ca <sup>2+</sup> Sensitization of Vascular Smooth Muscle Contractility
Authors: Ko Momotani, Mykhaylo V. Artamonov, Darkhan Utepbergenov, Urszula Derewenda, Zygmunt S. Derewenda, Avril V. Somlyo
Journal: Circulation Research (2011)

In normal and diseased vascular smooth muscle (SM), the RhoA pathway, which is activated by multiple agonists through G protein-coupled receptors (GPCRs), plays a central role in regulating basal tone and peripheral resistance. This occurs through inhibition of myosin light chain phosphatase, leading to increased phosphorylation of the myosin regulatory light chain. Although it is thought that specific agonists and GPCRs may couple to distinct RhoA guanine nucleotide exchange factors (GEFs), thus raising the possibility of selective targeting of specific GEFs for therapeutic use, this notion is largely unexplored for SM contraction.We examine whether p63RhoGEF, known to couple specifically to Gα(q/11) in vitro, is functional in blood vessels as a mediator of RhoA activation and if it is selectively activated by Gα(q/11) coupled agonists.We find that p63RhoGEF is present across SM tissues and demonstrate that silencing of the endogenous p63RhoGEF in mouse portal vein inhibits contractile force induced by endothelin-1 to a greater extent than the predominantly Gα(12/13)-mediated thromboxane analog U46619. This is because endothelin-1 acts on Gα(q/11) as well as Gα(12/13). Introduction of the exogenous isolated pleckstrin-homology (PH) domain of p63RhoGEF (residues 331-580) into permeabilized rabbit portal vein inhibited Ca2+ sensitized force and activation of RhoA, when phenylephrine was used as an agonist. This reinforces the results based on endothelin-1, because phenylephrine is thought to act exclusively through Gα(q/11).We demonstrate that p63RhoGEF selectively couples Gα(q/11) but not Gα(12/13), to RhoA activation in blood vessels and cultured cells and thus mediates the physiologically important Ca2+ sensitization of force induced with Gα(q/11)-coupled agonists. Our results suggest that signaling through p63RhoGEF provides a novel mechanism for selective regulation of blood pressure.
The Clinician's Guide to Gastrointestinal Oncology
Authors: Joanne K. Tobacman
Journal: Annals of Internal Medicine (2006)

Medical Writings: Book Notes3 January 2006The Clinician's Guide to Gastrointestinal OncologyJoanne K. Tobacman, MDJoanne K. Tobacman, MDFrom the University of Illinois at Chicago, Chicago, Illinois.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-144-1-200601030-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Kochman ML, ed. 403 pages. Thorofare, NJ: SLACK; 2005. $59.95. ISBN 1556426828. Order at www.slackbooks.com.Field of medicine: Gastrointestinal oncology.Format: Softcover book.Audience: Physicians who care for patients with gastrointestinal malignant or premalignant conditions.Purpose: To provide an up-to-date, concise, and multidisciplinary guide to current management of gastrointestinal malignant conditions, including care delivered by internists, gastroenterologists, interventional radiologists, oncologists, and surgeons.Content: Thirty-one expert authors from 13 institutions survey the gastrointestinal tract, describing current diagnostic and therapeutic techniques for esophageal, gastric, pancreaticobiliary, and colorectal malignancies. Therapeutic interventions are presented from the perspectives of the endoscopist, the interventional radiologist, the ... Author, Article, and Disclosure InformationAffiliations: From the University of Illinois at Chicago, Chicago, Illinois. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 3 January 2006Volume 144, Issue 1Page: 72KeywordsEpidemiologyGastrointestinal tractNutritionPain managementPatientsRadiation therapyRadiologistsSoftware toolsSurgeonsUltrasound imaging ePublished: 3 January 2006 Issue Published: 3 January 2006 Copyright & PermissionsCopyright © 2006 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Effects of three different training modalities on the cross sectional area of the lumbar multifidus muscle in patients with chronic low back pain
Authors: L A Danneels, G G Vanderstraeten, D C Cambier, E E Witvrouw, J Bourgois, W Dankaerts, H J De Cuyper
Journal: British Journal of Sports Medicine (2001)

Objectives —To determine the effect of different training schedules on the cross sectional area (CSA) of the lumbar multifidus muscle in patients with chronic low back pain. Methods —Each of 59 nine patients was randomly assigned to one of three programmes: 10 weeks of stabilisation training (group 1; n = 19); 10 weeks of stabilisation training combined with dynamic resistance training (group 2; n = 20); 10 weeks of stabilisation training combined with dynamic-static resistance training (group 3; n = 20). Before and after 10 weeks of training, multifidus CSAs were measured from standard computed tomography images at three different levels (upper end plate of L3 and L4, and lower end plate of L4). Results —The CSA of the multifidus muscle was significantly increased at all levels after training in group 3. In contrast, no significant differences were found in groups 1 and 2. Conclusions —General stabilisation exercises and dynamic intensive lumbar resistance training have no significant effect on the CSA of the lumbar multifidus muscle in patients with chronic low back pain. The static holding component between the concentric and eccentric phase was found to be critical in inducing muscle hypertrophy during the first 10 weeks. Treatment consisting of stabilisation training combined with an intensive lumbar dynamic-static strengthening programme seems to be the most appropriate method of restoring the size of the multifidus muscle.
Mercury Exposure and Antinuclear Antibodies among Females of Reproductive Age in the United States: NHANES
Authors: Emily C. Somers, Martha A. Ganser, Jeffrey S. Warren, Niladri Basu, Lu Wang, Suzanna M. Zick, Sung Kyun Park
Journal: Environmental Health Perspectives (2015)

Immune dysregulation associated with mercury has been suggested, although data in the general population are lacking. Chronic exposure to low levels of methylmercury (organic) and inorganic mercury is common, such as through fish consumption and dental amalgams.We examined associations between mercury biomarkers and antinuclear antibody (ANA) positivity and titer strength.Among females 16-49 years of age (n = 1,352) from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, we examined cross-sectional associations between mercury and ANAs (indirect immunofluorescence; cutoff ≥ 1:80). Three biomarkers of mercury exposure were used: hair (available 1999-2000) and total blood (1999-2004) predominantly represented methylmercury, and urine (1999-2002) represented inorganic mercury. Survey statistics were used. Multivariable modeling adjusted for several covariates, including age and omega-3 fatty acids.Sixteen percent of females were ANA positive; 96% of ANA positives had a nuclear speckled staining pattern. Geometric mean (geometric SD) mercury concentrations were 0.22 (0.03) ppm in hair, 0.92 (0.05) μg/L blood, and 0.62 (0.04) μg/L urine. Hair and blood, but not urinary, mercury were associated with ANA positivity (sample sizes 452, 1,352, and 804, respectively), after adjusting for confounders: for hair, odds ratio (OR) = 4.10 (95% CI: 1.66, 10.13); for blood, OR = 2.32 (95% CI: 1.07, 5.03) comparing highest versus lowest quantiles. Magnitudes of association were strongest for high-titer (≥ 1:1,280) ANA: hair, OR = 11.41 (95% CI: 1.60, 81.23); blood, OR = 5.93 (95% CI: 1.57, 22.47).Methylmercury, at low levels generally considered safe, was associated with subclinical autoimmunity among reproductive-age females. Autoantibodies may predate clinical disease by years; thus, methylmercury exposure may be relevant to future autoimmune disease risk.
Elevated von Willebrand factor antigen is an early plasma predictor of acute lung injury in nonpulmonary sepsis syndrome.
Authors: D B Rubin, J P Wiener-Kronish, J F Murray, D R Green, J Turner, J M Luce, A B Montgomery, J D Marks, M A Matthay
Journal: Journal of Clinical Investigation (1990)

In this prospective study of 45 patients, we tested the hypothesis that markedly elevated levels of plasma von Willebrand antigen (vWf-Ag) a marker of endothelial cell injury, might predict the development of acute lung injury in patients with nonpulmonary sepsis syndrome. Acute lung injury was quantified on a four-point scoring system. At the time of entry into the study, none of the 45 patients had evidence of lung injury. Subsequently, 15 patients developed lung injury and 30 patients did not develop lung injury. The mean plasma vWf-Ag level was markedly elevated in the 15 patients who developed lung injury compared with the 30 patients who did not develop lung injury (588 +/- 204 vs. 338 +/- 196, percentage of control, P less than 0.01). Furthermore, a plasma vWf-Ag level greater than or equal to 450 was 87% sensitive and 77% specific for predicting the development of acute lung injury in the setting of nonpulmonary sepsis. In addition, the combination of a plasma vWf-Ag greater than 450 and nonpulmonary organ failure at the time of entry into the study had a positive predictive value of 80% for acute lung injury. Also, a plasma vWf-Ag level greater than 450 had a positive predictive value of 80% for identifying nonsurvivors. Thus, in patients with nonpulmonary sepsis, an elevated level of plasma vWf-Ag is a useful, early biochemical marker of endothelial injury and it has both predictive and prognostic value.
An International Exhibition in Nice
Authors: C. West
Journal: BMJ (1883)

narily practised&mdash;that is to say, by rrzonnq of the various forms of oral and naso-oral inhalers, whicli are manufactured and used by thousands, and its object was to prove whether this mode of inhalation was eitioieiit or not.I showed hy experiment, what certainly was not g-euerally known, or the method would not have been so extensively employed, that the greater portion of the more powerful antiseptics uqed was retained by the sponge, so little being unaccounted for that the conclusion seemed warranted that this method of inhalation was very ineflicient, if not without v.due.I pur- posely refrained from discussing other modes of inhalation, as by ppray or steam ; these I hope to refer to later on, but I think it questionable how far a steam inhaler is likely to prove beneficial in certain di4ea,,eq, not of the throat, but of the lungs themselves, even although, as in the case of Dr. Lee's 'steam draft inhaler, the temperature can, it is aflirmed be regulated from 75&ogr; to 120&deg; F.
The source and role of RANTES in interstitial lung disease
Authors: M Petrek, P Pantelidis, AM Southcott, P Lympany, P Safranek, CM Black, V Kolek, E Weigl, RM du Bois
Journal: European Respiratory Journal (1997)

The chemokine "regulated on activation, normal T-cell expressed and secreted" (RANTES) is a potent eosinophil and lymphocyte attractant with particular preference for CD45RO+ T-cells and eosinophils. These cells accumulate in the lungs of patients with sarcoidosis and fibrosing alveolitis. The purpose of this study was to determine whether RANTES mediates the inflammatory cell influx in these diffuse lung diseases. Cell types and number of bronchoalveolar cells expressing RANTES protein were investigated by immunocytochemistry using lavage cells obtained from 22 patients and 11 control subjects. Subsequently, RANTES messenger ribonucleic acid (mRNA) was semiquantitated using reverse transcription polymerase chain reaction (RT-PCR) methodology in unseparated lavage cell pellets in 26 patients and 13 control subjects. Cells expressing RANTES mRNA were identified by in situ hybridization. RANTES protein expression in lower respiratory tract (LRT) cells was identified in all study groups. The percentage of RANTES+ lavage cells in sarcoidosis was higher than in controls. RANTES was localized in the cytoplasm, mainly in alveolar macrophages (CD68+ cells) in sarcoidosis, and both in alveolar macrophages and eosinophils in fibrosing alveolitis. The same cell types which expressed RANTES protein expressed RANTES mRNA, as assessed by in situ hybridization. Sarcoidosis patients had higher levels of RANTES mRNA than the other groups. RANTES protein was higher in individuals with abnormal lymphocyte numbers: RANTES protein and mRNA expression was significantly correlated with lavage CD45RO+ lymphocyte numbers. These results indicate that RANTES may mediate T-lymphocyte influx in diffuse lung disease, particularly sarcoidosis. Moreover, they suggest that the cellular source of RANTES is the alveolar macrophage in sarcoidosis, and both macrophages and eosinophils in fibrosing alveolitis.
COMPARATIVE ASPECTS OF LOUPING-ILL IN SHEEP AND POLIOMYELITIS OF MAN
Authors: W. S. Gordon
Journal: BMJ (1934)

By louping-ill in sheep is currently understood a disease characterized by cerebellar ataxia and disorder of brain and spinal cord functions, lasting about a day in acute infections to some weeks in chronic cases.In the latter type paralysis of one or more limbs is generally-present.The mortality in definite clinical cases is high, but animals which recover do not usually develop another attack.The association of the disease with particular pastures is well established, and a large proportion of sheep brought from a locality in which louping-ill does not occur into a louping-ill district are liable to develop the disease.The first conclusive contribution on the causation of this disease was made by Pool, Brownlee, and Wilson1 in 1930, and the earlier literature on louping-ill has already been reviewed by Pool.2 3 These authors recorded the successful transmissiofi of loupirng-ill in series from sheep to sheep by intracerebral inoculation with material obtained from the central nervous system of affected animals.The pig was also shown to be susceptible. FEATURES OF LOUPING-ILLIn continuation of the work of Pool, Brownlee, and Wilson, investigations4 5 6 8 9 at the laboratories of the Animal Diseases Research Association established that:1.The infective agent is a filterable virus which is communicable to mice as well as to sheep.2. The pathological changes in the disease are essen- tially those of an encephalomyelitis.3. The virus may be present in an infected sheep with- out producing typical louping-ill, but blood drawn at an early stage of the febrile reaction, which is a prodromal symptom of this infection, contains the virus.4. Atypical manifestations may comprise merely a febrile reaction, or the sheep may die without lesions in the brain and spinal cord.5. Under natural conditions louping-ill is tick-borne, the vector being Ixodes ricinus L., which is habitually present on louping-ill pastures.6. Recovery from infection, either naturally or experi- mentally produced, results in immunity.7. The investigation of louping-ill has revealed the presence of another tick-borne infection of sheep.This disease, which has been named " tick-borne fever,"-is clinically, pathologically, immunologically, and aetio- logically distinguishable from louping-ill, but it probably aggravates the harmful effects of the latter.That the causal organismof louping-ill is a filterable virus is now generally accepted (Alston and Gibson,i 0 and Czarkowska-Gladney and Hurst"1).Hurst12 infected monkeys, and Findlay and Elton13 tranismitted the disease to field voles.We possess unpublished evidence that
Different Prognostic Roles of Mutations in the Helical and Kinase Domains of the <i>PIK3CA</i> Gene in Breast Carcinomas
Authors: Mattia Barbareschi, Fiamma Buttitta, Lara Felicioni, Sabrina Cotrupi, Fabio Barassi, Maela Del Grammastro, Antonella Ferro, Paolo Dalla Palma, Enzo Galligioni, Antonio Marchetti
Journal: Clinical Cancer Research (2007)

Abstract Purpose: In breast cancer, the PIK3CA gene is frequently mutated at “hotspots” in exons 9 and 20, corresponding to the helical and kinase domains, respectively. We decided to investigate the association of PIK3CA mutations with pathologic features and clinical outcome in a large series of patients with breast cancer. Experimental Design: Frozen samples from 163 consecutive patients were analyzed for PIK3CA mutations using PCR single-strand conformation polymorphism and sequence analyses. Results: We identified 46 missense mutations, 24 (53%) in exon 9, and 21 (47%) in exon 20. Twelve (50%) of the 24 mutations in exon 9 were of the E542K type and 11 (46%) were of the E545K type. Twenty (95%) of the 21 mutations in exon 20 were H1047R substitutions. Mutations in exon 9 were more frequent in lobular carcinomas (42% of cases) than in ductal carcinoma (11% of cases; P = 0.002). At univariate survival analysis, PIK3CA exon 20 mutations were associated with prolonged overall and disease-free survival, whereas mutations in exon 9 were associated with significantly worse prognosis. At multivariate analysis, exon 9 PIK3CA mutations were the strongest independent factor to predict poor prognosis for disease-free survival (P = 0.0003) and overall survival (P = 0.001). Conclusion: Our data show that exon 9 PIK3CA mutations are typical of infiltrating lobular carcinomas. In addition, they indicate that PIK3CA mutations in different exons are of different prognostic value: exon 9 mutations are independently associated with early recurrence and death, whereas exon 20 PIK3CA mutations are associated with optimal prognosis.
Bone marrow-CNS connections: Implications in the pathogenesis of diabetic retinopathy
Authors: Jane Yellowlees Douglas, Ashay D. Bhatwadekar, Sergio Li Calzi, Lynn C. Shaw, Debra Carnegie, Sergio Caballero, Quihong Li, Alan W. Stitt, Mohan K. Raizada, Maria B. Grant
Journal: Progress in Retinal and Eye Research (2012)
Join us at The Lancet Clinic
Authors: Sabine Kleinert, Richard Horton, Elena Becker-Barroso, Niall Boyce, David Collingridge, Justine Davies, Emma Grainger, Peter Hayward, John McConnell, Zoë Mullan, Lan-Lan Smith
Journal: The Lancet HIV (2015)

On Oct 5, 2015, we launch the first 45 disease-specific pages of a major new online initiative involving all Lancet journals that will bring together an overview Seminar and relevant Reviews, Clinical Series, Commissions, research, Case Reports, and Clinical Pictures. Over the next 18 months or so when The Lancet Clinic is complete, there will be online pages for 135 diseases, which we have identified by a combination of global burden of disease data and clinical practice needs. We hope that The Lancet Clinic will help practising doctors make better informed decisions that ultimately lead to better lives of people worldwide, and help others who want to educate or update themselves keep abreast of the evolving evidence base. Importantly, these pages will be updated at regular intervals. The authors of newly commissioned Seminars have agreed to provide regular summaries of important new evidence for 4 years. Individual clinical editors will pull together newly published material from across the Lancet journals and post links to these on the page regularly. In addition, we are continuing our regular editorial policies of commissioning more specialised Clinical Reviews and Series across The Lancet Group to provide a more focused and in-depth assessment for key diseases. And beyond providing knowledge and information, we want to encourage academic and practising clinicians to use this knowledge for advocacy and change. In 2014, The Lancet published the first Clinical Commission on liver disease in the UK and in February, 2015, we launched our first Clinical Campaign based on this Commission. A Cancer Campaign as a joint effort between The Lancet and The Lancet Oncology followed in April. Clinical Campaigns aim to effect change based on data, knowledge, and expert interpretation in partnership with others. Further Clinical Commissions on asthma, hypertension, dementia, tuberculosis, traumatic brain injury, psychotherapy, chronic obstructive pulmonary disease, and others are underway across all Lancet journals. With these Clinical Commissions and Campaigns, we hope to extend our goal to publish the best science for better lives to being an active partner in using this science for actual change. Commissions and Campaigns will be part of the disease pages to encourage engagement and actions. The Lancet Clinic invites you to be part of this endeavour.
Complement receptor type 3 (CR3) binds to an Arg-Gly-Asp-containing region of the major surface glycoprotein, gp63, of Leishmania promastigotes.
Authors: D G Russell, S D Wright
Journal: The Journal of Experimental Medicine (1988)

The major surface glycoprotein of Leishmania promastigotes, gp63, was isolated and reconstituted into a lipid membrane immobilized on the surface of 5-micron-diameter silica beads. These beads bound to the macrophage (MO), and the extent of binding correlated with the density of gp63 on the bead. The bead thus facilitated analysis of the binding specificity of a single ligand, gp63, without contribution from other molecules present on the surface of intact promastigotes. Plating of MO onto substrates coated with antibodies directed against several cell surface receptors indicated that the complement receptor CR3 was necessary for binding gp63. CR3 recognizes a portion of C3 that contains the sequence R G D. Since gp63 also contains such a sequence, we tested the ability of a synthetic peptide based on the R G D-containing region of gp63 to inhibit the binding of gp63 beads. The R G D-containing peptide from gp63 inhibited the binding of both gp63 beads and EC3bi to MO. Similarly, peptides previously shown to inhibit the binding of C3bi also inhibited the attachment of gp63 beads. The synthetic peptide from the R G D region of gp63 also reduced the binding of intact promastigotes to MO. These results indicate that gp63 binds directly to CR3.