tbuckley/cabot-search huggingface dataset:
Deduced amino acid sequences of class 1 protein (PorA) from three strains of Neisseria meningitidis. Synthetic peptides define the epitopes responsible for serosubtype specificity.
Authors: B McGuinness, A K Barlow, I N Clarke, J E Farley, A Anilionis, J T Poolman, J E Heckels
Journal: The Journal of Experimental Medicine (1990)

The previously determined nucleotide sequence of the porA gene, encoding the class 1 outer membrane protein of meningococcal strain MC50, has been used to clone and sequence the porA gene from two further strains with differing serosubtype specificities. Comparison of the predicted amino acid sequences of the three class 1 proteins revealed considerable structural homology with major variation confined to two discrete regions (VR1 and VR2). The high degree of structural homology between the sequences gave predicted secondary structures that were almost identical, with the variable domains located in hydrophilic regions that are likely to be surface located and hence accessible to antibody binding. The predicted amino acid sequences have been used to define the epitopes recognized by mAbs with serosubtype specificity. A series of overlapping decapeptides spanning each of the class 1 protein sequences have been synthesized on solid-phase supports and probed with mAbs. Antibodies with P1.16 and P1.15 subtype specificity reacted with sequences in the VR2 domain, while antibodies with P1.7 subtype specificity reacted with sequences in the VR1 domain. Further peptides have been constructed to define the minimum epitopes recognized by each antibody. Thus we have been able to define linear peptides on each class 1 protein molecule that are responsible for subtype specificity and that represent targets for a protective immune response.
834 REDUCTION OF MIR-122 EXPRESSION IS ASSOCIATED WITH IL28B RS12979860 TT POLYMORPHISM AND IS INDEPENDENT OF SUSTAINED VIROLOGICAL RESPONSE IN PATIENTS WITH CHRONIC HEPATITIS C
Authors: E. Estrabaud, S. De Muynck, M. Lapalus, O. Lada, M. Martinot-Peignoux, I. Bieche, P. Bedossa, P. Marcellin, M. Vidaud, T. Asselah
Journal: Journal of Hepatology (2012)
Elite athletes travelling to international destinations &gt;5 time zone differences from their home country have a 2–3-fold increased risk of illness
Authors: Martin P Schwellnus, Wayne Elton Derman, Esme Jordaan, Tony Page, Mike Ian Lambert, Clint Readhead, Craig Roberts, Ryan Kohler, Robert Collins, Stephen Kara, Michael Ian Morris, Org Strauss, Sandra Webb
Journal: British Journal of Sports Medicine (2012)

Illness accounts for a significant proportion of consultations with a team physician travelling with elite athletes.To determine if international travel increases the incidence of illness in rugby union players participating in a 16-week tournament.2010 Super 14 Rugby Union tournament.259 elite rugby players from eight teams were followed daily over the 16-week competition period (22 676 player-days).Team physicians completed a logbook detailing the daily squad size and illness in any player (system affected, final diagnosis, type and onset of symptoms, training/match days lost and suspected cause) with 100% compliance. Time periods during the tournament were divided as follows: located and playing in the home country before travelling (baseline), located and playing abroad in countries >5 h time zone difference (travel) and located back in the home country following international travel (return).Incidence of illness (illness per 1000 player-days) during baseline, travel and return.The overall incidence of illness in the cohort was 20.7 (95% CI 18.5 to 23.1). For all teams, the incidence of illness according to location and travelling was significantly higher in the time period following international travel (32.6; 95% CI 19.6 to 53.5) compared with the baseline (15.4; 95% CI 8.7 to 27.0) or after returning to their home country (10.6; 95% CI 6.1 to 18.2).There is a higher incidence of illness in athletes following international travel to a foreign country that is >5 h time difference and this returns to baseline on return to the home country.
Validation of assays for inflammatory mediators in exhaled breath condensate
Authors: D. L. Bayley, H. Abusriwil, A. Ahmad, R. A. Stockley
Journal: European Respiratory Journal (2008)

The use of exhaled breath condensate (EBC) as a tool for noninvasive assessment of lung inflammation is becoming commonplace. Many authors use commercial ELISA kits to measure inflammatory mediators within EBC. However, the very low concentrations of mediators within EBC are often below the commercially validated concentration range of the relevant ELISA and crucially below the linear part of the sigmoid standard curve. The present study seeks to validate a series of assays for use in EBC and to compare the results in EBC with those from matched sol phase sputum samples. The following mediators were measured by ELISA: leukotriene (LT)B<sub>4</sub>, interleukin (IL)-8, secretory leukoprotease inhibitor and α<sub>1</sub>-antitrypsin (AAT). Myeloperoxidase was measured by chromogenic substrate assay. Mediator concentrations reached the lower limit of quantification in only one assay (AAT) in 19.6% of subjects, while mediator concentrations reached the lower limit of detection in three assays (LTB<sub>4</sub>, IL-8 and AAT in 31, 6.5 and 61% of subjects, respectively). No significant correlations were present between any mediators in EBC and sol phase sputum. The results of the present study indicate that care must be exercised when interpreting mediator measurements in exhaled breath condensate and that assays must be validated at concentrations relevant to those found within the biological fluid.
Immunological functions of the gut in relation to nutritional state and mode of delivery of nutrients.
Authors: A Ferguson
Journal: Gut (1994)

Gut immunology encompasses the need for local cellular immunity and prevention of systemic immune reactions to dietary antigens. The relation between these factors and nutritional state or the presence of luminal nutrients in the enterally fed and parenterally fed is poorly defined. Most studies suggest that acquisition of lymphoid characteristics is independent of luminal nutrition and its responsiveness is related more to bacterial challenge. Protein malnutrition may impair immune responsiveness by moderating the generalised inflammatory response, rather than through reduced T cell function and IgA synthesis. Predisposition to the development of gut hypersensitivity can be induced in animals by longterm feeding with elemental diets. The efficient absorption of these diets reduces the caecal microflora burden and together with changed gastric acid secretion and small bowel motility, may affect the composition of the gut flora. Changed luminal nutrition, enhanced tissue damage and inappropriately increased mucosal T cell function may thus be related. The clinical effectiveness, however, of elemental diets in treatment of unresponsive coeliac disease is reassuring. To investigate intestinal immunity in humans, an approach based on whole gut lavage has been developed. Data from this non-invasive human technique will prove to be a useful means of assessing the effects of nutritional rehabilitation on mucosal immunity.
Lenalidomide-Induced Immunomodulation in Multiple Myeloma: Impact on Vaccines and Antitumor Responses
Authors: Kimberly Noonan, Lakshmi Rudraraju, Anna Ferguson, Amy Emerling, Marcela F. Pasetti, Carol A. Huff, Ivan Borrello
Journal: Clinical Cancer Research (2012)

To show that the immunomodulatory drug lenalidomide can be used in patients with relapsed multiple myeloma to augment vaccine responses.Early phase clinical trial of patients with multiple myeloma who received at least one prior therapy. Patients were treated with single-agent lenalidomide and randomized to receive two vaccinations with pneumococcal 7-valent conjugate vaccine (PCV) on different schedules. Cohort A received the first PCV vaccination prior to the initiation of lenalidomide and the second vaccination while on lenalidomide. Cohort B received both vaccinations while on lenalidomide.PCV-specific humoral and cellular responses were greater in cohort B than A and were more pronounced in the bone marrow than the blood, suggesting that maximal vaccine efficacy was achieved when both vaccines were administered concomitantly with lenalidomide. Patients with a clinical myeloma response showed evidence of a tumor-specific immune response with increases in myeloma-specific IFN-γ(+) T cells and reductions in Th-17 cells.This is the first clinical evidence showing that lenalidomide augments vaccine responses and endogenous antitumor immunity in patients and as such may serve as an adjuvant for cancer and possibly infectious vaccines.
Podocyte Purinergic P2X4 Channels Are Mechanotransducers That Mediate Cytoskeletal Disorganization
Authors: Anna-Lena Forst, Vlad Sorin Olteanu, Géraldine Mollet, Tanja Wlodkowski, Franz Schaefer, Alexander Dietrich, Jochen Reiser, Thomas Gudermann, Michael Mederos y Schnitzler, Ursula Storch
Journal: Journal of the American Society of Nephrology (2015)

Podocytes are specialized, highly differentiated epithelial cells in the kidney glomerulus that are exposed to glomerular capillary pressure and possible increases in mechanical load. The proteins sensing mechanical forces in podocytes are unconfirmed, but the classic transient receptor potential channel 6 (TRPC6) interacting with the MEC-2 homolog podocin may form a mechanosensitive ion channel complex in podocytes. Here, we observed that podocytes respond to mechanical stimulation with increased intracellular calcium concentrations and increased inward cation currents. However, TRPC6-deficient podocytes responded in a manner similar to that of control podocytes, and mechanically induced currents were unaffected by genetic inactivation of TRPC1/3/6 or administration of the broad-range TRPC blocker SKF-96365. Instead, mechanically induced currents were significantly decreased by the specific P2X purinoceptor 4 (P2X4) blocker 5-BDBD. Moreover, mechanical P2X4 channel activation depended on cholesterol and podocin and was inhibited by stabilization of the actin cytoskeleton. Because P2X4 channels are not intrinsically mechanosensitive, we investigated whether podocytes release ATP upon mechanical stimulation using a fluorometric approach. Indeed, mechanically induced ATP release from podocytes was observed. Furthermore, 5-BDBD attenuated mechanically induced reorganization of the actin cytoskeleton. Altogether, our findings reveal a TRPC channel-independent role of P2X4 channels as mechanotransducers in podocytes.
Identification of CD8+CD25+Foxp3+ suppressive T cells in colorectal cancer tissue
Authors: N Chaput, S Louafi, A Bardier, F Charlotte, J-C Vaillant, F Menegaux, M Rosenzwajg, F Lemoine, D Klatzmann, J Taieb
Journal: Gut (2008)

<h3>Background:</h3> The antitumoral immune response is one determinant of colorectal cancer (CRC) outcome. Recent work suggests that Foxp3<sup>+</sup>CD25<sup>+</sup>CD4<sup>+</sup> regulatory T cells (T4reg) might hamper effective immunosurveillance of emerging cancer cells and impede effective immune responses to established tumours. In this descriptive study, we analysed blood and tissue regulatory T cell populations in patients with CRC. <h3>Methods:</h3> Blood and tissue regulatory Foxp3<sup>+</sup> T cells from 40 patients with CRC were compared to regulatory Foxp3<sup>+</sup> T cells from normal colonic tissue and from blood of 26 healthy volunteers. Flow cytometry was used to quantify and phenotype all Foxp3<sup>+</sup> T cell populations. Correlations were sought with the tumour stage and with micro-invasive status. The suppressive capacity of regulatory Foxp3<sup>+</sup> T cells was assessed by their effect on CD4<sup>+</sup>CD25<sup>−</sup> T cell proliferation in vitro and by their capacity to inhibit cytokine production by conventional T cells. <h3>Results:</h3> We found a significant increase of CD8<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> cells (T8reg) in blood and CRC tissue; their phenotype was close to that of T4reg. T8reg cells infiltrating CRC were activated, as suggested by increased cytoxic T lymphocyte-associated antigen-4, glucocorticoid-induced tumour necrosis factor-related protein, and transforming growth factor (TGF)β1 expression compared to T8reg from normal autologous colonic tissue. Moreover, T8reg were able to suppress CD4<sup>+</sup>CD25<sup>−</sup> T cell proliferation and Th1 cytokine production ex vivo, demonstrating that tumour-infiltrating T8reg have strong suppressive capacities. T8reg numbers correlated with the tumour stage and with micro-invasive status. Finally, interleukin 6 and TGFβ1 synergistically induced the generation of CD8<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> T cells ex vivo. <h3>Conclusions:</h3> We have identified a new regulatory T cell population (CD8<sup>+</sup>Foxp3<sup>+</sup>) in colorectal tumours. After isolation from cancer tissue these CD8<sup>+</sup>Foxp3<sup>+</sup> cells demonstrated strong immunosuppressive properties in vitro. These data suggest that these cells may contribute to tumoral immune escape and disease progression.
RECOMBINATION OF HEAVY AND LIGHT CHAINS OF HUMAN γA-MYELOMA PROTEINS: FORMATION OF HYBRID MOLECULES AND CONFIGURATIONAL SPECIFICITY
Authors: Robert A. Prendergast, Howard M. Grey, Henry G. Kunkel
Journal: The Journal of Experimental Medicine (1966)

The present studies demonstrate that the conditions necessary for reductive cleavage, isolation, and recombination of L and H polypeptide chains of human gammaA-myeloma globulins parallel those required for similar manipulation of the component chains of gammaG-globulin. Specificity of recombination was shown for chains derived from the same protein. In contrast, no intradass preferential recombination was demonstrable. Hybrid molecules, formed by reassociation of noncovalent bonds, could be synthesized from isolated chains of two immunoglobulin classes resulting in the formation of molecules of the type gammaA-H-gammaG-L and gammaG-H-gammaA-L. Several sera containing both gammaA- and gammaG-"monoclonal" peaks were studied, one of which demonstrated the L chains associated with both peaks to be identical both by electrophoretic mobility in acid-urea gel and antigenic analysis. The possibility is considered that this case represents a naturally occurring analogue of the artificially produced hybrid molecules described in this study. Configurational antigenic specificity of gammaA-myeloma proteins, imposed by the presence of kappa L chains in native and appropriately recombined molecules, provides a further indication of the importance of noncovalent bonds in the establishment of the quaternary structure of these proteins.
Secondary Prevention of Venous Thromboembolism with the Oral Direct Thrombin Inhibitor Ximelagatran
Authors: Sam Schulman, Karin Wåhlander, Torbjörn Lundström, Solveig Billing Clason, Henry Eriksson
Journal: New England Journal of Medicine (2003)

For many patients with venous thromboembolism, secondary prevention with vitamin K antagonists is not extended beyond six months, since the risk of recurrence may be outweighed by the risk of major bleeding.
Pleiotrophin regulates the ductular reaction by controlling the migration of cells in liver progenitor niches
Authors: Gregory A Michelotti, Anikia Tucker, Marzena Swiderska-Syn, Mariana Verdelho Machado, Steve S Choi, Leandi Kruger, Erik Soderblom, J Will Thompson, Meredith Mayer-Salman, Heather A Himburg, Cynthia A Moylan, Cynthia D Guy, Katherine S Garman, Richard T Premont, John P Chute, Anna Mae Diehl
Journal: Gut (2015)

<h3>Objective</h3> The ductular reaction (DR) involves mobilisation of reactive-appearing duct-like cells (RDC) along canals of Hering, and myofibroblastic (MF) differentiation of hepatic stellate cells (HSC) in the space of Disse. Perivascular cells in stem cell niches produce pleiotrophin (PTN) to inactivate the PTN receptor, protein tyrosine phosphatase receptor zeta-1 (PTPRZ1), thereby augmenting phosphoprotein-dependent signalling. We hypothesised that the DR is regulated by PTN/PTPRZ1 signalling. <h3>Design</h3> PTN-GFP, PTN-knockout (KO), PTPRZ1-KO, and wild type (WT) mice were examined before and after bile duct ligation (BDL) for PTN, PTPRZ1 and the DR. RDC and HSC from WT, PTN-KO, and PTPRZ1-KO mice were also treated with PTN to determine effects on downstream signaling phosphoproteins, gene expression, growth, and migration. Liver biopsies from patients with DRs were also interrogated. <h3>Results</h3> Although quiescent HSC and RDC lines expressed PTN and PTPRZ1 mRNAs, neither PTN nor PTPRZ1 protein was demonstrated in healthy liver. BDL induced PTN in MF-HSC and increased PTPRZ1 in MF-HSC and RDC. In WT mice, BDL triggered a DR characterised by periportal accumulation of collagen, RDC and MF-HSC. All aspects of this DR were increased in PTN-KO mice and suppressed in PTPRZ1-KO mice. In vitro studies revealed PTN-dependent accumulation of phosphoproteins that control cell-cell adhesion and migration, with resultant inhibition of cell migration. PTPRZ1-positive cells were prominent in the DRs of patients with ductal plate defects and adult cholestatic diseases. <h3>Conclusions</h3> PTN, and its receptor, PTPRZ1, regulate the DR to liver injury by controlling the migration of resident cells in adult liver progenitor niches.
Clinical and scintigraphic assessment of the role of endoscopic sphincterotomy in the treatment of sphincter of Oddi dysfunction.
Authors: G M Fullarton, T Hilditch, A Campbell, W R Murray
Journal: Gut (1990)

Postcholecystectomy pain caused by sphincter of Oddi dysfunction remains a difficult condition to treat. Endoscopic sphincterotomy has been recommended for those patients with confirmed sphincter of Oddi motor abnormalities. We have studied sphincter of Oddi dysfunction patients to evaluate the effects of endoscopic sphincterotomy on both clinical symptoms and previously reported scintigraphic parameters to determine the efficacy of this method of treatment. Nine postcholecystectomy patients (seven women: two men, median age 59 years) with clinical and manometric evidence of sphincter of Oddi dysfunction underwent endoscopic sphincterotomy for persisting biliary type pain. Each patient had scintigraphy before and eight weeks after endoscopic sphincterotomy. The patients symptomatic response was assessed independently at three monthly intervals after endoscopic sphincterotomy. Scintigraphic analysis showed that the TMAX (time in minutes to maximum counts) was significantly reduced from 25.0 (20-36) (median [range]) before endoscopic sphincterotomy to 15.0 (13-25) after endoscopic sphincterotomy (p less than 0.01). Seven of nine (78%) sphincter of Oddi dysfunction patients had significant improvement in their symptoms after a mean follow up period of 12 months (range 6-19) although only six of nine were totally pain free. These results suggest that endoscopic sphincterotomy in manometrically confirmed sphincter of Oddi dysfunction improves bile drainage as measured by quantitative cholescintigraphy and is associated with at least short term symptom relief in the majority of patients.
The Goulstonian Lectures on Some Cerebral Lesions
Authors: G. N. Pitt
Journal: BMJ (1890)

OTORRHEA is but too frequently looked upon as a troublesome complaint that must be endured, and when patients have had a discharge which has persisted for many years in spite of all treatment, they, at any rate, if not their medical attendant as well, are apt to con3ider that they have done with it, that it is hopeless for them to trouble any more about it, and that it will never alter.Yet there can be no greater mistake, for occasionally, under some exciting condition, the inflammation spreads to the cranial cavity, the patient rapidly becomes mortally ill, and in many instances dies after an illness of a few days', or it may be some weeks', duration.
IL-10–producing NKT10 cells are a distinct regulatory invariant NKT cell subset
Authors: Duygu Sag, Petra Krause, Catherine C. Hedrick, Mitchell Kronenberg, Gerhard Wingender
Journal: Journal of Clinical Investigation (2014)

Invariant natural killer T (iNKT) cells rapidly produce copious amounts of multiple cytokines after activation, thereby impacting a wide variety of different immune reactions. However, strong activation of iNKT cells with α-galactosylceramide (αGalCer) reportedly induces a hyporeactive state that resembles anergy. In contrast, we determined here that iNKT cells from mice pretreated with αGalCer retain cytotoxic activity and maintain the ability to respond to TCR-dependent as well as TCR-independent cytokine-mediated stimulation. Additionally, αGalCer-pretreated iNKT cells acquired characteristics of regulatory cells, including production and secretion of the immunomodulatory cytokine IL-10. Through the production of IL-10, αGalCer-pretreated iNKT cells impaired antitumor responses and reduced disease in experimental autoimmune encephalomyelitis, a mouse model of autoimmune disease. Furthermore, a subset of iNKT cells with a similar inhibitory phenotype and function were present in mice not exposed to αGalCer and were enriched in mouse adipose tissue and detectable in human PBMCs. These data demonstrate that IL-10–producing iNKT cells with regulatory potential (NKT10 cells) represent a distinct iNKT cell subset.
Infant pulmonary hemorrhage in a suburban home with water damage and mold (Stachybotrys atra).
Authors: S M Flappan, J Portnoy, P Jones, C Barnes
Journal: Environmental Health Perspectives (1999)

The American Academy of Pediatrics recently issued guidelines regarding the potential toxic effect of indoor molds. We now report another case of an infant with pulmonary hemorrhage whose residential environmental assessment revealed the presence of the toxigenic mold Stachybotrys atra. We used a questionnaire to identify environmental factors that could predispose the home to fungal contamination. We collected air samples from multiple locations in the home that we felt would reflect areas of relevant exposure. Surface samples were collected with a piece of transparent tape for semiquantitative measurement of spores present. We classified spores into their respective genera based on shape, size, and color. We also measured mycotoxin levels. Air sampling revealed significantly elevated total spore counts in the patient's bedroom and in the attic. Aspergillus/Penicillium species were predominant. Stachybotrys spores were found in the air sampled in the patient's bedroom, as well as from surfaces sampled in the patient's closet and the attic ceiling. Additionally, a small patch of Stachybotrys-contaminated area in the closet ceiling was sent for mycotoxin analysis. This material proved to be highly toxigenic. As the link between the presence of Stachybotrys in the home and pulmonary hemorrhage in infants increases, further efforts should be made to educate physicians, health care providers, and new parents about the potential toxic effects of this mold.