tbuckley/cabot-search huggingface dataset:
Antigen-induced aggregation and modulation of receptors on hapten-specific B lymphocytes.
Authors: G J Nossal, J E Layton
Journal: The Journal of Experimental Medicine (1976)

Mouse spleen cells were subjected to a fractionation procedure designed to enrich for 4-hydroxy-3-iodo-5-nitro-phenylacetyl (NIP)- or DNP-specific B lymphocytes, which depended on adherence of specific cells to a layer of hapten-gelatin at 4 degrees C, recovery of bound cells by melting, and digestion of adherent antigen by collagenase. A population of cells resulted which contained 90% typical B cells and 37% of cells capable of binding a fluorescent, haptenated polymeric protein. Fractionated cells were reacted in vitro with fluorescent conjugates of the specific haptens with polymerized flagellin [NIP-polymerized flagellin (POL)-tetramethylrhodamine isothiocyanate conjugate or DNP-POL-fluorescein isothiocyanate conjugate] under a variety of conditions, with the aim of investigating the behavior of Ig receptors on B lymphocytes after exposure to antigen; Experiments were performed with immunogenic and tolerogenic concentrations of antigen. Furthermore, four experimental designs were used, namely: (a) brief labeling with fluorescent antigen followed by culture without antigen (pulse design); (b) culture in the continuous presence of fluorescent antigen (continuous-labeling design); (c) culture in the continuous presence of nonlabeled antigen followed by labeling of unoccupied receptors by fluorescent antigen (receptor status design); and (d) culture with nonlabeled antigen for 2 h followed by incubation without further antigen for 20 h and labeling with fluorescent antigen (modulation design). Further insight into receptor occupancy and distribution was gained by the use of fluorescent antihapten and antiglobulin reagents. It was found that both immunogenic and tolerogenic antigen concentrations caused rapid patching and capping of the receptors to which they attached, followed by endocytosis and probably some shedding of Ig receptors. However, a proportion of cells continued to bear some cell surface antigen for 24 h. The immunogenic antigen concentration failed to completely remove the receptor coat from the cell surface. At all stages of immunogenesis, plentiful unoccupied receptors could be demonstrated. The tolerogenic concentration nearly saturated available receptors, and in its continuous presence, only few unoccupied or antigen-occupied surface receptors could be detected after 24 h of culture. Experiments of the modulation design showed that brief incubation with the tolerogenic concentration appeared to suppress receptor resynthesis, as few new receptors could be demonstrated after 20 h of further culture without antigen. Experiments were performed to determine whether fractionated cells prepared from spleens of 8-day-old mice showed an unusual tendency for modulation, even with immunogenic antigen concentrations. They were found to behave essentially like adult fractionated cells. The results are discussed in the framework of current theories of B-lymphocyte activation and tolerization.
Provision of Antioxidant Therapy in Hemodialysis (PATH)
Authors: Jonathan Himmelfarb, T. Alp Ikizler, Charles Ellis, Pingsheng Wu, Ayumi Shintani, Sanjay Dalal, Mark Kaplan, Michel Chonchol, Raymond M. Hakim
Journal: Journal of the American Society of Nephrology (2013)

Increased markers of oxidative stress and acute-phase inflammation are prevalent in patients undergoing maintenance hemodialysis therapy (MHD), and are associated with increased mortality and hospitalization rates and decreased erythropoietin responsiveness. No adequately powered studies have examined the efficacy of antioxidant therapies on markers of inflammation and oxidative stress. We tested the hypothesis that oral antioxidant therapy over 6 months would decrease selected biomarkers of acute-phase inflammation and oxidative stress and improve erythropoietic response in prevalent MHD patients. In total, 353 patients were enrolled in a prospective, placebo-controlled, double-blind clinical trial and randomly assigned to receive a combination of mixed tocopherols (666 IU/d) plus α-lipoic acid (ALA; 600 mg/d) or matching placebos for 6 months (NCT00237718); 238 patients completed the study. High-sensitivity C-reactive protein (hsCRP) and IL-6 concentration were measured as biomarkers of systemic inflammation, and F2 isoprostanes and isofurans were measured as biomarkers of oxidative stress. The groups did not significantly differ at baseline. At 3 and 6 months, the treatment had no significant effect on plasma hsCRP, IL-6, F2 isoprostane, or isofuran concentrations and did not improve the erythropoietic response. No major adverse events were related to the study drug, and both groups had similar mortality and hospitalization rates during the study. In conclusion, the administration of mixed tocopherols and ALA was generally safe and well tolerated, but did not influence biomarkers of inflammation and oxidative stress or the erythropoietic response.
Monocyte Subpopulations in Angiogenesis
Authors: Heather J. Dalton, Guillermo N. Armaiz-Pena, Vianey Gonzalez-Villasana, Gabriel Lopez-Berestein, Menashe Bar-Eli, Anil K. Sood
Journal: Cancer Research (2014)

Growing understanding of the role of the tumor microenvironment in angiogenesis has brought monocyte-derived cells into focus. Monocyte subpopulations are an increasingly attractive therapeutic target in many pathologic states, including cancer. Before monocyte-directed therapies can be fully harnessed for clinical use, understanding of monocyte-driven angiogenesis in tissue development and homeostasis, as well as malignancy, is required. Here, we provide an overview of the mechanisms by which monocytic subpopulations contribute to angiogenesis in tissue and tumor development, highlight gaps in our existing knowledge, and discuss opportunities to exploit these cells for clinical benefit.
The transcription factor RBP-J-mediated signaling is essential for dendritic cells to evoke efficient anti-tumor immune responses in mice
Authors: Fan Feng, Yao-Chun Wang, Xing-Bin Hu, Xiao-Wei Liu, Gang Ji, Yun-Ru Chen, Lin Wang, Fei He, Guo-Rui Dou, Liang Liang, Hong-Wei Zhang, Hua Han
Journal: Molecular Cancer (2010)

Abstract Background Dendritic cells (DCs) are professional antigen presenting cells that initiate specific immune responses against tumor cells. Transcription factor RBP-J-mediated Notch signaling regulates DC genesis, but whether this pathway regulates DC function in anti-tumor immunity remains unclear. In the present work we attempted to identify the role of Notch signaling in DC-mediated anti-tumor immune response. Results When DCs were co-inoculated together with tumor cells, while the control DCs repressed tumor growth, the RBP-J deficient DCs had lost tumor repression activity. This was most likely due to that DCs with the conditionally ablated RBP-J were unable to evoke anti-tumor immune responses in the solid tumors. Indeed, tumors containing the RBP-J deficient DCs had fewer infiltrating T-cells, B-cells and NK-cells. Similarly, the draining lymph nodes of the tumors with RBP-J -/- DCs were smaller in size, and contained fewer cells of the T, B and NK lineages, as compared with the controls. At the molecular level, the RBP-J deficient DCs expressed lower MHC II, CD80, CD86, and CCR7, resulting in inefficient DC migration and T-cell activation in vitro and in vivo. T-cells stimulated by the RBP-J deficient DCs did not possess efficient cytotoxicity against tumor cells, in contrast to the control DCs. Conclusion The RBP-J-mediated Notch signaling is essential for DC-dependent anti-tumor immune responses. The deficiency of RBP-J impairs the DC-based anti-tumor immunity through affecting series of processes including maturation, migration, antigen presentation and T-cell activation. The Notch signaling pathway might be a target for the establishment of the DC-based anti-tumor immunotherapies.
Transplantation Behavior of Hodgkin's-Like Reticulum Cell Neoplasms of Strain SJL/J Mice and Results of Tumor Reinoculation&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Edwin D. Murphy
Journal: JNCI Journal of the National Cancer Institute (1969)

The Hodgkin's-like reticulum cell neoplasms of SJL/J mice are malignant by cytological criteria and by the criteria of invasiveness and dissemination. However, they show unusual transplantation behavior. Of 20 spontaneous tumors transplanted to SJL/J hosts, 9 grew progressively in from 17–100% of animals in the first generation. Of these, 5 have grown for 69,45,41,6, and 3 generations, but not always in 100% of the animals. One failed to grow in the 28th generation, and one in the second. Two grew in the first and second generation, respectively, but were not transplanted further. Evidence for tumor-specific antigens has been obtained by reinoculation of the tumors in animals in which the tumors had previously failed to grow. Among 20 animals in which tumor T5205 failed to grow, reinoculation was successful in only 1 animal as compared with control growth in 95% of mice that had never been tumor hosts. Similarly, in (C57BL × SJL)F1 mice, reinoculation of T5205 was unsuccessful in 32 mice as compared with control growth in 75%. T5633 grew on reinoculation in only 2 of 23 mice as compared with 91% in controls. T5418 grew on reinoculation in 7 of 38 mice as compared with 68% in controls. In contrast, when 15 animals that had failed to grow T5418 were then inoculated with T5205, the latter grew in 93%, suggesting the existence of more than one specific antigen among these tumors. There was a lowered incidence of new spontaneous tumors in mice that had rejected T5633 and T5205.
Do changes in prescription practice in patients with rheumatoid arthritis treated with biological agents affect treatment response and adherence to therapy? Results from the nationwide Danish DANBIO Registry
Authors: M L Hetland, H M Lindegaard, A Hansen, J Podenphant, J Unkerskov, V S Ringsdal, M Ostergaard, U Tarp
Journal: Annals of the Rheumatic Diseases (2008)

Prescription practice for tumour necrosis factor alpha (TNFalpha) inhibitors has changed towards treating patients with lower disease activity.To determine the trend in treatment response in cohorts of patients with rheumatoid arthritis who started TNFalpha inhibitor treatment between 2000 and 2005.1813 patients with RA starting treatment with biological agents in 2000-5 were registered prospectively in the nationwide DANBIO Registry. Baseline disease activity and 12 months' treatment responses were determined in cohorts based on start year (2000/1; 2002; 2003; 2004; 2005).Despite decreasing baseline disease activity from the 2000/2001 cohort to 2005 cohort (28-joint count Disease Activity Score (DAS28): from 5.9 to 5.3 (p<0.001)), the 12 months' DAS improvement increased from 1.8 units (2000/2001 cohort) to 2.2 units (2005 cohort) (p<0.001). The fraction with good EULAR response increased from 28% (2000/2001 cohort) to 50% (2005 cohort); the fraction with no response decreased from 29% (2000/2001 cohort) to 16% (2005 cohort). ACR20/50/70 response rates increased from 53%/31%/13% (2000/2001 cohort) to 69%/51%/30% (2005 cohort). After correction for withdrawals, treatment responses were lower, but patterns unchanged. One-year drug survival was for the 2000/2001 cohort: 73%, 2002: 62%, 2003: 67%, 2004: 70%, 2005: 69%.From 2000 to 2005, significantly improved treatment responses to TNF inhibitors were seen in clinical practice despite decreasing baseline disease activity levels. This lends support to the less stringent prescription practice towards treating patients with lower disease activity that has been observed in several countries.
P276 Characterisation Of Reflux And Aspiration In Idiopathic Pulmonary Fibrosis; An Integrated Approach
Authors: R. Jones, A. Krishnan, G. Zeybel, J. Pearson, A. Simpson, S. Griffin, C. Ward, I. Forrest
Journal: Thorax (2014)

<h3>Background</h3> Idiopathic pulmonary fibrosis (IPF) is a progressive condition with limited treatment options and median survival of 3–5 years. Gastro-oesophageal reflux (GOR) has been described in up to 90% of patients. Pulmonary aspiration has been suggested to contribute to IPF, with calls for aggressive antireflux therapy. We investigated reflux and aspiration in an unselected IPF cohort. <h3>Methods</h3> Symptoms were assessed using a validated questionnaire. Patients with IPF underwent oesophageal manometry, pH-impedance analysis and a standardised bronchoalveolar lavage (BAL). Pepsin and bile salts were quantified in lavage supernatant using a validated ELISA and tandem mass spectrometry, respectively. Patient management was planned by an “aerodigestive” multidisciplinary team. <h3>Results</h3> 35 patients were studied. Oesophageal manometry suggested normal oesophageal function in 46%. pH-impedance demonstrated supranormal GOR in 24 patients (69%). In nine of these, the combination of clinical history and structured questionnaire revealed no evidence of GORD. BAL pepsin concentrations were higher than those measured in four healthy volunteer controls: median 9.0 ng/ml (range 0–35) vs 1.1 ng/ml (0–3); p = 0.02. Bile salt concentrations were comparable in the two groups. To date, none of these patients have undergone fundoplication. <h3>Discussion</h3> Oesophageal physiology and BAL assays may be combined to investigate reflux and aspiration in IPF. Our data suggest that acid reflux and weakly acid reflux is common and frequently asymptomatic. Our study suggests the need for carefully integrated assessments to inform potential treatment of reflux in IPF. High levels of oesophageal dysmotility and patient complexity support a cautious approach to antireflux surgery, which may be facilitated by multidisciplinary review.
Large-Scale Appearance of Ultraconserved Elements in Tetrapod Genomes and Slowdown of the Molecular Clock
Authors: S. Stephen, M. Pheasant, I. V. Makunin, J. S. Mattick
Journal: Molecular Biology and Evolution (2007)

Mammalian genomes contain millions of highly conserved noncoding sequences, many of which are regulatory. The most extreme examples are the 481 ultraconserved elements (UCEs) that are identical over at least 200 bp in human, mouse, and rat and show 96% identity with chicken, which diverged approximately 310 MYA. If the substitution rate in UCEs remained constant, these elements should also be present with a high level of identity in fish (approximately 450 Myr), but this is not the case, suggesting that many appeared in the amniotes or tetrapods or that the molecular clock has slowed down in these lineages, or both. Taking advantage of the availability of multiple genomes, we identified 13,736 UCEs in the human genome that are identical over at least 100 bp in at least 3 of 5 placental mammals, including 2,189 sequences over at least 200 bp, thereby greatly expanding the repertoire of known UCEs, and investigated the evolution of these sequences in opossum, chicken, frog, and fish. We conclude that there was a massive genome-wide acquisition and expansion of UCEs during tetrapod and then amniote evolution, accompanied by a slowdown of the molecular clock, particularly in the amniotes, a process consistent with their functional exaptation in these lineages. The majority of tetrapod-specific UCEs are noncoding and associated with genes involved in regulation of transcription and development. In contrast, fish genomes contain relatively few UCEs, the majority of which are common to all bony vertebrates. These elements are different from other conserved noncoding elements and appear to be important regulatory innovations that became fixed following the emergence of vertebrates from the sea to the land.
Time-dependent association of total serum cholesterol and cancer incidence in a cohort of 172 210 men and women: a prospective 19-year follow-up study
Authors: A. M. Strasak, R. M. Pfeiffer, L. J. Brant, K. Rapp, W. Hilbe, W. Oberaigner, S. Lang, W. Borena, H. Concin, G. Diem, E. Ruttmann, B. Glodny, K. P. Pfeiffer, H. Ulmer
Journal: Annals of Oncology (2009)
CRTH2 mediates the activation of human Th2 cells in response to PGD<sub>2</sub> released from IgE/anti‐IgE treated nasal polyp tissue
Authors: C. A. Pérez‐Novo, G. Holtappels, S. L. Vinall, L. Xue, N. Zhang, C. Bachert, R. Pettipher
Journal: Allergy (2009)

To cite this article: Pérez‐ Novo CA, Holtappels G, Vinall SL, Xue L, Zhang N, Bachert C, Pettipher R. CRTH2 mediates the activation of human Th2 cells in response to PGD 2 released from IgE/anti‐IgE treated nasal polyp tissue. Allergy 2010; 65 : 304–310. Abstract Background: Mast cells release mediators upon stimulation that contribute to the pathogenesis of chronic airway disease, including the recruitment and activation of Th2 lymphocytes. The objective was to determine the involvement of prostaglandin D 2 (PGD 2 ) and its receptors in the chemotaxis of Th2 cells, using nasal polyp tissue. Methods: Tissue explants from ten patients with nasal polyposis were incubated with RPMI alone or RPMI containing IgE/anti‐IgE for 30 min. Some samples were treated with diclofenac to inhibit the production of PGD 2 . Supernatants were assayed for PGD 2 content and for their ability to promote human Th2 cell chemotaxis in the presence and absence of a CRTH2 antagonist. Transcript levels of D protanoid receptor type 1 (DP 1 ), chemoattractant receptor‐homologous receptor expressed on Th2 cells (CRTH2) and PGD 2 synthase were analysed by real time PCR. Results: Increased release of PGD 2 by nasal polyp tissue treated with IgE/anti‐IgE was significantly inhibited by preincubation of the tissue with diclofenac. Transcript levels of PGD 2 synthase, DP 1 and CRTH2 receptors increased after stimulation with IgE/anti‐IgE. Supernatants from IgE/anti‐IgE‐stimulated nasal polyp tissue caused significantly increased chemotaxis of Th2 cells. The levels of PGD 2 produced and the degree of Th2 cell chemotaxis were highly correlated. Diclofenac inhibited the production of Th2 cell chemotactic activity, and the chemotactic effect of the supernatant on Th2 cells was inhibited by the CRTH2 antagonist ramatroban. Conclusion: These data suggest that in immunologically activated nasal polyp tissue, PGD 2 produced by mast cells promotes the migration of Th2 cells through a CRTH2 dependent mechanism.
The amino acid sequences of two alpha chains of hemoglobins from Komodo dragon Varanus komodoensis and phylogenetic relationships of amniotes
Authors: K. Fushitani, K. Higashiyama, E. N. Moriyama, K. Imai, K. Hosokawa
Journal: Molecular Biology and Evolution (1996)

To elucidate phylogenetic relationships among amniotes and the evolution of alpha globins, hemoglobins were analyzed from the Komodo dragon (Komodo monitor lizard) Varanus komodoensis, the world's largest extant lizard, inhabiting Komodo Islands, Indonesia. Four unique globin chains (alpha A, alpha D, beta B, and beta C) were isolated in an equal molar ratio by high performance liquid chromatography from the hemolysate. The amino acid sequences of two alpha chains were determined. The alpha D chain has a glutamine at E7 as does an alpha chain of a snake, Liophis miliaris, but the alpha A chain has a histidine at E7 like the majority of hemoglobins. Phylogenetic analyses of 19 globins including two alpha chains of Komodo dragon and ones from representative amniotes showed the following results: (1) The a chains of squamates (snakes and lizards), which have a glutamine at E7, are clustered with the embryonic alpha globin family, which typically includes the alpha D chain from birds; (2) birds form a sister group with other reptiles but not with mammals; (3) the genes for embryonic and adult types of alpha globins were possibly produced by duplication of the ancestral alpha gene before ancestral amniotes diverged, indicating that each of the present amniotes might carry descendants of the two types of alpha globin genes; (4) squamates first split off from the ancestor of other reptiles and birds.
New Genetic Evidence Resolves Origins of Modern Japanese
Authors: Joseph Caspermeyer
Journal: Molecular Biology and Evolution (2015)

Was there a single migration event or gradual mixing of cultures that gave rise to modern Japanese? According to current theory, about 2,000–3,000 years ago, two populations, the hunter-gatherer Jomon from the Japanese archipelago and the agricultural Yayoi from continental East Asia, intermingled to give rise to the modern Japanese population. However, some researchers have suggested otherwise, with the Jomon culture gradually transformed into the Yayoi culture without large migrations into modern day Japan. To resolve the controversy, researchers Nakagome et al. (2015) identified the differences between the Ainu people (direct descendants of indigenous Jomon) with Chinese from Beijing (same ancestry as Yayoi). The results from ag enome-wide, single nucleotide polymorphism data strongly support the hybridization model as the best fit for Japanese population history. An initial divergence between the Ainu and Beijing group was dated to approximately 20,000 years ago, whereas evidence of genetic mixing occurred 5,000–7,000 years ago, older than estimates from the archaeological records, probably due to the effect of a further subpopulation structure of the Jomon people. The authors caution that further studies will need to be undertaken (especially ancient genome analysis of Jomon and Yayoi skeletal remains and genomic analysis of northeast Asians) to untangle the true evolutionary history of Japanese, in particular, the origins of the Jomon and Yayoi people and the source of gene flow to the Ainu. Reference
Effects of ouabain and vagal stimulation on sinus nodal function in conscious dogs.
Authors: R J Hariman, B F Hoffman
Journal: Circulation Research (1982)

We studied the effects of intravenous ouabain administration (15 micrograms/kg) and vagal stimulation on instrumented conscious dogs. In these dogs, a special electrode was implanted on the epicardial surface over the sinus node and plaque electrodes were placed on the superior vena cava and left atrial appendage. Unipolar sinus electrograms were recorded through the terminals of the sinus electrode paired with the superior vena caval electrode. An electrode also was implanted around the desheathed cervical vagosympathetic trunk, and a coiled polyethylene tube with side holes was implanted cranial to it. Ouabain administration resulted in: (1) an increase in the sinus cycle lengths and sinoatrial intervals and increase in beat-to-beat variation of the sinus cycles and sinoatrial intervals, and (2) periods of sinus pacemaker shift, sinus arrest and sinoatrial block that occurred spontaneously or after atrial overdrive stimulation delivered through the electrode on the left atrial appendage. These effects of ouabain were abolished by intravenous administration of atropine (2 mg). Prior to vagal stimulation, intravenous propranolol (0.5 mg/kg) was administered to block sympathetic responses and 0.75% bupivacaine was injected through the polyethylene tube to block afferent transmission. Vagal stimulation in conscious dogs resulted in two types of responses: (1) slowing of sinus pacemaker rate accompanied by a decrease in diastolic slope and followed by sinus pacemaker shifts, and (2) gradual prolongation of the sinoatrial intervals followed by failure of sinoatrial conduction. An intravenous bolus of acetylcholine (0.1 mg) resulted in a response of type 2 in dogs in which vagal stimulation produced a response of type 1. The marked similarity between the effects of ouabain and vagal stimulation on sinus function and the abolition of the effects of ouabain by atropine suggest that the ouabain effects are vagally mediated.
Residual vitreous cortex after surgical posterior vitreous separation visualized by intravitreous triamcinolone acetonide
Authors: Koh-Hei Sonoda, Taiji Sakamoto, Hiroshi Enaida, Miho Miyazaki, Yoshihiro Noda, Takao Nakamura, Akifumi Ueno, Mitsunobu Yokoyama, Toshiaki Kubota, Tatsuro Ishibashi
Journal: Ophthalmology (2004)