tbuckley/cabot-search huggingface dataset:
Lateral Symbiont Acquisition in a Maternally Transmitted Chemosynthetic Clam Endosymbiosis
Authors: F. J. Stewart, C. R. Young, C. M. Cavanaugh
Journal: Molecular Biology and Evolution (2008)

Deep-sea clams of the family Vesicomyidae live in symbiosis with intracellular chemosynthetic bacteria. These symbionts are transmitted maternally (vertically) between host generations and should therefore show a pattern of genetic variation paralleling that of the cotransmitted host mitochondrion. However, instances of lateral (nonvertical) symbiont acquisition could still occur, thereby decoupling symbiont and mitochondrial phylogenies. Here, we provide the first evidence against strict maternal cotransmission of symbiont and mitochondrial genomes in vesicomyids. Analysis of Vesicomya sp. mt-II clams from hydrothermal vents on the Juan de Fuca Ridge (northeastern Pacific) revealed a symbiont phylotype (designated symB(VII)) highly divergent from previously described symbionts of the same host lineage. SymB(VII)-hosting clams occurred at low frequency (0.02) relative to individuals hosting the dominant symbiont phylotype. Phylogenetic analysis of 16S rRNA genes from a wide range of symbionts and free-living bacteria clustered symB(VII) within the monophyletic clade of vesicomyid symbionts. Further analysis of 3 symbiont loci (23S, dnaK, and soxA) across 11 vesicomyid taxa unambiguously placed symB(VII) as sister to the symbiont of a distantly related host lineage, Vesicomya sp. from the Mid-Atlantic Ridge (98.9% median nucleotide identity across protein-coding loci). Using likelihood and Bayesian model discrimination methods, we rejected the strict maternal cotransmission hypothesis by showing a significant decoupling of symbiont and host mitochondrial (COI and mt16S genes) phylogenies. Indeed, decoupling occurred even when symB(VII) was excluded from phylogenetic reconstructions, suggesting a history of host switching in this group. Together, the data indicate a history of lateral symbiont transfer in vesicomyids, with symB(VII) being the most conspicuous example. Interpreted alongside previous studies of the vesicomyid symbiosis, these results suggest a mixed mode of symbiont transmission characterized by predominantly vertical transmission punctuated with instances of lateral symbiont acquisition. Lateral acquisition may facilitate the exchange of genetic material (recombination) among divergent symbiont lineages, rendering the evolutionary history of vesicomyid symbiont genomes much more complex than previously thought.
Selective Suppression of Interleukin-12 Induction after Macrophage Receptor Ligation
Authors: Fayyaz S. Sutterwala, Gary J. Noel, Raphael Clynes, David M. Mosser
Journal: The Journal of Experimental Medicine (1997)

Interleukin (IL)-12 is a monocyte- and macrophage-derived cytokine that plays a crucial role in both the innate and the acquired immune response. In this study, we examined the effects that ligating specific macrophage receptors had on the induction of IL-12 by lipopolysaccharide (LPS). We report that ligation of the macrophage Fcγ, complement, or scavenger receptors inhibited the induction of IL-12 by LPS. Both mRNA synthesis and protein secretion were diminished to near-undetectable levels following receptor ligation. Suppression was specific to IL-12 since IL-10 and tumor necrosis factor-α (TNF-α) production were not inhibited by ligating macrophage receptors. The results of several different experimental approaches suggest that IL-12 downregulation was due to extracellular calcium influxes that resulted from receptor ligation. First, preventing extracellular calcium influxes, by performing the assays in EGTA, abrogated FcγR-mediated IL-12(p40) mRNA suppression. Second, exposure of macrophages to the calcium ionophores, ionomycin or A23187, mimicked receptor ligation and inhibited IL-12(p40) mRNA induction by LPS. Finally, bone marrow–derived macrophages from FcR γ chain–deficient mice, which fail to flux calcium after receptor ligation, failed to inhibit IL-12(p40) mRNA induction. These results indicate that the calcium influxes that occur as a result of receptor ligation are responsible for inhibiting the induction of IL-12 by LPS. Hence, the ligation of phagocytic receptors on macrophages can lead to a dramatic decrease in IL-12 induction. This downregulation may be a way of limiting proinflammatory responses of macrophages to extracellular pathogens, or suppressing the development of cell-mediated immunity to intracellular pathogens.
In vivo antigen delivery by aSalmonella typhimurium type III secretion system for therapeutic cancer vaccines
Authors: H. Nishikawa
Journal: Journal of Clinical Investigation (2006)

Bacterial vectors may offer many advantages over other antigen delivery systems for cancer vaccines. We engineered a Salmonella typhimuriumvaccine strain to deliver the NY-ESO-1 tumor antigen (S. typhimurium–NY-ESO-1) through a type III protein secretion system. The S. typhimurium–NY-ESO-1 construct elicited NY-ESO-1–specific CD8+ and CD4+ T cells from peripheral blood lymphocytes ofcancer patients in vitro. Oral administration of S. typhimurium–NY-ESO-1 to mice resulted in the regression of established NY-ESO-1–expressing tumors. Intratumoral inoculation of S. typhimurium–NY-ESO-1 to NY-ESO-1–negative tumors resulted in delivery of antigen in vivo and led to tumor regression in the presence of preexisting NY-ESO-1–specific CD8+ T cells. Specific T cell responses against at least 2 unrelated tumor antigens not contained in the vaccine were observed, demonstrating epitope spreading. We propose that antigen delivery through the S. typhimuriumtype III secretion system is a promising novel strategy for cancer vaccine development.
Requirement of Essential Fatty Acids in the Diet for Development of the Mouse Mammary Gland2
Authors: Richard A. Knazek, Sue C. Liu, Jeffrey S. Bodwin, Barbara K. Vonderhaar
Journal: JNCI Journal of the National Cancer Institute (1980)

Journal Article Requirement of Essential Fatty Acids in the Diet for Development of the Mouse Mammary Gland Get access Richard A. Knazek, Richard A. Knazek 4 3Laboratory of Pathophysiology, Division of Cancer Biology and Diagnosis, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare, Bethesda, Md. 20205. 4Address reprint requests to Dr. Knazek at Bldg. 10, Rm. 5B36, National Cancer Institute. Search for other works by this author on: Oxford Academic PubMed Google Scholar Sue C. Liu, Sue C. Liu 3Laboratory of Pathophysiology, Division of Cancer Biology and Diagnosis, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare, Bethesda, Md. 20205. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jeffrey S. Bodwin, Jeffrey S. Bodwin 3Laboratory of Pathophysiology, Division of Cancer Biology and Diagnosis, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare, Bethesda, Md. 20205. Search for other works by this author on: Oxford Academic PubMed Google Scholar Barbara K. Vonderhaar Barbara K. Vonderhaar 3Laboratory of Pathophysiology, Division of Cancer Biology and Diagnosis, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare, Bethesda, Md. 20205. 5We thank Miss. A. E. Greco, Dr. E. B. Gould, Mr. R. H. Lewis, Mr. R. L. Graeter, Miss J. R. Mayer, Mr. P. C. Wright, Miss J. A. Keller, Miss K. E. Nickols, Mr. M. J. Gillogley, Miss D. Barrett, Mr. D. L. Whitcomb, Mr. K. W. Wolfe, Dr. M. Wicha, Dr. W. R. Kidwell, and Dr. P. M. Gullino for their assistance. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 64, Issue 2, February 1980, Pages 377–382, https://doi.org/10.1093/jnci/64.2.377 Published: 01 February 1980 Article history Received: 07 May 1979 Accepted: 16 August 1979 Published: 01 February 1980
Anti-CarP antibodies in two large cohorts of patients with rheumatoid arthritis and their relationship to genetic risk factors, cigarette smoking and other autoantibodies
Authors: Xia Jiang, Leendert A Trouw, Tineke J van Wesemael, Jing Shi, Camilla Bengtsson, Henrik Källberg, Vivi Malmström, Lena Israelsson, Hulda Hreggvidsdottir, Willem Verduijn, Lars Klareskog, Lars Alfredsson, Tom W J Huizinga, Rene E M Toes, Karin Lundberg, Diane van der Woude
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Introduction</h3> In rheumatoid arthritis (RA), several genetic risk factors and smoking are strongly associated with the presence of anticitrullinated protein antibodies (ACPA), while much less is known about risk factors for ACPA-negative RA. Antibodies against carbamylated proteins (anti-CarP) have been described in both ACPA-positive and ACPA-negative RA patients. In this study, we have analysed the relationships among anti-CarP antibodies, ACPA, genetic risk factors (<i>HLA-DRB1</i> alleles and <i>PTPN22</i>) and smoking in RA. <h3>Methods</h3> Presence of antibodies to carbamylated fetal calf serum (CarP-FCS) and fibrinogen (CarP-Fib) was determined by inhouse ELISAs among RA cases in the Leiden Early Arthritis Clinic (n=846) and in the Swedish Epidemiological Investigation of Rheumatoid Arthritis (n=1985) cohorts. ORs for associations with different <i>HLA-DRB1</i> alleles, <i>PTPN22</i> genotypes and smoking were calculated separately for each cohort as well as in meta-analysis in RA subsets defined by the presence/absence of anti-CarP and anticyclic citrullinated peptide (anti-CCP) antibodies. <h3>Results</h3> In both cohorts, anti-CarP antibody positivity was mainly detected in the anti-CCP-positive population (49%–73%), but also in the anti-CCP-negative population (8%–14%). No associations between anti-CarP antibodies and <i>HLA-DRB1</i> shared epitope alleles could be identified, while there were data to support an association between anti-CarP-FCS and <i>HLA-DRB1*</i>03. Further analyses did not reveal any specific associations of anti-CarP antibodies with other <i>HLA-DRB1</i> alleles, <i>PTPN22</i> genotypes or smoking. <h3>Conclusions</h3> Anti-CarP antibodies were present in both ACPA-positive and ACPA-negative RA. There were no significant associations among anti-CarP antibodies and <i>HLA-DRB1</i> alleles, <i>PTPN22</i> or smoking. These data suggest that different biological mechanisms may underlie anti-CarP versus anti-CCP antibody formation.
Acute renal failure due to lymphomatous infiltration of the kidneys.
Authors: G T Obrador, B Price, Y O'Meara, D J Salant
Journal: Journal of the American Society of Nephrology (1997)

Acute renal failure (ARF) is an unusual manifestation of lymphomatous infiltration of the kidneys. In this article, a patient whose initial presentation of lymphoma was the sudden onset of painless hematuria and ARF is described. The absence of other causes of ARF, together with massively enlarged unobstructed kidneys on renal ultrasonography, strongly suggested an infiltrative process. Renal biopsy established the diagnosis of non-Hodgkin's lymphoma. Pulse steroid therapy was associated with rapid improvement of renal function and kidney size, but a moderate degree of tumor lysis syndrome ensued. Further recovery followed with chemotherapy. Whereas widespread infiltration of the kidneys is present in almost one third of patients with lymphoma at autopsy, this rarely causes clinical symptoms. Nevertheless, because it often responds to therapy, lymphomatous infiltration should be suspected in any patient presenting with unexplained ARF and enlarged kidneys, especially in the setting of widespread lymphoma.
Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial
Authors: Gilles Salles, John Francis Seymour, Fritz Offner, Armando López-Guillermo, David Belada, Luc Xerri, Pierre Feugier, Réda Bouabdallah, John Vincent Catalano, Pauline Brice, Dolores Caballero, Corinne Haioun, Lars Moller Pedersen, Alain Delmer, David Simpson, Sirpa Leppa, Pierre Soubeyran, Anton Hagenbeek, Olivier Casasnovas, Tanin Intragumtornchai, Christophe Fermé, Maria Gomes da Silva, Catherine Sebban, Andrew Lister, Jane A Estell, Gustavo Milone, Anne Sonet, Myriam Mendila, Bertrand Coiffier, Hervé Tilly
Journal: The Lancet (2010)
CD28 Costimulation Is Required for In Vivo Induction of Peripheral Tolerance in CD8 T Cells
Authors: Melanie S. Vacchio, Richard J. Hodes
Journal: The Journal of Experimental Medicine (2002)

Whereas ligation of CD28 is known to provide a critical costimulatory signal for activation of CD4 T cells, the requirement for CD28 as a costimulatory signal during activation of CD8 cells is less well defined. Even less is known about the involvement of CD28 signals during peripheral tolerance induction in CD8 T cells. In this study, comparison of T cell responses from CD28-deficient and CD28 wild-type H-Y–specific T cell receptor transgenic mice reveals that CD8 cells can proliferate, secrete cytokines, and generate cytotoxic T lymphocytes efficiently in the absence of CD28 costimulation in vitro. Surprisingly, using pregnancy as a model to study the H-Y–specific response of maternal T cells in the presence or absence of CD28 costimulation in vivo, it was found that peripheral tolerance does not occur in CD28KO pregnants in contrast to the partial clonal deletion and hyporesponsiveness of remaining T cells observed in CD28WT pregnants. These data demonstrate for the first time that CD28 is critical for tolerance induction of CD8 T cells, contrasting markedly with CD28 independence of in vitro activation, and suggest that the role of CD28/B7 interactions in peripheral tolerance of CD8 T cells may differ significantly from that of CD4 T cells.
Extracts from "Concise Clinical Evidence": Diabetic retinopathy * Commentary: Treatment of diabetic retinopathy
Authors: S. Harding
Journal: BMJ (2003)

Definition Diabetic retinopathy is characterised by varying degrees of microaneurysms, haemorrhages, exudates (known as hard exudates in the United States), venous changes, new vessel formation, and retinal thickening.It can involve the peripheral retina or the macula, or both.The range of severity of retinopathy includes background (mild nonproliferative), preproliferative (moderate or severe non-proliferative), proliferative, and advanced retinopathy.Involvement of the macula can be focal, diffuse, ischaemic, or mixed.
A P element has induced intron formation in Drosophila
Authors: D. Nouaud, B. Boeda, L. Levy, D. Anxolabehere
Journal: Molecular Biology and Evolution (1999)

We report evidence supporting the hypothesis that some introns could be originated from transposable elements. In the Drosophila montium species subgroup, we recently described a novel example of domestication by the host genome of a P transposable element. The element is a unique truncated P sequence transcribed into a polyadenylated RNA encoding a putative 66-kDa transposition repressor-like protein. Here, we analyze the genomic modifications associated with this transition of a transposable element into a stationary gene that is useful for the host. Study of the transcription modalities of this neogene reveals that the new transcriptional unit harbors a de novo synthesis of a new exon and a new intron upstream of the original P sequence initiation site. The new exon was constructed from the genomic flanking sequence of the P sequence, whereas the first half of the new intron is composed of genomic flanking sequence and the second half is composed of P sequence. This domestication event has involved the capture of a new promoter. An investigation of a large number of species belonging to the melanogaster species group revealed that this P element domestication is restricted to the species of the montium subgroup and that the new exon-intron structure is present in at least three other species. From sequence data, we hypothesize that cryptic acceptor and donor splicing sites present on the P element and flanking sequences have been under selective constraints which have led to the emergence of a new intron.
PF4/heparin complexes are T cell–dependent antigens
Authors: Shayela Suvarna, Lubica Rauova, Emily K. E. McCracken, Christina M. Goss, Bruce S. Sachais, Steven E. McKenzie, Michael P. Reilly, Michael Dee Gunn, Douglas B. Cines, Mortimer Poncz, Gowthami Arepally
Journal: Blood (2005)
Antibody inhibits defined stages in the pathogenesis of reovirus serotype 3 infection of the central nervous system.
Authors: K L Tyler, H W Virgin, R Bassel-Duby, B N Fields
Journal: The Journal of Experimental Medicine (1989)

The mammalian reoviruses provide a model for studying specific aspects of the immunopathogenesis of viral infection. We have used two serotype 3 reoviruses to define stages in the pathogenesis of central nervous system (CNS) infection at which a mAb specific for the reoviral cell attachment protein sigma 1 (sigma 1mAbG5) acts to protect mice against lethal disease. sigma 1mAbG5 administered either before or at the time of footpad inoculation with reovirus T3D prevented entry of T3D into the CNS. sigma 1mAbG5 also inhibited the spread of reovirus T3C9 from the gastrointestinal tract to the CNS after peroral inoculation with T3C9. These effects occurred in the absence of a significant effect of sigma 1mAbG5 on primary replication in skeletal muscle (T3D) or the gastrointestinal tract (T3C9). sigma 1mAbG5 administered after T3D had reached the spinal cord inhibited subsequent spread of infectious virus from spinal cord to brain. Even after direct intracerebral inoculation of T3D, sigma 1mAbG5 prevented both growth in the brain and spread of infectious virus from brain to eye, spinal cord, and muscle. Treatment with sigma 1mAbG5 after intracerebral inoculation with T3D prevented neuronal necrosis and resulted in a delayed and topographically restricted inflammatory response. We detected no antibody-resistant T3D variants in vivo after treatment with sigma 1mAbG5. We conclude that systemic IgG does not play a significant role at the primary site of infection with reoviruses, while it clearly acts to prevent infection of the CNS and extension of infection with the CNS. Further study will be directed to defining what components of the immune system do act at primary sites of infection, and to defining the mechanisms by which antibody acts at defined stages in pathogenesis.
Ontogeny of B-lymphocyte function. III. In vivo and in vitro studies on the ease of tolerance induction in B lymphocytes from fetal, neonatal, and adult mice
Authors: MR Szewczuk, GW Siskind
Journal: The Journal of Experimental Medicine (1977)

The ease of tolerance induction in B lymphocytes from fetal, neonatal, and adult mice was studied in vivo, in a cell transfer system, and in vitro. Three different tolerogens were used: ultracentrifuged BGG, DNP(6)-D-GL, and ultracentrifuged DNP(22)-BGG. Irradiated thymectomized mice were reconstituted with B cells from fetal or neonatal liver or adult spleen or bone marrow. The mice were injected with tolerogen 1 day later. They were given normal thymus cells and challenged with either BGG or DNP(44)-BGG between 4 and 14 days after tolerance induction. With BGG no difference in ease of B-cell tolerance induction was observed in mice reconstituted with B cells from 17-day fetal liver, neonatal liver, 8- day-old spleen, adult spleen, or adult bone marrow. B cells from 14-day fetal donors are relatively resistant to tolerance induction. In contrast, with DNP(6)-D-GL and DNP(22)-BGG B cells from neonatal donors were clearly more susceptible to tolerance induction than were B cells from adult donors. Comparable results were obtained in studies on tolerance induction in vitro. Neonatal B cells were more susceptible than adult B cells to tolerance induction upon culture with DNP(6)-D-GL or DNP(22)-BGG. However, neonatal and adult B cells were identical with respect to ease of tolerance induction in vitro with deaggregated BGG. The results suggest that there are multiple mechanisms for B-cell tolerance induction. Immature B cells appear to be more susceptible to tolerance induction by some mechanisms but not by others. It is suggested that immature B cells are more susceptible to tolerance induction with moderately polyvalent antigens such as hapten-carrier conjugates. With antigens like BGG which do not haverepeated epitopes no difference between mature and fetal B cells in regard to ease of tolerance induction is observed. These observations raise questions about the importance of relative ease of tolerance induction in immature B cells as a mechanism controlling the normal induction of self tolerance.
Endothelial dysfunction and pathogenesis of diabetic angiopathy
Authors: C Stehouwer
Journal: Cardiovascular Research (1997)

Objective and Methods: To review, from the clinical perspective, the contribution of dysfunction of the vascular endothelium to the pathogenesis of diabetic micro- and macroangiopathy. Results: Available data indicate that endothelial dysfunction in diabetes complicated by micro- or macroalbuminuria (renal microangiopathy) is generalised. The close linkage between microalbuminuria and endothelial dysfunction is an attractive explanation for the fact that microalbuminuria is a risk marker for atherosclerotic cardiovascular disease in diabetes. Endothelial dysfunction precedes the occurrence of even early diabetic microangiopathy. However, it is not clear whether endothelial dysfunction is a feature of the diabetic state per se or whether additional factors are required to induce endothelial dysfunction given the presence of diabetes. Convincing data from animal and in vitro models exist to indicate that endothelial dysfunction in diabetes may be related to hyperglycaemic pseudohypoxia, activation of protein kinase C, increased expression of transforming growth factor-β and vascular endothelial growth factor, non-enzymatic glycation, oxidative stress, activation of the coagulation cascade, increased expression of tumour necrosis factor-α, and high levels of insulin and insulin precursor molecules. However, the importance of these proposed mechanisms have not yet been extensively assessed in diabetes in man. Conclusions: Endothelial dysfunction plays a key role in the pathogenesis of diabetic angiopathy in man. The biochemical basis of endothelial dysfunction in diabetic man, however, has yet to be fully elucidated.
Targeting NF- B activation via pharmacologic inhibition of IKK2-induced apoptosis of human acute myeloid leukemia cells
Authors: Catherine Frelin, Véronique Imbert, Emmanuel Griessinger, Annie-Claude Peyron, Nathalie Rochet, Patrick Philip, Christian Dageville, Anne Sirvent, Michaël Hummelsberger, Etienne Bérard, Michel Dreano, Nicolas Sirvent, Jean-François Peyron
Journal: Blood (2004)