tbuckley/cabot-search huggingface dataset:
Antibodies to peptidoglycan in patients with spondylarthritis: a clue to disease aetiology?
Authors: H Park, H.R Schumacher, A.R Zeiger, J.T Rosenbaum
Journal: Annals of the Rheumatic Diseases (1984)

Although the aetiology of the spondylarthritic diseases, ankylosing spondylitis and Reiter's syndrome, is obscure, a clue to the pathogenesis might be an animal model, adjuvant arthritis. Rats with this disease develop a spectrum of pathology with marked similarity to the spondylarthritides. Since peptidoglycan, a major cell wall component of most bacteria is causally implicated in adjuvant arthritis, we sought evidence that peptidoglycan exposure accompanies both Reiter's syndrome and ankylosing spondylitis. Antibodies to the D-Ala-D-Ala moiety of peptidoglycan were measured by a sensitive and specific ELISA. Antibodies were elevated significantly in patients with ankylosing spondylitis or Reiter's syndrome, but not in patients with rheumatoid arthritis or degenerative joint disease in comparison with normal controls. The findings should be considered preliminary, since only a minority of patients had increased antibody titres. However, the findings are compatible with the hypothesis that peptidoglycan is causally related to spondylarthritis. Antibodies to other moieties in the peptidoglycan molecule might be a more sensitive test for significant exposure.
Cognitive and Neurologic Outcomes after Coronary-Artery Bypass Surgery
Authors: Ola A. Selnes, Rebecca F. Gottesman, Maura A. Grega, William A. Baumgartner, Scott L. Zeger, Guy M. McKhann
Journal: New England Journal of Medicine (2012)

For patients undergoing coronary-artery bypass grafting (CABG), adverse neurologic outcomes, including stroke and cognitive decline, are major concerns. Even mild cognitive deficits before surgery may be a marker for cerebrovascular disease and increased risk.
Healing of Benign Gastric Ulcer: Comparison of Cimetidine and Placebo in the United States
Authors: DAVID Y. GRAHAM
Journal: Annals of Internal Medicine (1985)

Recently the Food and Drug Administration approved cimetidine for the treatment of benign gastric ulcer. Approval was based in part on the results of our large multicenter trial involving 172 patients with benign gastric ulcer between 0.5 and 2.5 cm in diameter: 87 were randomly assigned to receive cimetidine (300 mg four times daily) and 85 to receive placebo. Cimetidine treatment resulted in significantly more rapid healing than placebo; after 2 and 6 weeks of therapy, 10.0% and 44.8% of patients receiving placebo were healed, as compared to 22.6% and 65.1% receiving cimetidine. The results of our study were compared with the time-response curve previously published (0, 4, and 8 weeks of therapy). The combined data yielded linear healing rates for the first 8 weeks of therapy (r > 0.99 for both cimetidine and placebo). These studies can be used to define expectations for healing of benign gastric ulcer, and we recommend follow-up intervals of 8 and, if unhealed, 16 weeks.
Diagnosis of pulmonary embolism by multidetector CT alone or combined with venous ultrasonography of the leg: a randomised non-inferiority trial
Authors: Marc Righini, Grégoire Le Gal, Drahomir Aujesky, Pierre-Marie Roy, Olivier Sanchez, Franck Verschuren, Olivier Rutschmann, Michel Nonent, Jacques Cornuz, Frédéric Thys, Cédric Petit Le Manach, Marie-Pierre Revel, Pierre-Alexandre Poletti, Guy Meyer, Dominique Mottier, Thomas Perneger, Henri Bounameaux, Arnaud Perrier
Journal: The Lancet (2008)
Riluzole Enhances Ionizing Radiation–Induced Cytotoxicity in Human Melanoma Cells that Ectopically Express Metabotropic Glutamate Receptor 1 <i>In Vitro</i> and <i>In Vivo</i>
Authors: Atif J. Khan, Brian Wall, Stuti Ahlawat, Camille Green, Devora Schiff, Janice M. Mehnert, James S. Goydos, Suzie Chen, Bruce G. Haffty
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Brain metastases are a common preterminal event in patients with metastatic melanoma and require radiation therapy. Our group has previously shown that human GRM1 (hGRM1) expressing melanoma cells release excess extracellular glutamate and are growth inhibited by riluzole, an inhibitor of glutamate release. Riluzole-treated cells accumulate in G2/M phase of the cell cycle at 24 hours, and then undergo apoptotic cell death. We evaluated whether riluzole enhanced radiosensitivity in melanoma cells. Experimental Design: Clonogenic assays were performed to evaluate clonogenic survival after treatment in hGRM1 expressing and nonexpressing melanoma cells. Western immunoblots were performed to confirm apoptotic cell death. A xenograft mouse model was used to validate the in vitro experiments. Tumors harvested from the xenografts were fixed and stained for apoptosis and DNA damage markers. Results: In the hGRM1-positive cell lines C8161 and UACC903, riluzole enhanced the lethal effects of ionizing radiation; no difference was seen in the hGRM1-negative UACC930 cell line. C8161 cells treated with riluzole plus irradiation also showed the highest levels of the cleaved forms of PARP and caspase-3; excised C8161 xenografts showed the greatest number of apoptotic cells by immunohistochemistry (P &amp;lt; 0.001). On cell cycle analysis, a sequence-dependent enrichment in the G2/M phase was shown with the combination of riluzole and irradiation. Xenografts treated with riluzole and weekly radiation fractions showed significant growth inhibition and revealed markedly increased DNA damage. Conclusions: We have shown, in vitro and in vivo, that the combination of riluzole and ionizing radiation leads to greater cytotoxicity. These results have clinical implications for patients with brain metastases receiving whole brain radiation therapy. Clin Cancer Res; 17(7); 1807–14. ©2011 AACR.
Tumor necrosis factor alpha/cachectin and interleukin 1 beta initiate meningeal inflammation.
Authors: O Ramilo, X Sáez-Llorens, J Mertsola, H Jafari, K D Olsen, E J Hansen, M Yoshinaga, S Ohkawara, H Nariuchi, G H McCracken
Journal: The Journal of Experimental Medicine (1990)

Although previous studies using human cytokines in rabbits and rats have provided evidence of the participation of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) in the meningeal inflammatory cascade, the results obtained by several groups of investigators have been discordant or, at times, contradictory. In the present study, homologous cytokines were applied to the rabbit meningitis model. Intracisternal administration of 10(2)-10(5) IU of purified rabbit TNF-alpha (RaTNF-alpha) produced significant cerebrospinal fluid (CSF) inflammation. A similar response was observed after intracisternal inoculation of 5-200 ng of rabbit recombinant IL-1 beta (rrIL-1 beta). Preincubation of these two mediators with their specific antibodies resulted in an almost complete suppression of the CSF inflammatory response. In animals with Haemophilus influenzae type b lipooligosaccharide-induced meningitis, intracisternal administration of anti-rrIL-1 beta, anti-RaTNF-alpha, or both resulted in a significant modulation of meningeal inflammation. Simultaneous administration of 10(3) IU of RaTNF-alpha and 5 ng of rrIL-1 beta resulted in a synergistic inflammatory response manifested by a more rapid and significantly increased influx of white blood cells into the CSF compared with results after each cytokine given alone. These data provide evidence for a seminal role of TNF-alpha and IL-1 beta in the initial events of meningeal inflammation.
Identification of an immunodominant region on the I-A beta chain using site-directed mutagenesis and DNA-mediated gene transfer.
Authors: J M Buerstedde, L R Pease, M P Bell, A E Nilson, G Buerstedde, D Murphy, D J McKean
Journal: The Journal of Experimental Medicine (1988)

To identify which polymorphic residues determine the allospecific antibody binding sites on A beta polypeptides, mutant Ak beta genes were constructed encoding single or multiple amino acids of the d allele at 14 polymorphic positions in the beta 1 domain. Cell lines expressing these genes were analyzed by quantitative immunofluorescence using 16 mAbs reactive to Ak beta or Ad beta. Substitution of d allele residues at positions 63 and 65-67 in the Ak beta polypeptide resulted in the loss of binding of all Ak beta-reactive antibodies and the gain of binding of most Ad beta-reactive antibodies. Two Ad beta-reactive mAbs bound to the mutant Ak beta polypeptide containing d allele-characteristic residue at position 40. In contrast, substitution of the other polymorphic residues in the NH2-terminal and COOH-terminal regions of the beta 1 domain did not alter antibody binding.
Oral Contraceptive Use and Risk of Gestational Trophoblastic Tumors
Authors: J R Palmer, S G Driscoll, L Rosenberg, R S Berkowitz, J R Lurain, J Soper, L B Twiggs, D M Gershenson, E I Kohorn, M Berman, S Shapiro, R S Rao
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Gestational trophoblastic disease refers to a spectrum of rare benign and malignant gynecologic disorders whose pathogenesis is not well understood. Recent studies from China and the United States have raised the hypothesis that long-term use of oral contraceptives before conception may increase the risk of gestational trophoblastic tumors. A multicenter case-control study of gestational trophoblastic tumors was undertaken to test this hypothesis. METHODS: Telephone interviews were conducted with 235 case patients, including 50 with gestational choriocarcinoma, and 413 control subjects matched on recentness of pregnancy, age at pregnancy, and area of residence. Relative risks (odds ratios) were computed by conditional logistic regression. Reported P values are two-sided. RESULTS: The relative risk estimate for ever having used oral contraceptives before the index pregnancy was 1.9 (95% confidence interval [CI] = 1.2-3.0), and the risk increased with duration of use ( P for trend = .05). The estimate was highest for women who used oral contraceptives during the cycle in which they became pregnant (relative risk = 4.0; 95% CI = 1.6-10), but there was no consistent pattern according to the time interval since last use. Separate analyses of choriocarcinoma and persistent mole yielded similar results, i.e., the relative risk estimates for oral contraceptive use were 2.2 (95% CI = 0.8-6.4) and 1.8 (95% CI = 1.0-3.0), respectively. Control for the number of sexual partners, which was independently associated with risk ( P for trend = .05), did not materially change the results. CONCLUSIONS: This study, the largest to date, indicates that long duration of oral contraceptive use before conception increases the risk of gestational trophoblastic tumors. These findings may provide clues to the pathogenesis of this rare disease. Changes in use of oral contraceptives are not warranted, however, because the incidence attributable to oral contraceptive use is very low.
Association of <i>TNFSF4 (OX40L)</i> polymorphisms with susceptibility to systemic sclerosis
Authors: Pravitt Gourh, Frank C Arnett, Filemon K Tan, Shervin Assassi, Dipal Divecha, Gene Paz, Terry McNearney, Hilda Draeger, John D Reveille, Maureen D Mayes, Sandeep K Agarwal
Journal: Annals of the Rheumatic Diseases (2009)

Objective It is increasingly being appreciated that multiple autoimmune diseases share common susceptibility genes. The tumour necrosis factor ligand superfamily member 4 gene ( TNFSF4 , OX40L ), which encodes for the T cell costimulatory molecule OX40 ligand, has been identified as a susceptibility gene for the development of systemic lupus erythematosus (SLE). Accordingly, the aim of the current study was to investigate the possible association of the TNFSF4 gene region with systemic sclerosis (SSc), an autoimmune disease that leads to the development of cutaneous and visceral fibrosis. Methods A total of 9 single nucleotide polymorphisms (SNPs) in the TNFSF4 gene region, previously associated with susceptibility to SLE, were tested for association with SSc in a collection of 1059 patients with SSc and 698 controls. Results Case-control comparisons revealed a significant association between susceptibility to SSc and the minor alleles at SNPs rs1234314 (OR 1.20, 95% CI 1.04 to 1.4, p FDR =0.019), rs2205960 (OR 1.24, 95% CI 1.10 to 1.50, p FDR =0.019) and rs844648 (OR 1.16, 95% CI 1.01 to 1.30, p FDR =0.032). The minor allele at rs844644 was protective (OR 0.84, 95% CI 0.70 to 0.97, p FDR =0.038). Analysis of subsets of patients with SSc demonstrated significant associations of the TNFSF4 SNPs with limited and diffuse SSc as well as specific SNPs that were associated with SSc-associated autoantibodies. Finally, the analyses suggest a potential interaction between two TNFSF4 SNPs, rs2205960 and rs844648, with regards to SSc susceptibility. Conclusions Polymorphisms in the TNFSF4 gene region are associated with susceptibility to SSc and its clinical and autoantibody subsets. TNFSF4 may be another gene that confers risk to multiple autoimmune diseases.
A New Method of Performing Resection of the Knee-Joint
Authors: W. M. Campbell
Journal: BMJ (1883)

late years than I used, and that is, Always when we change a @res- ,4,ing, invariably first to cover the wound with something pure; not to twah the surrounding parts-with antiseptic solbtion, ancd then, -after this has been done1 put a dciessing on the wound; but before -we begin to.defile the lotion at all, put on the wound what Jis pure, and, last thing of all, wash the surrounding parts, >which, though they look the same to our eyes, are different toto
Murine autoimmune hearing loss mediated by CD4+ T cells specific for inner ear peptides
Authors: C. Arturo Solares, Andrea E. Edling, Justin M. Johnson, Moo-Jin Baek, Keiko Hirose, Gordon B. Hughes, Vincent K. Tuohy
Journal: Journal of Clinical Investigation (2004)

Autoimmune sensorineural hearing loss (ASNHL) is characterized typically by bilateral, rapidly progressive hearing loss that responds therapeutically to corticosteroid treatment. Despite its name, data implicating autoimmunity in the etiopathogenesis of ASNHL have been limited, and targeted self-antigens have not been identified. In the current study we show that the inner ear–specific proteins cochlin and β-tectorin are capable of targeting experimental autoimmune hearing loss (EAHL) in mice. Five weeks after immunization of SWXJ mice with either Coch 131–150 or β-tectorin 71–90, auditory brainstem responses (ABR) showed significant hearing loss at all frequencies tested. Flow cytometry analysis showed that each peptide selectively activated CD4+ T cells with a proinflammatory Th1-like phenotype. T cell mediation of EAHL was determined by showing significantly increased ABR thresholds 6 weeks after adoptive transfer of peptide-activated CD4+ T cells into naive SWXJ recipients. Immunocytochemical analysis showed that leukocytic infiltration of inner ear tissues coincided with onset of hearing loss. Our study provides a contemporary mouse model for clarifying our understanding of ASNHL and facilitating the development of novel effective treatments for this clinical entity. Moreover, our data provide experimental confirmation that ASNHL may be a T cell–mediated organ-specific autoimmune disorder of the inner ear.
Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover
Authors: Jorge R. Almeida, David A. Price, Laura Papagno, Zaïna Aït Arkoub, Delphine Sauce, Ethan Bornstein, Tedi E. Asher, Assia Samri, Aurélie Schnuriger, Ioannis Theodorou, Dominique Costagliola, Christine Rouzioux, Henri Agut, Anne-Geneviève Marcelin, Daniel Douek, Brigitte Autran, Victor Appay
Journal: The Journal of Experimental Medicine (2007)

The key attributes of CD8+ T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8+ T cell responses specific for Gag and, in particular, the immunodominant p24 epitope KK10 correlate with control of HIV-1 replication in human histocompatibility leukocyte antigen (HLA)–B27 patients. To understand further the nature of CD8+ T cell–mediated antiviral efficacy, we performed a comprehensive study of CD8+ T cells specific for the HLA-B27–restricted epitope KK10 in chronic HIV-1 infection based on the use of multiparametric flow cytometry together with molecular clonotypic analysis and viral sequencing. We show that B27-KK10–specific CD8+ T cells are characterized by polyfunctional capabilities, increased clonal turnover, and superior functional avidity. Such attributes are interlinked and constitute the basis for effective control of HIV-1 replication. These data on the features of effective CD8+ T cells in HIV infection may aid in the development of successful T cell vaccines.
Emotion and Decision Making: Multiple Modulatory Neural Circuits
Authors: Elizabeth A. Phelps, Karolina M. Lempert, Peter Sokol-Hessner
Journal: Annual Review of Neuroscience (2014)

Although the prevalent view of emotion and decision making is derived from the notion that there are dual systems of emotion and reason, a modulatory relationship more accurately reflects the current research in affective neuroscience and neuroeconomics. Studies show two potential mechanisms for affect's modulation of the computation of subjective value and decisions. Incidental affective states may carry over to the assessment of subjective value and the decision, and emotional reactions to the choice may be incorporated into the value calculation. In addition, this modulatory relationship is reciprocal: Changing emotion can change choices. This research suggests that the neural mechanisms mediating the relation between affect and choice vary depending on which affective component is engaged and which decision variables are assessed. We suggest that a detailed and nuanced understanding of emotion and decision making requires characterizing the multiple modulatory neural circuits underlying the different means by which emotion and affect can influence choices.
Fibroblast Growth Factor Receptor 1–Transformed Mammary Epithelial Cells Are Dependent on RSK Activity for Growth and Survival
Authors: Wa Xian, Leontios Pappas, Darshan Pandya, Laura M. Selfors, Patrick W. Derksen, Michiel de Bruin, Nathanael S. Gray, Jos Jonkers, Jeffrey M. Rosen, Joan S. Brugge
Journal: Cancer Research (2009)

Fibroblast growth factor receptor 1 (FGFR1) is frequently amplified and highly expressed in lobular carcinomas of the breast. In this report, we evaluated the biological activity of FGFR1 in a wide range of in vitro assays. Conditional activation of FGFR1 in the nontransformed MCF10A human mammary cell line, MCF10A, resulted in cellular transformation marked by epidermal growth factor-independent cell growth, anchorage-independent cell proliferation and survival, loss of cell polarity, and epithelial-to-mesenchymal transition. Interestingly, small-molecule or small interfering RNA inhibition of ribosomal S6 kinase (RSK) activity induced death of the FGFR1-transformed cells, but not of the parental MCF10A cell line. The dependence of FGFR1-transformed cells on RSK activity was further confirmed in cell lines derived from mouse and human lobular carcinomas that possess high FGFR1 activity. Taken together, these results show the transforming activity of FGFR1 in mammary epithelial cells and identify RSK as a critical component of FGFR1 signaling in lobular carcinomas, thus implicating RSK as a candidate therapeutic target in FGFR1-expressing tumors.
Screening for Lung Cancer: For Patients at Increased Risk for Lung Cancer, It Works
Authors: James R. Jett, David E. Midthun
Journal: Annals of Internal Medicine (2011)

Screening for lung cancer is not currently recommended, even in persons at high risk for this condition. Most patients with lung cancer present with symptomatic disease that is usually at an incurable, advanced stage. The recently reported NLST (National Lung Screening Trial) showed a 20% decrease in deaths from lung cancer in high-risk persons undergoing screening with low-dose computed tomography of the chest compared with chest radiography. The high-risk group included in the trial comprised asymptomatic persons aged 55 to 74 years, with smoking history of at least 30 pack-years. Screening with low-dose computed tomography detected more cases of early-stage lung cancer and fewer cases of advanced-stage cancer, confirming that screening has shifted the stage of cancer at diagnosis and provides more persons with the opportunity for curative treatment. Although computed tomography screening has risks and limitations, the 20% decrease in deaths is the single most dramatic decrease ever reported for deaths from lung cancer, with the possible exception of smoking cessation. Physicians should offer computed tomography screening for lung cancer to patients who fit the high-risk profile defined in the NLST.
Sex and strain differences in adult mouse cardiac repolarization: importance of androgens
Authors: J BROUILLETTE, K RIVARD, E LIZOTTE, C FISET
Journal: Cardiovascular Research (2004)

Gender differences in mouse cardiac repolarization have been reported to be due to the stimulatory action of androgens on the ultrarapid delayed rectifier K(+) current (I(Kur)) and its underlying Kv1.5 channel. To confirm the regulation of ventricular repolarization by androgens, the present study compared two strains of mice (CD-1 and C57BL/6) that present different androgen levels.Measurement of testosterone levels in different strains of mice (CD-1, C57BL/6, C3H and FVB) revealed that male C57BL/6 mice had very low levels of testosterone, whereas males of the other strains displayed normal testosterone levels. Furthermore, whole-cell voltage clamp recordings in isolated ventricular myocytes showed that the current density of I(Kur) in male C57BL/6 mice was similar to that in female mice but smaller with respect to male CD-1 mice. Androgen replacement in male C57BL/6 mice as well as in castrated male CD-1 mice shortened ventricular repolarization, increased I(Kur) current density, and increased expression of Kv1.5 channels.Strain and gender differences observed in mouse cardiac repolarization can be explained by different androgen levels. As a consequence, androgens are major regulatory factors in cardiac repolarization and special attention should be paid to the hormonal status of the animal when studying hormonal regulation of cardiac repolarization.