tbuckley/cabot-search huggingface dataset:
In vivo effects of anti-Ia alloantisera. I. Elimination of specific suppression by in vivo administration of antisera specific for I-J controlled determinants.
Authors: M Pierres, R N Germain, M E Dorf, B Benacerraf
Journal: The Journal of Experimental Medicine (1978)

The in vivo effects of intravenous administration of alloantisera directed to I-J subregion coded determinants were investigated. In confirmation and extension of our previous results, anti-I-Jk [B10.A(3R) anti-B10.A(5R)] and anti-I-Js ([B10.A(3R) X B10.S(9R)]F1 anti-B10.HTT) antisera, when administered in 1 to 10 microliter amounts at the time of immunization, led to twofold increases in the IgM and IgG plaque-forming cells (PFC) responses to suboptimal doses of sheep erythrocytes in A/J (I-Jk) and SJL (I-Js) mice, respectively. To assess whether this immunopotentiation was due to a decrease in specific suppression, experiments were carried out using the polypeptide antigens random linear terpolymer of L-glutamic acid60, L-alanine30, and L-tyrosine10 (GAT) and random linear copolymer of L-glutamic acid50-L-tyrosine50 (GT), since administration of GAT to the nonresponder strain SJL, or GT to the nonresponder strain CBA fails to induce a primary PFC response and stimulates specific suppressor T cells able to prevent PFC responses to subsequent challenge with the immunogens GAT-methylated bovine serum albumin (MBSA) or GT-MBSA, respectively. The current study demonstrates that CBA (I-Jk) mice given 100 microgram GT in Maalox-pertussis adjuvant on day 0, and 10 microliter anti-I-Jk antiserum i.v. on days 0, 1, and 2, develop a significant primary specific PFC response on day 7. A similar responsiveness to 10 microgram GAT is found in SJL mice treated with 10 microliter anti-I-Js antiserum for 3 days. This same active anti-I-Js antiserum does not permit CBA mice to respond to GT, demonstrating the specificity of the anti-I-J effect. These data suggest that anti-I-J antiserum treatment at the time of antigen administration reduces suppressor responses to GAT or GT, permitting primary PFC responses. To directly demonstrate such an effect on suppressor activity, SJL or CBA mice treated, respectively, with GAT or GT to induce suppressor cells active on GAT-MBSA or GT-MBSA responses after adoptive transfer to normal syngeneic recipients were also given anti-I-J antisera (10 microliter/day) for 3 days, at which time their spleen cells were tested for suppressive activity upon transfer. Cells from such treated mice failed to show detectable suppressive activity upon transfer to syngeneic recipients challenged with GAT-MBSA or GT-MBSA, confirming the hypothesis of an in vivo effect of anti-I-J antiserum on suppressor activity.
Interspecies extrapolation in carcinogenesis: prediction between rats and mice.
Authors: L S Gold, L Bernstein, R Magaw, T H Slone
Journal: Environmental Health Perspectives (1989)

Interspecies extrapolation in carcinogenesis is studied by evaluating prediction from rats to mice and from mice to rats. The Carcinogenic Potency Database, which includes 3500 cancer tests conducted in rats or mice on 955 compounds, is used for the analysis. About half of the chemicals tested for carcinogenicity are positive in at least one test, and this proportion is similar when rats and mice are considered separately. For 392 chemicals tested in both species, 76% of the rat carcinogens are positive in the mouse, and 70% of mouse carcinogens are positive in the rat. When compounds composed solely of chlorine, carbon, hydrogen, and, optionally, oxygen are excluded from the analysis, 75% of mouse carcinogens are positive in the rat. Overall concordance (the percentage positive in both species plus the percentage negative in both) is 76%. Three factors that affect prediction between rats and mice are discussed: chemical class, mutagenicity in the Salmonella assay, and the dose level at which a chemical is toxic. Prediction is more accurate for mutagens than non-mutagens and for substances that are toxic at low (versus only at high) doses. Species differences are not the result of failure in the bioassay to attain the maximum tolerated dose in the negative species or of more frequent testing in the positive species. An analysis of the predictive value of positivity for the 10 most common target sites indicates that most sites are good predictors of carcinogenicity at some site in the other species; the poorest predictors among these common sites are the rat urinary bladder and the mouse liver.
Physical signs of diffuse airways obstruction and lung distension
Authors: E. J. M. Campbell
Journal: Thorax (1969)

The following are physical signs which can be elicited in patients with chronic airways obstruction: a reduction in the length of the trachea palpable above the sternal notch; tracheal descent with inspiration; excessive use of the scalene and sternomastoid muscles; excavation of the suprasternal and supraclavicular fossae during inspiration; jugular venous filling during expiration; loss of bucket-handle movement of the upper ribs; paradoxical movement of the lower ribs; and prolonged forced expiratory time.
“A NEW PHASE IN EARLY SYPHILIS”: SOME EXPLANATIONS.
Authors: E. TYTLER BURKE
Journal: British Journal of Dermatology (1933)

Journal Article “A NEW PHASE IN EARLY SYPHILIS”: SOME EXPLANATIONS. Get access E. TYTLER BURKE E. TYTLER BURKE Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 45, Issue 3, 1 March 1933, Pages 87–94, https://doi.org/10.1111/j.1365-2133.1933.tb10151.x Published: 01 March 1933
An overview on the neurological readiness for running
Authors: Kathleen M. Haywood
Journal: British Journal of Sports Medicine (1974)

In developing from a neonate totally dependent on others for his existence to a highly skilled and reasoning adult, the human organism undergoes rapid physical changes. Almost none of those changes are more important to him than those which allow him to make finely coordinated movements to manipulate his body parts, to undertake locomotion, to respond to objects, to project other objects. It is well known that neurological processes make motor activity possible. Unfortunately, little is known about the relationship between a specific neurological development and the initial occurrence of some motor activity at a later time.
Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial
Authors: Nita Bhandari, Temsunaro Rongsen-Chandola, Ashish Bavdekar, Jacob John, Kalpana Antony, Sunita Taneja, Nidhi Goyal, Anand Kawade, Gagandeep Kang, Sudeep Singh Rathore, Sanjay Juvekar, Jayaprakash Muliyil, Alok Arya, Hanif Shaikh, Vinod Abraham, Sudhanshu Vrati, Michael Proschan, Robert Kohberger, Georges Thiry, Roger Glass, Harry B Greenberg, George Curlin, Krishna Mohan, G V J A Harshavardhan, Sai Prasad, T S Rao, John Boslego, Maharaj Kishan Bhan
Journal: The Lancet (2014)
Potential Surrogate Endpoints for Prostate Cancer Survival: Analysis of a Phase III Randomized Trial
Authors: Michael E. Ray, Kyounghwa Bae, Maha H. A. Hussain, Gerald E. Hanks, William U. Shipley, Howard M. Sandler
Journal: JNCI Journal of the National Cancer Institute (2009)

BackgroundThe identification of surrogate endpoints for prostate cancer–specific survival may shorten the length of clinical trials for prostate cancer. We evaluated distant metastasis and general clinical treatment failure as potential surrogates for prostate cancer–specific survival by use of data from the Radiation Therapy and Oncology Group 92-02 randomized trial.
UPA promotes lipid-loaded vascular smooth muscle cell migration through LRP-1
Authors: Roberta Lugano, Esther Peña, Laura Casani, Lina Badimon, Teresa Padró
Journal: Cardiovascular Research (2013)

Migration of vascular smooth muscle cells (VSMCs) is a crucial event in atherosclerosis and vascular repair. Low-density lipoprotein (LDL) infiltrated in the vessel wall become aggregated (agLDL) and internalized by VSMC through the LDL receptor-related protein LRP1, deriving in lipid-loaded cells with reduced motility capacity. The urokinase–plasminogen activator (UPA)/UPA receptor (UPAR) system plays a relevant role in vascular remodelling. Here, we investigated whether UPA-ligand binding is involved in the detrimental effects of lipid loading in VSMC migration. Animals fed a high-fat diet had 10-fold higher cholesterol-LDL plasma levels, >60% decrease in aortic UPA-protein expression, and VSMC showed impaired outgrowth from aortic explants. Angiotensin II infusion significantly increased aortic UPA expression and accelerated VSMC migration. Using an in vitro model of wound repair, we showed that agLDL inhibits UPA-mediated VSMC migration. UPA silencing reduced migration in control cells to levels observed in lipid-loaded VSMC. UPA silencing did not affect migration in lipid-loaded VSMC. UPA expression was significantly decreased in agLDL-exposed VSMC. agLDL also induced changes in the subcellular localization of UPA, with a reduction in colocalization with UPAR strongly evident at the front edge of agLDL-treated migrating cells. Rescue experiments showed that UPA acting as UPAR ligand restored migration capacity of agLDL-VSMC to control levels. The effects of UPA/UPAR on migration of lipid-loaded cells occurred through the binding to LRP-1. UPA-ligand binding regulates VSMC migration, a process that is interfered by LDL. Thus, tissue infiltrated LDL through the abrogation of UPA function reduces VSMC-regulated vascular repair.
Development of Two Manifestations of T-Lymphocyte Reactivity During Tumor Growth: Altered Kinetics Associated With Elevated Growth Rates2
Authors: P. G. Holt, J. Chalmer, D. Keast
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Development of Two Manifestations of T-Lymphocyte Reactivity During Tumor Growth: Altered Kinetics Associated With Elevated Growth Rates Get access P. G. Holt, P. G. Holt Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Chalmer, J. Chalmer Search for other works by this author on: Oxford Academic PubMed Google Scholar D. Keast D. Keast Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 55, Issue 5, November 1975, Pages 1135–1142, https://doi.org/10.1093/jnci/55.5.1135 Published: 01 November 1975 Article history Received: 07 March 1975 Accepted: 27 June 1975 Published: 01 November 1975
Shop for Quality or Volume? Volume, Quality, and Outcomes of Coronary Artery Bypass Surgery
Authors: Andrew D. Auerbach
Journal: Annals of Internal Medicine (2009)

Background: Care from high-volume centers or surgeons has been associated with lower mortality rates in coronary artery bypass surgery, but how volume and quality of care relate to each other is not well understood. Objective: To determine how volume and differences in quality of care influence outcomes after coronary artery bypass surgery. Design: Observational cohort. Setting: 164 hospitals in the United States. Patients: 81 289 patients 18 years or older who had coronary artery bypass grafting from 1 October 2003 to 1 September 2005. Measurements: Hospital and surgeon case volumes were estimated by using a data set. Quality measures were defined by whether patients received specific medications and by counting the number of measures missed. Hierarchical models were used to estimate effects of volume and quality on death and readmission up to 30 days. Results: After adjustment for clinical factors, lowest surgeon volume and highest hospital volume were associated with higher mortality rates and lower readmission risk, respectively. Patients who did not receive aspirin (odds ratio, 1.89 [95% CI, 1.65 to 2.16) or β-blockers (odds ratio, 1.29 [CI, 1.12 to 1.49]) had higher odds for death, after adjustment for clinical risk factors and case volume. Adjustment for individual quality measures did not alter associations between volume and readmission or death. However, if no quality measures were missed, mortality rates at the lowest-volume centers (adjusted mortality rate, 1.05% [CI, 0.81% to 1.29%]) and highest-volume centers (adjusted mortality rate, 0.98% [CI, 0.72% to 1.25%]) were similar. Limitation: Because administrative data were used, the quality measures may not replicate measures collected through chart abstraction. Conclusion: Maximizing adherence to quality measures is associated with improved mortality rates, independent of hospital or surgeon volume. Primary Funding Source: California HealthCare Foundation.
Neurotrophin Overexpression in Lower Airways of Infants with Respiratory Syncytial Virus Infection
Authors: Luca Tortorolo, Arianna Langer, Giancarlo Polidori, Giovanni Vento, Barbara Stampachiacchere, Luigi Aloe, Giovanni Piedimonte
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Nerve growth factor and its receptors are upregulated in the lungs of weanling rats with lower respiratory tract infection caused by the respiratory syncytial virus (RSV), and this is a major mechanism of the inflammatory response against the virus. However, no information is available in humans.We sought to determine whether the expression of neurotrophic factors and receptors is increased in human infants infected with RSV.We used a highly sensitive immunoassay to measure the concentrations of nerve growth factor and brain-derived neurotrophic factor proteins in serum samples and in the supernatants and cell fractions of nonbronchoscopic bronchoalveolar lavage fluid. We also used immunofluorescence to detect expression in airway cells of the tyrosine kinase receptor TrkA, which binds nerve growth factor with high affinity. Samples were obtained at 24 and 48 hours postintubation from 31 mechanically ventilated infants: 15 patients with RSV infection, 5 patients with respiratory infection negative for RSV, and 11 postsurgical patients without respiratory infection.Data show significantly higher concentrations of both neurotrophins in the cell fractions of bronchoalveolar lavage samples obtained from infants with RSV infection compared with control infants, whereas no significant difference was found in supernatants or serum samples. We also detected tyrosine kinase receptor immunoreactivity only in cells from airways infected with RSV.We conclude that neurotrophic factors and receptors are overexpressed in human airways infected by RSV, and may contribute to airway inflammation and hyperreactivity.
Upregulation of matrix metalloproteinases in a model of T cell mediated tissue injury in the gut: analysis by gene array and in situ hybridisation
Authors: M T Salmela
Journal: Gut (2002)

<b>Background and aim:</b> Matrix metalloproteinases (MMPs) have been implicated in tissue remodelling and ulceration in inflammatory bowel disease and coeliac disease. Studies to date have concluded that stromelysin 1 is functionally involved in mucosal degradation. However, there are many other MMPs whose function in the gut is currently unknown. This work had two aims: firstly, to use gene array technology to measure changes in MMP and tissue inhibitor of metalloproteinase (TIMP) expression in a model of T cell mediated injury in the gut, and secondly, to correlate data from gene arrays with that generated by in situ hybridisation. <b>Methods:</b> T cells in explants of human fetal gut were activated with pokeweed mitogen or anti-CD3 plus interleukin 12. Gene array analysis and in situ hybridisation were performed to investigate changes in MMP gene expression. <b>Results:</b> Both gene array analysis and in situ hybridisation indicated marked upregulation of stromelysin 2 and macrophage metalloelastase expression in the explants associated with mucosal destruction. The arrays also confirmed our previous observation that interstitial collagenase (MMP-1), stromelysin 1 (MMP-3), and gelatinase B (MMP-9) are upregulated but there was no change in MMP-2, -7, -8, -9, -11, -13, -14–17, or -19. Following T cell activation, transcripts for TIMPs were reduced. <b>Conclusions:</b> These results show that there is differential upregulation of MMPs during T cell responses in the gut and suggest that further studies on the role of stromelysin 2 and macrophage metalloelastase may show that they have a functional role. In addition, the increase in MMPs and reduction in TIMPs suggest that the protease/antiprotease balance in the mucosa may determine the extent of mucosal degradation.
Deregulated E2f Transcriptional Activity in Autonomously Growing Melanoma Cells
Authors: Ruth Halaban, Elaine Cheng, Yoel Smicun, Joseph Germino
Journal: The Journal of Experimental Medicine (2000)

Inactivation of the retinoblastoma tumor suppressor protein (pRb) has been implicated in melanoma cells, but the molecular basis for this phenotype has not yet been elucidated, and the status of additional family members (p107 and p130, together termed pocket proteins) or the consequences on downstream targets such as E2F transcription factors are not known. Because cell cycle progression is dependent on the transcriptional activity of E2F family members (E2F1–E2F6), most of them regulated by suppressive association with pocket proteins, we characterized E2F–pocket protein DNA binding activity in normal versus malignant human melanocytes. By gel shift analysis, we show that in mitogen-dependent normal melanocytes, external growth factors tightly controlled the levels of growth-promoting free E2F DNA binding activity, composed largely of E2F2 and E2F4, and the growth-suppressive E2F4–p130 complexes. In contrast, in melanoma cells, free E2F DNA binding activity (E2F2 and E2F4, to a lesser extent E2F1, E2F3, and occasionally E2F5), was constitutively maintained at high levels independently of external melanocyte mitogens. E2F1 was the only family member more abundant in the melanoma cells compared with normal melanocytes, and the approximately fivefold increase in DNA binding activity could be accounted for mostly by a similar increase in the levels of the dimerization partner DP1. The continuous high expression of cyclin D1, A2, and E, the persistent cyclin-dependent kinase 4 (CDK4) and CDK2 activities, and the presence of hyperphosphorylated forms of pRb, p107, and p130, suggest that melanoma cells acquired the capacity for autonomous growth through inactivation of all three pocket proteins and release of E2F activity, otherwise tightly regulated in normal melanocytes by external growth factors.
The interleukin 12 p40 gene promoter is primed by interferon gamma in monocytic cells.
Authors: X Ma, J M Chow, G Gri, G Carra, F Gerosa, S F Wolf, R Dzialo, G Trinchieri
Journal: The Journal of Experimental Medicine (1996)

Interleukin (IL) 12 is a proinflammatory cytokine produced by phagocytic cells, B cells, and other antigen-presenting cells that modulates adaptive immune responses by favoring the generation of T helper type 1 cells. IL-12 mediates some of its physiological activities by acting as a potent inducer of interferon (IFN) gamma production by T and natural killer cells. IFN-gamma enhances the ability of the phagocytic cells to produce IL-12 and other proinflammatory cytokines. Thus, IL-12-induced IFN-gamma acts in a positive feedback loop that represents an important amplifying mechanism in the inflammatory response to infections. We show here that IFN-gamma enhances IL-12 production mostly by priming phagocytic cells for lipopolysaccharide (LPS)-induced transcription of the IL-12 p40 gene, which encodes the heavy chain of the IL-12 heterodimer; furthermore, IFN-gamma directly induces transcription of the IL-12 p35 gene, which encodes the light chain of IL-12, and has at least an additive effect with LPS stimulation in inducing its transcription. The priming effect of IFN-gamma on the LPS-induced p40 gene transcription requires preincubation of the cells with IFN-gamma for at least 8 h to obtain a maximal effect. The priming effect of IFN-gamma for IL-12 production is predominantly at the transcriptional level for both the p40 and the p35 gene, and no evidence for a major role of posttranscriptional or translational mechanisms was found. A 3.3-kb human IL-12 p40 promoter construct transfected into cell lines recapitulated the tissue specificity of the endogenous gene, being silent in two human T cell lines, constitutively active in two human Epstein-Barr virus-positive B lymphoblastoid cell lines, and LPS inducible in the human THP-1 and mouse RAW264.7 monocytic cell lines. Because the RAW264.7 cell line is easily transfectable and regulates the endogenous IL-12 p40 gene in response to IFN-gamma or LPS similarly to human monocytes, it was used for analysis of the regulation of the cloned human IL-12 p40 promoter. A requirement for the region between -222 and -204 in both LPS responsiveness and IFN-gamma priming was established. This region contains an ets consensus sequence that was shown to mediate activation of the promoter by IFN-gamma and LPS, as well as by a cotransfected ets-2. The -222 construct was also regulated in a tissue-specific manner. Two other elements, IRF-1 located at -730 to -719, and NF-IL6 at -520 to -512, were also studied by deletion analysis, which did not result in decreased response to IFN-gamma and LPS stimulation.
Transplantation of normal bone marrow into a pig with severe von Willebrand's disease.
Authors: E J Bowie, L A Solberg, D N Fass, C M Johnson, G J Knutson, M L Stewart, L J Zoecklein
Journal: Journal of Clinical Investigation (1986)

Bone marrow from a normal male pig was transplanted into a related female pig with severe homozygous von Willebrand's disease (vWd). After engraftment the circulating leukocytes were of the male karyotype, and the platelets were strongly positive for von Willebrand factor (vWF) by indirect immunofluorescence. The average level of vWF was 1.96 U/dl and of ristocetin cofactor was 2.8 U/dl. The ear immersion bleeding time before transplantation was consistently more than 15 min and afterwards varied between 5 min and more than 15 min. Transfused vWF corrected the bleeding time at a level of 10 U/dl, which is lower than that required for a von Willebrand pig. We concluded that: the plasmatic compartment is only minimally replenished by the vWF from platelets and megakaryocytes; and the platelet vWF alone only partially corrects the abnormal tests of the hemostatic mechanism in severe vWd.
EFFECTS OF BACTERIAL ENDOTOXIN ON RABBIT PLATELETS
Authors: Roger M. Des Prez, Herbert I. Horowitz, Edward W. Hook
Journal: The Journal of Experimental Medicine (1961)

Incubation of platelet-rich rabbit plasma with E. coli endotoxin at 37°C results in platelet aggregation and transfer of platelet 5-hydroxytryptamine to plasma. Release of 5HT is influenced by dose of endotoxin, type of anticoagulant, and temperature of incubation. A heat-labile plasma factor is necessary for the platelet-endotoxin interaction. Additional studies have shown that incubation of endotoxin with platelet-rich rabbit plasma also results in release of platelet phospholipid and bactericidins active against B. subtilis.
Diagnostic Performance of Cardiovascular Magnetic Resonance in Patients With Suspected Acute Myocarditis
Authors: Hassan Abdel-Aty, Philipp Boyé, Anja Zagrosek, Ralf Wassmuth, Andreas Kumar, Daniel Messroghli, Petra Bock, Rainer Dietz, Matthias G. Friedrich, Jeanette Schulz-Menger
Journal: Journal of the American College of Cardiology (2005)
Safety and Efficacy Of ARRY-502, a Potent, Selective, Oral CRTh2 Antagonist, In Patients With Mild To Moderate Th2-Driven Asthma
Authors: Sally E. Wenzel, Robert Hopkins, Michael Saunders, David Chantry, Lisa Anderson, Roger Aitchison, Christine Eberhardt, Stacie Bell, Jeremy Cole, James Wolfe, Sheldon L. Spector, Lawrence D. Sher, Edward M. Kerwin, Larry Burgess
Journal: Journal of Allergy and Clinical Immunology (2014)