tbuckley/cabot-search huggingface dataset:
Tir8/Sigirr prevents murine lupus by suppressing the immunostimulatory effects of lupus autoantigens
Authors: Maciej Lech, Onkar P. Kulkarni, Stephanie Pfeiffer, Emina Savarese, Anne Krug, Cecilia Garlanda, Alberto Mantovani, Hans-Joachim Anders
Journal: The Journal of Experimental Medicine (2008)

The Sigirr gene (also known as Tir8) encodes for an orphan receptor of the Toll-like receptor (TLR)/interleukin 1 receptor family that inhibits TLR-mediated pathogen recognition in dendritic cells. Here, we show that Sigirr also inhibits the activation of dendritic cells and B cells upon exposure to RNA and DNA lupus autoantigens. To evaluate the functional role of Sigirr in the pathogenesis of systemic lupus erythematosus (SLE), we generated Sigirr-deficient C57BL/6-lpr/lpr mice. These mice developed a progressive lymphoproliferative syndrome followed by severe autoimmune lung disease and lupus nephritis within 6 mo of age as compared with the minor abnormalities observed in C57BL/6-lpr/lpr mice. Lack of Sigirr was associated with enhanced activation of dendritic cells and increased expression of multiple proinflammatory and antiapoptotic mediators. In the absence of Sigirr, CD4 T cell numbers were increased and CD4+CD25+ T cell numbers were reduced. Furthermore, lack of Sigirr enhanced the activation and proliferation of B cells, including the production of autoantibodies against multiple nuclear lupus autoantigens. These data identify Sigirr as a novel SLE susceptibility gene in mice.
Enhanced TCR-induced Apoptosis in Interferon Regulatory Factor 4–deficient CD4+ Th Cells
Authors: Michael Lohoff, Hans-Willi Mittrücker, Anne Brüstle, Frank Sommer, Bärbel Casper, Magda Huber, David A. Ferrick, Gordon S. Duncan, Tak W. Mak
Journal: The Journal of Experimental Medicine (2004)

Transcription factors of the interferon regulatory factor (IRF) family contribute to the regulation of cell proliferation and apoptosis. Here, we show that CD4+ T helper (Th) cells lacking IRF4 (IRF4−/−) are highly sensitive to apoptosis. After infection of IRF4−/− mice with the protozoan parasite Leishmania major, the lesion-draining lymph nodes developed the prototypic lymphadenopathy of wild-type mice after 4 wk, but demonstrated almost total loss of cellularity and enhanced apoptosis after 7 wk. In vitro, activation of IRF4−/− CD4+ Th cells led to greatly increased apoptosis compared with wild-type cells. Coculture of IRF4−/− and IRF4+/+ CD4+ cells did not increase survival of IRF4−/− CD4+ cells, indicating that the enhanced rate of IRF4−/− Th cell apoptosis was neither transferable nor due to lack of a cytokine. Enhanced CD4+ cell apoptosis was also observed after anti-CD95 mAb treatment, despite normal CD95 expression. Removal of endogenous cytokines, notably interleukin (IL)-4, led to increased and equally high levels of IRF4−/− and IRF4+/+ cell apoptosis, whereas the protective activity of exogenous IL-4 was reduced in IRF4−/− CD4+ cells despite normal expression of the IL-4 receptor. Therefore, IRF4 is central in protecting CD4+ cells against proapoptotic stimuli.
Dexamethasone/ifosfamide/cisplatin/etoposide (DICE) as therapy for patients with advanced refractory non-Hodgkin's lymphoma: Preliminary report of a phase II study
Authors: Paul E. Goss, Frances A. Shepherd, J. Gerald Scott, Ellen Warner, Michael A. Baker, David Sutton, Helen A. Farquharson, Susan Buick, Simon Sutcliffe
Journal: Annals of Oncology (1991)
Human Endothelial Progenitor Cells From Type II Diabetics Exhibit Impaired Proliferation, Adhesion, and Incorporation Into Vascular Structures
Authors: Oren M. Tepper, Robert D. Galiano, Jennifer M. Capla, Christoph Kalka, Paul J. Gagne, Glen R. Jacobowitz, Jamie P. Levine, Geoffrey C. Gurtner
Journal: Circulation (2002)

Background— The recent discovery of circulating endothelial progenitor cells (EPCs) has altered our understanding of new blood vessel growth such as occurs during collateral formation. Because diabetic complications occur in conditions in which EPC contributions have been demonstrated, EPC dysfunction may be important in their pathophysiology. Methods and Results— EPCs were isolated from human type II diabetics (n=20) and age-matched control subjects (n=20). Proliferation of diabetic EPCs relative to control subjects was decreased by 48% ( P &lt;0.01) and inversely correlated with patient levels of hemoglobin A1C ( P &lt;0.05). Diabetic EPCs had normal adhesion to fibronectin, collagen, and quiescent endothelial cells but a decreased adherence to human umbilical vein endothelial cells activated by tumor necrosis factor-α (TNF-α) ( P &lt;0.05). In a Matrigel assay, diabetic EPCs were 2.5 times less likely to participate in tubule formation compared with controls ( P &lt;0.05). Conclusions— These findings suggest that type II diabetes may alter EPC biology in processes critical for new blood vessel growth and may identify a population at high risk for morbidity and mortality after vascular occlusive events.
Expression of S100A12 (EN-RAGE) in cystic fibrosis
Authors: D Foell
Journal: Thorax (2003)

Chronic airway inflammation and recurrent infections are a core phenomenon in cystic fibrosis (CF). Diagnosing acute infectious exacerbations is difficult in the presence of chronic inflammatory processes. S100A12 exhibits proinflammatory functions via interaction with the multiligand receptor for advanced glycation end products. Blocking this interaction inhibits inflammatory processes in mice.The expression of S100A12 in lung specimens of patients with end stage lung disease of CF was investigated, and S100A12 levels in the serum of patients with acute infectious exacerbations of CF were measured.Immunohistochemical studies of CF lung biopsy specimens revealed a significant expression of S100A12 by infiltrating neutrophils. High S100A12 levels were found in the sputum of patients with CF, and serum levels of S100A12 during acute infectious exacerbations were significantly increased compared with healthy controls (median 225 ng/ml v 46 ng/ml). After treatment with intravenous antibiotics the mean S100A12 level decreased significantly. There was also a significant difference between S100A12 levels in patients with acute infectious exacerbations and 18 outpatients without exacerbations (median 225 ng/ml v 105 ng/ml).S100A12 is extensively expressed at local sites of inflammation in CF. It is a serum marker for acute infectious exacerbations. High local expression of S100A12 suggests that this protein has a proinflammatory role during airway inflammation and may serve as a novel target for anti-inflammatory treatments.
Etanercept Therapy in Rheumatoid Arthritis
Authors: Larry W. Moreland
Journal: Annals of Internal Medicine (1999)

Background: In a phase II study, etanercept (recombinant human tumor necrosis factor receptor [p75]:Fc fusion protein) safely produced rapid, dose-dependent improvement in rheumatoid arthritis over 3 months. Objective: To confirm the benefit of etanercept therapy of longer duration and simplified dosing in patients with rheumatoid arthritis. Design: Randomized, double-blind, placebo-controlled trial with blinded joint assessors. Setting: 13 North American centers. Patients: 234 patients with active rheumatoid arthritis who had an inadequate response to disease-modifying antirheumatic drugs. Intervention: Twice-weekly subcutaneous injections of etanercept, 10 or 25 mg, or placebo for 6 months. Measurements: The primary end points were 20% and 50% improvement in disease activity according to American College of Rheumatology (ACR) responses at 3 and 6 months. Other end points were 70% ACR responses at 3 and 6 months and other measures of disease activity at 3 and 6 months. Results: Etanercept significantly reduced disease activity in a dose-related fashion. At 3 months, 62% of the patients receiving 25 mg of etanercept and 23% of the placebo recipients achieved 20% ACR response (P < 0.001). At 6 months, 59% of the 25-mg group and 11% of the placebo group achieved a 20% ACR response (P < 0.001); 40% and 5%, respectively, achieved a 50% ACR response (P < 0.01). The respective mean percentage reduction in the number of tender and swollen joints at 6 months was 56% and 47% in the 25-mg group and 6% and −7% in the placebo group (P < 0.05). Significantly more etanercept recipients achieved a 70% ACR response, minimal disease status (0 to 5 affected joints), and improved quality of life. Etanercept was well tolerated, with no dose-limiting toxic effects. Conclusions: Etanercept can safely provide rapid, significant, and sustained benefit in patients with active rheumatoid arthritis.
Effect of Aldosterone Antagonism on Myocardial Dysfunction in Hypertensive Patients With Diastolic Heart Failure
Authors: Philip M. Mottram, Brian Haluska, Rodel Leano, Diane Cowley, Michael Stowasser, Thomas H. Marwick
Journal: Circulation (2004)

Specific treatments targeting the pathophysiology of hypertensive heart disease are lacking. As aldosterone has been implicated in the genesis of myocardial fibrosis, hypertrophy, and dysfunction, we sought to determine the effects of aldosterone antagonism on myocardial function in hypertensive patients with suspected diastolic heart failure by using sensitive quantitative echocardiographic techniques in a randomized, double-blinded, placebo-controlled study.Thirty medically treated ambulatory hypertensive patients (19 women, age 62+/-6 years) with exertional dyspnea, ejection fraction >50%, and diastolic dysfunction (E/A <1, E deceleration time >250 m/sec) and without ischemia were randomized to spironolactone 25 mg/d or placebo for 6 months. Patients were overweight (31+/-5 kg/m2) with reduced treadmill exercise capacity (6.7+/-2.1 METS). Long-axis strain rate (SR), peak systolic strain, and cyclic variation of integrated backscatter (CVIB) were averaged from 6 walls in 3 standard apical views. Mean 24-hour ambulatory blood pressure at baseline (133+/-17/80+/-7 mm Hg) did not change in either group. Values for SR, peak systolic strain, and CVIB were similar between groups at baseline and remained unchanged with placebo. Spironolactone therapy was associated with increases in SR (baseline: -1.57+/-0.46 s(-1) versus 6-months: -1.91+/-0.36 s(-1), P<0.01), peak systolic strain (-20.3+/-5.0% versus -26.9+/-4.3%, P<0.001), and CVIB (7.4+/-1.7 dB versus 8.6+/-1.7 dB, P=0.08). Each parameter was significantly greater in the spironolactone group compared with placebo at 6 months (P=0.05, P=0.02, and P=0.02, respectively), and the increases remained significant after adjusting for baseline differences. The increase in strain was independent of changes in blood pressure with intervention. The spironolactone group also exhibited reduction in posterior wall thickness (P=0.04) and a trend to reduced left atrial area (P=0.09).Aldosterone antagonism improves myocardial function in hypertensive heart disease.
Vasovagal Pseudohemorrhage Complication of Percutaneous Renal Biopsy
Authors: W. Kline Bolton
Journal: JAMA (1977)

PERCUTANEOUS renal biopsy is associated with a low risk of morbidity and mortality when precise localization techniques are used.<sup>1,2</sup>Nonetheless, a small number of patients will have complications from percutaneous renal biopsy.<sup>2,3</sup>One of the most serious complications is biopsyrelated bleeding requiring surgical intervention. The present report describes a patient who was initially considered to have hemorrhagic complications from a percutaneous biopsy but probably presented this clinical picture through the circumstantial interaction of diverse events. <h3>Report of a Case</h3> A 22-year-old woman with systemic lupus erythematosus was admitted to the University of Virginia Hospital for a percutaneous renal biopsy. The physical examination was essentially unremarkable. Her weight was 46.3 kg; blood pressure, 130/90 mm Hg; and pulse, 73 beats per minute. The creatinine clearance was 80 ml/min; quantitative urinary protein level, 6 gm/24 hr; hematocrit reading, 29%; platelet count, 197,000/cu mm; fibrinogen, 500 mg/100 ml; prothrombin time, 12.0/
Characterization and Localization of the Neonatal Fc Receptor in Adult Human Kidney
Authors: JEAN-PHILIPPE HAYMANN, JEAN-PIERRE LEVRAUD, SANDRINE BOUET, VINCENT KAPPES, JACQUELINE HAGÈGE, GENEVIEVE NGUYEN, YICHUN XU, ERIC RONDEAU, JEAN-DANIEL SRAER
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The binding of Fc fragments of Ig on glomerular epithelial cells (GEC) was observed previously, but the receptor could not be identified. In immunofluorescence and immunohistochemical studies using normal adult human kidney sections, the presence of the so-called neonatal Fc receptor (FcRn) was demonstrated on GEC as well as in the brush border of proximal tubular cells. FcRn transcripts were also detected on isolated glomeruli by reverse transcription-PCR. Using an immortalized GEC line, the presence of the FcRn was confirmed by flow cytometry, reverse transcription-PCR, Western blotting, and by the pH dependence of the binding of heat-aggregated IgG. Because it is well established that the FcRn is involved in IgG transcytosis, it is hypothesized that the FcRn in the kidney may play a role in the reabsorption of IgG. Ongoing studies should clarify the role of the FcRn as a potential target for immune complexes on GEC and should assess its relevance in physiology and pathology.
A nonrandom association of gastrointestinal stromal tumor (GIST) and desmoid tumor (deep fibromatosis): case series of 28 patients
Authors: A.G. Dumont, L. Rink, A.K. Godwin, M. Miettinen, H. Joensuu, J.R. Strosberg, A. Gronchi, C.L. Corless, D. Goldstein, B.P. Rubin, R.G. Maki, A.J. Lazar, D. Lev, J.C. Trent, M. von Mehren
Journal: Annals of Oncology (2011)
P54 CHASE-B (Chinese Hepatitis Awareness, Surveillance and Education): a pilot of targeted case finding for hepatitis B virus (HBV) in the British-Chinese community
Authors: S. McPherson, M. Valappil, S. Moses, G. Eltringham, C. Miller, K. Baxter, B. Brown, P. Clapper, A. Chan, M. Hudson, M. Bassendine
Journal: Gut (2011)

<h3>Introduction</h3> Chronic HBV (cHBV) is a frequent cause of cirrhosis and liver cancer. Many infected individuals are unaware of their condition. Migrants from countries with high prevalence of cHBV, such as China and the Far East (seroprevalence 7–12%), are a high risk group for cHBV. Targeted HBV screening and vaccination is recommended by the AASLD1 and the European Liver Patients Association (ELPA)2 in high risk groups including subjects born in endemic areas. However, there are no current UK guidelines. <h3>Aim</h3> To apply AASLD and ELPA recommendations to British-Chinese community of North East (NE) England. <h3>Method</h3> Members of the NE Chinese community were invited to attend screening sessions at the Newcastle Chinese Healthy Living Centre [charity registration no. 1125227]. Dry blood spots were obtained by finger prick and tested for HBsAg and HBcAb (Abbott ARCHITECT). HBsAg positive individuals were advised to undergo confirmatory testing and be referred for specialist assessment. <h3>Results</h3> 575 subjects were screened in 10 sessions (mean age 49±17 years, 61% female). 53 (9%) were HBsAg positive (48% female) indicating cHBV. 10 of these reported being previously diagnosed with HBV, but were not under follow-up. The prevalence of HBsAg positivity was 7.5% when previously diagnosed individuals were excluded. 80 (14%) subjects had past infection with HBV (HBsAg negative, HBcAb positive). Individuals with past HBV were significantly older than HBsAg positive and HBsAg, HBcAb negative subjects (p&lt;0.001). The prevalence of HBsAg positivity was highest in subjects born in Vietnam (17.4%, 4/23), followed by China (11.5%, 24/157), Hong Kong (8.3%, 18/288), the UK (6.7%, 5/75) and other (6.2%, 2/32). Only 12% of subjects reported previous vaccination against HBV. To date, 25 of the HBsAg positive individuals have been seen in our clinic. 1 was HBeAg positive (immunotolerant) and 24 were HBeAg negative. Of these, 3 have active disease (including 1 cirrhotic) and have been started on treatment. 14 have inactive cHBV and 7 are undergoing observation to determine disease activity. No cases of co-infection with HCV, HIV or Delta were found. <h3>Conclusion</h3> 1. Undiagnosed cHBV is common in the British-Chinese community of NE England, including subjects born in the UK. 2. A proportion had active cHBV requiring treatment. 3. If these results were applied to the entire UK British-Chinese population targeted screening should lead to approximately 32 250 newly diagnosed cases of cHBV. 4. These results provide evidence for a UK HBV screening and vaccination program for the British-Chinese community.
PERSONNEL AWARENESS OF PATIENTS' SOCIALIZING CAPACITY
Authors: FRANCOISE R. MORIMOTO, MILTON GREENBLATT
Journal: American Journal of Psychiatry (1953)

Interviews of ward personnel and families of patients were conducted to determine the quantity and quality of patients' leisure-time pursuits; to determine the degree of personnel's awareness of these pursuits; and to determine the sources utilized by personnel for gaining information on the leisure-time activities prior to hospitalization. The findings were as follows: 1. Before illness, patients primarily selected leisure-time activities that required skill rather than passive watching. Most popular were activities of a routine, everyday nature pursued casually in groups. A few patients had more specialized skills and interests such as ballet, clothes designing, etc. 2. Personnel were aware of only 23.3% of patients' pre-illness leisure-time activities. There was high awareness on 3 patients, partial awareness on 8, and no awareness on 19. Although they were in agreement with family members as to patients' being doers rather than spectators (more active than passive pursuits), personnel saw patients as pursuing their leisure-time activities alone rather than in groups. They showed their highest awareness in the case of patients who had already begun to socialize. 3. Two main sources for gaining information regarding patients' prehospitalization activities were conversation with and observation of the patients on the ward. In only a few instances did they communicate with other personnel or with patients' families before the patients themselves made their interests known. These findings have special relevance to the nurse's role as a socializing influence. It is clear that nurses are very often unaware of the socializing capacities of their patients. Without this information, the possibilities of bringing patients into social interaction remain limited, and many opportunities to help them emerge from their withdrawn state are missed. On the other hand, if fully informed of the patients' potentialities, the nurse may carry out more effectively her important function as a socializing leader.
Arterial Wall Changes in Chronic Cerebrovasospasm: In Vitro and In Vivo Pharmacological Evidence
Authors: J. A. Bevan, R. D. Bevan
Journal: The Annual Review of Pharmacology and Toxicology (1988)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
Tumor Regression and Autoimmunity after Reversal of a Functionally Tolerant State of Self-reactive CD8+ T Cells
Authors: Willem W. Overwijk, Marc R. Theoret, Steven E. Finkelstein, Deborah R. Surman, Laurina A. de Jong, Florry A. Vyth-Dreese, Trees A. Dellemijn, Paul A. Antony, Paul J. Spiess, Douglas C. Palmer, David M. Heimann, Christopher A. Klebanoff, Zhiya Yu, Leroy N. Hwang, Lionel Feigenbaum, Ada M. Kruisbeek, Steven A. Rosenberg, Nicholas P. Restifo
Journal: The Journal of Experimental Medicine (2003)

Many tumor-associated antigens are derived from nonmutated “self” proteins. T cells infiltrating tumor deposits recognize self-antigens presented by tumor cells and can be expanded in vivo with vaccination. These T cells exist in a functionally tolerant state, as they rarely result in tumor eradication. We found that tumor growth and lethality were unchanged in mice even after adoptive transfer of large numbers of T cells specific for an MHC class I–restricted epitope of the self/tumor antigen gp100. We sought to develop new strategies that would reverse the functionally tolerant state of self/tumor antigen-reactive T cells and enable the destruction of large (with products of perpendicular diameters of &amp;gt;50 mm2), subcutaneous, unmanipulated, poorly immunogenic B16 tumors that were established for up to 14 d before the start of treatment. We have defined three elements that are all strictly necessary to induce tumor regression in this model: (a) adoptive transfer of tumor-specific T cells; (b) T cell stimulation through antigen-specific vaccination with an altered peptide ligand, rather than the native self-peptide; and (c) coadministration of a T cell growth and activation factor. Cells, vaccination, or cyto-kine given alone or any two in combination were insufficient to induce tumor destruction. Autoimmune vitiligo was observed in mice cured of their disease. These findings illustrate that adoptive transfer of T cells and IL-2 can augment the function of a cancer vaccine. Furthermore, these data represent the first demonstration of complete cures of large, established, poorly immunogenic, unmanipulated solid tumors using T cells specific for a true self/tumor antigen and form the basis for a new approach to the treatment of patients with cancer.
The in-betweeners: MAIT cells join the innate-like lymphocytes gang
Authors: David H. Margulies
Journal: The Journal of Experimental Medicine (2014)

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Insight from David Margulies



Recent studies of mucosal-associated invariant T (MAIT) cells indicate that they respond to a range of pathogen-derived vitamin metabolites presented at the cell surface by the evolutionarily conserved and nonpolymorphic MHC-related class I-like