tbuckley/cabot-search huggingface dataset:
CCR4-dependent regulatory T cell function in inflammatory bowel disease
Authors: Qian Yuan, Shannon K. Bromley, Terry K. Means, Krister J. Jones, Fumitaka Hayashi, Atul K. Bhan, Andrew D. Luster
Journal: The Journal of Experimental Medicine (2007)

Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease of the intestine. CD4+ T lymphocytes play an important role in both initiating and regulating intestinal inflammatory immune responses. CD4+CD25+CD45RBlow regulatory T (T reg) cells are capable of preventing the development of colitis in a mouse model of IBD. The precise mechanism of T reg cell–mediated prevention of colitis in this model is unclear, and the role of chemokine receptors in the trafficking and function of T reg cells in this model has not been determined. We examined the role of the chemokine receptor CCR4 in in vivo trafficking and suppressive function of T reg cells in a mouse adoptive transfer model of IBD. CCR4-deficient T reg cells failed to accumulate in the mesenteric lymph nodes (MLNs) at early time points (2–5 d) after adoptive transfer, resulting in a failure to suppress the generation of pathogenic T cells and the development of colitis. Moreover, although CCR4-deficent T cells had equivalent in vitro suppressive activity and accumulated in MLNs at later time points (42–56 d), they were unable to suppress colitis. Our study demonstrates that CCR4 plays an important role in T reg cell trafficking in LNs and that this is critical for T reg cell suppressive function in vivo.
Preprocedural Level of Soluble CD40L Is Predictive of Enhanced Inflammatory Response and Restenosis After Coronary Angioplasty
Authors: Francesco Cipollone, Claudio Ferri, Giovambattista Desideri, Leonardo Paloscia, Guido Materazzo, Marco Mascellanti, Maria Fazia, Annalisa Iezzi, Chiara Cuccurullo, Barbara Pini, Marco Bucci, Anna Santucci, Franco Cuccurullo, Andrea Mezzetti
Journal: Circulation (2003)

Inflammation plays a pathogenic role in the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA). CD40-CD40L interaction is involved in the pathogenesis of atherosclerosis; however, its role in the pathophysiology of restenosis is still unclear. We tested the hypothesis that soluble CD40L (sCD40L) may be involved in the process of restenosis and that it exerts its effect by triggering a complex group of inflammatory reactions on endothelial and mononuclear cells.We studied 70 patients who underwent PTCA and who had repeated angiograms at 6-month follow-up. Plasma sCD40L was measured before and 1, 5, 15, and 180 days after PTCA, whereas plasma soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, E-selectin, and monocyte chemoattractant protein (MCP)-1 were measured before and 24 hours after PTCA. Furthermore, the release of adhesion molecules and MCP-1 and the ability to repair an injury in endothelial cells, as well as the generation of O2- in monocytes, were analyzed in vitro after stimulation with serum from patients or healthy control subjects. Restenosis occurred in 18 patients (26%). Restenotic patients had preprocedural sCD40L significantly higher than patients with favorable outcomes (2.13+/-0.3 versus 0.87+/-0.12 ng/mL, P<0.0001). Elevated sCD40L at baseline was significantly correlated with adhesion molecules and MCP-1 generation after PTCA and with lumen loss at 6-month follow-up. Furthermore, high sCD40L was directly associated in vitro with adhesion molecules and MCP-1 generation and impaired migration in endothelial cells and with enhanced O2- generation in monocytes.We conclude that increased sCD40L is associated with late restenosis after PTCA. This may provide an important biochemical link between restenosis and aspirin-insensitive platelet activation. These results provide a rationale for studies with new antiplatelet treatments in patients who underwent PTCA.
Olfactory detection of human bladder cancer by dogs: proof of principle study
Authors: Carolyn M Willis, Susannah M Church, Claire M Guest, W Andrew Cook, Noel McCarthy, Anthea J Bransbury, Martin R T Church, John C T Church
Journal: BMJ (2004)

To determine whether dogs can be trained to identify people with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone.Experimental, "proof of principle" study in which six dogs were trained to discriminate between urine from patients with bladder cancer and urine from diseased and healthy controls and then evaluated in tests requiring the selection of one bladder cancer urine sample from six controls.36 male and female patients (age range 48-90 years) presenting with new or recurrent transitional cell carcinoma of the bladder (27 samples used for training; 9 used for formal testing); 108 male and female controls (diseased and healthy, age range 18-85 years--54 samples used in training; 54 used for testing).Mean proportion of successes per dog achieved during evaluation, compared with an expected value of 1 in 7 (14%).Taken as a group, the dogs correctly selected urine from patients with bladder cancer on 22 out of 54 occasions. This gave a mean success rate of 41% (95% confidence intervals 23% to 58% under assumptions of normality, 26% to 52% using bootstrap methods), compared with 14% expected by chance alone. Multivariate analysis suggested that the dogs' capacity to recognise a characteristic bladder cancer odour was independent of other chemical aspects of the urine detectable by urinalysis.Dogs can be trained to distinguish patients with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. This suggests that tumour related volatile compounds are present in urine, imparting a characteristic odour signature distinct from those associated with secondary effects of the tumour, such as bleeding, inflammation, and infection.
A Robust Measure of HIV-1 Population Turnover Within Chronically Infected Individuals
Authors: G Achaz, S Palmer, M Kearney, F Maldarelli, J W Mellors, J M Coffin, J Wakeley
Journal: Molecular Biology and Evolution (2004)

A simple nonparameteric test for population structure was applied to temporally spaced samples of HIV-1 sequences from the gag-pol region within two chronically infected individuals. The results show that temporal structure can be detected for samples separated by about 22 months or more. The performance of the method, which was originally proposed to detect geographic structure, was tested for temporally spaced samples using neutral coalescent simulations. Simulations showed that the method is robust to variation in samples sizes and mutation rates, to the presence/absence of recombination, and that the power to detect temporal structure is high. By comparing levels of temporal structure in simulations to the levels observed in real data, we estimate the effective intra-individual population size of HIV-1 to be between 10(3) and 10(4) viruses, which is in agreement with some previous estimates. Using this estimate and a simple measure of sequence diversity, we estimate an effective neutral mutation rate of about 5 x 10(-6) per site per generation in the gag-pol region. The definition and interpretation of estimates of such "effective" population parameters are discussed.
Evidence for a streptococcal superantigen-driven process in acute guttate psoriasis.
Authors: D Y Leung, J B Travers, R Giorno, D A Norris, R Skinner, J Aelion, L V Kazemi, M H Kim, A E Trumble, M Kotb
Journal: Journal of Clinical Investigation (1995)

Recent studies have suggested that T cells play a critical role in the pathogenesis of psoriasis. Guttate psoriasis is a well-defined form of psoriasis frequently associated with streptococcal throat infection. This study tested the hypothesis that T cells in acute guttate psoriasis skin lesions may be activated by streptococcal superantigens. Peripheral blood as well as lesional and perilesional skin biopsies were analyzed for T cell receptor V beta repertoire using monoclonal antibodies against 10 different V beta families. Skin biopsies from all patients with acute guttate psoriasis, but not skin biopsies from patients with acute atopic dermatitis or inflammatory skin lesions induced in normal subjects with sodium lauryl sulfate, demonstrated selective accumulation of V beta 2+ T cells (P < 0.05). The expansion of V beta 2+ T cells occurred in both the CD4+ and the CD8+ T cell subsets. Sequence analysis of T cell receptor beta chain genes of V beta 2-expressing T cells from skin biopsies of patients with guttate psoriasis showed extensive junctional region diversity that is more compatible with a superantigen rather than a conventional (nominal) antigen-driven T cell response. All streptococcal isolates from patients with guttate psoriasis secreted streptococcal pyrogenic exotoxin C, a superantigen known to stimulate marked V beta 2+ T cell expansion. These data support the concept that acute guttate psoriasis is associated with superantigenic stimulation of T cells triggered by streptococcal superantigen(s).
One-Carbon Metabolism,<i>MTHFR</i>Polymorphisms, and Risk of Breast Cancer
Authors: Jia Chen, Marilie D. Gammon, Wendy Chan, Caroline Palomeque, James G. Wetmur, Geoffrey C. Kabat, Susan L. Teitelbaum, Julie A. Britton, Mary Beth Terry, Alfred I. Neugut, Regina M. Santella
Journal: Cancer Research (2005)

Accumulating evidence from epidemiologic studies suggests that risk of breast cancer is reduced in relation to increased consumption of folate and related B vitamins. We investigated independent and joint effects of B vitamin intake as well as two polymorphisms of a key one-carbon metabolizing gene [i.e., methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C] on breast cancer risk. The study uses the resources of a population-based case-control study, which includes 1,481 cases and 1,518 controls. Significant inverse associations between B vitamin intake and breast cancer risk were observed among non-supplement users. The greatest reduction in breast cancer risk was observed among non-supplement users in the highest quintile of dietary folate intake [odds ratio (OR), 0.61; 95% confidence interval (95% CI), 0.41-0.93] as compared with non-supplement users in the lowest quintile of dietary folate intake (high-risk individuals). The MTHFR 677T variant allele was associated with increased risk of breast cancer (P, trend = 0.03) with a multivariate-adjusted OR of 1.37 (95% CI, 1.06-1.78) for the 677TT genotype. The 1298C variant allele was inversely associated with breast cancer risk (P, trend = 0.03), and was likely due to the linkage of this allele to the low-risk allele of 677C. The MTHFR-breast cancer associations were more prominent among women who did not use multivitamin supplements. Compared with 677CC individuals with high folate intake, elevation of breast cancer risk was most pronounced among 677TT women who consumed the lowest levels of dietary folate (OR, 1.83; 95% CI, 1.13-2.96) or total folate intake (OR, 1.71; 95% CI, 1.08-2.71). From a public heath perspective, it is important to identify risk factors, such as low B vitamin consumption, that may guide an effective prevention strategy against the disease.
464 TREATMENT OF THE “UNCOMMON” HCV GENOTYPE 4 INFECTION RECURRENCE AFTER LIVER TRANSPLANTATION. AN ITALIAN MULTICENTRIC EXPERIENCE
Authors: F.R. Ponziani, A. Gasbarrini, A. Milani, R. Viganò, M. Marino, M.F. Donato, M. Rendina, P. Toniutto, L. Pasulo, M.C. Morelli, E. De Martin, L. Miglioresi, V. Giannelli, D. Di Paolo, S. Fagiuoli, M. Pompili
Journal: Journal of Hepatology (2011)
Soluble E-selectin in sera of patients with atopic dermatitis and psoriasis-correlation with disease activity
Authors: W. CZECH, E. SCHÖPE, A. KAPP
Journal: British Journal of Dermatology (1996)

E-selectin endothelial leucocyte adhesion molecule-1 is expressed on endothelial cells in distinct inflammatory skin diseases. E-selectin mediates the adhesion between activated endothelium and different inflammatory cells. To evaluate soluble E-selectin as a marker of disease activity in patients with atopic dermatitis and psoriasis, the concentration of soluble E-selectin, determined by ELISA, was studied in sera of patients before and after treatment and compared with normal non-atopic controls. The disease severity was established using clinical scoring systems. Levels of soluble E-selectin were significantly elevated in sera of patients with atopic dermatitis and psoriasis (as compared with controls). Clinical improvement, after treatment, in patients with atopic dermatitis, but not in psoriasis, was associated with a significant decrease in serum levels of soluble E-selectin. There was a significant correlation of soluble E-selectin and disease activity in patients with atopic dermatitis. These data indicate that soluble E-selectin is another parameter to evaluate the inflammatory response in atopic dermatitis and psoriasis. Determination of soluble E-selectin may be a useful measure of disease activity in atopic dermatitis.
Results of Prevention of REStenosis with Tranilast and its Outcomes (PRESTO) Trial
Authors: David R. Holmes, Michael Savage, J.-M. LaBlanche, Lars Grip, P.W. Serruys, Peter Fitzgerald, David Fischman, Sheldon Goldberg, Jeffrey A. Brinker, A.M. Zeiher, Leonard M. Shapiro, James Willerson, Barry R. Davis, James J. Ferguson, Jeffrey Popma, Spencer B. King, A. Michael Lincoff, James E. Tcheng, Robert Chan, Jeffrey R. Granett, Marcia Poland
Journal: Circulation (2002)

Background— Restenosis after percutaneous coronary intervention (PCI) is a major problem affecting 15% to 30% of patients after stent placement. No oral agent has shown a beneficial effect on restenosis or on associated major adverse cardiovascular events. In limited trials, the oral agent tranilast has been shown to decrease the frequency of angiographic restenosis after PCI. Methods and Results— In this double-blind, randomized, placebo-controlled trial of tranilast (300 and 450 mg BID for 1 or 3 months), 11 484 patients were enrolled. Enrollment and drug were initiated within 4 hours after successful PCI of at least 1 vessel. The primary end point was the first occurrence of death, myocardial infarction, or ischemia-driven target vessel revascularization within 9 months and was 15.8% in the placebo group and 15.5% to 16.1% in the tranilast groups ( P =0.77 to 0.81). Myocardial infarction was the only component of major adverse cardiovascular events to show some evidence of a reduction with tranilast (450 mg BID for 3 months): 1.1% versus 1.8% with placebo ( P =0.061 for intent-to-treat population). The primary reason for not completing treatment was ≥1 hepatic laboratory test abnormality (11.4% versus 0.2% with placebo, P &lt;0.01). In the angiographic substudy composed of 2018 patients, minimal lumen diameter (MLD) was measured by quantitative coronary angiography. At follow-up, MLD was 1.76±0.77 mm in the placebo group, which was not different from MLD in the tranilast groups (1.72 to 1.78±0.76 to 80 mm, P =0.49 to 0.89). In a subset of these patients (n=1107), intravascular ultrasound was performed at follow-up. Plaque volume was not different between the placebo and tranilast groups (39.3 versus 37.5 to 46.1 mm 3 , respectively; P =0.16 to 0.72). Conclusions— Tranilast does not improve the quantitative measures of restenosis (angiographic and intravascular ultrasound) or its clinical sequelae.
OBSERVATIONS ON THE RELATION OF THE VIRUS CAUSING RABBIT PAPILLOMAS TO THE CANCERS DERIVING THEREFROM
Authors: Peyton Rous, J. W. Beard, John G. Kidd
Journal: The Journal of Experimental Medicine (1936)

The papillomas caused by the Shope virus sometimes grow down spontaneously into the subcutaneous tissue and extend along the lymphatics in the same way as do many cancers of the human breast. They may even invade the voluntary muscle under such circumstances, taking on an aspect suggestive of squamous cell carcinomatosis, but ultimately they differentiate in the way characteristic of the papilloma. Slight operative interferences with papillomas may be followed by a development of secondary nodules in the lungs. These result from cell emboli, and the same local conditions determine their fate as are effective in the case of emboli composed of human cancer cells. The virus-induced papilloma is not only a neoplasm in its immediate aspect and habit but sometimes one that verges upon malignancy. The tumors, including the cancers, which eventually derive from it in favorable hosts, are representative of more than a mere enhancement of the activity of the growth. They develop within a relatively brief period of time but only after the papilloma has grown for a long while; and they are morphologically various whereas the parent tumor is remarkably constant in its form. Some of the new growths differ but little from the papilloma, however, even when possessed of the ability to metastasize, and many continue to be influenced by the virus. The Shope virus is heavily conditioned in its carcinogenic activity, yet it is the nearest cause for cancer now known.
Initial FGF23-Mediated Signaling Occurs in the Distal Convoluted Tubule
Authors: Emily G. Farrow, Siobhan I. Davis, Lelia J. Summers, Kenneth E. White
Journal: Journal of the American Society of Nephrology (2009)

Fibroblast growth factor-23 (FGF23), a hormone central to phosphate and vitamin D metabolism, reduces renal absorption of phosphate by downregulating the sodium-phosphate cotransporter Npt2a. However, the mechanisms of FGF23 action in the kidney are unclear, as Npt2a localizes to the proximal tubule (PT) and the FGF23 coreceptor alpha-Klotho (KL) localizes to the distal convoluted tubule (DCT). Immunofluorescent analyses following FGF23 injection in mice showed robust staining for phospho-ERK1/2, a marker of FGF23 bioactivity, only within the DCT in a subset of KL-positive cells. This activity colocalized with the FGF23 receptor FGFR1 and was present in DCT cells that were adjacent to Npt2a-expressing PT segments. Although KL is expressed as both secreted and membrane-bound isoforms, only the membrane-bound isoform was capable of mediating FGF23 bioactivity. These findings provide novel insight into the mechanisms of hormone-regulated phosphate metabolism by identifying an intrarenal signaling axis for FGF23.
Unlooked-for Significance of Cardiac Versus Vascular Effects of Endothelin-1 in the Pathophysiology of Pulmonary Arterial Hypertension
Authors: Kumiko Taguchi, Yuichi Hattori
Journal: Circulation Research (2013)

P ulmonary arterial hypertension (PAH) is a progressive and devastating condition that is characterized by pulmonary vascular remodeling resulting in increased pulmonary vascular resistance and raised pulmonary arterial pressure, eventually leading to right ventricular (RV) failure and premature death. 1,2PAH carries a poor prognosis.][5] Unlooked-for Significance of Cardiac Versus Vascular Effects of Endothelin-1 in the Pathophysiology of PulmonaryArterial Hypertension
Sentinel node biopsy in melanoma delays recurrence but does not change melanoma-related survival: a retrospective analysis of 673 patients
Authors: R. Gutzmer, M. Al Ghazal, H. Geerlings, A. Kapp
Journal: British Journal of Dermatology (2005)

The status of the sentinel lymph node (SLN) is an important parameter to predict the prognosis of melanoma patients but it is a matter of debate if removal of micrometastases by SLN biopsy (SLNB) influences the prognosis of melanoma patients.We sought to investigate the impact of SLNB in melanoma patients with regard to recurrence-free survival, overall survival and metastatic pathways.We studied, retrospectively, 673 melanoma patients with a primary melanoma (tumour thickness > or = 1 mm) and without clinical evidence of metastases at the time of melanoma diagnosis. In 377 patients the melanoma was removed without SLNB between January 1995 and March 2000 (pre-SLNB group). In 296 patients the melanoma was removed with SLNB between April 2000 and March 2003 (SLNB group). Otherwise, both groups received identical surgical treatment of the primary melanoma and initial staging procedures performed by the same team of physicians. Follow-up recommendations were also identical in both groups.Both groups showed no significant differences with regard to characteristics of the primary melanoma, sex and age. By Kaplan-Meier analyses, melanoma-related overall survival was comparable in both groups. However, recurrence-free survival was increased in pre-SLNB patients due to significantly fewer regional lymph node metastases, whereas frequencies of locoregional cutaneous and distant metastases were comparable in both groups.SLNB advances the detection of regional lymph node metastases and therefore avoids nodal recurrences but does not influence metastatic behaviour of melanoma cells and does not protect patients from melanoma-related death caused by distant metastases. Thus, our retrospective data favour the marker hypothesis for melanoma metastasation. To elucidate further if subgroups of patients benefit from SLNB, prospective randomized studies with long-term follow-up are needed.
Cooling methods used in the treatment of exertional heat illness
Authors: J E Smith
Journal: British Journal of Sports Medicine (2005)

Objective: To review the different methods of reducing body core temperature in patients with exertional heatstroke. Methods: The search strategy included articles from 1966 to July 2003 using the databases Medline and Premedline, Embase, Evidence Based Medicine (EBM) reviews, SPORTDiscus, and cross referencing the bibliographies of relevant papers. Studies were included if they contained original data on cooling times or cooling rates in patients with heat illness or normal subjects who were subjected to heat stress. Results: In total, 17 papers were included in the analysis. From the evidence currently available, the most effective method of reducing body core temperature appears to be immersion in iced water, although the practicalities of this treatment may limit its use. Other methods include both evaporative and invasive techniques, and the use of chemical agents such as dantrolene. Conclusions: The main predictor of outcome in exertional heatstroke is the duration and degree of hyperthermia. Where possible, patients should be cooled using iced water immersion, but, if this is not possible, a combination of other techniques may be used to facilitate rapid cooling. There is no evidence to support the use of dantrolene in these patients. Further work should include a randomised trial comparing immersion and evaporative therapy in heatstroke patients.
Trabectedin in myxoid liposarcomas (MLS): a long-term analysis of a single-institution series
Authors: F. Grosso, R. Sanfilippo, E. Virdis, C. Piovesan, P. Collini, P. Dileo, C. Morosi, J.C. Tercero, J. Jimeno, M. D'Incalci, A. Gronchi, S. Pilotti, P.G. Casali
Journal: Annals of Oncology (2009)
Increased risk of pregnancy complications in patients with essential thrombocythemia carrying the JAK2 (617V&gt;F) mutation
Authors: Francesco Passamonti, Maria Luigia Randi, Elisa Rumi, Ester Pungolino, Chiara Elena, Daniela Pietra, Margherita Scapin, Luca Arcaini, Fabiana Tezza, Remigio Moratti, Cristiana Pascutto, Fabrizio Fabris, Enrica Morra, Mario Cazzola, Mario Lazzarino
Journal: Blood (2007)