tbuckley/cabot-search huggingface dataset:
IL-10/TGF-β–Modified Macrophages Induce Regulatory T Cells and Protect against Adriamycin Nephrosis
Authors: Qi Cao, Yiping Wang, Dong Zheng, Yan Sun, Ya Wang, Vincent W.S. Lee, Guoping Zheng, Thian Kui Tan, Jon Ince, Stephen I. Alexander, David C.H. Harris
Journal: Journal of the American Society of Nephrology (2010)

IL-10/TGF-β–modified macrophages, a subset of activated macrophages, produce anti-inflammatory cytokines, suggesting that they may protect against inflammation-mediated injury. Here, macrophages modified ex vivo by IL-10/TGF-β (IL-10/TGF-β Μ2) significantly attenuated renal inflammation, structural injury, and functional decline in murine adriamycin nephrosis (AN). These cells deactivated effector macrophages and inhibited CD4+ T cell proliferation. IL-10/TGF-β Μ2 expressed high levels of the regulatory co-stimulatory molecule B7-H4, induced regulatory T cells from CD4+CD25− T cells in vitro, and increased the number of regulatory T cells in lymph nodes draining the kidneys in AN. The phenotype of IL-10/TGF-β Μ2 did not switch to that of effector macrophages in the inflamed kidney, and these cells did not promote fibrosis. Taken together, these data demonstrate that IL-10/TGF-β–modified macrophages effectively protect against renal injury in AN and may become part of a therapeutic strategy for chronic inflammatory disease.
Concurrent use of indacaterol plus tiotropium in patients with COPD provides superior bronchodilation compared with tiotropium alone: a randomised, double-blind comparison
Authors: Donald A Mahler, Anthony D'Urzo, Eric D Bateman, Serir A Özkan, Tracy White, Clare Peckitt, Cheryl Lassen, Benjamin Kramer
Journal: Thorax (2012)

<h3>Background</h3> Current guidelines recommend treatment with one or more long-acting bronchodilators for patients with moderate or more severe chronic obstructive pulmonary disease (COPD). The authors investigated the approach of dual bronchodilation using indacaterol, a once-daily long-acting β<sub>2</sub> agonist, and the long-acting muscarinic antagonist tiotropium, compared with tiotropium alone. <h3>Methods</h3> In two identically designed, double-blind, 12-week studies, patients with moderate to severe COPD were randomised to indacaterol 150 μg once daily or matching placebo. All patients concurrently received open-label tiotropium 18 μg once daily. The primary outcome was standardised area under the curve of forced expiratory volume in 1 s (FEV<sub>1</sub>) from 5 min to 8 h post dose at week 12. The key secondary outcome was 24 h post-dose ('trough') FEV<sub>1</sub> at week 12. Resting inspiratory capacity (IC) was measured in a subgroup. <h3>Results</h3> 1134 and 1142 patients were randomised in studies 1 and 2; 94% and 94% completed. Compared with monotherapy, concurrent therapy increased FEV<sub>1</sub> (area under the curve by 130 and 120 ml, trough by 80 and 70 ml; all p&lt;0.001) and trough IC (by 130 and 100 ml, p&lt;0.01). Cough was more common with indacaterol plus tiotropium (10% and 9%) than with tiotropium alone (4% and 4%). Most cases (∼90%) of cough were mild. Other adverse events were similar for the treatment groups. <h3>Conclusions</h3> Compared with tiotropium monotherapy, indacaterol plus tiotropium provided greater bronchodilation and lung deflation (reflected by increased resting IC). Adverse events were similar between treatments apart from mild cough being more common with indacaterol plus tiotropium. These results support COPD guideline recommendations to combine bronchodilators with different mechanisms of action. <h3>Trial registration numbers</h3> NCT00846586 and NCT00877383.
DARPP-32: An Integrator of Neurotransmission
Authors: Per Svenningsson, Akinori Nishi, Gilberto Fisone, Jean-Antoine Girault, Angus C. Nairn, Paul Greengard
Journal: The Annual Review of Pharmacology and Toxicology (2004)

Dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32), was identified initially as a major target for dopamine and protein kinase A (PKA) in striatum. However, recent advances now indicate that regulation of the state of DARPP-32 phosphorylation provides a mechanism for integrating information arriving at dopaminoceptive neurons, in multiple brain regions, via a variety of neurotransmitters, neuromodulators, neuropeptides, and steroid hormones. Activation of PKA or PKG stimulates DARPP-32 phosphorylation at Thr34 and thereby converts DARPP-32 into a potent inhibitor of protein phosphatase-1 (PP-1). DARPP-32 is also phosphorylated at Thr75 by Cdk5 and this converts DARPP-32 into an inhibitor of PKA. Thus, DARPP-32 has the unique property of being a dual-function protein, acting either as an inhibitor of PP-1 or of PKA. The state of phosphorylation of DARPP-32 at Thr34 depends on the phosphorylation state of two serine residues, Ser102 and Ser137, which are phosphorylated by CK2 and CK1, respectively. By virtue of its ability to modulate the activity of PP-1 and PKA, DARPP-32 is critically involved in regulating electrophysiological, transcriptional, and behavioral responses to physiological and pharmacological stimuli, including antidepressants, neuroleptics, and drugs of abuse.
Antigenic analysis of gonococcal pili using monoclonal antibodies.
Authors: M Edwards, R L McDade, G Schoolnik, J B Rothbard, E C Gotschlich
Journal: The Journal of Experimental Medicine (1984)

A bank of mouse monoclonal antibodies has been produced with reactivity to gonococcal pili to investigate epitopes of the pilus structural protein, pilin. Pili of Neisseria gonorrhoeae strains R10 and MS11 were used as immunogens to elicit 19 monoclonal antibodies reactive with the homologous pili type in ELISA. Of the 19 antibodies, 16 demonstrated type-specific reactivity and 3 were cross-reactive with heterologous pili. Reactivity of the antibodies with the carboxyterminal, cyanogen bromide fragment (CB-3) of R10 pilin allowed their classification into three groups. The first group (10 antibodies) were R10 specific and equally reactive with the R10 CB-3 fragment. The second group (6) were also type specific but demonstrated poor reactivity with the CB-3 fragment. This suggested that the epitopes of the first group are linear, and those of the second group, nonlinear. The third group (3), consisting of the cross-reactive antibodies, were not reactive with the CB-3 fragment. Two of the antibodies in group 3 were examined in detail to localize their epitopes. The epitope of one, 9B9/H5, was shown to be a linear determinant. This antibody was reactive with a fragment of MS11 pilin (residues 31-111) and to a synthetic peptide representing residues 69-84 in MS11 pilin. The epitope was more finely mapped, with shorter synthetic peptides conjugated to bovine serum albumin, to an eight amino acid segment (residues 69-76). The epitope of 1E8/G8, a strongly reactive antibody, proved elusive to this type of analysis and probably results from conformational restraints. The significance of species-specific epitopes in the pilin protein is discussed.
Evidence for Cardiomyocyte Repopulation by Extracardiac Progenitors in Transplanted Human Hearts
Authors: Michael A. Laflamme, David Myerson, Jeffrey E. Saffitz, Charles E. Murry
Journal: Circulation Research (2002)

Human myocardium has long been considered to have essentially no intrinsic regenerative capacity. Recent studies in rodent models, however, have suggested the presence of an extracardiac stem cell population, perhaps in bone marrow, that is capable of some reconstitution of cardiomyocytes after injury. To determine whether similar mechanisms exist in the human heart, we evaluated human female allograft hearts transplanted into male patients. The presence of Y chromosomes in cardiomyocytes would indicate these cells arose from the recipient, rather than the donor heart. We identified 5 male patients who had retained a female heart at least 9 months before death and necropsy. Remarkably, in each case, the transplanted heart contained a minute but readily detectable fraction of Y chromosome-positive cardiomyocytes. The mean percentage of cardiomyocytes arising from the host was estimated to be 0.04% with a median of 0.016%. Most Y-positive cardiomyocytes were associated with regions of acute rejection, suggesting such chimerism involves an injury event. Furthermore, the sole patient whose immediate cause of death was allograft rejection showed a much higher percentage of host-derived cardiomyocytes, up to 29% in local, 1-mm 2 “hot spots.” Thus, adult humans have extracardiac progenitor cells capable of migrating to and repopulating damaged myocardium, but this process occurs at very low levels.
Differences in Time to Disease Progression Do Not Predict for Cancer-specific Survival in Patients Receiving Immediate or Deferred Androgen-deprivation Therapy for Prostate Cancer: Final Results of EORTC Randomized Trial 30891 with 12 Years of Follow-up
Authors: Urs E Studer, Peter Whelan, Florian Wimpissinger, Jacques Casselman, Theo M de Reijke, Hartmut Knönagel, Wolfgang Loidl, Santiago Isorna, Subramanian K Sundaram, Laurence Collette
Journal: European Urology (2013)
Long-term follow-up of patients on home parenteral nutrition in Europe: implications for intestinal transplantation
Authors: L. Pironi, F. Joly, A. Forbes, V. Colomb, M. Lyszkowska, J. Baxter, S. Gabe, X. Hebuterne, M. Gambarara, F. Gottrand, C. Cuerda, P. Thul, B. Messing, O. Goulet, M. Staun, A. Van Gossum
Journal: Gut (2010)

<h3>Background</h3> The indications for intestinal transplantation (ITx) are still debated. Knowing survival rates and causes of death on home parenteral nutrition (HPN) will improve decisions. <h3>Methods</h3> A prospective 5-year study compared 389 non-candidates (no indication, no contraindication) and 156 candidates (indication, no contraindication) for ITx. Indications were: HPN failure (liver failure; multiple episodes of catheter-related venous thrombosis or sepsis; severe dehydration), high-risk underlying disease (intra-abdominal desmoids; congenital mucosal disorders; ultra-short bowel), high morbidity intestinal failure. Causes of death were defined as: HPN-related, underlying disease, or other cause. <h3>Results</h3> The survival rate was 87% in non-candidates, 73% in candidates with HPN failure, 84% in those with high-risk underlying disease, 100% in those with high morbidity intestinal failure and 54%, in ITx recipients (one non-candidate and 21 candidates) (p&lt;0.001). The primary cause of death on HPN was underlying disease-related in patients with HPN duration ≤2 years, and HPN-related in those on HPN duration &gt;2 years (p=0.006). In candidates, the death HRs were increased in those with desmoids (7.1; 95% CI 2.5 to 20.5; p=0.003) or liver failure (3.4; 95% CI 1.6 to 7.3; p=0.002) compared to non-candidates. In deceased candidates, the indications for ITx were the causes of death in 92% of those with desmoids or liver failure, and in 38% of those with other indications (p=0.041). In candidates with catheter-related complications or ultra-short bowel, the survival rate was 83% in those who remained on HPN and 78% after ITx (p=0.767). <h3>Conclusions</h3> HPN is confirmed as the primary treatment for intestinal failure. Desmoids and HPN-related liver failure constitute indications for life-saving ITx. Catheter-related complications and ultra-short bowel might be indications for pre-emptive/rehabilitative ITx. In the early years after commencing HPN a life-saving ITx could be required for some patients at higher risk of death from their underlying disease.
Impact of Viability, Ischemia, Scar Tissue, and Revascularization on Outcome After Aborted Sudden Death
Authors: Alida E. Borger van der Burg, Jeroen J. Bax, Eric Boersma, Ernest K.J. Pauwels, Ernst E. van der Wall, Martin J. Schalij
Journal: Circulation (2003)

Survivors of aborted sudden death attributable to ventricular arrhythmias in the presence of coronary artery disease are at risk for recurrences. The substrate underlying these arrhythmias is not clear, and therefore the relation between ischemia, viability, scar tissue (and revascularization), and the incidence of ventricular arrhythmias (and survival) was studied over up to 3 years.One hundred fifty-three survivors of sudden death underwent stress-rest perfusion imaging. Patients with ischemic/viable myocardium (n=73) were revascularized if possible. Final antiarrhythmic therapy was based on the outcome of electrophysiological testing or left ventricular ejection fraction (LVEF). Implantation of a defibrillator was performed in 112 (72%) patients. During 3-year follow-up, 15 cardiac deaths occurred and 42 (29%) patients had recurrent ventricular arrhythmias. Patients with events (death or recurrence) exhibited more often a severely depressed LVEF (< or =30%), more extensive scar tissue, and less ischemic/viable myocardium on perfusion imaging and less frequently underwent revascularization. Multivariate analysis identified extensive scar tissue and LVEF < or =30% as the only predictors of death/recurrent ventricular arrhythmias.In patients with aborted sudden death, extensive scar tissue and severely depressed LVEF are the only predictors of death or recurrent ventricular arrhythmias. These patients should be considered for implantation of a defibrillator.
Incidence and Outcome of Male Breast Cancer: An International Population-Based Study
Authors: Hui Miao, Helena M. Verkooijen, Kee-Seng Chia, Christine Bouchardy, Eero Pukkala, Siri Larønningen, Lene Mellemkjær, Kamila Czene, Mikael Hartman
Journal: Journal of Clinical Oncology (2011)

Purpose Male breast cancer is a rare disease with an incidence rate less than 1% of that of female breast cancer. Given its low incidence, few studies have assessed risk and prognosis. Methods This population-based study, including 459,846 women and 2,665 men diagnosed with breast cancer in Denmark, Finland, Geneva, Norway, Singapore, and Sweden over the last 40 years, compares trends in incidence, relative survival, and relative excess mortality between the sexes. Results World standardized incidence rates of breast cancer were 66.7 per 10 5 person-years in women and 0.40 per 10 5 person-years in men. Women were diagnosed at a younger median age (61.7 years) than men (69.6 years). Male patients had a poorer 5-year relative survival ratio than women (0.72 [95% CI, 0.70 to 0.75] v 0.78 [95% CI, 0.78 to 0.78], respectively), corresponding to a relative excess risk (RER) of 1.27 (95% CI, 1.13 to 1.42). However, after adjustment for age and year of diagnosis, stage, and treatment, male patients had a significantly better relative survival from breast cancer than female patients (RER, 0.78; 95% CI, 0.62 to 0.97). Conclusion Male patients with breast cancer have later onset of disease and more advanced disease than female patients. Male patients with breast cancer have lower risk of death from breast cancer than comparable female patients.
CodABC: A Computational Framework to Coestimate Recombination, Substitution, and Molecular Adaptation Rates by Approximate Bayesian Computation
Authors: M. Arenas, J. S. Lopes, M. A. Beaumont, D. Posada
Journal: Molecular Biology and Evolution (2015)

The estimation of substitution and recombination rates can provide important insights into the molecular evolution of protein-coding sequences. Here, we present a new computational framework, called "CodABC," to jointly estimate recombination, substitution and synonymous and nonsynonymous rates from coding data. CodABC uses approximate Bayesian computation with and without regression adjustment and implements a variety of codon models, intracodon recombination, and longitudinal sampling. CodABC can provide accurate joint parameter estimates from recombining coding sequences, often outperforming maximum-likelihood methods based on more approximate models. In addition, CodABC allows for the inclusion of several nuisance parameters such as those representing codon frequencies, transition matrices, heterogeneity across sites or invariable sites. CodABC is freely available from http://code.google.com/p/codabc/, includes a GUI, extensive documentation and ready-to-use examples, and can run in parallel on multicore machines.
Critical role of stearoyl-CoA desaturase-1 (SCD1) in the onset of diet-induced hepatic insulin resistance
Authors: R. Gutierrez-Juarez
Journal: Journal of Clinical Investigation (2006)

Stearoyl-CoA desaturase-1 (SCD1) catalyzes the synthesis of monounsaturated fatty acids from saturated fatty acids. Mice with a targeted disruption of Scd1 gene locus are lean and display increased insulin sensitivity. To examine whether Scd1 activity is required for the development of diet-induced hepatic insulin resistance, we used a sequence-specific antisense oligodeoxynucleotide (ASO) to lower hepatic Scd1 expression in rats and mice with diet-induced insulin resistance. Treatment of rats with Scd1 ASO markedly decreased liver Scd1 expression (approximately 80%) and total Scd activity (approximately 50%) compared with that in rats treated with scrambled ASO (control). Insulin clamp studies revealed severe hepatic insulin resistance in high-fat-fed rats and mice that was completely reversed by 5 days of treatment with Scd1 ASO. The latter treatment decreased glucose production (by approximately 75%), gluconeogenesis, and glycogenolysis. Downregulation of Scd1 also led to increased Akt phosphorylation and marked decreases in the expression of glucose-6-phosphatase (Glc-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK). Thus, Scd1 is required for the onset of diet-induced hepatic insulin resistance.
Improving Gemcitabine-Mediated Radiosensitization Using Molecularly Targeted Therapy: A Review
Authors: Meredith A. Morgan, Leslie A. Parsels, Jonathan Maybaum, Theodore S. Lawrence
Journal: Clinical Cancer Research (2008)

Abstract In the last three decades, gemcitabine has progressed from the status of a laboratory cytotoxic drug to a standard clinical chemotherapeutic agent and a potent radiation sensitizer. In an effort to improve the efficacy of gemcitabine, additional chemotherapeutic agents have been combined with gemcitabine (both with and without radiation) but with toxicity proving to be a major limitation. Therefore, the integration of molecularly targeted agents, which potentially produce less toxicity than standard chemotherapy, with gemcitabine radiation is a promising strategy for improving chemoradiation. Two of the most promising targets, described in this review, for improving the efficacy of gemcitabine radiation are epidermal growth factor receptor and checkpoint kinase 1.
The Secret of Immortal Time Bias in Epidemiologic Studies
Authors: Salimah Z Shariff, Meaghan S Cuerden, Arsh K Jain, Amit X Garg
Journal: Journal of the American Society of Nephrology (2008)

In the March 2007 issue of JASN , Hemmelgarn et al. [1][1] reported a 50% reduction in the risk for all-cause mortality for patients who had chronic kidney disease (CKD) and attended multidisciplinary care (MDC) clinics compared with those who received usual care. Their survival curves showed a
How not to get scar(r)ed: pointers to the correct diagnosis in patients with suspected primary cicatricial alopecia
Authors: M.J. Harries, R.M. Trueb, A. Tosti, A.G. Messenger, I. Chaudhry, D.A. Whiting, R. Sinclair, C.E.M. Griffiths, R. Paus
Journal: British Journal of Dermatology (2009)

Journal Article How not to get scar(r)ed: pointers to the correct diagnosis in patients with suspected primary cicatricial alopecia Get access M.J. Harries, M.J. Harries Dermatological Sciences, The University of Manchester, Salford Royal Hospital, Manchester M6 8HD, U.K.Department of Dermatology, University of Lübeck, D‐23538 Lübeck, Germany Correspondence: Matthew Harries. E‐mail: mjharries@doctors.org.uk Search for other works by this author on: Oxford Academic Google Scholar R.M. Trueb, R.M. Trueb Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland Search for other works by this author on: Oxford Academic Google Scholar A. Tosti, A. Tosti Department of Dermatology, University of Bologna, Bologna, Italy Search for other works by this author on: Oxford Academic Google Scholar A.G. Messenger, A.G. Messenger Department of Dermatology, University of Sheffield, Hallamshire Hospital, Sheffield, U.K. Search for other works by this author on: Oxford Academic Google Scholar I. Chaudhry, I. Chaudhry Department of Histopathology, Manchester Royal Infirmary, Manchester, U.K. Search for other works by this author on: Oxford Academic Google Scholar D.A. Whiting, D.A. Whiting Baylor Hair Research and Treatment Centre, Dallas, TX, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar R. Sinclair, R. Sinclair Department of Dermatology, University of Melbourne, Melbourne, Australia Search for other works by this author on: Oxford Academic Google Scholar C.E.M. Griffiths, C.E.M. Griffiths Dermatological Sciences, The University of Manchester, Salford Royal Hospital, Manchester M6 8HD, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. Paus R. Paus Dermatological Sciences, The University of Manchester, Salford Royal Hospital, Manchester M6 8HD, U.K.Department of Dermatology, University of Lübeck, D‐23538 Lübeck, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 160, Issue 3, 1 March 2009, Pages 482–501, https://doi.org/10.1111/j.1365-2133.2008.09008.x Published: 01 March 2009
Testosterone and Sex Hormone–Binding Globulin Predict the Metabolic Syndrome and Diabetes in Middle-Aged Men
Authors: David E. Laaksonen, Leo Niskanen, Kari Punnonen, Kristiina Nyyssönen, Tomi-Pekka Tuomainen, Veli-Pekka Valkonen, Riitta Salonen, Jukka T. Salonen
Journal: Diabetes Care (2004)

In men, hypoandrogenism is associated with features of the metabolic syndrome, but the role of sex hormones in the pathogenesis of the metabolic syndrome and diabetes is not well understood. We assessed the association of low levels of testosterone and sex hormone-binding globulin (SHBG) with the development of the metabolic syndrome and diabetes in men.Concentrations of SHBG and total and calculated free testosterone and factors related to insulin resistance were determined at baseline in 702 middle-aged Finnish men participating in a population-based cohort study. These men had neither diabetes nor the metabolic syndrome.After 11 years of follow-up, 147 men had developed the metabolic syndrome (National Cholesterol Education Program criteria) and 57 men diabetes. Men with total testosterone, calculated free testosterone, and SHBG levels in the lower fourth had a severalfold increased risk of developing the metabolic syndrome (odds ratio [OR] 2.3, 95% CI 1.5-3.4; 1.7, 1.2-2.5; and 2.8, 1.9-4.1, respectively) and diabetes (2.3, 1.3-4.1; 1.7, 0.9-3.0; and 4.3, 2.4-7.7, respectively) after adjustment for age. Adjustment for potential confounders such as cardiovascular disease, smoking, alcohol intake, and socioeconomic status did not alter the associations. Factors related to insulin resistance attenuated the associations, but they remained significant, except for free testosterone.Low total testosterone and SHBG levels independently predict development of the metabolic syndrome and diabetes in middle-aged men. Thus, hypoandrogenism is an early marker for disturbances in insulin and glucose metabolism that may progress to the metabolic syndrome or frank diabetes and may contribute to their pathogenesis.