tbuckley/cabot-search huggingface dataset:
Characterization of the Mouse IFN-λ Ligand-Receptor System: IFN-λs Exhibit Antitumor Activity against B16 Melanoma
Authors: Ahmed Lasfar, Anita Lewis-Antes, Sergey V. Smirnov, Shubha Anantha, Walid Abushahba, Bin Tian, Kenneth Reuhl, Harold Dickensheets, Faruk Sheikh, Raymond P. Donnelly, Elizabeth Raveche, Sergei V. Kotenko
Journal: Cancer Research (2006)

Abstract Recently discovered type III IFNs (IFN-λ) exert their antiviral and immunomodulatory activities through a unique receptor complex composed of IFN-λR1 and interleukin-10 receptor 2. To further study type III IFNs, we cloned and characterized mouse IFN-λ ligand-receptor system. We showed that, similar to their human orthologues, mIFN-λ2 and mIFN-λ3 signal through the IFN-λ receptor complex, activate IFN stimulated gene factor 3, and are capable of inducing antiviral protection and MHC class I antigen expression in several cell types including B16 melanoma cells. We then used the murine B16 melanoma model to investigate the potential antitumor activities of IFN-λs. We developed B16 cells constitutively expressing murine IFN-λ2 (B16.IFN-λ2 cells) and evaluated their tumorigenicity in syngeneic C57BL/6 mice. Although constitutive expression of mIFN-λ2 in melanoma cells did not affect their proliferation in vitro, the growth of B16.IFN-λ2 cells, when injected s.c. into mice, was either retarded or completely prevented. We found that rejection of the modified tumor cells correlated with their level of IFN-λ2 expression. We then developed IFN-λ-resistant B16.IFN-λ2 cells (B16.IFN-λ2Res cells) and showed that their tumorigenicity was also highly impaired or completely abolished similar to B16.IFN-λ2 cells, suggesting that IFN-λs engage host mechanisms to inhibit melanoma growth. These in vivo experiments show the antitumor activities of IFN-λs and suggest their strong therapeutic potential. (Cancer Res 2006; 66(8): 4468-77)
Sacroiliitis and HLA. A clinical and genetical study.
Authors: N Migone, V Modena, V Daneo, A O Carbonara, R Ceppellini
Journal: Annals of the Rheumatic Diseases (1978)

Among 39 patients (23 males, 16 females) with sacroiliitis (SI) 17 were HLA-B27 positive. The female/male ratio in the B27-positive group was 2/15. Seventy-four first-degree relatives of 26 probands were also investigated. A high occurrence of SI (20%) was observed in the families of B27-positive probands compared with only 3.7% in the families of B27-negative probands. In the former families SI occurred only in B27-positive subjects with an earlier onset of symptoms and a male prevalence. In the latter, the disease showed a later onset and a lack of male preponderance. The nosological and prognostic relevance of the B27 typing is stressed.
Raised Sympathetic Nerve Activity in Heart Failure and Central Sleep Apnea Is Due to Heart Failure Severity
Authors: Darren Mansfield, David M. Kaye, Hanspeter Brunner La Rocca, Peter Solin, Murray D. Esler, Matthew T. Naughton
Journal: Circulation (2003)

Background— Congestive heart failure (CHF) patients with central sleep apnea (CHF-CSA) have elevated plasma norepinephrine (NE) compared with CHF patients without apnea (CHF-N). Patients with CHF-CSA also demonstrate higher mean pulmonary artery pressure (PAP), which is suggestive of worse cardiac function. Whether CSA contributes to chronic elevation of sympathetic nerve activity or is associated with more severe CHF remains unknown. We measured awake total body and cardiac NE spillover and related these to measurements of cardiac hemodynamics and apnea severity in CHF patients with CSA, with normal breathing, and with obstructive sleep apnea (CHF-OSA). Methods and Results— A total of 55 CHF patients underwent right heart catheterization and measurements of total body and cardiac NE spillover using NE radioisotope dilution methodology. After polysomnography, patients were grouped by apnea type: 19 were CHF-N, 15 were CHF-OSA, and 21 were CHF-CSA. Compared with the CHF-N and CHF-OSA groups, the CHF-CSA group had significantly higher total body NE spillover (4.62±0.56 versus 4.47±0.54 versus 6.95±0.89 nmol/min, respectively; P =0.03), cardiac NE spillover (0.25±0.05 versus 0.21±0.05 versus 0.42±0.06 nmol/min, respectively; P =0.02) and mean PAP (23.5±2.4 versus 21.2±0.8 versus 30.4±0.2 mm Hg, respectively; P &lt;0.02). However, controlling for severity of CHF resulted in no significant differences in NE kinetics among the 3 groups. In a stepwise regression, only mean PAP independently correlated with total body ( r =0.33, P =0.03) and cardiac NE spillover ( r =0.44, P =0.002). Sleep apnea severity bore no relationship to markers of sympathetic nerve activity. Conclusion— Total body and cardiac sympathetic nerve activity are elevated in CHF-CSA compared with CHF-OSA and CHF-N patients and are related to heart failure not apnea severity.
Gain of Glucose-Independent Growth upon Metastasis of Breast Cancer Cells to the Brain
Authors: Jinyu Chen, Ho-Jeong Lee, Xuefeng Wu, Lei Huo, Sun-Jin Kim, Lei Xu, Yan Wang, Junqing He, Lakshmi R. Bollu, Guang Gao, Fei Su, James Briggs, Xiaojing Liu, Tamar Melman, John M. Asara, Isaiah J. Fidler, Lewis C. Cantley, Jason W. Locasale, Zhang Weihua
Journal: Cancer Research (2014)

Abstract Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells, but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustain the nonoxidative pentose pathway for purine synthesis. Silencing expression of fructose-1,6-bisphosphatases (FBP) in brain metastatic cells reduced their viability and improved the survival of metastasis-bearing immunocompetent hosts. Clinically, we showed that brain metastases from human breast cancer patients expressed higher levels of FBP and glycogen than the corresponding primary tumors. Together, our findings identify a critical metabolic condition required to sustain brain metastasis and suggest that targeting gluconeogenesis may help eradicate this deadly feature in advanced breast cancer patients. Cancer Res; 75(3); 554–65. ©2014 AACR.
844 POLYMER LIBRARY SCREENING IDENTIFIES AN EXTRACELLULAR MATRIX THAT PROMOTES AND STABILISES HUMAN EMBRYONIC STEM CELL-DERIVED HEPATOCYTE FUNCTION
Authors: D.C. Hay, S. Pernagallo, J.J. Diaz-Mochon, J. Fletcher, J. Black, A. Thompson, Z. Hannoun, P. Newsome, S. Forbes, J. Ross, M. Bradley, J.P. Iredale
Journal: Journal of Hepatology (2009)
Is Substance Abuse in Schizophrenia Related to Impulsivity, Sensation Seeking, or Anhedonia?
Authors: Alain Dervaux, Franck J. Baylé, Xavier Laqueille, Marie-Chantal Bourdel, Michèle-Hélène Le Borgne, Jean-Pierre Olié, Marie-Odile Krebs
Journal: American Journal of Psychiatry (2001)

The authors compared impulsivity, sensation seeking, and anhedonia in a group of schizophrenic patients with and without lifetime substance abuse or dependence.Patients (N=100) with schizophrenia or schizoaffective disorder (per DSM-III-R criteria) were assessed with the Composite International Diagnostic Interview's section on psychoactive substance use disorder, the Positive and Negative Syndrome Scale, the Barratt Impulsivity Scale, the Zuckerman Seeking Sensation Scale, and the Chapman Physical Anhedonia Scale.The mean scores for impulsivity and sensation seeking were higher in the group with substance abuse (N=41) than in the group without substance abuse (N=59). No significant difference between groups was found regarding physical anhedonia.As in the general population, high levels of impulsivity and sensation seeking are associated with substance abuse in patients with schizophrenia.
Human papillomavirus type 16-induced skin squamous cell carcinoma located on the groin of immunocompetent patients
Authors: A. Croci-Torti, C. Tamalet, M. Segondy, M. Dandurand, L. Meunier, P.-E. Stoebner
Journal: British Journal of Dermatology (2013)

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Criminal Records of Homicide Offenders
Authors: Philip J. Cook
Journal: JAMA (2005)

Homicide prevention strategies can be either targeted toward high-risk groups or addressed to the population at large. One high-risk group of particular interest is adults with a criminal record. But the prevalence of a criminal record among homicide offenders has not been reliably quantified, nor has the prevalence of criminal record in the general population.To determine what portion of the homicide problem would be addressed by interventions linked to arrest or conviction.A case-control analysis was performed using a comprehensive data set of all arrests and felony convictions in Illinois for 1990-2001. Cases were defined as Illinois residents aged 18 to 64 years who were arrested for homicide in 2001. Controls were all other Illinois residents aged 18 to 64 years in 2001. Illinois criminal and juvenile record information for cases and controls was compiled for 1990-2000. Five definitions of previous record were considered (arrest, arrest for a violent crime, 5 or more arrests with at least 1 for a violent crime, felony conviction, and violent-felony conviction), each measured for 1990-2000 and for 1996-2000.The population-attributable risk: the portion of homicide offenses that would be eliminated by a hypothetical intervention that reduced the offending risk of individuals with a record to the offending risk of those who lack a record.For 1990-2000, 42.6% of 884 cases had at least 1 felony conviction compared with 3.9% of nearly 7.9 million controls, for a population-attributable risk of 40.3% (95% CI, 37.0%-43.8%); among cases, 71.6% had experienced any arrest from 1990-2000 compared with 18.2% of controls, for a population-attributable risk of 65.3% (95% CI, 61.6%-68.8%). For 1996-2000, the population-attributable risk among individuals with a felony conviction or any arrest was 31.0% (95% CI, 27.9%-34.2%) and 58.5% (95% CI, 54.9%-62.1%), respectively.Interventions after arrest or conviction, such as supervised release, imprisonment, correctional programs, or bans on firearm possession, are targeted toward a group that has relatively high incidence of lethal violence, but they leave a large portion of the problem untouched.
PTU-078 The Application Of A Markov Model For Evauating Asa Therapy For Ulcerative Colitis
Authors: V Mukhekat, I Ahmad, Y Merali, D Aldulaimi
Journal: Gut (2014)

Introduction We developed a Markov model for ulcerative colitis that calculated the costs of two different treatment strategies for 1000 patients and healthcare providers and ran the model over a ten year cycle to evaluate each treatment arm. Methods Healthcare costs were calculated from the published study of costs of ulcerative colitis at Aintree University Hospital, Liverpool, UK. Effects were quantified with the EQ-5D visual analogue scale and Work Productivity and Activity Impairment (WPAI) study. Lost income for patients was calculated assuming that the patient was self employed, earning the national average wage and had no sickness benefits. Results Cohort simulation is used to present the results. At the end of exercise, 277 patients were in the phase of remission in ASA continuing arm and 232 patients were in the same phase in ASA discontinuing arm. Total costs to the healthcare providers for providing treatment to the patients were found to be £15,390,139.81 (discounted-£12,825,018.45) for ASA continuing arm and that for ASA discontinuing arm were £12,911,557.43 (discounted-£10,752,633.35). These costs were incurred to gain QALYs of 31,682.14 (discounted-26713.79) for the ASA continuing arm and of 31,307.73 (discounted-26,405.89 for ASA discontinuing arm). Primary outcome in terms of ICER (Incremental Cost-Effectiveness Ratio) is £6730.55 per QALY (acceptable range <£20,000–30,000). Secondary outcomes such as Discounted total earnings lost due to illness and Discounted total earnings affected due to work impairment were found to be in favour of ASA continuation by 19.43% (£3.7 million) and 11.15% (£7.8 million) in favour of ASA continuing arm. Sensitivity analysis was conducted to challenge both the cost and effect assumptions. CEAC (Cost Effectiveness Acceptability Curve) revealed the probability of 1 is reached with the cost-effectiveness acceptability limit of £40,000 ceiling limit. Conclusion Markov models have been used extensively to study the cost-effectiveness of healthcare interventions in chronic diseases. Our Markov model considered costs for both patients and healthcare providers, rather than solely considering the costs for healthcare providers. Results not only revealed the cost-effectiveness of ASA for the healthcare provider but also potential benefits for the broader economy. Disclosure of Interest None Declared.
Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension
Authors: M. Humbert, O. Sitbon, A. Yaïci, D. Montani, D.S. O'Callaghan, X. Jaïs, F. Parent, L. Savale, D. Natali, S. Günther, A. Chaouat, F. Chabot, J-F. Cordier, G. Habib, V. Gressin, Z-C. Jing, R. Souza, G. Simonneau
Journal: European Respiratory Journal (2010)

Pulmonary arterial hypertension (PAH) is a progressive, fatal disease. We studied 674 consecutive adult patients who were prospectively enrolled in the French PAH registry (121 incident and 553 prevalent cases). Two survival analyses were performed. First, the cohort of 674 patients was followed for 3 yrs after study entry and survival rates described. Then, we focused on the subset with incident idiopathic, familial and anorexigen-associated PAH (n = 56) combined with prevalent patients who were diagnosed &lt;3 yrs prior to study entry (n = 134). In the cohort of 674 patients, 1-, 2-, and 3-yr survival rates were 87% (95% CI 84–90), 76% (95% CI 73–80), and 67% (95% CI 63–71), respectively. In prevalent idiopathic, familial and anorexigen-associated PAH, 1-, 2-, and 3-yr survival rates were higher than in incident patients (p = 0.037). In the combined cohort of patients with idiopathic, familial and anorexigen-associated PAH, multivariable analysis showed that survival could be estimated by means of a novel risk-prediction equation using patient sex, 6-min walk distance, and cardiac output at diagnosis. This study highlights survivor bias in prevalent cohorts of PAH patients. Survival of idiopathic, familial and anorexigen-associated PAH can be characterised by means of a novel risk-prediction equation using patients' characteristics at diagnosis.
Two-Year Clinical Follow-Up After Sirolimus-Eluting Versus Bare-Metal Stent Implantation Assisted by Systematic Glycoprotein IIb/IIIa Inhibitor Infusion in Patients With Myocardial Infarction
Authors: Marco Valgimigli, Gianluca Campo, Chiara Arcozzi, Patrizia Malagutti, Roberto Carletti, Fabrizio Ferrari, Dario Barbieri, Giovanni Parrinello, Gianfranco Percoco, Roberto Ferrari
Journal: Journal of the American College of Cardiology (2007)
Correlating Phosphatidylinositol 3-Kinase Inhibitor Efficacy with Signaling Pathway Status: <i>In silico</i> and Biological Evaluations
Authors: Shingo Dan, Mutsumi Okamura, Mariko Seki, Kanami Yamazaki, Hironobu Sugita, Michiyo Okui, Yumiko Mukai, Hiroyuki Nishimura, Reimi Asaka, Kimie Nomura, Yuichi Ishikawa, Takao Yamori
Journal: Cancer Research (2010)

The phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in human cancers, and several agents targeting this pathway including PI3K/Akt/mammalian target of rapamycin inhibitors have recently entered clinical trials. One question is whether the efficacy of a PI3K pathway inhibitor can be predicted based on the activation status of pathway members. In this study, we examined the mutation, expression, and phosphorylation status of PI3K and Ras pathway members in a panel of 39 pharmacologically well-characterized human cancer cell lines (JFCR39). Additionally, we evaluated the in vitro efficacy of 25 PI3K pathway inhibitors in addition to conventional anticancer drugs, combining these data to construct an integrated database of pathway activation status and drug efficacies (JFCR39-DB). In silico analysis of JFCR39-DB enabled us to evaluate correlations between the status of pathway members and the efficacy of PI3K inhibitors. For example, phospho-Akt and KRAS/BRAF mutations prominently correlated with the efficacy and the inefficacy of PI3K inhibitors, respectively, whereas PIK3CA mutation and PTEN loss did not. These correlations were confirmed in human tumor xenografts in vivo, consistent with their ability to serve as predictive biomarkers. Our findings show that JFCR39-DB is a useful tool to identify predictive biomarkers and to study the molecular pharmacology of the PI3K pathway in cancer.
Genetic deletion of chemokine receptor Ccr7 exacerbates atherogenesis in ApoE-deficient mice
Authors: Wuzhou Wan, Michail S. Lionakis, Qian Liu, Ester Roffê, Philip M. Murphy
Journal: Cardiovascular Research (2012)

AimsRecent evidence suggests that both Ccr7 and its ligands, Ccl19 and Ccl21, are present in mouse and human atherosclerotic plaques; however, the role of Ccr7 in atherogenesis is still controversial. Here, we addressed this question by using the classic apolipoprotein E-deficient (ApoE−/−) mouse model of atherosclerosis.
MARF and Opa1 Control Mitochondrial and Cardiac Function in Drosophila
Authors: Gerald W. Dorn, Charles F. Clark, William H. Eschenbacher, Min-Young Kang, John T. Engelhard, Stephen J. Warner, Scot J. Matkovich, Casey C. Jowdy
Journal: Circulation Research (2010)

Mitochondria interact via actions of outer and inner membrane fusion proteins. The role of mitochondrial fusion in functioning of the heart, where mitochondria comprise ≈30% of cardiomyocyte volume and their intermyofilament spatial arrangement with other mitochondria is highly ordered, is unknown.Model and analyze mitochondrial fusion defects in Drosophila melanogaster heart tubes with tincΔ4Gal4-directed expression of RNA interference (RNAi) for mitochondrial assembly regulatory factor (MARF) and optic atrophy (Opa)1.Live imaging analysis revealed that heart tube-specific knockdown of MARF or Opa1 increases mitochondrial morphometric heterogeneity and induces heart tube dilation with profound contractile impairment. Sarcoplasmic reticular structure was unaffected. Cardiomyocyte expression of human mitofusin (mfn)1 or -2 rescued MARF RNAi cardiomyopathy, demonstrating functional homology between Drosophila MARF and human mitofusins. Suppressing mitochondrial fusion increased compensatory expression of nuclear-encoded mitochondrial genes, indicating mitochondrial biogenesis. The MARF RNAi cardiomyopathy was prevented by transgenic expression of superoxide dismutase 1.Mitochondrial fusion is essential to cardiomyocyte mitochondrial function and regeneration. Reactive oxygen species are key mediators of cardiomyopathy in mitochondrial fusion-defective cardiomyocytes. Postulated mitochondrial-endoplasmic reticulum interactions mediated uniquely by mfn2 appear dispensable to functioning of the fly heart.
Heartburn--the acid test.
Authors: B Joelsson, F Johnsson
Journal: Gut (1989)

To determine whether symptoms of gastro-oesophageal reflux are related to the degree of oesophageal acid exposure, 190 patients (of 220 referred) with heartburn and acid regurgitation were compared with 50 normal subjects. A definite relationship between frequency of reflux symptoms and degree of oesophageal acid exposure was found both in patients with and without oesophagitis. We conclude that the frequency of gastro-oesophageal reflux symptoms is related to degree of oesophageal acid exposure.
OC-079 FGF19 expression is highly responsive to bile acids compared to other bile acid regulatory genes within the human ileum
Authors: J D Nolan, J H Zhang, I Johnston, S Kennie, T Dew, P Dixon, C Williamson, J R Walters
Journal: Gut (2012)

<h3>Introduction</h3> The expression of the enteric hormone FGF15 is largely restricted to the ileum in the mouse. FGF15 has also been shown to be the most BA responsive gene in mouse ileum. FGF19 is the human orthologue of FGF15 and is thought to have roles in the regulation of bile acid pool sizes and BA homeostasis. We set out to investigate the distribution of FGF19 expression in the human GI tract and FGF19 gene responses to BA in human ileum. <h3>Methods</h3> Biopsies of normal ileal mucosa were obtained from 29 patients undergoing colonoscopy. Basal ileal FGF19 expression was compared to colonic (n=9) and duodenal FGF19 expression (n=3). Ileal biopsies (explants) from 20 patients were incubated for 6h in short term tissue culture in parallel with BA (chenodeoxycholic acid [CDCA] or glyco-chenodeoxycholic acid [GCDCA]) or without (control explants). 3 Duodenal and colonic explants from were also studied. Real-time qRT-PCR was used to measure expression of transcripts for FGF19, and several other ileal BA regulatory genes (ASBT, IBABP, SHP, FXR, OSTα and OSTβ). FGF19 protein levels in culture fluid were also measured by specific ELISA. <h3>Results</h3> Transcripts for FGF19 were detected in human ileum, but not colon or duodenum. FGF19 expression was greatly induced in all ileal explants incubated with BA: geometric mean induction of 316-fold by 50 μM CDCA (n=17, p=0.0003), and 231-fold by 50 μM GCDCA (n=11, p=0.001). Measured by ELISA, the amount of FGF19 protein released into the culture media was significantly higher from the explants incubated with 50 μM of BA (CDCA 51 pg/explant, range 8–169, n=11 and GCDCA 38 pg/explant, range 3–113, n=10) compared to the matched control explants (8pg/explant, range 0–46 [p=0.0008] and 6 pg/explant, range 0–13 [p=0.0022] respectively). The EC50 for CDCA was 20 μM and 24 μM for GCDCA. Responses to both BA were similar at 50 μM and 100 μM. 6 h incubation of duodenal and colonic explants with 100 μM CDCA or GCDCA showed that FGF19 expression levels were &lt;0.35 times the FGF19 expression seen in the control ileal explants at 6 h. In ileal explants, responses of other genes to CDCA and GCDCA at 50 μM (n=3–4) showed median increases for IBABP, OSTα, OSTβ and SHP between 2.4 and 4.0-fold, whereas ASBT and FXR showed little change. <h3>Conclusion</h3> FGF19 is expressed in human ileum but not the colon or duodenum. Ileal FGF19 expression is highly responsive to CDCA and GCDCA, compared to other BA regulatory genes. No significant induction of FGF19 expression is observed in duodenum or colon with BA. Ileal BA induced FGF19 responses could be studied in clinical conditions of dysregulated BA homeostasis. <h3>Competing interests</h3> None declared.
Regulatory T Cells in Autoimmmunity
Authors: Ethan M. Shevach
Journal: Annual Review of Immunology (2000)

Clonal deletion of autoreactive T cells in the thymus is not the sole mechanism for the induction of tolerance to self-antigens since partial depletion of peripheral CD4 + T cells from neonatal and adult animals results in the development of organ-specific autoimmunity. Reconstitution of these immunodeficient animals with populations of regulatory CD4 + T cells prevents the development of autoimmunity. The lineage of regulatory CD4 + T cells is generated in the thymus and can be distinguished from effector cells by the expression of unique membrane antigens. The target antigens for these suppressor populations and their mechanisms of action remain poorly defined. Depletion of regulatory T cells may be useful in the induction of immunity to weak antigens, such as tumor-specific antigens. Conversely, enhancement of regulatory T cell function may be a useful adjunct to the therapy of autoimmune diseases and for prevention of allograft rejection.