tbuckley/cabot-search huggingface dataset:
Tumor immunogenicity determines the effect of B7 costimulation on T cell-mediated tumor immunity.
Authors: L Chen, P McGowan, S Ashe, J Johnston, Y Li, I Hellström, K E Hellström
Journal: The Journal of Experimental Medicine (1994)

A costimulatory signal through B7 to its counter-receptor CD28 on T cells enhances T cell activation. We have generated recombinant retroviruses containing cDNA for murine B7 and transduced a panel of murine tumor lines with varying immunogenicity to study the effect of B7 costimulation on antitumor immunity. In contrast to the progressive outgrowth of all wild-type (B7-) tumors in unimmunized syngeneic mice, four immunogenic tumors, lymphoma RMA, EL4, mastocytoma P815, and melanoma E6B2, regressed completely when transduced with the B7 gene. In contrast, four nonimmunogenic tumors, sarcomas MCA101, MCA102, and Ag104, and melanoma B16, remained tumorigenic after transduction of the B7 gene. Immunization with B7-transduced immunogenic tumors enhanced protective immunity and increased specific cytotoxic T lymphocyte (CTL) activity against the respective wild-type tumors as compared to immunization with nontransduced or mock-transduced tumors. Moreover, cocultivation of CTL with B7-transduced EL4 cells augmented the specificity of tumor-reactive CTL in long-term cultures. Treatment by injection of B7-transduced tumor cells cured 60% of mice with established wild-type EL4 lymphoma. In contrast, immunization with nonimmunogenic tumors transduced with B7 did not provide protective immunity and did not increase specific CTL activity. Our results show that tumor immunogenicity is critical to the outcome of costimulation of T cell-mediated tumor immunity by B7.
The association between childhood asthma and adult chronic obstructive pulmonary disease
Authors: Andrew Tai, Haily Tran, Mary Roberts, Nadeene Clarke, John Wilson, Colin F Robertson
Journal: Thorax (2014)

<h3>Introduction</h3> There is epidemiological evidence to suggest that events in childhood influence lung growth and constitute a significant risk for adult COPD. The aim of the study is to evaluate for an association between childhood asthma and adult COPD. <h3>Methods</h3> This longitudinal, prospective study of 6–7-year-old children with asthma has been regularly reviewed every 7 years to the current analysis at 50 years of age. Participants completed respiratory questionnaires and lung function spirometry with postbronchodilator response. At the age of 50, subjects were classified to the following subgroups: non-asthmatics, asthma remission, current asthma and COPD which was defined by FEV<sub>1</sub> to FVC ratio postbronchodilator of less than 0.7. <h3>Results</h3> Of the remaining survivors, 346 participated in the current study (participation rate of 76%) of whom 197 completed both questionnaire and lung function testing. As compared with children without symptoms of wheeze to the age of 7, (non-asthmatics) children with severe asthma had an adjusted 32 times higher risk for developing COPD (95% CI 3.4 to 269). In this cohort, 43% of the COPD group had never smoked. There was no evidence of a difference in the rate of decline in FEV<sub>1</sub> (mL/year, 95th CI) between the COPD group (17, 10 to 23) and the other groups: non-asthmatics (16, 12 to 21), asthma remission (20, 16 to 24) and current asthma (19, 13 to 25). <h3>Conclusions</h3> Children with severe asthma are at increased risk of developing COPD.
Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen–specific CD8+ T cell dysfunction in melanoma patients
Authors: Julien Fourcade, Zhaojun Sun, Mourad Benallaoua, Philippe Guillaume, Immanuel F. Luescher, Cindy Sander, John M. Kirkwood, Vijay Kuchroo, Hassane M. Zarour
Journal: The Journal of Experimental Medicine (2010)

The paradoxical coexistence of spontaneous tumor antigen–specific immune responses with progressive disease in cancer patients furthers the need to dissect the molecular pathways involved in tumor-induced T cell dysfunction. In patients with advanced melanoma, we have previously shown that the cancer-germline antigen NY-ESO-1 stimulates spontaneous NY-ESO-1–specific CD8+ T cells that up-regulate PD-1 expression. We also observed that PD-1 regulates NY-ESO-1–specific CD8+ T cell expansion upon chronic antigen stimulation. In the present study, we show that a fraction of PD-1+ NY-ESO-1–specific CD8+ T cells in patients with advanced melanoma up-regulates Tim-3 expression and that Tim-3+PD-1+ NY-ESO-1–specific CD8+ T cells are more dysfunctional than Tim-3−PD-1+ and Tim-3−PD-1− NY-ESO-1–specific CD8+ T cells, producing less IFN-γ, TNF, and IL-2. Tim-3–Tim-3L blockade enhanced cytokine production by NY-ESO-1–specific CD8+ T cells upon short ex vivo stimulation with cognate peptide, thus enhancing their functional capacity. In addition, Tim-3–Tim-3L blockade enhanced cytokine production and proliferation of NY-ESO-1–specific CD8+ T cells upon prolonged antigen stimulation and acted in synergy with PD-1–PD-L1 blockade. Collectively, our findings support the use of Tim-3–Tim-3L blockade together with PD-1–PD-L1 blockade to reverse tumor-induced T cell exhaustion/dysfunction in patients with advanced melanoma.
Drug Resistance Caused by Reversion Mutation
Authors: Alan Ashworth
Journal: Cancer Research (2008)

Abstract Cells carrying mutated BRCA1 or BRCA2 genes are defective in DNA repair by homologous recombination and, as a consequence, are highly sensitive to inhibitors of poly (ADP-ribose) polymerase (PARP). This provides the basis for a novel “synthetic lethal” approach to cancer therapy. We have recently shown that this sensitivity can be reversed, and resistance to PARP inhibition can be acquired by deletion of a mutation in BRCA2. Furthermore, a similar mechanism seems to be associated with carboplatin resistance in some BRCA2 mutation carriers with ovarian cancer. [Cancer Res 2008;68(24):10021–3]
Parallel decrease of Na+ -taurocholate cotransport and its encoding mRNA in primary cultures of rat hepatocytes
Authors: Dana Liang, Bruno Hagenbuch, Bruno Stieger, Peter J. Meier
Journal: Hepatology (1993)

We investigated the molecular mechanism underlying the progressive loss of Na(+)-dependent bile salt uptake in primary cultured rat hepatocytes. A specific cDNA probe was used to quantitate the levels of mRNA encoding the Na(+)-taurocholate-cotransporting polypeptide at various culture times. Hepatocytes were cultured on collagen in the presence of insulin (10(-7) mol/L), dexamethasone (10(-7) mol/L) and 10% fetal calf serum for up to 72 hr. During this time period the dissociation constant of Na(+)-dependent taurocholate uptake remained stable (19 to 39 mumol/L), whereas the maximum velocity values decreased from 100% at 3 hr to 55%, 22% and 4% at 24, 48 and 72 hr, respectively. Concomitantly the levels of the Na(+)-taurocholate-cotransporting polypeptide mRNA also decreased from 100% at 3 hr to 41%, 24% and 4% at the later time points. In contrast, Northern hybridization with complementary DNA probes for three common housekeeping gene products revealed a 1.8- to 3.4-fold increase in the levels of mRNA encoding the alpha-subunit of the Na+K(+)-ATPase, beta-actin and glycerol-3-phosphate dehydrogenase. These data indicate that the loss of Na(+)-dependent bile salt uptake in primary cultures of rat hepatocytes is caused by decreased levels of its specific mRNA. Hence the studies further confirm that without specific measures (primary) cultured rat hepatocytes reverse their liver-specific phenotype to a more fetal pattern of gene expression.
TOWARD SOCIOCULTURAL FLEXIBILITY IN RESIDENT EDUCATION
Authors: SHERWYN M. WOODS
Journal: American Journal of Psychiatry (1966)

Today's psychiatrist should possess sufficient sociocultural flexibility in his professional abilities to work effectively with patients whose cultural class and economic or educational backgrounds differ considerably from his own. Otherwise, his effectiveness is limited by his own class- and culture-bound rigidities, attitudes and value systems. Specific additions to a residency training program are suggested in order to assist the resident in reaching such professional flexibility and capability.
Intracoronary administration of acetyl-tyrosinyl-valyl-alanyl-aspartyl-chloro-methylketone (Ac-YVAD-cmk) reduces neointimal hyperplasia after stenting of the porcine coronary artery
Authors: Mariann Gyongyosi, Wolfgang Sperker, Ursula Windberger, Michael Gottsauner-Wolf, Paul Wexberg, Diana Bonderman, Irene Lang, Peter Ferdinandy, Stefan Mariovits, Dietmar Giogar
Journal: Journal of the American College of Cardiology (2002)
Flow cytometric evaluation of circulating endothelial cells: A new protocol for identifying endothelial cells at several stages of differentiation
Authors: Hakan Ozdogu, Oktay Sozer, Can Boga, llknur Kozanoglu, Erkan Maytalman, Meral Guzey
Journal: American Journal of Hematology (2007)

Abstract Several factors may influence the analysis of endothelial cells (ECs) by flow cytometry: separation of mononuclear cell, washing and centrifugation steps, panel of monoclonal antibodies, and the lack of standardization of gating technique. Therefore, the reliable quantification of ECs remains a technical challenge. The purpose of this study is to define a new flow cytometric protocol to characterize and quantitate ECs. In previous investigations, increased numbers of circulating ECs have been found in sickle cell disease. The patients with sickle cell disease might provide useful material for the study. We performed flow cytometry on whole blood from 20 normal controls and 31 patients with sickle cell disease (20 patients with steady‐state disease and 11 patients with vaso‐occlusive crises) using a lyse/no‐wash procedure, specific and nonspecific antibody combinations (CD146, CD144, CD34, and CD117), and broad gating. This protocol produced much higher values for the number of circulating ECs (a mean of 2,396.55 ± 658.37 ECs/mL in controls vs 6,709.60 ± 1,772.32 ECs/mL in the steady‐state group, or 18,213.50 ± 8,451 in the vaso‐occlusive crises group, P &lt; 0.001 for both), and also showed variable EC size and granularity, which may reflect activated, or early release ECs. This novel protocol performed comparably in terms of reproducibility, reliability, and dilution linearity with a previously described protocol. This approach has significant advantages for the characterization and quantitation ECs compatible with the pathophysiology. Using the specific antibodies, CD146 and CD144, together may give more informative EC data than the general approach used. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.
Minimally invasive surgery for pneumothorax: The evidence, changing practice and current opinion
Authors: Tom Treasure
Journal: Journal of the Royal Society of Medicine (2007)

Spontaneous pneumothorax is a common problem and in patients at risk of recurrence, excision of the source of the air leak and pleurodesis is very effective in reducing further episodes. In the 15 years since the introduction of video assisted thoracic surgery (VATS), practice has changed towards this much less invasive procedure and away from thoracotomy. The evidence from randomized trials, non-randomized comparative studies, the consensus of surgeons and the documented change in practice from registry data are concordant. Unless there are specific clinical indications for more invasive surgery, it would seem reasonable for VATS to become the recommended approach.
Individual and Community Risks of Measles and Pertussis Associated With Personal Exemptions to Immunization
Authors: D R Feikin, D C Lezotte, R F Hamman, D A Salmon, R T Chen, R E Hoffman
Journal: JAMA (2000)

The risk of vaccine-preventable diseases among children who have philosophical and religious exemptions from immunization has been understudied.To evaluate whether personal exemption from immunization is associated with risk of measles and pertussis at individual and community levels.Population-based, retrospective cohort study using data collected on standardized forms regarding all reported measles and pertussis cases among children aged 3 to 18 years in Colorado during 1987-1998.Relative risk of measles and pertussis among exemptors and vaccinated children; association between incidence rates among vaccinated children and frequency of exemptors in Colorado counties; association between school outbreaks and frequency of exemptors in schools; and risk associated with exposure to an exemptor in measles outbreaks.Exemptors were 22.2 times (95% confidence interval [CI], 15.9-31.1) more likely to acquire measles and 5.9 times (95% CI, 4.2-8.2) more likely to acquire pertussis than vaccinated children. After adjusting for confounders, the frequency of exemptors in a county was associated with the incidence rate of measles (relative risk [RR], 1.6; 95% CI, 1.0-2.4) and pertussis (RR, 1.9; 95% CI, 1.7-2.1) in vaccinated children. Schools with pertussis outbreaks had more exemptors (mean, 4.3% of students) than schools without outbreaks (1. 5% of students; P =.001). At least 11% of vaccinated children in measles outbreaks acquired infection through contact with an exemptor.The risk of measles and pertussis is elevated in personal exemptors. Public health personnel should recognize the potential effect of exemptors in outbreaks in their communities, and parents should be made aware of the risks involved in not vaccinating their children.
Regular Aerobic Exercise Training Improves Endothelium-Dependent Arterial Dilation in Patients With Impaired Fasting Glucose
Authors: Xiang Guang-da, Wang Yun-lin
Journal: Diabetes Care (2004)

Vehkavaara et al. (1) demonstrated that impaired endothelium-dependent arterial dilation characterizes patients with impaired fasting glucose (IFG). The purpose of the study was to investigate the effects of exercise training on endothelium-dependent arterial dilation in subjects with IFG using noninvasive measurement of flow-mediated, endothelium-dependent dilation of the brachial artery.

The study group included 30 sedentary Chinese Han men with IFG between 48 and 74 years of age, mean age 63 ± 12 years. The diagnosis of IFG fulfilled the diagnostic criteria proposed by the American Diabetes Association. The subjects participated in a 6-month exercise training program. Of them, eight discontinued the study after 1 month of training. Additionally, 30 sedentary healthy men aged 46–76 years, mean age 65 ± 11 years, were selected as control subjects.

Subjects with IFG underwent a supervised orientation and thereafter performed …
The Utility of Carotid Ultrasonography in Identifying Severe Coronary Artery Disease in Asymptomatic Type 2 Diabetic Patients Without History of Coronary Artery Disease
Authors: Yoko Irie, Naoto Katakami, Hideaki Kaneto, Mayu Nishio, Ryuichi Kasami, Ken’ya Sakamoto, Yutaka Umayahara, Satoru Sumitsuji, Yasunori Ueda, Keisuke Kosugi, Iichiro Shimomura
Journal: Diabetes Care (2013)

Although many studies have shown that carotid intima-media thickness (IMT) is associated with coronary artery disease (CAD), it remains inconclusive whether assessment of carotid IMT is useful as a screening test for asymptomatic but severe CAD in diabetic patients.A total of 333 asymptomatic type 2 diabetic patients without history of CAD underwent exercise electrocardiogram or myocardial perfusion scintigraphy for detection of silent myocardial ischemia, and those whose test results were positive were subjected to coronary computed tomography angiography or coronary angiography. The ability of carotid IMT to identify severe CAD corresponding to treatment with revascularization was examined by receiver-operating characteristic (ROC) curve analyses.Among the 333 subjects, 17 were treated with revascularization. A multiple logistic regression analysis showed that maximum IMT was an independent predictor of severe CAD even after adjustment for conventional risk factors. ROC curve analyses revealed that the addition of maximum IMT to conventional risk factors significantly improved the prediction ability for severe CAD (from area under the curve, 0.67 to 0.79; P = 0.039). The greatest sensitivity and specificity were obtained when the cut-off value of maximum IMT was set at 2.45 mm (pretest probability, 5%; posttest probability, 11%; sensitivity, 71%). When we applied age-specific cut-off values, the sensitivity of screening further increased in both the nonelderly (pretest probability, 6%; posttest probability, 10%; sensitivity, 100%) and the elderly subjects (pretest probability, 5%; posttest probability, 15%; sensitivity, 100%).Our study suggests that carotid maximum IMT is useful for screening asymptomatic type 2 diabetic patients with severe CAD equivalent to revascularization.
Role of Cetuximab in the Treatment of Patients With NSCLC: Are We Throwing Out the Baby With the Bath Water?
Authors: Irene Floriani, Marina Chiara Garassino, Massimo Broggini, Silvio Veronese, Silvia Marsoni, Mirko Marabese, Gabriella Farina, Alberto Scanni
Journal: Journal of Clinical Oncology (2010)
Inflammatory chemokine receptors regulate CD8+ T cell contraction and memory generation following infection
Authors: Jacob E. Kohlmeier, William W. Reiley, Georgia Perona-Wright, Michael L. Freeman, Eric J. Yager, Lisa M. Connor, Erik L. Brincks, Tres Cookenham, Alan D. Roberts, Claire E. Burkum, Stewart Sell, Gary M. Winslow, Marcia A. Blackman, Markus Mohrs, David L. Woodland
Journal: The Journal of Experimental Medicine (2011)

The development of T cell memory from naive precursors is influenced by molecular cues received during T cell activation and differentiation. In this study, we describe a novel role for the chemokine receptors CCR5 and CXCR3 in regulating effector CD8+ T cell contraction and memory generation after influenza virus infection. We find that Ccr5−/− Cxcr3−/− cells show markedly decreased contraction after viral clearance, leading to the establishment of massive numbers of memory CD8+ T cells. Ccr5−/− Cxcr3−/− cells show reduced expression of CD69 in the lung during the peak of infection, which coincides with differential localization and the rapid appearance of memory precursor cells. Analysis of single chemokine receptor–deficient cells revealed that CXCR3 is primarily responsible for this phenotype, although there is also a role for CCR5 in the enhancement of T cell memory. The phenotype could be reversed by adding exogenous antigen, resulting in the activation and contraction of Ccr5−/− Cxcr3−/− cells. Similar results were observed during chronic Mycobacterium tuberculosis infection. Together, the data support a model of memory CD8+ T cell generation in which the chemokine-directed localization of T cells within infected tissues regulates antigen encounter and controls the extent of CD8+ T cell activation and differentiation, which ultimately regulates effector versus memory cell fate decisions.
How adult second language learning differs from child first language development
Authors: Harald Clahsen, Pieter Muysken
Journal: Behavioral and Brain Sciences (1996)

Abstract We argue that the model developed in Epstein et al.'s target article does not explain differences between child first language (LI) acquisition and adult second language (L2) acquisition. We therefore sketch an alternative view, originally developed in Clahsen and Muysken (1989), in the light of new empirical findings and theoretical developments.
Satraplatin, an Oral Platinum, Administered on a Five-day Every-Five-Week Schedule: a Pharmacokinetic and Food Effect Study
Authors: Alejandro D. Ricart, John Sarantopoulos, Emiliano Calvo, Quincy S. Chu, Douglas Greene, Faith E. Nathan, Michael E. Petrone, Anthony W. Tolcher, Kyriakos P. Papadopoulos
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The study aimed to assess the pharmacokinetic behavior of satraplatin under fasted and fed conditions, and its safety and preliminary antitumor activity in adults with advanced solid tumors. Experimental Design: Satraplatin was administered orally at 80 mg/m2 once daily with prophylactic antiemetics for 5 consecutive days every 5 weeks. Patients were randomized to receive day 1 and day 5 doses of satraplatin in either the fed or fasted state, the order being reversed for cycle 2. Pharmacokinetic sampling was done during the first two cycles. For all subsequent cycles, patients received satraplatin in the fasted state. Results: Seventeen patients were treated with 60 total cycles of satraplatin. There was no dose-limiting toxicity during cycle 1. Severe hematologic toxicity was rare and the hematologic nadir occurred during week 4. Nausea, vomiting, and diarrhea were grade 1/2. No significant cardiac, renal, hepatic, or neurologic toxicity was observed. The hypothesis that food decreased ultrafiltrate platinum bioavailability could not be rejected, as the lower limit of the 90% confidence intervals for peak plasma concentration and area under the concentration-time curve from time 0 to 24 hours were 56.14% and 73.53%, respectively, both below the 80% bioequivalence acceptance criterion. One partial response (hormone refractory prostate cancer) and four durable stable diseases (breast, ovarian, parotid, and hormone refractory prostate cancer) were confirmed. Conclusions: There is an effect of food on the pharmacokinetics of satraplatin, the clinical significance of which is unclear. It is recommended that satraplatin be administered in the fasting state. This 5-week interval schedule of satraplatin was well tolerated in heavily pretreated patients.
Description and implementation of U-Turn Medical, a comprehensive lifestyle intervention programme for chronic disease in the sport and exercise medicine setting: pre–post observations in 210 consecutive patients
Authors: Wayne Derman, Martin Schwellnus, Fallon Hope, Esme Jordaan, Trishanta Padayachee
Journal: British Journal of Sports Medicine (2014)

Background Non-communicable disease (NCD) is increasing, but management remains mostly curative, disease-centred and focused on single interventions. We describe the development and implementation of a patient-centred, comprehensive, multidisciplinary lifestyle intervention programme (LIP) for patients with NCD in the sport and exercise medicine (SEM) setting (part 1) and present preliminary observational data (part 2). Methods Part 1 is a description of the programme development and implementation. In part 2, 210 participants with NCD underwent a 12-week LIP (U-Turn Medical). Physiological, functional and metabolic outcomes were assessed at baseline and at completion. Results 84% of patients had two or more comorbidities, requiring additional considerations for exercise rehabilitation. On completion, there were decreases in % body fat (29.8±6.7% vs 28.5±6.6%), waist (100.2±16.2 vs 97.3±14.8 cm) and hip circumference (105.4±13 vs 104±12 cm), resting heart rate (74.2±13.4 vs 71.4±11.9 bpm), resting systolic blood pressure (125.7±16.1 vs 120.1±13 mm Hg) and cholesterol (4.7±1.2 vs 4.3±0.9 mmol/L), low-density lipoprotein (3±0.9 vs 2.7±0.8 mmol/L) and triglyceride (1.4±0.7 vs 1.3±0.6 mmol/L), and increases in flexibility (12.1±11.6 vs 16.1±10.8 cm) and 6 min walk distance (559.4±156.6 vs 652.3±193.6 m; all p&lt;0.05). Conclusions A 12-week comprehensive, patient-centred LIP can be implemented successfully in the SEM setting in patients with NCDs with multiple comorbidities. Observed results show improvements in the majority of outcome variables.