tbuckley/cabot-search huggingface dataset:
Portable Filter-Based Microdevice for Detection and Characterization of Circulating Tumor Cells
Authors: Henry K. Lin, Siyang Zheng, Anthony J. Williams, Marija Balic, Susan Groshen, Howard I. Scher, Martin Fleisher, Walter Stadler, Ram H. Datar, Yu-Chong Tai, Richard J. Cote
Journal: Clinical Cancer Research (2010)

Sensitive detection and characterization of circulating tumor cells (CTC) could revolutionize the approach to patients with early-stage and metastatic cancer. The current methodologies have significant limitations, including limited capture efficiency and ability to characterize captured cells. Here, we report the development of a novel parylene membrane filter-based portable microdevice for size-based isolation with high recovery rate and direct on-chip characterization of captured CTC from human peripheral blood.We evaluated the sensitivity and efficiency of CTC capture in a model system using blood samples from healthy donors spiked with tumor cell lines. Fifty-nine model system samples were tested to determine the recovery rate of the microdevice. Moreover, 10 model system samples and 57 blood samples from cancer patients were subjected to both membrane microfilter device and CellSearch platform enumeration for direct comparison.Using the model system, the microdevice achieved >90% recovery with probability of 95% recovering at least one cell when five are seeded in 7.5 mL of blood. CTCs were identified in 51 of 57 patients using the microdevice, compared with only 26 patients with the CellSearch method. When CTCs were detected by both methods, greater numbers were recovered by the microfilter device in all but five patients.This filter-based microdevice is both a capture and analysis platform, capable of multiplexed imaging and genetic analysis. The microdevice presented here has the potential to enable routine CTC analysis in the clinical setting for the effective management of cancer patients.
Influenza Virus–induced Dendritic Cell Maturation Is Associated with the Induction of Strong T Cell Immunity to a Coadministered, Normally Nonimmunogenic Protein
Authors: Marie K. Brimnes, Laura Bonifaz, Ralph M. Steinman, Thomas M. Moran
Journal: The Journal of Experimental Medicine (2003)

We evaluated the proposal that during microbial infection, dendritic cells (DCs) undergo maturation and present a mixture of peptides derived from the microbe as well as harmless environmental antigens. Mice were exposed to an aerosol of endotoxin free ovalbumin (OVA) in the absence or presence of influenza virus. In its absence, OVA failed to induce B and T cell responses and even tolerized, but with influenza, OVA-specific antibodies and CD8+ cytolytic T lymphocytes developed. With or without infection, OVA was presented selectively in the draining mediastinal lymph nodes, as assessed by the comparable proliferation of infused, CD8+ and CD4+, TCR transgenic T cells. In the absence of influenza, these OVA-specific T cells produced little IL-2, IL-4, IL-10, and IFN-γ, but with infection, both CD4+ and CD8+ T cells made high levels of IL-2 and IFN-γ. The OVA plus influenza-treated mice also showed accelerated recovery to a challenge with recombinant vaccinia OVA virus. CD11c+ DCs from the mediastinal lymph nodes of infected mice selectively stimulated both OVA- and influenza-specific T cells and underwent maturation, with higher levels of MHC class II, CD80, and CD86 molecules. The relatively slow (2–3 d) kinetics of maturation correlated closely to the time at which OVA inhalation elicited specific antibodies. Therefore respiratory infection can induce DC maturation and simultaneously B and T cell immunity to an innocuous antigen inhaled concurrently.
Effects of brief repetitive ischemia on contractility, relaxation, and coronary flow. Exaggerated postischemic diastolic dysfunction in pressure-overload hypertrophy.
Authors: T Mochizuki, F R Eberli, S Ngoy, C S Apstein, B H Lorell
Journal: Circulation Research (1993)

The recovery of systolic and diastolic function during unstable angina may be modified by the repetition of brief episodes of ischemia and by the presence of left ventricular hypertrophy (LVH). We studied the effects of six consecutive 5-minute cycles of no-flow ischemia and reperfusion followed by 25 minutes of recovery in isovolumic red blood cell-perfused hearts from aortic-banded rats with chronic LVH (n = 8) and sham-operated control rats (n = 8). At baseline (left ventricular end-diastolic pressure [LVEDP], 10 mm Hg), left ventricular developed pressure (123 +/- 5 versus 114 +/- 5 mm Hg/g) and coronary flow [2.5 +/- 0.3 versus 2.2 +/- 0.2 (mL/min)/g] were similar in LVH versus control rats. Repetitive ischemia was associated with progressive depression of postischemic recovery of left ventricular systolic function, and the recovery of left ventricular developed pressure after the final 25-minute reperfusion period was similar in LVH versus control rats (61 +/- 6% versus 72 +/- 4% of baseline, P = NS). Although there was no increase in isovolumic LVEDP during the initial cycle of transient ischemia, both groups showed a rapid and similar rise in LVEDP during subsequent ischemic cycles (delta 82 +/- 8 versus delta 89 +/- 7 mm Hg/g in response to the final ischemia cycle for LVH versus control rats, respectively; P = NS). The control hearts showed complete restoration of LVEDP to baseline during final reperfusion, whereas the LVH hearts showed prolonged and severe postischemic diastolic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)
Rocky Mountain spotted fever: legal duty to warn for noncontagious disease
Authors: M. S. Getfand
Journal: JAMA (1995)

To the Editor.  —Physicians have both a medical and a legal duty to warn the family members of patients with contagious diseases, such as meningococcemia or tuberculosis, about a potential for contracting the disease as a result of exposure. On the other hand, no presumption of a legal duty has until recently existed for infectious but noncontagious diseases, such as Rocky Mountain spotted fever.  In a 1993 decision, the Tennessee Supreme Court ruled that a physician treating a patient with documented or suspected Rocky Mountain spotted fever has a legal duty to warn identifiable third parties in the patient's immediate family about the risk of contracting the disease.1Clustering of Rocky Mountain spotted fever and the simultaneous illness in the family have been reported in a small number of cases.2,3Of note, major internal medicine and infectious diseases textbooks do not mention either family clustering or duty to
Use of Statins and Breast Cancer: A Meta-Analysis of Seven Randomized Clinical Trials and Nine Observational Studies
Authors: Stefanos Bonovas, Kalitsa Filioussi, Nikolaos Tsavaris, Nikolaos M. Sitaras
Journal: Journal of Clinical Oncology (2005)

Purpose A growing body of evidence suggests that statins may have chemopreventive potential against breast cancer. Laboratory studies demonstrate that statins induce apoptosis and reduce cell invasiveness in various cell lines, including breast carcinoma cells. However, the clinical relevance of these data remains unclear. The nonconclusive nature of the epidemiologic data prompted us to conduct a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. Patients and Methods A comprehensive search for articles published up until 2005 was performed; reviews of each study were conducted; and data were abstracted. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% CIs were calculated using the random and the fixed-effects models. Subgroup and sensitivity analyses were also performed. Results Seven large randomized trials and nine observational studies (five case-control and four cohort studies) contributed to the analysis. We found no evidence of publication bias or heterogeneity among the studies. Statin use did not significantly affect breast cancer risk (fixed effects model: RR = 1.03; 95% CI, 0.93 to 1.14; random effects model: RR = 1.02; 95% CI, 0.89 to 1.18). When the analyses were stratified into subgroups, there was no evidence that study design substantially influenced the estimate of effects. Furthermore, the sensitivity analysis confirmed the stability of our results. Conclusion Our meta-analysis findings do not support a protective effect of statins against breast cancer. However, this conclusion is limited by the relatively short follow-up times of the studies analyzed. Further studies are required to investigate the potential decrease in breast cancer risk among long-term statin users.
Epithelial cell specificity and apotope recognition by serum autoantibodies in primary biliary cirrhosis
Authors: Guanghua Rong, Renqian Zhong, Ana Lleo, Patrick S.C. Leung, Christopher L. Bowlus, Guo-Xiang Yang, Chen-Yen Yang, Ross L. Coppel, Aftab A. Ansari, Dean A. Cuebas, Howard J. Worman, Pietro Invernizzi, Gregory J. Gores, Gary Norman, Xiao-Song He, Eric M. Gershwin
Journal: Hepatology (2011)

Abstract: A major enigma of primary biliary cirrhosis (PBC) is the selective targeting of biliary cells. Our laboratory has reported that after apoptosis, human intrahepatic biliary epithelial cells (HiBECs) translocate the E2 subunit of the pyruvate dehydrogenase complex immunologically intact into apoptotic bodies, forming an apotope. However, the cell type and specificity of this reaction has not been fully defined. To address this issue, we investigated whether the E2 subunit of the pyruvate dehydrogenase complex, the E2 subunit of the branched chain 2-oxo acid dehydrogenase complex, the E2 subunit of the oxo-glutarate dehydrogenase complex, four additional inner mitochondrial enzymes, and four nuclear antigens remain immunologically intact with respect to postapoptotic translocation in HiBECs and three additional control epithelial cells. We report that all three 2-oxo acid dehydrogenase enzymes share the ability to remain intact within the apotope of HiBECs. Interestingly, the E2 subunit of the branched chain 2-oxo acid dehydrogenase complex also remained intact in the other cell types tested. We extended the data, using sera from 95 AMA-positive and 19 AMA-negative patients with PBC and 76 controls, by testing for reactivity against the seven mitochondrial proteins studied herein and also the ability of AMA-negative sera to react with HiBEC apotopes. Sera from 3 of 95 AMA-positive sera, but none of the controls, reacted with 2,4-dienoyl coenzyme A reductase 1, an enzyme also present intact only in the HiBEC apotope, but which has not been previously associated with any autoimmune disease. Finally, the specificity of HiBEC apotope reactivity was confined to AMA-positive sera. Conclusion: We submit that the biliary specificity of PBC is secondary to the unique processes of biliary apoptosis. (HEPATOLOGY 2011)
Antitumor Activity of Killed Corynebacterium parvum Suspensions in a Murine Mammary Adenocarcinoma (CaD2) System2
Authors: Dallas M. Purnell, Janet R. Otterstrom, Gerald L. Bartlett, John W. Kreider
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Antitumor Activity of Killed Corynebacterium parvum Suspensions in a Murine Mammary Adenocarcinoma (CaD2) System Get access Dallas M. Purnell, Dallas M. Purnell Search for other works by this author on: Oxford Academic PubMed Google Scholar Janet R. Otterstrom, Janet R. Otterstrom Search for other works by this author on: Oxford Academic PubMed Google Scholar Gerald L. Bartlett, Gerald L. Bartlett Search for other works by this author on: Oxford Academic PubMed Google Scholar John W. Kreider John W. Kreider Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 56, Issue 6, June 1976, Pages 1171–1175, https://doi.org/10.1093/jnci/56.6.1171 Published: 01 June 1976 Article history Received: 20 August 1975 Accepted: 15 December 1975 Published: 01 June 1976
Management and outcomes for patients with TTP: analysis of 100 cases at a single institution
Authors: Shruti Chaturvedi, Desiree Carcioppolo, Li Zhang, Keith R. McCrae
Journal: American Journal of Hematology (2013)

The advent of plasma exchange has led to a dramatic improvement in the survival of patients with thrombotic thrombocytopenic purpura (TTP), though approximately 10% of patients still die and a third suffer relapses. Clinical features that identify poor risk patients have not been clearly identified. We reviewed 100 patients who were treated for a first episode of TTP at the Cleveland Clinic between 2000 and 2012 to identify factors predictive of poor outcomes. On multivariate analysis, increasing age, especially age > 60 (RR: 7.08, 95% CI: 2.15-23.39, P = 0.002), severe neurological symptoms at presentation (RR: 18.37, 95% CI: I4.19-80.13, P < 0.001) and a persistently elevated LDH level after two plasma exchanges were predictive of mortality. Patients with ADAMTS13 activity above or below 5% did not differ in terms of clinical presentation or mortality and relapse rates, although ADAMTS13 activity > 5% was an independent predictor of adverse renal outcomes (need for dialysis and progression to chronic kidney disease). These variables may be useful for risk stratification and identification of patients who could potentially benefit from early institution of adjunctive therapy.
Linsitinib (OSI-906) versus placebo for patients with locally advanced or metastatic adrenocortical carcinoma: a double-blind, randomised, phase 3 study
Authors: Martin Fassnacht, Alfredo Berruti, Eric Baudin, Michael J Demeure, Jill Gilbert, Harm Haak, Matthias Kroiss, David I Quinn, Elizabeth Hesseltine, Cristina L Ronchi, Massimo Terzolo, Toni K Choueiri, Srinivasu Poondru, Tanya Fleege, Ramona Rorig, Jihong Chen, Andrew W Stephens, Francis Worden, Gary D Hammer
Journal: The Lancet Oncology (2015)
Neurone specific enolase: a useful diagnostic serum marker for small cell carcinoma of the lung.
Authors: T Esscher, L Steinholtz, J Bergh, E Nou, K Nilsson, S Pahlman
Journal: Thorax (1985)

Among lung cancers small cell carcinoma is the most sensitive to chemotherapy and radiation. This has emphasised the importance of an accurate diagnosis of this cell type, and the present study examined the use of serum neurone specific enolase (NSE) as a diagnostic marker for small cell carcinoma. NSE was measured in pretreatment sera from 103 patients with small cell carcinoma and in sera from relevant controls, including patients with other lung cancers, non-malignant lung diseases, and healthy adults. Serum NSE concentration was raised (greater than 25 ng/ml) in 72% of patients with small cell carcinoma. Ninety one per cent of patients with extensive disease and 50% of patients with limited disease were serum NSE positive. Patients with extensive disease in general had higher serum NSE concentrations than patients with limited disease. No definite difference in serum NSE positivity could be shown between oat cell and intermediate cell subtypes. Out of 51 patients with other lung cancers, four (8%) had a raised serum concentration, whereas all patients with non-malignant diseases and healthy individuals had normal serum NSE concentrations. Serum NSE determination seems to be a valuable tool for the diagnosis of small cell carcinoma.
The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics
Authors: N Carroll, C Cooke, A James
Journal: European Respiratory Journal (1997)

Airway inflammation in asthma consists of variably increased numbers of mononuclear and polymorphonuclear cells, and there is a growing body of evidence to suggest a primary role for lymphocytes and eosinophils in the pathogenesis of asthma. The aim of this study was to examine the distribution of lymphocytes and eosinophils in the bronchial tree of cases of mild and severe asthma. In cases of fatal asthma (n = 10), nonfatal asthma (sudden nonrespiratory death with a history of asthma n = 10), and control cases (sudden death with no history of respiratory illness, n = 10), lymphocytes and eosinophils were counted in transverse sections of large and small airways stained with haematoxylin and eosin. Cases of fatal asthma had longstanding severe asthma and nonfatal cases generally had mild asthma. Lymphocytes were increased in all airway size groups both in fatal and nonfatal cases of asthma compared to control cases (p < 0.001). Eosinophils were increased (p < 0.001) in all airway size groups in the cases of fatal asthma compared to the nonfatal asthma and control groups, which were similar. These differences between case groups were of similar magnitude, when only a random single airway section from each case in each size group was examined. The numbers of lymphocytes correlated with the number of eosinophils in the fatal asthma group (r = 0.60; p < 0.0001), and to a lesser extent in the nonfatal (r = 0.34; p = 0.001) and control groups (r = 0.32; p = 0.001). These findings suggest that increased numbers of lymphocytes are uniformly distributed in the large and small airways in cases of asthma, independently of asthma severity, and that eosinophil recruitment may be related to asthma severity. Hence, biopsy specimens of the proximal airways are likely to be representative of the cellular infiltrate in large and small airways in mild and severe asthma.
Homozygous deletion of the activin A receptor, type IB gene is associated with an aggressive cancer phenotype in pancreatic cancer
Authors: Yosuke Togashi, Hiroki Sakamoto, Hidetoshi Hayashi, Masato Terashima, Marco A de Velasco, Yoshihiko Fujita, Yasuo Kodera, Kazuko Sakai, Shuta Tomida, Masayuki Kitano, Akihiko Ito, Masatoshi Kudo, Kazuto Nishio
Journal: Molecular Cancer (2014)

Transforming growth factor, beta (TGFB) signal is considered to be a tumor suppressive pathway based on the frequent genomic deletion of the SMAD4 gene in pancreatic cancer (PC); however; the role of the activin signal, which also belongs to the TGFB superfamily, remains largely unclear. We found a homozygous deletion of the activin A receptor, type IB (ACVR1B) gene in 2 out of 8 PC cell lines using array-comparative genomic hybridization, and the absence of ACVR1B mRNA and protein expression was confirmed in these 2 cell lines. Activin A stimulation inhibited cellular growth and increased the phosphorylation level of SMAD2 and the expression level of p21CIP1/WAF1 in the Sui66 cell line (wild-type ACVR1B and SMAD4 genes) but not in the Sui68 cell line (homozygous deletion of ACVR1B gene). Stable ACVR1B-knockdown using short hairpin RNA cancelled the effects of activin A on the cellular growth of the PC cell lines. In addition, ACVR1B-knockdown significantly enhanced the cellular growth and colony formation abilities, compared with controls. In a xenograft study, ACVR1B-knockdown resulted in a significantly elevated level of tumorigenesis and a larger tumor volume, compared with the control. Furthermore, in clinical samples, 6 of the 29 PC samples (20.7%) carried a deletion of the ACVR1B gene, while 10 of the 29 samples (34.5%) carried a deletion of the SMAD4 gene. Of note, 5 of the 6 samples with a deletion of the ACVR1B gene also had a deletion of the SMAD4 gene. We identified a homozygous deletion of the ACVR1B gene in PC cell lines and clinical samples and proposed that the deletion of the ACVR1B gene may mediate an aggressive cancer phenotype in PC. Our findings provide novel insight into the role of the activin signal in PC.
A phase 2 clinical study of SU5416 in patients with refractory acute myeloid leukemia
Authors: Walter Fiedler, Rolf Mesters, Heike Tinnefeld, Sonja Loges, Peter Staib, Ulrich Dührsen, Michael Flasshove, Oliver G. Ottmann, Wolfram Jung, Franco Cavalli, Rolf Kuse, Joerg Thomalla, Hubert Serve, Anne M. O'Farrell, Mark Jacobs, Nicoletta M. Brega, Paul Scigalla, Dieter K. Hossfeld, Wolfgang E. Berdel
Journal: Blood (2003)
Cost-Effectiveness of Providing Full Drug Coverage to Increase Medication Adherence in Post–Myocardial Infarction Medicare Beneficiaries
Authors: Niteesh K. Choudhry, Amanda R. Patrick, Elliott M. Antman, Jerry Avorn, William H. Shrank
Journal: Circulation (2008)

Effective therapies for the secondary prevention of coronary heart disease-related events are significantly underused, and attempts to improve adherence have often yielded disappointing results. Elimination of patient out-of-pocket costs may be an effective strategy to enhance medication use. We sought to estimate the incremental cost-effectiveness of providing full coverage for aspirin, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins (combination pharmacotherapy) to individuals enrolled in the Medicare drug benefit program after acute myocardial infarction.
Type II collagen is a target antigen of clonally expanded T cells in the synovium of patients with rheumatoid arthritis
Authors: T. Sekine, T. Kato, K. Masuko-Hongo, H. Nakamura, S.-i. Yoshino, K. Nishioka, K. Yamamoto
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> To investigate whether type II collagen (CII) is recognised by oligoclonally expanded synovial T cells of patients with rheumatoid arthritis (RA). <h3>METHODS</h3> Peripheral blood mononuclear cells (PBMC) from 15 RA patients were stimulated with CII in vitro. T cell clones expanded by such stimulation were compared with the clonally expanded synovial T cells by using T cell receptor (TCR) B chain gene specific reverse transcription-polymerase chain reaction and subsequent single strand conformation polymorphism analyses. <h3>RESULTS</h3> Stimulation of the heterogeneous peripheral T cells with CII induced clonal expansion of T cells. In three of 15 patients, a proportion of these clones (approximately 17% to 25%) was found to be identical to expanded T cell clones in the synovium in vivo. <h3>CONCLUSION</h3> T cell clones that had TCR CDR3 sequences identical to those induced by purified CII were found in a proportion of RA patients. This finding suggests that CII is recognised by T cells that accumulate clonally in RA joints. Oligoclonal T cell expansion in RA joints is probably driven, at least in part, by intra-articular components such as CII.
785 ADIPOSE TRIGLYCERIDE LIPASE (ATGL) IS A NOVEL MODULATOR OF HEPATIC ER-STRESS
Authors: C.D. Fuchs, T. Moustafa, G. Haemmerle, E. Halilbasic, J. Gumhold, D. Silbert, P. Fickert, R. Zechner, M. Trauner
Journal: Journal of Hepatology (2010)