tbuckley/cabot-search huggingface dataset:
Detection of Lymph Node Micrometastases by Gene Promoter Hypermethylation in Samples Obtained by Endosonography- Guided Fine-Needle Aspiration Biopsy
Authors: Maria Pellisé, Antoni Castells, Àngels Ginès, Rubén Agrelo, Manel Solé, Sergi Castellví-Bel, Glòria Fernández-Esparrach, Josep Llach, Manel Esteller, Josep M. Bordas, Josep M. Piqué
Journal: Clinical Cancer Research (2004)

Abstract Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become a fundamental procedure for gastrointestinal and lung cancer staging. However, there is growing evidence that micrometastases are present in lymph nodes, which cannot be detected with standard pathological methods. The aim of this study was to evaluate whether hypermethylation gene promoter analysis was feasible on samples obtained by EUS-FNA from lymph nodes, as well as to establish the usefulness of this strategy for the detection of micrometastases in patients with gastrointestinal and non-small cell lung cancer. Suspicious lymph nodes based on EUS findings from consecutive patients with esophageal, gastric, rectal, and non-small cell lung cancer were sampled by EUS-FNA. Hypermethylation analysis of the MGMT, p16INK4a, and p14ARF gene promoter CpG islands were performed by methylation-specific PCR. Effectiveness of conventional cytology, methylation analysis, and their combination were established with respect to the definitive diagnosis. Twenty-seven patients were included, thus representing a total of 42 lymph nodes (esophageal cancer, n = 11; rectal cancer, n = 7; gastric cancer, n = 3; and lung cancer, n = 21). According to definitive diagnosis, 21 (50%) corresponded to metastatic lymph nodes. Sensitivity, specificity, and overall accuracy of conventional cytology were 76%, 100%, and 88%, respectively, whereas the corresponding values for the methylation analysis were 81%, 67%, and 74%, respectively. Combination of both techniques increased sensitivity (90%) but decreased specificity (67%) with respect to conventional cytology. In conclusion, it is feasible to detect occult neoplastic cells in EUS-FNA samples by hypermethylation gene promoter analysis. Moreover, addition of methylation analysis to conventional cytology may increase its sensitivity at the expenses of a decrease in its specificity.
AN EPIZOOTIC DISEASE OF FERRETS CAUSED BY A FILTERABLE VIRUS
Authors: C. A. Slanetz, Hans Smetana
Journal: The Journal of Experimental Medicine (1937)

1. An epizootic disease of ferrets with a very high case fatality rate is described. 2. By the use of suitable material the natural disease can be transmitted experimentally. 3. The primary causative agent of the disease is a filterable virus. 4. Secondary invasion by bacteria of the respiratory tract of infected animals frequently occurs. The most important secondary invader is hemolytic streptococcus. 5. There seems to be no immunological relationship between the virus of the ferret disease and the viruses of canine distemper and of human influenza. 6. Histologically the disease is characterized by cytoplasmic and intranuclear inclusion bodies in epithelial cells of many organs. 7. These inclusion bodies are indistinguishable from those occurring in canine distemper.
Marburg virus infection in nonhuman primates: Therapeutic treatment by lipid-encapsulated siRNA
Authors: Emily P. Thi, Chad E. Mire, Raul Ursic-Bedoya, Joan B. Geisbert, Amy C. H. Lee, Krystle N. Agans, Marjorie Robbins, Daniel J. Deer, Karla A. Fenton, Ian MacLachlan, Thomas W. Geisbert
Journal: Science Translational Medicine (2014)

Lipid nanoparticle delivery of anti-MARV nucleoprotein–targeting small interfering RNA can treat Marburg virus in nonhuman primates after symptom onset.
Biomedical Applications of Graphene
Authors: He Shen, Liming Zhang, Min Liu, Zhijun Zhang
Journal: Theranostics (2012)

Graphene exhibits unique 2-D structure and exceptional phyiscal and chemical properties that lead to many potential applications.Among various applications, biomedical applications of graphene have attracted ever-increasing interests over the last three years.In this review, we present an overview of current advances in applications of graphene in biomedicine with focus on drug delivery, cancer therapy and biological imaging, together with a brief discussion on the challenges and perspectives for future research in this field.
Diet-induced atherosclerosis in mice heterozygous and homozygous for apolipoprotein E gene disruption.
Authors: S H Zhang, R L Reddick, B Burkey, N Maeda
Journal: Journal of Clinical Investigation (1994)

With the aim of establishing whether a genetically reduced capability of producing apolipoprotein E (apo E) can affect atherogenesis, we have compared the consequences of dietary stress on normal mice and on mice heterozygous or homozygous for a disrupted apo E gene. A dramatically accelerated development of lesions occurred in the vasculature of the homozygous mutants as a result of feeding an atherogenic diet for 12 wk, and extensive deposition of lipid-filled macrophages was found outside the cardiovascular system. In nine heterozygotes fed the atherogenic diet for 12 wk, the amount of apo E in their total plasma lipoproteins increased to a level comparable to normal, but all nine developed much larger foam cell lesions in their proximal aorta than those found in 3 of 9 normal mice fed the same diet. The other six normals had no lesions. Our study demonstrates that heterozygous mice with only one functional apo E gene are more susceptible to diet-induced atherosclerosis than are normal, two-copy mice. Genetically determined quantitative limitations of apo E could, therefore, have similar effects in humans when they are stressed by an atherogenic diet.
Alpha 1-adrenergic receptors in pulmonary and systemic vascular smooth muscle. Alterations with development and pregnancy.
Authors: P W Shaul, R R Magness, K H Muntz, D DeBeltz, L M Buja
Journal: Circulation Research (1990)

alpha 1-Adrenergic receptors mediate vasoconstriction in the pulmonary and systemic vasculature. In sheep the in vivo vasoconstrictor response to alpha 1-adrenergic stimulation is less in the pulmonary circulation compared with the systemic circulation of the fetus, the response increases in both vascular beds with fetal and postnatal development, and it decreases in the systemic vasculature with pregnancy. In an effort to determine the mechanisms underlying these differences, alpha 1-adrenergic receptor binding characteristics were determined by using [3H]prazosin in intrapulmonary and systemic (thoracic aorta) vascular smooth muscle (VSM) from late-gestation fetal lambs and from pregnant and nonpregnant ewes. alpha 1-Adrenergic receptor density was less in fetal intrapulmonary VSM that in fetal aortic VSM (12.4 +/- 1.5 versus 29.4 +/- 3.2 fmol/mg protein, p less than 0.05), and it was less (p less than 0.05) in the fetus compared with the pregnant ewe in both intrapulmonary and aortic VSM (51.0 +/- 5.2 and 76.5 +/- 5.9 fmol/mg protein, respectively). alpha 1-Adrenergic receptor density in intrapulmonary VSM was similar in the pregnant and nonpregnant ewe (61.9 +/- 7.2 fmol/mg protein), whereas in aortic VSM it was less (p less than 0.05) in pregnant ewes compared with nonpregnant ewes (101.0 +/- 5.5 fmol/mg protein). alpha 1-Adrenergic receptor affinity was similar in all the VSM sources tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Dry-Contact and Noncontact Biopotential Electrodes: Methodological Review
Authors: Yu Mike Chi, Tzyy-Ping Jung, Gert Cauwenberghs
Journal: IEEE Reviews in Biomedical Engineering (2010)

Recent demand and interest in wireless, mobile-based healthcare has driven significant interest towards developing alternative biopotential electrodes for patient physiological monitoring. The conventional wet adhesive Ag/AgCl electrodes used almost universally in clinical applications today provide an excellent signal but are cumbersome and irritating for mobile use. While electrodes that operate without gels, adhesives and even skin contact have been known for many decades, they have yet to achieve any acceptance for medical use. In addition, detailed knowledge and comparisons between different electrodes are not well known in the literature. In this paper, we explore the use of dry/noncontact electrodes for clinical use by first explaining the electrical models for dry, insulated and noncontact electrodes and show the performance limits, along with measured data. The theory and data show that the common practice of minimizing electrode resistance may not always be necessary and actually lead to increased noise depending on coupling capacitance. Theoretical analysis is followed by an extensive review of the latest dry electrode developments in the literature. The paper concludes with highlighting some of the novel systems that dry electrode technology has enabled for cardiac and neural monitoring followed by a discussion of the current challenges and a roadmap going forward.
Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of SAR245409 (XL765), a Novel, Orally Administered PI3K/mTOR Inhibitor in Patients with Advanced Solid Tumors
Authors: Kyriakos P. Papadopoulos, Josep Tabernero, Ben Markman, Amita Patnaik, Anthony W. Tolcher, José Baselga, Weiliang Shi, Coumaran Egile, Rodrigo Ruiz-Soto, A. Douglas Laird, Dale Miles, Patricia M. LoRusso
Journal: Clinical Cancer Research (2014)

This phase I, first-in-human study evaluated the safety, maximum-tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and preliminary efficacy of SAR245409, an inhibitor of pan-Class I phosphoinositide 3-kinase (PI3K) and mTOR, administered orally once or twice daily in patients with advanced solid tumors.Eighty-three patients received SAR245409. Doses ranged from 15 to 120 mg twice daily, and 70 to 100 mg once daily. A 3+3 dose-escalation design was used to determine the MTD. Patients were evaluated for adverse events and response. Assessments included pharmacokinetic, pharmacodynamic impact of SAR245409 on PI3K pathway signaling in hair sheath cells, skin and tumor, and characterization of tumor molecular alterations.The MTDs were 50 mg twice daily and 90 mg once daily. The most frequent treatment-related adverse events were nausea (36.1%), diarrhea (21.7%), vomiting (19.3%), and decreased appetite (16.9%). The most frequent treatment-related grade 3/4 adverse events were increases in alanine aminotransferase (6.0%) and aspartate aminotransferase (4.8%). SAR245409 had a relatively short plasma half-life (2.96-7.52 hours). At MTDs, once- and twice-daily regimens yielded similar mean steady-state plasma exposure. A reduction in PI3K and mTORC1/mTORC2 pathway signaling was observed in serial hair sheath cells, skin, and tumor samples. Best response was stable disease in 48% of evaluable patients; seven patients had minor tumor regression. Twelve patients with stable disease were treated for ≥16 weeks. No trend was observed correlating tumor molecular alteration with antitumor activity.SAR245409 had a manageable safety profile, demonstrated reduced PI3K and mTORC1/mTORC2 pathway signaling and was associated with clinically relevant stable disease.
Human complement receptor type 1–directed loading of tissue plasminogen activator on circulating erythrocytes for prophylactic fibrinolysis
Authors: Sergei Zaitsev, Kristina Danielyan, Juan-Carlos Murciano, Kumkum Ganguly, Tatiana Krasik, Ronald P. Taylor, Steven Pincus, Steven Jones, Douglas B. Cines, Vladimir R. Muzykantov
Journal: Blood (2006)
Natural History of Adenocarcinoma-Large Cell Carcinoma of the Lung: Conclusions From Screening Programs in New York and Baltimore
Authors: B. J. Flehinger, M. Kimmel, M. R. Melamed
Journal: JNCI Journal of the National Cancer Institute (1988)

A mathematical model of the progression kinetics of lung cancer was described and used to shed light on the natural history of adenocarcinoma and large cell carcinoma of lung from data collected in screening studies of male smokers by the Memorial Sloan-Kettering Cancer Center and The Johns Hopkins Medical Institutions. In both programs, estimates of the mean duration of early-stage adenocarcinoma or large cell carcinoma of lung ranged upward from 4 years, and estimates of the probability of detecting it in early-stage disease ranged downward from .16. The probabilities of curing early-stage disease through surgical treatment were found to be at most .52 and .13 in the New York and Baltimore studies, respectively. These estimates led to the conclusion that expected reduction in mortality from adenocarcinoma and large cell carcinoma of lung as due to annual x-ray screening from age 45 to 80 years is not greater than 18% in New York and 5% in Baltimore.
Di(2-ethylhexyl) Adipate: Condensation of the Carcinogenesis Bioassay Technical Report
Authors: James Huff
Journal: Environmental Health Perspectives (1982)

Di(2-ethylhexyl) Adipate: Condensation of the Carcinogenesis Bioassay Technical Report* Di(2-ethylhexyl) adipate [bis(2-ethylhexyl) adipate, DEHA, octyl adipate, dioctyl adipate, DOA, CAS No. 103-23-1], a plasticizer added to vinyl plastics to give low temperature flexibility, is dispersed (not bound) in the polymer chain matrix.Approved by the U.S. Food and Drug Administration for use in plastics that may contact nonfatty, nonalcoholic foods (not to exceed 24% by weight of the plastic polymer), DEHA has wide use in vinyl packaging ifim for refrigerated and frozen food products.Other products containing DEHA include electric wire insulation, garden hoses, vinyl coated fabrics for automotive and upholstery use, synthetic rub- ber, base oils for hydraulic fluids, and, among others, polyvinyl tubing for hemodialysis.For these uses 44 million pounds were produced in 1978.DEHA was selected as a representative of the adipate class of plasticizers, because it is structur- ally related to di(2-ethylhexyl) phthalate, because human exposure is widespread, and because no carcinogenesis studies had been done.
Spiral computed tomography for stratification of pulmonary embolism: ready for prime time?
Authors: Guy Meyer, Olivier Sanchez
Journal: European Respiratory Journal (2014)

The risk stratification of patients with pulmonary embolism has been the subject of a large number of studies in recent years. Current guidelines suggest that patients be stratified in order to identify low-risk patients, who might benefit from outpatient treatment, and high-risk patients, who should be admitted to hospital and who might benefit from more aggressive forms of treatment [1]. This can be achieved by clinical examination alone using either an explicit risk stratification tool or a more empirical set of criteria [2–5]. Subclinical myocardial injury and right ventricular dysfunction, assessed by biomarkers, echocardiography or spiral computed tomography, also have been shown to be associated with an increased risk of an adverse outcome in patients with pulmonary embolism [6–8].

The study by Becattini et al . [9], published in this issue of the European Respiratory Journal , reinforces the role of computed tomography (CT) in the risk stratification of patients with pulmonary …
Barrier function regulates epidermal DNA synthesis.
Authors: E Proksch, K R Feingold, M Q Man, P M Elias
Journal: Journal of Clinical Investigation (1991)

We examined the possibility that the cutaneous permeability barrier regulates epidermal DNA synthesis in two acute and two chronic models of barrier perturbation. In animals treated topically with acetone, DNA synthesis is increased 102%, in tape-stripped animals 127%, in essential fatty acid deficient animals 50%, and in animals chronically treated with topical lovastatin 64%. This linkage between disturbances in barrier function and increased DNA synthesis is further supported by specific and correlative observations: (a) in these disparate models, artificial replacement of the barrier with a water-impermeable membrane inhibits the expected increase in DNA synthesis; (b) the extent of the burst in DNA synthesis is proportional to the degree of barrier abrogation; (c) the inhibition of DNA synthesis by membranes is directly related to the degree of permeability of these occlusive membranes, i.e., the more impermeable the greater the degree of inhibition; (d) topical treatment with lipids that restore barrier function corrects the increase in DNA synthesis; and (e) barrier abrogation with acetone produces an increase in epidermal DNA synthesis without altering bulk protein synthetic rates in contrast to events known to follow injury or cell replacement. Autoradiographic studies show that the increase in DNA synthesis after acetone treatment is limited to the epidermal basal layer. This constellation of findings strongly suggests that cutaneous barrier function is one factor that regulates epidermal DNA synthesis.
Effect of High Glucose on Mesangial Cell Protein Kinase C-δ and -ε is Polyol Pathway-Dependent
Authors: JOVANA KAPOR-DREZGIC, XIAOPENG ZHOU, TETSUYA BABAZONO, JOHN A. DLUGOSZ, THOMAS HOHMAN, CATHARINE WHITESIDE
Journal: Journal of the American Society of Nephrology (1999)

Abstract. In diabetes mellitus, enhanced activity of mesangial cell protein kinase C (PKC) may contribute to nephropathy. The purpose of this study was to determine whether high glucose alters mesangial cell diacylglycerol-sensitive PKC-α, -β 2 , -δ, and -ε content, cellular distribution, and activity through polyol pathway activation. Primary cultured rat mesangial cells (passage 10) were growth-arrested in 0.5% fetal bovine serum and cultured in 5.6 mM glucose (NG) or 30 mM glucose (HG) for 48 h, with or without the aldose reductase inhibitor tolrestat or ARI-509. PKC isoform content in total cell lysates, or cytosol, membrane (Triton X-soluble), and particulate (sodium dodecyl sulfate-soluble) fractions was analyzed by immunoblotting, and band density in HG was expressed as a percentage of corresponding NG values. In HG at 48 h, increased total PKC-α (222 ± 17% of NG, P &lt; 0.001), -β 2 (209 ± 12%, P &lt; 0.001), and -ε (195 ± 19%, P &lt; 0.001) were observed. L-Glucose had no effect on total PKC isoform content. HG caused increased membrane- and particulate-associated PKC-α (257 ± 87 and 327 ± 66%, respectively, P &lt; 0.05), membrane-associated PKC-δ (143 ± 10%, P &lt; 0.05), and membrane-associated PKC-ε (186 ± 11%, P &lt; 0.001), with no change in cytosol contents. The HG effects were not mimicked by L-glucose. In NG or HG, PKC-β 2 was not detected in the cytosol fraction, and membrane and particulate association were unchanged with phorbol ester stimulation. Confocal immunofluorescence imaging revealed that in HG, PKC-α, -δ, and -ε translocate to the nucleus and plasma membrane. Total PKC activity measured by in situ 32 P-phosphorylation of the epidermal growth factor receptor substrate increased from 18 ± 1 pmol/min per mg cell protein in NG to 33 ± 3 pmol/min per mg cell protein in HG ( P &lt; 0.002 versus NG). In NG, tolrestat and ARI-509 exposure caused increased PKC activity, enhanced accumulation of total PKC-α and -β 2 , with no change in total or fractional recovery of PKC-δ or -ε. In HG, tolrestat and ARI-509 prevented the increase in total PKC-ε and membrane-associated PKC-δ and -ε. It is concluded that within 48 h of HG, enhanced mesangial cell PKC activity is associated with accumulation and cellular redistribution of diacylglycerol-sensitive PKC isoforms, and that increased PKC-ε content and membrane-associated PKC-δ and -ε are dependent on polyol pathway activation.
Long-lived virus-reactive memory T cells generated from purified cytokine-secreting T helper type 1 and type 2 effectors
Authors: Max Löhning, Ahmed N. Hegazy, Daniel D. Pinschewer, Dorothea Busse, Karl S. Lang, Thomas Höfer, Andreas Radbruch, Rolf M. Zinkernagel, Hans Hengartner
Journal: The Journal of Experimental Medicine (2008)

Many vaccination strategies and immune cell therapies aim at increasing the numbers of memory T cells reactive to protective antigens. However, the differentiation lineage and therefore the optimal generation conditions of CD4 memory cells remain controversial. Linear and divergent differentiation models have been proposed, suggesting CD4 memory T cell development from naive precursors either with or without an effector-stage intermediate, respectively. Here, we address this question by using newly available techniques for the identification and isolation of effector T cells secreting effector cytokines. In adoptive cell transfers into normal, nonlymphopenic mice, we show that long-lived virus-specific memory T cells can efficiently be generated from purified interferon γ–secreting T helper (Th) type 1 and interleukin (IL)-4– or IL-10–secreting Th2 effectors primed in vitro or in vivo. Importantly, such effector-derived memory T cells were functional in viral challenge infections. They proliferated vigorously, rapidly modulated IL-7 receptor expression, exhibited partial stability and flexibility of their cytokine patterns, and exerted differential effects on virus-induced immunopathology. Thus, cytokine-secreting effectors can evade activation-induced cell death and develop into long-lived functional memory cells. These findings demonstrate the efficiency of linear memory T cell differentiation and encourage the design of vaccines and immune cell therapies based on differentiated effector T cells.
A comparison of heritable abnormal lipoprotein patterns as defined by two different techniques
Authors: D. S. Fredrickson, R. I. Levy, F. T. Lindgren
Journal: Journal of Clinical Investigation (1968)

Eight plasma lipoprotein patterns currently employed in attempts to identify different forms of familial dyslipoproteinemia have been compared by two methods. The first (NIH method) is based on paper electrophoretic patterns produced by the four lipoprotein classes obtained by paper electrophoresis in albuminated buffer, coupled with the measurement of the total cholesterol of three of these lipoprotein classes and ascertainment of abnormal flotation of beta-migrating lipoproteins. The second (Donner method) is based on lipoprotein patterns obtained in the analytical ultracentrifuge, adapted for computer analysis and complemented by chemical determination of the concentration of chylomicrons (lipoproteins of Sf° > 400). Pooled samples representing patients with five types of familial hyperlipoproteinemia and three different forms of inherited lipoprotein dificiency were separately analyzed. For six of the eight pools, both methods provided a distinctive lipoprotein pattern in terms of changes in one or more variables. For the remaining two pools, type IV hyperlipoproteinemia and the heterozygote for Tangier disease, both methods provided identical but not unique patterns. The results indicate that lipoprotein analyses obtained by either method may be used interconvertibly in further genetic and other clinical studies.