tbuckley/cabot-search huggingface dataset:
A Virus-Like Particle Enzyme-Linked Immunosorbent Assay Detects Serum Antibodies in a Majority of Women Infected With Human Papillomavirus Type 16
Authors: R Kirnbauer, N L Hubbert, C M Wheeler, T M Becker, D R Lowy, J T Schiller
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article A Virus-Like Particle Enzyme-Linked Immunosorbent Assay Detects Serum Antibodies in a Majority of Women Infected With Human Papillomavirus Type 16 Get access Reinhard Kirnbauer, Reinhard Kirnbauer Search for other works by this author on: Oxford Academic PubMed Google Scholar Nancy L. Hubbert, Nancy L. Hubbert Search for other works by this author on: Oxford Academic PubMed Google Scholar Cosette M. Wheeler, Cosette M. Wheeler Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas M. Becker, Thomas M. Becker Search for other works by this author on: Oxford Academic PubMed Google Scholar Douglas R. Lowy, Douglas R. Lowy Search for other works by this author on: Oxford Academic PubMed Google Scholar John T. Schiller John T. Schiller Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 7, 6 April 1994, Pages 494–499, https://doi.org/10.1093/jnci/86.7.494 Published: 06 April 1994 Article history Received: 19 August 1993 Revision received: 30 November 1993 Accepted: 05 January 1994 Published: 06 April 1994
Structural and Functional Changes in the Airway Smooth Muscle of Asthmatic Subjects
Authors: CHUN Y. SEOW, R. ROBERT SCHELLENBERG, PETER D. PARÉ
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Section:ChooseTop of pageAbstract <<STRUCTURAL ALTERATIONS IN...FUNCTIONAL ALTERATIONS IN...FUNCTIONAL ALTERATIONS IN...ReferencesCITING ARTICLES
STRESS PROTEIN EXPRESSION KINETICS
Authors: Kenneth R. Diller
Journal: Annual Review of Biomedical Engineering (2006)

In all organisms there is an elevated synthesis of a select family of "stress proteins" in response to a broad array of environmentally driven stress vectors including elevated or depressed temperature, changes in pH, treatment with many classes of chemicals, ischemia, desiccation, and UV irradiation. The presence of stress proteins, often termed heat shock proteins (HSPs), has been recognized for more than four decades, and there is an extensive literature that addresses the structure and properties of HSPs, their function in normal and injured cells and tissues, and the molecular mechanisms of HSP expression in response to stress. Owing to this substantial aggregate of research, there is a growing appreciation of the potential for manipulating the magnitude and timing of elevated HSP expression to achieve targeted therapeutic objectives. The successful realization of this potential requires an understanding of the kinetics of the HSP expression process in response to sublethal stress regimens along with the ability to model the governing events in the process to design practical protocols that could be applied in therapeutic settings. Significant progress has been made in recent years in defining and developing capabilities in these two areas.
Anesthetics and Ion Channels: Molecular Models and Sites of Action
Authors: Tomohiro Yamakura, Edward Bertaccini, James R Trudell, R Adron Harris
Journal: The Annual Review of Pharmacology and Toxicology (2001)

The mechanisms of general anesthesia in the central nervous system are finally yielding to molecular examination. As a result of research during the past several decades, a group of ligand-gated ion channels have emerged as plausible targets for general anesthetics. Molecular biology techniques have greatly accelerated attempts to classify ligand-gated ion channel sensitivity to general anesthetics, and have identified the sites of receptor subunits critical for anesthetic modulation using chimeric and mutated receptors. The experimental data have facilitated the construction of tenable molecular models for anesthetic binding sites, which in turn allows structural predictions to be tested. In vivo significance of a putative anesthetic target can now be examined by targeted gene manipulations in mice. In this review, we summarize from a molecular perspective recent advances in our understanding of mechanisms of action of general anesthetics on ligand-gated ion channels.
Sports utility vehicles and older pedestrians
Authors: Robert A Davis
Journal: BMJ (2005)

Simms and O'Neill point out the problems posed by a particular class of private motor vehicles (sports utility vehicles, SUVs) to one group of other road users. The danger posed by SUVs is simply a more extreme version of the problems posed by all motor vehicles to all other road users, not just elderly pedestrians. The fundamental reason for a higher involvement of SUVs in pedestrian and other road user road traffic accidents is that SUV drivers feel better protected in their vehicle than in smaller motor vehicles. SUVs are frequently advertised as being safer than smaller vehicles and give the impression of crashworthiness to potential buyers irrespective of any advertising campaigns.
Gemcitabine and oxaliplatin (GEMOX) in patients withcisplatin-refractory germ cell tumors: a phase II study
Authors: D. Pectasides, M. Pectasides, D. Farmakis, G. Aravantinos, M. Nikolaou, M. Koumpou, A. Gaglia, V. Kostopoulou, N. Mylonakis, D. Skarlos
Journal: Annals of Oncology (2004)
Ovarian cancer in elderly patients: carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in late relapse: a Gynecologic Cancer Intergroup (GCIG) CALYPSO sub-study
Authors: J.E. Kurtz, M.C. Kaminsky, A. Floquet, A.S. Veillard, R. Kimmig, A. Dorum, L. Elit, M. Buck, E. Petru, N. Reed, G. Scambia, N. Varsellona, C. Brown, E. Pujade-Lauraine
Journal: Annals of Oncology (2011)
A Zebrafish Compound Screen Reveals Modulation of Neutrophil Reverse Migration as an Anti-Inflammatory Mechanism
Authors: Anne L. Robertson, Geoffrey R. Holmes, Aleksandra N. Bojarczuk, Joseph Burgon, Catherine A. Loynes, Myriam Chimen, Amy K. Sawtell, Bashar Hamza, Joseph Willson, Sarah R. Walmsley, Sean R. Anderson, Mark C. Coles, Stuart N. Farrow, Roberto Solari, Simon Jones, Lynne R. Prince, Daniel Irimia, G. Ed Rainger, Visakan Kadirkamanathan, Moira K. B. Whyte, Stephen A. Renshaw
Journal: Science Translational Medicine (2014)

The proresolution therapeutic tanshinone IIA drives inflammation resolution by reverse migration.
Phase I Trial of the Antivascular Agent Combretastatin A4 Phosphate on a 5-Day Schedule to Patients With Cancer: Magnetic Resonance Imaging Evidence for Altered Tumor Blood Flow
Authors: James P. Stevenson, Mark Rosen, Weijing Sun, Maryann Gallagher, Daniel G. Haller, David Vaughn, Bruce Giantonio, Ross Zimmer, William P. Petros, Michael Stratford, David Chaplin, Scott L. Young, Mitchell Schnall, Peter J. O’Dwyer
Journal: Journal of Clinical Oncology (2003)

Purpose: Combretastatin A4 (CA4) phosphate (CA4P) inhibits microtubule polymerization and is toxic to proliferating endothelial cells in vitro. It causes reversible vascular shutdown in established tumors in vivo, consistent with an antivascular mechanism of action. The present study investigated escalating doses of CA4P administered intravenously to patients with advanced cancer. Patients and Methods: Patients with solid malignancies and good performance status received CA4P as a 10-minute infusion daily for 5 days repeated every 3 weeks. Pharmacokinetic sampling was performed during cycle 1. Patients receiving ≥ 52 mg/m 2 /d had serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies to measure changes in tumor perfusion with CA4P treatment. Results: Thirty-seven patients received 133 treatment cycles. CA4P dose levels ranged from 6 mg/m 2 to 75 mg/m 2 daily. Severe pain at sites of known tumor was dose limiting at 75 mg/m 2 . Dose-limiting cardiopulmonary toxicity (syncope and dyspnea or hypoxia) was noted as well in two patients treated at 75 mg/m 2 . Other toxicities included hypotension, ataxia, dyspnea, nausea or vomiting, headache, and transient sensory neuropathy. Plasma CA4P and CA4 area under the concentration-time curve and maximal concentration values increased linearly with dose. Tumor perfusion, as measured by the first-order rate constant of gadolinium plasma to tissue transfer during DCE-MRI studies, was found to decrease in eight of 10 patients. Relationships were also demonstrated between perfusion changes and pharmacokinetic indices. A partial response was observed in a patient with metastatic soft tissue sarcoma, and 14 patients exhibited disease stability for a minimum of two cycles. Conclusion: Doses of CA4P on a daily times five schedule of 52 to 65 mg/m 2 were reasonably well-tolerated. The 52 mg/m 2 dose is recommended for further study based on cumulative phase I experience with CA4P. Antitumor efficacy was observed, and the use of DCE-MRI provided a valuable noninvasive measure of the vascular effects of CA4P treatment.
A Simple “New” Method to Accelerate Clearance of Carbon Monoxide
Authors: AKINORI TAKEUCHI, ALEX VESELY, JOSHUA RUCKER, LEEOR Z. SOMMER, JANET TESLER, ELANA LAVINE, ARTHUR S. SLUTSKY, WOLFGANG H. MALECK, GEORGE VOLGYESI, LUDWIK FEDORKO, STEVE ISCOE, JOSEPH A. FISHER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The currently recommended prehospital treatment for carbon monoxide (CO) poisoning is administration of 100% O2. We have shown in dogs that normocapnic hyperpnea with O2 further accelerates CO elimination. The purpose of this study was to examine the relation between minute ventilation (V˙ e) and the rate of elimination of CO in humans. Seven healthy male volunteers were exposed to CO (400 to 1,000 ppm) in air until their carboxyhemoglobin (COHb) levels reached 10 to 12%. They then breathed either 100% O2 at resting V˙ e (4.3 to 9.0 L min) for 60 min or O2 containing 4.5 to 4.8% CO2 (to maintain normocapnia) at two to six times resting V˙ e for 90 min. The half-time of the decrease in COHb fell from 78 ± 24 min (mean ± SD) during resting V˙ e with 100% O2 to 31 ± 6 min (p < 0.001) during normocapnic hyperpnea with O2. The relation between V˙ e and the half-time of COHb reduction approximated a rectangular hyperbola. Because both the method and circuit are simple, this approach may enhance the first-aid treatment of CO poisoning.
A Caveolae-Targeted L-Type Ca <sup>2+</sup> Channel Antagonist Inhibits Hypertrophic Signaling Without Reducing Cardiac Contractility
Authors: Catherine A. Makarewich, Robert N. Correll, Hui Gao, Hongyu Zhang, Baohua Yang, Remus M. Berretta, Victor Rizzo, Jeffery D. Molkentin, Steven R. Houser
Journal: Circulation Research (2012)

Rationale: The source of Ca 2+ to activate pathological cardiac hypertrophy is not clearly defined. Ca 2+ influx through the L-type Ca 2+ channels (LTCCs) determines “contractile” Ca 2+ , which is not thought to be the source of “hypertrophic” Ca 2+ . However, some LTCCs are housed in caveolin-3 (Cav-3)–enriched signaling microdomains and are not directly involved in contraction. The function of these LTCCs is unknown. Objective: To test the idea that LTCCs in Cav-3–containing signaling domains are a source of Ca 2+ to activate the calcineurin–nuclear factor of activated T-cell signaling cascade that promotes pathological hypertrophy. Methods and Results: We developed reagents that targeted Ca 2+ channel-blocking Rem proteins to Cav-3–containing membranes, which house a small fraction of cardiac LTCCs. Blocking LTCCs within this Cav-3 membrane domain eliminated a small fraction of the LTCC current and almost all of the Ca 2+ influx-induced NFAT nuclear translocation, but it did not reduce myocyte contractility. Conclusions: We provide proof of concept that Ca 2+ influx through LTCCs within caveolae signaling domains can activate “hypertrophic” signaling, and this Ca 2+ influx can be selectively blocked without reducing cardiac contractility.
A functional integrin ligand on the surface of platelets: intercellular adhesion molecule-2.
Authors: T G Diacovo, A R deFougerolles, D F Bainton, T A Springer
Journal: Journal of Clinical Investigation (1994)

Activated platelets express P-selectin and release leukocyte chemoattractants; however, they have not been known to express integrin ligands important in the stabilization of leukocyte interactions with the vasculature. We now demonstrate the presence of intercellular adhesion molecular-2 (ICAM-2) (CD102), and lack of expression of other beta 2-integrin ligands, ICAM-1 (CD54) and ICAM-3 (CD50), on the surface of resting and stimulated platelets. ICAM-2 isolated from platelets migrates as a band of 59,000 M(r) in reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Staining of bone marrow aspirates with anti-ICAM-2 mAb demonstrates strong reactivity to megakaryocytes. Using frozen thin sections and immunogold labeling, the antigen was shown to be present on the plasma membrane and surface-connected canalicular system of resting platelets. The average number of ICAM-2 molecules per platelet is 3,000 +/- 230 and does not change after activation. In adhesion assays, resting and stimulated platelets were capable of binding through ICAM-2 to purified leukocyte function-associated antigen-1. Activation of T lymphocytes with PMA stimulated binding to platelets that was Mg2+ dependent and could be specifically inhibited by mAbs to either ICAM-2 or leukocyte function-associated antigen-1. ICAM-2 is the only known beta 2-integrin ligand present on platelets, suggesting that it may play an important role in leukocyte-platelet interactions in inflammation and thrombosis.
Polymorphism of human minor histocompatibility antigens: T cell recognition of human minor histocompatibility peptides presented by HLA-B35 subtype molecules.
Authors: Y Beck, L Satz, Y Takamiya, S Nakayama, L Ling, Y Ishikawa, T Nagao, H Uchida, K Tokunaga, C Müller
Journal: The Journal of Experimental Medicine (1995)

To investigate the polymorphism of human minor histocompatibility (mH) antigens, PBLs from 23 Japanese individuals and 25 German individuals with HLA-B35 were studied by using four human mH antigen-specific, HLA-B35-restricted CTL clones. The CTL clones killed PHA-stimulated PBLs from all 23 Japanese individuals. On the other hand, they killed the PHA-stimulated PBLs from 19 of 25 German individuals and partially killed the PHA-stimulated PBLs from three German individuals (CTL weakly sensitive cell line); those from another three individuals (CTL-resistant cell line) were not killed by the CTL clones. All of three CTL weakly sensitive cell lines carry HLA-B*3503 molecules, whereas the three CTL-resistant cell lines carry HLA-B*3502, B*3507, and B*3508 molecules. The cytotoxicity of the CTL clones for three CTL weakly sensitive cell lines was enhanced by stimulation of human mH peptides isolated from HLA-B*3501 molecules purified from C1R-B*3501 cells. Small amounts of human mH peptides were isolated from B*3503 molecules purified from these three CTL weakly sensitive cell lines. Taken together, these results indicate that weak recognition by the CTL clones of three CTL weakly sensitive cell line results from a small amount of the human mH peptides presented by B*3503 molecules. The CTL-resistant cell line carrying B*3507 loaded with the human mH peptides was killed by four CTL clones, whereas the cell lines carrying B*3502 or B*3508 loaded with the peptides were not. The human mH peptides were not isolated from B*3507 molecules purified from the cell lines expressing this subtype, whereas small amounts of the human mH peptides were isolated from B*3502 and B*3508 molecules purified from the cell lines expressing the subtypes. These results indicate that failure of the CTL recognition of the cell line carrying B*3507 is due to a lack of human mH antigens in this cell line. The failure of the CTL recognition of the cell lines carrying B*3502 and B*3508 is not explained by only the amount of the human mH peptides binding to these B35 subtype molecules because the amount of the human mH peptides eluted from B*3502 and B*3508 molecules purified from the cell lines carrying these B35 subtypes is almost the same as that eluted from B*3503 molecules purified from the cell lines carrying B*3503.(ABSTRACT TRUNCATED AT 400 WORDS)
Latex Allergy: Low Prevalence of IgE to Highly Purified Hev b 2 and Hev b 13
Authors: T. Palosuo, M. Lehto, A. Kotovuori, N. Kalkkinen, C. Blanco, P. Poza, T. Carrillo, R.G. Hamilton, H. Alenius, T. Reunala, K. Turjanmaa
Journal: Journal of Allergy and Clinical Immunology (2007)
Health Disparities Research in Global Perspective: New Insights and New Directions
Authors: Shiriki Kumanyika
Journal: Annual Review of Public Health (2012)

This commentary introduces this volume's symposium on "Comparative Approaches to Reducing Health Disparities." Disparities in the health of socially and economically disadvantaged compared with more advantaged populations are observed worldwide. The lack of progress in addressing these disparities compels a continuing search for new ideas and evidence about potential solutions as well as efforts to understand when and where these solutions work and how they work. The symposium consists of five in-depth reviews led by established scholars who approach the topic from their different disciplinary and topical perspectives. Taken together, these reviews point out the conceptual and methodological opportunities for generating more effective disparities research within biomedical, public health, and health services approaches, the value of also applying theory and methods from disciplines such as political science and economics to health disparities research, and insights to be gained from comparisons of how disparities occur and are remedied in different societies.
Diversification and Specialization of HIV Protease Function During In Vitro Evolution
Authors: T. L. O'Loughlin
Journal: Molecular Biology and Evolution (2006)

Our goal is to understand how enzymes adapt to utilize novel substrates. We and others have shown that directed evolution tends to generate enzyme variants with broadened substrate specificity. Broad-specificity enzymes are generally deleterious to living cells, so this observed trend might be an artifact of the most commonly employed high throughput screens. Here, we demonstrate a more natural and effective screening strategy for directed evolution. The gene encoding model enzyme HIV protease was randomly mutated, and the resulting library was expressed in Escherichia coli cells to eliminate cytotoxic broad-specificity variants. The surviving variants were screened for clones with activity against a reporter enzyme. The wild-type human immunodeficiency virus type I protease (HIV PR) is cytotoxic and exhibits no detectable activity in reactions with beta-galactosidase (BGAL). In contrast, the selected variants were nontoxic and exhibited greater activity and specificity against BGAL than did the wild-type HIV PR in reactions with any substrate. A single round of whole gene random mutagenesis and conventional high-throughput screening does not usually effect complete inversions of substrate specificity. This suggests that a combination of positive and purifying selection engenders more rapid adaptation than positive selection alone.
Sarcopenia as a Determinant of Chemotherapy Toxicity and Time to Tumor Progression in Metastatic Breast Cancer Patients Receiving Capecitabine Treatment
Authors: Carla M.M. Prado, Vickie E. Baracos, Linda J. McCargar, Tony Reiman, Marina Mourtzakis, Katia Tonkin, John R. Mackey, Sheryl Koski, Edith Pituskin, Michael B. Sawyer
Journal: Clinical Cancer Research (2009)

Body composition has emerged as an important prognostic factor in cancer patients. Severe depletion of skeletal muscle (sarcopenia) and, hence, of overall lean body mass may represent an occult condition in individuals with normal or even high body weight. Sarcopenia has been associated with poor performance status, 5-fluorouracil toxicity, and shortened survival in cancer patients. Here, we prospectively studied patients with metastatic breast cancer receiving capecitabine treatment in order to determine if sarcopenia was associated with a higher incidence of toxicity and a shorter time to tumor progression (TTP).Fifty-five women with metastatic breast cancer resistant to anthracycline and/or taxane treatment were included. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured by computerized tomography, and sarcopenia was defined using a previously published cutoff point. Toxicity was assessed after cycle 1 of treatment, and TTP was determined prospectively.Approximately 25% of patients were classified as sarcopenic, and this feature was seen in normal weight, overweight, and obese individuals. Toxicity was present in 50% of sarcopenic patients, compared with only 20% of nonsarcopenic patients (P = 0.03), and TTP was shorter in sarcopenic patients (101.4 days; confidence interval, 59.8-142.9) versus nonsarcopenic patients (173.3 days; confidence interval, 126.1-220.5; P = 0.05).Sarcopenia is a significant predictor of toxicity and TTP in metastatic breast cancer patients treated with capecitabine. Our results raise the potential use of body composition assessment to predict toxicity and individualize chemotherapy dosing.
Large-Scale Genome Projects Enter the Clinic on Both Sides of the Atlantic
Authors: R. S. Tuma
Journal: JNCI Journal of the National Cancer Institute (2011)

Genetic testing has become more common in cancer care in recent years. However, nearly all such tests are limited to a few genetic alterations that affect patient responses to targeted agents. Now, several groups are working to expand that approach to more patients and more genes, including many with unknown function or import. Earlier this fall, researchers launched two programs designed to offer genetic testing to thousands of patients in routine care. Cancer Research UK is running one program, and Dana – Farber Cancer Institute and Brigham and Women ’ s Hospital in Boston are running the other. Together, the projects will probably speed uptake of genetic testing in regular cancer care, as well as provide the raw data that researchers need for future drug development and improved interventions.
Segmental Bronchial Provocation Induces Nasal Inflammation in Allergic Rhinitis Patients
Authors: GERT-JAN BRAUNSTAHL, ALEX KLEINJAN, SHELLEY E. OVERBEEK, JAN-BAS PRINS, HENK C. HOOGSTEDEN, WYTSKE J. FOKKENS
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Allergic rhinitis and asthma often coexist and share a genetic background. Pathophysiologic connections between the nose and lungs are still not entirely understood. This study was undertaken to compare allergic inflammation and clinical findings in the upper and lower airways after segmental bronchial provocation (SBP) in nonasthmatic allergic rhinitis patients. Eight nonasthmatic, grass pollen-sensitive patients with allergic rhinitis and eight healthy controls were included. Bronchial biopsies and blood samples were taken before (T0) and 24 h (T24) after SBP. Nasal biopsies were obtained at T0, 1 h after SBP (T1), and T24. Immunohistochemical staining was performed for eosinophils (BMK13), interleukin (IL)-5, and eotaxin. The number of eosinophils increased in the challenged and unchallenged bronchial mucosa (p < 0.05) and in the blood (p = 0.03) of atopic subjects at T24. We detected an increase of BMK13-positive and eotaxin-positive cells in the nasal lamina propria and enhanced expression of IL-5 in the nasal epithelium of atopic subjects only at T24 (p < 0.05). SBP induced nasal and bronchial symptoms as well as reductions in pulmonary and nasal function in the allergic group. No significant changes could be observed in healthy controls. The study shows that SBP in nonasthmatic allergic rhinitis patients results in peripheral blood eosinophilia, and that SBP can induce allergic inflammation in the nose.