tbuckley/cabot-search huggingface dataset:
Ultrasound evaluation of the paralyzed diaphragm.
Authors: E Gottesman, F D McCool
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Ultrasound has been used to evaluate diaphragm thickness in the zone of apposition of the diaphragm to the rib cage. The purpose of this study was to determine if ultrasonography could distinguish between a paralyzed and normally functioning diaphragm. We predicted that a paralyzed diaphragm would be atrophic and not shorten, therefore it would be thin and not thicken during inspiration. Thirty subjects (five with bilateral diaphragm paralysis, seven with unilateral diaphragm paralysis, three with inspiratory weakness but normally functioning diaphragms, and 15 healthy control subjects) had diaphragm ultrasound performed with a 7.5 to 10.0 MHz transducer placed over the lower rib cage in the mid-axillary line. The thickness of the diaphragm (tdi) was measured to the nearest 0.1 mm at FRC (t(di)FRC) and TLC (t(di)TLC). Diaphragm thickening during inspiration (delta t(di)) was calculated as (t(di)TLC - t(di)FRC)/t(di)FRC. In patients with unilateral paralysis, t(di) and delta t(di) for the paralyzed hemidiaphragm were significantly less than those values for the normally functioning hemidiaphragm (1.7 +/- 0.2 mm versus 2.7 +/- 0.5 mm [mean + SD] p < 0.01 for t(di), and -8.5 +/- 13% versus 65 +/- 26% [p < 0.001] for delta t(di)). The t(di) and delta t(di) for patients with bilateral diaphragm paralysis were significantly less than those values for the healthy volunteers (1.8 +/- 0.2 versus 2.8 +/- 0.4 and -1 +/- 15% versus 37 +/- 9% for t(di) and delta t(di), respectively) (p < 0.001). We conclude that ultrasound measurements of t(di) and delta t(di) can be used to determine if a diaphragm is paralyzed and confirm our predictions that a chronically paralyzed diaphragm is atrophic and does not thicken during inspiration.
<i>In silico</i> Modeling and <i>In vivo</i> Efficacy of Cancer-Preventive Vaccinations
Authors: Arianna Palladini, Giordano Nicoletti, Francesco Pappalardo, Annalisa Murgo, Valentina Grosso, Valeria Stivani, Marianna L. Ianzano, Agnese Antognoli, Stefania Croci, Lorena Landuzzi, Carla De Giovanni, Patrizia Nanni, Santo Motta, Pier-Luigi Lollini
Journal: Cancer Research (2010)

Cancer vaccine feasibility would benefit from reducing the number and duration of vaccinations without diminishing efficacy. However, the duration of in vivo studies and the huge number of possible variations in vaccination protocols have discouraged their optimization. In this study, we employed an established mouse model of preventive vaccination using HER-2/neu transgenic mice (BALB-neuT) to validate in silico-designed protocols that reduce the number of vaccinations and optimize efficacy. With biological training, the in silico model captured the overall in vivo behavior and highlighted certain critical issues. First, although vaccinations could be reduced in number without sacrificing efficacy, the intensity of early vaccinations was a key determinant of long-term tumor prevention needed for predictive utility in the model. Second, after vaccinations ended, older mice exhibited more rapid tumor onset and sharper decline in antibody levels than young mice, emphasizing immune aging as a key variable in models of vaccine protocols for elderly individuals. Long-term studies confirmed predictions of in silico modeling in which an immune plateau phase, once reached, could be maintained with a reduced number of vaccinations. Furthermore, that rapid priming in young mice is required for long-term antitumor protection, and that the accuracy of mathematical modeling of early immune responses is critical. Finally, that the design and modeling of cancer vaccines and vaccination protocols must take into account the progressive aging of the immune system, by striving to boost immune responses in elderly hosts. Our results show that an integrated in vivo-in silico approach could improve both mathematical and biological models of cancer immunoprevention.
Screening for Cutaneous Melanoma by Skin Self-Examination
Authors: M. Berwick, C. B. Begg, J. A. Fine, G. C. Roush, R. L. Barnhill
Journal: JNCI Journal of the National Cancer Institute (1996)

Background:Although some evidence indicates that early detection protects against the development of lethal melanoma, no randomized clinical trials have been conducted to measure the efficacy of early detection (or screening) in preventing death from this disease. Since melanoma incidence in the United States is relatively rare, a randomized clinical trial to test the efficacy of screening would be extremely expensive.
Effect of short-term NO2 exposure on induced sputum in normal, asthmatic and COPD subjects
Authors: B Vagaggini, PL Paggiaro, D Giannini, AD Franco, S Cianchetti, S Carnevali, M Taccola, E Bacci, L Bancalari, FL Dente, C Giuntini
Journal: European Respiratory Journal (1996)

The aim of this study was to assess the effects of short-term exposure to low levels of nitrogen dioxide (NO2) on airway inflammation. We studied seven normal, eight mild asthmatic and seven chronic obstructive pulmonary disease (COPD) subjects. All subjects were exposed to air or to 0.3 parts per million (ppm) NO2 for 1 h, with moderate intermittent exercise, on different days and in random order. Before and 2 h after exposure, symptom score and results of pulmonary function tests (PFTs) were assessed. All subjects performed nasal lavage and hypertonic saline (HS) inhalation to collect sputum 2 h after both exposures. Asthmatic subjects had a higher percentage of eosinophils than normal and COPD subjects in HS-induced sputum after air (asthmatics: median 13 (range 0.4-37)%; normals: 0 (range 0-2)%; COPD 1.8 (range 0.1-19)%), whilst COPD patients showed a higher percentage of neutrophils than the two others groups. No significant differences in PFT values or percentages of inflammatory cells were observed in nasal lavage and in HS-induced sputum in normal, asthmatic and COPD subjects after NO2 exposure compared to air exposure, except for a mild decrease in forced expiratory volume in one second (FEV1) 2 h after NO2 exposure in COPD patients. Symptom score showed a mild increase after NO2 exposure both in normal subjects and in COPD patients. We conclude that short-term exposure to 0.3 ppm nitrogen dioxide does not induce an early detectable acute inflammation in proximal airways of normal subjects or of patients with asthma or chronic obstructive pulmonary disease.
Transient Virus Expression During Murine Leukemia Induction by X-Irradiation 2
Authors: Martin Haas
Journal: JNCI Journal of the National Cancer Institute (1977)

Most X-irradiation-induced thymomas in C57BL/6 mice are virus-free when assayed by immunofluorescence for the gs antigen (gsa) of murine leukemia virus (MuLV). Virus was induced transiently in bone marrow cells and later appeared in thymus cells. Six to 7 weeks post irradiation, thymocytes and bone marrow cells were MuLV gsa-negative and remained negative for the lifetime of most animals, whether or not they contracted overt leukemia. During the period when MuLV gsa-positive bone marrow cells were found, XC-positive syncytia-producing bone marrow cells were also found. Virus information was expressed, therefore, for a limited duration, long before any signs of leukemia in the animals were evident. MuLV gsa-positive thymocytes taken from mice 4 weeks after X-irradiation were cocultivated with a series of indicator cells. B-tropic virus, in addition to a xenotropic virus, was isolated from these cells. Ecotropic virus was not found in normal mouse thymocytes, in irradiated thymocytes a few days after termination of the X-irradiation sequence, or in most primary thymomas. All thymocytes produced only xenotropic virus in the cocultivation assays. Expression of the ecotropic virus was, therefore, transient, as assayed by immunofluorescence, XC syncytia formation, and virus isolation from MuLV gsa-positive thymus cells.
Effects of reperfusion on the regional contraction of ischemic and nonischemic myocardium following partial coronary obstruction.
Authors: K B Ramanathan, S Raina, V S Banka, M M Bodenheimer, R H Helfant
Journal: Circulation (1978)

In 14 dogs the effects on regional tension (Walton-Brodie gauges) and length (mercury-in-silastic) following 50% reduction (52.9 +/- 2.1) in coronary flow for two hours and reperfusion afterwards for one hour were addressed. Within five minutes of partial coronary occlusion, ejection tension in the ischemic zone decreased to 36.3 +/- 7.2% (P less than 0.001) and total tension to 64.4 +/- 5.7% of control (P less than 0.001) while phasic segment length increased to 165.2 +/- 16.3% control. No further significant changes in regional tension or length were observed throughout the two hour period of partial occlusion. Ejection tension remained positive and segment length maintained systolic shortening during the ejection phase throughout the period of occlusion. Following reperfusion, ejection tension in the ischemic zone increased from 35.1 +/- 5.9 to 87.0 +/- 22.0% (P less than 0.05) and total tension increased from 56.6 +/- 5.4 to 70.2 +/- 7.2% (P less than 0.02) while segment length decreased from 149.3 +/- 6.5 to 105.7 +/- 5.7% (P less than 0.001) within five to 15 min of reperfusion. The improvement in both regional tension development and segment length shortening was maintained throughout the one hour period of reperfusion. No significant changes were seen in the nonischemic zone. The present experimental study suggests that partial coronary occlusion producing a 50% reduction in coronary blood flow results in regional contractile changes. These changes are reversible at least twice as long as those following complete occlusion.
Health Promotion in Smaller Workplaces in the United States
Authors: Jeffrey R. Harris, Peggy A. Hannon, Shirley A.A. Beresford, Laura A. Linnan, Deborah L. McLellan
Journal: Annual Review of Public Health (2014)

Most American workplaces are smaller, with fewer than 1,000 employees. Many of these employees are low-wage earners and at increased risk for chronic diseases. Owing to the challenges smaller workplaces face to offering health-promotion programs, their employees often lack access to health-promotion opportunities available at larger workplaces. Many smaller employers do not offer health insurance, which is currently the major funding vehicle for health-promotion services. They also have few health-promotion vendors to serve them and low internal capacity for, and commitment to, delivery of on-site programs. The programs they offer, whether aimed at health promotion alone or integrated with health protection, are rarely comprehensive and are understudied. Research priorities for health promotion in smaller workplaces include developing programs feasible for the smallest workplaces with fewer than 20 employees. Policy priorities include incentives for smaller workplaces to implement comprehensive programs and an ongoing system for monitoring and evaluation.
Abnormal autonomic cardiovascular control in ankylosing spondylitis
Authors: E. Toussirot, M. Bahjaoui-Bouhaddi, J.-C. Poncet, S. Cappelle, M.-T. Henriet, D. Wendling, J. Regnard
Journal: Annals of the Rheumatic Diseases (1999)

This study was aimed at assessing the contribution of the autonomic nervous system to adjustments of cardiovascular function in patients with ankylosing spondylitis (AS).In 18 AS patients (mean age: 34.9; mean disease duration: 6.4 years) and 13 healthy controls (mean age: 31.7) the changes of heart rate (HR) with deep breathing (E/I ratio) and standing up (30/15 ratio) were recorded. The slope of cardiac baroreflex, the times series of blood pressure and HR values upon lying and standing, and venous plasma concentrations of catecholamines were also analysed. Erythrocyte sedimentation rate (ESR), plasma C reactive protein (CRP) concentration and a clinical index (BASDAI score) were used to assess the degree of disease activity in patients.In the standing patients, blood pressure was found to decrease progressively (p< 0.001). Furthermore, the patients with a BASDAI score > 5 had a higher heart rate than patients with a BASDAI score < 5 (p<0.02), and there was a trend for a similar difference when patients were classified according to their ESR and CRP. Plasma catecholamine concentrations and the E/I ratio were not different in patients from controls. The 30/15 ratio and the slope of the spontaneous baroreflex during standing were both lower in AS patients than controls (p< 0.01).This study demonstrated a change in autonomic nervous system function of AS patients, with a decreased parasympathetic activity, as evidenced by higher HR and lower baroreflex slope. As these significant deviances were mainly observed in patients with more active (or more inflammatory) disease, the autonomic nervous system involvement could be related to the inflammatory process. This autonomic strain may be related to the cardiac involvement in AS patients.
Carrier detection in X-linked severe combined immunodeficiency based on patterns of X chromosome inactivation.
Authors: J M Puck, R L Nussbaum, M E Conley
Journal: Journal of Clinical Investigation (1987)

The X-linked form of severe combined immunodeficiency (XSCID) is underdiagnosed because no methods have been available for detecting carriers. Although boys with XSCID are deficient in T cells, female carriers are immunologically normal. Carriers' normal immune function would be expected if all their T cells were derived from precursors whose X chromosome bearing the XSCID mutation was inactivated early in embryogenesis. Using somatic cell hybridization to separate the active and inactive X chromosomes and restriction fragment length polymorphisms to distinguish them, we have determined the lymphocyte X inactivation pattern in XSCID carriers and their female relatives. In the T cells of three carriers, the X chromosome bearing the XSCID mutation was consistently inactive. Nonrandom X inactivation was also found in the T cells of one at-risk female, while two others had normal, random X inactivation. This method constitutes a generally applicable carrier test for XSCID.
Human and murine cutaneous graft-versus-host diseases. Potential models for the study of immunologically mediated skin diseases
Authors: J. H. SAURAT, P. F. PIGUET
Journal: British Journal of Dermatology (1984)

Cutaneous graft-versus-host disease in humans can be regarded as a potential model for the study of lymphocytotoxic reactions directed against the epidermis, and immunologically mediated cutaneous sclerosis. Toxic epidermal necrolysis and lichen planus are closely reproduced in graft-versus-host disease; sclerosis of chronic graft-versus-host disease cannot be regarded as strictly similar to any type of scleroderma. Sclerosis is the most consistently reproducible feature of cutaneous graft-versus-host disease in mouse chimeras; it offers the opportunity to study a dermal sclerosing reaction which may be considered as T cell dependent. Murine graft-versus-host disease presently appears debatable for use as a model of T cell dependent injury of the epidermis since stable established epidermal lesions are difficult to reproduce.
Behavioral Science Research in the Cooperative Group Setting: the Southwest Oncology Group Experience
Authors: C. C. Gotay
Journal: JNCI Journal of the National Cancer Institute (2000)

Cancer prevention, detection, treatment, and continuing care require individuals to behave in specified ways, whether abstaining from certain behaviors (e.g., sun exposure) or adopting others (e.g., following recommendations for state-of-the-art treatment).Thus, behavior is one of the keys to controlling cancer.Much progress in cancer control has stemmed from behavioral research and interventions.For example, reductions in tobacco use are largely responsible for lower rates of lung cancer (1), and increased use of mammography has led to decreases in breast cancer mortality (2).Moreover, a recent meta-analysis of psychosocial interventions in adult cancer patients (3) concluded that such interventions have a positive effect on emotional, physical, and social outcomes.According to Dr. Richard Klausner (4), Director of the National Cancer Institute (NCI), Bethesda, MD, "behavioral research is fundamental to the mission of [NCI] and the broader social goal of reducing cancer incidence, morbidity, and mortality."Clinical cooperative groups represent a rich potential resource to promote and support behavioral research in cancer.Each year, more than 20 000 new patients participate in cooperative group clinical trials, most of which test cancer therapies, that are conducted under the auspices of the NCI's Division of Cancer Therapy and Diagnosis.In addition, most cooperative groups also sponsor behavioral research studies, although this emphasis is relatively new.In this commentary, we illustrate the distinct contributions and challenges that behavioral studies pose within the cooperative group setting, drawing on our experiences over the past 10 years as members of the Southwest Oncology Group (SWOG).
Heterotrimerization of the Growth Factor Receptors erbB2, erbB3, and Insulin-like Growth Factor-I Receptor in Breast Cancer Cells Resistant to Herceptin
Authors: Xiaoping Huang, Lizhi Gao, Shuiliang Wang, James L. McManaman, Ann D. Thor, XiaoHe Yang, Francisco J. Esteva, Bolin Liu
Journal: Cancer Research (2010)

Abstract Primary and acquired resistance to the breast cancer drug trastuzumab (Herceptin) is a significant clinical problem. Here, we report enhanced activation of downstream signaling pathways emanating from the growth factor receptors erbB2, erbB3, and insulin-like growth factor-I receptor (IGF-IR) in trastuzumab-resistant breast cancer cells. Interactions between IGF-IR and erbB2 or erbB3 occur exclusively in trastuzumab-resistant cells, where enhanced erbB2-erbB3 interactions are also observed. Moreover, these three receptors form a heterotrimeric complex in resistant cells. erbB3 or IGF-IR knockdown by short hairpin RNA–mediated strategies upregulates p27kip1, inactivates downstream receptor signaling, and resensitizes resistant cells to trastuzumab. Our findings reveal a heterotrimer complex with a key role in trastuzumab resistance. On the basis of our results, we propose that trastuzumab resistance in breast cancer might be overcome by therapeutic strategies that jointly target erbB3, erbB2, and IGF-IR. Cancer Res; 70(3); 1204–14
Rat T cell responses to superantigens. II. Allelic differences in V beta 8.2 and V beta 8.5 beta chains determine responsiveness to staphylococcal enterotoxin B and mouse mammary tumor virus-encoded products.
Authors: D P Gold, C D Surh, K S Sellins, K Schroder, J Sprent, D B Wilson
Journal: The Journal of Experimental Medicine (1994)

The previous paper in this series demonstrates that rat T cells developing de novo in the presence of mouse mammary tumor virus (Mtv) antigens in rat--&amp;gt;severe combined immunodeficiency (SCID) mouse xenochimeras display a distinct pattern of V beta-restricted deletion; this deletion pattern is remarkably similar to that occurring during thymic development of mouse T cells in Mtv+ strains. In addition, T cells developing in the absence of Mtv antigens in these rat--&amp;gt;mouse xenochimeras are tolerant of host antigens, but show strong primary proliferative responses in cultures stimulated with Mtv-7+ (Mlsa) mouse cells; like the mouse, these rat T cell responses are dominated by V beta 6 and V beta 8 T cells. Here, we continue analysis of rat T cell responses to superantigens; we show that T cells from Lewis and Fischer 344 rats expressing V beta 8.2 display an important all-or-nothing difference in their responses to Mtv-7 superantigens. This all-or-none strain difference in the response to Mtv-7 applies also to the response by V beta 8.2 and V beta 8.5 T cells to the soluble superantigen staphylococcal enterotoxin B. Because these two rat strains express different alleles of these two V beta 8 family members, this finding identifies additional, hitherto unreported residues of the T cell receptor beta chain important in T cell responses to superantigens.
Effect of Dipyridamole plus Aspirin on Hemodialysis Graft Patency
Authors: Bradley S. Dixon, Gerald J. Beck, Miguel A. Vazquez, Arthur Greenberg, James A. Delmez, Michael Allon, Laura M. Dember, Jonathan Himmelfarb, Jennifer J. Gassman, Tom Greene, Milena K. Radeva, Ingemar J. Davidson, T. Alp Ikizler, Gregory L. Braden, Andrew Z. Fenves, James S. Kaufman, James R. Cotton, Kevin J. Martin, James W. McNeil, Asif Rahman, Jeffery H. Lawson, James F. Whiting, Bo Hu, Catherine M. Meyers, John W. Kusek, Harold I. Feldman
Journal: New England Journal of Medicine (2009)

Arteriovenous graft stenosis leading to thrombosis is a major cause of complications in patients undergoing hemodialysis. Procedural interventions may restore patency but are costly. Although there is no proven pharmacologic therapy, dipyridamole may be promising because of its known vascular antiproliferative activity.We conducted a randomized, double-blind, placebo-controlled trial of extended-release dipyridamole, at a dose of 200 mg, and aspirin, at a dose of 25 mg, given twice daily after the placement of a new arteriovenous graft until the primary outcome, loss of primary unassisted patency (i.e., patency without thrombosis or requirement for intervention), was reached. Secondary outcomes were cumulative graft failure and death. Primary and secondary outcomes were analyzed with the use of a Cox proportional-hazards regression with adjustment for prespecified covariates.At 13 centers in the United States, 649 patients were randomly assigned to receive dipyridamole plus aspirin (321 patients) or placebo (328 patients) over a period of 4.5 years, with 6 additional months of follow-up. The incidence of primary unassisted patency at 1 year was 23% (95% confidence interval [CI], 18 to 28) in the placebo group and 28% (95% CI, 23 to 34) in the dipyridamole-aspirin group, an absolute difference of 5 percentage points. Treatment with dipyridamole plus aspirin significantly prolonged the duration of primary unassisted patency (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P=0.03) and inhibited stenosis. The incidences of cumulative graft failure, death, the composite of graft failure or death, and serious adverse events (including bleeding) did not differ significantly between study groups.Treatment with dipyridamole plus aspirin had a significant but modest effect in reducing the risk of stenosis and improving the duration of primary unassisted patency of newly created grafts. (ClinicalTrials.gov number, NCT00067119.)