tbuckley/cabot-search huggingface dataset:
Use of snail neurons in developing quantitative ultrastructural parameters for neurotoxic side effects of Vinca antitumor agents.
Authors: Müller Lj, Moorer-van Delft Cm, Zijl R, Roubos Ew
Journal: Cancer Research (1990)

Abstract  The central nervous system of the snail  Lymnaea stagnalis  was studied in order to develop a test system to predict the neurotoxic side effects of the three cytostatic  Vinca  alkaloids, vincristine (VCR), vindesine (VDS), and vinblastine (VLB).  Vinca  alkaloids appear to interfere with microtubule formation by the induction of paracrystalline inclusions. After  in vitro  incubation the numbers of these inclusions were counted in cross-sections of the cerebral commissure using electron microscopy. For each compound the number of paracrystalline profiles increases with increasing concentrations and incubation times. At equimolar concentrations (0.15 mm), VCR induces more paracrystals than VDS, and VDS induces more than VLB. These effects are clear after short periods of incubation ( e.g. , after 2 h, VCR:VDS:VLB = 5:2:1). Equitoxic concentrations of VCR, VDS, and VLB induce similar numbers of paracrystals. Furthermore, morphological changes in the cell bodies of identified neurons (light green cells) in the cerebral ganglia were observed. Quantitative analysis shows that at equimolar concentrations the surface area of nuclear chromatin of all  Vinca  alkaloid-treated cells is approximately 30% lower than that of the controls. The lamellae of the rough endoplasmic reticulum are swollen and have lost their regular arrangement. For VDS and VLB this swelling is accompanied by a strong increase (about 3-fold) in the total surface area of the rough endoplasmic reticulum. No increase was observed for VCR. The compounds do not affect the number of secretory granules. In contrast to the controls, all  Vinca -treated cells show lipid droplets. After VCR treatment they are about 5-fold as numerous as after treatment with VDS or VLB. The total surface area of lysosomes increases about 1.3-fold by VDS and VLB treatment and about 3-fold by VCR treatment.  From these quantitative data it is concluded that VCR is more neurotoxic than VDS and VLB. VDS appears to be more neurotoxic than VLB as judged from the data on paracrystal induction. On the basis of a comparison of these data with clinical data on  Vinca -induced neurotoxicities, it is proposed that neurons of the snail  L. stagnalis  may be suitable for the development of a test system to predict the degree of clinical neurotoxicity induced by  Vinca  antitumor drugs.
Pharmacoeconomics: State of the Art in 1997
Authors: Kevin A. Schulman, Benjamin P. Linas
Journal: Annual Review of Public Health (1997)

▪ Abstract Economic evaluation of pharmaceutical products, or pharmacoeconomics, is a rapidly growing area of research. Pharmacoeconomic evaluation is important in helping clinicians and managers make choices about new pharmaceutical products and in helping patients obtain access to new medications. Over the last few years, the scientific rigor of this field has increased greatly. At the same time, new types of analysis, based on prospective data collection, have been developed. This article reviews the basic concept of pharmacoeconomics, the types of data available for economic evaluation, and the “state of the art” in pharmacoeconomics as reported in the medical literature.
On a confusion about a function of consciousness
Authors: Ned Block
Journal: Behavioral and Brain Sciences (1995)

Abstract Consciousness is a mongrel concept: there are a number of very different “consciousnesses.” Phenomenal consciousness is experience; the phenomenally conscious aspect of a state is what it is like to be in that state. The mark of access-consciousness, by contrast, is availability for use in reasoning and rationally guiding speech and action. These concepts are often partly or totally conflated, with bad results. This target article uses as an example a form of reasoning about a function of “consciousness” based on the phenomenon of blindsight. Some information about stimuli in the blind field is represented in the brains of blindsight patients, as shown by their correct “guesses.” They cannot harness this information in the service of action, however, and this is said to show that a function of phenomenal consciousness is somehow to enable information represented in the brain to guide action. But stimuli in the blind field are both access-unconscious and phenomenally unconscious. The fallacy is: an obvious function of the machinery of accessconsciousness is illicitly transferred to phenomenal consciousness.
Costophrenic Septal Lines in Pulmonary Venous Hypertension
Authors: ANDRÉ J. BRUWER, F. HENRY ELLIS, JOHN W. KIRKLIN
Journal: Circulation (1955)

On the thoracic roentgenograms of patients with mitral stenosis, costophrenic septal lines are frequently seen. These lines are a sign of pulmonary venous hypertension. They were not seen in a representative group of patients with pulmonary arterial hypertension but without pulmonary venous hypertension.
Effects of cytochalasin D-eluting stents on intimal hyperplasia in a porcine coronary artery model
Authors: K SALU, J BOSMANS, Y HUANG, M HENDRIKS, M VERHOEVEN, A LEVELS, S COOPER, I DESCHEERDER, C VRINTS, H BULT
Journal: Cardiovascular Research (2005)

To investigate whether cytochalasin D-eluting stents (CDES) suppress intimal hyperplasia in porcine coronary arteries and to compare the efficacy of paclitaxel and cytochalasin D as inhibitors of vascular smooth muscle cell (SMC) proliferation and platelet aggregation in vitro.Rabbit platelet-rich plasma and SMC cultures derived from rabbit aortas were exposed to 10(-8)-10(-5) M cytochalasin D or paclitaxel. Stents directly coated with 2 microg cytochalasin D (low-dose CDES, n=12) and bare stents (n=12) were randomly deployed in the right and left coronary artery of 12 pigs. Six weeks later, neointima was studied using quantitative coronary angiography (QCA) and morphometry. To examine a ten-fold higher dose, polybutyl methacrylate/polyvinyl acetate-coated stents were loaded with 20 microg cytochalasin D. High-dose CDES (n=10) and polymer-only stents (n=11) were deployed in 11 pigs.After 7 days, cytochalasin D (IC(50) 9.9+/-0.4 10(-8) M) and paclitaxel (IC(50) 1.1+/-0.4 10(-8) M) inhibited SMC proliferation in vitro (n=4). In contrast, cytochalasin D (10(-6)-10(-5) M, n=5), but not paclitaxel, attenuated platelet shape change and aggregation induced by ADP. In vivo QCA showed less late lumen loss in low-dose CDES (0.08+/-0.07 vs. 0.32+/-0.08 mm, P=0.05), but morphometry demonstrated only a tendency toward a decreased intimal area. High-dose CDES inhibited both late lumen loss (0.31+/-0.08 vs. 0.91+/-0.06 mm, P<0.01) and intimal area (1.57+/-0.20 vs. 2.46+/-0.22 mm(2), P<0.01). Immunohistochemistry revealed that CDES suppressed peri-strut macrophage recruitment (CD68, P=0.04) and cell proliferation (Ki67, P=0.03) as compared to polymer-only stents without interfering with endothelial cell recovery or the density of alpha-SMC actin staining. Thromboses or edge effects were not observed in either study.CDES inhibited in-stent hyperplasia. The reduction (39%) with 20 mug CDES was equivalent to that reported for paclitaxel-eluting stents in pigs. Interference with platelet aggregation, SMC migration, SMC proliferation, and leukocyte recruitment could contribute to the benefit. The data indicate that targeting of actin microfilaments has a potential to suppress in-stent restenosis.
Lack of genetic association of the three more common polymorphisms of CARD15 with psoriatic arthritis and psoriasis in a German cohort
Authors: J Lascorz
Journal: Annals of the Rheumatic Diseases (2004)

To determine whether the three common independent sequence variants of the putative pleiotropic non-MHC autoimmune gene CARD15 influence disease susceptibility in large German cohorts of patients with psoriatic arthritis and psoriasis vulgaris, before and after stratification to HLA-C.DNA was obtained from 375 patients with psoriatic arthritis, 281 patients with psoriasis vulgaris without joint involvement, and 376 controls. The three variants of the CARD15 gene (R702W, G908R, leu1007fsinsC), and two single nucleotide polymorphisms of the HCR gene (HCR-325, HCR-2327) for HLA-C stratification were genotyped using allelic discrimination Taqman assays.No significant differences in genotype frequencies were observed between controls and either the psoriatic arthritis or the psoriasis vulgaris patient population, even after stratification to HLA-C in both patient cohorts, or to the type of joint involvement within the psoriatic arthritis group.The lack of genetic association between the most common Crohn's disease alleles of the CARD15 gene and psoriatic joint disease on large cohorts of white patients does not support a recently claimed role for CARD15 as the first non-MHC susceptibility gene in the pathogenesis of psoriatic arthritis, but confirms and extends previous studies in the case of psoriasis vulgaris.
Association Among Acrylamide, Blood Insulin, and Insulin Resistance in Adults
Authors: Chien-Yu Lin, Yu-Chuan Lin, Hsu-Ko Kuo, Juey-Jen Hwang, Jiunn-Lee Lin, Pau-Chung Chen, Lian-Yu Lin
Journal: Diabetes Care (2009)

Exposure to acrylamide in foodstuffs and smoking has become a worldwide concern. The effect of acrylamide on glucose homeostasis is not known. The goal of the present study was to test the hypothesis that trace acrylamide exposure might be independently associated with both reduced blood insulin and reduced insulin resistance.We examined 1,356 participants with reliable measures of glucose homeostasis and Hb adducts of acrylamide (HbAA) and glycidamide from the National Health and Nutrition Examination Survey, 2003-2004. Glucose homeostasis was assessed by the measurement of plasma glucose, serum insulin, and the homeostasis model assessment of insulin resistance (HOMA-IR).In a linear regression model, a 1-unit increase in log HbAA was associated with a decrease in serum insulin (beta coefficient = -0.20 +/- 0.05, P = 0.001) and HOMA-IR (beta coefficient = -0.23 +/- 0.05, P < 0.001). After HbAA concentrations were divided into quartiles in the fully adjusted models, the adjusted serum insulin level and HOMA-IR significantly decreased across quartiles of HbAA (P(trend) < 0.001 for both). In subgroup analysis, the association of HbAA levels with HOMA-IR and insulin levels was stronger in subjects who were white or had ever smoked or in subjects with a lower education level or a BMI <25 or >30 kg/m(2).Acrylamide is associated with reduced serum insulin levels in adults. Further clinical and animal studies are warranted to clarify the putative causal relationship.
Cardiorespiratory Fitness Attenuates Metabolic Risk Independent of Abdominal Subcutaneous and Visceral Fat in Men
Authors: SoJung Lee, Jennifer L. Kuk, Peter T. Katzmarzyk, Steven N. Blair, Timothy S. Church, Robert Ross
Journal: Diabetes Care (2005)

OBJECTIVE—Moderate to high levels of cardiorespiratory fitness (CRF) are associated with a lower risk of the metabolic syndrome and all-cause mortality. Unknown is whether CRF attenuates health risk for a given level of abdominal visceral fat, subcutaneous fat, and/or waist circumference. RESEARCH DESIGN AND METHODS—The sample studied comprised 297 apparently healthy men with available computed tomography or magnetic resonance imaging scans of the abdomen, metabolic data, and maximal treadmill exercise test results. Men were categorized into low-CRF (20%, n = 56), moderate-CRF (40%, n = 94), and high-CRF (40%, n = 147) groups based on age and exercise test results. All analyses were adjusted for age. RESULTS—For a given level of waist circumference, visceral fat, or subcutaneous fat, the high-CRF group had lower triglyceride levels (P &amp;lt; 0.05) and higher HDL cholesterol levels than the low- or moderate-CRF groups. There was a significant group interaction (P &amp;lt; 0.01) for blood pressure, indicating that the increase in blood pressure per unit increase in visceral fat or waist circumference was greater in men in the low-CRF group compared with the high-CRF group. The relative risks of having the metabolic syndrome were 1.8 (95% CI 1.0–3.1) and 1.6 (0.9–2.7) times higher in the low- and moderate-CRF groups, respectively, compared with the high-CRF group after adjusting for age, visceral fat, and subcutaneous fat (P for trend = 0.06). CONCLUSIONS—High levels of CRF are associated with a substantial reduction in health risk for a given level of visceral and subcutaneous fat.
Brain-Selective Overexpression of Human Angiotensin-Converting Enzyme Type 2 Attenuates Neurogenic Hypertension
Authors: Yumei Feng, Huijing Xia, Yanhui Cai, Carmen M. Halabi, Lenice K. Becker, Robson A.S. Santos, Robert C. Speth, Curt D. Sigmund, Eric Lazartigues
Journal: Circulation Research (2009)

Angiotensin converting enzyme type 2 (ACE2) is a new member of the brain renin-angiotensin system, that might be activated by an overactive renin-angiotensin system.To clarify the role of central ACE2 using a new transgenic mouse model with human (h)ACE2 under the control of a synapsin promoter, allowing neuron-targeted expression in the central nervous system.Syn-hACE2 (SA) transgenic mice exhibit high hACE2 protein expression and activity throughout the brain. Baseline hemodynamic parameters (telemetry), autonomic function, and spontaneous baroreflex sensitivity (SBRS) were not significantly different between SA mice and nontransgenic littermates. Brain-targeted ACE2 overexpression attenuated the development of neurogenic hypertension (Ang II infusion: 600 ng/kg per minute for 14 days) and the associated reduction of both SBRS and parasympathetic tone. This prevention of hypertension by ACE2 overexpression was reversed by blockade of the Ang-(1-7) receptor (d-Ala7-Ang-[1-7]; 600 ng/kg per minute). Brain angiotensin II type 2 (AT(2))/AT(1) and Mas/AT(1) receptor ratios were significantly increased in SA mice. They remained higher following Ang II infusion but were dramatically reduced after Ang-(1-7) receptor blockade. ACE2 overexpression resulted in increased NOS and NO levels in the brain, and prevented the Ang II-mediated decrease in NOS expression in regions modulating blood pressure regulation.ACE2 overexpression attenuates the development of neurogenic hypertension partially by preventing the decrease in both SBRS and parasympathetic tone. These protective effects might be mediated by enhanced NO release in the brain resulting from Mas and AT(2) receptor upregulation. Taken together, our data highlight the compensatory role of central ACE2 and its potential benefits as a therapeutic target for neurogenic hypertension.
Prognostic Variables in Osteosarcoma: A Multi-Institutional Study
Authors: W. F. Taylor, J. C. Ivins, K. K. Unni, J. W. Beabout, H. J. Golenzer, L. E. Black
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Prognostic Variables in Osteosarcoma: A Multi-Institutional Study Get access William F. Taylor, William F. Taylor * Department of Health Sciences Research, Mayo Clinic and Mayo FoundationRochester, MN 55905 *Correspondence to: Dr. William F. Taylor, c/o Section of Publications, Mayo Clinic, 200 First St. S. W., Rochester, MN 55905. Search for other works by this author on: Oxford Academic PubMed Google Scholar John C. Ivins, John C. Ivins Department of Orthopedics, Mayo Clinic and Mayo FoundationRochester, MN 55905 Search for other works by this author on: Oxford Academic PubMed Google Scholar K. Krishnan Unni, K. Krishnan Unni Division of Pathology, Mayo Clinic and Mayo FoundationRochester, MN 55905 Search for other works by this author on: Oxford Academic PubMed Google Scholar John W. Beabout, John W. Beabout Department of Diagnostic Radiology, Mayo Clinic and Mayo FoundationRochester, MN 55905 Search for other works by this author on: Oxford Academic PubMed Google Scholar Helen J. Golenzer, Helen J. Golenzer Department of Health Sciences Research, Mayo Clinic and Mayo FoundationRochester, MN 55905 Search for other works by this author on: Oxford Academic PubMed Google Scholar Lynn E. Black Lynn E. Black Department of Health Sciences Research, Mayo Clinic and Mayo FoundationRochester, MN 55905 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 1, January 1989, Pages 21–30, https://doi.org/10.1093/jnci/81.1.21 Published: 01 January 1989 Article history Received: 22 February 1988 Revision received: 13 October 1988 Accepted: 31 October 1988 Published: 01 January 1989
Relationship between bone marrow lesions, cartilage loss and pain in knee osteoarthritis: results from a randomised controlled clinical trial using MRI
Authors: Lukas Martin Wildi, Jean-Pierre Raynauld, Johanne Martel-Pelletier, François Abram, Marc Dorais, Jean-Pierre Pelletier
Journal: Annals of the Rheumatic Diseases (2010)

To assess in a multicentre randomised double-blind phase III clinical trial evaluating the effect of licofelone in comparison with naproxen on knee osteoarthritis (OA) the presence of, and change in, bone marrow lesions (BML) over time, their relationship to cartilage volume loss, meniscal extrusion and pain.Patients with knee OA were selected from the dataset of a recently published randomised controlled trial. MRI was performed at baseline, 6, 12 and 24 months to assess BML score (modified Whole-Organ MRI Score) and cartilage volume changes over time. Pain levels were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire.One hundred and sixty-one patients completed the study according to protocol. The global knee and all subregions showed increased BML scores over time (p <0.001, 24 months) except for the medial tibial plateau in the licofelone group. In multivariate regression analysis, licofelone treatment predicted reduction in BML score in the medial tibial plateau (β= -0.280, p = 0.026). BML scores at baseline correlated with cartilage volume over time; however, correlation was limited to 12 months. No positive correlation was found between BML and WOMAC scores.BML scores were found to increase over time, probably owing to accumulation of chronic structural changes. Correlation between BML and cartilage volume was strong at baseline but not over time, probably due to the study drug. Licofelone reduced the BML score in the medial tibial plateau. In contrast to previous reports, no positive relationship was found between BML score (baseline or change over time) and pain, probably an effect of the selected population.
Imatinib Sensitivity in BCR-ABL1–Positive Chronic Myeloid Leukemia Cells Is Regulated by the Remaining Normal <i>ABL1</i> Allele
Authors: Anna Virgili, Mateusz Koptyra, Yashodhara Dasgupta, Eliza Glodkowska-Mrowka, Tomasz Stoklosa, Elisabeth P. Nacheva, Tomasz Skorski
Journal: Cancer Research (2011)

Abstract Chronic myeloid leukemia in chronic phase (CML-CP) cells that harbor oncogenic BCR-ABL1 and normal ABL1 allele often become resistant to the ABL1 kinase inhibitor imatinib. Here, we report that loss of the remaining normal ABL1 allele in these tumors, which results from cryptic interstitial deletion in 9q34 in patients who did not achieve a complete cytogenetic remission (CCyR) during treatment, engenders a novel unexpected mechanism of imatinib resistance. BCR-ABL1–positive Abl1−/− leukemia cells were refractory to imatinib as indicated by persistent BCR-ABL1–mediated tyrosine phosphorylation, lack of BCR-ABL1 protein degradation, increased cell survival, and clonogenic activity. Expression of ABL1 kinase, but not a kinase-dead mutant, restored the antileukemic effects of imatinib in ABL1-negative chronic myelogenous leukemia (CML) cells and in BCR-ABL1–positive Abl1−/− murine leukemia cells. The intracellular concentration of imatinib and expression of its transporters were not affected, although proteins involved in BCR-ABL1 degradation were downregulated in Abl1−/− cells. Furthermore, 12 genes associated with imatinib resistance were favorably deregulated in Abl1−/− leukemia. Taken together, our results indicate that loss of the normal ABL1 kinase may serve as a key prognostic factor that exerts major impact on CML treatment outcomes. Cancer Res; 71(16); 5381–6. ©2011 AACR.
The continuum of “looking forward,” and paradoxical requirements from memory
Authors: Moshe Bar
Journal: Behavioral and Brain Sciences (2007)

Abstract The claim that nonhuman animals lack foresight is common and intuitive. I propose an alternative whereby foresight is a gradual continuum in that it is present in animals to the extent that it is needed. A second aspect of this commentary points out that the requirements that the memory that mediates foresight be both specific yet flexible seem contradictory.
Modular organization in the reductive evolution of protein-protein interaction networks
Authors: Javier Tamames, Andrés Moya, Alfonso Valencia
Journal: Genome biology (2007)

The variation in the sizes of the genomes of distinct life forms remains somewhat puzzling. The organization of proteins into domains and the different mechanisms that regulate gene expression are two factors that potentially increase the capacity of genomes to create more complex systems. High-throughput protein interaction data now make it possible to examine the additional complexity generated by the way that protein interactions are organized.We have studied the reduction in genome size of Buchnera compared to its close relative Escherichia coli. In this well defined evolutionary scenario, we found that among all the properties of the protein interaction networks, it is the organization of networks into modules that seems to be directly related to the evolutionary process of genome reduction.In Buchnera, the apparently non-random reduction of the modular structure of the networks and the retention of essential characteristics of the interaction network indicate that the roles of proteins within the interaction network are important in the reductive process.
Intravenous or inhaled salbutamol in severe acute asthma?
Authors: S Williams, A Seaton
Journal: Thorax (1977)

Ten patients with life-threatening attacks of asthma (status asthmatiucus9) were treated with salbutamol inhaled by intermittent positive pressure breathing, and their response in terms of rise in peak flow rate was measured. They were then given intravenous salbutamol and any further increment in peak flow was measured. Hydrocortisone treatment was started simultaneously and the responses to salbutamol were re-measured on each of the next three days. Only two patients initially responded to the aerosol, whereas all save one responded to the intravenous drug. The two who responded initially to the aerosol were the two who were able to produce sputum at the time of admission. All patients subsequently responded to the aerosol, and the onset of this response correlated closely with the beginning of sputum production. Sympathominetics should be given parenterally to patients in severe asthma if the response to inhaled drug is reduced or absent.