tbuckley/cabot-search huggingface dataset:
Intracoronary Radiation Before Stent Implantation Inhibits Neointima Formation in Stented Porcine Coronary Arteries
Authors: Ron Waksman, Keith A. Robinson, Ian R. Crocker, Michael B. Gravanis, Spencer J. Palmer, Chris Wang, Gustavo D. Cipolla, Spencer B. King
Journal: Circulation (1995)

Stent implantation has been shown to reduce restenosis by establishing a larger lumen but not by reducing neointima formation. We have previously shown that ionizing radiation reduced neointima formation after balloon injury in a swine model of restenosis. The purpose of this study was to determine whether endovascular irradiation of the coronary artery before stent implantation would affect neointima formation.Nine normolipemic pigs underwent coronary angiography, and segments of the left anterior descending and left circumflex arteries were chosen as targets for stenting. A high-activity 192Ir source was used to deliver 14 Gy by random assignment to one of the vessels. After this, 3.5-mm tantalum stents were implanted in both arteries. Three additional pigs were treated with a 90Sr/Y source (a pure beta-emitter) delivering 14 Gy to five segments of coronary vessels that were stented immediately after irradiation. Stent-to-artery ratio was similar in the radiated and the control arteries. Animals received aspirin 325 mg daily and were killed at 28 days. The intimal area was significantly reduced in the irradiated stented arteries compared with control arteries treated with stent only (1.98 mm2 with 192Ir and 2.53 mm2 with 90Sr/Y versus 3.82 mm2 in the control stented arteries, P < .005).Endovascular radiation before coronary stenting reduces neointima formation and may further reduce the restenosis rate after stent implantation.
INCLUSION BODIES IN EXPERIMENTAL HERPETIC INFECTION OF RABBITS
Authors: E. V. Cowdry, F. M. Nicholson
Journal: The Journal of Experimental Medicine (1923)

We have thus far failed to observe any inclusion bodies in herpetic lesions which in our opinion may properly be interpreted as microorganisms. Concerning the exact nature of the granules so fully reported by others before us, we hesitate to commit ourselves other than to indicate certain points of resemblance to nuclear débris, red blood cells in the process of phagocytosis, mitochondria, pigment, the "methylene blue granules" of neuroglia cells, and the Russell bodies of plasma cells. Obviously, the fact that the individual granules in a section stain in the same way by Giemsa's method, or the technique of Borrel, and look alike is no good reason to suppose that they are of the same composition. We suspect that several of our methods of staining depend more upon physical forces than upon the actual chemical constitution of the substances which become colored. So that granules which stain alike may not only differ in composition but may also have been recruited from different sources. This fact makes inferential chemical analysis extremely difficult since it is next to impossible to superpose all our reactions upon a single granule of microscopic size. Consequently, if we apply one microchemical test to a group of granules, another test to another group, and so on, we cannot be sure that we have been dealing throughout with the same substance or substances. It is our belief that the inclusions which are so abundant in herpetic lesions do not represent a concrete class of granulations sui generis but that they are of variable composition and are derived from several sources.
Stress ventricular function test in conscious, nonthoracotomised dogs to assess cardiac drug efficacy
Authors: W. J FRENCH, W. AVERILL, S. UNG, M. M LAKS
Journal: Cardiovascular Research (1985)

The measurement of left ventricular (LV) function is frequently performed in unconscious or thoracotomised animals in the resting state; these conditions may seriously affect the basal haemodynamic state. To assess myocardial function in conscious animals, a technique was developed to place a catheter across the atrial septum into the left ventricle without a thoracotomy. A stress ventricular function test (SVFT) was performed by raising the systemic blood pressure with methoxamine in the conscious dog. In order to demonstrate the effectiveness of the SVFT in the detection of a decrease in ventricular function, a SVFT was performed before and after the acute infusion of verapamil to determine resting and reserve LV function. A slope relating systolic aortic pressure to the LV end-diastolic pressure was obtained in 10 dogs using a low dose (0.005) and in four dogs a high dose (0.01 microgram X kg-1 X min-1) verapamil (V). The mean slope before V was 3.6 +/- 1.2 and after 2.0 +/- 0.92 (p less than 0.001). The day-to-day variability of the SVFT was less than 22% (coefficient of variability). The SVFT is a sensitive, reproducible method to assess resting and increased or decreased myocardial contractility and is useful in selecting appropriate doses of cardiac drugs to determine their effect on the myocardium during acute and chronic infusion studies in the conscious, nonthoracotomised dog.
A quantitative study of the effect of topical indomethacin on cutaneous erythema induced by UVB and UVC radiation
Authors: P.M. FARR, B.L. DIFFEY
Journal: British Journal of Dermatology (1986)

The effect of indomethacin gel on UVB and UVC erythema was assessed objectively using a reflectance instrument. When indomethacin was applied immediately after irradiation, UVR (ultraviolet radiation) dose-dependent suppression of erythema was demonstrated for both wavelengths until 36 h after irradiation when both indomethacin and control gel base-treated sites were equally erythematous. Suppression of erythema also occurred when application of indomethacin was delayed until 24 h after irradiation, showing that for both wavelengths prostaglandin synthesis remains increased throughout this period. The degree of suppression at any time, however, was no greater than that achieved by a single application immediately after irradiation, indicating that the eventual equal erythema of indomethacin and gel base-treated sites was not due to tachyphylaxis or inadequate dosage. Construction of dose-response curves for the indomethacin-responsive and indomethacin-unresponsive components of erythema shows that in human skin the difference in erythemal response to UVB and UVC radiation is not due to the formation of different mediators at these wavelengths.
Calpain-Mediated Impairment of Na <sup>+</sup> /K <sup>+</sup> –ATPase Activity During Early Reperfusion Contributes to Cell Death After Myocardial Ischemia
Authors: Javier Inserte, David Garcia-Dorado, Victor Hernando, Jordi Soler-Soler
Journal: Circulation Research (2005)

Na + overload and secondary Ca 2+ influx via Na + /Ca 2+ exchanger are key mechanisms in cardiomyocyte contracture and necrosis during reperfusion. Impaired Na + /K + –ATPase activity contributes to Na + overload, but the mechanism has not been established. Because Na + /K + –ATPase is connected to the cytoskeleton protein fodrin through ankyrin, which are substrates of calpains, we tested the hypothesis that calpain mediates Na + /K + –ATPase impairment in reperfused cardiomyocytes. In isolated rat hearts reperfused for 5 minutes after 60 minutes of ischemia, Na + /K + –ATPase activity was reduced by 80%, in parallel with loss of α-fodrin and ankyrin-B and detachment of α 1 and α 2 subunits of Na + /K + –ATPase from the membrane–cytoskeleton complex. Calpain inhibition with MDL-7943 during reperfusion prevented the loss of these proteins, increased Na + /K + –ATPase activity, attenuated lactate dehydrogenase release, and improved contractile recovery, and these beneficial effects of MDL-7943 were reverted by ouabain. The impairment of Na + /K + –ATPase was not a mere consequence of cell death because it was not altered in hearts in which contracture and cell death had been prevented by contractile blockade with 2,3-butanedione monoxime. In these hearts, concomitant calpain inhibition preserved Na + /K + –ATPase content and function and attenuated cell death occurring on withdrawal of 2,3-butanedione monoxime. In vitro assay showed no detectable degradation of Na + /K + –ATPase subunits after 10 minutes of incubation with activated calpain. Thus, we conclude that calpain activation contributes to the impairment of Na + /K + –ATPase during early reperfusion and that this effect is mainly mediated by degradation of the anchorage of Na + /K + –ATPase to the membrane cytoskeleton.
Molecular Correlates of Imatinib Resistance in Gastrointestinal Stromal Tumors
Authors: Michael C. Heinrich, Christopher L. Corless, Charles D. Blanke, George D. Demetri, Heikki Joensuu, Peter J. Roberts, Burton L. Eisenberg, Margaret von Mehren, Christopher D.M. Fletcher, Katrin Sandau, Karen McDougall, Wen-bin Ou, Chang-Jie Chen, Jonathan A. Fletcher
Journal: Journal of Clinical Oncology (2006)

Purpose Gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the KIT or platelet-derived growth factor alpha (PDGFRA) kinases, which are targets for imatinib. In clinical studies, 75% to 90% of patients with advanced GISTs experience clinical benefit from imatinib. However, imatinib resistance is an increasing clinical problem. Patients and Methods One hundred forty-seven patients with advanced, unresectable GISTs were enrolled onto a randomized, phase II clinical study of imatinib. Specimens from pretreatment and/or imatinib-resistant tumors were analyzed to identify molecular correlates of imatinib resistance. Secondary kinase mutations of KIT or PDGFRA that were identified in imatinib-resistant GISTs were biochemically profiled for imatinib sensitivity. Results Molecular studies were performed using specimens from 10 patients with primary and 33 patients with secondary resistance. Imatinib-resistant tumors had levels of activated KIT that were similar to or greater than those typically found in untreated GISTs. Secondary kinase mutations were rare in GISTs with primary resistance but frequently found in GISTs with secondary resistance (10% v 67%; P = .002). Evidence for clonal evolution and/or polyclonal secondary kinase mutations was seen in three (18.8%) of 16 patients. Secondary kinase mutations were nonrandomly distributed and were associated with decreased imatinib sensitivity compared with typical KIT exon 11 mutations. Using RNAi technology, we demonstrated that imatinib-resistant GIST cells remain dependent on KIT kinase activity for activation of critical downstream signaling pathways. Conclusion Different molecular mechanisms are responsible for primary and secondary imatinib resistance in GISTs. These findings have implications for future approaches to the growing problem of imatinib resistance in patients with advanced GISTs.
Ozone-induced lung function decrements do not correlate with early airway inflammatory or antioxidant responses
Authors: A Blomberg, IS Mudway, C Nordenhall, H Hedenstrom, FJ Kelly, AJ Frew, ST Holgate, T Sandstrom
Journal: European Respiratory Journal (1999)

This study sought to clarify the early events occurring within the airways of healthy human subjects performing moderate intermittent exercise following ozone challenge. Thirteen healthy nonsmoking subjects were exposed in a single blinded, crossover control fashion to 0.2 parts per million (ppm) O3 and filtered air for 2 h, using a standard intermittent exercise and rest protocol. Lung function was assessed pre- and immediately post-exposure. Bronchoscopy was performed with endobronchial mucosal biopsies, bronchial wash (BW) and bronchoalveolar lavage (BAL) 1.5 h after the end of the exposure period. Respiratory tract lining fluid (RTLF) redox status was assessed by measuring a range of antioxidants and oxidative damage markers in BW and BAL fluid samples. There was a significant upregulation after O3 exposure in the expression of vascular endothelial P-selectin (p&lt;0.005) and intercellular adhesion molecule-1 (p&lt;0.005). This was associated with a 2-fold increase in submucosal mast cells (p&lt;0.005) in biopsy samples, without evidence of neutrophilic inflammation, and a decrease in BAL fluid macrophage numbers (1.6-fold, p&lt;0.005), with an activation of the remaining macrophage subset (2.5-fold increase in % human leukocyte antigen (HLA)-DR+ cells, p&lt;0.005). In addition, exposure led to a 4.5-fold and 3.1-fold increase of reduced glutathione (GSH) concentrations, in BW and BAL fluid respectively (p&lt;0.05), with alterations in urate and alpha-tocopherol plasma/RTLF partitioning ratios (p&lt;0.05). Spirometry showed reductions in forced vital capacity (p&lt;0.05) and forced expiratory volume in one second (p&lt;0.01), with evidence of small airway narrowing using forced expiratory flow values (p&lt;0.005). Evidence was found of O3-induced early adhesion molecule upregulation, increased submucosal mast cell numbers and alterations to the respiratory tract lining fluid redox status. No clear relationship was demonstrable between changes in these early markers and the lung function decrements observed. The results therefore indicate that the initial lung function decrements are not predictive of, or causally related to the O3-induced inflammatory events in normal human subjects.
Aerosolized PGE<sub>1</sub>, PGI<sub>2</sub>and nitroprusside protect against vascular leakage in lung ischaemia-reperfusion
Authors: H. Schütte, A. Löckinger, W. Seeger, F. Grimminger
Journal: European Respiratory Journal (2001)

High permeability oedema is an important feature in lung injury secondary to ischaemia-reperfusion. This study investigated the influence of aerosolized prostaglandin E 1 (PGE 1 ), prostaglandin I 2 (PGI 2 ) and the nitric oxide (NO)-donor, sodium nitroprusside (SNP) on microvascular barrier function in pulmonary ischaemia-reperfusion. Buffer-perfused rabbit lungs were exposed to 180 or 210 min of warm ischaemia while maintaining anoxic ventilation and a positive intravascular pressure. Reperfusion provoked a transient, mostly precapillary elevation of vascular resistance, followed by a severe increase of the capillary filtration coefficient (Kfc) versus nonischaemic controls (3.17±0.34 versus 0.85±0.05 cm 3 s −1 ·cmH 2 O −1 ·g −1 ·10 −4 after 30 min of reperfusion), and progressive oedema formation. Short-term aerosolization of SNP, PGE 1 or PGI 2 at the beginning of ischaemia largely suppressed the Kfc increase (1.36±0.22, 1.32±0.23 and 1.32±0.22 cm 3 ·s −1 ·cmH 2 O −1 ·g −1 ·10 −4 , respectively) and oedema formation. In contrast, application prior to reperfusion was much less effective, with some reduction of Kfc increase by PGI 2 and SNP and no effect of PGE 1 (1.79±0.31, 2.2±0.53 and 3.2±0.05 cm 3 ·s −1 ·cmH 2 O −1 ·g −1 ·10 −4 , respectively). Haemodynamics, including microvascular pressure, were only marginally affected by the chosen doses of aerosolized vasodilators. It is concluded that short-term aerosolization of prostaglandin E 1 , prostaglandin I 2 and sodium nitroprusside at the onset of ischaemia is highly effective in maintaining endothelial barrier properties in pulmonary ischaemia-reperfusion. This effect is apparently attributable to nonvasodilatory mechanisms exerted by these agents. Alveolar deposition of prostaglandins and/or nitric oxide donors by the aerosol technique may offer pulmonary protection in ischaemia-reperfusion injury.
Pazopanib Efficacy in Renal Cell Carcinoma: Evidence for Predictive Genetic Markers in Angiogenesis-Related and Exposure-Related Genes
Authors: Chun-Fang Xu, Nan X. Bing, Howard A. Ball, Dilip Rajagopalan, Cora N. Sternberg, Thomas E. Hutson, Paul de Souza, Zhengyu G. Xue, Lauren McCann, Karen S. King, Leigh J. Ragone, John C. Whittaker, Colin F. Spraggs, Lon R. Cardon, Vincent E. Mooser, Lini N. Pandite
Journal: Journal of Clinical Oncology (2011)

Purpose Pazopanib, an oral angiogenesis inhibitor, is approved for the treatment of advanced renal cell carcinoma (RCC). Response to pazopanib monotherapy varies between patients, and no validated biomarkers predictive of treatment outcome have been identified. We tested the hypothesis that this variability is partially dependent on germline genetic variants that may affect pazopanib exposure or angiogenesis pathways. Patients and Methods Twenty-seven functional polymorphisms within 13 genes were evaluated in 397 patients with RCC. Genetic association with progression-free survival (PFS) and objective response rate (RR) was analyzed using the Cox proportional hazards model and proportional odds model, respectively. Results Three polymorphisms in IL8 and HIF1A and five polymorphisms in HIF1A, NR1I2, and VEGFA showed nominally significant association (P ≤ .05) with PFS and RR, respectively. Compared with the wild-type AA genotype (median PFS, 48 weeks), the IL8 2767TT variant genotype showed inferior PFS (27 weeks, P = .009). The HIF1A 1790AG genotype was associated with inferior PFS and reduced RR, compared with the wild-type GG genotype (median PFS, 20 v 44 weeks; P = .03; RR, 30% v 43%, P = .02). Reductions in RR were detected for the NR1I2 −25385TT genotype, compared with the wild-type CC genotype (37% v 50%, P = .03), and for the VEGFA −1498CC genotype compared with the TT genotypes (33% v 51%). Conclusion Germline variants in angiogenesis- and exposure-related genes may predict treatment response to pazopanib monotherapy in patients with RCC. If validated, these markers may explain why certain patients fail antiangiogenesis therapy and they may support the use of alternative strategies to circumvent this issue.
Soy Milk Consumption, Inflammation, Coagulation, and Oxidative Stress Among Type 2 Diabetic Patients With Nephropathy
Authors: Maryam Sadat Miraghajani, Ahmad Esmaillzadeh, Mojgan Mortazavi Najafabadi, Maryam Mirlohi, Leila Azadbakht
Journal: Diabetes Care (2012)

To determine the effects of soy milk consumption compared with cow's milk on inflammation, coagulation, and oxidative stress among patients with diabetic nephropathy.This randomized, crossover clinical trial was conducted on 25 type 2 diabetic patients with nephropathy. This study had two trial phases, each for 4 weeks and one washout period for 2 weeks. Patients were randomly assigned to consume a diet containing soy milk or a diet containing cow's milk.Soy milk consumption resulted in a significant reduction in d-dimer level (percent change: -3.77 vs. 16.13%; P < 0.05). This significant effect remained even after adjusting for confounding factor (carbohydrate intake). However, soy milk consumption had no significant effects on tumor necrosis factor-α, interleukin-6, high-sensitivity C-reactive protein (hs-CRP), and malondialdehyde levels. The result was near to significance regarding the effect of soy milk consumption on hs-CRP (percent change: -35.45 vs. 36.76%; P = 0.05). However, this effect was not significant after adjusting for the confounding variable (carbohydrate intake).Soy milk consumption could decrease serum d-dimer level among type 2 diabetic patients with nephropathy. However, markers of inflammation and oxidative stress did not change following soy milk intake among these patients.
Polyendocrinopathy in Children, Adolescents, and Young Adults With Type 1 Diabetes
Authors: Katharina Warncke, Elke E. Fröhlich-Reiterer, Angelika Thon, Sabine E. Hofer, Dagobert Wiemann, Reinhard W. Holl
Journal: Diabetes Care (2010)

OBJECTIVE To investigate diabetes-specific autoantibodies and additional autoimmune phenomena in a large cohort of young patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Data from 28,671 patients &amp;lt;30 years with type 1 diabetes from 242 specialized centers in Germany and Austria were analyzed. RESULTS At least one β-cell antibody was present in 81.6% of patients. β-cell–Ab-negative patients were significantly younger at diabetes onset (P &amp;lt; 0.0001). A total of 19.6% had positive thyroid antibodies with female predominance (62%, P &amp;lt; 0.0001). Antibodies to tissue transglutaminase were present in 10.7%, with a significantly longer duration of diabetes (P &amp;lt; 0.0001). Parietal cell antibodies were found in 283 patients, associated with older age (P &amp;lt; 0.001), and adrenal antibodies were present in 94 patients. In 575 patients, at least three different autoimmune phenomena were present. CONCLUSIONS Thyroid autoimmunity and antibodies suggestive for celiac disease are the most prevalent additional immune phenomena in type 1 diabetes. Parietal/adrenal antibodies are rare.
Genetic Testing in Pheochromocytoma or Functional Paraganglioma
Authors: Laurence Amar, Jérôme Bertherat, Eric Baudin, Christiane Ajzenberg, Brigitte Bressac-de Paillerets, Olivier Chabre, Bernard Chamontin, Brigitte Delemer, Sophie Giraud, Arnaud Murat, Patricia Niccoli-Sire, Stéphane Richard, Vincent Rohmer, Jean-Louis Sadoul, Laurence Strompf, Martin Schlumberger, Xavier Bertagna, Pierre-François Plouin, Xavier Jeunemaitre, Anne-Paule Gimenez-Roqueplo
Journal: Journal of Clinical Oncology (2005)

To assess the yield and the clinical value of systematic screening of susceptibility genes for patients with pheochromocytoma (pheo) or functional paraganglioma (pgl).We studied 314 patients with a pheo or a functional pgl, including 56 patients having a family history and/or a syndromic presentation and 258 patients having an apparently sporadic presentation. Clinical data and blood samples were collected, and all five major pheo-pgl susceptibility genes (RET, VHL, SDHB, SDHD, and SDHC) were screened. Neurofibromatosis type 1 was diagnosed from phenotypic criteria.We have identified 86 patients (27.4%) with a hereditary tumor. Among the 56 patients with a family/syndromic presentation, 13 have had neurofibromatosis type 1, and germline mutations on the VHL, RET, SDHD, and SDHB genes were present in 16, 15, nine, and three patients, respectively. Among the 258 patients with an apparently sporadic presentation, 30 (11.6%) had a germline mutation (18 patients on SDHB, nine patients on VHL, two patients on SDHD, and one patient on RET). Mutation carriers were younger and more frequently had bilateral or extra-adrenal tumors. In patients with an SDHB mutation, the tumors were larger, more frequently extra-adrenal, and malignant.Genetic testing oriented by family/sporadic presentation should be proposed to all patients with pheo or functional pgl. We suggest an algorithm that would allow the confirmation of suspected inherited disease as well as the diagnosis of unexpected inherited disease.