tbuckley/cabot-search huggingface dataset:
Pharmacologic Studies of Hepatic Intra-Arterial Chemotherapy
Authors: William D. Ensminger, John W. Gyves
Journal: Liver Cancer (1985)

Hepatic arterial chemotherapy is based upon the premise that most chemotherapeutic agents display a steep dose response for toxicity and for therapeutic effect [1]. Even when systemically administered (intravenous) chemotherapy is relatively ineffective, intra-arterial chemotherapy may still improve the likelihood of response by the generation of much greater drug exposures (defined by the concentration × time integral). Hepatic arterial chemotherapy administration can potentially generate increased drug exposure in the region where the tumor resides while maintaining a lower drug exposure at the level of dose-limiting normal host tissues elsewhere in the body. Ideally, the higher level of drug generated regionally will be cytotoxic to the tumor within the liver while the lower systemic drug level will be below the toxic threshold for the usual dose-limiting tissues such as the bone marrow and gastrointestinal mucosa. When there is sufficient regional selectivity, dose-limiting toxicity should be manifested by the normal liver tissue and not by tissues elsewhere in the body.
Abstract 13821: Peripheral Metabolite Profiles Discriminate Coronary Artery Disease in a Sequential Cohort of Cardiac Catheterization Patients
Authors: Sayanti Bhattacharya, Damian Craig, Carol Haynes, Christopher B Granger, Robert D Stevens, Elizabeth R Hauser, William E Kraus, Christopher B Newgard, L. K Newby, Svati H Shah
Journal: Circulation (2011)

Background: Profiling of peripheral blood metabolites may improve clinical models for coronary artery disease (CAD). We previously showed that levels of branched chain amino acids (BCAA) and other ...
Genetic Response of Inbred Lines of Chickens to Rous Sarcoma Virus
Authors: Nelson F. Waters, A. K. Fontes
Journal: JNCI Journal of the National Cancer Institute (1960)

This study demonstrates the genetic variation among families of White Leghorn chickens, representing 5 different and unrelated inbred lines, when they were inoculated intracerebrally at 1 day of age with Rous sarcoma virus. The differences in response to inoculation of chickens with Rous sarcoma virus, both within and between lines, were marked. The progeny from line 10 representing 4 different sire matings, each mated to different groups of females, were completely susceptible and all died from the effects of the disease induced by inoculation. In contrast the progeny from line 7, representing 3 different sire matings, were highly resistant and only 2 chickens of 327 died. Progeny from lines 6, 9, and 15 showed considerable genetic diversity in response to Rous sarcoma virus. Within lines the progeny from certain males showed considerable resistance, while the progeny of other males in these same lines all died before 25 days of age. Likewise, progeny from dams, within sires and lines, showed similar genetic diversity in response to Rous sarcoma virus, some being completely resistant and others completely susceptible.
Deficient Activity of von Willebrand Factor–Cleaving Protease in Chronic Relapsing Thrombotic Thrombocytopenic Purpura
Authors: Miha Furlan, Rodolfo Robles, Max Solenthaler, Max Wassmer, Pierre Sandoz, Bernhard Lämmle
Journal: Blood (1997)

Abstract In patients with thrombotic thrombocytopenic purpura (TTP), excessive intravascular platelet aggregation has been associated with appearance in plasma of unusually large von Willebrand factor (vWF ) multimers. These extremely adhesive vWF multimers may arise due to deficiency of a “depolymerase” cleaving vWF to smaller molecular forms, either by reducing the interdimeric disulfide bridges or by proteolytic degradation. We studied the activity of a recently described vWF-cleaving protease in four patients with chronic relapsing TTP. Diluted plasma samples of TTP patients were incubated with purified normal human vWF in the presence of a serine protease inhibitor, at low ionic strength, and in the presence of urea and barium ions. The extent of vWF degradation was assayed by electrophoresis in sodium dodecyl sulfate-agarose gels and immunoblotting. Four patients, that included two brothers, with chronic relapsing TTP displayed either substantially reduced levels or a complete absence of vWF-cleaving protease activity. In none of these patient plasmas was an inhibitor of or an antibody against the vWF-cleaving protease established. Our data suggest that the unusually large vWF multimers found in TTP patients may be caused by deficient vWF-cleaving protease activity. Deficiency of this protease may be inherited in an autosomal recessive manner and seems to predispose to chronic relapsing TTP. The assay of the vWF-cleaving protease activity may be used as a sensitive diagnostic tool for identification of subjects with a latent TTP tendency.
Abstract 2656: Copeptin Predicts Cardiovascular Death in STEMI Independent of Clinical Factors and NT-proBNP
Authors: Nihar R Desai, David A Morrow, Songtao Jiang, Christoph Bode, Nader Rifai, Christopher P Cannon, Robert E Gerszten, Marc S Sabatine
Journal: Circulation (2008)

Background : Elevated levels of copeptin, the c-terminal portion of provasopressin, add significantly to natriuretic peptides for mortality prediction in heart failure. We hypothesized that elevated levels would predict mortality in ST-elevation myocardial infarction (STEMI). Methods : Circulating copeptin levels were measured at baseline in a case-cohort of 535 STEMI patients undergoing fibrinolysis in CLARITY-TIMI 28. Patients were stratified into quartiles by baseline copeptin. Multivariable logistic regression was used to examine the association between copeptin and 30-d cardiovascular (CV) mortality independent of clinical factors and NT-proBNP. Results : The median level of copeptin was 615 pg/ml (IQR 333–728 pg/ml). Baseline levels of copeptin tended to be higher in patients who were older, had a prior MI, were treated sooner after sx onset, and were in Killip class II-IV. For each 1-SD increase in log-transformed copeptin, the OR for CV death was 1.45 (p=0.01). After adjusting for differences in baseline characteristics patients in the highest copeptin quartile were at a significantly higher risk of CV death compared with patients in quartiles 1–3 (OR 1.99 [1.05–3.78]). Copeptin was not significantly correlated with NT-proBNP (r=0.09). In a multivariable model, copeptin and NT-proBNP were each significant independent predictors of CV death (Figure ); the c-statistic went from 0.75 to 0.81 with their addition to a model containing clinical risk factors. Conclusion : In a multimarker model, circulating levels of copeptin and NT-proBNP at presentation were powerful and complementary predictors of CV death beyond traditional risk factors in patients with STEMI.
Reconstitution of activated transcription factor Stat5a in poorly differentiated human breast cancer cell lines promotes differentiation and inhibits invasive potential.
Authors: Ahmed S. Sultan, Jainwu Xie, Hallgeir Rui
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

3425 

Signal transducer and activator of transcription-5a (Stat5a) is critical for mammary epithelial cell differentiation and normal mammary gland development. Identifying the role of Stat5a in human breast cancer growth and progression has been complicated by the diverse functions of Stat5a. We have investigated the role of Stat5a as a regulator of differentiation and invasion of human breast cancer cell lines. Using expression and activation studies by adenoviral gene delivery of wild type and dominant-negative (DN) mutants of Stat5a in a panel of human ER (+) and ER (-) breast cancer cell lines that display different phenotypic characteristics, ranging from poorly invasive to highly invasive, we found that DN-Stat5a, but not DN-Stat3, stimulated invasive characteristics of well-differentiated breast cancer cells that expressed activated Stat5a/b. Moreover, the enhancement of invasive characteristics by DN-Stat5a correlated with basal expression levels of activated Stat5a and the differentitaition levels of breast cancer cell lines. We also investigated the invasive inhibitory role of activated Stat5a by its reconstitution in poorly differentiated breast cancer cells that show no Stat5a/b activation. Adenoviral gene delivery of wild type Stat5a induced dramatic changes in cell morphology on Matrigel with a decrease in cellular invasion potential. Furthermore, viral co-delivery of wild type Stat5a and wild type Jak2 genes showed a synergistic effect by induction of mammosphere-like structures on Matrigel with a sharp decrease in invasion characteristics. In contrast, DN-Stat5a blocked mammosphere formation with a marked increase in cell mobility and invasion potential. Collectively, our data demonstrated an important role of Stat5a as a novel invasion suppressor factor in breast cancer.
Abstract 15574: High Frequency of Anti-Heart and Anti-Intercalated Disk Autoantibodies in Acute Myocardial Infarction with Normal Coronary Arteries: Evidence for Unsuspected Immune-Mediated Myocarditis
Authors: Alida L Caforio, Ilaria Loddo, Francesco Bagato, Omar Paccagnella, Stefania Bottaro, Annalisa Angelini, Luisa Cacciavillani, Martina Perazzolo Marra, Luciano Daliento, Vera Renier, Gino Gerosa, Gaetano Thiene, Sabino Iliceto
Journal: Circulation (2010)

Acute myocardial infarction with angiographically normal coronary arteries (MINC) is a poorly understood and likely heterogeneous entity. Although acute biopsy-proven myocarditis (My) may present a...
Abstract 3932: Central Role Of Toll-like Receptor 4 In Oxidized Low Density Lipoprotein-and Lipopolysaccharide-Induced Bone Morphogenetic Protein-2 Expression In Human Coronary Artery Endothelial Cells
Authors: Xin Su, Thomas R Johnson, Lihua Ao, Bruce L Paschall, Xiaoping Yang, Joseph C Cleveland, David A Fullerton, Xianzhong Meng
Journal: Circulation (2008)

Previous studies demonstrated that osteogenic mediators, in particular bone morphogenetic protein-2 (BMP-2), play an important role in the progression of atherosclerosis and vascular calcification. Although it is known that the atherogenic factor oxidized low density lipoprotein (oxLDL) up-regulates BMP-2 expression in endothelial cells, the signaling mechanisms involved are not well understood. In macrophages, oxLDL up-regulates Toll-like receptor 4 (TLR4) expression, and this innate immunoreceptor appears to be involved in oxLDL-induced macrophage actin polymerization. We earlier found that stimulation of TLR4 with lipopolysac-charide (LPS) increases cellular BMP-2 protein levels in human aortic valve interstitial cells. We hypothesized that the TLR4 pathway plays a central role in mediating BMP-2 expression in human coronary artery endothelial cells (CAECs). The purposes of this study were to examine whether TLR4 mediates oxLDL- and/or LPS-induced BMP-2 expression in human CAECs, and to determine whether the p38 and/or p44/42 MAPKs are involved. Methods and results : Stimulating human CAECs with LPS (E. coli 0111:B4, 200 ng/ml) for 24 h up-regulated BMP-2 protein expression. Similarly, stimulation with oxLDL (from human plasma, CuSO 4 -oxidized, LPS-free, 40–160 μg/ml) for 24 h induced BMP-2 expression in a dose-dependent manner. Pretreatment with either TLR4-neutralizing antibody or TLR4 siRNA significantly attenuated oxLDL-induced BMP-2 expression and abrogated the effect of LPS on BMP-2 expression. Over-expression of TLR4 enhanced the cellular BMP-2 response to oxLDL and LPS. Further, immunofluorescent staining co-localized oxLDL with TLR4. Although LPS induced ICAM-1 expression in human CAECs, oxLDL had no effect, indicating that oxLDL and LPS have different pro-inflammatory effects. BMP-2 expression was associated with activation of p38 and p44/42 MAPKs. Inhibiting p44/42, but not p38, reduced BMP-2 expression. Conclusions: In human CAECs, TLR4 plays a central role in regulating BMP-2 expression induced by either oxLDL or LPS, and the signaling mechanism involves the p44/42 MAPK pathway. These novel findings underscore an important role of TLR4 in atherosclerosis and vascular calcification.
A Clinical Randomized Trial to Evaluate the Safety of a Noninvasive Approach in High-Risk Patients Undergoing Major Vascular Surgery
Authors: Don Poldermans, Olaf Schouten, Radosav Vidakovic, Jeroen J. Bax, Ian R. Thomson, Sanne E. Hoeks, Harm H.H. Feringa, Martin Dunkelgrün, Peter de Jaegere, Alexander Maat, Marc R.H.M. van Sambeek, Miklos D. Kertai, Eric Boersma
Journal: Journal of the American College of Cardiology (2007)
The World Health Organisation: WHO fellowships--what do they achieve?
Authors: F. Godlee
Journal: BMJ (1995)

Training health professionals is one of WHO's major strategies for improving health care in the developing world. The aim, to strengthen a country's own capacity rather than injecting expertise from outside, is in the best tradition of sustainable development. But how effective is this so called "capacity building in human resources"? Since it accounted for $43m of WHO's budget in 1992-3 and is considered by WHO to be a major contribution to health in individual countries, it deserves detailed examination.
Abstract 617: Inhibition of Bone Marrow Derived CD40 Limits Atherosclerosis by Reducing Leukocyte Adhesion, Involving the CD40-TRAF6 Axis
Authors: Dirk Lievens, Linda Beckers, Alma Zernecke, Erwin Wijnands, Randy J Noelle, Christian Weber, Menno De Winther, Mat J Daemen, Esther Lutgens
Journal: Circulation (2007)
Peanut sensitisation is independently associated with increased airways inflammation in allergic asthma
Authors: Andrei Malinovschi, Christer Janson, Pia Kalm-Stephens, Katarina Nisser, Lennart Nordvall, Kjell Alving
Journal: European Respiratory Journal (2011)

Background:  The fraction of nitric oxide in exhaled air (FeNO) is increased in allergic asthma and the degree of IgE sensitisation to aeroallergens relates to FeNO levels. An additional IgE sensitisation to food allergens is known to increase asthma risk, but the relation between IgE sensitisation to food allergens and FeNO has been little studied previously.   Aim:  To investigate in an ongoing asthma study if the presence of food allergy influences the levels of exhaled NO and which food allergens appear to be important.   Methods:  Within the frame of an industry-academy collaboration on minimally-invasive diagnostics (MIDAS), measurements of FeNO and specific IgE (sIgE) against the allergens included in ImmunoCAP Phadiatop and fx5 (Phadia AB, Sweden) were done in 170 patients with physician-diagnosed asthma.   Results:  Asthmatic subjects with IgE sensitisation to both aero- and food allergens (n=77) had higher FeNO levels than subjects sensitised to only aeroallergens (n=93) (21.2 ppb (18.4, 24.4) vs 15.6 ppb (13.2, 18.6), p=0.006). This difference was confirmed (p=0.03) in a multiple linear regression model after adjustments for sex, height, lung function and age. The sIgE levels to aeroallergens were higher in subjects also sensitised to food allergens (p   Conclusion:  Peanut sensitisation was independently associated with increased airways inflammation in allergic asthma. A possible mechanism might be a further enhanced Th 2  cytokine-driven inflammation related to peanut IgE sensitisation.
Abstract 3623: Selective Inhibition of Connexin 43 Hemichannels by GAP26 Confers Cardioprotection Against Ischemia-Reperfusion Injury: In vivo Study
Authors: Ghayda Hawat, Ghayath Baroudi
Journal: Circulation (2009)

Introduction: Connexins are the basic units in the composition of gap junction channels but also of unapposed hemichannels (Hc). Hc exert functions different from those achieved by gap junction cha...
AKT activity following exposure to IMC-C225 alone, radiation alone or a combination of both treatments
Authors: Hoa Q. Trummell, Kevin P. Raisch, Leisa L. Seay, James A. Bonner
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1293 

Inhibition of EGFr-induced cellular proliferation has been accomplished with anti-EGFr monoclonal antibodies or small molecules. These agents inhibit activation of the receptor tyrosine kinase domain and the subsequent activation of downstream events. The physiological process of EGFr-mediated proliferation involves several downstream cellular events including activation of AKT as measured by Thr308 and Ser473 AKT phosphorylation. We explored the inhibition of EGFr with the blocking antibody, IMC-C225, in relation to AKT inhibition in A431 squamous cell carcinoma cells. Time course studies of this process revealed that receptor inhibition resulted in decreased AKT activation for exposure to IMC-C225 (5μg/ml) for less than 12 hours. This effect was not found for 24-hour exposures to IMC-C225. Furthermore, greater inhibition of AKT activation occurred as time of exposure to IMC-C225 was reduced from 12 hours to 1.5 hours. Next, exposure of cells to radiation alone (3 or 10 Gy) resulted in increased activation of AKT. The time course of this effect revealed that it was more prominent for time periods of less than 4 hours after radiation treatment compared to greater post-radiation time periods. Combination treatments of IMC-C225 and radiation also showed the greatest inhibition of activated AKT during the first 6 hours after treatment with radiation and IMC-C225. The potential significance of these time course studies will be discussed.
Abstract 17101: Mitochondrial Ros Activates Golgi Resident eNOS in the Vascular Endothelium Following Hypoxia-Reoxygenation (h/r): Role of Oxygen Sensing in Cellular Adaptation
Authors: Saradhadevi Varadharaj, Lawrence J Druhan, Joe R Zweier, Chun-An Chen, Murugesan Velayutham, Tse-Yao Wang, Xiaoping Liu, Rajasekaran N Soorappan, Jay L Zweier
Journal: Circulation (2011)

Adaptation to hypoxia (H) is achieved by the cell's ability to sense alterations in O 2 and respond accordingly. Changes in cellular oxygenation trigger signaling pathways with reactive oxygen species (ROS) and nitric oxide (NO) playing critical roles. ROS and NO also regulate the tissue inflammation and injury associated with ischemia/reperfusion as occurs in unstable coronary syndromes. While moderate periods of H followed by reoxygenation (R) can induce vascular protection, questions remain regarding how this occurs. Therefore, studies were performed to elucidate the mechanisms responsible for protection of vascular endothelium following H/R with particular focus on ROS-induced NO production and its downstream targets, in endothelial cells (BAECs). We hypothesize that mitochondrial ROS-mediated activation of Golgi eNOS-NO is integral in inducing the vasculoprotective mechanisms critical for cellular adaptation to H/R. BAECs were subjected to H (2 hr) and R (10 - 60 min). H triggered clustering of mitochondria toward nuclei and upon R perinuclear ROS production was seen (Fig). This was associated with activation of Golgi resident ser/thr kinase (Akt) as evidenced by the presence of pAkt in the Golgi fraction that in turn activates Golgi resident eNOS. The H/R-induced activation of Golgi eNOS was attenuated by pretreatment with complex III inhibitor, myxothiazol confirming the role of mitochondrial ROS. NO produced at the vicinity of the Golgi inhibited vWF release. Thus, in response to R, eNOS in endothelial cells is activated due to serine 1179 phosphorylation within the Golgi by mitochondrial ROS-induced activation of PI3K/Akt. A discrete intracellular NOS pool is activated by H/R that serves to inhibit exocytosis of WPB that in turn can decrease inflammation and thrombosis. This knowledge of how cells sense and adapt following hypoxia provides a framework to understand the role of H/R in cardiovascular diseases that can be ultimately used toward treatment.
Poly [ADP-Ribose] Polymerase 1 (PARP-1) Expression Before and After Immunochemotherapy In Patients With B Chronic Lymphocytic Leukemia
Authors: Panagiotis Theodorou Diamantopoulos, Maria Sofotasiou, Vasiliki Papadopoulou, Katerina Polonyfi, Theodoros Iliakis, Fani Kalala, Konstantinos Zervakis, Niki Rougala, Nefeli Giannakopoulou, Xenia Hatzinikolaou, Athanassios Galanopoulos, Eleni Variami, Gerassimos A Pangalis, Nora-Athina Viniou
Journal: Blood (2013)
Abstract 11897: Cardiovascular Phenotype of the Recently Discovered Aggressive Aneurysms-Osteoarthritis Syndrome (aos) Caused by Smad3 Mutations
Authors: Denise van der Linde, Ingrid van de Laar, Marja W Wessels, Rogier A Oldenburg, Jos A Bekkers, Francesco U Mattace-Raso, Anton H van den Meiracker, Adriaan Moelker, Hervé L Tanghe, Fop van Kooten, Aida M Bertoli-Avella, Jolien W Roos-Hesselink
Journal: Circulation (2011)

Background Aneurysms-osteoarthritis syndrome (AOS), caused by SMAD3 mutations, is a recently described autosomal dominant syndrome characterized by arterial tortuosity and aneurysms throughout the ...
Contraceptive failure may be a major factor in teenage pregnancy
Authors: E S Williams
Journal: BMJ (1995)

Psychiatric tourism is overloading London beds EDITOR,-A recent conference on metropolitan health care highlighted the plight of mentally ill people in London.Of special note was the serious shortage of admission beds in all urban areas in the United Kingdom,'2 with the bed occupancy rate for mental health now well above 100%, with some units actually running at over 120%.3Pressure seems greatest in inner London, and it is a far cry from the therapeutic standard of a bed occupancy rate no greater than about 85%.4Such occupancy would allow patients to be placed in their catchment area ward, with effective aftercare and an allocated key worker, as envisaged in the care programme approach.This shortage is generating extracontractual referrals to hospitals, both NHS and private, that are often far removed from the community from which the patient originates.The situation is exacerbated by the current shortfall in community care resources, and the increasing diversion of patients from the criminal justice system into the NHS.The lack of medium secure beds compounds the problem further.Such bed pressures have been identified as a key factor in the recent tragedy involving the homicide committed by Christopher Clunis.5A factor not previously noted, in our view, is
Outpatient mental health care in nonhospital settings: distribution of patients across provider groups
Authors: M Olfson, H A Pincus
Journal: American Journal of Psychiatry (1996)

A national overview of outpatient mental health care in nonhospital settings is provided, focusing on the distribution of patients among psychiatrists, psychologists, general medical physicians, and other health professionals.Data from the household section of the 1987 National Medical Expenditure Survey were analyzed to determine the volume and characteristics of patients receiving mental health care from these four professional groups.In 1987 an estimated 4.1% of noninstitutionalized Americans (9.0 million) made 84 million outpatient mental health visits to nonhospital settings. Psychiatrists provided significantly more visits than psychologists for schizophrenia, bipolar disorder, substance abuse, and depression, but significantly fewer visits for anxiety disorders and symptoms such as "nervousness." General medical physicians provided the most visits for adjustment disorders and substance abuse, while the other professionals provided the most visits for childhood mental disorders and mental retardation.In 1987 important differences existed between the outpatients who received mental health care from psychologists, psychiatrists, general medical physicians, and other health professionals.