tbuckley/cabot-search huggingface dataset:
Prostacyclin biosynthesis in cultured vascular endothelium is limited by deactivation of cyclooxygenase.
Authors: A F Brotherton, J C Hoak
Journal: Journal of Clinical Investigation (1983)

Primary monolayer cultures of human umbilical vein endothelium produce prostacyclin (PGI2) in response to stimulation by thrombin, ionophore A23187, arachidonic acid, and the prostaglandin endoperoxide, PGH2. None of these treatments had a significant effect on the capacity of the endothelium to produce PGI2 in response to subsequent stimulation by PGH2. By contrast, endothelium initially exposed to thrombin, A23187, or arachidonic acid produced approximately 37, 68, and 84% less PGI2, respectively, upon subsequent stimulation by arachidonic acid. These findings suggest that PGI2 biosynthesis in cultured endothelium results in deactivation of cyclooxygenase-hydroperoxidase but not PGI2 synthetase. To test the hypothesis that PGI2 biosynthesis alone causes deactivation of cyclooxygenase, thrombin, A23187, and arachidonic acid were added to monolayers that had been preincubated with ibuprofen (250 microM), a rapidly reversible, competitive inhibitor of this enzyme. After removal of the ibuprofen and the initial stimulus, PGI2 production in response to subsequent stimulation by arachidonic acid was maximal. These findings suggest that the metabolism of arachidonic acid itself causes a direct deactivation of cyclooxygenase. After an initial exposure to arachidonic acid, PGI2 production in response to a second stimulation by arachidonic acid was restored to approximately 34, 69, and 74% of maximal, after recovery periods of 1, 24, and 48 h, respectively. We conclude that the regulation of PGI2 biosynthesis in normal vascular endothelium may be in part a function of the activity and biosynthesis of cyclooxygenase-hydroperoxidase and the deactivation of this enzyme may be a primary factor limiting the capacity of the endothelium to produce PGI2.
TCT-563 Fusion of intravascular ultrasound and X-ray angiography does not allow accurate evaluation of the endothelial shear stress patterns and neointimal distribution after bioresorbable scaffold implantation. A comparison with optical coherence tomography-derived reconstructions
Authors: Christos Bourantas, Michail I. Papafaklis, Lampros Lakkas, Yoshinobu Onuma, Roberto Diletti, Takashi Muramatsu, Cécile Dorange, Dimitrios I. Fotiadis, Fanis Kalatzis, Jin Wang, Katerina K. Naka, Richard Rapoza, Hector M. Garcia-Garcia, Lampros Michalis, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2013)
Systematic Review: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers for Treating Essential Hypertension
Authors: David B. Matchar, Douglas C. McCrory, Lori A. Orlando, Manesh R. Patel, Uptal D. Patel, Meenal B. Patwardhan, Benjamin Powers, Gregory P. Samsa, Rebecca N. Gray
Journal: Annals of Internal Medicine (2008)

Background: The relative effectiveness of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) for lowering blood pressure is unknown. Purpose: To compare the benefits and harms of ACE inhibitors versus ARBs for treating essential hypertension in adults. Data Sources: MEDLINE (1966 to May 2006), the Cochrane Central Register of Controlled Trials (Issue 2, 2006), and selected reference lists were searched for relevant English-language trials. The MEDLINE search was updated to August 2007 to identify head-to-head trials that reported blood pressure outcomes and major cardiovascular events. Study Selection: 61 clinical studies that directly compared ACE inhibitors versus ARBs in adult patients with essential hypertension, reported an outcome of interest, lasted at least 12 weeks, and included at least 20 patients. Data Extraction: A standardized protocol with predefined criteria was used to extract data on study design, interventions, population characteristics, and outcomes; evaluate study quality and applicability; and assess the strength of the body of evidence for key outcomes. Data Synthesis: ACE inhibitors and ARBs had similar long-term effects on blood pressure (50 studies; strength of evidence, high). No consistent differential effects were observed for other outcomes (few studies reported long-term outcomes), including death, cardiovascular events, quality of life, rate of single antihypertensive agent use, lipid levels, progression to diabetes, left ventricular mass or function, and kidney disease. Consistent fair- to good-quality evidence showed that ACE inhibitors were associated with a greater risk for cough. There were fewer withdrawals due to adverse events and greater persistence with therapy for ARBs than for ACE inhibitors, although this evidence was not definitive. Patient subgroups for whom ACE inhibitors or ARBs were more effective, associated with fewer adverse events, or better tolerated were not identified. Limitations: Few studies involved a representative sample treated in a typical clinical setting over a long duration, treatment protocols had marked heterogeneity, and substantive amounts of data about important outcomes and patient subgroups were missing. Conclusion: Available evidence shows that ACE inhibitors and ARBs have similar effects on blood pressure control, and that ACE inhibitors have higher rates of cough than ARBs. Data regarding other outcomes are limited.
SUPPORT FOR ADRENALINE-HYPERTENSION HYPOTHESIS: 18 HOUR PRESSOR EFFECT AFTER 6 HOURS ADRENALINE INFUSION
Authors: PeterJ. Blankestijn, Joke Tulen, Frans Boomsma, H.J. Ritsema Van Eck, Paul Mulder, ArieJ. MAN IN'T VELD, A.H. Van Den Meiracker, Peter Moleman, FransH.M. Derkx, StevenJ. Lamberts, MaartenA.D.H. Schalekamp
Journal: The Lancet (1988)
Two-dimensional echocardiographic demonstration of left atrial thrombi in patients with prosthetic mitral valves.
Authors: F L Mikell, R W Asinger, T Rourke, M Hodges, B Sharma, G S Francis
Journal: Circulation (1979)

Although M-mode echocardiography (MME) is not a reliable method for detecting left atrial thrombi, recent reports suggest that two-dimensional echo (2DE) may be more effective than MME in identifying intracardiac thrombi. In three patients with prosthetic mitral valves who presented with either arterial embolization or prosthetic valvular dysfunction, 2DE demonstrated left atrial masses consistent with thrombi, while MME was either negative (two patients) or suspicious (one patient) for left atrial thrombus. Thrombi were documented by surgical or postmortem examination in all cases. Clear delineation of the atrial cavity and the margins of the masses, visualization on multiple echocardiographic views and comparison of serial examinations were helpful in identifying these masses as thrombi. In addition, the masses visualized had certain patterns of motion which seem unique and may allow characterization of atrial masses as thrombi.
Therapeutic and Tumor-specific Immunity Induced by Combination of Dendritic Cells and Oncolytic Adenovirus Expressing IL-12 and 4-1BBL
Authors: Jing-Hua Huang, Song-Nan Zhang, Kyung-Ju Choi, Il-Kyu Choi, Joo-Hang Kim, Mingul Lee, Hoguen Kim, Chae-Ok Yun
Journal: Molecular Therapy (2009)

Recently, gene-based cytokine treatment has been actively pursued as a new promising approach in treating cancer. In an effort to augment the efficiency of antitumor effect by cytokine-mediated immunotherapy, we selected both interleukin (IL)-12 and 4-1BB ligand (4-1BBL) as suitable cytokines to fully activate the type-1 immune response. Coexpression of IL-12 and 4-1BBL mediated by oncolytic adenovirus (Ad) greatly enhanced the antitumor effect. Further, synergistic enhancement in interferon (IFN)-γ levels were seen in mice treated with oncolytic Ad expressing both IL-12 and 4-1BBL. Next, to improve the overall antitumor immune response, we coadministered IL-12- and 4-1BBL-coexpressing oncolytic Ad with dendritic cells (DCs). Combination treatment of IL-12- and 4-1BBL-coexpressing oncolytic Ad and DCs elicited greater antitumor and antimetastatic effects than either treatment alone. Moreover, enhanced type-1 antitumor immune response and higher migratory abilities of DCs in tumors were also observed in the combination arms. The nature of the enhanced antitumor immune response seems to be mediated through the enhanced cytolytic activity of cytotoxic T lymphocytes (CTLs) and IFN-γ-releasing immune cells. Taken together, these data highlight the potential therapeutic benefit of combining IL-12- and 4-1BBL-coexpressing oncolytic Ad with DCs and warrants further evaluation in the clinic. Recently, gene-based cytokine treatment has been actively pursued as a new promising approach in treating cancer. In an effort to augment the efficiency of antitumor effect by cytokine-mediated immunotherapy, we selected both interleukin (IL)-12 and 4-1BB ligand (4-1BBL) as suitable cytokines to fully activate the type-1 immune response. Coexpression of IL-12 and 4-1BBL mediated by oncolytic adenovirus (Ad) greatly enhanced the antitumor effect. Further, synergistic enhancement in interferon (IFN)-γ levels were seen in mice treated with oncolytic Ad expressing both IL-12 and 4-1BBL. Next, to improve the overall antitumor immune response, we coadministered IL-12- and 4-1BBL-coexpressing oncolytic Ad with dendritic cells (DCs). Combination treatment of IL-12- and 4-1BBL-coexpressing oncolytic Ad and DCs elicited greater antitumor and antimetastatic effects than either treatment alone. Moreover, enhanced type-1 antitumor immune response and higher migratory abilities of DCs in tumors were also observed in the combination arms. The nature of the enhanced antitumor immune response seems to be mediated through the enhanced cytolytic activity of cytotoxic T lymphocytes (CTLs) and IFN-γ-releasing immune cells. Taken together, these data highlight the potential therapeutic benefit of combining IL-12- and 4-1BBL-coexpressing oncolytic Ad with DCs and warrants further evaluation in the clinic.
Incidence of inflammatory bowel disease across Europe: is there a difference between north and south? Results of the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD).
Authors: S Shivananda, J Lennard-Jones, R Logan, N Fear, A Price, L Carpenter, M van Blankenstein
Journal: Gut (1996)

BACKGROUND: It has been suggested that the incidence of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn9s disease (CD), is three or more times higher in northern than in southern Europe. The aim of this EC funded study was to investigate this apparent variation by ascertaining the incidence of IBD across Europe. METHODS: For the period 1 October 1991 to 30 September 1993 all new patients diagnosed with IBD were prospectively identified in 20 European centres according to a standard protocol for case ascertainment and definition. FINDINGS: Altogether 2201 patients aged 15 years or more were identified, of whom 1379 were diagnosed as UC (including proctitis), 706 as CD, and 116 as indeterminate. The overall incidence per 100,000 at ages 15-64 years (standardised for age and sex) of UC was 10.4 (95% confidence interval (95% CI) 7.6 to 13.1) and that of CD was 5.6 (95% CI 2.8 to 8.3). Rates of UC in northern centres were 40% higher than those in the south (rate ratio (RR) = 1.4 (95% CI 1.2 to 1.5)) and for CD they were 80% higher (RR = 1.8 (95% CI 1.5 to 2.1)). For UC the highest reported incidence was in Iceland (24.5, 95% CI 17.4 to 31.5) and for CD, Maastricht (The Netherlands; 9.2, 95% CI 6.5 to 11.8) and Amiens (north west France; 9.2, 95% CI 6.3 to 12.2). The lowest incidence of UC was in Almada (southern Portugal) (1.6, 95% CI 0.0 to 3.2) and of CD in Ioannina (north west Greece) (0.9, 95% CI 0.0 to 2.2). An unexpected finding was a difference in the age specific incidence of UC in men and women with the incidence in women but not men declining with age. INTERPRETATION: The higher overall incidence rates in northern centres did not seem to be explained by differences in tobacco consumption or education. Nevertheless, the magnitude of the observed excess for both conditions is less than expected on the basis of previous studies. This may reflect recent increases in the incidence of IBD in southern Europe whereas those in the north may have stabilised.
Maternal Enterovirus Infection as a Risk Factor for Type 1 Diabetes in the Exposed Offspring
Authors: Hanna Viskari, Mikael Knip, Sisko Tauriainen, Heini Huhtala, Riitta Veijola, Jorma Ilonen, Olli Simell, Heljä-Marja Surcel, Heikki Hyöty
Journal: Diabetes Care (2012)

Maternal enterovirus infections during pregnancy have been linked to an increased risk of type 1 diabetes in the offspring. The aim of this study was to evaluate this association in a unique series of pregnant mothers whose child progressed to clinical type 1 diabetes.Maternal and in utero enterovirus infections were studied in 171 offspring who presented with type 1 diabetes before the age of 11 years and in 316 control subjects matched for date and place of birth, sex, and HLA-DQ risk alleles for diabetes. Acute enterovirus infections were diagnosed by increases in enterovirus IgG and IgM in samples taken from the mother at the end of the first trimester of pregnancy and cord blood samples taken at delivery.Signs of maternal enterovirus infection were observed in altogether 19.3% of the mothers of affected children and in 12.0% of the mothers of control children (P = 0.038). This difference was seen in different HLA risk groups and in both sexes of the offspring, and it was unrelated to the age of the child at the diagnosis of diabetes or the age of the mother at delivery.These results suggest that an enterovirus infection during pregnancy is not a major risk factor for type 1 diabetes in childhood but may play a role in some susceptible subjects.
Hepatic copper in primary biliary cirrhosis: biliary excretion and response to penicillamine treatment.
Authors: M P Salaspuro, P Pikkarainen, P Sipponen, E Vuori, T A Miettinen
Journal: Gut (1981)

Excessive hepatic copper accumulation occurs in long-lasting cholestatic liver disorders especially in primary biliary cirrhosis. As in Wilson's disease, penicillamine has recently been introduced for the treatment of primary biliary cirrhosis. In Wilson's disease there is decreased biliary excretion of copper. The present study shows that as compared with controls the biliary excretion of copper is not decreased in primary biliary cirrhosis; instead it may be increased in some patients. However, when compared with high hepatic copper concentration biliary copper excretion was low. In contrast with copper, biliary secretion of bile acids was decreased in eight of the 17 patients. Treatment with oral penicillamine (600 mg/day) for one year resulted in a significant decrease of hepatic copper concentration, but had no consistent effect on the biliary excretion of copper or on the amount of histologically stainable orcein-positive copper-binding protein. The results suggest that excessive hepatic copper accumulation in primary biliary cirrhosis may not be primarily caused by a decreased biliary excretion, or that a new equilibrium is achieved in advanced primary biliary cirrhosis. D-penicillamine appears to improve significantly the biliary excretion of bile acids.
Histamine <i>N</i>‐methyltransferase 939A&gt;G polymorphism affects mRNA stability in patients with acetylsalicylic acid‐intolerant chronic urticaria
Authors: S.‐H. Kim, Y.‐M. Kang, S.‐H. Kim, B.‐Y. Cho, Y.‐M. Ye, G.‐Y. Hur, H.‐S. Park
Journal: Allergy (2008)

Histamine plays an important role in allergic inflammation. Histamine levels are regulated by histamine N-methyltransferase (HNMT).To investigate the functional variability of HNMT gene in relation to genetic polymorphisms in patients with aspirin intolerant chronic urticaria (AICU).Two single-nucleotide polymorphisms of the HNMT gene (314C>T, 939A>G) were genotyped in chronic urticaria patients. The functional variability of 3'-untranslated region polymorphism (3'-UTR) was assessed using the pEGFP-HNMT 3'-UTR reporter construct to examine mRNA stability and fluorescence-tagged protein expression. The HNMT enzymatic activities related to the 939A>G polymorphism were examined both in the human mast cells (HMC-1) transfected with the pHNMT CDS-3'-UTR construct and in the patients' red blood cells (RBCs). Histamine release from the basophils of AICU patients was examined.The 939A>G polymorphism was significantly associated with the AICU phenotype, while no association was found with the 314C>T polymorphism. An in vitro functional study using HMC-1 cells demonstrated that the 939A allele gave lower levels of HNMT mRNA stability, HNMT protein expression, and HNMT enzymatic activity and higher histamine release than the 939G allele. The in vivo functional study demonstrated that the AICU patients with the 939A allele had lower HNMT activity in RBC lysates and higher histamine release from their basophils.The HNMT 939A>G polymorphism lowers HNMT enzymatic activity by decreasing HNMT mRNA stability, which leads to an increase in the histamine level and contributes to the development of AICU.
Is Maturation Required for Langerhans Cell Migration?
Authors: Gwendalyn J. Randolph
Journal: The Journal of Experimental Medicine (2002)

Key papers in scientific literature sometimes bring a definitive resolution to a long-awaited issue. Others may be far less decisive but importantly implore us to question the fitness of prevailing models. So it is that a paper in this issue by F. Geissmann and colleagues (1), albeit subject to some variety of interpretation, nevertheless compels us to reexamine the widely accepted idea that migration of Langerhans cells in response to inflammatory stimuli is necessarily coupled to and follows from their maturation. It is well established that in the steady-state Langerhans cells turn over very slowly, but they can be mobilized en masse by inflammatory or antigenic stimuli. In vitro and in vivo, these inflammatory mediators have also been observed to promote maturation, and Langerhans cells that migrate from skin explants in culture usually display a mature phenotype. In further agreement with the idea that migration is linked with maturation is evidence that molecules associated with migration, particularly CCR7 (2), are induced during Langerhans cell maturation (3).

Dendritic cell (DC) “maturation” is defined functionally as the acquisition of potent immunogenic capacity. Among DC biologists, this term signifies a particular program of gene expression that typically includes the upregulation of CD40, CD83, CD86, MHC products, and other molecules associated with antigen presentation, along with simultaneous induction of CCR7 (4). At the same time, the ability to acquire and process antigen, a feature that characterizes immature DCs, is downregulated. Understanding the extent to which maturation and migration are coupled lies at the heart of understanding how DCs regulate T cell differentiation. If immature DCs promote naive T cells to develop a tolerogenic phenotype (5), then one is left wondering whether immature DCs traffic efficiently to lymph nodes from the periphery. If they do, then what of the belief that CCR7 is needed for DC migration to lymph nodes and that CCR7 is expressed only by mature DCs? Clearly, the fit of some pieces of the puzzle have to be reevaluated.
Contributions of ACE and mast cell chymase to endogenous angiotensin II generation and leucocyte recruitment in vivo
Authors: Chantal Company, Laura Piqueras, Yafa Naim Abu Nabah, Paula Escudero, Jose Ignacio Blanes, Peter J. Jose, Esteban J. Morcillo, Maria-Jesus Sanz
Journal: Cardiovascular Research (2011)

In vitro studies suggest that mast cell chymase (MCP) is more important than angiotensin-converting enzyme (ACE) for generating angiotensin II (Ang II) within the cardiovascular system. We investigated in vivo the relative contributions of ACE and MCP to leucocyte recruitment induced by endogenously generated Ang II.Exposure of the murine cremasteric microcirculation of C57BL/6 mice to Ang I (100 nM for 4 h) induced leucocyte-endothelium interactions. Either losartan (an Ang II receptor-1 antagonist, AT(1)) or enalapril (an ACE inhibitor), but not chymostatin (a chymase inhibitor), inhibited Ang I-induced responses. Mast cell degranulation with compound 48/80 (CMP48/80, 1 μg/mL) also induced leucocyte adhesion but this was only weakly affected by the inhibitors. When Ang I and CMP48/80 were co-administered, AT(1B) receptor expression was increased, MCP-4 was found surrounding the vessel wall, and ACE was detected in the endothelium. Ang I + CMP48/80 induced enhanced leucocyte adhesion that was attenuated by losartan, enalapril, enalapril + chymostatin, and cromolyn (a mast cell stabilizer). The use of male mast cell-deficient WBB6F1/J-Kit(w)/Kit(w-v) mice (C57BL/6 background) confirmed these findings.In vivo, Ang II is primarily generated by ACE under basal conditions, but in inflammatory conditions, the release of MCP amplifies local Ang II concentrations and the associated inflammatory process. Thus, AT(1) receptor antagonists may be more effective than ACE inhibitors for treating ongoing Ang II-mediated vascular inflammation.
Intact insulin stimulation of skeletal muscle blood flow, its heterogeneity and redistribution, but not of glucose uptake in non-insulin-dependent diabetes mellitus.
Authors: T Utriainen, P Nuutila, T Takala, P Vicini, U Ruotsalainen, T Rönnemaa, T Tolvanen, M Raitakari, M Haaparanta, O Kirvelä, C Cobelli, H Yki-Järvinen
Journal: Journal of Clinical Investigation (1997)

We tested the hypothesis that defects in insulin stimulation of skeletal muscle blood flow, flow dispersion, and coupling between flow and glucose uptake contribute to insulin resistance of glucose uptake in non-insulin-dependent diabetes mellitus (NIDDM). We used positron emission tomography combined with [15O]H2O and [18F]-2-deoxy--glucose and a Bayesian iterative reconstruction algorithm to quantitate mean muscle blood flow, flow heterogeneity, and their relationship to glucose uptake under normoglycemic hyperinsulinemic conditions in 10 men with NIDDM (HbA1c 8.1+/-0.5%, age 43+/-2 yr, BMI 27.3+/-0.7 kg/m2) and in 7 matched normal men. In patients with NIDDM, rates of whole body (35+/-3 vs. 44+/-3 micromol/kg body weight.min, P < 0.05) and femoral muscle (71+/-6 vs. 96+/-7 micromol/kg muscle.min, P < 0.02) glucose uptake were significantly decreased. Insulin increased mean muscle blood flow similarly in both groups, from 1.9+/-0.3 to 2.8+/-0.4 ml/100 g muscle.min in the patients with NIDDM, P < 0.01, and from 2.3+/-0.3 to 3.0+/-0.3 ml/100 g muscle.min in the normal subjects, P < 0.02. Pixel-by-pixel analysis of flow images revealed marked spatial heterogeneity of blood flow. In both groups, insulin increased absolute but not relative dispersion of flow, and insulin-stimulated but not basal blood flow colocalized with glucose uptake. These data provide the first evidence for physiological flow heterogeneity in human skeletal muscle, and demonstrate that insulin increases absolute but not relative dispersion of flow. Furthermore, insulin redirects flow to areas where it stimulates glucose uptake. In patients with NIDDM, these novel actions of insulin are intact, implying that muscle insulin resistance can be attributed to impaired cellular glucose uptake.
Serum Levels of Adipokine Retinol-Binding Protein-4 in Relation to Renal Function
Authors: Michaela Ziegelmeier, Anette Bachmann, Jeannette Seeger, Ulrike Lossner, Matthias Blüher, Michael Stumvoll, Mathias Fasshauer
Journal: Diabetes Care (2008)

We thank Papavasileiou et al. (1) for their comments concerning our recent findings on circulating retinol-binding protein (RBP)-4 in relation to renal function. The authors describe findings similar to those in our study: upregulation of circulating RBP-4 in hemodialysis patients and a significant correlation between RBP-4 and serum creatinine in univariate analysis. …