tbuckley/cabot-search huggingface dataset:
Chronic inhibition of cyclooxygenase-2 does not alter plaque composition in a mouse model of advanced unstable atherosclerosis
Authors: Florian Bea, Erwin Blessing, Brian J Bennett, Cho Chou Kuo, Lee Ann Campbell, Jörg Kreuzer, Michael E Rosenfeld
Journal: Cardiovascular Research (2003)

Inflammation contributes to atherosclerotic plaque initiation and progression. Recent studies suggest that anti-inflammatory drugs such as cyclooxygenase-2 (Cox-2) inhibitors have anti-atherogenic effects. The current study was designed to investigate whether administration of a Cox-2 inhibitor to older apolipoprotein E deficient (apo E-/-) mice with established lesions alters the composition and increases the stability of the lesions.The Cox-2 inhibitor Celecoxib was administered in chow to 26-week-old, male, apo E-/- mice exhibiting advanced, unstable atherosclerotic lesions within the innominate/brachiocephalic artery. Mice administered Celecoxib had no significant changes in serum cholesterol or the average cross sectional area of atherosclerotic lesion in the innominate artery after 15 weeks of treatment in comparison to non-treated control mice. Histological analyses of sections of the innominate artery demonstrated no significant changes in the frequency of markers of advanced and unstable atherosclerotic plaques, including intra-plaque hemorrhage, vascular calcification, thinning of the fibrous cap, size of the necrotic core and macrophage content. There were also no significant differences in the content of Cox-2 within the lesions. Quantitative real time polymerase chain reaction with mRNA isolated from the aorta of each mouse revealed no significant changes in the expression of tissue factor and inducible nitric oxide synthase. However, mRNA levels for MCP-1 were increased fivefold following 15 weeks of treatment with Celecoxib in comparison to non-treated control mice.These data suggest that Celecoxib has no effect on the composition of advanced atherosclerotic lesions in older apo E-/- mice.
Orthotopic liver transplantation: the first 60 patients.
Authors: R Y Calne, R Williams
Journal: BMJ (1977)

Between May 1968 and 31 December 1976 60 orthotopic liver allografts were transplanted by the Cambridge-King9s College Hospital team. During this period there were changes in the selection of patients and their management. Initially some patients were operated on when they were too ill, often because of a prolonged wait for a donor. There was a high incidence of fatal complications of biliary drainage in patients who survived longer than the first week after operation. Improved results have been due to the development of a simple method of preserving the liver, thereby increasing the pool of potential donors, and by a new technique of biliary drainage, which allows well-vascularised anastomoses without tension, retains the sphincter of Oddi, and leaves access for radiological examination of the biliary tree. Uncontrollable rejection of the liver has occurred in less than 10% of cases. This contrasts strongly with the incidence of rejection among kidney transplants. Six patients have lived for over a year, the longest surviving for more than five years, and 13 patients were still alive at the beginning of 1977.
Phase II trial of docetaxel–irinotecan combination in advanced esophageal cancer
Authors: B. Burtness, M. Gibson, B. Egleston, R. Mehra, L. Thomas, R. Sipples, M. Quintanilla, J. Lacy, S. Watkins, J.R. Murren, A.A. Forastiere
Journal: Annals of Oncology (2009)
A Comparison of Myocardial Function after Primary Cardiac and Primary Asphyxial Cardiac Arrest
Authors: TAKASHI KAMOHARA, MAX HARRY WEIL, WANCHUN TANG, SHIJIE SUN, HITOSHI YAMAGUCHI, KADA KLOUCHE, JOE BISERA
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Although myocardial dysfunction after resuscitation from ventricular fibrillation (VF) has been extensively investigated, less is known of the function of the myocardium after asphyxial cardiac arrest. The present experimental study was designed to compare postresuscitation left ventricular (LV) function after cardiac arrest caused by asphyxia with that of cardiac arrest induced by dysrhythmia. Four groups of Sprague-Dawley rats, which included eight animals in each group, were investigated. In the first two groups, cardiac arrest followed asphyxia produced by neuromuscular blockade with and without airway obstruction. In a third group, cardiac arrest was induced by electrical fibrillation of the ventricle. The fourth group represented animals in which the duration of asphyxial cardiac arrest was maintained for a time interval corresponding to that of the VF group. The fourth group received approximately the same number of electrical shocks as the third (VF) group. All animals were successfully resuscitated with precordial compression and mechanical ventilation. Postresuscitation measurements, including cardiac output, LV end-diastolic pressure (LVEDP), rate of pressure rise at LV pressure of 40 mm Hg (LV dP/dt40), and negative LV dP/dt, demonstrated decreased myocardial function in each group. No differences in cardiac function were observed between the animals with primary respiratory arrest whether or not the airway was obstructed. However, disproportionate and consistently greater impairment in myocardial function followed primary cardiac arrest due to VF when compared with equal duration of asphyxial cardiac arrest. We conclude that in this healthy animal model, asphyxial cardiac arrest resulted in significantly lesser impairment of postresuscitation myocardial function when compared with cardiac arrest caused by VF.
THE EFFECTS OF SUBDURAL INJECTIONS OF LEUCOCYTES ON THE DEVELOPMENT AND COURSE OF EXPERIMENTAL TUBERCULOUS MENINGITIS
Authors: Wilfred H. Manwaring
Journal: The Journal of Experimental Medicine (1912)

Subdural inoculation of tubercle bacilli of established virulence for guinea pigs and rabbits, produces in the dog a tuberculous meningitis, followed by paralysis and death. When suspensions of canine leucocytes are injected subdurally, following such inoculations there occurs uniformly a delay in the development of the paralysis and a prolongation of the life of the treated animal. In dogs inoculated with small doses of tubercle bacilli of low virulence, the development of paralysis has been prevented by this means for periods of seven months (up to the present date), while the untreated animals injected with the same cultures have all developed paralytic symptoms within a period of about four weeks.
Hepatitis C virus production requires apolipoprotein A-I and affects its association with nascent low-density lipoproteins
Authors: C. Mancone, C. Steindler, L. Santangelo, G. Simonte, C. Vlassi, M. A. Longo, G. D'Offizi, C. Di Giacomo, L. P. Pucillo, L. Amicone, M. Tripodi, T. Alonzi
Journal: Gut (2010)

<h3>Background/aims</h3> The life cycle of hepatitis C virus (HCV) is intimately linked to the lipid metabolism of the host. In particular, HCV exploits the metabolic machinery of the lipoproteins in several steps of its life cycle such as circulation in the bloodstream, cell attachment and entry, assembly and release of viral particles. However, the details of how HCV interacts with and influences the metabolism of the host lipoproteins are not well understood. A study was undertaken to investigate whether HCV directly affects the protein composition of host circulating lipoproteins. <h3>Methods</h3> A proteomic analysis of circulating very low-, low- and high-density lipoproteins (VLDL, LDL and HDL), isolated from either in-treatment naïve HCV-infected patients or healthy donors (HD), was performed using two-dimensional gel electrophoresis and tandem mass spectrometry (MALDI-TOF/TOF). The results obtained were further investigated using in vitro models of HCV infection and replication. <h3>Results</h3> A decreased level of apolipoprotein A-I (apoA-I) was found in the LDL fractions of HCV-infected patients. This result was confirmed by western blot and ELISA analysis. HCV cellular models (JFH1 HCV cell culture system (HCVcc) and HCV subgenomic replicons) showed that the decreased apoA-I/LDL association originates from hepatic biogenesis rather than lipoprotein catabolism occurring in the circulation, and is not due to a downregulation of the apoA-I protein concentration. The sole non-structural viral proteins were sufficient to impair the apoA-I/LDL association. Functional evidence was obtained for involvement of apoA-I in the viral life cycle such as RNA replication and virion production. The specific siRNA-mediated downregulation of apoA-I led to a reduction in both HCV RNA and viral particle levels in culture. <h3>Conclusions</h3> This study shows that HCV induces lipoprotein structural modification and that its replication and production are linked to the host lipoprotein metabolism, suggesting apoA-I as a new possible target for antiviral therapy.
Effect of pregnancy on prognosis for young women with breast cancer
Authors: F. Guinee, K.R. Hess, S.H. Taylor, H. Olsson, T. Möller, T. Fahey, J.V. Gladikov, JW van den Blink, F. Bonichon, S. Dische, J.W. Yates, Fj Cleton
Journal: The Lancet (1994)
Treatment of <i>Helicobacter pylori</i> and <i>Chlamydia pneumoniae</i> Infections Decreases Fibrinogen Plasma Level in Patients With Ischemic Heart Disease
Authors: Giuseppe Torgano, Roberto Cosentini, Clara Mandelli, Rodolfo Perondi, Francesco Blasi, Giovanni Bertinieri, Tu Van Tien, Giuliana Ceriani, Paolo Tarsia, Cristina Arosio, Maria Luisa Ranzi
Journal: Circulation (1999)

Background —Chronic Chlamydia pneumoniae and Helicobacter pylori infections could be a risk factor for ischemic heart disease (IHD), possibly by increasing fibrinogen levels. The aim of our study was to evaluate changes in fibrinogen level in patients with IHD and H pylori and/or C pneumoniae positivity randomly assigned to antibiotic treatment. Methods and Results —Eighty-four patients with chronic IHD, H pylori and/or C pneumoniae antibodies, and normal acute-phase reactants were randomly assigned to treatment or no treatment. Treatment consisted of omeprazole, clarithromycin, and tinidazole in H pylori –positive patients and clarithromycin alone in C pneumoniae –positive patients. The effect of treatment and other baseline variables on fibrinogen levels, determined at 6 months, was evaluated by multivariate analysis. Treatment significantly reduced fibrinogen level at 6 months in the overall study population and in the groups of patients divided according to H pylori or C pneumoniae positivity. In the 43 treated patients, mean (±SD) basal fibrinogen was 3.65±0.58 g/L, and mean final fibrinogen was 3.09±0.52 g/dL ( P &lt;0.001), whereas in the 41 untreated patients, mean basal and final fibrinogen levels were 3.45±0.70 and 3.61±0.71 g/L, respectively. The largest decrease was observed in patients with both infections. Fibrinogen changes were also significantly and negatively correlated with age. Conclusions —Our data suggest that a short, safe, and effective course of antibiotic therapy might be suggested as a means of interacting with an “emerging” risk factor.
Anemia and neutropenia associated with copper deficiency of unclear etiology
Authors: William Harless, Edward Crowell, Jame Abraham
Journal: American Journal of Hematology (2006)

Copper deficiency is rarely reported as a cause of neutropenia and anemia through mechanisms not clearly understood. Most cases have been found in malnourished infants or persons receiving total parenteral nutrition without adequate copper. We report on two otherwise healthy young adults with severe neutropenia and anemia secondary to copper deficiency of unclear etiology, which quickly resolved after supplementation with copper gluconate. Both women consumed excessive quantities of soft drinks, which may have contributed to the development of their copper deficiency. Two cases of an unexplained copper deficiency anemia and neutropenia in otherwise healthy young adults found at a single institution over a short period of time suggests that this problem may be more widespread than is currently realized. Am. J. Hematol. 81:546–549, 2006. © 2006 Wiley-Liss, Inc.
The specific recognition by macrophages of CD8+,CD45RO+ T cells undergoing apoptosis: a mechanism for T cell clearance during resolution of viral infections.
Authors: A N Akbar, J Savill, W Gombert, M Bofill, N J Borthwick, F Whitelaw, J Grundy, G Janossy, M Salmon
Journal: The Journal of Experimental Medicine (1994)

During viral infections, CD8+,CD45RO+ T populations expand. These primed cells express abundant levels of cytoplasmic granules that contain perforin and TIA-1. Recent work has suggested that the majority of this CD8+ population downregulates Bcl-2 protein expression and is destined to undergo apoptosis. In this study we have investigated the elimination of these apoptotic CD8+ T cells by both human monocyte-derived and murine bone marrow macrophages. We have found that these phagocytes recognize and ingest both apoptotic CD8+ and CD4+ T cells using an alpha v beta 3 (vitronectin receptor)/CD36/thrombospondin recognition system, with the same receptors being used in the recognition of apoptotic neutrophils. These data provide new evidence for a mechanism that enables the clearance of greatly increased populations of CD8+ effector cells which are found during viral infections. This enables cellular homeostasis to occur in the host upon resolution of viral diseases in vivo.
Epidemiology of chronic rhinosinusitis
Authors: P Van Cauwenberge
Journal: Thorax (2000)

Epidemiological and prevalence data for chronic sinusitis are relatively rare.In children, in particular, the precise incidence of chronic sinusitis has not been established.This paucity of information contrasts with the abundant literature on the microbiology, diagnosis, treatment, and the financial repercussions of chronic sinusitis.
Effect of Patients’ Risks and Preferences on Health Gains With Plasma Glucose Level Lowering in Type 2 Diabetes Mellitus
Authors: Sandeep Vijan, Jeremy B. Sussman, John S. Yudkin, Rodney A. Hayward
Journal: JAMA Internal Medicine (2014)

Type 2 diabetes mellitus is common, and treatment to correct blood glucose levels is standard. However, treatment burden starts years before treatment benefits accrue. Because guidelines often ignore treatment burden, many patients with diabetes may be overtreated.To examine how treatment burden affects the benefits of intensive vs moderate glycemic control in patients with type 2 diabetes.We estimated the effects of hemoglobin A1c (HbA1c) reduction on diabetes outcomes and overall quality-adjusted life years (QALYs) using a Markov simulation model. Model probabilities were based on estimates from randomized trials and observational studies. Simulated patients were based on adult patients with type 2 diabetes drawn from the National Health and Nutrition Examination Study.Glucose lowering with oral agents or insulin in type 2 diabetes.Main outcomes were QALYs and reduction in risk of microvascular and cardiovascular diabetes complications.Assuming a low treatment burden (0.001, or 0.4 lost days per year), treatment that lowered HbA1c level by 1 percentage point provided benefits ranging from 0.77 to 0.91 QALYs for simulated patients who received a diagnosis at age 45 years to 0.08 to 0.10 QALYs for those who received a diagnosis at age 75 years. An increase in treatment burden (0.01, or 3.7 days lost per year) resulted in HbA1c level lowering being associated with more harm than benefit in those aged 75 years. Across all ages, patients who viewed treatment as more burdensome (0.025-0.05 disutility) experienced a net loss in QALYs from treatments to lower HbA1c level.Improving glycemic control can provide substantial benefits, especially for younger patients; however, for most patients older than 50 years with an HbA1c level less than 9% receiving metformin therapy, additional glycemic treatment usually offers at most modest benefits. Furthermore, the magnitude of benefit is sensitive to patients' views of the treatment burden, and even small treatment adverse effects result in net harm in older patients. The current approach of broadly advocating intensive glycemic control should be reconsidered; instead, treating patients with HbA1c levels less than 9% should be individualized on the basis of estimates of benefit weighed against the patient's views of the burdens of treatment.
Neurotropic viruses and cerebral palsy: population based case-control study
Authors: Catherine S Gibson, Alastair H MacLennan, Paul N Goldwater, Eric A Haan, Kevin Priest, Gustaaf A Dekker
Journal: BMJ (2006)

To investigate the association between cerebral palsy and direct evidence for perinatal exposure to neurotropic viruses.Population based case-control study.Adelaide Women's and Children's Hospital Research Laboratory.Newborn screening cards of 443 white case patients with cerebral palsy and 883 white controls were tested for viral nucleic acids from enteroviruses and herpes viruses by using polymerase chain reaction. Herpes group A viruses included herpes simplex viruses 1 and 2 (HSV-1 and HSV-2), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpes virus 8 (HHV-8), and herpes group B viruses included varicella zoster virus (VZV) and human herpes viruses 6 and 7 (HHV-6 and HHV-7).The prevalence of viral nucleic acids in the control population was high: 39.8% of controls tested positive, and the prevalence was highest in preterm babies. The detection of herpes group B viral nucleic acids increased the risk of developing cerebral palsy (odds ratio 1.68, 95% confidence interval 1.09 to 2.59).Perinatal exposure to neurotropic viruses is associated with preterm delivery and cerebral palsy.
Attenuation of bleomycin induced pulmonary fibrosis in mice using the heme oxygenase inhibitor Zn-deuteroporphyrin IX-2,4-bisethylene glycol
Authors: L Atzori
Journal: Thorax (2004)

Pulmonary fibrosis is associated with a poor prognosis. The pathogenesis of fibrotic lung disorders remains unclear, but the extent of tissue damage due to the persistent presence of oxidants or proteases is believed to be important. The heme degrading enzyme heme oxygenase (HO) has been found to be expressed in experimental fibrosis, and generation of free iron and carbon monoxide (CO) by HO has been implicated in oxidant induced lung damage. A study was undertaken to examine the effects of the HO inhibitor Zn-deuteroporphyrin-IX-2,4-bisethylene glycol (Zndtp) on the development of pulmonary fibrosis in the bleomycin model of lung injury and repair.Zndtp (10 micro mol/kg) was administered subcutaneously twice daily to mice 1 week following the intratracheal instillation of 0.025 U bleomycin. Animals were killed 10 or 21 days after bleomycin instillation and indices of lung damage and fibrosis were evaluated.Bleomycin treatment induced pulmonary cytotoxicity, increased levels of active transforming growth factor beta (TGF-beta), enhanced lung collagen accumulation, and decreased glutathione content. Zndtp administration significantly attenuated these indices.Administration of Zndtp in the bleomycin model resulted in appreciable alveolar cytoprotection and amelioration of pulmonary fibrosis. This molecule and its analogues may warrant further consideration in the treatment of acute lung injury and fibrotic lung disorders.
Different Patterns of Gene Expression in ras-Resistant and ras-Sensitive Cells
Authors: A. B. Truck, S. M. Wilson, R. Khokha, A. F. Chambers
Journal: JNCI Journal of the National Cancer Institute (1991)

We have shown previously that nontumorigenic NIH 3T3 cells can be made tumorigenic and metastatic by transfection and expression of activated ras, whereas in LTA cells, which are tumorigenic but nonmetastatic, the degree of malignancy is not altered by ras. To investigate possible mechanisms of natural ras resistance, we compared the expression patterns of several genes thought to be involved in ras-induced metastatic progression in LTA (ras-resistant) and NIH 3T3 (ras-sensitive) cells, before and after constitutive expression of transfected T24-H-ras. We examined the expression of the nuclear "early-response" genes jun and fos and the "tumor-suppressor" retinoblastoma (Rb) gene, as well as genes involved in invasion (major excreted protein [MEP], tissue inhibitor of metalloproteinases [TIMP]), and cell adhesion (secreted phosphoprotein 1 [SPP1; also known as osteopontin]). We found distinct differences in both the basal and ras-induced levels of expression of most of these genes in LTA versus NIH 3T3 cells. High levels of MEP and low levels of TIMP were induced in ras-transfected NIH 3T3 cells, whereas LTA cells showed intermediate levels of MEP and high levels of TIMP that were only marginally affected by the expression of transfected ras. Similarly, SPP1 expression was strongly induced by ras in NIH 3T3 cells but was repressed by ras in LTA cells. Enzymogram assays for functional gelatinase activity showed an increase in 67-kd and 62-kd bands in NIH 3T3 cells in the presence of ras. LTA cells showed no gelatinolytic activity in the presence or absence of ras. Data from an in vitro assay for chemoinvasiveness showed a pattern as predicted from the expression of invasion-related genes; chemoinvasiveness in ras-transfected NIH 3T3 was greater than in LTA and ras-transfected LTA cells, which was greater than in NIH 3T3 cells. Differences in expression of the genes examined are believed to contribute to the ras responsiveness of NIH 3T3 cells and the ras resistance of LTA cells.
Compound heterozygosity of the novel −186C&gt;T mutation in the<i>COL7A1</i>promoter and the recurrent c.497insA mutation leads to generalized dystrophic epidermolysis bullosa
Authors: M. Ritelli, N. Chiarelli, S. Quinzani, C. Dordoni, M. Venturini, P. Calzavara-Pinton, M. Colombi
Journal: British Journal of Dermatology (2012)
Small Heat-Shock Protein Hsp20 Phosphorylation Inhibits β-Agonist-Induced Cardiac Apoptosis
Authors: Guo-Chang Fan, Guoxiang Chu, Bryan Mitton, Qiujing Song, Qunying Yuan, Evangelia G. Kranias
Journal: Circulation Research (2004)

Activation of the sympathetic nervous system is a common compensatory feature in heart failure, but sustained beta-adrenergic activation induces cardiomyocyte death, leading to cardiac remodeling and dysfunction. In mouse cardiomyocytes, we recently reported that prolonged exposure to beta-agonists is associated with transient increases in expression and phosphorylation of a small heat-shock protein, Hsp20. To determine the functional significance of Hsp20, we overexpressed this protein and its constitutively phosphorylated (S16D) or nonphosphorylated (S16A) mutant in adult rat cardiomyocytes. Hsp20 protected cardiomyocytes from apoptosis triggered by activation of the cAMP-PKA pathway, as indicated by decreases in the number of pyknotic nuclei, terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling, and DNA laddering, which were associated with inhibition of caspase-3 activity. These protective effects were further increased by the constitutively phosphorylated Hsp20 mutant (S16D), which conferred full protection from apoptosis. In contrast, the nonphosphorylatable mutant (S16A) exhibited no antiapoptotic properties. Immunostaining studies and immunoprecipitations with Hsp20 or actin antibodies demonstrated that Hsp20 translocated to cytoskeleton and associated with actin on isoproterenol stimulation. These findings suggest that Hsp20 and its phosphorylation at Ser16 may provide cardioprotection against beta-agonist-induced apoptosis. Thus, Hsp20 may represent a novel therapeutic target in the treatment of heart failure.