tbuckley/cabot-search huggingface dataset:
Biphasic Actions of Prostaglandin E <sub>2</sub> on the Renal Afferent Arteriole
Authors: Lilong Tang, Kathy Loutzenhiser, Rodger Loutzenhiser
Journal: Circulation Research (2000)

Abstract —Prostaglandin (PG) E 2 is an important modulator of the actions of angiotensin (Ang) II. In the present study, we investigated the renal microvascular actions of PGE 2 and the EP receptor subtypes involved. Ibuprofen potentiated Ang II–induced vasoconstriction in in vitro perfused normal rat kidneys and augmented afferent arteriolar, but not efferent arteriolar, responses in the hydronephrotic rat kidney model. This preglomerular effect of endogenous prostanoids was mimicked by exogenous PGE 2 , which reversed Ang II–induced afferent arteriolar vasoconstriction at concentrations of 0.1 to 10 nmol/L without affecting the efferent arteriole. The PGE 2 -induced vasodilation was potentiated by the phosphodiesterase inhibitor Ro 20-1724 and was mimicked by 11-deoxy-PGE 1 (0.01 to 1 nmol/L). Butaprost, which acts preferentially at EP 2 receptors, was relatively ineffective. Whereas 0.1 to 10 nmol/L PGE 2 elicited vasodilation, higher concentrations (1 to 10 μmol/L) restored Ang II–induced afferent arteriolar vasoconstriction. This response was blocked by pertussis toxin (200 μg/mL) and was mimicked by the EP 1 /EP 3 agonist sulprostone (1 to 300 nmol/L). Reverse transcription–polymerase chain reaction of individually isolated afferent arterioles revealed the presence of message for EP 4 and all 3 EP 3 splice variants (α, β, and γ) but not EP 1 or EP 2 . Our findings thus indicate that PGE 2 elicits both vasodilatory and vasoconstrictor actions on the afferent arteriole. The vasodilation is mediated by EP 4 receptors coupled to cAMP, presumably via G αs . The vasoconstriction is mediated by an EP 3 receptor coupled to G αi and appears to reflect a functional antagonism of the EP 4 -induced vasodilation.
Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity
Authors: Peter X. Shaw, Sohvi Hörkkö, Mi-Kyung Chang, Linda K. Curtiss, Wulf Palinski, Gregg J. Silverman, Joseph L. Witztum
Journal: Journal of Clinical Investigation (2000)

The immune response to oxidized LDL (OxLDL) may play an important role in atherogenesis. Working with apoE-deficient mice, we isolated a panel of OxLDL-specific B-cell lines that secrete IgM Abs that specifically bind to oxidized phospholipids such as 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine (POVPC). These Abs block uptake of OxLDL by macrophages, recognize similar oxidation-specific epitopes on apoptotic cells, and are deposited in atherosclerotic lesions. The Abs were found to be structurally and functionally identical to classic "natural" T15 anti-PC Abs that are of B-1 cell origin and are reported to provide optimal protection from virulent pneumococcal infection. These findings suggest that there has been natural selection for B-1 cells secreting oxidation-specific/T15 antibodies, both for their role in natural immune defense and for housekeeping roles against oxidation-dependent neodeterminants in health and disease.
Serum cholesterol, haemorrhagic stroke, ischaemic stroke, and myocardial infarction: Korean national health system prospective cohort study
Authors: Shah Ebrahim, Joohon Sung, Yun-Mi Song, Robert L Ferrer, Debbie A Lawlor, George Davey Smith
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To investigate risk factors, such as heavy alcohol consumption, that might explain any increased risk of haemorrhagic stroke associated with low blood cholesterol. <b>Design</b> Prospective cohort study. <b>Setting</b> Korea. <b>Participants</b> 787 442 civil servants (661 700 men, 125 742 women) aged 30-64. <b>Main outcome measures</b> Cardiovascular risk factors were assessed at biennial health check. Data on morbidity and mortality were ascertained from 1990 to 2001 using hospital admissions and mortality surveillance systems. <b>Results</b> 6328 cases of ischaemic stroke (6021 men, 307 women), 3947 cases of haemorrhagic stroke (3748 men, 199 women), 3170 cases of undefined stroke (2902 men, 268 women), and 4417 cases of myocardial infarction (4305 men, 112 women) occurred. Ischaemic stroke and myocardial infarction were strongly and positively associated with blood cholesterol (hazard ratio per 1 mmol/l cholesterol 1.20 (95% confidence 1.16 to 1.24) and 1.48 (1.43 to 1.53), respectively). Haemorrhagic stroke showed an inverse association in fully adjusted models (0.91, 0.87 to 0.95). This inverse association was confined to participants with hypertension. When stratified by concentration of γ glutamyl transferase (GGT), an indicator of alcohol consumption, the association was not seen in participants with low concentrations of GGT, and it was independent of hypertension in those with high concentrations of GGT (&gt; 80 U/l). <b>Conclusion</b> High alcohol consumption may underlie the association between low blood cholesterol and increased risk of haemorrhagic stroke.
Expression of bcl-2 and Epstein-Barr virus LMP1 in lymphocytic interstitial pneumonia
Authors: P. M. Kaan, R. G. Hegele, S. Hayashi, J. C. Hogg
Journal: Thorax (1997)

BACKGROUND: Epstein-Barr virus (EBV) genome has been demonstrated in lung tissues of patients with lymphocytic interstitial pneumonia (LIP) but its role in the pathogenesis of this condition is unclear. In vitro studies have shown that EBV can immortalise and transform cells by upregulation of the cellular proto-oncogene, B cell leukaemia-2 (bcl-2), via the viral latent membrane protein, LMP1. The purpose of this study was to determine whether bcl-2 expression is upregulated in the lungs of patients with LIP and whether EBV LMP1 has a role in this bcl-2 expression. METHODS: Immunohistochemical analysis using alkaline phosphatase anti-alkaline phosphatase (APAAP) was performed on formalin fixed, paraffin embedded lung tissues from 13 patients with LIP using anti-LMP1 and anti-bcl-2 monoclonal antibodies. Lung tissues from nine patients with idiopathic pulmonary fibrosis (IPF) and nine necropsy cases without pulmonary disease served as controls. LMP1 positivity was estimated as the number of LMP1 positive cells per unit area of lung tissue. Immunostaining for bcl-2 expression was assessed by a pictorial-based semiquantitative grading system. RESULTS: Positive immunostaining for LMP1 was localised to airway epithelial cells of lung tissue. Ten out of 13 (77%) patients with LIP were positive for LMP1 compared with three of nine cases (33%) in each control group. LMP1 positivity of LIP cases was significantly greater than that of non-LIP cases: LIP versus IPF (mean difference, 95% confidence interval (CI)) 2.39 (1.54 to 3.24); LIP versus necropsy controls 2.62 (1.77 to 3.47). bcl-2 immunostaining was localised to lymphocytes within the alveolar septa and lymphoid aggregates of patients with LIP. The cumulative score for bcl-2 immunostaining was significantly higher in the lungs of patients with LIP than in those of patients with IPF and necropsy controls: LIP versus IPF and LIP versus necropsy controls (mean difference, 95% CI) 7.55 (7.18 to 7.92). CONCLUSIONS: These immunohistochemical studies have shown the presence of EBV LMP1 protein in airway epithelial cells and overexpression of the cellular bcl-2 protein in lymphoid cells of lung tissue in patients with LIP. These geographically distinct staining patterns of immunostaining suggest that the involvement of EBV LMP1 in the upregulation of cellular bcl-2 is more complex in LIP than was thought from previous in vitro observations. The respective roles of EBV LMP1 and bcl-2 in the pathogenesis of LIP require further studies.
Clinical outcome after front-line intensive sequential chemotherapy (ISC) in patients with aggressive non-Hodgkin’s lymphoma and high-risk international prognostic index (IPI 3): Final analysis of survival in two consecutive ISC trials
Authors: R. Bouabdallah, A.M. Stoppa, D. Coso, V.J. Bardou, D. Blaise, C. Chabannon, J.A. Gastaut, D. Maraninchi
Journal: Annals of Oncology (2001)
Expression of Heme Oxygenase-1 in Thick Ascending Loop of Henle Attenuates Angiotensin II-Dependent Hypertension
Authors: David E. Stec, Heather A. Drummond, Monette U. Gousette, Megan V. Storm, Nader G. Abraham, Eva Csongradi
Journal: Journal of the American Society of Nephrology (2012)

Kidney-specific induction of heme oxygenase-1 (HO-1) attenuates the development of angiotensin II (Ang II) -dependent hypertension, but the relative contribution of vascular versus tubular induction of HO-1 is unknown. To determine the specific contribution of thick ascending loop of Henle (TALH) -derived HO-1, we generated a transgenic mouse in which the uromodulin promoter controlled expression of human HO-1. Quantitative RT-PCR and confocal microscopy confirmed successful localization of the HO-1 transgene to TALH tubule segments. Medullary HO activity, but not cortical HO activity, was significantly higher in transgenic mice than control mice. Enhanced TALH HO-1 attenuated the hypertension induced by Ang II delivered by an osmotic minipump for 10 days (139 ± 3 versus 153 ±2 mmHg in the transgenic and control mice, respectively; P<0.05). The lower blood pressure in transgenic mice associated with a 60% decrease in medullary NKCC2 transporter expression determined by Western blot. Transgenic mice also exhibited a 36% decrease in ouabain-sensitive sodium reabsorption and a significantly attenuated response to furosemide in isolated TALH segments. In summary, these results show that increased levels of HO-1 in the TALH can lower blood pressure by a mechanism that may include alterations in NKCC2-dependent sodium reabsorption.
Relationship Between Duration of Untreated Psychosis and Outcome in First-Episode Schizophrenia: A Critical Review and Meta-Analysis
Authors: Diana O. Perkins, Hongbin Gu, Kalina Boteva, Jeffrey A. Lieberman
Journal: American Journal of Psychiatry (2005)

The duration of untreated psychosis may influence response to treatment, reflecting a potentially malleable progressive pathological process. The authors reviewed the literature on the association of duration of untreated psychosis with symptom severity at first treatment contact and with treatment outcomes and conducted a meta-analysis examining these relationships.English-language articles on duration of untreated psychosis published in peer-reviewed journals through July 2004 were reviewed. Studies that quantitatively assessed the duration of untreated psychosis; identified study subjects who met the criteria for nonaffective psychotic disorders at or close to first treatment; employed cross-sectional analyses of duration of untreated psychosis and of baseline symptoms, neurocognition, brain morphology, or functional measures or prospectively analyzed symptom change, response, or relapse; assessed psychopathology with clinician-rated instruments; and reported subjects' diagnoses (a total of 43 publications from 28 sites) were included in the meta-analysis.Shorter duration of untreated psychosis was associated with greater response to antipsychotic treatment, as measured by severity of global psychopathology, positive symptoms, negative symptoms, and functional outcomes. At the time of treatment initiation, duration of initially untreated psychosis was associated with the severity of negative symptoms but not with the severity of positive symptoms, general psychopathology, or neurocognitive function.Duration of untreated psychosis may be a potentially modifiable prognostic factor. Understanding the mechanism by which duration of untreated psychosis influences prognosis may lead to better understanding of the pathophysiology of schizophrenia and to improved treatment strategies.
L-Ornithine vs. L-ornithine-L-aspartate as a treatment for hyperammonemia-induced encephalopathy in rats
Authors: B.A.P.M. Vogels, O.T. Karlsen, M.A.W. Maas, W.M.M.J. Boveé, R.A.F.M. Chamuleau
Journal: Journal of Hepatology (1997)
Factors involved in the progress of preclinical atherosclerosis associated with systemic lupus erythematosus: a 2-year longitudinal study
Authors: I Rua-Figueroa, O Arencibia-Mireles, M Elvira, C Erausquin, S Ojeda, F Francisco, A Naranjo, C Rodríguez-Gallego, I Garcia-Laorden, J Rodríguez-Perez, C Rodríguez-Lozano
Journal: Annals of the Rheumatic Diseases (2009)

Objectives To assess the changes in carotid intima-media thickness (IMT) and the associated risks factors in patients with low severity systemic lupus erythematosus (SLE). Methods Common carotid IMT measurements were obtained by ultrasound from 101 patients with SLE at an interval of 2 years. Cardiovascular risk factors, disease activity, accumulated damage, severity (Katz index) and biochemical parameters (including high sensitivity C-reactive protein, interleukin 6, C3a, C4a, C5a and homocysteine) were also assessed. Multiple linear regression was used to assess the effect of these variables on the end IMT measurement (eIMT) adjusted to the baseline measurement (bIMT). Results The cohort comprised 94.1% women, with a mean age at entry of 41.5 years and a mean disease duration of 12.1 years. An increase of 0.078 mm in IMT was detected over 2 years, from a mean bIMT of 0.37 mm to a mean eIMT of 0.44 mm (p&lt;0.001). When adjusted for the bIMT, multiple linear regression identified bIMT, age at diagnosis, homocysteine, C3 and C5a as risk factors for IMT progression. Conclusions IMT significantly increases over 2 years in patients with SLE. Age, baseline IMT, C3, C5a anaphylatoxin and homocysteine are all associated risk factors, supporting a role for complement and homocysteine in the early stages of premature SLE-associated atherosclerosis.
Prevention of type II collagen-induced arthritis by in vivo treatment with anti-L3T4.
Authors: G E Ranges, S Sriram, S M Cooper
Journal: The Journal of Experimental Medicine (1985)

The effect of in vivo administration of monoclonal anti-L3T4 antibody on the development of murine collagen-induced arthritis (CIA) was assessed. Treatment with anti-L3T4 resulted in a greater than 90% depletion of L3T4+ T cells in lymph nodes and spleen, an effect that appears entirely reversed 30 d after treatment. Administration of anti-L3T4 before immunization with type II collagen resulted in a significant decrease in arthritis incidence and delayed onset of the disease while treatment begun after a strong anticollagen IgG humoral response was underway was not effective in altering disease expression. These results suggest a prominent role for L3T4+ T cells in the pathogenesis of CIA.
The Sequence Alteration Associated with a Mutational Hotspot in p53 Protects Cells From Lysis by Cytotoxic T Lymphocytes Specific for a Flanking Peptide Epitope
Authors: Matthias Theobald, Thomas Ruppert, Ulrike Kuckelkorn, Javier Hernandez, Annett Häussler, Edite Antunes Ferreira, Ulrike Liewer, Judith Biggs, Arnold J. Levine, Christoph Huber, Ulrich H. Koszinowski, Peter-M. Kloetzel, Linda A. Sherman
Journal: The Journal of Experimental Medicine (1998)

A high proportion of tumors arise due to mutation of the p53 tumor suppressor protein. A p53 hotspot mutation at amino acid position 273 from R to H, flanking a peptide epitope that spans residues 264-272, renders cells resistant to killing by human histocompatibility leukocyte antigen (HLA)-A*0201-restricted cytotoxic T lymphocytes (CTLs) specific for this epitope. Acquisition of the R to H mutation at residue 273 of the human p53 protein promotes tumor growth in vivo by selective escape from recognition by p53.264-272 peptide-specific CTLs. Synthetic 27-mer p53 polypeptides covering the antigenic nonamer region 264-272 of p53 were used as proteasome substrates to investigate whether the R to H mutation at the P1' position of the COOH terminus of the epitope affects proteasome-mediated processing of the protein. Analysis of the generated products by tandem mass spectrometry and the kinetics of polypeptide processing in conjunction with CTL assays demonstrate that the R to H mutation alters proteasomal processing of the p53 protein by inhibiting proteolytic cleavage between residues 272 and 273. This prevents the release of the natural CTL epitope that spans flanking residues 264-272 as well as a putative precursor peptide. These results demonstrate that mutation of p53 not only leads to malignant transformation but may also, in some instances, affect immune surveillance and should be considered in the design of cancer vaccines.
Pilot Trial of Cryoplasty or Conventional Balloon Post-Dilation of Nitinol Stents for Revascularization of Peripheral Arterial Segments
Authors: Subhash Banerjee, Tony S. Das, Mazen S. Abu-Fadel, Eric J. Dippel, Nicolas W. Shammas, Daniel L. Tran, Ahmad Zankar, Cyril Varghese, Kevin C. Kelly, Rick A. Weideman, Bertis B. Little, Robert F. Reilly, Tayo Addo, Emmanouil S. Brilakis
Journal: Journal of the American College of Cardiology (2012)
Inhibition of DNA Methylation Sensitizes Glioblastoma for Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Mediated Destruction
Authors: Adriana Eramo, Roberto Pallini, Fiorenza Lotti, Giovanni Sette, Mariella Patti, Monica Bartucci, Lucia Ricci-Vitiani, Michele Signore, Giorgio Stassi, Luigi M. Larocca, Lucio Crinò, Cesare Peschle, Ruggero De Maria
Journal: Cancer Research (2005)

Abstract Life expectancy of patients affected by glioblastoma multiforme is extremely low. The therapeutic use of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) has been proposed to treat this disease based on its ability to kill glioma cell lines in vitro and in vivo. Here, we show that, differently from glioma cell lines, glioblastoma multiforme tumors were resistant to TRAIL stimulation because they expressed low levels of caspase-8 and high levels of the death receptor inhibitor PED/PEA-15. Inhibition of methyltransferases by decitabine resulted in considerable up-regulation of TRAIL receptor-1 and caspase-8, down-regulation of PED/PEA-15, inhibition of cell growth, and sensitization of primary glioblastoma cells to TRAIL-induced apoptosis. Exogenous caspase-8 expression was the main event able to restore TRAIL sensitivity in primary glioblastoma cells. The antitumor activity of decitabine and TRAIL was confirmed in vivo in a mouse model of glioblastoma multiforme. Evaluation of tumor size, apoptosis, and caspase activation in nude mouse glioblastoma multiforme xenografts showed dramatic synergy of decitabine and TRAIL in the treatment of glioblastoma, whereas the single agents were scarcely effective in terms of reduction of tumor mass, apoptosis induction, and caspase activation. Thus, the combination of TRAIL and demethylating agents may provide a key tool to overcome glioblastoma resistance to therapeutic treatments. (Cancer Res 2005; 65(24): 11469-77)
Prognostic value of changes in radionuclide right ventricular ejection fraction in pulmonary arterial hypertension
Authors: Vincent Cottin, Pierre-Yves Courand, Chahéra Khouatra, Géraldine Pina-Jomir, Christian Scheiber, Julie Traclet, Jean-Charles Glerant, Ségolène Turquier, Marc Humbert, Gérald Simonneau, Jean-François Mornex, Jean-François Cordier
Journal: European Respiratory Journal (2013)

Background. We have previously shown that right ventricular ejection fraction (RVEF) at baseline predicts outcomes in pulmonary arterial hypertension (PAH).  Objective : To evaluate the prognostic value of changes (increase or decrease) in RVEF after initiation of PAH-specific therapy.  Methods. In a prospective cohort of 222 newly diagnosed patients with idiopathic, heritable, or drug-induced PAH, RVEF was measured as part of routine evaluation at baseline in 101 and 3-6 months after initiation of PAH-therapy in 78, using planar equilibrium radionuclide angiography.  Results. Patients (51 women) had a mean age of 55 ± 18 yrs. PAH was idiopathic in 60, heritable in 4, and drug-induced in 14. The mean value of RVEF did not significantly change between baseline and the first follow-up visit (25.9 ± 9.1%) 3 to 6 months after initiation of PAH therapy. Changes in RVEF from baseline to the follow-up visit correlated significantly with changes in cardiac index and mixed venous blood saturation, and negatively correlated with the change in right atrial pressure, mean PAP and PVR. Patients with stable or increased RVEF at 3-6 months had similar demographic characteristics and aetiology of PAH, lower baseline RVEF and more severe hemodynamic characteristics at baseline, had a trend for improved all-cause survival (p=0.064) and had less cardiovascular mortality (p=0.012) by Kaplan Meier analysis than those in whom RVEF decreased despite therapy. Similar results were obtained using multivariable Cox analysis (HR: 2.44, p=0.072; and HR: 3.54, p=0.018, respectively).  Conclusion. Increase or stability in RVEF is associated with less cardiovascular mortality in patients with PAH.
Feasibility Study of a Head and Neck (Upper Aero-Digestive Tract) Cancer Examination&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C Moore, R A Greenberg, L Kane
Journal: JNCI Journal of the National Cancer Institute (1987)

Nearly all of the requirements for a cancer screening program can be met for head and neck--upper aero-digestive tract (UADT)--cancers. These UADT squamous cancers have a clearly definable high-risk group (smokers, greater than or equal to 40 yr), known etiology (tobacco and alcohol), identifiable premalignant lesions, a high prevalence rate worldwide, and high curability with "early" diagnosis. However, a need exists for an efficient detection examination suitable for physicians and dentists alike. Such an examination was designed and field tested as a feasibility study. The examination consisted of a six-step, dentist-oriented, site-targeted, 10-minute procedure, including the use of a fiberoptic pharyngoscope. Two practicing dentists were instructed in the procedure and used it on a randomly selected, high-risk Health America, Inc.--Park DuValle Community Health Center population, who were voluntary responders to a questionnaire and a phone call. Analysis of results showed easy and reproducible teachability, a high degree of acceptance by dentists and examinees, accuracy, and low cost. Associated findings were the following: Of 6,206 respondents, ages 40 and over, 27% were current smokers; 29% were ex-smokers; and 33% never smoked. Of invited current and ex-smokers, ages 40 and over, 51% appeared for a single examination. Compliance emerged as the major problem. The feasibility demonstrated in this study appears to justify a larger, controlled investigation.