tbuckley/cabot-search huggingface dataset:
Large scaled analysis of hepatitis B virus (HBV) DNA integration in HBV related hepatocellular carcinomas
Authors: Y Murakami
Journal: Gut (2005)

Hepatitis B virus (HBV) DNA integration into or close to cellular genes is frequently detected in HBV positive hepatocellular carcinomas (HCC). We have previously shown that viral integration can lead to aberrant target gene transcription. In this study, we attempted to investigate common pathways to hepatocarcinogenesis.By using a modified Alu-polymerase chain reaction approach, we analysed 50 HCCs along with 10 previously published cases.Sixty eight cellular flanking sequences (seven repetitive or unidentified sequences, 42 cellular genes, and 19 sequences potentially coding for unknown proteins) were obtained. Fifteen cancer related genes and 25 cellular genes were identified. HBV integration recurrently targeted the human telomerase reverse transcriptase gene (three cases) and genes belonging to distinct pathways: calcium signalling related genes, 60s ribosomal protein encoding genes, and platelet derived growth factor and mixed lineage leukaemia encoding genes. Two tumour suppressor genes and five genes involved in the control of apoptosis were also found at the integration site. The viral insertion site was distributed over all chromosomes except 13, X, and Y.In 61/68 (89.7%) cases, HBV DNA was integrated into cellular genes potentially providing cell growth advantage. Identification of recurrent viral integration sites into genes of the same family allows recognition of common cell signalling pathways activated in hepatocarcinogenesis.
Low density lipoprotein metabolism by human macrophages activated with low density lipoprotein immune complexes. A possible mechanism of foam cell formation.
Authors: R L Griffith, G T Virella, H C Stevenson, M F Lopes-Virella
Journal: The Journal of Experimental Medicine (1988)

Human macrophages play a key role in atherogenesis and are believed to be the progenitors of the cholesteryl ester (CE)-laden foam cells present in early atherosclerotic lesions. Several mechanisms by which macrophages accumulate CE have been recently described. One involves a perturbation in LDL metabolism subsequent to macrophage activation. Thus, we decided to study the effect of macrophage activation by immune complexes on N-LDL metabolism. Initially, LDL-containing immune complexes (LDL-IC) were chosen, since increased plasma levels of these IC have been reported in patients with coronary heart disease. Human macrophages stimulated for 22 h with LDL-IC (250 micrograms/ml) and incubated afterwards for 20 h with 10 micrograms/ml 125I-N-LDL showed a six- and fourfold increase in the accumulation and degradation, respectively, of 125I-N-LDL over the values observed in nonstimulated cells. Scatchard analysis of 125I-N-LDL-specific binding suggests an increase (20-fold) in the number of LDL receptors in macrophages stimulated with LDL-IC. We studied other immune complexes varying in size and antigen composition. Some of the IC were able to stimulate, although to a lesser degree, the uptake of N-LDL by macrophages. Lipoprotein IC are more efficient and have the greatest capacity to increase N-LDL uptake and CE accumulation. We conclude that human macrophage activation by LDL-IC leads to an increase in LDL receptor activity and promotes in vitro foam cell formation.
Normative data for lung function and exhaled nitric oxide in unsedated healthy infants
Authors: O. Fuchs, P. Latzin, C. Thamrin, G. Stern, P. Frischknecht, F. Singer, E. Kieninger, E. Proietti, T. Riedel, U. Frey
Journal: European Respiratory Journal (2010)

Despite association with lung growth and long-term respiratory morbidity, there is a lack of normative lung function data for unsedated infants conforming to latest European Respiratory Society/American Thoracic Society standards. Lung function was measured using an ultrasonic flow meter in 342 unsedated, healthy, term-born infants at a mean±sd age of 5.1±0.8 weeks during natural sleep according to the latest standards. Tidal breathing flow–volume loops (TBFVL) and exhaled nitric oxide (eNO) measurements were obtained from 100 regular breaths. We aimed for three acceptable measurements for multiple-breath washout and 5–10 acceptable interruption resistance (<i>R</i><sub>int</sub>) measurements. Acceptable measurements were obtained in ≤285 infants with high variability. Mean values were 7.48 mL·kg<sup>−1</sup> (95% limits of agreement 4.95–10.0 mL·kg<sup>−1</sup>) for tidal volume, 14.3 ppb (2.6–26.1 ppb) for eNO, 23.9 mL·kg<sup>−1</sup> (16.0–31.8 mL·kg<sup>−1</sup>) for functional residual capacity, 6.75 (5.63–7.87) for lung clearance index and 3.78 kPa·s·L<sup>−1</sup> (1.14–6.42 kPa·s·L<sup>−1</sup>) for <i>R</i><sub>int</sub>. In males, TBFVL outcomes were associated with anthropometric parameters and in females, with maternal smoking during pregnancy, maternal asthma and Caesarean section. This large normative data set in unsedated infants offers reference values for future research and particularly for studies where sedation may put infants at risk. Furthermore, it highlights the impact of maternal and environmental risk factors on neonatal lung function.
Distinct patterns of expression of fibroblast growth factors and their receptors in human atheroma and nonatherosclerotic arteries. Association of acidic FGF with plaque microvessels and macrophages.
Authors: E Brogi, J A Winkles, R Underwood, S K Clinton, G F Alberts, P Libby
Journal: Journal of Clinical Investigation (1993)

Because fibroblast growth factors (FGFs) modulate important functions of endothelial cells (EC) and smooth muscle cells (SMC), we studied FGF expression in human vascular cells and control or atherosclerotic arteries. All cells and arteries contained acidic (a) FGF and basic (b) FGF mRNA. Northern analysis detected aFGF mRNA only in one of five control arteries but in all five atheroma tested, while levels of bFGF mRNA did not differ among control (n = 3) vs. plaque specimens (n = 6). Immunolocalization revealed abundant bFGF protein in control vessels (n = 10), but little in plaques (n = 14). In contrast, atheroma (n = 14), but not control arteries (n = 10), consistently exhibited immunoreactive aFGF, notably in neovascularized and macrophage-rich regions of plaque. Because macrophages colocalized with aFGF, we tested human monocytoid THP-1 cells and demonstrated accumulation of aFGF mRNA during PMA-induced differentiation. We also examined the expression of mRNA encoding FGF receptors (FGFRs). All cells and arteries contained FGFR-1 mRNA. Only SMC and control vessels had FGFR-2 mRNA, while EC and some arteries contained FGFR-4 mRNA. The relative lack of bFGF in plaques vs. normal arteries suggests that this growth factor may not contribute to cell proliferation in advanced atherosclerosis. However, aFGF produced by plaque macrophages may stimulate the growth of microvessels during human atherogenesis.
Prenatal exposure to antidepressants and persistent pulmonary hypertension of the newborn: systematic review and meta-analysis
Authors: S. Grigoriadis, E. H. VonderPorten, L. Mamisashvili, G. Tomlinson, C.-L. Dennis, G. Koren, M. Steiner, P. Mousmanis, A. Cheung, L. E. Ross
Journal: BMJ (2014)

<b>Objective</b> To examine the risk for persistent pulmonary hypertension of the newborn associated with antenatal exposure to antidepressants. <b>Design</b> Systematic review and meta-analysis. <b>Data sources</b> Embase, Medline, PsycINFO, and CINAHL from inception to 30 December 2012. <b>Eligibility</b> English language studies reporting persistent pulmonary hypertension of the newborn associated with exposure to antidepressants. Two independent reviewers extracted data and assessed the quality of each article. <b>Results</b> Of the 3077 abstracts reviewed, 738 papers were retrieved and seven included. All seven studies were above our quality threshold. Quantitative analysis was only possible for selective serotonin reuptake inhibitors (SSRIs). Although exposure to SSRIs in early pregnancy was not associated with persistent pulmonary hypertension of the newborn (odds ratio 1.23, 95% confidence interval 0.58 to 2.60; P=0.58), exposure in late pregnancy was (2.50, 1.32 to 4.73; P=0.005). Effects were not significant for any of the moderator variables examined, including study design, congenital malformations, and meconium aspiration. It was not possible to assess for the effect of caesarean section, body mass index, or preterm delivery. The absolute risk difference for development of persistent pulmonary hypertension of the newborn after exposure to SSRIs in late pregnancy was 2.9 to 3.5 per 1000 infants; therefore an estimated 286 to 351 women would need to be treated with an SSRI in late pregnancy to result in an average of one additional case of persistent pulmonary hypertension of the newborn. <b>Conclusions</b> The risk of persistent pulmonary hypertension of the newborn seems to be increased for infants exposed to SSRIs in late pregnancy, independent of the potential moderator variables examined. A significant relation for exposure to SSRIs in early pregnancy was not evident. Although the statistical association was significant, clinically the absolute risk of persistent pulmonary hypertension of the newborn remained low even in the context of late exposure to SSRIs.
Clinical impact of a program to educate community pharmacists in providing proper inhalation technique for asthma patients
Authors: Masaya Takemura, Katsumi Mitsui, Masako Ido, Misuzu Koyama, Masataka Matsumoto, Daiki Inoue, Kazufumi Takamatsu, Ryo Itotani, Manabu Ishitoko, Shinko Suzuki, Kensaku Aihara, Hitoshi Kagioka, Motonari Fukui
Journal: European Respiratory Journal (2011)

Background:  Currently, more than 10 types of inhaler devices are available in the asthma treatment. The prevalence of these inhalers has resulted in a wide range of choices for clinicians but in confusion for both medical staffs and patients regarding how to use inhaler devices correctly.   Objective:  To evaluate the clinical impact of an educational program for community pharmacists to provide repeated instructions of correct and consistent inhalation technique to asthma patients.   Methods:  Since 2007, Kitano hospital and Kita-ku Pharmaceutical Association Osaka have provided community-pharmacists with a regular educational program on correct inhaler use once a year. Certified participants have instructed asthma patients to use inhalers with proper technique at regular intervals (at least 6 months). We examined the frequency of asthma exacerbations, adherence to inhalation regimen using a 5-point Likert scale questionnaire, and health status assessed by St George9s Respiratory Questionnaire (SGRQ) in asthma patients before starting the program and after four years.   Results:  Usable information was obtained from 146 asthma patients at baseline and 143 those at 4 years. Compared with baseline values, significant decreases were found in the frequency of asthma exacerbations (1.4±1.6 vs 1.0±1.4 times/yr, p=0.042) and emergency room visits (0.5±1.0 vs 0.2±0.5 times/yr, p=0.004). Adherence to the inhalation regimen significantly increased (p=0.041), but SGRQ scores unchanged.   Conclusion:  A regular program which educates community-pharmacists about how to instruct patients in proper inhaler use may improve asthma control and adherence to patients9 inhalation regimen.
Purification and characterization studies of cadmium-binding proteins from the American oyster, Crassostrea virginica.
Authors: B A Fowler, D W Engel, M Brouwer
Journal: Environmental Health Perspectives (1986)

The previously reported low molecular weight cadmium-binding protein (CdBP) from the American oyster, Crassostrea virginica, has been further purified and characterized by improved technical methods. The internal organ distribution of the protein within the oyster and effects of life cycle/season on CdBP production also have been evaluated. CdBP isolated by extended ion-exchange gradients or double ion-exchange chromatography followed by HPLC analysis possesses an electrophoretic Rf of about 0.7 and contains relatively little Zn, as previously reported. Cysteine, lysine, and glycine are the dominant amino acids. When ion-exchange columns are developed with NaCl gradients, the aromatic residues tryptophan, tyrosine, and phenylalanine are found to be present, but these may be largely removed depending upon whether the protein is denatured and carboxymethylated prior to analysis. The ultraviolet absorption spectrum of CdBP also was variable, with 250/280 nm ratios ranging from 17:1 immediately after ion-exchange chromatography to 2:1 following concentration procedures. Internal organ distribution studies showed that the visceral mass contained most of the Cd present with lesser amounts in the gills and mantle. In contrast with mammals, CdBP accounts for only about 30% of the total cell Cd burden in these tissues. Cu displacement of Cd from the protein is a particular problem during the summer spawning season and appears to stem from altered Cu metabolism during this period. Relative oyster dormancy during the winter also reduces CdBP production in response to Cd, and the protein is obtained most readily during the fall and spring.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of hemoglobin precipitation on erythrocyte metabolism in alpha and beta thalassemia
Authors: David G. Nathan, Thomas B. Stossel, Robert B. Gunn, Harold S. Zarkowsky, Mitsuko T. Laforet
Journal: Journal of Clinical Investigation (1969)

Certain aspects of the metabolism of centrifuged young and old erythrocytes in hemoglobin H disease have been examined and compared with similar studies of beta thalassemia and normal cells. Glycolysis, hexose monophosphate shunt activity (HMPS), potassium flux, and glutathione (GSH) content were measured. The distributions of hemoglobins H and F, as well as the activities of erythrocyte glucose-6-phosphate dehydrogenase (G6PD) and glutamic oxalacetic transaminase (GOT), were utilized for estimations of the relative ages of the cell samples. The young erythrocytes in hemoglobin H disease differed in several respects from older hemoglobin H cells. They contained more soluble hemoglobin H and GSH and, after splenectomy, fewer inclusions. HMPS activity was subnormal in hemoglobin H young cells and rose to normal activity in old cells. Potassium flux tended to increase in old cells when inclusions were present.
Long-Term Follow-Up of Indolent Lymphoma Patients Treated With High-Dose Sequential Chemotherapy and Autografting: Evidence That Durable Molecular and Clinical Remission Frequently Can Be Attained Only in Follicular Subtypes
Authors: Paolo Corradini, Marco Ladetto, Francesco Zallio, Monica Astolfi, Elena Rizzo, Selina Sametti, Alessandra Cuttica, Rosalba Rosato, Lucia Farina, Mario Boccadoro, Fabio Benedetti, Alessandro Pileri, Corrado Tarella
Journal: Journal of Clinical Oncology (2004)

To evaluate the prognostic relevance of molecular monitoring of minimal residual disease in indolent lymphomas receiving high-dose sequential chemotherapy and autografting.A polymerase chain reaction- (PCR-)based strategy was used to evaluate the presence of residual tumor cells in a panel of 70 indolent lymphoma patients: 40 with follicular (FCL), 14 with small lymphocytic (SLL), and 16 with mantle-cell (MCL) lymphomas. They were treated either with first-line (n = 61) or second-line (n = 9) therapy with an intensified high-dose chemotherapy program followed by peripheral-blood progenitor cells autografting. The Bcl-1, Bcl-2, and immunoglobulin gene rearrangements were used as lymphoma-specific markers. Overall, a molecular marker was obtained from the diagnostic tissue in 60 of 70 patients (86%). Results The collection of PCR-negative cells and the achievement of posttransplantation molecular remission (MR) were common in patients with FCL subtype (54% and 70%, respectively), whereas they were not frequent among SLL and MCL (25% and 12.5%, respectively) patients. With a median molecular follow-up of 75 months, an 88% incidence of relapse was observed among patients never attaining MR. In contrast, relapse incidence was only 8% among patients attaining a durable MR (P <.005). At present, 26 patients (20 with FCL and six with non-FCL) are long-term survivors in absence of clinical and molecular disease.Our results indicate that among indolent lymphomas, FCL and non-FCL subtypes show a significantly different behavior in terms of MR achievement, and MR after intensive chemotherapy and autografting is predictive for a prolonged disease-free survival, whereas persistent PCR positivity is associated with a high risk of relapse.
Preoperative PSA Velocity Is an Independent Prognostic Factor for Relapse After Radical Prostatectomy
Authors: Deep A. Patel, Joseph C. Presti, John E. McNeal, Harcharan Gill, James D. Brooks, Christopher R. King
Journal: Journal of Clinical Oncology (2005)

Purpose Preoperative prostate-specific antigen (PSA) velocity (PSAV), or the rate of PSA rise before diagnosis, predicts for risk of cancer death after radical prostatectomy (RP). We evaluated the relative merit of established preoperative factors, including biopsy indices and preoperative PSAV, for their impact on relapse after RP. Patients and Methods The outcomes of 202 men who underwent RP were reviewed. Biopsies were characterized for grade, percentage positive cores, and total linear tumor length. Surgical specimens were characterized for cancer volume, relative percentage by grade, extracapsular extension, and margin status. Univariate and multivariate analyses were performed with respect to relapse-free survival after RP. Results Thirty-one patients relapsed after RP (defined as PSA ≥ 0.2 ng/mL), with a median time to failure of 16 months. Median follow-up was 48 months. Kaplan-Meier relapse-free survival at 5 years was 89%, compared with 73% for PSAV ≤ 2 v &gt; 2 ng/mL/year (P = .003). On multivariate analysis, only the biopsy Gleason sum (P &lt; .008; relative risk, &gt; 4.8) and the preoperative PSAV (P &lt; .04; relative risk, 3.0 to 4.7) remained significant. Patients with a PSAV of &gt; 2 ng/mL/year were more likely to be pT3 (P = .007), have positive margins (P = .01), have tumors &gt; 1 mL (P = .05), and possess &gt; 10% grade 4/5 tumors (P = .04). Conclusion The preoperative PSAV is a significant independent clinical factor predicting for relapse after RP and also predicts for larger, more aggressive, and more locally advanced tumors. Its inclusion will be useful in risk stratification, evaluation for alternatives to surgery, and patient selection for neoadjuvant or adjuvant therapies as part of randomized clinical trials.
T-B+NK+ Severe Combined Immunodeficiency Caused by Complete Deficiency of the CD3zeta Subunit of the T Cell Antigen Receptor Complex
Authors: J.L. Roberts, J.P.H. Lauritsen, M. Cooney, R.E. Parrott, E.O. Sajaroff, C.M. Win, M.D. Keller, J.H. Carpenter, M. Sarzotti, X. Zhong, D.L. Wiest, R.H. Bucley
Journal: Journal of Allergy and Clinical Immunology (2007)
Retinal Abnormalities Characteristic of Inherited Renal Disease
Authors: Judy Savige, Sujiva Ratnaike, Deb Colville
Journal: Journal of the American Society of Nephrology (2011)

Many inherited renal diseases have retinal features that are helpful diagnostically. These include coloboma, drusen, atrophy and pigmentation (retinitis pigmentosa), hamartoma, vascular anomalies, and crystals. Retinal abnormalities occur because the kidney and retina share developmental pathways and structural features including basement membrane collagen IV protomer composition and their vascularity, and because both the kidney and retina are functionally dependent on ciliated cells. Diagnosis of inherited renal disease is important because of the risks of further renal and systemic complications, the implications for other family members, the predictability of the clinical course, and the possibility of treatment. Furthermore, retinal abnormalities may help explain the pathogenesis of the renal disease, and can sometimes be used to monitor its course.
A phase Ib dose-escalation study of everolimus combined with cisplatin and etoposide as first-line therapy in patients with extensive-stage small-cell lung cancer
Authors: B. Besse, R.S. Heist, V.A. Papadmitrakopoulou, D.R. Camidge, J.T. Beck, P. Schmid, C. Mulatero, N. Miller, S. Dimitrijevic, S. Urva, I. Pylvaenaeinen, K. Petrovic, B.E. Johnson
Journal: Annals of Oncology (2013)
P-selectin upregulation in bleomycin induced lung injury in rats: effect of N-acetyl-L-cysteine
Authors: A Serrano-Mollar
Journal: Thorax (2002)

<b>Background:</b> A number of adhesion molecules are involved in the process of neutrophil infiltration into the lung. P-selectin is one of these neutrophil-endothelial cell adhesion molecules. A study was undertaken to examine the involvement of P-selectin in the development of bleomycin induced inflammation and the ability of <i>N</i>-acetyl-l-cysteine to reduce the potential expression of this selectin in rats. <b>Methods:</b><i>N</i>-acetyl-l-cysteine (3 mmol/kg po) was administered daily for seven days prior to bleomycin administration (2.5 U/kg). The kinetics of P-selectin expression and the effect of <i>N</i>-acetyl-l-cysteine after bleomycin treatment were measured using radiolabelled antibodies. P-selectin localisation was evaluated by immunohistochemistry and neutrophil infiltration was assessed by myeloperoxidase activity. <b>Results:</b> Bleomycin administration resulted in an upregulation of P-selectin at 1 hour, returning to baseline at 3 hours. Myeloperoxidase activity showed a significant increase at 6 hours after bleomycin administration that lasted for 3 days. <i>N</i>-acetyl-l-cysteine treatment completely prevented these increases. <b>Conclusion:</b> Upregulation of P-selectin in the lung is associated with neutrophil recruitment in response to bleomycin. The beneficial effect of <i>N</i>-acetyl-l-cysteine on bleomycin induced lung injury may be explained in part by the prevention of neutrophil recruitment in the inflammatory stage of the disease.