tbuckley/cabot-search huggingface dataset:
Allogeneic Stem-Cell Transplantation As Salvage Therapy for Patients With Diffuse Large B-Cell Non-Hodgkin's Lymphoma Relapsing After an Autologous Stem-Cell Transplantation: An Analysis of the European Group for Blood and Marrow Transplantation Registry
Authors: Roel J.W. van Kampen, Carmen Canals, Harry C. Schouten, Arnon Nagler, Kirsty J. Thomson, Jean-Paul Vernant, Agnes Buzyn, Marc A. Boogaerts, Jian-Jian Luan, Sébastien Maury, Noel J. Milpied, Jean-Pierre Jouet, Gert J. Ossenkoppele, Anna Sureda
Journal: Journal of Clinical Oncology (2011)

Purpose To analyze the outcome, including nonrelapse mortality (NRM), relapse rate (RR), progression-free survival (PFS), and overall survival (OS), of patients with diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) relapsed after an autologous stem-cell transplantation (ASCT) and treated with an allogeneic stem-cell transplantation (allo-SCT). Patients and Methods The European Group for Blood and Marrow Transplantation database was scanned for a first allo-SCT in relapsed DLBCL after a previous ASCT between 1997 and 2006. Other inclusion criteria were age at allo-SCT ≥ 18 years and availability of an HLA-identical sibling or a matched unrelated donor. A total of 101 patients (57 males; median age, 46 years) were included. Median follow-up for survivors was 36 months. Results Myeloablative conditioning regimen was used in 37 patients and reduced intensity conditioning (RIC) was used in 64 patients. Three-year NRM was 28.2% (95% CI, 20% to 39%), RR was 30.1% (95% CI, 22% to 41%), PFS was 41.7% (95% CI, 32% to 52%), and OS was 53.8% (95% CI, 44% to 64%). NRM was significantly increased in patients ≥ 45 years (P = .01) and in those with an early relapse (&lt; 12 months) after ASCT (P = .01). RR was significantly higher in refractory patients (P = .03). A time interval to relapse after ASCT of &lt; 12 months was associated with lower PFS (P = .03). The use of RIC regimens was followed by a trend to a lower NRM (P = .1) and a trend to a higher RR (P = .1), with no differences in PFS and OS. No differences were seen between HLA-identical siblings and matched unrelated donors. Conclusion Allo-SCT in relapsed DLBCL after ASCT is a promising therapeutic modality. Patients with a long remission after ASCT and with sensitive disease at allo-SCT are the best candidates for this approach.
Cyclooxygenase-1 and cyclooxygenase-2 gene expression in human colorectal adenocarcinomas and in azoxymethane induced colonic tumours in rats.
Authors: C Gustafson-Svard, I Lilja, O Hallbook, R Sjodahl
Journal: Gut (1996)

Increased prostaglandin E2 synthesis is considered important in both human and experimental colon carcinogenesis. It is not known, however, which cyclooxygenase isoenzyme is involved. The aim of this study was to compare the content of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in colorectal cancers with the content in normal colonic specimens. Fifteen human colorectal adenocarcinomas, 35 azoxymethane induced colonic tumours from rats, and specimens of normal colon were analysed by reverse transcription and polymerase chain reaction (RT-PCR). It was found that cyclooxygenase-1 and cyclooxygenase-2 mRNA were increased in azoxymethane induced colonic tumours, compared with specimens taken adjacent to the tumours or from the macroscopically normal intestine distant from the tumours. Cyclooxygenase-1 and cyclooxygenase-2 mRNA were increased in specimens from the macroscopically normal intestine of azoxymethane treated animals, compared with colonic specimens from saline treated rats. Cyclooxygenase-2 mRNA, but not cyclooxygenase-1 mRNA, was increased in human colorectal cancers, compared with the adjacent mucosa or macroscopically normal mucosa distant from the tumours. The results suggest that cyclooxygenase-2 is involved in the increased prostaglandin E2 synthesis in colonic cancers, and that activation of this isoenzyme is an early event in colon carcinogenesis. However, cyclooxygenase-1 may also be involved, at least in experimental colon carcinogenesis.
CXCR4 and CXCL12 (SDF-1) in Prostate Cancer
Authors: Gayle G. Vaday, Shao-Bing Hua, Donna M. Peehl, Michelle H. Pauling, Yu-Huei Lin, Li Zhu, Diana M. Lawrence, Hussein D. Foda, Stanley Zucker
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Metastasis is a major cause of morbidity in prostate cancer (PCa). Several studies have shown that the chemokine receptor CXCR4 and its ligand, CXCL12 (stromal cell-derived factor-1), regulate tumor cell metastasis to specific organs. Recently, it was demonstrated that CXCL12 enhances PCa cell adhesion, migration, and invasion, implicating CXCR4 in PCa metastasis. In this study, we examined the inhibitory effects of anti-CXCR4 antibodies on CXCL12-mediated PCa cell activities. Experimental Design: We developed fully human single chain Fv antibodies (scFv), Ab124 and Ab125, against CXCR4 using the yeast two-hybrid system. We performed immunofluorescent staining, flow cytometry, and ELISA-binding assays to measure scFv binding to PCa cells. We also examined the effects of scFv on CXCL12-mediated calcium mobilization, cell migration, and invasion. Results: Our results confirmed that PCa cell lines express cell-surface CXCR4. Real-time quantitative reverse transcription-PCR and immunohistochemical staining also verified that CXCR4 is expressed in primary cultures of prostate epithelial cells from adenocarcinomas and in human prostate tissues. Ab124 and Ab125 demonstrated specific binding to PCa cell lines by flow cytometry and in binding assays. Preincubation with scFv resulted in significant reduction of CXCL12-induced calcium mobilization in PC-3 and LNCaP cells. Ab124 and Ab125 also inhibited PCa cell migration toward CXCL12, as well as invasion through extracellular matrix gels. Conclusions: Ab124 and Ab125 inhibit CXCL12-mediated cellular activities by binding the receptor CXCR4. Recombinant scFv are an efficient mode of targeting tumor antigens. Considering the high incidence of PCa, the development of fully human scFv may be a useful therapeutic approach in the prevention and treatment of PCa metastasis.
&lt;EMPH TYPE="ITAL"&gt;Chlamydia pneumoniae&lt;/EMPH&gt; as an Emerging Risk Factor in Cardiovascular Disease
Authors: Murat V Kalayoglu, Peter Libby, Gerald I Byrne
Journal: JAMA (2002)

Recent appreciation of atherosclerosis as a chronic, inflammatory disease has rekindled efforts to examine the role that infectious agents may play in atherogenesis. In particular, much interest has focused on infection with Chlamydia pneumoniae. The possibility that a prokaryote contributes to atherogenesis has high clinical interest, as C pneumoniae infection may be a treatable risk factor. To review the evidence implicating C pneumoniae in the pathogenesis of atherosclerosis, we searched MEDLINE for articles published between January 1966 and October 2002 on the association of C pneumoniae and atherosclerosis. We also used online resources, texts, meeting abstracts, and expert opinion. We included 5 types of studies (epidemiological, pathology based, animal model, cell biology, and human antibiotic treatment trials) and extracted diagnostic, pathophysiologic, and therapeutic information from the selected literature; consensus was reached on interpretation discrepancies. Chlamydia pneumoniae is associated with atherosclerosis by epidemiological and pathology-based studies. Animal model and cell biology studies suggest that the pathogen can modulate atheroma biology, including lipid- and inflammatory-related processes. Although some preliminary antibiotic treatment trials in patients with coronary artery disease indicated a reduction in recurrent coronary events, larger studies have not shown benefits in individuals with stable coronary artery disease. It is unlikely that C pneumoniae infection is necessary to initiate atherosclerosis. Furthermore, conventional antibiotic therapy may not eradicate the organism or reduce mortality in individuals with atherosclerotic vascular disease. Nevertheless, the current body of evidence establishes this pathogen as a plausible, potentially modifiable risk factor in cardiovascular disease.
The AP-1 site at -150 bp, but not the NF-kappa B site, is likely to represent the major target of protein kinase C in the interleukin 2 promoter.
Authors: J Jain, V E Valge-Archer, A J Sinskey, A Rao
Journal: The Journal of Experimental Medicine (1992)

Stimulation of T cells with antigen results in activation of several kinases, including protein kinase C (PKC), that may mediate the later induction of activation-related genes. We have examined the potential role of PKC in induction of the interleukin 2 (IL-2) gene in T cells stimulated through the T cell receptor/CD3 complex. We have previously shown that prolonged treatment of the untransformed T cell clone Ar-5 with phorbol esters results in downmodulation of the alpha and beta isozymes of PKC, and abrogates induction of IL-2 mRNA and protein. Here we show that phorbol ester treatment also abolishes induction of chloramphenicol acetyltransferase activity in Ar-5 cells transfected with a plasmid containing the IL-2 promoter linked to this reporter gene. The IL-2 promoter contains binding sites for nuclear factors including NFAT-1, Oct, NF-kappa B, and AP-1, which are all potentially sensitive to activation of PKC. We show that induction of a trimer of the NFAT and Oct sites is not sensitive to phorbol ester treatment, and that mutations in the NF-kappa B site have no effect on inducibility of the IL-2 promoter. In contrast, mutations in the AP-1 site located at -150 bp almost completely abrogate induction of the IL-2 promoter, and appearance of an inducible nuclear factor binding to this site is sensitive to PKC depletion. Moreover, cotransfections with c-fos and c-jun expression plasmids markedly enhance induction of the IL-2 promoter in minimally stimulated T cells. Our results indicate that the AP-1 site at -150 bp represents a major, if not the only, site of PKC responsiveness in the IL-2 promoter.
Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial
Authors: Peter Malfertheiner, Franco Bazzoli, Jean-Charles Delchier, Krysztof Celiñski, Monique Giguère, Marc Rivière, Francis Mégraud
Journal: The Lancet (2011)
Randomised controlled trial of smoking cessation intervention after admission for coronary heart disease
Authors: P. Quist-Paulsen
Journal: BMJ (2003)

We previously reported that both systemic administration and brief local application of ethanol potentiated gamma-aminobutyric acid (GABA)-induced depressions of cerebellar Purkinje neurons when the GABA responses were concomitantly facilitated (modulated) by catecholaminergic agonists. In the present study, we further investigated the effects of prolonged local applications of ethanol, which more closely mimic the systemic application of ethanol, and we characterized the pharmacological specificity of the catecholaminergic interaction with these ethanol effects. As has been previously observed, iontophoretic applications of isoproterenol (ISO), a beta adrenergic agonist, facilitated GABA-induced depressions of cerebellar Purkinje neurons. The prolonged local application of ethanol produced a long-lasting potentiation of the ISO-modulated GABA responses that was similar in duration to that caused by systemic ethanol administration. The ethanol-induced augmentation of the ISO-modulated GABA responses was diminished both by terminating the beta adrenergic agonist application as well as by administering the beta adrenergic antagonist timolol. The alpha adrenergic agonist phenylephrine, on the other hand, either attenuated or had no effects on the GABA-induced depressions of cerebellar Purkinje neurons, and a subsequent application of ethanol did not potentiate GABA responses in the presence of phenylephrine. We conclude that prolonged local application of ethanol mimics the interaction of systemic ethanol with GABA-induced depressions of cerebellar Purkinje neurons. Furthermore, the catecholaminergic sensitization of GABA responses to these potentiative effects of ethanol is mediated by a beta adrenergic mechanism.
Prostaglandin-secreting cells: a portable first aid kit for tissue repair
Authors: Seth Rakoff-Nahoum, Ruslan Medzhitov
Journal: Journal of Clinical Investigation (2007)

After intestinal injury, both the number and type of intestinal epithelial cells must be restored. Intestinal stem cells, located at the base of the intestinal crypt, repopulate the depleted crypt in a process known as compensatory proliferation. In this issue of the JCI, Brown et al. describe a new mechanism by which this process is regulated (see the related article beginning on page 258). Surprisingly, they find that a subset of stromal cells present within the intestinal tissue and expressing the proliferative factor prostaglandin-endoperoxidase synthase 2 (Ptgs2) is repositioned next to the intestinal stem cell compartment where local production of PGE2 controls injury-induced epithelial cell proliferation.
HCV testing in low-risk population
Authors: AmyJ. Weiner, MarthaA. Truett, Jang Han, AlanJ. Polito, Qui-Lim Choo, Jody Rosenblatt, Stella Quan, George Kuo, Michael Houghton, Eileen Page, Charles Agius, MitchellJ. Nelles
Journal: The Lancet (1990)
Abstract 15199: Nadolol Decreases Incidence and Severity of Ventricular Arrhythmias at Exercise Compared to Metoprolol SR in Patients with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
Authors: Ida S Leren, Eman Majid, Trine F Haland, Jørg Saberniak, Thor Edvardsen, Kristina H Haugaa
Journal: Circulation (2014)

Introduction:  Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inheritable cardiac disease predisposing to malignant ventricular arrhythmias at exercise. Beta blockers are mainstay of treatment, but not all beta blockers are equally effective. We explored the incidence and severity of exercise induced arrhythmias in CPVT patients on metoprolol SR, on nadolol medication and without medication.   Methods:  In this cross over study, 9 CPVT patients were included and completed the study (age 30±15, 56% female, 8 RYR2 mutation positive). We performed 3 bicycle exercise stress tests (50W+25W increase every 2. minute until exhaustion) in each patient; 1) before start of beta blocker treatment, 2) >6 weeks on maximum tolerated dose of metoprolol SR and 3) >6 weeks on maximum tolerated dose of nadolol. We recorded resting and maximum heart rate (HR) and the most severe arrhythmia occurring. Severity of arrhythmias was scored as: no arrhythmias (0), single ventricular extra systoles (1), bigemini (2), couplets (3) and non-sustained VT (4).   Results:  HR was similar on metoprolol SR and nadolol at rest (53±13bpm vs. 54±9bpm, p=0.72), while maximum HR was lower on nadolol (147±23bpm vs. 120±24bpm p=0.004). The incidence of arrhythmias was lower on nadolol compared to both metoprolol SR (5/9 (56%) vs. 9/9 (100%)) and no medication (8/9 (89%)). There was a shift towards less severe arrhythmias during exercise on nadolol compared to metoprolol SR (0.9±1.1 vs. 2.6±0.7, p=0.001) and compared to no medication (0.9±1.1 vs. 1.9±1.1, p=0.04) but not on metoprolol SR compared to no medication (2.6±0.7 vs 1.9±1.1, p=0.20)(Figure).   Conclusion:  Incidence and severity of ventricular arrhythmias at exercise decreased on nadolol compared to metoprolol SR. Metoprolol SR did not change occurrence of arrhythmias compared to no medication. Our results indicate that nadolol is superior to metoprolol SR in arrhythmia control in CPVT patients.
Australia Antigen (a Hepatitis-Associated Antigen) in Leukemia&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Alton I. Sutnick, M.D., F.A.C.P., W. Thomas London, M.D., F.A.C.P., Baruch S. Blumberg, M.D., D.Phil., F.A.C.P., Ronald A. Yankee, M.D., Betty Jane S. Gerstley, M.D., F.A.C.P., Irving Millman, Ph.D.
Journal: JNCI Journal of the National Cancer Institute (1970)

Australia antigen [Au(1)] occurs in high frequency in patiente with leukemia and Hodgkin's disease; its frequency in the normal U.S. population is 0.1%. It is relatively common in patients with Down's syndrome and other chromosome abnormalities (increased incidence of leukemia). We previously reported transient Au(1) in acute viral hepatites; current evidence indicates that it might be a virus which causes much of the hepatitis in this country. The frequency of Au(1) in 688 leukemia patients is 7.0%, and in 80 with Hodgkin's disease, 6.3%. The frequency in acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and acute myelogenous leukemia (AML) is 9.8, 6.7, and 9.0%, respectively, but only 2.7% in chronic myelogenous leukemia (CML). Au(1) was detected in 16 of 147 patients from whom serial samples were obtained. In 14, it was absent in the initial specimen. The relation of Au(1) to blood transfusion and other forms of therapy was studied in 512 patients; it was found to be associated only with transfusion. This study confirms an increased frequency of persistent Au(1) in patients with leukemia and Hodgkin's disease. The antigen is associated with preceding blood transfusions, but may occur without transfusion. Au(1) probably represents chronic anicteric hepatitis in leukemia patients. When compared with transfused nonleukemic patients, the frequency of Au(1) in transfused ALL and CLL patients is very high, while there is no significant difference in AML and CML. This favors the explanation that persistent infection results from immune defects in lymphocytic leukemias, but other mechanisms for this association are possible.
<i>In vivo</i> and Microarray Analysis of Rexinoid-Responsive Anaplastic Thyroid Carcinoma
Authors: Joshua P. Klopper, Andrew Berenz, William R. Hays, Vibha Sharma, Umarani Pugazhenthi, Jennifer Janssen, Meenakshi Singh, Reid P. Bissonnette, Bryan R. Haugen
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Anaplastic thyroid carcinoma is rare, yet lethal despite aggressive therapy. Molecular targeting may be beneficial using the rexinoid LGD1069, a retinoid X receptor–selective agonist, as a novel treatment. In this report, we describe the efficacy of LGD1069 in anaplastic thyroid carcinoma in vitro and assess the in vivo treatment effects on a responsive cancer. Additionally, we explore potential mediators of the rexinoid effect on a responsive anaplastic thyroid cancer using comparative microarray analysis. Experimental Design: Anaplastic thyroid cancer cell lines DRO, ARO, and FRO were treated with LGD1069 in vitro. Responsive DRO xenograft tumors were treated with control chow or chow containing a low dose (30 mg/kg/d) or a high dose (100 mg/kg/d) of LGD1069. Comparative microarray analysis of DRO cells treated with LGD1069 compared with volume-equivalent control was assessed after 24 h of treatment to evaluate early gene expression changes. Results: DRO xenograft tumor growth was inhibited by LGD1069 treatment in a dose-dependent manner. Comparative microarray analysis showed that 80 genes had a significant increase in expression and 29 genes had a decrease in expression after 24 h of treatment with LGD1069. Expression of angiopoietin-like 4 (ANGPTL4) mRNA was increased 6.5-fold. A trend towards an increase in ANGPTL4 mRNA (not statistically significant) was seen in treated tumors in vivo and this correlated with decreased tumor vascularity and increased necrosis. Conclusions: LGD1069 therapy decreases proliferation in an anaplastic thyroid cancer cell line that expresses retinoid X receptor-γ, and this effect is confirmed with decreased tumor size in vivo in a nude mouse model. ANGPTL4 is increased in DRO in response to LGD1069 and may be a potential mediator of the effects of rexinoid treatment.
Role of interleukin-6 in acute pancreatitis. Comparison with C-reactive protein and phospholipase A.
Authors: J A Viedma, M Perez-Mateo, J E Dominguez, F Carballo
Journal: Gut (1992)

Plasma values of immunoreactive interleukin-6, C-reactive protein and phospholipase A have been determined in serial samples from 24 patients with acute pancreatitis (9mild9 pancreatitis nine, 9severe9 pancreatitis 15). Median plasma concentrations of interleukin-6, C-reactive protein, and phospholipase A activity were significantly higher in patients with 9severe9 illness (p &lt; 0.001) than those with 9mild9 illness. A particularly marked increase in interleukin-6 was found in two patients with necrotising pancreatitis and fatal outcome. Significant correlations between plasma concentrations of interleukin-6 and phospholipase A (p = 0.0218) and C-reactive protein and phospholipase A activity (p &lt; 0.0001) were found in patients with 9severe9 disease. These findings in a limited number of patients with acute pancreatitis are promising in that raised interleukin-6 correlated with clinical severity and with two other established markers, C-reactive protein, and phospholipase A activity.
Quality of survival in patients with surgically treated bronchial carcinoma.
Authors: E Nou, T Aberg
Journal: Thorax (1980)

Quality of survival was studied in 69 surgically treated bronchial carcinoma patients (25% of a total 273 patients in an unselected epidemiological sample). The Carlens vitagram index was used. The quality of survival in patients cured by pulmonary resection was excellent. It was poor in patients who underwent resection and subsequently died, and especially in patients who had non-resectional thoracotomies. The patients who were operated on and later died did not have a better quality of survival than non-surgically treated patients in the same stage. Thus pulmonary resection has no palliative effect in bronchial carcinoma patients who are not cured. The possible benefit of "removing the tumour burden" in patients treated with operation alone can, therefore, be dismissed. The only aim of the operation at present must be to cure.
Defective binding of spectrin to ankyrin in a kindred with recessively inherited hereditary elliptocytosis.
Authors: S S Zail, T L Coetzer
Journal: Journal of Clinical Investigation (1984)

The interaction of spectrin with spectrin-depleted inside-out membrane vesicles was studied in a kindred with an atypical variant of hereditary elliptocytosis inherited in a recessive manner. The probands are characterized by prominent elliptocytosis, decreased erythrocyte thermal stability, an altered limited tryptic peptide pattern of spectrin digested at low ionic strength, and defective spectrin dimer-dimer association. The parents are normal. The spectrin/band 3 ratio determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of isolated membranes of the probands was decreased to approximately 70% of control values, and total erythrocyte spectrin content in one proband was also decreased on SDS-PAGE. When a monospecific antispectrin antibody was used, a faintly labeled fragment of molecular weight approximately 28,000 was detected on immunoblots of whole cell lysates of one proband and a control, but could not account for the decreased erythrocyte spectrin content of the proband on SDS-PAGE. Binding and competitive inhibition studies revealed an alteration in the spectrin-ankyrin interaction due to an abnormality of spectrin in the probands. No defect was found in the mother; the father's spectrin showed decreased binding affinity, although it was not so severe as in the probands. Separation of bound and unbound spectrin dimers from one proband and subsequent conversion to tetramers showed that the self-association defect was detectable only on the bound subpopulation of her spectrin. These findings demonstrate a hitherto undescribed functional abnormality of spectrin in this kindred which could result in decreased stability of the membrane skeleton and contribute to the elliptocytic shape of these erythrocytes.