tbuckley/cabot-search huggingface dataset:
Pravastatin Improves Function in Hibernating Myocardium by Mobilizing CD133 <sup>+</sup> and cKit <sup>+</sup> Bone Marrow Progenitor Cells and Promoting Myocytes to Reenter the Growth Phase of the Cardiac Cell Cycle
Authors: Gen Suzuki, Vijay Iyer, Thomas Cimato, John M. Canty
Journal: Circulation Research (2008)

3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors have been reported to increase circulating bone marrow progenitor cells and variably improve global function in heart failure. The potential role of improved perfusion versus direct effects of statins on cardiac myocytes has not been established. We chronically instrumented swine with a left anterior descending artery (LAD) stenosis to produce chronic hibernating myocardium with regional contractile dysfunction in the absence of heart failure. Hemodynamics, function, perfusion, and histopathology were assessed in pigs treated for 5 weeks with pravastatin (n=12) versus untreated controls (n=10). Regional LAD wall thickening was depressed under baseline conditions (LAD 3.7+/-0.3 versus 6.6+/-0.3 in remote regions, P<0.01). It remained unchanged in untreated animals but increased from 3.8+/-0.6 to 5.2+/-0.5 mm after pravastatin (P<0.01). There was no increase in myocardial perfusion at rest or during vasodilation. Pravastatin mobilized circulating CD133(+)/cKit(+) bone marrow progenitor cells and increased myocardial tissue levels (LAD CD133(+) cells from 140+/-33 to 884+/-167 cells/10(6) myocyte nuclei and cKit(+) cells from 223+/-49 to 953+/-123 cells/10(6) myocyte nuclei). Pravastatin increased myocytes in mitosis (phospho-histone-H3; 9+/-5 to 43+/-7 nuclei/10(6) myocyte nuclei, P<0.05) and the growth phase of the cell cycle (Ki67; 410+/-82 to 1261+/-235 nuclei/10(6) myocyte nuclei, P<0.05) in diseased but not normal hearts. As a result, pravastatin increased LAD myocyte nuclear density from 830+/-41 to 1027+/-55 nuclei/mm(2) (P<0.05). These data indicate that, in the absence of impaired endothelial function and heart failure, dysfunctional hibernating myocardium improves after pravastatin. This effect is independent of myocardial perfusion and related to mobilization of CD133(+)/cKit(+) bone marrow progenitor cells which stimulate myocyte proliferation resulting in quantitative increases in myocyte nuclear density.
RESTRICTION OF HERPES SIMPLEX VIRUS BY MACROPHAGES
Authors: Jack G. Stevens, Margery L. Cook
Journal: The Journal of Experimental Medicine (1971)

Macrophages restrict herpes simplex virus replication and can prevent the development of herpetic disease in mice. In an attempt to define the nature of this restriction, an analysis of virus-specified macromolecular syntheses in infected macrophages was undertaken. The significant results were the following: All cells were killed, but the infection was considered to be abortive since the level of infectious virus in macrophage cultures dropped steadily to a level beyond detection by 25 hr after infection. This restriction appeared to be specific for macrophages; the virus replicated efficiently in other mouse cells. DNA with a density characteristic for herpes simplex virus DNA was extracted from infected cultures, and the proportion of macrophages synthesizing DNA increased from less than 1% to greater than 50% by 6 hr after infection. Studies employing polyacrylamide gel electrophoresis indicated that the major viral-specific proteins were induced in macrophage cultures. In addition, all cells showing cytopathic changes characteristic of herpes virus infection also contained viral antigens which could be detected by fluorescent antibody techniques and, by 15 hr after infection, most contained nascent capsids lacking central dense cores. It is suggested that an error in DNA metabolism may be the primary cause of restriction.
Note upon the Causation of Cancer
Authors: H. J. Campbell
Journal: BMJ (1904)

statements seem to be quite warranted by the facts observed:.i That a bacillus, -identical -with the B. dysenteriae, described by Shiga as the specific cause of acute dysentery in* Japan, can be isolated from the stools of many cases of asylum dysentery.',2. That the blood serum of some of these cases of asylum dysentery possesses a specific agglutinative action when tested against B. dysenteriae isolated from the stools of other' similar cases, and also against other.strains of B. dysenteriae isolated from cases of dysentery in tropical countries.On the other hand, the experience of an extended series of examinations of the stools of patients suffering from asylum dysentery will permit me to state:3.-That in order to detect the presence of B. dysenteriae, the stools must be examined when fresh.4. That post-mortem material, must be collected and examined as soon after death as possible, as after a few hours', delay, even in quite acute cases B. coli becomes the predominant organism in the intestinal canal.,.That under these conditions (3 and, 4) the isolation of
Reactivation of Latent Epstein-Barr Virus by Methotrexate: A Potential Contributor to Methotrexate-Associated Lymphomas
Authors: W.-h. Feng, J. I. Cohen, S. Fischer, L. Li, M. Sneller, R. Goldbach-Mansky, N. Raab-Traub, H.-J. Delecluse, S. C. Kenney
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Patients with rheumatoid arthritis or polymyositis treated with methotrexate (MTX) develop Epstein–Barr virus (EBV)–positive lymphomas more frequently than patients treated with other, equally immunosuppressive regimens. Here we determined whether MTX, in contrast to other commonly used medications for rheumatoid arthritis or polymyositis, is unique in its ability to induce the release of infectious EBV from latently infected cells. Methods: The effect of MTX and other immunosuppressant drugs on EBV replication in vitro was assessed using latently infected EBV-positive lymphoblastoid and gastric carcinoma cell lines. Inhibitors of signal transduction pathways were used to define requirements for induction of lytic infection. Drug effects on transcription of the two EBV immediate-early promoters (BRLF1 and BZLF1) and on promoter constructs lacking cis -acting sequences required for activation by other effectors was examined using reporter gene assays. EBV viral load in rheumatoid arthritis and polymyositis patients receiving MTX was compared with that in patients receiving other immunosuppressive medications. Statistical tests were two-sided. Results: MTX activated the release of infectious EBV from latently infected cell lines in vitro , and MTX treatment was associated with activation of the two viral immediate-early promoters in reporter gene assays. Induction of lytic EBV infection by MTX required the p38 MAP kinase, PI3 kinase, and MEK pathways and specific cis -acting motifs in the two viral immediate-early promoters. Patients treated with MTX-containing regimens had statistically significantly higher mean EBV loads in their blood than patients treated with immunosuppressing regimens that did not include MTX (40 EBV copies per 10 6 cellular genomes versus 5.1 copies; geometric mean fold difference in copies = 10.8, 95%, confidence interval = 3.0 to 38; P = .011). Conclusion: MTX may promote EBV-positive lymphomas in rheumatoid arthritis and polymyositis patients by its immunosuppressive properties as well as by reactivating latent EBV.
European evidence-based consensus on the diagnosis and management of Crohn's disease
Authors: S B Hanauer, W J Sandborn
Journal: Gut (2007)

When is a consensus not a consensus?E duard Stange and Simon Travis 1 are to be congratulated on their magnum opus encompassing 234 statements and 727 references pertaining to the diagnosis and management of Crohn's disease.The aim of the consensus was not to ''supersede guidelines of different countries'', but to ''promote a European perspective on the management of Crohn's disease'' under the auspices of the European Crohn's and Colitis Organization (ECCO).ECCO is a forum established in 2000 for specialists interested in inflammatory bowel disease (IBD) to promote European views, clinical trials and specialist training in IBD.We agree with many, if not most, of the statements and recommendations, and note that the European consensus with regard to diagnosis and management of Crohn's disease is substantially aligned with practice guidelines from the US. 2 3The methods (strategy) of the Consensus entailed five steps.Fourteen separate topics were assigned to 13 working parties whose chairmen developed questions that were distributed to the working parties.The working parties dealt with the questions on the basis of their experience and evidence from the literature (gained from a systematic literature search).An evidence level was graded (1-5) according to the guidelines of the Oxford Centre for Evidence Based Medicine (Oxford, UK).Provisional guideline statements were then written by the chairmen and circulated among the working parties, which met, first, in Prague at the 2004 United European Gastroenterology Week Conference, where 61 participants from 20 countries gathered to agree on the final versions of each guideline statement.The participants continued to discuss the individual statements until a consensus (.80% agreement) was reached.
Can GC Content at Third-Codon Positions Be Used as a Proxy for Isochore Composition?
Authors: E. Elhaik, G. Landan, D. Graur
Journal: Molecular Biology and Evolution (2009)

The isochore theory depicts the genomes of warm-blooded vertebrates as a mosaic of long genomic regions that are characterized by relatively homogeneous GC content. In the absence of genomic data, the GC content at third-codon positions of protein-coding genes (GC3) was commonly used as a proxy for the GC content of isochores. Oddly, in the postgenomic era, GC3 is still sometimes used as a proxy for the GC composition of isochores. Here, we use genic and genomic sequences from human, chimpanzee, cow, mouse, rat, chicken, and zebrafish to show that GC3 only explains a very small proportion of the variation in GC content of long genomic sequences flanking the genes (GCf), and what little correlation there is between GC3 and GCf was found to decay rapidly with distance from the gene. The coefficient of variation of GC3 was found to be much larger than that of GCf and, therefore, GC3 and GCf values are not comparable with each other. Comparisons of orthologous gene pairs from 1) human and chimpanzee and 2) mouse and rat show strong correlations between their GC3 values, but very weak correlations between their GCf values. We conclude that the GC content of third-codon position cannot be used as stand-in for isochoric composition.
Transthoracic bioimpedance and brain natriuretic peptide levels accurately indicate additional diastolic dysfunction in patients with chronic advanced systolic heart failure
Authors: Gabriella Malfatto, Giovanna Branzi, Alessia Giglio, Alessandra Villani, Camilla Facchini, Francesca Ciambellotti, Mario Facchini, Gianfranco Parati
Journal: European Journal of Heart Failure (2010)
Transcriptional Diversification and Functional Conservation between DELLA Proteins in Arabidopsis
Authors: J. Gallego-Bartolome, E. G. Minguet, J. A. Marin, S. Prat, M. A. Blazquez, D. Alabadi
Journal: Molecular Biology and Evolution (2010)

Plasticity and robustness of signaling pathways partly rely on genetic redundancy, although the precise mechanism that provides functional specificity to the different redundant elements in a given process is often unknown. In Arabidopsis, functional redundancy in gibberellin signaling has been largely attributed to the presence of five members of the DELLA family of transcriptional regulators. Here, we demonstrate that two evolutionarily and functionally divergent DELLA proteins, RGL2 and RGA, can perform exchangeable functions when they are expressed under control of the reciprocal promoter. Furthermore, both DELLA proteins display equivalent abilities to interact with PIF4 and with other bHLH transcription factors with a reported role in the control of cell growth and seed germination. Therefore, we propose that functional diversification of Arabidopsis DELLA proteins has largely relied on changes in their gene expression patterns rather than on their ability to interact with different regulatory partners, model also supported by a clustering analysis of DELLA transcript profiles over a range of organs and growth conditions that revealed specific patterns of expression for each of these genes.
The Reversible Dementias: Do They Reverse?
Authors: A.M. Clarfield
Journal: Annals of Internal Medicine (1988)

Thirty-two studies (2889 subjects) that investigated the prevalence of the causes of dementia were critically reviewed. Particular attention was paid to potential and actual reversibility. Although dementia manifests itself primarily in old age (particularly age 75 and older), the mean age of patients for the studies that reported age data (56%) was 72.3 years. Twenty-five studies originated from secondary or tertiary centers, and four were community-based. Dementias consisted of Alzheimer disease, 56.8%; multi-infarct, 13.3%; depression, 4.5%; alcoholic, 4.2%; and drugs, 1.5%. No single other cause contributed more than 1.6% of the cases. Potentially reversible causes made up 13.2% of all cases. However, the more important question of whether patients with potentially reversible causes were followed and reversal actually seen was not always examined. In 11 studies (34%) that provided follow-up, 11% of dementias resolved, either partially (8%) or fully (3%). The commonest reversible causes were drugs, 28.2%; depression, 26.2%; and metabolic, 15.5%. Due to the presence of various biases (selection, lack of "blinded" investigators, and others) in the surveyed works, it is probable that the true incidence of reversible dementias in the community is even lower than that reported. Research implications as well as a conservative approach to the workup of a new case of dementia are offered.
Anti-endothelial cell antibodies in systemic sclerosis
Authors: C Mihai, J W C Tervaert
Journal: Annals of the Rheumatic Diseases (2010)

Anti-endothelial cell antibodies (AECA) are a heterogeneous class of antibodies whose role in the pathogenesis of autoimmune diseases with vascular involvement has been extensively studied. Systemic sclerosis (SSc) is one of the systemic autoimmune diseases in which endothelial dysfunction is well defined and important in the development of the disease. AECA are present in the serum samples of many patients with SSc. Depending on the detection method and on patient selection, 22–86% of patients test positive for AECA. Among the demonstrated clinical associations, lung and peripheral vascular involvement are the most common. In this paper, the methods of detection, various molecular specificities and the possible pathogenic mechanisms of AECA in SSc are reviewed.
Telomerase- and Alternative Telomere Lengthening–Independent Telomere Stabilization in a Metastasis-Derived Human Non–Small Cell Lung Cancer Cell Line: Effect of Ectopic hTERT
Authors: Andreas Brachner, Soleman Sasgary, Christine Pirker, Chantal Rodgarkia, Mario Mikula, Wolfgang Mikulits, Helga Bergmeister, Ulrike Setinek, Matthias Wieser, Suet-Feung Chin, Carlos Caldas, Michael Micksche, Christa Cerni, Walter Berger
Journal: Cancer Research (2006)

Abstract In the majority of human malignancies, maintenance of telomeres is achieved by reactivation of telomerase, whereas a smaller fraction uses an alternative telomere lengthening (ALT) mechanism. Here, we used 16 non–small cell lung cancer (NSCLC) cell lines to investigate telomere stabilization mechanisms and their effect on tumor aggressiveness. Three of 16 NSCLC cell lines (VL-9, SK-LU-1, and VL-7) lacked telomerase activity, correlating with significantly reduced tumorigenicity in vitro and in vivo. Of the three telomerase-negative cell lines, only SK-LU-1 displayed characteristics of an ALT mechanism (i.e., highly heterogeneous telomeres and ALT-associated promyelocytic leukemia bodies). VL-9 cells gained telomerase during in vitro propagation, indicating incomplete immortalization in vivo. In contrast, NSCLC metastasis-derived VL-7 cells remained telomerase and ALT negative up to high passage numbers and following transplantation in severe combined immunodeficient mice. Telomeres of VL-7 cells were homogenously short, and chromosomal instability (CIN) was comparable with most telomerase-positive cell lines. This indicates the presence of an efficient telomere stabilization mechanism different from telomerase and ALT in VL-7 cells. To test the effect of ectopic telomerase reverse transcriptase (hTERT) in these unique ALT- and telomerase-negative tumor backgrounds, hTERT was transfected into VL-7 cells. The activation of telomerase led to an excessively rapid gain of telomeric sequences resulting in very long (∼14 kb), uniform telomeres. Additionally, hTERT expression induced a more aggressive growth behavior in vitro and in vivo without altering the level of CIN. These data provide further evidence for a direct oncogenic activity of hTERT not based on the inhibition of CIN. (Cancer Res 2006; 66(7): 3584-92)
A marriage of mice produces answers to old questions about man
Authors: Allan Cooper
Journal: Hepatology (1994)

The atherogenic macromolecule lipoprotein(a) [Lp(a)] has resisted in vivo analyses partly because it is found in a limited number of experimental animals. Although transgenic mice expressing human apolipoprotein (a) [apo(a)] have previously been described, they failed to assemble Lp(a) particles because of the inability of human apo(a) to associate with mouse apolipoprotein B (apoB). We isolated a 90-kilobase P1 phagemid containing the human apoB gene and with this DNA generated 13 lines of transgenic mice of which 11 expressed human apoB. The human apoB transcript was expressed and edited in the liver of the transgenic mice. Plasma concentrations of human apoB, as well as low density lipoprotein (LDL), were related to transgene copy number; the transgenic line with the most copies of human apoB had a &gt;4-fold increase in LDL cholesterol compared with nontransgenics and a lipoprotein profile similar to that of humans. When human apoB and apo(a) transgenic mice were bred together, plasma apo(a) in mice expressing both human proteins was tightly associated with lipoproteins in the LDL density region. These studies demonstrate the successful expression of human apoB and the efficient assembly of Lp(a) in mice.
Rapid electrophysiological changes leading to arrhythmias in the aerobic rat heart. Photosensitization studies with rose bengal-derived reactive oxygen intermediates.
Authors: D J Hearse, Y Kusama, M Bernier
Journal: Circulation Research (1989)

The objective of this study was to determine whether reactive oxygen intermediates (e.g., singlet oxygen and the superoxide radical) can rapidly induce electrophysiological disturbances leading to the genesis of arrhythmias, even in the absence of ischemia and reperfusion. Rat hearts (n = 6 per group) were perfused aerobically at 37 degrees C for 10 minutes without rose bengal and for 5 minutes with rose bengal (250 nmol/l), during which time no changes in coronary flow or heart rate were observed. Hearts were then uniformly illuminated for 20 minutes with green light (530-590 nm) from 200 fiber optic cables. With light and without rose bengal, or vice versa, all hearts remained stable. However, in the illuminated rose bengal group, electrophysiological changes (inversion of the terminal portion of the T wave and an increase in Q-T interval) were observed within 11.8 +/- 2.1 seconds (i.e., less than 60 beats). All hearts exhibited ventricular premature beats (within 2.2 +/- 0.7 minutes) and ventricular tachycardia (within 2.8 +/- 0.7 minutes) before the occurrence of complete atrioventricular block (within 5.5 +/- 0.9 minutes). During the illumination period, coronary flow progressively fell in the rose bengal-perfused hearts from 11.6 +/- 0.5 ml/min to 2.0 +/- 0.4 ml/min (p less than 0.05 when compared with any control group). When a similar progressive reduction in coronary flow was mimicked (with or without rose bengal), no arrhythmias occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
Periodontal disease in patients with ankylosing spondylitis
Authors: N Pischon, T Pischon, E Gülmez, J Kröger, P Purucker, B-M Kleber, H Landau, P-G Jost-Brinkmann, P Schlattmann, J Zernicke, G-R Burmester, J-P Bernimoulin, F Buttgereit, J Detert
Journal: Annals of the Rheumatic Diseases (2009)

Objective: Ankylosing spondylitis (AS) and periodontal disease (PD) are characterised by dysregulation of the host inflammatory response, resulting in soft and hard connective tissue destruction. AS has been related to other inflammatory diseases, however, there is a paucity of data on whether AS is associated with inflammatory PD. Methods: The association between AS and PD was examined in 48 patients with AS and 48 healthy controls, matched for age and gender. AS was diagnosed according to the modified New York criteria. Periodontal examination included probing pocket depth (PPD), clinical attachment loss (CAL), plaque index (PI) and bleeding on probing (BOP). Potential risk factors of PD such as smoking, low education, alcohol consumption, body mass index (BMI), as well as chronic diseases associated with PD and AS were assessed through questionnaires. Results: In stepwise logistic regression, including AS status, age, gender, education, smoking, alcohol consumption and BMI, only AS status, age and education remained significant predictors of PD. Patients with AS had significant 6.81-fold increased odds (95% CI 1.96 to 23.67) of PD (defined as mean attachment loss &gt;3 mm) compared to controls. The strength of the association was attenuated but remained statistically significant after further adjustment for plaque accumulation (odds ratio (OR) 5.48, 95% CI 1.37 to 22.00). Conclusions: The present study shows that patients with AS have a significantly higher risk of PD, strongly suggesting the need for close collaboration between rheumatologists, periodontists and dental hygienists when treating patients with AS.