tbuckley/cabot-search huggingface dataset:
Chronic Arterial Responses to Polymer-Controlled Paclitaxel-Eluting Stents
Authors: Kengo Tanabe, Patrick W. Serruys, Muzaffer Degertekin, Giulio Guagliumi, Eberhard Grube, Charles Chan, Thomas Munzel, Jorge Belardi, Witold Ruzyllo, Luc Bilodeau, Henning Kelbaek, John Ormiston, Keith Dawkins, Louis Roy, Bradley H. Strauss, Clemens Disco, Jörg Koglin, Mary E. Russell, Antonio Colombo
Journal: Circulation (2003)

Polymer-controlled paclitaxel-eluting stents have shown a pronounced reduction in neointimal hyperplasia compared with bare metal stents (BMS). The aim of this substudy was to evaluate local arterial responses through the use of serial quantitative intravascular ultrasound (IVUS) analyses in the TAXUS II trial.TAXUS II was a randomized, double-blind study with 536 patients in 2 consecutive cohorts comparing slow-release (SR; 131 patients) and moderate-release (MR; 135 patients) paclitaxel-eluting stents with BMS (270 patients). This IVUS substudy included patients treated with one study stent who underwent serial IVUS examination after the procedure and at 6-month follow-up (BMS, 152 patients; SR, 81; MR, 81). The analyzed stented segment (15 mm) was divided into 5 subsegments in which mean vessel area (VA), stent area (SA), lumen area (LA), intrastent neointimal hyperplasia area (NIHA), and peristent area (VA-SA) were measured. NIHA was significantly reduced in SR (0.7+/-0.9 mm2, P<0.001) and MR (0.6+/-0.8 mm2, P<0.001) compared with BMS (1.9+/-1.5 mm2), with no differences between the two paclitaxel-eluting release formulations. Longitudinal distribution of neointimal hyperplasia throughout the paclitaxel-eluting stent was uniform. Neointimal growth was independent of peristent area at postprocedure examination in all groups. There were progressive increases in peristent area from BMS to SR to MR (0.5+/-1.7, 1.0+/-1.8, and 1.4+/-2.0 mm2, respectively; P<0.001). The increase in peristent area was directly correlated with increases in VA.Both SR and MR paclitaxel-eluting stents prevent neointimal formation to the same degree compared with BMS. However, the difference in peristent remodeling suggests a release-dependent effect between SR and MR.
Crucial timing in schizophrenia: role of DNA methylation in early neurodevelopment
Authors: Joanne Ryan, Richard Saffery
Journal: Genome biology (2014)

An exciting recent study examining the methylation profile of human brain tissue implicates early-life epigenetic disruption in the neurodevelopmental origin of schizophrenia. See related research, http://genomebiology.com/2014/15/10/483
Zebularine reactivates silenced E-cadherin but unlike 5-Azacytidine does not induce switching from latent to lytic Epstein-Barr virus infection in Burkitt's lymphoma Akata cells
Authors: Sieta P Rao, Markus P Rechsteiner, Christoph Berger, Jürg A Sigrist, David Nadal, Michele Bernasconi
Journal: Molecular Cancer (2007)

Abstract Epigenetic silencing of regulatory genes by aberrant methylation contributes to tumorigenesis. DNA methyltransferase inhibitors (DNMTI) represent promising new drugs for anti-cancer therapies. The DNMTI 5-Azacytidine is effective against myelodysplastic syndrome, but induces switching of latent to lytic Epstein-Barr virus (EBV) in vitro and results in EBV DNA demethylation with the potential of induction of lytic EBV in vivo . This is of considerable concern given that recurrent lytic EBV has been linked with an increased incidence of EBV-associated lymphomas. Based on the distinct properties of action we hypothesized that the newer DNMTI Zebularine might differ from 5-Azacytidine in its potential to induce switching from latent to lytic EBV. Here we show that both 5-Azacytidine and Zebularine are able to induce expression of E-cadherin , a cellular gene frequently silenced by hypermethylation in cancers, and thus demonstrate that both DNMTI are active in our experimental setting consisting of EBV-harboring Burkitt's lymphoma Akata cells. Quantification of mRNA expression of EBV genes revealed that 5-Azacytidine induces switching from latent to lytic EBV and, in addition, that the immediate-early lytic infection progresses to early and late lytic infection. Furthermore, 5-Azacytidine induced upregulation of the latent EBV genes LMP2A, LMP2B, and EBNA2 in a similar fashion as observed following switching of latent to lytic EBV upon cross-linking of the B-cell receptor. In striking contrast, Zebularine did not exhibit any effect neither on lytic nor on latent EBV gene expression. Thus, Zebularine might be safer than 5-Azacytidine for the treatment of cancers in EBV carriers and could also be applied against EBV-harboring tumors, since it does not induce switching from latent to lytic EBV which may result in secondary EBV-associated malignancies.
Acetylcholinesterase and lymphocyte function-associated antigen 3 found on decay-accelerating factor-negative erythrocytes from some patients with paroxysmal nocturnal hemoglobinuria are lost during erythrocyte aging
Authors: E Ueda, T Kinoshita, T Terasawa, T Shichishima, Y Yawata, K Inoue, T Kitani
Journal: Blood (1990)
Using an Epidemiological Model for Phylogenetic Inference Reveals Density Dependence in HIV Transmission
Authors: Gabriel E. Leventhal, Huldrych F. Günthard, Sebastian Bonhoeffer, Tanja Stadler
Journal: Molecular Biology and Evolution (2013)

The control, prediction, and understanding of epidemiological processes require insight into how infectious pathogens transmit in a population. The chain of transmission can in principle be reconstructed with phylogenetic methods which analyze the evolutionary history using pathogen sequence data. The quality of the reconstruction, however, crucially depends on the underlying epidemiological model used in phylogenetic inference. Until now, only simple epidemiological models have been used, which make limiting assumptions such as constant rate parameters, infinite total population size, or deterministically changing population size of infected individuals. Here, we present a novel phylogenetic method to infer parameters based on a classical stochastic epidemiological model. Specifically, we use the susceptible-infected-susceptible model, which accounts for density-dependent transmission rates and finite total population size, leading to a stochastically changing infected population size. We first validate our method by estimating epidemic parameters for simulated data and then apply it to transmission clusters from the Swiss HIV epidemic. Our estimates of the basic reproductive number R0 for the considered Swiss HIV transmission clusters are significantly higher than previous estimates, which were derived assuming infinite population size. This difference in key parameter estimates highlights the importance of careful model choice when doing phylogenetic inference. In summary, this article presents the first fully stochastic implementation of a classical epidemiological model for phylogenetic inference and thereby addresses a key aspect in ongoing efforts to merge phylogenetics and epidemiology.
Hypertension and Recovery After Nephrectomy
Authors: A. I. L. Maitland
Journal: BMJ (1949)

and Conclusions In this series of observations all the rats in which a severe degree of residual renal damage was produced by a short period of choline deficiency during early life later developed a definite hypertension.The average blood pressure of this test series was 195 mm.Hg as determined by arterial cannulization, while that of the controls was 118 mm.Hg.The average weight of the hearts of the hypertensive animals was almost double that of the controls.The histological picture of the arterioles of these animals was charac- teristic of advanced hypertension.When only a moderate degree of residual kidney damage was produced by choline deficiency the hyper- tension, cardiac hypertrophy, and other pathological changes were correspondingly less.There is no apparent immediate ciinical application of these findings.Our results suggest that further work may provide a simple way of consistently producing hypertension in an experimental animal by dietary means.
Adalimumab: a new modality for Behcet's disease?
Authors: J A M van Laar, T Missotten, P L A van Daele, A Jamnitski, G S Baarsma, P M van Hagen
Journal: Annals of the Rheumatic Diseases (2006)

Aberrant T cell function,1 subsequently accompanied by increased tumour necrosis factor α (TNFα) levels, induces inflammatory symptoms in patients with Behcet’s disease (BD).2 Subsequently, treatment usually involves T cell-directed immunosuppressive or anti-TNFα treatment in patients with severe disease.3–7 Administration of the new human monoclonal TNFα antibody adalimumab has only been described in three patients with BD with uveitis.8 We analysed the effects of adalimumab on severe and often chronic disease in six heavily pretreated patients with BD in whom immunosuppressive therapy had failed (table 1).

View this table:

 Table 1  
 Clinical effects in patients treated with infliximab or adalimumab for Behcet’s disease



These patients were treated in the past with infliximab.9 Indications for anti-TNFα treatment …
New Concepts in the Treatment of Rheumatoid Arthritis
Authors: Raphaela Goldbach-Mansky, Peter E. Lipsky
Journal: Annual Review of Medicine (2003)

Recent advances have made rheumatoid arthritis (RA) amenable to treatment. Clinical studies in patients with early and established RA have broadened understanding of its pathogenesis and have fundamentally changed the therapeutic approach to this disease. Quantum leaps in therapy—including the use of early, aggressive therapy, combination therapy, and the introduction of anti-cytokine agents—have improved patients' quality of life, eased clinical symptoms, retarded the progression of joint destruction, and delayed disability. We review clinical evidence supporting these therapeutic approaches. Diagnostic and therapeutic challenges are highlighted, and a decision tree to guide treatment in patients with early or established RA is provided.
Kinetics of restitution of left ventricular relaxation.
Authors: S D Prabhu, G L Freeman
Journal: Circulation Research (1992)

Although the kinetics of cardiac systolic force restitution have been well described, the restitution kinetics of left ventricular relaxation have not been examined. To define relaxation restitution behavior, we studied seven dogs chronically instrumented with left ventricular high-fidelity micromanometers and piezoelectric dimension crystals. After a priming period at a basic cycle length of 375 msec, test extrastimuli were introduced after a range of extrasystolic intervals (ESIs). Relaxation behavior of control and extrasystolic beats was characterized by the time constant of isovolumic relaxation, tau. Relaxation restitution can be described by two concatenated monoexponential curves, an early phase described by a rapid time constant and a late phase described by a slower time constant (TC1, 36.21 +/- 7.90 msec; TC2, 75.94 +/- 10.65 msec; p less than 0.05). The first phase of relaxation restitution parallels systolic force restitution over the same range and displays faster recovery (TCs, 58.93 +/- 10.01 msec, p less than 0.05). Postextrasystolic restitution of test pulses after beats at fixed ESIs depends on the initial ESI. Relaxation recovery of postextrasystolic beats proceeds faster with smaller initial ESIs (TC1 for ESI of 300 msec, 13.27 +/- 4.05 msec; TC1 for ESI of 450 msec, 72.85 +/- 21.72 msec; p less than 0.0001). The monoexponential pattern of restitution was seen with model-independent descriptors of relaxation as well as with tau.
Reduction of Vein Graft Disease Using Photodynamic Therapy with Motexafin Lutetium in a Rodent Isograft Model
Authors: A Yamaguchi, K W Woodburn, M Hayase, R C Robbins
Journal: Circulation (2000)

Motexafin lutetium (Lu-Tex) is a photosensitizer that targets atheromatous plaque. Subsequent photoactivation (photodynamic therapy [PDT]) induces local cytotoxic effects. The aim of the present study was to investigate whether Lu-Tex targets vein graft intimal hyperplasia and whether subsequent photoactivation attenuates the disease process.The subcellular localization of Lu-Tex and postillumination viability were studied in cultured human vein graft smooth muscle cells. Inferior vena cava-grafted rats were injected with Lu-Tex (10 mg/kg) 4 or 12 weeks after grafting. Biodistribution was assessed in a subgroup 24 hours after administration. Light therapy (742 nm) was performed 24 hours after Lu-Tex injection by illuminating intraperitoneally placed isografts using a laparotomy. Animals were divided into the following 4 groups: PDT (n=15), Lu-Tex injection and laparotomy (n=13), light treatment (n=14), and laparotomy only (n=13). Grafts were harvested 14 days after treatment for histochemical analysis. Lu-Tex localized within subcellular organelles of smooth muscle cells, and subsequent photoactivation induced cell death via apoptosis. The Lu-Tex concentrations present in the vein grafts were 9.3 times higher than those in the normal inferior vena cava. Postoperative PDT at 4 weeks after surgery significantly reduced the intima/media ratio, whereas treatment at 12 weeks did not reduce the intima/media ratio. Activated macrophages were observed 4 weeks after grafting; however, a significant reduction occurred in these cells by 12 weeks. The mechanism by which PDT works may be related to the presence of activated macrophages.PDT significantly reduces the intima/media ratio in the early phase of vein graft disease. Lu-Tex-mediated PDT may be a viable method for the attenuation of atherosclerotic disease in vein grafts.
Hepatitis C virus(HCV) infection in a community in the nile delta: Population description and HCV prevalence
Authors: Fatma Abdel-Aziz, Mostafa Habib, Mostafa K. Mohamed, Mohamed Abdel-Hamid, Foda Gamil, Salah Madkour, Nabiel N. Mikhail, David Thomas, Alan D. Fix, Thomas G. Strickland, Wagida Anwar, Ismail Sallam
Journal: Hepatology (2000)

This report describes a cross-sectional survey of the prevalence of antibodies to hepatitis C virus (anti-HCV) in a rural Egyptian community in the Nile Delta. One half of the village households were systematically selected and examined by questionnaire and testing sera for anti-HCV and HCV RNA. Blood samples were obtained from 3, 888 (75.4%) of 5,156 residents >/=5 years of age; an additional 111 samples were obtained from children younger than 5 years. Overall, 973 (24.3%) of 3,999 residents were anti-HCV-positive, and the age- and gender-adjusted seroprevalence was 23.7%. Anti-HCV prevalence increased sharply with age, from 9.3% in those 20 years of age and younger to >50% in those older than 35 years. Currently or previously married individuals were more likely to be seropositive than those never married, controlling for age (Mantel-Haenszel risk ratio = 1.8; 95% CI: 1.3, 2.6). Of the 905 anti-HCV-positive samples tested, 65% were also positive for HCV RNA. Active schistosomal infection was not associated with anti-HCV status; however, history of antischistosomal injection therapy (reported by 19% of anti-HCV positives) was a risk for anti-HCV (age-adjusted risk ratio = 1.3; 95% CI: 1.2, 1.5). This study, the largest community-based survey to date, supports earlier reports of high levels of anti-HCV among adults in rural areas of Egypt, although many of those who are seropositive will not have active liver disease. The large reservoir of HCV infection in the community provides an opportunity to investigate risk factors for transmission, the natural history of infection and effectiveness of preventive methodologies, and raises concern about the prospect of an increasing incidence of chronic liver disease in the coming decades.
Angiotensin II Stimulates c-Jun NH <sub>2</sub> -Terminal Kinase in Cultured Cardiac Myocytes of Neonatal Rats
Authors: Sumiyo Kudoh, Issei Komuro, Takehiko Mizuno, Tsutomu Yamazaki, Younzeng Zou, Ichiro Shiojima, Noboru Takekoshi, Yoshio Yazaki
Journal: Circulation Research (1997)

Many lines of evidence have suggested that angiotensin II (Ang II) plays an important role in cardiac hypertrophy. Ang II not only increases protein synthesis but also induces the reprogramming of gene expression in cultured cardiac myocytes. In the present study, to elucidate the mechanism by which Ang II regulates gene expression in cardiac myocytes, we examined whether Ang II activates c-Jun NH 2 -terminal kinase (JNK), which is a member of the mitogen-activated protein kinase family and activates the transcription factor, activator protein-1 (AP-1). The activity of JNK increased 5 minutes after the addition of Ang II, peaked at 20 minutes, and gradually decreased thereafter. Examination of the Ang II dose-response relation revealed detectable JNK activation at 10 −9 mol/L and maximal activation at 10 −6 mol/L. Ang II activated JNK through the AT 1 receptor, and the activation was attenuated by the downregulation of protein kinase C or the chelation of intracellular Ca 2+ . Although the addition of either Ca 2+ ionophore or phorbol ester resulted in little or no activation of JNK, simultaneous addition of both Ca 2+ ionophore and phorbol ester markedly activated JNK. Slight expressions of the c- jun gene were observed in unstimulated cardiac myocytes, and Ang II increased expressions of the c- jun gene as well as the c- fos gene. Ang II increased transcription of the endothelin-1 gene through the AP-1 binding site. In conclusion, Ang II may activate JNK in cultured cardiac myocytes through an increase in intracellular Ca 2+ and activation of protein kinase C, and the activated JNK may regulate gene expression by activating AP-1 during Ang II–induced cardiac hypertrophy.
ABORTION with SEPTICAeMIA: TREATMENT by ANTISTREPTOCOCCUS SERUM: RECOVERY
Authors: J. M. Campbell
Journal: BMJ (1898)

pregnant two months with her third child, was first seen on September 20th, complaining of severe vomiting, which had existed throughout the pregnancy, but had latterly become much worse.The tongue was clean, the abdomen not at all tender, the temperature normal, and no evidence was found of any internal abnormality.Treatment
Effect of Doxorubicin Plus Cyclophosphamide on Left Ventricular Ejection Fraction in Patients With Breast Cancer in the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial
Authors: Edith A. Perez, Vera J. Suman, Nancy E. Davidson, Peter A. Kaufman, Silvana Martino, Shaker R. Dakhil, James N. Ingle, Richard J. Rodeheffer, Bernard J. Gersh, Allan S. Jaffe
Journal: Journal of Clinical Oncology (2004)

Purpose To evaluate changes in left ventricular ejection fraction (LVEF) after four cycles of adjuvant doxorubicin plus cyclophosphamide (AC) in women with human epidermal growth factor receptor 2–positive (node-positive or node-negative) breast cancer enrolled onto the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial. Patients and Methods Patients were randomly assigned to receive standard doxorubicin (60 mg/m 2 ) plus cyclophosphamide (600 mg/m 2 ) every 3 weeks for four cycles followed by (1) weekly paclitaxel for 12 weeks; (2) weekly paclitaxel for 12 weeks, then weekly trastuzumab for 52 weeks; or (3) weekly paclitaxel plus trastuzumab for 12 weeks, then weekly trastuzumab for 40 weeks. LVEF was monitored before and after AC. Results Of the 1,576 eligible patients who completed AC, 1,458 had pre- and post-AC LVEF measurements taken using the same methodology (multiple-gated acquisition in 1,153 patients and echocardiogram in 305 patients). Among these 1,458 patients, 745 (51.1%) had ≤ 15% decrease in LVEF and LVEF that remained at or above the radiologic lower limit of normal (LLN); 42 patients (2.9%) had ≤ 15% decrease in LVEF and LVEF that decreased to or below the LLN; and 37 patients (2.5%) had an LVEF decrease of more than 15%. There was grade 2 LVEF toxicity in 96 (6.6%) of the 1,458 patients. Conclusion Standard AC chemotherapy is associated with frequent decreases in LVEF, which are noted when measured 3 weeks after completion of the fourth cycle. Patients are being observed to determine the long-term significance of this and the potential impact on subsequent treatment options.
A childhood subepidermal autoimmune bullous disease resembling mechanobullous epidermolysis bullosa acquisita
Authors: P. Agrawal, R. George, M. Thomas, C. Has, H. Pas, E. Schmidt, M. Leverkus
Journal: British Journal of Dermatology (2015)

Journal Article A childhood subepidermal autoimmune bullous disease resembling mechanobullous epidermolysis bullosa acquisita Get access P. Agrawal, P. Agrawal Department of Dermatology, Venereology and Leprosy Christian Medical College and Hospital Vellore 632004 India Search for other works by this author on: Oxford Academic Google Scholar R. George, R. George Department of Dermatology, Venereology and Leprosy Christian Medical College and Hospital Vellore 632004 India Search for other works by this author on: Oxford Academic Google Scholar M. Thomas, M. Thomas Department of Pathology Christian Medical College and Hospital Vellore 632004 India Search for other works by this author on: Oxford Academic Google Scholar C. Has, C. Has Department of Dermatology University of Freiburg Freiburg Germany Search for other works by this author on: Oxford Academic Google Scholar H. Pas, H. Pas Department of Dermatology University Medical Centre Groningen Groningen the Netherlands Search for other works by this author on: Oxford Academic Google Scholar E. Schmidt, E. Schmidt Department of Dermatology University Hospital Schleswig‐Holstein Campus Lübeck Ratzeburger Allee 160 Lübeck 23538 Germany Search for other works by this author on: Oxford Academic Google Scholar M. Leverkus M. Leverkus Section of Molecular Dermatology Department of Dermatology, Venereology and Allergology University Hospital Mannheim University of Heidelberg Theodor‐Kutzer‐Ufer 1–3 Mannheim 68167 Germany Correspondence: Martin Leverkus. E‐mail: mleverkus@ukaachen.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 3, 1 September 2015, Pages 871–874, https://doi.org/10.1111/bjd.13833 Published: 01 September 2015
Enhanced neutrophilic inflammation in IL-10-deficient mice exposed to cigarette smoke via TNF-α regulation
Authors: Manabu Higaki, Hiroo Wada, Shin-ichiro Mikura, Tetsuo Yasutake, Masuo Nakamura, Mamoru Niikura, Fumie Kobabyashi, Hiroshi Kamma, Shigeru Kamiya, Hajime Takizawa, Hajime Goto
Journal: European Respiratory Journal (2012)

BACKGROUND  We established a mouse model of short-term cigarette smoke (CS) exposure, which shares common molecular features with COPD patients. Interleukin (IL) -10 has a suppressive effect on inflammatory reactions and we previously presented that nasal administration of IL-10 attenuated CS-induced neutrophil recruitment to the lung (Higaki et al., ERS 2011). The effect of IL-10 on cigarette smoke-induced inflammation was investigated, using IL-10-deficient mice.   METHODS  Both IL-10-deficient mice and wild-type mice were exposed to CS. Total cell counts, as well as cell defferentiations, in bronchoalveolar lavage (BAL) fluid were determined. TNF-α GM-CSF, and KC mRNA levels in lung tissue were estimated using quantitative RT-PCR. MMP-9 expression in lung tissue was investigated by immunohistochemical analysis.   RESULTS & DISCUSSION  CS exposure significantly enhanced recruitment of neutrophils and macrophages to the lung (p   CONCLUSION  Our result indicated that anti-inflammatory effect of IL-10 on CS-induced inflammatory reactions, espicially neutrophilic recruitment to the lung, is probably via reducing TNF-α levels.