tbuckley/cabot-search huggingface dataset:
Nonuniform Strut Distribution Correlates With More Neointimal Hyperplasia After Sirolimus-Eluting Stent Implantation
Authors: Hideo Takebayashi, Gary S. Mintz, Stéphane G. Carlier, Yoshio Kobayashi, Kenichi Fujii, Takenori Yasuda, Ricardo A. Costa, Issam Moussa, George D. Dangas, Roxana Mehran, Alexandra J. Lansky, Edward Kreps, Michael B. Collins, Antonio Colombo, Gregg W. Stone, Martin B. Leon, Jeffrey W. Moses
Journal: Circulation (2004)

Little is known about causes of intimal hyperplasia (IH) after sirolimus-eluting stent (SES) implantation.Intravascular ultrasound was performed in 24 lesions with intra-SES restenosis and a comparison group of 25 nonrestenotic SESs. To assess stent strut distribution, the maximum interstrut angle was measured with a protractor centered on the stent, and the visible struts were counted and normalized for the number of stent cells. In SES restenosis patients, minimum lumen site was compared with image slices 2.5, 5.0, 7.5, and 10.0 mm proximal and distal to this site. The minimum lumen site had a smaller IVUS lumen area at follow-up (2.7+/-0.9 versus 6.2+/-1.9 mm2; P<0.01), larger maximum interstrut angle (135+/-39 degrees versus 72+/-23 degrees; P<0.01), larger IH area (3.4+/-1.5 versus 0.6+/-1.1 mm2; P<0.01) and thickness (0.7+/-0.3 versus 0.1+/-0.2 mm; P<0.01) at maximum interstrut angle, and fewer stent struts (4.9+/-1.0 versus 6.0+/-0.5; P<0.01) even when normalized for the number of stent cells (0.78+/-0.15 versus 0.97+/-0.07; P<0.01). Compared with nonrestenotic SES, the restenosis lesions also had a smaller minimal lumen area, larger IH area, thicker IH at maximum interstrut angle, fewer stent struts, and larger maximum interstrut angle. Multivariate analysis identified the number of visualized stent struts normalized for the number of stent cells and maximum interstrut angle as the only independent IVUS predictor of IH cross-sectional area (P<0.01 and P<0.01), minimum lumen area (P<0.01 and P<0.01), and IH thickness (P<0.01 and P<0.01).The number and distribution of stent struts affect the amount of neointima after SES implantation.
Nosocomial Transmission of Tuberculosis in a Hospital Unit for HIV-lnfected Patients
Authors: Samuel W. Dooley
Journal: JAMA (1992)

<h3>Objective.</h3> —To assess nosocomial transmission of tuberculosis (TB). Design.—A historical cohort study of hospitalized patients with the human immunodeficiency virus (HIV) and a purified protein derivative (PPD) tuberculin skin test survey of health care workers (HCWs). <h3>Setting.</h3> —A large public teaching hospital in San Juan, Puerto Rico. <h3>Patients.</h3> —For the cohort study, a case patient was defined as any patient in the HIV unit at the hospital who developed culture-positive TB from 31 days or more after admission through December 31, 1989. For the PPD survey, of 1420 HCWs from the hospital, 908 agreed to participate and had sufficient data for analysis. <h3>Main Outcome Measures.</h3> —For the cohort study, to compare the risk of developing active TB among patients who were exposed to hospital roommates with infectious TB and the risk among nonexposed patients. For the HCW PPD survey, to determine the prevalence of and risk factors for tuberculous infection. <h3>Results.</h3> —Eight of 48 (9.7/10000 person-days) exposed case patients vs four of 192 (0.8/10000 person-days) nonexposed case patients developed active TB (relative risk [RR]=11; 95% confidence interval [CI], 2.3, 50.3). Positive PPDs (≥10 mm of induration) in HCWs were associated with older age (<i>P</i>=.0001) and with history of community TB exposure (<i>P</i>=.0002). In a multivariable logistic model that adjusted for these variables, HIV unit nurses (nine of 19) and nurses in the internal medicine ward (45 of 90) had a higher proportion of positive PPDs than the reference group (clerical personnel on other floors: 35 of 188,<i>P</i>=.0005). <h3>Conclusions.</h3> —These data suggest that patient-to-patient transmission of TB in HIV units can occur and that HCWs are at risk of acquiring TB infection. (<i>JAMA</i>. 1992;267:2632-2635)
Metabolic Regulation and Function of Glutathione Peroxidase-1
Authors: Xin Gen Lei, Wen-Hsing Cheng, James P. McClung
Journal: Annual Review of Nutrition (2007)

Glutathione peroxidase-1 (GPX1) represents the first identified mammalian selenoprotein, and our understanding in the metabolic regulation and function of this abundant selenoenzyme has greatly advanced during the past decade. Selenocysteine insertion sequence-associating factors, adenosine, and Abl and Arg tyrosine kinases are potent, Se-independent regulators of GPX1 gene, protein, and activity. Overwhelming evidences have been generated using the GPX1 knockout and transgenic mice for the in vivo protective role of GPX1 in coping with oxidative injury and death mediated by reactive oxygen species. However, GPX1 exerts an intriguing dual role in reactive nitrogen species (RNS)-related oxidative stress. Strikingly, knockout of GPX1 rendered mice resistant to toxicities of drugs including acetaminophen and kainic acid, known as RNS inducers. Intracellular and tissue levels of GPX1 activity affect apoptotic signaling pathway, protein kinase phosphorylation, and oxidant-mediated activation of NFkappaB. Data are accumulating to link alteration or abnormality of GPX1 expression to etiology of cancer, cardiovascular disease, neurodegeneration, autoimmune disease, and diabetes. Future research should focus on the mechanism of GPX1 in the pathogeneses and potential applications of GPX1 manipulation in the treatment of these disorders.
Familial Lung Adenocarcinoma Caused by the <i>EGFR</i> V843I Germ-Line Mutation
Authors: Kouki Ohtsuka, Hiroaki Ohnishi, Daisuke Kurai, Satsuki Matsushima, Yukio Morishita, Mayumi Shinonaga, Hajime Goto, Takashi Watanabe
Journal: Journal of Clinical Oncology (2010)
Virus-specific CD4+ T cells: ready for direct attack
Authors: Kevin N. Heller, Cagan Gurer, Christian Münz
Journal: The Journal of Experimental Medicine (2006)

CD4+ T cells are classically thought to orchestrate adaptive immune responses. But recent studies demonstrate that they can also kill infected cells directly. A new paper shows that highly efficient processing of Epstein Barr virus (EBV) glycoproteins for presentation on MHC class II makes virus-transformed B cells susceptible to lysis by CD4+ T cells. Thus, antiviral vaccines should aim to stimulate both helper and cytolytic CD4+ T cells.
AMPK Activation by Oncogenesis Is Required to Maintain Cancer Cell Proliferation in Astrocytic Tumors
Authors: Marcos Ríos, Marc Foretz, Benoit Viollet, Angel Prieto, Máximo Fraga, Jose A. Costoya, Rosa Señarís
Journal: Cancer Research (2013)

5'-AMP-activated protein kinase (AMPK) is an energy sensor that controls cell metabolism, and it has been related to apoptosis and cell-cycle arrest. Although its role in metabolic homeostasis is well documented, its function in cancer is much less clear. In this study, we examined the role of AMPK in a mouse model of astrocytoma driven by oncogenic H-Ras(V12) and/or with PTEN deletion based on the common constitutive activation of the Raf/MEK/ERK and PI3K/AKT cascades in human astrocytomas. We also evaluated the activity and role of AMPK in human glioblastoma cells and xenografts. AMPK was constitutively activated in astrocytes expressing oncogenic H-Ras(V12) in parallel with high cell division rates. Genetic deletion of AMPK or attenuation of its activity in these cells was sufficient to reduce cell proliferation. The levels of pAMK were always related to the levels of phosphorylated retinoblastoma (Rb) at Ser804, which may indicate an AMPK-mediated phosphorylation of Rb. We confirmed this AMPK-Rb relationship in human glioblastoma cell lines and xenografts. In clinical specimens of human glioblastoma, elevated levels of activated AMPK appeared especially in areas of high proliferation surrounding the blood vessels. Together, our findings indicate that the initiation and progression of astrocytic tumors relies upon AMPK-dependent control of the cell cycle, thereby identifying AMPK as a candidate therapeutic target in this setting.
Lower airway responses to rhinovirus 39 in healthy allergic and nonallergic subjects
Authors: D.P. Skoner, W.J. Doyle, J. Seroky, M.A. Van Deusen, P. Fireman
Journal: European Respiratory Journal (1996)

Acute asthma is considered to be a complication of respiratory viral infections. This investigation assessed the effects of rhinovirus 39 (RV-39) infection both on the patency and responsiveness of the lower airways. Subjects with allergic rhinitis (AR; n = 50) and without AR (non-AR; n = 46) were intranasally inoculated with RV-39, and monitored for 8 days in an enclosed environment for changes in symptoms, signs, and airway physiology (pulmonary function, bronchial methacholine provocation). All subjects were infected postinoculation. Significant increases in nasal symptoms and secretion weights were observed, with peak effects on days 2-3. Cough was a relatively minor symptom and none of the subjects developed wheezing. Likewise, there were no significant changes in the measured functions of the lower airways. No allergy status effects were observed. Under these experimental conditions, rhinovirus 39 infection did not produce detectable alterations in lower airway function in healthy subjects with and without allergic rhinitis.
Catechins prevent vascular smooth muscle cell invasion by inhibiting MT1-MMP activity and MMP-2 expression
Authors: J ELBEDOUI, M OAK, P ANGLARD, V SCHINIKERTH
Journal: Cardiovascular Research (2005)

Objective: Regular consumption of green tea is associated with a reduced risk of mortality due to coronary diseases and cancer. The present study examined whether a green tea extract (GTE) inhibits activation of matrix metalloproteinase-2 (MMP-2), a major collagenase involved in vascular remodeling of atherosclerotic plaques, in vascular smooth muscle cells (VSMCs). Methods and results: The expression of MMP-2 was assessed by Northern and Western blot analyses in human aortic VSMCs. MMP-2 activity was evaluated by zymography, membrane-type1-MMP (MT1-MMP, MMP-14) activity by an enzymatic assay, and cell invasion by a modified Boyden chamber assay. The thrombin-induced activation of secreted MMP-2 was abolished by GTE and the green tea polyphenols (−)-epigallocatechin-3-gallate (EGCG) and (−)-epicatechin-3-gallate (ECG). GTE reduced the expression of MMP-2 mRNA and protein. GTE, EGCG and ECG directly inhibited cell-associated MT1-MMP activity, the physiological activator of MMP-2, in a reversible manner. Thrombin-stimulated VSMCs invasion was abolished by EGCG and ECG, and reduced by GTE. Conclusions: GTE inhibits thrombin-induced VSMCs invasion most likely by preventing MMP-2 expression and its activation by a direct inhibition of MT1-MMP. The ability of green tea to prevent cell invasion and matrix degradation might contribute to its protective effect on atherosclerosis and cancer.
Increasing incidence of bullous pemphigoid in Northern Finland: a retrospective database study in Oulu University Hospital
Authors: A.‐K. Försti, J. Jokelainen, M. Timonen, K. Tasanen
Journal: British Journal of Dermatology (2014)

Background Bullous pemphigoid (BP) is an autoimmune blistering skin disease of elderly people. Some studies have suggested that the incidence of BP has increased, but the diagnostic accuracy and methodology of studies have varied considerably. Objectives To examine the incidence of BP in Northern Finland, and whether the incidence has changed over time. Methods This was a retrospective database study of all BP cases diagnosed in the Oulu University Hospital, Finland between 1985 and 2009. The diagnostic criteria were clinical features characteristic of BP (all patients) and positive direct or indirect immunofluorescence in the skin biopsy. The age-standardized incidences were calculated by the direct standardization method. Incidence rate ratios (IRR) were estimated by the Poisson regression model. To derive adjusted IRRs, age and sex were used as potential confounding factors. Results The crude incidence of BP was 17 per 1 million person-years [95% confidence interval (CI) 15–20] between 1985 and 2009. Using the general European population as a reference, the age-standardized incidence was 14 per 1 million person-years (95% CI 12–17). The incidence of BP increased 1·8-fold (IRR 1·8, 95% CI 1·3–2·6; P < 0·001) in 2005–09 compared with the mean incidence of BP between 1985 and 2004, but after the adjustment for age and sex the increase was 1·4-fold (IRR 1·4, 95% CI 1·0–2·0; P = 0·043). Conclusions This is the first study with immunohistologically verified BP diagnoses that reports the increase in the incidence of BP in age- and sex-adjusted populations.
Synergistic Interactions between Tamoxifen and Trastuzumab (Herceptin)
Authors: Athanassios Argiris, Chun-Xia Wang, Steve G. Whalen, Michael P. DiGiovanna
Journal: Clinical Cancer Research (2004)

Abstract Purpose: HER-2/neu and estrogen receptor (ER) are critical in the biology of breast carcinoma, and both are validated therapeutic targets. Extensive interactions between the signaling pathways of these receptors have been demonstrated. This suggests that targeting both receptors simultaneously may have a dramatic effect on the biology of breast cancer. This hypothesis was tested in cell culture experiments. Experimental Design: ER-positive, HER-2/neu-overexpressing BT-474 human breast carcinoma cells were cultured in the presence of the anti-HER-2/neu therapeutic antibody trastuzumab (Herceptin), the antiestrogen tamoxifen, or both. The effects on cell growth, cell cycle distribution, clonogenicity, survival, and the level and activity of HER-2/neu were examined. Results: The combination of tamoxifen and Herceptin resulted in synergistic growth inhibition and enhancement of cell accumulation in the G0-G1 phase of the cell cycle, with a decrease in cells in S phase. Clonogenicity was inhibited in the presence of each drug and more so by the combination, although prior exposure to drugs did not affect subsequent clonogenicity in drug-free media, and neither drug nor the combination induced apoptosis. Herceptin, but not tamoxifen, inhibited signaling by HER-2/neu. Conclusions: The combination of tamoxifen and Herceptin is formally demonstrated to result in synergistic growth inhibition and enhancement of G0-G1 cell cycle accumulation. In vitro, the individual drugs or combination produces a cytostatic effect. These results suggest that combined inhibition of ER and HER-2/neu signaling may represent a powerful approach to the treatment of breast cancer.
Increased In Vivo Expression and Production of Endothelin-1 by Porcine Cardiomyocytes Subjected to Ischemia
Authors: Theis Tønnessen, Adel Giaid, Dina Saleh, Pål A. Naess, Masashi Yanagisawa, Geir Christensen
Journal: Circulation Research (1995)

Abstract Circulating levels of the endothelium-derived vasoconstrictor peptide endothelin-1 (ET-1) are increased in association with myocardial ischemia and infarction. The present study investigates whether ET-1 is synthesized and produced locally in the ischemic heart. Sixteen pigs were divided into three groups. In the first group, the left anterior descending coronary artery was occluded for 90 minutes, followed by 150 minutes of reperfusion (group A, n=8). Two additional groups were subjected to 90 minutes (group B, n=4) or 240 minutes (group C, n=4) of ischemia without reperfusion. Biopsies from the nonischemic and ischemic myocardium were rapidly obtained from the beating heart and subsequently examined by Northern blot, in situ hybridization, and immunohistochemistry. Arterial plasma ET-1 was measured before ischemia and at the end of the experiments. Northern blot revealed a twofold increase in ET-1 mRNA in the ischemic myocardium compared with the nonischemic myocardium. In situ hybridization showed a considerable increase in ET-1 mRNA over the ischemic cardiomyocytes. Substantial ET-1–like immunoreactivity (ET-1-ir) was detected in cardiomyocytes in the ischemic region. In contrast, little or no ET-1-ir or mRNA was detected in nonischemic cardiomyocytes. Both in the ischemic and nonischemic regions, little ET-1-ir was detected in vascular endothelial cells or vascular smooth muscle cells. There was no difference in the intensity and distribution of ET-1 mRNA expression or ET-1-ir among experimental groups A, B, and C. Arterial plasma ET-1 was increased only in group A, the reperfused group. In conclusion, these findings provide a definitive evidence for a de novo synthesis of ET-1 by cardiomyocytes subjected to ischemia in vivo.
Blood-Derived Progenitor Cells After Recanalization of Chronic Coronary Artery Occlusions in Humans
Authors: James T. Willerson, Edward T.H. Yeh, Yong-Jian Geng, Emerson C. Perin
Journal: Circulation Research (2005)

he first studies to treat patients with acute ST segment elevation myocardial infarction were by Strauer et al and Zeiher et al. 1,2 In these studies, percutaneous transluminal coronary angioplasty (PTCA) was used to open the infarct related artery, and bone marrow-derived mononuclear cells or circulating endothelial progenitor cells were injected into the infarct-related arteries. 1,2The cell-based therapy in these 2 initial studies improved coronary blood flow and segmental left ventricular (LV) function in the treated regions.Wollert et al subsequently reproduced the earlier findings in a blinded randomized study, again in patients with acute ST segment elevation myocardial infarcts (MIs). 3These 3 studies were the first to treat patients with acute ST segment elevation MIs after PTCA with cell-based therapy, and each used intracoronary injections in patients who did not have severe heart failure.At the same time that Strauer et al and Zeiher et al were performing their initial studies in Germany (2000 -2002), Texas Heart Institute cardiologists, Drs Perin and Willerson and Brazilian cardiologists led by Dr Dohmann in Rio de Janeiro, Brazil, were treating patients with chronic coronary heart disease, prior myocardial infarction, and severe heart failure with transendocardial injections of bone marrowderived mononuclear cells using electromechanical mapping to identify sites of reversible myocardial injury. 4This was the initial study in the world done with cell-based therapy for patients with severe heart failure with direct transendocardial injections of bone marrow-derived mononuclear cells into the human heart.We also reported improved coronary blood flow and segmental and global LV function within two months after the cell-based treatment. 4The imaging results in these patients suggesting improved coronary blood flow were confirmed by postmortem examination in 1 patient who died of a seizure 11 months after treatment. 5New blood vessel formation and new myocytes in the treated region were found at post-mortem examination in this patient. 5rbs et al, in this issue of Circulation Research, present a randomized blinded study in humans with chronic coronary artery occlusions but without heart failure. 6The occluded
Regulation of nuclear factor of activated T cells by phosphotyrosyl-specific phosphatase activity: a positive effect on HIV-1 long terminal repeat–driven transcription and a possible implication of SHP-1
Authors: Jean-François Fortin, Benoit Barbeau, Gilles A. Robichaud, Marie-Ève Paré, Anne-Marie Lemieux, Michel J. Tremblay
Journal: Blood (2001)
Phase I study of MEN-10755, a new anthracycline in patients with solid tumours: a report from the European Organization for Research and Treatment of Cancer, Early Clinical Studies Group
Authors: D. Schrijvers, A.M.E. Bos, J. Dyck, E.G.E. de Vries, J. Wanders, M. Roelvink, P. Fumoleau, S. Bortini, J.B. Vermorken
Journal: Annals of Oncology (2002)
BIOMECHANICAL CONSIDERATIONS IN THE DESIGN OF GRAFT: THE HOMEOSTASIS HYPOTHESIS
Authors: Ghassan S. Kassab, José A. Navia
Journal: Annual Review of Biomedical Engineering (2006)

Since its inception in the 1960s, coronary artery bypass graft (CABG) evolved as one of the most common, best documented, and most effective of all major surgical treatments for ischemic heart disease. Despite its widespread use, however, the outcome is not always completely satisfactory. The objective of this review is to highlight the physical determinants of biomechanical design of CABG so that future procedures would have prolonged patency and better outcome. Our central axiom postulates the existence of a mechanical homeostatic state of the blood vessel, i.e., the variation in vessel wall stresses and strains are relatively small under physiological conditions. Any perturbation of mechanical homeostasis leads to growth and remodeling. In this sense, stenosis and failure of a graft may be viewed as an adaptation process gone awry. We outline the principles of engineering design and discuss the biofluid and biosolid mechanics principles that may have the greatest bearing on mechanical homeostasis and the long-term outcome of CABG.
Real-Time Electronic Ambulatory Monitoring of Substance Use and Symptom Expression in Schizophrenia
Authors: Joel Swendsen, Dror Ben-Zeev, Eric Granholm
Journal: American Journal of Psychiatry (2010)

Despite evidence demonstrating elevated comorbidity between schizophrenia and substance use disorders, the underlying mechanisms of association remain poorly understood. The brief time intervals that characterize interactions between substance use and psychotic symptoms in daily life are inaccessible to standard research protocols. The authors used electronic personal digital assistants (PDAs) to examine the temporal association of diverse forms of substance use with psychotic symptoms and psychological states in natural contexts. Of 199 community-dwelling individuals with schizophrenia or schizoaffective disorder who were contacted to participate in the study, 92% accepted and 73% completed the study. The 145 participants who completed the study provided reports of substance use, psychotic symptoms, mood, and event negativity multiple times per day over 7 consecutive days through PDAs. Participants responded to 72% of the electronic interviews (N=2,737) across daily life contexts. Strong within-day prospective associations were observed in both directions between substance use and negative psychological states or psychotic symptoms, but considerable variation was observed by substance type. Consistent with the notion of self-medication, alcohol use was most likely to follow increases in anxious mood or psychotic symptoms. Cannabis and other illicit substances, demonstrating more complex patterns, were more likely to follow certain psychological states but were also associated with the later onset of psychotic symptoms. The dynamic interplay of substance use and psychotic symptoms is in many cases consistent with both causal and self-medication mechanisms, and these patterns of association should be considered in the design of treatment and prevention strategies.