tbuckley/cabot-search huggingface dataset:
Intramyocyte Detection of Epstein-Barr Virus Genome by Laser Capture Microdissection in Patients With Inflammatory Cardiomyopathy
Authors: Cristina Chimenti, Andrea Russo, Maurizio Pieroni, Fiorella Calabrese, Romina Verardo, Gaetano Thiene, Matteo A. Russo, Attilio Maseri, Andrea Frustaci
Journal: Circulation (2004)

The causal role of Epstein-Barr virus (EBV) in inflammatory cardiomyopathy (IC) is still unclear, because this virus is present in latently infected circulating B lymphocytes in 90% of adults. Laser capture microdissection (LCM) has been applied on endomyocardial biopsy samples from patients with IC to assess the presence of EBV genome in separately dissected lymphocytes and myocytes.Among 142 patients with cardiac dilation and dysfunction and a histological and immunohistochemical diagnosis of myocarditis, 44 had a myocardial viral infection detected by polymerase chain reaction on frozen endomyocardial biopsy samples. In 9 of them, the virus detected was EBV. LCM was performed on 5-microm-thick paraffin sections of EBV-infected hearts. Lymphocytes and myocytes were microdissected and analyzed separately by polymerase chain reaction analysis on DNA extracted from the collected cells. Blood and myocardial samples from patients with positive and negative serology for EBV were used as controls. EBV genome was detected in myocytes but not in infiltrating lymphocytes of patients, nor in myocardial samples from controls. Despite full conventional antifailure therapy, a progressive cardiac dilation and dysfunction was documented in patients with EBV-related IC at a mean of 31+/-14 months of follow-up.Intramyocyte detection of EBV can be obtained by LCM in up to 6.3% of patients with IC. This supports a cytopathic EBV role and suggests the opportunity for an antiviral/immunomodulatory therapy.
Short segment Barrett's oesophagus: prevalence, diagnosis and associations.
Authors: S Nandurkar, N J Talley, C J Martin, T H Ng, S Adams
Journal: Gut (1997)

BACKGROUND: Prevalence of short segment Barrett9s (SSB) oesophagus, defined as the absence of macroscopic Barrett9s but histologically identifiable intestinal metaplasia, has been reported to be 18% based on haematoxylin and eosin (H&amp;E) staining. AIMS: To define the prevalence of SSB oesophagus using H&amp;E and alcian blue staining and to determine whether SSB oesophagus is associated with inflammation at the gastro-oesophageal junction (GOJ). SUBJECTS: Consecutive patients (n = 158) presenting for endoscopy completed a structured interview. METHODS: Two biopsy specimens taken from the GOJ were stained with H&amp;E, alcian blue and Giemsa. A third specimen was obtained from the distal oesophagus. Intestinal metaplasia was diagnosed if goblet cells were definitely identified by two independent observers. RESULTS: SSB oesophagus was present in 46 (prevalence 36%, 95% confidence interval (CI) 28.5-43.5) using alcian blue staining. If H&amp;E had been the sole staining method used, 50% cases of intestinal metaplasia would have been overlooked. There were no cases of intestinal metaplasia identified by H&amp;E but missed by alcian blue staining. Logistic regression analysis identified age (odds ratio (OR) per decade 1.03, 95% CI 1.01-1.06), histological oesophagitis (OR 3.2, 95% CI 1.4-7.2) and inflammation at the gastrooesophageal junction (OR 5.9, 95% CI 2.2-15.6) as independent risk factors for SSB oesophagus. CONCLUSION: Unrecognised SSB oesophagus is highly prevalent in patients presenting for diagnostic upper endoscopy if alcian blue staining is applied.
Portal hypertension in lymphoproliferative and myeloproliferative disorders: Hemodynamic and histological correlations
Authors: Alain Dubois, Michel Dauzat, Christine Pignodel, Gilles Pomier-Layrargues, Christiane Marty-Double, François-Michel Lopez, Charles Janbon
Journal: Hepatology (1993)

The pathogenesis of portal hypertension in patients with lymphoproliferative and myeloproliferative disorders is not fully understood. We investigated 20 patients with myeloproliferative disease and 47 patients with lymphoproliferative disease. Transvenous liver biopsies and hepatic vein pressure gradient measurements were performed in all patients, and portal vein blood flow was measured by pulsed Doppler sonography in 31 of these patients and in 22 normal volunteers. The hepatic vein pressure gradient was significantly higher in patients with hepatic infiltrates, fibrosis or both than in patients without hepatic lesions (8.3 +/- 5.0 mmHg vs. 4.1 +/- 2.3 mmHg; p < 0.01). Portal vein blood flow was significantly higher in patients with hematological disease than in normal volunteers (31.2 +/- 15.5 ml/min.kg vs. 14.2 +/- 4.6 ml/min.kg;p < 0.01). In 81.8% of patients with hepatic infiltrates, fibrosis or both and increased portal vein blood flow, the hepatic vein pressure gradient was greater than 6 mm Hg. Although we saw a significant correlation between splenic vein blood flow and portal vein blood flow (n = 20; p < 0.01), we found no significant correlation between splenic vein blood flow and hepatic vein pressure gradient or spleen size. Hepatic infiltration and fibrosis appear to be major determinants of increased hepatic vein pressure gradient, probably because they increase intrahepatic vascular resistance. The role of increased splenic blood flow is probably not determinant. However, because portal pressure was not measured directly in this study, the incidence of portal hypertension may have been underestimated.
Statin-Associated Myopathy with Normal Creatine Kinase Levels
Authors: Paul S. Phillips, Richard H. Haas, Sergei Bannykh, Stephanie Hathaway, Nancy L. Gray, Bruce J. Kimura, Georgirene D. Vladutiu, John D.F. England
Journal: Annals of Internal Medicine (2002)

Background: Muscle symptoms in patients who are treated with statins and have normal creatine kinase levels are not well understood. Objective: To report biopsy-confirmed myopathy and normal creatine kinase levels associated with statin use. Design: Case reports from preliminary analysis of an ongoing clinical trial. Setting: Clinical research center in a community hospital. Patients: Four patients with muscle symptoms that developed during statin therapy and reversed during placebo use. Measurements: 1] Patients' ability to identify blinded statin therapy and 2) standard measures of functional capacity and muscle strength. Results: All four patients repeatedly distinguished blinded statin therapy from placebo. Strength testing confirmed weakness during statin therapy that reversed during placebo use. Muscle biopsies showed evidence of mitochondrial dysfunction, including abnormally increased lipid stores, fibers that did not stain for cytochrome oxidase activity, and ragged red fibers. These findings reversed in the three patients who had repeated biopsy when they were not receiving statins. Creatine kinase levels were normal in all four patients despite the presence of significant myopathy. Conclusion: Some patients who develop muscle symptoms while receiving statin therapy have demonstrable weakness and histopathologic findings of myopathy despite normal serum creatine kinase levels. *For members of the Scripps Mercy Clinical Research Center, see the Appendix.
Failure to cleave measles virus fusion protein in lymphoid cells. A possible mechanism for viral persistence in lymphocytes
Authors: RS Fujinami, MBA Oldstone
Journal: The Journal of Experimental Medicine (1981)

The host-directed cleavage of measles virus fusion protein on infected lymphoid cells was studied to understand the mechanism of viral persistence in lymphoid cells in vivo. Several lymphoblastoid cell lines were infected with measles virus, and the viral glycoproteins expressed on the cell's surface were radiolabeled and analyzed for cleavage of fusion (F(0)) to F(1) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Daudi and Ramos lymphoblastoid cells were deficient in their ability to cleave measles virus fusion protein and correspondingly produced low titers of infectious measles virus, Daudi cells being more defective than Ramos cells. In contrast, other lymphoblastoid cells studied, Victor, Raji, Wi-L2, RPMI 8866, and Seraphine, cleaved the fusion polypeptide and made significantly more infectious virus. Despite their defect in cleaving F protein, Daudi cells were able to assemble and release (noninfectious) measles virus particles into the fluid phase. The deficit in Daudi cells was corrected by fusing infected Daudi cells with cleavage-competent cells such as Victor or Raji. Furthermore, the cleavage event performed by competent cells could be mimicked at the plasma membrane by treating infected Daudi cells with trypsin, implicating the role of a plasma membrane enzyme in cleaving F(0) to F(1) during measles virus infection. Hence, lymphoid cells deficient in the plasma membrane enzyme required to cleave F protein are permissive for measles virus, maintain viral gene products, produce mostly noninfectious virus, and fail to place the biologic activity F(1) protein on their surfaces.
Alternative Macrophage Activation and Metabolism
Authors: Justin I. Odegaard, Ajay Chawla
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

Obesity and its attendant metabolic disorders represent the great public health challenge of our time. Recent evidence suggests that onset of inflammation in metabolic tissues pathogenically links obesity to insulin resistance and type 2 diabetes. In this review, we briefly summarize the extant literature, paying special attention to the central role of the tissue-associated macrophage in the initiation of metabolic inflammation. We argue that rather than representing simple inflammatory disease, obesity and metabolic syndrome represent derangements in macrophage activation with concomitant loss of metabolic coordination. As such, the sequelae of obesity are as much products of the loss of positive macrophage influences as they are of the presence of deleterious inflammation. The therapeutic implications of this conclusion are profound because they suggest that pharmacologic targeting of macrophage activation, rather than simply inflammation, might be efficacious in treating this global epidemic.
Inflammatory markers in cystic fibrosis patients with transmissible<i>Pseudomonas aeruginosa</i>
Authors: A.M. Jones, L. Martin, R.J. Bright-Thomas, M.E. Dodd, A McDowell, K.L. Moffitt, J.S. Elborn, A.K. Webb
Journal: European Respiratory Journal (2003)

Chronic Pseudomonas aeruginosa infection in cystic fibrosis (CF) leads to a damaging host inflammatory response. There are an increasing number of reports of P. aeruginosa cross-infection at CF centres. The clinical significance of acquisition of a transmissible strain for patients who already harbour P. aeruginosa is unclear. In this study, levels of inflammatory markers in clinically stable adult CF patients who harbour transmissible and sporadic strains of P. aeruginosa have been compared. Patients with CF and chronic P. aeruginosa infection were grouped into those who harbour a transmissible P. aeruginosa and those who harbour their own sporadic strains. Total white cell and differential counts, sputum neutrophil elastase (NE), interleukin (IL)‐8, tumour necrosis factor (TNF)‐α, plasma IL‐6 and NE/α 1 ‐antitrypsin complexes, serum C‐reactive protein, and urine TNF receptor 1 were all measured in clinically stable patients 4–6 weeks following completion of intravenous antibiotic therapy. The two groups (both n=20) were well matched for per cent predicted forced expiratory volume in one second, per cent predicted forced vital capacity and body mass index. There were no significant differences in levels of white cell counts or inflammatory markers between the two groups. At times of clinical stability, cystic fibrosis patients infected with transmissible Pseudomonas aeruginosa do not have a heightened inflammatory response above that of those harbouring sporadic strains.
The importance of nef in the induction of human immunodeficiency virus type 1 replication from primary quiescent CD4 lymphocytes.
Authors: C A Spina, T J Kwoh, M Y Chowers, J C Guatelli, D D Richman
Journal: The Journal of Experimental Medicine (1994)

The viral regulatory gene, nef, is unique to the human immunodeficiency viruses (HIV) and their related primate lentiviruses. Expression of the nef gene has been shown to be essential to the maintenance of high levels of virus replication and the development of pathogenesis in the animal model of simian immunodeficiency virus (SIV) infection. In contrast to this in vivo model, the use of standard T cell culture systems to study nef function in vitro has produced a spectrum of contradictory results, and has failed to demonstrate a significant positive influence of nef on viral life cycle. We have developed a cell model to study regulation of HIV-1 replication that we believe reflects more accurately virus-cell interactions as they occur in vivo. Our experimental system used acute virus infection of purified, quiescent CD4 lymphocytes and subsequent induction of viral replication through T cell activation. With this cell model, NL4-3 virus clones with open and mutated nef reading frames were compared for replication competence. The clones with nef mutations showed reproducible and significant reductions in both rates of growth and maximal titers achieved. The degree of reduced replication was dependent on initial virus inoculum and the timing of T cell activation. The influence of nef was highly significant for induction of virus replication from a latent state within resting CD4 cells. Its effect was less apparent for virus infection of fully proliferating CD4 cells. This study demonstrates that nef confers a positive growth advantage to HIV-1 that becomes readily discernable in the primary cell setting of virus induction through T cell activation. The experimental cell model, which we describe here, provides not only a means to study nef function in vitro, but also provides important clues to the function of nef in HIV infection in vivo.
Combined Immunosuppression in High-Risk Patients with IgA Nephropathy?
Authors: Jürgen Floege, Frank Eitner
Journal: Journal of the American Society of Nephrology (2010)

In autopsy studies or 0-hour renal allograft biopsies, IgA nephropathy (IgAN) can be found in up to 1.5% of the normal population.1 Thus, the vast majority of patients seem not to need us and do well without a nephrologist. Patients who are in need of renal care and therapy are those with a proteinuria level of >0.5 to 1.0 g/d and/or a decline in GFR. A favorable outcome was noted in observational studies when proteinuria was reduced to <1 g/d in such patients.2 Similarly, loss of GFR can be retarded, albeit not absolutely prevented, with angiotensin-converting enzyme inhibitor (ACEI) therapy,3 corticosteroid therapy,4 or combined corticosteroid and ACEI therapy.5,6 There is uncertainty, however, whether an even more intense therapy might result in even better outcomes.

In this issue of JASN , Pozzi et al. 7 describe the outcome of a long-awaited Italian and Swiss multicenter, randomized, controlled trial (RCT)8 in which they tested the hypothesis that adding a 6-month course of azathioprine to a 6-month corticosteroid regimen would further reduce the loss of GFR in high-risk, adult patients with IgAN. At inclusion, all patients exhibited a GFR of >50 ml/min per d and a proteinuria level of 1.5 to 3.5 g/d. Most also had advanced inflammatory and/or sclerosing histologic lesions in their baseline …
“Full access” and the history of linguistics
Authors: Margaret Thomas
Journal: Behavioral and Brain Sciences (1996)

Abstract This commentary addresses two pervasive misconceptions which emerge in Epstein et al.'s target article: (1) that study of second language acquisition (SLA) began in the mid-twentieth century; (2) that SLA has only recently become able to contribute to linguistic theory. There is abundant historical counterevidence; I argue that (1) and (2) obscure the legitimacy of Epstein et al.'s “full access” hypothesis.
Endothelial Injuries of Coronary Arteries Distal to Thrombotic Sites
Authors: Hiroyuki Eguchi, Hisao Ikeda, Toyoaki Murohara, Hideo Yasukawa, Nobuya Haramaki, Shotaro Sakisaka, Tsutomu Imaizumi
Journal: Circulation Research (1999)

Abstract —Intracoronary thrombus formation is associated with epicardial vasoconstriction distal to the thrombotic site. To investigate the mechanisms of abnormal vasomotor function of the artery distal to the thrombotic site, we studied coronary vessels in dogs with cyclic flow variations (CFVs) of the left anterior descending coronary artery (LAD) stenosis with endothelial injury. Coronary rings isolated from the LAD (proximal, stenotic, and distal sites) and control circumflex coronary arteries were tested for responsiveness to endothelium-dependent (acetylcholine and A23187) and endothelium-independent vasodilators (NaNO 2 ). Endothelium-independent relaxation was intact in all 4 sites. Endothelium-dependent relaxation was intact in the control and proximal sites and impaired in the stenotic sites. Relaxations not only to acetylcholine and A23187 but also to serotonin, ADP, and thrombin were impaired in the distal sites after observing CFVs for 80 minutes. Electron microscopy revealed the loss of endothelial integrity with leukocyte adherence to the endothelium in the distal sites. Immunohistochemical expression of P-selectin on the endothelial cells was more upregulated in the distal site than in the proximal site, and P-selectin mRNA expression was significantly greater in the ischemic region distal to the thrombotic site than in the proximal nonischemic region. PB1.3, a neutralizing monoclonal antibody against P-selectin, and sialyl Lewis X (SLe X )–containing oligosaccharide SLe X , a carbohydrate analogue of selectin ligand, preserved endothelial function without affecting CFVs. SLe X -containing oligosaccharide preserved endothelial integrity of the distal site and inhibited P-selectin expression of the distal site. Thus, the adhesive interaction between endothelial P-selectin and leukocyte SLe X may play an important role in endothelial injuries of the coronary artery distal to the thrombotic site.
Targeted Next-generation Sequencing of Advanced Prostate Cancer Identifies Potential Therapeutic Targets and Disease Heterogeneity
Authors: Himisha Beltran, Roman Yelensky, Garrett M. Frampton, Kyung Park, Sean R. Downing, Theresa Y. MacDonald, Mirna Jarosz, Doron Lipson, Scott T. Tagawa, David M. Nanus, Philip J. Stephens, Juan Miguel Mosquera, Maureen T. Cronin, Mark A. Rubin
Journal: European Urology (2012)
Persisting Haemophilus influenzae strains induce lower levels of interleukin-6 and interleukin-8 in H292 lung epithelial cells than nonpersisting strains
Authors: P Bresser, L van Alphen, FJ Habets, AA Hart, J Dankert, HM Jansen, R Lutter
Journal: European Respiratory Journal (1997)

Nonencapsulated Haemophilus influenzae strains isolated from patients with chronic bronchitis can be divided into those that persist in the lower respiratory tract and those that do not. We tested the hypothesis that persisting and nonpersisting strains differ in the extent to which they activate epithelial cells to produce two potent inflammatory mediators, interleukin (IL)-6 and IL-8. A suspension of 10(7) and 10(8) colony forming units (cfu) x mL(-1) of H. influenzae, persisting and nonpersisting, induced a dose- and time-dependent production of IL-6 and IL-8 by the human pulmonary mucoepidermoid carcinoma-derived cell line H292, but levels of IL-6 were lower after exposure to persisting H. influenzae (p&lt;0.05). IL-8 production showed a similar trend (p&lt;0.02; analysis of variance). H. influenzae bacteria that adhered to H292 cells were equally distributed over persisting and nonpersisting isolates and induced IL-6 and IL-8 levels similar to their nonadhering counterparts. The difference between persisting and nonpersisting H. influenzae was not due to cytotoxic, antimetabolic or antiproliferative effects on H292 cells. Furthermore, pre-exposure of cells to persisting and nonpersisting isolates did not block subsequent IL-1beta-induced IL-6 production. We conclude that persisting clinical isolates induce less interleukin-6 and interleukin-8 in H292 cells than nonpersisting isolates, probably because they excrete lower amounts of a stimulus of H292 cells. The stimulus is heat stable, hydrophilic and nonproteinous and probably not lipopolysaccharide alone. These findings support the suggestion that some strains of Haemophilus influenzae that persist in the airways of patients, may do so because they induce only a weak inflammatory response.
Evidence for an Indirect Sympathetic Control of Atrial Stretch Receptor Discharge in the Dog
Authors: IRVING H. ZUCKER, JOSEPH P. GILMORE
Journal: Circulation Research (1974)

Experiments were performed to determine the influence of cardiac sympathetic efferent nerve stimulation on the discharge rate of atrial type B stretch receptors in the anesthetized, open-chest dog. In all experiments, the left stellate ganglion was stimulated following volume expansion. To determine the effects of stellate stimulation, the responses of atrial receptors were observed during the withdrawal of blood in steps following intravascular volume expansion. Stimulation of the stellate ganglion decreased receptor discharge and left atrial pressure in all experiments. A change from a control left atrial pressure of 2.5 cm H 2 O (in peak left atrial v -wave pressure) resulted in a mean increase in receptor discharge of 6.6 ± 1.4 spikes/cardiac cycle during stellate stimulation; however, a change from a control pressure of 0.0 cm H 2 O resulted in a mean decrease in receptor discharge of 1.5 ± 1.5 spikes/cardiac cycle. The curves relating the change in atrial receptor discharge to the change in left atrial pressure during hemorrhage and the curve for these parameters during stellate stimulation were not significantly different from each other. Apparently, the decreased discharge during sympathetic stimulation was the result of a decline in left atrial pressure rather than a result of any direct effect on the receptor per se.