tbuckley/cabot-search huggingface dataset:
Microsatellite DNA Instability and Loss of Heterozygosity in Pulmonary Sarcoidosis
Authors: DIMITRIS A. VASSILAKIS, GEORGE SOURVINOS, MILTIADIS MARKATOS, KOSTAS PSATHAKIS, DEMETRIOS A. SPANDIDOS, NIKOLAOS M. SIAFAKAS, DEMOSTHENES BOUROS
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

In the present study we investigated the incidence of microsatellite instability (MI) and loss of heterozygosity (LOH) in sarcoidosis, a multisystem disease of unknown origin. We examined sputum cytological specimens from 30 patients with sarcoidosis and 30 healthy, matched subjects, using 10 highly polymorphic microsatellite markers located at several chromosomal arms. The electrophoretic pattern of each specimen was compared with the corresponding pattern of peripheral blood and any difference in the mobility of the microsatellite alleles was interpreted as MI-positive. LOH was scored as decrease in intensity of one allele relative to the other as determined from comparison of sputum and normal (blood) DNA. We found that 14 (47%) sarcoidosis patients showed genetic alterations, either MI or LOH. Six (20%) patients exhibited MI and nine (30%) exhibited LOH in at least one microsatellite marker. One of the patients exhibited MI in two microsatellite markers and three (10%) showed LOH in more than one marker. One patient showed complete deletion of the chromosomal arm 17q11.2-q21. None of the healthy subjects exhibited any genetic alteration in the studied markers. No correlation was found between the genetic alterations detected and age, disease duration, blood gases, or spirometric parameters of the patients. Our findings suggest that MI is a detectable phenomenon in sarcoidosis and seems not to be related with the severity of the disease. The detection of LOH indicates the presence of putative tumor suppressor genes at loci examined, which may play an important role in the etiopathogenesis of sarcoidosis. Vassilakis DA, Sourvinos G, Markatos M, Psathakis K, Spandidos DA, Siafakas NM, Bouros D. Microsatellite instability and loss of heterozygosity in pulmonary sarcoidosis.
Interferon/ribavirin combination therapy with and without daily dosing in retreatment of chronic hepatitis C
Authors: M.H. Frieser, T. Bernatik, H. Klinker, M. Scheurlen, H. Meyer, W. Norgauer, W. Rambach, K. Meier, E. Hahn, D. Schuppan, H.T. Schneider
Journal: Journal of Hepatology (2001)
Role of activated macrophages in antibody-dependent lysis of tumor cells.
Authors: C Nathan, L Brukner, G Kaplan, J Unkeless, Z Cohn
Journal: The Journal of Experimental Medicine (1980)

Treatment of mice with Bacille Calmette-Guérin (BCG) or C parvum activates their peritoneal macrophages to release increased amounts of H2O2, and thereby to lyse extracellular tumor cells, in response to a pharmacologic agent, phorbol myristate acetate (PMA) (1-3). In the present study, the same bacterial vaccines activated peritoneal cells to become cytolytic to lymphoma cells sensitized with alloantiserum, in the absence of PMA. Resident peritoneal cells, or those elicited with thioglycollate broth, were ineffective, not only in PMA-induced lysis, but also in antibody-dependent lysis of tumor cells. The cytolytic effect of BCG peritoneal cells toward sensitized tumor cells appeared to be mediated mostly by macrophages. Cytotoxicity was immunologically specific, contact dependent, rapid, and efficient. Phagocytosis of intact tumor cells was not involved. Alloantiserum-dependent cytolysis was specifically blocked by the Fab fragment of a monoclonal antibody directed against the trypsin-resistant macrophage Fc receptor (FcR II). Thus, tumor cells coated with homologous immunoglobulin interact with FcR II on activated macrophages to trigger an extra-cellular cytolytic response.
Defining a second epitope for heparin-induced thrombocytopenia/thrombosis antibodies using KKO, a murine HIT-like monoclonal antibody
Authors: Zhong Q. Li, Weiyi Liu, Kwang S. Park, Brue S. Sachais, Gowthani M. Arepally, Douglas B. Cines, Mortimer Poncz
Journal: Blood (2002)
Factors associated with COPD exacerbation frequency in a UK primary care cohort
Authors: Hana Müllerová, Amit Shukla, Adam Hawkins, Jennifer Quint
Journal: European Respiratory Journal (2013)

Aim: To determine factors associated with frequency of COPD exacerbations in primary care.

Method: Retrospective cohort study of COPD patients identified from the UK Clinical Practice Research Datalink, aged ≥40years, with ≥1 COPD diagnosis ≥01/04/2009, FEV1/FVC <0.7 and ≥12 mo data pre/post cohort entry. Moderate (diagnoses or concurrent Rx ATB+ OCS) or Severe (hospital admission) exacerbations were defined 12mo pre/post cohort entry. MRC dyspnoea score, GOLD stage of airflow limitation nearest to cohort entry, and comorbidities any time were flagged. Logistic regression produced odds ratios for frequent (≥2) vs. infrequent (0,1) exacerbations over 12mo follow-up.

Results: 58,589 COPD patients were included: 47% females, mean age 69yrs, mean FEV1 60% pred. Over 12mo follow-up, the rate of moderate-to-severe exacerbations was 0.89/person/year; 23% (n=13,351) reported ≥2 exacerbations. Odds of ≥2 exacerbations increased with prior history of exacerbations (OR 8.50 [95%CI:8.00-9.03] for ≥2 episodes, OR 2.64 [95%CI: 2.50-2.79] for 1 episode), increasing airflow limitation (from OR 1.16 [95%CI: 1.08-1.25] for GOLD II, to OR 2.01 [95%CI: 1.80-2.26] for GOLD IV), increasing dyspnoea grade (from OR 1.30 [95%CI: 1.21-1.41] for MRC 2 to OR 2.49 [95%CI: 2.17-2.85] for MRC5), and prevalent comorbidities (history of asthma, cancer, depression, and congestive heart failure).

Conclusion: In this UK primary care cohort, prior exacerbation history together with increasing airflow limitation and dyspnoea were the strongest risk factors for future frequent exacerbations.

Funded by GlaxoSmithKline (WEUSKOP5903 study).
Overexpression of Platelet-Derived Growth Factor Receptor α in Endothelial Cells of Hepatocellular Carcinoma Associated with High Metastatic Potential
Authors: Ti Zhang, Hui-Chuan Sun, Yang Xu, Ke-Zhi Zhang, Lu Wang, Lun-Xiu Qin, Wei-Zhong Wu, Yin-Kun Liu, Sheng-Long Ye, Zhao-You Tang
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Little information is available on the heterogeneity of the vascular endothelium in hepatocellular carcinoma. The aim of this study was to identify the differentially expressed genes in tumor endothelial cells from highly metastatic hepatocellular carcinoma. Experimental Design: Magnetic beads conjugated with anti-CD31 antibody were used to isolate vascular endothelial cells from hepatocellular carcinoma xenografts with different metastatic potentials in nude mice. Gene expression profiles for different endothelial cells were compared by use of cDNA microarray. The up-regulated gene was confirmed by reverse transcription-PCR, real-time PCR, and immunohistochemistry. Results: cDNA microarray analysis revealed differential expression patterns in seven genes consistently presented in endothelial cells isolated from hepatocellular carcinoma with different metastatic potentials. Overexpression of platelet-derived growth factor receptor α was found only in the endothelium of highly metastatic hepatocellular carcinoma, which was confirmed by reverse transcription-PCR, real-time PCR, and immunohistochemistry. Oral administration of STI571 (imatinib mesylate or Glivec), a protein tyrosine kinase inhibitor of platelet-derived growth factor receptor, combined with s.c. injection of IFN-α not only effectively reduced tumor weight (by 81.8%) and microvessel density (by 70.2%) but also inhibited lung metastasis (by 100%). Furthermore, immunohistochemical analysis of platelet-derived growth factor receptor α in human hepatocellular carcinoma tissues revealed its correlation with postoperative recurrence, especially in patients without microvessel invasion. Conclusions: The gene expression of hepatocellular carcinoma vascular endothelium is different between tumors with different metastatic potential. Platelet-derived growth factor receptor α, which is overexpressed in endothelium of highly metastatic hepatocellular carcinoma, may serve as a biomarker for predicting metastasis and a therapeutic target for highly metastatic hepatocellular carcinoma.
Uroporphyrinogen decarboxylase deficiency in hepatoerythropoietic porphyria: further evidence for genetic heterogeneity
Authors: F. KOSZO, G.H. ELDER, A. ROBERTS, N. SIMON
Journal: British Journal of Dermatology (1990)

Catalytic and immunoreactive erythrocyte uroporphyrinogen decarboxylase was measured in a woman with hepatoerythropoietic porphyria (HEP). The uroporphyrinogen decarboxylase activity was 24% of the mean value for normal controls and the concentration of the immunoreactive enzyme (106 ng/mgHb), measured with the rocket immunoelectrophoresis technique, did not differ from that of healthy controls. Consequently, catalytically inactive, cross‐reactive immunological material (CRIM) was present, and the patient was CRIM‐positive. This enzyme activity and immunoreactive enzyme concentration differs from those for previously known HEP patients, and represents a new mutation, evidence for heterogeneity in inherited uroporphyrinogen decarboxylase deficiency.
Effects of Fat on Blood Viscosity in Dogs
Authors: ROY L. SWANK
Journal: Circulation Research (1956)

Intravenous fat injections cause significant increases in blood viscosity. Nonemulsified or poorly emulsified oil produces pulmonary and other embolization. Plasma is lost rapidly and in alarming degree. The hematocrit increases rapidly and is accompanied by a nearly parallel increase in blood viscosity. Oil in stable emulsion in blood plasma or lymph can be injected in greater doses. Slow, but significant increases in the blood viscosity develop to maximum in 10 to 24 hours. Varying degrees of paralysis follow. The loss of plasma is not so marked, and increase in hematocrit is not sufficient to account for increase in viscosity.
All-trans retinoic acid- and N-(4-hydroxyphenil)-retinamide-induced growth arrest and apoptosis in orbital fibroblasts in Graves’ disease
Authors: Daniela Pasquali, Antonio Bellastella, Vittorio Colantuoni, Patrizia Vassallo, Giulio Bonavolontà, Valentina Rossi, Antonio Notaro, Antonio A Sinisi
Journal: Metabolism (2003)
Convergent evolution of the genomes of marine mammals
Authors: Andrew D Foote, Yue Liu, Gregg W C Thomas, Tomáš Vinař, Jessica Alföldi, Jixin Deng, Shannon Dugan, Cornelis E van Elk, Margaret E Hunter, Vandita Joshi, Ziad Khan, Christie Kovar, Sandra L Lee, Kerstin Lindblad-Toh, Annalaura Mancia, Rasmus Nielsen, Xiang Qin, Jiaxin Qu, Brian J Raney, Nagarjun Vijay, Jochen B W Wolf, Matthew W Hahn, Donna M Muzny, Kim C Worley, M Thomas P Gilbert, Richard A Gibbs
Journal: Nature Genetics (2015)

Andrew Foote and colleagues report the whole-genome sequences and de novo assemblies of three marine mammal species—the walrus, killer whale and manatee—and an improved bottlenose dolphin genome. Their comparative genomic analysis finds evidence of parallel evolution across the marine mammal genomes. Marine mammals from different mammalian orders share several phenotypic traits adapted to the aquatic environment and therefore represent a classic example of convergent evolution. To investigate convergent evolution at the genomic level, we sequenced and performed de novo assembly of the genomes of three species of marine mammals (the killer whale, walrus and manatee) from three mammalian orders that share independently evolved phenotypic adaptations to a marine existence. Our comparative genomic analyses found that convergent amino acid substitutions were widespread throughout the genome and that a subset of these substitutions were in genes evolving under positive selection and putatively associated with a marine phenotype. However, we found higher levels of convergent amino acid substitutions in a control set of terrestrial sister taxa to the marine mammals. Our results suggest that, whereas convergent molecular evolution is relatively common, adaptive molecular convergence linked to phenotypic convergence is comparatively rare.
Deafblindness in French Canadians from Quebec: a predominant founder mutation in the USH1C gene provides the first genetic link with the Acadian population
Authors: Inga Ebermann, Irma Lopez, Maria Bitner-Glindzicz, Carolyn Brown, Robert Karel Koenekoop, Hanno Jörn Bolz
Journal: Genome biology (2007)

Abstract Background Usher syndrome type 1 (USH1) is the leading cause of deafblindness. In most populations, many private mutations are distributed across the five known USH1 genes. We investigated patients from the French Canadian population of Quebec (approximately 6 million people) that descends from about 8,500 French settlers who colonized the St Lawrence River valley between 1608 and 1759. We hypothesized that founder mutations in USH1 genes exist in this population. Results We have genetically characterized 15 patients from different regions of Quebec who were clinically diagnosed as USH1. Of these cases, 60% carried mutations of the USH1C gene, a genetic subtype that is rare outside the Acadian population. We have discovered a founder effect of the c.216G&gt;A mutation, which has previously been designated the 'Acadian allele' because it accounts for virtually all Acadian USH1 cases. It represents 40% of disease alleles in Quebec, and a carrier of c.216G&gt;A was identified in the general population. Mutations in other genes, except CDH23 , are very rare. Conclusion Based on our findings, approximately 0.5% of congenitally deaf children in Quebec are at risk of developing retinal degeneration due to homozygosity for c.216G&gt;A. Although the Acadians and French Canadians from Quebec are descended from French ancestors, they have always been considered genetically distinct. The genetic conditions common in Quebec are generally not found in Acadians, or they are due to different mutations. Our results, however, show that carriers of the c.216G&gt;A allele haplotype belonged to the early founders of both the Acadian and the Quebec population.
STUDIES ON THE MECHANISM OF ENDOGENOUS PYROGEN PRODUCTION
Authors: Phyllis Bodel
Journal: The Journal of Experimental Medicine (1974)

The characteristics of pyrogen production and release by human blood monocytes were investigated. A dose-response assay of monocyte pyrogen in rabbits indicated a linear relationship of temperature elevation to dose of pyrogen at lower doses. Monocytes did not contain pyrogen when first obtained, nor did they release it spontaneously even after 5 days of incubation in vitro. Pyrogen production was apparent 4 h after stimulation by endotoxin or phagocytosis, and continued for 24 h or more. Puromycin, an inhibitor of protein synthesis, prevented both initiation and continuation of pyrogen production and release. Pyrogen-containing supernates retained most pyrogenic activity during overnight incubation even in the presence of activated cells. Lymphocytes appeared to play no role in either initiation or continuation of pyrogen production in these studies.
The Neural Basis of Decision Making
Authors: Joshua I. Gold, Michael N. Shadlen
Journal: Annual Review of Neuroscience (2007)

The study of decision making spans such varied fields as neuroscience, psychology, economics, statistics, political science, and computer science. Despite this diversity of applications, most decisions share common elements including deliberation and commitment. Here we evaluate recent progress in understanding how these basic elements of decision formation are implemented in the brain. We focus on simple decisions that can be studied in the laboratory but emphasize general principles likely to extend to other settings.
CORONARY ARTERY CALCIUM SCORE OF &lt;100 EFFECTIVELY RULES OUT PRESENCE OF SIGNIFICANT ISCHEMIA, WHILE &gt;=400 RULES IN-INSIGHT FROM A META-ANALYSIS OF 14 STUDIES
Authors: Chirag Bavishi, Saurav Chatterjee, Edgar Argulian, Taimur Mirza, Alan Rozanski
Journal: Journal of the American College of Cardiology (2014)
Planning differences for chromaticity- and luminance-defined stimuli: A possible problem for Glover's planning–control model
Authors: Charles E. Wright, Charles Chubb
Journal: Behavioral and Brain Sciences (2004)

We report data from an experiment using stimuli designed to differ in their availability for processing by the dorsal visual pathway, but which were equivalent in tasks mediated by the ventral pathway. When movements are made to these stimuli as targets, there are clear effects early in the movement. These effects appear at odds with the planning–control model of Glover.
Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence.
Authors: R Ahmed, A Salmi, L D Butler, J M Chiller, M B Oldstone
Journal: The Journal of Experimental Medicine (1984)

We studied the mechanism of lymphocytic choriomeningitis virus (LCMV) persistence and the suppression of cytotoxic T lymphocyte (CTL) responses in BALB/c WEHI mice infected at birth with LCMV Armstrong strain. Using adoptive transfer experiments we found that spleen cells from persistently infected (carrier) mice actively suppressed the expected LCMV-specific CTL response of spleen cells from normal adult mice. The suppression was specific for the CTL response and LCMV -specific antibody responses were not affected. Associated with the specific CTL suppression was the establishment of persistent LCMV infection. The transfer of spleen or lymph node cells containing LCMV -specific CTL resulted in virus clearance and prevented establishment of the carrier state. The suppression of LCMV -specific CTL responses by carrier spleen cells is not mediated by a suppressor cell, but is due to the presence of genetic variants of LCMV in spleens of carrier mice. Such virus variants selectively suppress LCMV-specific CTL responses and cause persistent infections in immunocompetent mice. In striking contrast, wild-type LCMV Armstrong, from which these variants were generated, induces a potent CTL response in immunocompetent mice and the LCMV infection is rapidly cleared. Our results show that LCMV variants that emerge during infection in vivo play a crucial role in the suppression of virus-specific CTL responses and in the maintenance of virus persistence.
Platelet-Derived Nitric Oxide Signaling and Regulation
Authors: Eugenia Gkaliagkousi, James Ritter, Albert Ferro
Journal: Circulation Research (2007)

Nitric oxide (NO) exerts important vasodilatory, antiplatelet, antioxidant, antiadhesive, and antiproliferative effects. Although endothelium derived NO has been shown to be of prime importance in cardio- and vasculoprotection, until recently little was known about the role of platelet-derived NO. New evidence suggests that NO synthesized by platelets regulates platelet functions, in particular suppressing platelet activation and intravascular thrombosis. Moreover, platelet NO biosynthesis may be decreased in patients with cardiovascular risk factors or with coronary heart disease, and this may contribute to arterial thrombotic disease in these patients. Here, we review the current state of knowledge as regards the role of platelet-derived NO, both in normal physiology and in cardiovascular disease states, and compare platelet NO signaling and regulation with that in endothelial cells.
Second World Congress on the Insulin Resistance Syndrome
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2005)

This is the first in a series of articles on the Second World Congress on the Insulin Resistance Syndrome, Universal City, California, 18–20 November 2004.

Yehuda Handelsman (Tarzana, CA) introduced the Second World Congress on the Insulin Resistance Syndrome, noting the importance of ICD-9 diagnostic code 277.7, which allows one to use insulin resistance syndrome as a specific medical diagnosis, although the nomenclature of the syndrome is complex (1). There is a continuous relationship between the number of risk factors and associated conditions and the severity of insulin resistance, so that it may be incorrect to suggest that a specific number of components is needed to determine the presence of this condition, a potential advantage of the American Association of Clinical Endocrinologists diagnostic criteria, which appears to be more strongly associated with diabetes than other criteria for the insulin resistance syndrome.

Gerald M. Reaven (Stanford, CA) discussed the relationship between obesity and the insulin resistance syndrome, noting that mean fat and energy intake increased between 1990 and 2000 from 81 to 86 g and from 1,969 to 2,200 calories daily, respectively, so that “we’re getting heavier because we’re eating more.” Obesity is associated with increased mortality, with insulin resistance the link between obesity and coronary heart disease. Reaven used 3-h somatostatin, insulin, and glucose infusion to measure the steady-state plasma glucose (SSPG), which is inversely related to insulin sensitivity. There is tremendous variability in healthy individuals, with SSPG in 490 people with normal glucose tolerance  300 mg/dl in the 10th decile. The lowest quartile of insulin sensitivity is strongly predictive of development of diabetes and of coronary artery disease. Both BMI and waist circumference correlate with SSPG, but “with enormous variation,” as some obese individuals have normal and some lean individuals have high …
Gut mucosal immunization with reovirus serotype 1/L stimulates virus-specific cytotoxic T cell precursors as well as IgA memory cells in Peyer's patches.
Authors: S D London, D H Rubin, J J Cebra
Journal: The Journal of Experimental Medicine (1987)

In this report we have shown that reovirus 1/L is an effective mucosal immunogen capable of generating a cytotoxic T cell (CTL) and associated helper T cell response to the nominal antigens associated with reovirus 1/L. The effectors that mediate reovirus-specific cytotoxicity are Thy-1+, Lyt-2+, and major histocompatibility complex (MHC)-restricted in their recognition of reovirus antigens, and can therefore be classified as CTLs. Frequency analysis of precursor CTLs occurring in Peyer's patches (PP) and peripheral lymph nodes (PLN) 6 d and 6 mo after intraduodenal stimulation have demonstrated that a persistent gradient of precursors is established, with higher frequencies present in PP. The generation of a CTL response in PP may be important in preferentially repopulating mucosal tissues with effector CTLs that could result in the local containment of infections in the gut. We also found that reovirus 1/L generates a virus-specific B cell response that is dominated by IgA memory cells after intraduodenal immunization. We hypothesize that the efficacy of reovirus 1/L at stimulating T and B cells in the gut mucosa is related to its ability to selectively enter PP via microfold (M) cells after enteric application. In this study we have also demonstrated that PP cells, upon in vitro culture and unrelated to prior reovirus priming, can generate natural killer-like (NK) cytotoxic activity. This may be an in vitro correlate of the in vivo generation of effectors that may populate mucosal tissues (i.e., the intestinal epithelium) with NK-like effector cells.