tbuckley/cabot-search huggingface dataset:
Evolutionary conservation of surface molecules that distinguish T lymphocyte helper/inducer and cytotoxic/suppressor subpopulations in mouse and man
Authors: JA Ledbetter, RL Evans, M Lipinski, C Cummingham-Rundles, RA Good, LA Herzenberg
Journal: The Journal of Experimental Medicine (1981)

We describe the biochemical properties and cell surface distributions of three human T cell antigens (Leu-1, Leu-2a, and Leu-2b) which we postulate to be the homologues of the Lyt-1, Lyt-2, and Lyt-3 antigens that distinguish functional T cell subsets in the mouse. Leu-l, like Lyt-1, is on all thymocytes and peripheral T cells and is present in greater amounts on the helper/inducer subset than on the cytotoxic/suppressor subset. Both antigens increase in parallel fashion during T cell maturation in the thymus and each antigen is carried on a single 67,000-molecular weight (relative) (M(r)) polypeptide chain. Surprisingly, Leu-1 and Lyt-1 each are also expressed in readily detectable amounts on some B celI Ieukemias but not detectably so on normal B cells. Leu-2a and Leu-2b are antigens found only on suppressor/cytotoxic cells in the human and are very similar to the murine Lyt-2 and Lyt-3 antigens. In both species, the two antigens are on the same disulfide- linked multimeric molecules. Disulfide-bond reduction in both species yields subunits of similar size and charge. Lyt-3 and Leu-2b are extremely sensitive to trypsin digestion on viable cells whereas Lyt-2 and Leu-2a are much less so. A different membrane antigen, Leu-3, is an exclusive marker of the helper/inducer subset in man. No mouse homologue for this 55,000-M(r) protein is known. The maintenance of the homologous molecules on functionally distinct T cell subpopulations in two evolutionarily distant species suggests that the Lyt and Leu antigens perform essential functions for the cells on which they are found.
INVESTIGATIONS ON THE OCCURRENCE OF Rh SUBSTANCES IN AMNIOTIC FLUID
Authors: Ernest Witebsky, James F. Mohn
Journal: The Journal of Experimental Medicine (1945)

1. Rh substances are found in amniotic fluid. Not all anti-Rh sera seem to be suitable for the detection of Rh substances in amniotic fluid. Careful selection of Rh antisera, as well as quantitative considerations, determine success or failure of their demonstration. 2. The baby's Rh type and not the mother's determines the occurrence of Rh substances in amniotic fluid. 3. There are Rh secretors and Rh non-secretors. At least four out of five individuals are secretors. 4. The secretion of Rh substance into the amniotic fluid would seem to be entirely independent of the secretion of the blood group specific substances. 5. The majority of Rh-positive amniotic fluids seem to contain both Rh(1) and Rh(2) substances. However, in certain instances fluids belonging to the pure Rh(1) type or pure Rh(2) type were found. 6. Three cases of erythroblastosis were described. All three came from Rh-negative mothers with Rh-positive babies. The amniotic fluids of all three failed to reveal the presence of Rh substances.
Quantitative magnetic resonance imaging as marker of synovial membrane regeneration and recurrence of synovitis after arthroscopic knee joint synovectomy: a one year follow up study
Authors: M Ostergaard
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVES</h3> By repeated magnetic resonance imaging (MRI) to study synovial membrane regeneration and recurrence of synovitis after arthroscopic knee joint synovectomy in patients with rheumatoid arthritis (RA) and other (non-RA) causes of persistent knee joint synovitis. <h3>METHODS</h3> Contrast enhanced MRI was performed in 15 knees (nine RA, six non-RA) before and one day, seven days, two months, and 12 months after arthroscopic synovectomy. Synovial membrane volumes, joint effusion volumes, and cartilage and bone destruction were assessed on each MRI set. Baseline microscopic and macroscopic assessments of synovitis and baseline and follow up standard clinical and biochemical examinations were available. <h3>RESULTS</h3> Synovial membrane and joint fluid volumes were significantly reduced two and 12 months after synovectomy. However, MRI signs of recurrent synovitis were already present in most knees at two months. No significant differences between volumes in RA and non-RA knees were seen. Synovial membrane volumes at two months were significantly inversely correlated with the duration of clinical remission, for all knees considered together (Spearman9s correlation<i>r</i><sub>s</sub>=−0.67; p&lt;0.05), for RA knees (<i>r</i><sub>s</sub>=−0.76; p&lt;0.05), and for non-RA knees (<i>r</i><sub>s</sub>=−0.83; p&lt;0.05). Baseline volumes were not significantly correlated with clinical outcome. Only three knees (all RA) showed erosive progression. The rate of erosive progression was not correlated with MRI volumes or with clinical or biochemical parameters. <h3>CONCLUSION</h3> The synovial membrane had regenerated two months after arthroscopic knee joint synovectomy and despite significant volume reductions compared with baseline it often showed signs of recurrent synovitis. MRI seems to be valuable as a marker of inflammation, destruction and, perhaps, as a predictor of therapeutic outcome in arthritis.
Both common variations and rare non-synonymous substitutions and small insertion/deletions in CLU are associated with increased Alzheimer risk
Authors: Karolien Bettens, Nathalie Brouwers, Sebastiaan Engelborghs, Jean-Charles Lambert, Ekaterina Rogaeva, Rik Vandenberghe, Nathalie Le Bastard, Florence Pasquier, Steven Vermeulen, Jasper Van Dongen, Maria Mattheijssens, Karin Peeters, Richard Mayeux, Peter St George-Hyslop, Philippe Amouyel, Peter P De Deyn, Kristel Sleegers, Christine Van Broeckhoven
Journal: Molecular Neurodegeneration (2012)

Abstract Background We have followed-up on the recent genome-wide association (GWA) of the clusterin gene ( CLU) with increased risk for Alzheimer disease (AD), by performing an unbiased resequencing of all CLU coding exons and regulatory regions in an extended Flanders-Belgian cohort of Caucasian AD patients and control individuals ( n = 1930). Moreover, we have replicated genetic findings by targeted resequencing in independent Caucasian cohorts of French ( n = 2182) and Canadian ( n = 573) origin and by performing meta-analysis combining our data with previous genetic CLU screenings. Results In the Flanders-Belgian cohort, we identified significant clustering in exons 5-8 of rare genetic variations leading to non-synonymous substitutions and a 9-bp insertion/deletion affecting the CLU β-chain ( p = 0.02). Replicating this observation by targeted resequencing of CLU exons 5-8 in 2 independent Caucasian cohorts of French and Canadian origin identified identical as well as novel non-synonymous substitutions and small insertion/deletions. A meta-analysis, combining the datasets of the 3 cohorts with published CLU sequencing data, confirmed that rare coding variations in the CLU β-chain were significantly enriched in AD patients (OR MH = 1.96 [95% CI = 1.18-3.25]; p = 0.009). Single nucleotide polymorphisms (SNPs) association analysis indicated the common AD risk association (GWA SNP rs11136000, p = 0.013) in the 3 combined datasets could not be explained by the presence of the rare coding variations we identified. Further, high-density SNP mapping in the CLU locus mapped the common association signal to a more 5' CLU region. Conclusions We identified a new genetic risk association of AD with rare coding CLU variations that is independent of the 5' common association signal identified in the GWA studies. At this stage the role of these coding variations and their likely effect on the β-chain domain and CLU protein functioning remains unclear and requires further studies.
Different effects of alpha- and beta-adrenergic stimulation on cytosolic pH and myofilament responsiveness to Ca2+ in cardiac myocytes.
Authors: G Gambassi, H A Spurgeon, E G Lakatta, P S Blank, M C Capogrossi
Journal: Circulation Research (1992)

alpha-Adrenergic stimulation (alpha-AS) and beta-adrenergic stimulation (beta-AS) of the myocardium are associated respectively with an increase and a decrease in myofilament responsiveness to Ca2+. We hypothesized that changes in cytosolic pH (pH(i)) may modulate these opposite actions of alpha-AS and beta-AS. The effects of alpha-AS (50 microM phenylephrine and 1 microM nadolol) and beta-AS (0.05 microM isoproterenol) on contraction and either cytosolic Ca2+ (Cai) or pH(i) were assessed in adult rat ventricular myocytes bathed in bicarbonate buffer (pH 7.36 +/- 0.05). In cells loaded with the ester derivative (AM form) of indo-1, the 410/490-nm ratio of emitted fluorescence indexed Cai. Myofilament responsiveness to Ca2+ was assessed by the relaxation phase of the length-indo-1 fluorescence relation during a twitch. alpha-AS and beta-AS shifted this relation in opposite directions, indicating that alpha-AS increased and beta-AS decreased myofilament responsiveness to Ca2+. In addition, the positive inotropic action of alpha-AS was associated with an increased Cai transient amplitude in 50% of the myocytes (n = 12), whereas beta-AS always increased Cai (n = 5). In cells loaded with the fluorescent pH(i) probe SNARF-1 AM, the emitted 590/640-nm fluorescence is a measure of pH(i). The effect of alpha-AS on the extent of cell shortening during the twitch (ES) was expressed as the percentage of resting cell length. Both ES and pH(i) were assessed in myocytes bathed in 1.5 mM [Ca2+] and stimulated at 0.5 Hz (control ES, 7.4 +/- 1.5%; control pH(i), 7.11 +/- 0.05; n = 10). alpha-AS enhanced both ES (delta ES, 1.8 +/- 0.6%; p less than 0.05) and pH(i) (delta pH(i), 0.06 +/- 0.01; p less than 0.005), and there was a significant correlation between delta ES and delta pH(i) (r = 0.76, p less than 0.05). A similar effect of alpha-AS on pH(i) was observed in the absence of electrical stimulation (n = 8). The alpha-AS-induced enhancement of ES and pH(i) was abolished by 10 microM ethylisopropylamiloride, a Na(+)-H+ exchange inhibitor (n = 7). In additional experiments, myocytes were preincubated either with 0.2 microM 4 beta-phorbol 12-myristate 13-acetate (n = 8) or with 5 nM staurosporine (n = 8), which have been shown to downregulate and inhibit Ca(2+)-activated phospholipid-dependent protein kinase C, respectively. In either group, alpha-AS had no effect on pH(i) and decreased ES to approximately 60% of control.(ABSTRACT TRUNCATED AT 400 WORDS)
Nutrigenomics and Selenium: Gene Expression Patterns, Physiological Targets, and Genetics
Authors: John Hesketh
Journal: Annual Review of Nutrition (2008)

Dietary selenium intake is regarded as an important factor in determining optimal health and susceptibility to disease. Therefore, it is critical to understand the interaction between selenium intake and molecular events at the genetic and cellular level. This article addresses two facets of this interaction. The first facet is how genomics is contributing to understanding the molecular mechanisms by which selenium affects cell function through selenoproteins and downstream targets of Se supply in other metabolic pathways. The contribution of transgenic animals in this field is emphasized, and the more recent studies using transcriptomics are discussed. The second facet is the extent to which single nucleotide polymorphisms (SNPs) in genes encoding selenoproteins and components of the selenoprotein synthetic machinery affect individual dietary requirements for optimal health. The state of knowledge of known functional SNPs in selenoprotein genes is presented, and a strategy for future studies is discussed.
Vascular Endothelial Growth Factor Secreted by Activated Stroma Enhances Angiogenesis and Hormone-Independent Growth of Estrogen Receptor–Positive Breast Cancer
Authors: Mauricio P. Pinto, Melanie M. Badtke, Michelle L. Dudevoir, J. Chuck Harrell, Britta M. Jacobsen, Kathryn B. Horwitz
Journal: Cancer Research (2010)

"Reactive" or activated stroma characterizes many malignancies including breast cancers. Recently, we isolated a reactive mouse mammary gland stromal cell line called BJ3Z. These cells express alpha-smooth muscle actin and stromal cell-derived factor 1 (SDF-1) and are tumorigenic when injected into mice. Here we show that, in vivo, BJ3Z cells influence the angiogenesis and proliferation of xenografted estrogen receptor (ER)-positive MCF-7 human breast cancer cell-derived solid tumors. The growth-promoting effects of BJ3Z cells are equivalent to those of estradiol (E(2)). BJ3Z cells also increase the proliferation of normal mouse mammary luminal cells adjacent to tumors. In vitro, BJ3Z cells reorganize and increase the proliferation of cocultured malignant MCF-7 and normal human breast MCF10A cells grown as organoids in three-dimensional culture. The effects of BJ3Z cells on MCF-7 cells are equivalent to those of E(2). In contrast, BJ3Z cells do not alter the growth of highly aggressive ER-negative MDA-MB-231 human breast cancer cells. We show that BJ3Z cells secrete vascular endothelial growth factor (VEGF). The growth of MCF-7 organoids induced by BJ3Z can be inhibited by antagonists of VEGF and SDF-1. Conversely, recombinant VEGF stimulates the proliferation of MCF-7, but not MDA-MB-231, organoids. We conclude that, in addition to angiogenesis, VEGF released by activated stroma increases the growth of ER-positive malignant epithelial cells and of adjacent normal epithelium. Because activated stroma can substitute for E(2) and fosters hormone-independent growth of ER-positive tumors, we suggest that breast cancers exhibiting intrinsic hormone resistance may respond to antiangiogenic therapies.
Identification of expandable human hepatic progenitors which differentiate into mature hepatic cells in vivo
Authors: G Nowak
Journal: Gut (2005)

Liver diseases include a wide spectrum of both acute and chronic conditions which are associated with significant morbidity and mortality worldwide. Hepatocyte transplantation has therapeutic potential in the treatment of liver diseases, but its clinical use is hampered by the lack of donor tissue. Generation of hepatocytes in vitro from adult or fetal liver cell progenitors or, alternatively, identification of a progenitor population which in vivo can generate mature liver cells could solve this problem.CD117+/CD34+/Lin- human fetal liver cells were isolated by magnetic cell sorting and expanded in culture. Both freshly isolated and in vitro expanded cells in various passages were studied for their ability to be functional in hepatic parenchyma following d-galactosamine (GalN) induced injury in nude C57 black mice.Freshly isolated and in vitro expanded CD117+/CD34+/Lin- cells, when transplanted intrasplenically into GalN treated mice, morphologically and functionally differentiated into hepatocytes and cholangiocytes. Human specific albumin, alpha fetoprotein, cytokeratin 19, and antitrypsin mRNA were expressed in mouse liver. In addition, the human progenitor cells expressed glucose-6-phosphatase, glycogen, albumin, gamma glutamyl transpeptidase, and dipeptidyl peptidase IV after transplantation. Expanded cells in various passages maintained their capacity to differentiate into functional liver cells.Fetal liver CD117+/CD34+/Lin- progenitors and their progeny proliferated in vitro and also functionally differentiated into mature hepatic cells in an acute liver injury model. Successful in vitro expansion of liver progenitor cells provides a basis for developing cell therapy strategies, metabolic and toxicity testing systems, and may serve as a vehicle for gene therapy.
Stable therapeutic effects of mesenchymal stem cell-based multiple gene delivery for cardiac repair
Authors: J. Shujia, H. K. Haider, N. M. Idris, G. Lu, M. Ashraf
Journal: Cardiovascular Research (2007)

AimsWe have previously shown that transplantation of mesenchymal stem cells (MSCs) co-overexpressing angiopoietin-1 (Ang-1) and Akt prevented cell apoptosis, enhanced angiogenesis, and improved left ventricular heart function. The present study was designed to determine the persistence of therapeutic benefits on longer term basis.
Gastrin-releasing peptide-like immunoreactive substance in bronchoalveolar lavage of idiopathic pulmonary fibrosis and sarcoidosis
Authors: M Takeyama, S Nagai, K Kondo, N Morikawa, T Mio, N Satake, M Kitaichi, T Izumi
Journal: European Respiratory Journal (1993)

The neuropeptide gastrin releasing peptide (GRP) is present in the lung, and functions as a modulator of tissue growth and repair in fibrotic processes, or as a modulator of cell movement and differentiation in various inflammatory processes, including granulomatous ones. In idiopathic pulmonary fibrosis (IPF), changes in the bronchoalveolar lavage (BAL) content of GRP can be expected. We measured GRP-like immunoreactive substances (GRP-IS) and another neuropeptide, vasoactive intestinal peptide (VIP)-IS in BAL by enzyme immunoassay. Our results showed a decrease in BAL GRP-IS in patients with IPF (26.5 +/- 5.5 pg.mg-1 protein) and sarcoidosis (35.9 +/- 9.2 pg.mg-1), compared to healthy nonsmokers (63.4 +/- 9.0 pg.mg-1). When data were expressed as pg.ml-1 BAL fluid recovered, a decrease was only seen in IPF, not in sarcoidosis. The levels of VIP-IS in BAL were not different between the groups studied. Increased protein levels in BAL had no correlation with the levels of GRP-IS or VIP-IS in BAL. Furthermore, BAL neutrophil percentages had no correlation with the levels of GRP-IS in BAL of patients with IPF. Using reversed phase high performance liquid chromatography (HPLC), several kinds of GRP-IS were detected in BAL. These findings suggest that the decreased level of GRP-IS in BAL may reflect a loss of GRP-producing cells due to chronic lung injury and fibrosis in patients with IPF.
Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies
Authors: Juan Antonio Avina-Zubieta, Jamie Thomas, Mohsen Sadatsafavi, Allen J Lehman, Diane Lacaille
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To determine the magnitude of the risk of incident cardiovascular disease (CVD; fatal and non-fatal), including acute myocardial infarction (MI), cerebrovascular accidents (CVA) and congestive heart failure (CHF), in patients with rheumatoid arthritis (RA) compared to the general population through a meta-analysis of controlled observational studies. <h3>Methods</h3> The authors searched the Medline, Embase, LILACS and Cochrane databases from their inception to June 2011. Observational studies meeting the following criteria were included: (1) prespecified RA criteria; (2) predefined CVD criteria for incident CVD (MI, CVA or CHF); (3) a comparison group; and (4) RR estimates, 95% CI or data for calculating them. The authors calculated the pooled RR using the random-effects model and tested for heterogeneity using the bootstrap version of the Q statistic. <h3>Results</h3> Fourteen studies comprising 41 490 patients met the inclusion criteria. Overall, there was a 48% increased risk of incident CVD in patients with RA (pooled RR 1.48 (95% CI 1.36 to 1.62)). The risks of MI and CVA were increased by 68% (pooled RR 1.68 (95% CI 1.40 to 2.03)) and 41% (pooled RR 1.41 (95% CI 1.14 to 1.74)). The risk of CHF was assessed in only one study (RR 1.87 (95% CI 1.47 to 2.39)). Significant heterogeneity existed in all main analyses. Subgroup analyses showed that inception cohort studies were the only group that did not show a significantly increased risk of CVD (pooled RR 1.12 (95% CI 0.97 to 1.65)). <h3>Conclusions</h3> Published data indicate that the risk of incident CVD is increased by 48% in patients with RA compared to the general population. Sample and cohort type influenced the estimates of RR.
Blockade of Tim-3 Pathway Ameliorates Interferon-γ Production from Hepatic CD8+ T Cells in a Mouse Model of Hepatitis B Virus Infection
Authors: Ying Ju, Nan Hou, Xiaoning Zhang, Di Zhao, Ying Liu, Jinjin Wang, Fang Luan, Wei Shi, Faliang Zhu, Wensheng Sun, Lining Zhang, Chengjiang Gao, Lifen Gao, Xiaohong Liang, Chunhong Ma
Journal: Cellular and Molecular Immunology (2009)
Neuronal basis of imagery
Authors: Evgeni N. Sokolov
Journal: Behavioral and Brain Sciences (2002)

The depiction of pictures as specified points in a functional space is achieved by vector encoding. Picture-selective neurons are added to the declarative memory in the process of learning. New neurons are recruited from stem cells through their proliferation and differentiation. Electrical stimulation of the temporo-parietal cortex produces subjective scenes of the past similar to imagery.
THE EVALUATION OF DIAGNOSTIC TESTS: Principles, Problems, and New Developments
Authors: Harold C. Sox, M.D
Journal: Annual Review of Medicine (1996)

This article describes the use of probability in reasoning about diagnostic test results and the importance of accurate measures of test performance. Most studies of test performance are retrospective analyses of unplanned observations. Retrospective studies are likely to result in biased estimates of test performance. This article shows how to adjust for biases in the results of retrospective studies and how to design a prospective study that will accurately measure the sensitivity and specificity of a test.
Protein kinase activity associated with the surface of guinea pig macrophages.
Authors: E Remold-O'Donnell
Journal: The Journal of Experimental Medicine (1978)

Protein kinase activity has been detected associated with the outer surface of guinea pig peritoneal macrophages. Macrophages incubated with [gamma-32P]ATP incorporated 32P-phosphate into cell-associated proteins. Inorganic phosphate did not compete, nor could inorganic [32P]phosphate substitute as the phosphate donor, demonstrating that transfer of phosphate from ATP to protein is direct and extracellular. The macrophage-associated protein kinase was also shown to phosphorylate added acceptor protein (histone) and to be tightly associated with the cell surface. Thus, a new ectoenzyme, a protein kinase, has been detected in macrophages.
Outcomes for COPD pharmacological trials: from lung function to biomarkers
Authors: M. Cazzola, W. MacNee, F. J. Martinez, K. F. Rabe, L. G. Franciosi, P. J. Barnes, V. Brusasco, P. S. Burge, P. M. A. Calverley, B. R. Celli, P. W. Jones, D. A. Mahler, B. Make, M. Miravitlles, C. P. Page, P. Palange, D. Parr, M. Pistolesi, S. I. Rennard, M. P. Rutten-van Mölken, R. Stockley, S. D. Sullivan, J. A. Wedzicha, E. F. Wouters
Journal: European Respiratory Journal (2008)

The American Thoracic Society/European Respiratory Society jointly created a Task Force on “Outcomes for COPD pharmacological trials: from lung function to biomarkers” to inform the chronic obstructive pulmonary disease research community about the possible use and limitations of current outcomes and markers when evaluating the impact of a pharmacological therapy. Based on their review of the published literature, the following document has been prepared with individual sections that address specific outcomes and markers, and a final section that summarises their recommendations.