tbuckley/cabot-search huggingface dataset:
Gastric secretion of platelet activating factor and precursors in healthy humans: effect of pentagastrin.
Authors: I Sobhani, Y Denizot, S Hochlaf, D Rigaud, J Vatier, J Benveniste, M J Lewin, M Mignon
Journal: Gut (1993)

<b>Aim:</b> To elucidate the optical basis for unilateral high myopia and to identify the factors associated with its development. <b>Methods:</b> Medical records of 48 children (aged 4 months to 17 years; mean age 6.8 years) with unilateral high myopia (5 dioptres or more) seen consecutively by the author during a 15 year period were reviewed. 45 (94%) of the 48 patients had unilateral axial myopia. <b>Results:</b> The mean refractive difference between paired eyes was 9.4 (SD 3.6) dioptres and the more myopic eye was on average 3.3 (1.8) mm longer than the less myopic eye. All but three of the patients had an ocular disorder associated with reduced acuity, central nervous system abnormality, or family history of high myopia. <b>Conclusion:</b> Clinical conditions associated with unilateral high myopia can be identified in the majority of patients and often account for the associated visual impairment.
Neutrophil elastase: alpha-1-proteinase inhibitor complex in serum and bronchoalveolar lavage fluid in patients with pulmonary fibrosis
Authors: H Yamanouchi, J Fujita, S Hojo, T Yoshinouchi, T Kamei, I Yamadori, Y Ohtsuki, N Ueda, J Takahara
Journal: European Respiratory Journal (1998)

It was hypothesized that neutrophil elastase released from activated neutrophils may play an important role in the pathogenesis of pulmonary fibrosis. In the present study, we measured the neutrophil elastase:alpha-1-proteinase inhibitor complex (E-PI) in serum and bronchoalveolar lavage fluid (BALF) in 26 patients with pulmonary fibrosis and evaluated the correlation between E-PI levels and several parameters. E-PI levels in serum of patients with pulmonary fibrosis (635.8+/-112.0 ng.mL(-1)) were significantly elevated compared to normal nonsmokers (122.0+/-4.0 ng.mL(-1)) as well as normal smokers (132.8+/-8.4 ng.mL(-1)) (p<0.01). E-PI levels in serum significantly correlated with hepatocyte growth factor (HGF) levels in serum, C-reactive protein (CRP), and negatively correlated with arterial oxygen tension (Pa,O2), and arterial carbon dioxide tension (Pa,CO2). E-PI/albumin levels in BALF significantly correlated with HGF/albumin levels in BALF, lactate dehydrogenase (LDH)/albumin in BALF, total number of inflammatory cells (alveolar macrophages and neutrophils) in BALF, and several markers derived from epithelial cells in BALF. Our data demonstrated: 1) neutrophil elastase:alpha-1-proteinase inhibitor complex in serum increased in patients with pulmonary fibrosis; and 2) neutrophil elastase:alpha-1-proteinase inhibitor complex in serum and bronchoalveolar lavage fluid correlated with clinical parameters in pulmonary fibrosis. These results suggest that neutrophil elastase may play a significant role in the process of lung injury in pulmonary fibrosis.
Microchimerism in Sjogren's syndrome
Authors: R Giacomelli
Journal: Annals of the Rheumatic Diseases (2002)

The evidence of microchimerism both lends support to and raises doubts about its specific role in SS

The advent of molecular biology techniques has led to the recognition that cells travel in both directions between mother and fetus. Fetal stem cells traverse the placenta and may persist in the maternal circulation for decades. Similarly, maternal cells may pass into the fetal circulation and persist into adult life.1 The persistence of genetically different cells in the same person has been called chimerism. When low levels of donor cells are present the term microchimerism is applied.

Clinical and immunological features of different autoimmune diseases strikingly resemble chronic graft versus host disease, which occurs in some patients after allogeneic bone marrow transplantation, a known condition of chimerism.2 The recent finding that increased amounts of fetal cells, which persisted after pregnancy, can be detected in autoimmune diseases3–8 has raised the possibility that an allogeneic process rather than an autologous breakdown in self tolerance may be involved in the pathogenesis of these diseases.9

Microchimerism has recently been investigated in Sjogren's syndrome (SS),10–15 a disease in which some histological patterns mirror the lesions seen in chronic graft versus host disease. In this issue of the Annals Kuroki and coworkers present their data concerning the presence of maternal fetal microchimeric cells in the salivary glands and lung tissue from 56 female patients with SS, 36 with primary SS, and 20 with SS associated with another autoimmune disease.16 Using both nested polymerase chain reaction (PCR) and fluorescence in situ hybridisation (FISH) techniques, they showed that male DNA were present in 10/28 …
Functional analysis of human and chimpanzee promoters.
Authors: Florian Heissig, Johannes Krause, Jaroslaw Bryk, Philipp Khaitovich, Wolfgang Enard, Svante Pääbo
Journal: Genome biology (2005)

Abstract Background It has long been argued that changes in gene expression may provide an additional and crucial perspective on the evolutionary differences between humans and chimpanzees. To investigate how often expression differences seen in tissues are caused by sequence differences in the proximal promoters, we tested the expression activity in cultured cells of human and chimpanzee promoters from genes that differ in mRNA expression between human and chimpanzee tissues. Results Twelve promoters for which the corresponding gene had been shown to be differentially expressed between humans and chimpanzees in liver or brain were tested. Seven showed a significant difference in activity between the human promoter and the orthologous chimpanzee promoter in at least one of the two cell lines used. However, only three of them showed a difference in the same direction as in the tissues. Conclusion Differences in proximal promoter activity are likely to be common between humans and chimpanzees, but are not linked in a simple fashion to gene-expression levels in tissues. This suggests that several genetic differences between humans and chimpanzees might be responsible for a single expression difference and thus that relevant expression differences between humans and chimpanzees will be difficult to predict from cell culture experiments or DNA sequences.
Expression of Tissue Inhibitor of Matrix Metalloproteinases 1 by Use of an Adenoviral Vector Inhibits Smooth Muscle Cell Migration and Reduces Neointimal Hyperplasia in the Rat Model of Vascular Balloon Injury
Authors: Clare M. Dollery, Steven E. Humphries, Alan McClelland, David S. Latchman, Jean R. McEwan
Journal: Circulation (1999)

Background —Cell migration is a major contributor to injury-induced neointimal hyperplasia and depends on alteration of the proteolytic balance within the arterial wall toward matrix breakdown. This is partly mediated by the matrix metalloproteinases (MMPs) and their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Methods and Results —An increase in expression of biologically active and immunoreactive TIMP-1 was seen in vitro after infection of rat smooth muscle cells (SMCs) with Av1.TIMP1 (an adenoviral vector containing the human TIMP1 cDNA). Infection of rat SMCs with Av1.TIMP1 reduced migration in vitro by 27% compared with control virus–infected cells (37.6±4.34 versus 51±5.01 cells per high-power field, P &lt;0.05). The adenoviral vector was delivered to the injured rat carotid artery, and 4 days later, immunoreactive protein was identified and migration of SMCs reduced by 60% (5.2±0.5 versus 12.8±1.5 cells per section, P &lt;0.05, n=5). Neointimal area 14 days after injury showed a 30% reduction in the animals receiving the Av1.TIMP1 virus compared with controls (0.09±0.01 versus 0.14±0.01 mm 2 , P =0.02, n=14). Conclusions —The response to arterial balloon injury involves MMP-dependent SMC migration and can be attenuated in vivo by the transmural expression of TIMP-1 by adenoviral gene transfer.
Endothelial Nitric Oxide Synthase in Vascular Disease
Authors: Ulrich Förstermann, Thomas Münzel
Journal: Circulation (2006)

Nitric oxide (NO·) is an important protective molecule in the vasculature, and endothelial NO· synthase (eNOS) is responsible for most of the vascular NO· produced. A functional eNOS oxidizes its substrate l -arginine to l -citrulline and NO·. This normal function of eNOS requires dimerization of the enzyme, the presence of the substrate l -arginine, and the essential cofactor (6 R )-5,6,7,8-tetrahydro- l -biopterin (BH 4 ), one of the most potent naturally occurring reducing agents. Cardiovascular risk factors such as hypertension, hypercholesterolemia, diabetes mellitus, or chronic smoking stimulate the production of reactive oxygen species in the vascular wall. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases represent major sources of this reactive oxygen species and have been found upregulated and activated in animal models of hypertension, diabetes, and sedentary lifestyle and in patients with cardiovascular risk factors. Superoxide (O 2 · − ) reacts avidly with vascular NO· to form peroxynitrite (ONOO − ). The cofactor BH 4 is highly sensitive to oxidation by ONOO − . Diminished levels of BH 4 promote O 2 · − production by eNOS (referred to as eNOS uncoupling). This transformation of eNOS from a protective enzyme to a contributor to oxidative stress has been observed in several in vitro models, in animal models of cardiovascular diseases, and in patients with cardiovascular risk factors. In many cases, supplementation with BH 4 has been shown to correct eNOS dysfunction in animal models and patients. In addition, folic acid and infusions of vitamin C are able to restore eNOS functionality, most probably by enhancing BH 4 levels as well.
The Contribution of Accessory Toxins of <i>Vibrio cholerae</i> O1 El Tor to the Proinflammatory Response in a Murine Pulmonary Cholera Model
Authors: Karla Jean Fullner, John C. Boucher, Martha A. Hanes, G. Kenneth Haines, Brian M. Meehan, Cynthia Walchle, Philippe J. Sansonetti, John J. Mekalanos
Journal: The Journal of Experimental Medicine (2002)

The contribution of accessory toxins to the acute inflammatory response to Vibrio cholerae was assessed in a murine pulmonary model. Intranasal administration of an El Tor O1 V. cholerae strain deleted of cholera toxin genes (ctxAB) caused diffuse pneumonia characterized by infiltration of PMNs, tissue damage, and hemorrhage. By contrast, the ctxAB mutant with an additional deletion in the actin-cross-linking repeats-in-toxin (RTX) toxin gene (rtxA) caused a less severe pathology and decreased serum levels of proinflammatory molecules interleukin (IL)-6 and murine macrophage inflammatory protein (MIP)-2. These data suggest that the RTX toxin contributes to the severity of acute inflammatory responses. Deletions within the genes for either hemagglutinin/protease (hapA) or hemolysin (hlyA) did not significantly affect virulence in this model. Compound deletion of ctxAB, hlyA, hapA, and rtxA created strain KFV101, which colonized the lung but induced pulmonary disease with limited inflammation and significantly reduced serum titers of IL-6 and MIP-2. 100% of mice inoculated with KFV101 survive, compared with 20% of mice inoculated with the ctxAB mutant. Thus, the reduced virulence of KFV101 makes it a prototype for multi-toxin deleted vaccine strains that could be used for protection against V. cholerae without the adverse effects of the accessory cholera toxins.
Effects of long-term exposure to air pollution on natural-cause mortality: an analysis of 22 European cohorts within the multicentre ESCAPE project
Authors: Rob Beelen, Ole Raaschou-Nielsen, Massimo Stafoggia, Zorana Jovanovic Andersen, Gudrun Weinmayr, Barbara Hoffmann, Kathrin Wolf, Evangelia Samoli, Paul Fischer, Mark Nieuwenhuijsen, Paolo Vineis, Wei W Xun, Klea Katsouyanni, Konstantina Dimakopoulou, Anna Oudin, Bertil Forsberg, Lars Modig, Aki S Havulinna, Timo Lanki, Anu Turunen, Bente Oftedal, Wenche Nystad, Per Nafstad, Ulf De Faire, Nancy L Pedersen, Claes-Göran Östenson, Laura Fratiglioni, Johanna Penell, Michal Korek, Göran Pershagen, Kirsten Thorup Eriksen, Kim Overvad, Thomas Ellermann, Marloes Eeftens, Petra H Peeters, Kees Meliefste, Meng Wang, Bas Bueno-de-Mesquita, Dorothea Sugiri, Ursula Krämer, Joachim Heinrich, Kees de Hoogh, Timothy Key, Annette Peters, Regina Hampel, Hans Concin, Gabriele Nagel, Alex Ineichen, Emmanuel Schaffner, Nicole Probst-Hensch, Nino Künzli, Christian Schindler, Tamara Schikowski, Martin Adam, Harish Phuleria, Alice Vilier, Françoise Clavel-Chapelon, Christophe Declercq, Sara Grioni, Vittorio Krogh, Ming-Yi Tsai, Fulvio Ricceri, Carlotta Sacerdote, Claudia Galassi, Enrica Migliore, Andrea Ranzi, Giulia Cesaroni, Chiara Badaloni, Francesco Forastiere, Ibon Tamayo, Pilar Amiano, Miren Dorronsoro, Michail Katsoulis, Antonia Trichopoulou, Bert Brunekreef, Gerard Hoek
Journal: The Lancet (2013)
ERG Status Is Unrelated to PSA Recurrence in Radically Operated Prostate Cancer in the Absence of Antihormonal Therapy
Authors: Sarah Minner, Malaika Enodien, Hüseyin Sirma, Andreas M. Luebke, Antje Krohn, Pascale S. Mayer, Ronald Simon, Pierre Tennstedt, Julia Müller, Laura Scholz, Jan C. Brase, Alvin Y. Liu, Hartmut Schlüter, Klaus Pantel, Udo Schumacher, Carsten Bokemeyer, Thomas Steuber, Markus Graefen, Guido Sauter, Thorsten Schlomm
Journal: Clinical Cancer Research (2011)

About 50% of prostate cancers have TMPRSS2-ERG fusions with concurrent ERG overexpression. The aim of this study was to determine whether clinical differences exist between ERG-positive and ERG-negative cancers in surgically treated patients not exposed to antihormonal therapy. A secondary aim was to search for differences between these tumor classes.A tissue microarray containing samples from more than 2,800 prostate cancers with clinical data was analyzed for ERG alterations by immunohistochemistry and FISH. Results were compared with tumor phenotype, biochemical recurrence, and molecular features considered important for prostate cancer. The effect of ERG on androgen receptor (AR)-dependent transcription was analyzed in cell lines.ERG expression was found in 52.4% of 2,805 cancers with a 95% concordance between ERG expression and ERG gene rearrangement detected by FISH. ERG expression was unrelated to clinical outcome and tumor phenotype. Differences in AMACR, Annexin A3, Bcl2, CD10, ALCAM, chromogranin A, epidermal growth factor receptor, HER2, mTOR, p53, and synaptophysin status were significant but minimal in absolute numbers. The most striking difference was found for AR expression, which was markedly higher in ERG-positive cancers. In vitro studies showed ERG-dependent impairment of AR-mediated transcriptional activity.The striking similarities between these two types of prostate cancers rules out a major impact of ERG on tumor aggressiveness in early, not hormonally treated cancer. The marked difference in AR levels between ERG-positive and -negative cancers supports a systematic difference in potential response to hormonal therapy as previously observed in clinical trials.
A New Three-Dimensional Ultrasound Microimaging Technology for Preclinical Studies Using a Transgenic Prostate Cancer Mouse Model
Authors: Lauren A. Wirtzfeld, Guojun Wu, Michael Bygrave, Yasuto Yamasaki, Hideki Sakai, Madeleine Moussa, Jonathan I. Izawa, Dónal B. Downey, Norman M. Greenberg, Aaron Fenster, Jim W. Xuan, James C. Lacefield
Journal: Cancer Research (2005)

Prostate cancer is the most common cancer in adult men in North America. Preclinical studies of prostate cancer employ genetically engineered mouse models, because prostate cancer does not occur naturally in rodents. Widespread application of these models has been limited because autopsy was the only reliable method to evaluate treatment efficacy in longitudinal studies. This article reports the first use of three-dimensional ultrasound microimaging for measuring tumor progression in a genetically engineered mouse model, the 94-amino acid prostate secretory protein gene-directed transgenic prostate cancer model. Qualitative comparisons of three-dimensional ultrasound images with serial histology sections of prostate tumors show the ability of ultrasound to accurately depict the size and shape of malignant masses in live mice. Ultrasound imaging identified tumors ranging from 2.4 to 14 mm maximum diameter. The correlation coefficient of tumor diameter measurements done in vivo with three-dimensional ultrasound and at autopsy was 0.998. Prospective tumor detection sensitivity and specificity were both >90% when diagnoses were based on repeated ultrasound examinations done on separate days. Representative exponential growth curves constructed via longitudinal ultrasound imaging indicated volume doubling times of 5 and 13 days for two prostate tumors. Compared with other microimaging and molecular imaging modalities, the application of three-dimensional ultrasound imaging to prostate cancer in mice showed advantages, such as high spatial resolution and contrast in soft tissue, fast and uncomplicated protocols, and portable and economical equipment that will likely enable ultrasound to become a new microimaging modality for mouse preclinical trial studies.
Regional hippocampal damage in heart failure
Authors: Mary A. Woo, Jennifer A. Ogren, Christiane M. Abouzeid, Paul M. Macey, Kevin G. Sairafian, Priya S. Saharan, Paul M. Thompson, Gregg C. Fonarow, Michele A. Hamilton, Ronald M. Harper, Rajesh Kumar
Journal: European Journal of Heart Failure (2015)
Failure of glycogen depletion to improve left ventricular function of the rabbit heart after hypothermic ischemic arrest.
Authors: C F Lagerstrom, W E Walker, H Taegtmeyer
Journal: Circulation Research (1988)

We tested the hypothesis that depletion of glycogen prior to myocardial ischemia diminishes lactate buildup and improves functional recovery on reperfusion in the isolated rabbit heart. Cardiac glycogen was reduced either by substituting N2 for O2 in the perfusate or by perfusion with substrate-free solution, before the onset of ischemia. Hearts were subjected to either 30 minutes of normothermic (37 degrees C) or 60 minutes of hypothermic (4 degrees C) ischemia followed by 30 minutes of reperfusion with oxygenated Krebs-Henseleit buffer. Function was assessed by measuring peak left ventricular pressure at end-diastolic pressures ranging from 0 to 20 mm Hg. N2 perfusion for 15 minutes lowered myocardial glycogen by 60% and decreased ATP and phosphocreatine (p less than 0.001). Glycogen depletion did not decrease lactate accumulation during ischemia, but it impaired recovery with reperfusion (-46%, p less than 0.05). N2 perfusion for 5 minutes also reduced glycogen by 60%, but energy-rich phosphates were not reduced and functional recovery was still impaired (-40%, p less than 0.05). Perfusion with substrate-free medium diminished glycogen by 33% (p less than 0.05). Although lactate accumulation was significantly reduced (-45%, p less than 0.05), recovery following reperfusion was not improved. The results suggest that preservation of glycogen stores, but not the prevention of lactate buildup during ischemia, is beneficial for the recovery of function with reperfusion.
Suppression of in vitro cytotoxic response by macrophages due to induced arginase.
Authors: J T Kung, S B Brooks, J P Jakway, L L Leonard, D W Talmage
Journal: The Journal of Experimental Medicine (1977)

Arginine was found to be completely depleted from cell-free supernates of mixed leukocyte cultures suppressed by the addition of excess macrophages. Partial reversal of macrophage-mediated suppression was accomplished by daily addition of a cocktail containing arginine and nonamino acid nutrients. Complete reversal of the suppression was accomplished by the addition of arginine and glucose to the medium and the nonadherent cells after their separation from the adherent macrophages. A marked increase in the enzyme arginase was found in macrophages that had been cultured 24 h in vitro in Eagle's minimum essential medium plus 10% fetal calf serum, in peritoneal cells activated by prior injection of thioglycollate, and in one spleen activated by a graft vs. host reaction.
Delayed Hypersensitivity to Penicillin
Authors: Michael J. Fellner
Journal: JAMA (1969)

Delayed skin-test hypersensitivity to penicillin G potassium has been associated with the occurrence of exanthematous, erythrodermic, local indurative, and generalized pruritic adverse clinical reactions to therapeutic doses of penicillin. A pronounced regular decrease in delayed skin-test hypersensitivity to penicillin G followed the administration of therapeutic doses of penicillin. In about one half of the patients, the delayed hypersensitivity was, at least temporarily, completely abolished. Preliminary data suggest that with the doses of penicillin given to our patients the decrease in delayed hypersensitivity lasts for a period of a few weeks to about five months.
Inhibition of CXCR4-Mediated Breast Cancer Metastasis: A Potential Role for Heparinoids?
Authors: James R. Harvey, Paul Mellor, Hesham Eldaly, Thomas W.J. Lennard, John A. Kirby, Simi Ali
Journal: Clinical Cancer Research (2007)

The pattern of breast cancer metastasis may be determined by interactions between CXCR4 on breast cancer cells and CXCL12 within normal tissues. Glycosaminoglycans bind chemokines for presentation to responsive cells. This study was designed to test the hypothesis that soluble heparinoid glycosaminoglycan molecules can disrupt the normal response to CXCL12, thereby reducing the metastasis of CXCR4-expressing cancer cells.Inhibition of the response of CXCR4-expressing Chinese hamster ovary cells to CXCL12 was assessed by measurement of calcium flux and chemotaxis. Radioligand binding was also assessed to quantify the potential of soluble heparinoids to prevent specific receptor ligation. The human breast cancer cell line MDA-MB-231 and a range of sublines were assessed for their sensitivity to heparinoid-mediated inhibition of chemotaxis. A model of hematogenous breast cancer metastasis was established, and the potential of clinically relevant doses of heparinoids to inhibit CXCL12 presentation and metastatic disease was assessed.Unfractionated heparin and the low-molecular-weight heparin tinzaparin inhibited receptor ligation and the response of CXCR4-expressing Chinese hamster ovary cells and human breast cancer cell lines to CXCL12. Heparin also removed CXCL12 from its normal site of expression on the surface of parenchymal cells in the murine lung. Both heparin and two clinically relevant dose regimens of tinzaparin reduced hematogenous metastatic spread of human breast cancer cells to the lung in a murine model.Clinically relevant concentrations of tinzaparin inhibit the interaction between CXCL12 and CXCR4 and may be useful to prevent chemokine-driven breast cancer metastasis.