tbuckley/cabot-search huggingface dataset:
A Study of Hepatic Hemodynamics in the Dog
Authors: CHARLES P. SHOEMAKER
Journal: Circulation Research (1964)

The effects of altered hepatic blood flow, of splanchnic and hepatic nerve stimulation, and of injecting epinephrine and vasopressin (Pitressin) were studied by perfusing canine livers in vitro. Controlled hepatic arterial perfusions demonstrated a linear relationship between arterial pressure and hepatic arterial inflow. It was found that increases of hepatic artery flow slightly increased portal vein pressure and vascular resistance of the portal vein, and that increases of portal vein flow slightly increased hepatic artery vascular resistance. Splanchnic nerve stimulation caused vasoconstriction of the hepatic artery, portal vein, and mesenteric vasculature. Hepatic nerve stimulation caused constriction of only the hepatic artery and portal vein vasculature. Similar results were obtained by the administration of epinephrine. Pitressin caused marked vasoconstriction of the mesenteric vasculature, vasodilatation of the portal vein vascular bed, and slightly increased hepatic artery vasomotor tone. It was noted that the rise in portal vein vasomotor tone with sympathetic stimulation was due in part to constriction of the "postjunctional" resistance.
Genetics of Behcet disease inside and outside the MHC
Authors: A. Meguro, H. Inoko, M. Ota, Y. Katsuyama, A. Oka, E. Okada, R. Yamakawa, T. Yuasa, T. Fujioka, S. Ohno, S. Bahram, N. Mizuki
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Background</h3> Behçet disease (BD) is a rare, chronic, systemic, inflammatory disorder characterised by recurrent ocular, genital and skin lesions. Although its aetiology is still uncertain, an intricate interplay between the environment (eg, viruses) and the host seems to initiate and/or perpetuate the disease, although the mechanism remains speculative. Since the identification of <i>HLA-B*5101</i> (and more recently of <i>MICA</i>) as a susceptibility locus for BD, the identification of additional genetic locus/loci, whether inside, or perhaps more importantly outside the MHC has clearly stalled. <h3>Objective</h3> To carry out a genome-wide association study (GWAS) of BD. <h3>Methods</h3> 300 Japanese patients with BD and an equal number of controls were recruited. The samples were screened using a dense panel of 23 465 microsatellites (MS) covering the entire genome. <h3>Results</h3> The six best (of a total of 147) positively associated MS with BD were identified. Of these six, two were located within the human leucocyte antigen (HLA) class I region itself. Although one of these was clearly reminiscent of the association with <i>HLA-B</i>, the second, not in linkage disequilibrium with the former, was in the telomeric side of the class I region and remained to be formally identified. HLA genotyping and haplotype analysis conclusively led to the deciphering of a dual, independent, contribution of two HLA alleles to the pathogenesis of BD: <i>HLA-B*5101</i> and <i>HLA-A*26</i>. <h3>Conclusions</h3> This GWAS highlights the premier genetic susceptibility locus for BD as the major histocompatibility complex itself, wherein reside two independent loci: <i>HLA-B</i> and <i>HLA-A</i>.
Chemotrap-1: An Engineered Soluble Receptor That Blocks Chemokine-Induced Migration of Metastatic Cancer Cells<i>In vivo</i>
Authors: Silvia Lanati, Darryl B. Dunn, Myriam Roussigné, Maxine S. Emmett, Virginie Carriere, Denis Jullien, Jessica Budge, Justin Fryer, Monique Erard, Françoise Cailler, Jean-Phillippe Girard, David O. Bates
Journal: Cancer Research (2010)

Cancer and dendritic cells recognize and migrate toward chemokines secreted from lymphatics and use this mechanism to invade the lymphatic system, and cancer cells metastasize through it. The lymphatic-secreted chemokine ligand CCL21 has been identified as a key regulatory molecule in the switch to a metastatic phenotype in melanoma and breast cancer cells. However, it is not known whether CCL21 inhibition is a potential therapeutic strategy for inhibition of metastasis. Here, we describe an engineered CCL21-soluble inhibitor, Chemotrap-1, which inhibits migration of metastatic melanoma cells in vivo. Two-hybrid, pull-down, and coimmunoprecipitation assays allowed us to identify a naturally occurring human zinc finger protein with CCL21 chemokine-binding properties. Further analyses revealed a short peptide (∼70 amino acids), with a predicted coiled-coil structure, which is sufficient for association with CCL21. This CCL21 chemokine-binding peptide was then fused to the Fc region of human IgG1 to generate Chemotrap-1, a human chemokine-binding Fc fusion protein. Surface plasmon resonance and chemotaxis assays showed that Chemotrap-1 binds CCL21 and inhibits CCL21-induced migration of melanoma cells in vitro with subnanomolar affinity. In addition, Chemotrap-1 blocked migration of melanoma cells toward lymphatic endothelial cells in vitro and in vivo. Finally, Chemotrap-1 strongly reduced lymphatic invasion, tracking, and metastasis of CCR7-expressing melanoma cells in vivo. Together, these results show that CCL21 chemokine inhibition by Chemotrap-1 is a potential therapeutic strategy for metastasis and provide further support for the hypothesis that lymphatic-mediated metastasis is a chemokine-dependent process.
Regulator defends its decision to delay use of hybrid embryos
Authors: Adrian O'Dowd
Journal: BMJ (2007)

The fertility regulator has defended its decision to halt applications for human hybrid research in the United Kingdom during a parliamentary inquiry. 

The Human Fertilisation and Embryology Authority (HFEA), independent regulator of in vitro fertilisation treatment and embryo research in the UK, said that research involving hybrids of human and animal cells was “very new and very controversial.” 

Representatives from the authority were giving evidence to the cross party science and technology committee of MPs as part of its inquiry into government proposals to regulate the creation of animal-human hybrid embryos for research. 

The government has published a white …
Superior Penetration and Retention Behavior of 50 nm Gold Nanoparticles in Tumors
Authors: Shuaidong Huo, Huili Ma, Keyang Huang, Juan Liu, Tuo Wei, Shubin Jin, Jinchao Zhang, Shengtai He, Xing-Jie Liang
Journal: Cancer Research (2012)

Nanoparticles offer potential as drug delivery systems for chemotherapeutics based on certain advantages of molecular drugs. In this study, we report that particle size exerts great influence on the penetration and retention behavior of nanoparticles entering tumors. On comparing gold-coated Au@tiopronin nanoparticles that were prepared with identical coating and surface properties, we found that 50 nanoparticles were more effective in all in vitro, ex vivo, and in vivo assays conducted using MCF-7 breast cells as a model system. Beyond superior penetration in cultured cell monolayers, 50 nm Au@tiopronin nanoparticles also penetrated more deeply into tumor spheroids ex vivo and accumulated more effectively in tumor xenografts in vivo after a single intravenous dose. In contrast, larger gold-coated nanoparticles were primarily localized in the periphery of the tumor spheroid and around blood vessels, hindering deep penetration into tumors. We found multicellular spheroids to offer a simple ex vivo tumor model to simulate tumor tissue for screening the nanoparticle penetration behavior. Taken together, our findings define an optimal smaller size for nanoparticles that maximizes their effective accumulation in tumor tissue.
Programming Smooth Muscle Plasticity With Chromatin Dynamics
Authors: Oliver G. McDonald, Gary K. Owens
Journal: Circulation Research (2007)

Smooth muscle cells (SMCs) possess remarkable phenotypic plasticity that allows rapid adaptation to fluctuating environmental cues. For example, vascular SMCs undergo profound changes in their phenotype during neointimal formation in response to vessel injury or within atherosclerotic plaques. Recent studies have shown that interaction of serum response factor (SRF) and its numerous accessory cofactors with CArG box DNA sequences within promoter chromatin of SMC genes is a nexus for integrating signals that influence SMC differentiation in development and disease. During development, SMC-restricted sets of posttranslational histone modifications are acquired within the CArG box chromatin of SMC genes. These modifications in turn control the chromatin-binding properties of SRF. The histone modifications appear to encode a SMC-specific epigenetic program that is used by extracellular cues to influence SMC differentiation, by regulating binding of SRF and its partners to the chromatin template. Thus, SMC differentiation is dynamically regulated by the interplay between SRF accessory cofactors, the SRF–CArG interaction, and the underlying histone modification program. As such, the inherent plasticity of the SMC lineage offers unique glimpses into how cellular differentiation is dynamically controlled at the level of chromatin within the context of changing microenvironments. Further elucidation of how chromatin regulates SMC differentiation will undoubtedly yield valuable insights into both normal developmental processes and the pathogenesis of several vascular diseases that display detrimental SMC phenotypic behavior.
Central melanocortin receptors regulate insulin action
Authors: Silvana Obici, Zhaohui Feng, Jianzhen Tan, LiSen Liu, George Karkanias, Luciano Rossetti
Journal: Journal of Clinical Investigation (2001)

Energy balance and insulin action are tightly coregulated. Leptin regulates energy intake and expenditure partly by modulation of the melanocortin pathway in the hypothalamus. Here we demonstrate potent effects of the melanocortin pathway on insulin action and body distribution of adiposity. Conscious rats received week-long infusions of either a melanocortin receptor agonist, α-melanocyte-stimulating hormone (α-MSH), or antagonist, SHU9119, in the third cerebral ventricle while food intake was maintained constant in each group. α-MSH decreased intra-abdominal fat and markedly enhanced the actions of insulin on both glucose uptake and production, while SHU9119 exerted opposite effects. Our findings elucidate a neuroendocrine network that is likely to play a central role in the coupling of energy intake and insulin action.
Protective effects of erythropoietin and N-acetyl cysteine on methotrexate-induced lung injury in rats
Authors: Hasan Kahraman, Mahmut Tokur, Ergul Kurutas, Selim Bozkurt, Vedat Bakan, Harun Ciralik, Nurhan Koksal
Journal: European Respiratory Journal (2012)

Material and Methods : Twenty-six female Sprague-Dawley rats were divided into 4 groups. Sham group was given subcutaneous (SC) injection of 0.3 ml of 0.9% NaCl (n= 5), MTX group was administered SC of 5 mg/kg methotrexate (MTX), EPO group was administered, SC of 5 mg/kg MTX and 2000 IU/kg EPO, and NAC group was given 5 mg/kg MTX and 200 mg/kg NAC once daily for 4 consecutive days. At the fifth day, the right lungs were extracted. Oxidative damage was evaluated by measuring the malondialdehyde (MDA) level and superoxide dismutase (SOD) and catalase (CAT) activities. Histological damage was evaluated by inflammation and congestion scores.   Results : In MTX group MDA levels were significantly higher, CAT and SOD activities were significantly lower than those in the Sham, EPO and NAC groups (P  0.05).   Conclusion : EPO and NAC have significant preventive effects on methotrexate-induced lung damage in rats.
Research Methods in Physical Activity. 2nd Edn
Authors: R. Maughan
Journal: British Journal of Sports Medicine (1991)

<h3>ABSTRACT</h3> The human liver is an essential multifunctional organ, and liver diseases are rising with limited treatment options. However, the cellular complexity and heterogeneity of the liver remain poorly understood. Here, we performed single-cell RNA-sequencing of ~5,000 cells from normal liver tissue of 6 human donors to construct the first human liver cell atlas. Our analysis revealed previously unknown sub-types among endothelial cells, Kupffer cells, and hepatocytes with transcriptome-wide zonation of these populations. We show that the EPCAM<sup>+</sup> population is highly heterogeneous and consists of hepatocyte progenitors, cholangiocytes and a <i>MUC6</i><sup>+</sup> stem cell population with a specific potential to form liver organoids. As proof-of-principle, we applied our atlas to unravel phenotypic changes in cells from hepatocellular carcinoma tissue and to investigate cellular phenotypes of human hepatocytes and liver endothelial cells engrafted into a humanized <i>FAH</i><sup>-/-</sup> mouse liver. Our human liver cell atlas provides a powerful and innovative resource enabling the discovery of previously unknown cell types in the normal and diseased liver.
Satisfaction with NHS is rising, but funding fears are high
Authors: A. O'Dowd
Journal: BMJ (2015)

The public’s satisfaction with the NHS has risen in the past two years, but most people are worried about its finances, a survey by an independent social research organisation has found.

The latest annual British Social Attitudes report by NatCen Social Research1 also found that satisfaction with accident and emergency (A&E) services had increased in recent years, while satisfaction with GP services had fallen.

The centre surveyed 2878 representative and random adults in Britain for its report, which examined how the public has responded to the changing political landscape and the policies of the coalition government.

Some of the data2 were revealed in January by the health think tank the …
The anti-inflammatory agent alpha-trinositol exerts its edema-preventing effects through modulation of beta 1 integrin function.
Authors: S A Rodt, R K Reed, M Ljungström, T O Gustafsson, K Rubin
Journal: Circulation Research (1994)

Edema formation in acute inflammation can be induced through lowering of interstitial fluid pressure (Pif) and seems to involve dynamic beta 1 integrin-mediated interactions between dermal cells and extracellular matrix fibers. The present experiments investigate the role of beta 1 integrins in the control of Pif. The anti-inflammatory drug alpha-trinositol (1,2,6-D-myo-inositol trisphosphate) stabilizes Pif in acute inflammation. Pretreatment with 5 mg IV alpha-trinositol in pentobarbital-anesthetized rats inhibited the lowering in Pif and the edema formation induced by subdermal injection of anti-beta 1 integrin IgG. This stabilization of the beta 1 integrin function in vivo was paralleled by effects of alpha-trinositol on contraction of fibroblast-populated three-dimensional collagen lattices in vitro. alpha-Trinositol was additive to the known stimulatory effect of platelet-derived growth factor-BB on the final gel size in the collagen gel contraction assay. Furthermore, alpha-trinositol counteracted the inhibitory effect of anti-beta 1 integrin Fab fragments on collagen gel contraction. Finally, subdermal injection of dibutyryl-cAMP (db-cAMP) induced increased negativity of Pif to the same extent as did anti-beta 1 integrin antibodies, and in vitro db-cAMP reduced the ability of fibroblasts to contract collagen gels. The latter effect was opposed by alpha-trinositol. The data demonstrate that alpha-trinositol modulates beta 1 integrin function and may do so via intracellular pathways in turn affecting the function and/or cell surface expression of beta 1 integrins and suggest that alpha-trinositol can serve as a tool to study integrin function. Furthermore, the data indicate that the collagen contraction assays may provide important information of the control of Pif in vivo.
Urinary albumin excretion in patients with systemic lupus erythematosus without renal disease
Authors: E. Batlle-Gualda, A. C. Martinez, R. A. Guerra, E. Pascual
Journal: Annals of the Rheumatic Diseases (1997)

To investigate the prevalence of microalbuminuria, urinary albumin excretion (UAE) between 20-200 micrograms/min, in systemic lupus erythematosus (SLE) patients without clinical renal disease, and to discover if this could predict the development of renal disease.This study made six monthly measurements of UAE, creatinine clearance, serological and clinical data in 22 ambulatory women patients with SLE, without clinical renal disease, hypertension, diabetes or heart failure. The patients were followed up for a period of 18 months (four measurements). Age and sex matched healthy controls were used as a comparative group. UAE was measured by nephelometry in three timed overnight urine samples at each visit.There were no significant differences in the creatinine clearance between the control group and the SLE patients. Creatinine clearance did not show significant changes throughout the study period. SLE patients had wide variations in the UAE rate compared with healthy controls. In five patients (5 of 22; 23%), on occasions, there was mild, transient increase in UAE reaching the level of microalbuminuria. During follow up, one patient with basal (4.67 micrograms/min) and six month (4.73 micrograms/min) normal UAE rate, was admitted with a nephrotic syndrome confirmed on biopsy examination to be proliferative lupus nephritis. Six months after beginning treatment with prednisone and cyclophosphamide her UAE rate returned to normal values (4.65 micrograms/min).SLE patients without clinical renal disease may have microalbuminuria, although this does not seem to warrant any specific action.
Protective Role of Heme Oxygenases against Endotoxin-induced Diaphragmatic Dysfunction in Rats
Authors: CAMILLE TAILLÉ, ROBERTA FORESTI, SOPHIE LANONE, CHRISTINE ZEDDA, COLIN GREEN, MICHEL AUBIER, ROBERTO MOTTERLINI, JORGE BOCZKOWSKI
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Reactive oxygen species are strongly implicated in diaphragmatic dysfunction during sepsis. We investigated whether the heme oxygenase (HO) pathway, which is a powerful protective cellular system, protects the diaphragm against oxidative stress and contractile failure during sepsis. A basal expression of both the inducible and constitutive HO protein isoforms (HO-1 and HO-2, respectively) was found in the diaphragm. Enhanced HO-1 expression in diaphragmatic myocytes was observed 24 h after Escherichia coli endotoxin (lipopolysaccharide, LPS) inoculation and remained elevated for at least 96 h. Enhanced HO-1 expression was also observed in the rectus abdominis and soleus muscles and in the left ventricular myocardium of endotoxemic animals. Diaphragmatic HO-2 expression was not modified by endotoxin. Diaphragmatic HO activity exhibited a biphasic time course characterized by a transient decrease during the first 12 h followed by a significant increase at 24 h, corresponding to HO-1 induction. Diaphragmatic force was significantly reduced 24 h after LPS, concomitantly with muscular oxidative stress. Administation of an inhibitor of heme oxygenase activity, zinc protoporphyrin IX (ZnPP-IX), further impaired muscular oxidative stress and contractile failure. By contrast, increased levels of HO-1 expression obtained by pretreatment of rats with hemin, a powerful inducer of HO-1, completely prevented LPS-mediated diaphragmatic oxidative stress and contractile failure. This protective effect was reversed by ZnPP-IX. These results show an important protective role for the HO pathway against sepsis-induced diaphragmatic dysfunction, which could be related to its antioxidant properties.
Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis
Authors: Heidi S. Phillips, Samir Kharbanda, Ruihuan Chen, William F. Forrest, Robert H. Soriano, Thomas D. Wu, Anjan Misra, Janice M. Nigro, Howard Colman, Liliana Soroceanu, P. Mickey Williams, Zora Modrusan, Burt G. Feuerstein, Ken Aldape
Journal: Cancer Cell (2006)
ISOLATION OF POLIOMYELITIS VIRUS FROM THE NASOPHARYNX
Authors: John R. Paul, James D. Trask, Leslie T. Webster
Journal: The Journal of Experimental Medicine (1935)

A single example of mild illness diagnosed as suspected abortive poliomyelitis is described in which the virus of poliomyelitis was recovered from the nasopharynx by three different methods. Failure to recover virus from a total of twenty-six cases diagnosed as suspected or abortive poliomyelitis and fourteen contacts is also reported. The original material from the nasopharynx of the positive case proved unusually infective for the monkey, apparently even more so than are the majority of suspensions of spinal cords from fatal human cases of poliomyelitis. An explanation of this fact is not clear. The method of isolating human virus from the throat, by means of preserving the sediment of washings from this site in glycerine, has been shown to be efficient in one case for a period of 101 days.
Steroids augment relengthening of contracted airway smooth muscle: potential additional mechanism of benefit in asthma
Authors: O. J. Lakser, M. L. Dowell, F. L. Hoyte, B. Chen, T. L. Lavoie, C. Ferreira, L. H. Pinto, N. O. Dulin, P. Kogut, J. Churchill, R. W. Mitchell, J. Solway
Journal: European Respiratory Journal (2008)

Breathing (especially deep breathing) antagonises development and persistence of airflow obstruction during bronchoconstrictor stimulation. Force fluctuations imposed on contracted airway smooth muscle (ASM) in vitro result in its relengthening, a phenomenon called force fluctuation-induced relengthening (FFIR). Because breathing imposes similar force fluctuations on contracted ASM within intact lungs, FFIR represents a likely mechanism by which breathing antagonises bronchoconstriction. While this bronchoprotective effect appears to be impaired in asthma, corticosteroid treatment can restore the ability of deep breaths to reverse artificially induced bronchoconstriction in asthmatic subjects. It has previously been demonstrated that FFIR is physiologically regulated through the p38 mitogen-activated protein kinase (MAPK) signalling pathway. While the beneficial effects of corticosteroids have been attributed to suppression of airway inflammation, the current authors hypothesised that alternatively they might exert their action directly on ASM by augmenting FFIR as a result of inhibiting p38 MAPK signalling. This possibility was tested in the present study by measuring relengthening in contracted canine tracheal smooth muscle (TSM) strips. The results indicate that dexamethasone treatment significantly augmented FFIR of contracted canine TSM. Canine tracheal ASM cells treated with dexamethasone demonstrated increased MAPK phosphatase-1 expression and decreased p38 MAPK activity, as reflected in reduced phosphorylation of the p38 MAPK downstream target, heat shock protein 27. These results suggest that corticosteroids may exert part of their therapeutic effect through direct action on airway smooth muscle, by decreasing p38 mitogen-activated protein kinase activity and thus increasing force fluctuation-induced relengthening.