tbuckley/cabot-search huggingface dataset:
Troponin I Degradation and Covalent Complex Formation Accompanies Myocardial Ischemia/Reperfusion Injury
Authors: Jason L. McDonough, D. Kent Arrell, Jennifer E. Van Eyk
Journal: Circulation Research (1999)

Abstract —Selective troponin I (TnI) modification has been demonstrated to be in part responsible for the contractile dysfunction observed with myocardial ischemia/reperfusion injury. We have isolated and characterized modified TnI products in isolated rat hearts after 0, 15, or 60 minutes of ischemia followed by 45 minutes of reperfusion using affinity chromatography with cardiac troponin C (TnC) and an anti-TnI antibody, immunological mapping, reversed-phase high-performance liquid chromatography, and mass spectrometry. Rat cardiac TnI becomes progressively degraded from 210 amino acid residues to residues 1–193, 63–193, and 73–193 with increased severity of injury. Degradation is accompanied by formation of covalent complexes between TnI 1–193 and, respectively, TnC residues 1–94 and troponin T (TnT) residues 191–298. The covalent complexes are likely a result of isopeptide bond formation between lysine 193 of TnI and glutamine 191 of TnT by the cross-linking enzyme transglutaminase. With severe ischemia, cellular necrosis results in specific release of TnI 1–193 into the reperfusion effluent and TnT degradation in the myocardium (25-, 27-, and 33-kDa products). Two-dimensional electrophoresis demonstrated that phosphorylation of TnI prevents ischemia-induced degradation. This study characterized the modified TnI products in isolated rat hearts reperfused after a brief or severe period of ischemia, revealing the progressive nature of TnI degradation, changes in phosphorylation, and covalent complexes with ischemia/reperfusion injury. Finally, we propose a model for ischemia/reperfusion injury in which the extent of proteolytic and transglutaminase activities ultimately determines whether apoptosis or necrosis is achieved.
A database for the provisional identification of species using only genotypes: web-based genome profiling
Authors: Takehiro Watanabe, Ayumu Saito, Yusuke Takeuchi, Mohammed Naimuddin, Koichi Nishigaki
Journal: Genome biology (2002)

For a long time one could not imagine being able to identify species on the basis of genotype only as there were no technological means to do so. But conventional phenotype-based identification requires much effort and a high level of skill, making it almost impossible to analyze a huge number of organisms, as, for example, in microbe-related biological disciplines. Comparative analysis of 16S rRNA has been changing the situation, however. We report here an approach that will allow rapid and accurate phylogenetic comparison of any unknown strain to all known type strains, enabling tentative assignments of strains to species. The approach is based on two main technologies: genome profiling and Internet-based databases.A complete procedure for provisional identification of species using only their genomes is presented, using random polymerase chain reaction, temperature-gradient gel electrophoresis, image processing to generate 'species-identification dots' (spiddos) and data processing. A database website for this purpose was also constructed and operated successfully. The protocol was standardized to make the system reproducible and reliable. The overall methodology thus established has remarkable aspects in that it enables non-experts to obtain an initial species identification without a lot of effort and is self-developing; that is, species can be determined more definitively as the database is used more and accumulates more genome profiles.We have devised a methodology that enables provisional identification of species on the basis of their genotypes only. It is most useful for microbe-related disciplines as they face the most serious difficulties in species identification.
Erythropoietin Synthesis in Renal Myofibroblasts Is Restored by Activation of Hypoxia Signaling
Authors: Tomokazu Souma, Masahiro Nezu, Daisuke Nakano, Shun Yamazaki, Ikuo Hirano, Hiroki Sekine, Takashi Dan, Kotaro Takeda, Guo-Hua Fong, Akira Nishiyama, Sadayoshi Ito, Toshio Miyata, Masayuki Yamamoto, Norio Suzuki
Journal: Journal of the American Society of Nephrology (2015)

Erythropoietin (Epo) is produced by renal Epo-producing cells (REPs) in a hypoxia-inducible manner. The conversion of REPs into myofibroblasts and coincident loss of Epo-producing ability are the major cause of renal fibrosis and anemia. However, the hypoxic response of these transformed myofibroblasts remains unclear. Here, we used complementary in vivo transgenic and live imaging approaches to better understand the importance of hypoxia signaling in Epo production. Live imaging of REPs in transgenic mice expressing green fluorescent protein from a modified Epo-gene locus revealed that healthy REPs tightly associated with endothelium by wrapping processes around capillaries. However, this association was hampered in states of renal injury-induced inflammation previously shown to correlate with the transition to myofibroblast-transformed renal Epo-producing cells (MF-REPs). Furthermore, activation of hypoxia-inducible factors (HIFs) by genetic inactivation of HIF-prolyl hydroxylases (PHD1, PHD2, and PHD3) selectively in Epo-producing cells reactivated Epo production in MF-REPs. Loss of PHD2 in REPs restored Epo-gene expression in injured kidneys but caused polycythemia. Notably, combined deletions of PHD1 and PHD3 prevented loss of Epo expression without provoking polycythemia. Mice with PHD-deficient REPs also showed resistance to LPS-induced Epo repression in kidneys, suggesting that augmented HIF signaling counterbalances inflammatory stimuli in regulation of Epo production. Thus, augmentation of HIF signaling may be an attractive therapeutic strategy for treating renal anemia by reactivating Epo synthesis in MF-REPs.
Tuberculosis, Public Health, and Civil Liberties
Authors: R Bayer, L Dupuis
Journal: Annual Review of Public Health (1995)

The resurgence of tuberculosis confronts policy-makers with difficult legal and ethical questions about the proper use of state power and resources to protect public health. This chapter examines the implications of expanded use of invasive or coercive measures—including directly observed therapy, involuntary detention of noncompliant patients, and forced administration of medications—designed to reduce the risk of tuberculosis transmission and to ensure that those with TB are fully treated. These measures focus attention on the limitations of government power and obligation and on the delicate balance between the demands of civil liberty and the demands of public health.
Extracellular Matrix Changes in Stented Human Coronary Arteries
Authors: Andrew Farb, Frank D. Kolodgie, Jin-Yong Hwang, Allen P. Burke, Kirubel Tefera, Deena K. Weber, Thomas N. Wight, Renu Virmani
Journal: Circulation (2004)

Restenosis after stenting occurs secondary to the accumulation of smooth muscle cells (SMCs) and extracellular matrix (ECM), with the ECM accounting for >50% of the neointimal volume. The composition of the in-stent ECM has not been well characterized in humans.Postmortem human coronary arteries (n=45) containing stents underwent histological assessment of neointimal proteoglycans, hyaluronan, collagen (types I and III), SMCs, and CD44 (a cell surface receptor for hyaluronan). The mean duration of stent implantation was 18.7 months; stents in place > or =3 to <9 months (n=17) were assigned to group 1, stents > or =9 to <18 months old (n=19) to group 2, and stents > or =18 months old (n=9) to group 3. In groups 1 and 2, neointimal versican and hyaluronan staining was strongly positive, colocalized with alpha-actin-positive SMCs, and was greater in intensity compared with group 3. Conversely, decorin staining was greatest in group 3. The neointima of both group 1 and 2 stents was rich in type III collagen, with reduced staining in group 3. Type I collagen staining was weakest in group 1 stents, with progressively stronger staining in groups 2 and 3. SMC density and stent stenosis were significantly reduced in group 3 stents compared with groups 1 and 2. CD44 staining colocalized with macrophages and was associated with increased neointimal thickness.The ECM within human coronary stents resembles a wound that is not fully healed until 18 months after deployment, followed by neointimal retraction. ECM contraction may be a target for therapies aimed at stent restenosis prevention.
Mouse Models of Subcutaneous Spleen Reservoir for Multiple Portal Venous Injections to Treat Liver Malignancies
Authors: Hideki Kasuya, Darshini K. Kuruppu, James M. Donahue, Enid W. Choi, Hiroshi Kawasaki, Kenneth K. Tanabe
Journal: Cancer Research (2005)

Abstract Dog and rat animal models have been developed for repeated intravascular administrations to the liver. However, mice have generally been considered too small to use for these models. This study describes the development of mouse models that permit the establishment of liver metastases that can be subsequently treated by repeated injections into the portal venous system. A mini-laparotomy is done to mobilize the spleen and transpose it to a s.c. pocket with its vascular pedicle intact. A suspension of single tumor cells is then inoculated into the portal vein to establish diffuse liver metastases. These tumors may be treated by simple percutaneous injections directly into the s.c. whole spleen reservoir. The ease of injection into the s.c. spleen permits repeated injections into the portal venous system. The usefulness of this model was shown in experiments revealing that multiple portal venous administrations of a replication-conditional, oncolytic herpes simplex virus mutant are more effective than a single portal venous administration. In a modification of this model, the spleen is first split into two, leaving intact the vascular pedicle for each half of the spleen. Tumor cells are inoculated into one hemi-spleen, which is then resected 10 minutes later. The other hemi-spleen is transposed to the s.c. position, thereby permitting subsequent repetitive portal venous injections via percutaneous injections into the s.c. hemi-spleen. These mouse models are useful for a wide range of studies.
High-Density Lipoprotein Stimulates Myocardial Perfusion In Vivo
Authors: Bodo Levkau, Sven Hermann, Gregor Theilmeier, Markus van der Giet, Jerold Chun, Otmar Schober, Michael Schäfers
Journal: Circulation (2004)

Several clinical studies have demonstrated a close association between plasma HDL cholesterol levels and endothelium-dependent vasodilation in peripheral arteries. In isolated arteries, HDL has been shown to mediate vasodilation via NO release. In vivo, administration of reconstituted HDL restored abnormal endothelial function of the brachial artery in hypercholesterolemic patients. However, no data are currently available on the effect of HDL on myocardial perfusion.In this study, administration of human HDL enhanced incorporation of the perfusion tracer 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) into the murine heart in vivo by approximately 18%. This increase was completely abolished in mice deficient for endothelial NO synthase. Because we have recently identified sphingosine 1-phosphate (S1P) as an important vasoactive component contained in HDL, we measured myocardial perfusion after administration of S1P in vivo. We observed an approximately 25% decrease in myocardial MIBI uptake, which was abolished in mice deficient for the S1P receptor S1P3. In S1P3-/- mice, the stimulatory effect of HDL on myocardial perfusion was preserved.HDL increased myocardial perfusion under basal conditions in vivo via NO-dependent mechanisms, whereas S1P inhibited myocardial perfusion through the S1P3 receptor. Thus, HDL may reduce coronary risk via direct NO-mediated vasodilatory effects on the coronary circulation.
Increased Intimal Hyperplasia and Smooth Muscle Cell Proliferation in Transgenic Mice With Heparan Sulfate–Deficient Perlecan
Authors: Phan-Kiet Tran, Karin Tran-Lundmark, Raija Soininen, Karl Tryggvason, Johan Thyberg, Ulf Hedin
Journal: Circulation Research (2004)

Smooth muscle cell (SMC) proliferation is a critical process in vascular disease. Heparan sulfate (HS) proteoglycans inhibit SMC growth, but the role of endogenous counterparts in the vessel wall in control of SMC function is not known in detail. Perlecan is the major HS proteoglycans in SMC basement membranes and in vessel wall extracellular matrix (ECM). In this study, transgenic mice with HS-deficient perlecan were analyzed with respect to vascular phenotype and intimal lesion formation. Furthermore, SMC cultures were established and characterized with respect to morphology, immunocytochemical features, proteoglycan synthesis, proliferative capacity, and ECM binding of basic fibroblast growth factor (FGF-2). In vitro, mutant SMCs formed basement membranes with perlecan core protein, but with decreased levels of HS, they showed diminished secretion of HS-containing perlecan into the medium and a defective ECM-binding capacity of FGF-2. In vitro, mutant SMCs showed increased proliferation compared with wild-type cells, and in vivo, enhanced SMC proliferation and intimal hyperplasia were observed after flow cessation of the carotid artery in mutant mice. The results indicate that the endogenous HS side-chains of perlecan contribute to SMC growth control both in vitro and during intimal hyperplasia, possibly by sequestering heparin-binding mitogens such as FGF-2.
Addressing inequalities in research capacity in Africa
Authors: Jimmy Volmink, Lola Dare
Journal: BMJ (2005)

Addressing inequalities in research capacity in AfricaAll sides in partnerships must ensure that research aims to improve the health of all T his special theme issue includes a feast of high quality papers by African researchers on a range of topics of great relevance to health and health care in Africa.Despite our best efforts we did not achieve the geographical spread of submissions that we hoped for, mostly because we receive articles from authors in only a few African countries.We do not know the extent to which this reflects lack of research capacity or whether the prevailing political, social, and economic conditions in these countries militate against meaningful research.Whatever the reasons, the dearth of research done in Africa for Africa is untenable.Research capacity-comprising the institutional and regulatory frameworks, infrastructure, investment, and sufficiently skilled people to conduct and publish research-varies widely across African countries.In a report to the World Bank that ranked countries according to their national investments and productivity in science and technology, South Africa, Egypt, and Mauritius did reasonably well, while the rest of Africa appeared at the bottom of the league table under "scientifically lagging countries." 1 Although this generalisation obscures the fact that scientifically less advanced countries may have excellent capacity in certain niche areas, there can be no doubt that African research is moribund.Inequalities in health research contribute to inequalities in health.If science is to live up to its promise to improve health and spur development, all countries should be able to participate in research.][4] Collaboration in research, widely represented in this theme issue, may be one vehicle for strengthening research capacity in less privileged countries.African scientists welcome collaboration with the North as a means of overcoming barriers to research and promoting exchange of ideas.Unfortunately, Africans seem less enthusiastic about collaboration between countries within their own continent.This situation may improve: the New Partnership for Africa's Development (NEPAD) is actively facilitating partnerships within Africa and with the international community. 5Given the unequal power relations between rich and poor nations, research collaboration between them poses certain risks.A promising future for health research in Africa
Restarting the Cell Cycle When the Checkpoint Comes to a Halt
Authors: Marcel A.T.M. van Vugt, Alexandra Bràs, René H. Medema
Journal: Cancer Research (2005)

Abstract The DNA damage checkpoint coordinates a block in cell proliferation with the DNA repair process that follows when lesions are inflicted on the genome. However, we do not know exactly how cell division can recommence following a DNA damage–induced arrest. Recent work from our lab has identified Polo-like kinase-1 and Cdc25B as two essential components of the machinery that sets the cell division process back in motion when the checkpoint response is abrogated. Here, we discuss these novel insights and discuss their possible implications for the treatment of cancer.
Renal Excretion of Renin in the Rat
Authors: ALESSANDRO RAPPELLI, W. STANLEY PEART
Journal: Circulation Research (1968)

The renal excretion of renin infused intravenously was studied in anesthetized rats. The renin in the urine was adsorbed onto DEAE cellulose and selectively eluted for separate assay on the rat blood pressure preparation. The influence of saline loading, furosemide, mercuric chloride, and maleic acid was determined by following the changes in renin excretion. Both mercuric chloride and maleic acid led to a sixfold increase in the amount of renin appearing in the urine. Among the various factors which might have led to this result, an effect on renal tubular reabsorption after glomerular filtration of the renin is the most likely.
Successful clearance of hepatitis C virus with pegylated interferon -2a and ribavirin in an etanercept-treated patient with psoriatic arthritis, hepatitis B virus coinfection and latent tuberculosis
Authors: I. Mederacke, T. Witte, H. Wedemeyer, D. Meyer-Olson
Journal: Annals of the Rheumatic Diseases (2010)

Treatment of viral hepatitis with interferon-based therapies carries the risk of exacerbating underlying autoimmune disorders.1 Tumour necrosis factor alpha (TNFα) inhibitors are widely used in patients with rheumatic diseases, but anti-TNFα treatment may be associated with the reactivation of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection.2 3 Current treatment guidelines on rheumatological diseases,4 chronic HBV5 or HCV6 do not address the possibility of the concomitant administration of interferon and TNFα inhibitors in patients with both rheumatic disease and viral hepatitis.

A 37-year-old man presented to our clinic with a history of HLA-B27-positive psoriatic arthritis and chronic HBV–HCV (genotype 3a) co-infection, with HCV dominance (HCV-RNA 1.88×106 IU/ml, HBV-DNA <12 IU/ml; Roche COBAS TaqMan; Roche, Germany) and hepatitis B e antigen negativity.7 Liver biopsy …
Conservative management and parenchyma-sparing resections of pancreatic neuroendocrine tumors: Literature review
Authors: Claudio Mauriello, Salvatore Napolitano, Claudio Gambardella, Giancarlo Candela, Ferdinando De Vita, Michele Orditura, Valerio Sciascia, Ernesto Tartaglia, Michele Lanza, Luigi Santini, Giovanni Conzo
Journal: International Journal of Surgery (2015)
Supervised and induced sputum among patients with smear-negative pulmonary tuberculosis
Authors: K. C. Chang, C. C. Leung, W. W. Yew, C. M. Tam
Journal: European Respiratory Journal (2008)

Sputum culture is essential for monitoring drug resistance. Although sputum induction may optimise culture yield, better selection criteria and simpler algorithms are needed for countries with intermediate tuberculosis burdens. From a cohort of 660 patients who registered for antituberculosis treatment in a government chest clinic from May 21, 2005 to February 28, 2007, 187 patients with pulmonary disease and a negative smear in two unsupervised sputum specimens were enrolled prospectively for collection of one specimen each of supervised and induced sputum in succession. Among enrolled patients, induced sputum significantly improved ease of expectoration on a subjective five-point scale. Among 78 patients with culture-proven pulmonary tuberculosis, analysis of matched sputum culture results showed that: 1) induced sputum outperformed supervised sputum; 2) the second unsupervised sputum was significantly inferior to the first and redundant in the presence of the others; 3) adding one specimen each of supervised and induced sputum to two unsupervised specimens increased culture yield significantly; and 4) patients with either extent of disease less than right upper lobe or no respiratory symptoms were more likely to benefit. In summary, it may be practical to collect a sample of unsupervised, supervised and induced sputum for smear-negative patients with extent of disease less than the right upper lobe, especially when respiratory symptoms are absent.
Enhancement of an anti-tumor immune response by transient blockade of central T cell tolerance
Authors: Imran S. Khan, Maria L. Mouchess, Meng-Lei Zhu, Bridget Conley, Kayla J. Fasano, Yafei Hou, Lawrence Fong, Maureen A. Su, Mark S. Anderson
Journal: The Journal of Experimental Medicine (2014)

Thymic central tolerance is a critical process that prevents autoimmunity but also presents a challenge to the generation of anti-tumor immune responses. Medullary thymic epithelial cells (mTECs) eliminate self-reactive T cells by displaying a diverse repertoire of tissue-specific antigens (TSAs) that are also shared by tumors. Therefore, while protecting against autoimmunity, mTECs simultaneously limit the generation of tumor-specific effector T cells by expressing tumor self-antigens. This ectopic expression of TSAs largely depends on autoimmune regulator (Aire), which is expressed in mature mTECs. Thus, therapies to deplete Aire-expressing mTECs represent an attractive strategy to increase the pool of tumor-specific effector T cells. Recent work has implicated the TNF family members RANK and RANK-Ligand (RANKL) in the development of Aire-expressing mTECs. We show that in vivo RANKL blockade selectively and transiently depletes Aire and TSA expression in the thymus to create a window of defective negative selection. Furthermore, we demonstrate that RANKL blockade can rescue melanoma-specific T cells from thymic deletion and that persistence of these tumor-specific effector T cells promoted increased host survival in response to tumor challenge. These results indicate that modulating central tolerance through RANKL can alter thymic output and potentially provide therapeutic benefit by enhancing anti-tumor immunity.
Targeted adenovirus mediated inhibition of NF-κB-dependent inflammatory gene expression in endothelial cells in vitro and in vivo
Authors: J M Kułdo, S A Ásgeirsdóttir, P J Zwiers, A R Bellu, M G Rots, J A C Schalk, K I Ogawara, C Trautwein, B Banas, H J Haisma, G Molema, J A A M Kamps
Journal: Journal of Controlled Release (2012)
Population-based survival of patients with peritoneal carcinomatosis from colorectal origin in the era of increasing use of palliative chemotherapy
Authors: Y.L.B. Klaver, V.E.P.P. Lemmens, G.J. Creemers, H.J.T. Rutten, S.W. Nienhuijs, I.H.J.T. de Hingh
Journal: Annals of Oncology (2011)