tbuckley/cabot-search huggingface dataset:
Induction of Oral Tolerance to Oxidized Low-Density Lipoprotein Ameliorates Atherosclerosis
Authors: G.H.M. van Puijvelde, A.D. Hauer, P. de Vos, R. van den Heuvel, M.J.C. van Herwijnen, R. van der Zee, W. van Eden, T.J.C. van Berkel, J. Kuiper
Journal: Circulation (2006)

Oxidation of low-density lipoprotein (LDL) and the subsequent processing of oxidized LDL (oxLDL) by macrophages results in activation of specific T cells, which contributes to the development of atherosclerosis. Oral tolerance induction and the subsequent activation of regulatory T cells may be an adequate therapy for the treatment of atherosclerosis.Tolerance to oxLDL and malondialdehyde-treated LDL (MDA-LDL) was induced in LDL receptor-/- mice fed a Western-type diet by oral administration of oxLDL or MDA-LDL before the induction of atherogenesis. Oral tolerance to oxLDL resulted in a significant attenuation of the initiation (30% to 71%; P<0.05) and progression (45%; P<0.05) of atherogenesis. Tolerance to oxLDL induced a significant increase in CD4+ CD25+ Foxp3+ cells in spleen and mesenteric lymph nodes, and these cells specifically responded to oxLDL with increased transforming growth factor-beta production. Tolerance to oxLDL also increased the mRNA expression of Foxp3, CTLA-4, and CD25 in the plaque. In contrast, tolerance to MDA-LDL did not affect atherogenesis.OxLDL-specific T cells, present in LDL receptor-/- mice and important contributors in the immune response leading to atherosclerotic plaque, can be counteracted by oxLDL-specific CD4+ CD25+ Foxp3+ regulatory T cells activated via oral tolerance induction to oxLDL. We conclude that the induction of oral tolerance to oxLDL may be a promising strategy to modulate the immune response during atherogenesis and a new way to treat atherosclerosis.
Bumetanide: Potent New "Loop" Diuretic
Authors: M. J. Asbury, P. B. B. Gatenby, S. O'Sullivan, E. Bourke
Journal: BMJ (1972)

Bumetanide, a pharmacologically new diuretic, was evaluated in 27 subjects. Its onset of action was within 30 minutes with a peak at 90 minutes and a total duration of action of about 270 minutes. In a controlled study in oedematous patients it was equipotent with frusemide at one-fortieth the molar dosage and did not differ from frusemide with regard to its pattern of electrolyte excretion. On continuous oral administration for eight days it produced effective diuresis with minimal alteration in biochemical and haematological status. The only adverse effect was gastric discomfort in one patient.
Stages in the incorporation of fatty acids into red blood cells
Authors: Stephen B. Shohet, David G. Nathan, Manfred L. Karnovsky
Journal: Journal of Clinical Investigation (1968)

Mature human erythrocytes were incubated with (14)C-labeled palmitic acid bound to crystalline human albumin. Energy-dependent incorporation of the labeled palmitic acid into cell membrane phospholipids occurred, and various stages in this incorporation were defined. Initially the palmitic acid was rapidy transferred from the albumin to a "superficial" membrane pool of free fatty acid (F-1), which was removable when the cells were washed with defatted albumin. This process was independent of red cell metabolism. The labeled fatty acid then passed into a second "deeper" membrane pool of free fatty acids (F-2), which was not extractable with albumin. This process was energy-dependent and proceeded at a slower rate than the initial transfer from albumin to F-1. Ultimately the labeled fatty acid was incorporated into phosphatides (PL). This process also was dependent upon cellular metabolism. The kinetics of pulse label studies suggest that the processes observed were sequential and that precursor-product relationships exist between the F-1 and F-2 pools and the F-2 and PL pools. [Formula: see text] From the size and specific activities of these pools, calculations of the extent of phospholipid turnover were made. An approximate figure of 2% /hr or 30 nmoles/ml of packed red blood cells per hr was obtained. The figure was further calculated to represent an energy cost to the red blood cell of approximately 5% of the energy available from glycolysis.
Poly(styrene oxide)-poly(ethylene oxide) block copolymers: From “classical” chemotherapeutic nanocarriers to active cell-response inducers
Authors: A. Cambón, A. Rey-Rico, S. Barbosa, J.F.A. Soltero, S.G. Yeates, J. Brea, M.I. Loza, C. Alvarez-Lorenzo, A. Concheiro, P. Taboada, V. Mosquera
Journal: Journal of Controlled Release (2013)
The NHS as a theological institution
Authors: J. Neuberger
Journal: BMJ (1999)

> “I believe with perfect faith in the NHS, in its ability to provide all health care for all people free at the point of use, in its ability to be equitable, fair, and compassionate, in its capacity to be efficient and effective, and, above all, in its capacity to give patients and users choices about the sorts of services they should receive.”

The NHS is like a theological institution. Its adherents, most of the population of the United Kingdom, believe in it passionately. Politicians who itch to reform it find themselves hopelessly out of sympathy with public opinion. Like the BBC, the NHS is an institution that binds the people of the UK together. It is seen to be fair, there when you need it, and the best in the world if you are seriously ill. No matter that the evidence is not necessarily there Like theological belief, belief in the NHS rests on assertions, apparently revealed truths—and woe betide those who try to say otherwise.

In part, that is because the NHS was set up with a moral purpose. It was new, exciting, encapsulating social progress, a guarantee of safety after the war, and a form of social contract. Fifty one years on, it is apparently much the same in the public mind: “[The NHS] symbolises the right of every human being to the dignity of health care based on need not wealth. It is the tangible experience of what I mean by community, working together—and paying taxes together—to create …
Fascia lata composite graft for right ventricular outflow tract and pulmonary artery reconstruction: Surgical technique
Authors: M. I. Ionescu, R. C. Deac
Journal: Thorax (1970)

Because there is no `ideal9 method for the complete correction of some of the more complex congenital cardiac abnormalities, a technique of making a composite graft of autologous fascia lata has been developed. Three types of grafts are described, all of them being based on the same general principle. The composite graft comprises a conduit, which serves to enlarge or reconstruct the outflow tract of the right ventricle and the main pulmonary artery, and an inner valve attached inside it, which provides the conduit with a one-way flow mechanism. The technique of preparing these composite grafts is outlined and the surgical implantation of the grafts in the right ventricular outflow is described. Since November 1969, fascia lata composite grafts have been used in 18 patients with a variety of complex congenital heart malformations with very good early results.
On the Origin and Evolution of Thermophily: Reconstruction of Functional Precambrian Enzymes from Ancestors of Bacillus
Authors: J. K. Hobbs, C. Shepherd, D. J. Saul, N. J. Demetras, S. Haaning, C. R. Monk, R. M. Daniel, V. L. Arcus
Journal: Molecular Biology and Evolution (2011)

Thermophily is thought to be a primitive trait, characteristic of early forms of life on Earth, that has been gradually lost over evolutionary time. The genus Bacillus provides an ideal model for studying the evolution of thermophily as it is an ancient taxon and its contemporary species inhabit a range of thermal environments. The thermostability of reconstructed ancestral proteins has been used as a proxy for ancient thermal adaptation. The reconstruction of ancestral "enzymes" has the added advantages of demonstrable activity, which acts as an internal control for accurate inference, and providing insights into the evolution of enzymatic catalysis. Here, we report the reconstruction of the structurally complex core metabolic enzyme LeuB (3-isopropylmalate dehydrogenase, E. C. 1.1.1.85) from the last common ancestor (LCA) of Bacillus using both maximum likelihood (ML) and Bayesian inference. ML LeuB from the LCA of Bacillus shares only 76% sequence identity with its closest contemporary homolog, yet it is fully functional, thermophilic, and exhibits high values for kcat, kcat/KM, and ΔG‡ for unfolding. The Bayesian version of this enzyme is also thermophilic but exhibits anomalous catalytic kinetics. We have determined the 3D structure of the ML enzyme and found that it is more closely aligned with LeuB from deeply branching bacteria, such as Thermotoga maritima, than contemporary Bacillus species. To investigate the evolution of thermophily, three descendents of LeuB from the LCA of Bacillus were also reconstructed. They reveal a fluctuating trend in thermal evolution, with a temporal adaptation toward mesophily followed by a more recent return to thermophily. Structural analysis suggests that the determinants of thermophily in LeuB from the LCA of Bacillus and the most recent ancestor are distinct and that thermophily has arisen in this genus at least twice via independent evolutionary paths. Our results add significant fluctuations to the broad trend in thermal adaptation previously proposed and demonstrate that thermophily is not exclusively a primitive trait, as it can be readily gained as well as lost. Our findings also demonstrate that reconstruction of complex functional Precambrian enzymes is possible and can provide empirical access to the evolution of ancient phenotypes and metabolisms.
Diabetes in St. Regis Mohawk Indians
Authors: Charlene B Martinez, Karen Strauss
Journal: Diabetes Care (1993)

Objective— To establish a registry of diabetes patients and to determine the point prevalence of diabetes in the St. Regis Mohawk New York community at the end of August 1989. Research Design and Methods— Participants in this study consisted of residents of the St. Regis Mohawk reservation in New York state, who were registered for health care at the St. Regis Mohawk Clinic. This study was a survey of diabetes cases using the National Diabetes Data Group criteria for diagnosis with comparison with the U.S. rates determined from the 1987–1982 National Health Interview Survey and Canadian Mohawk Indian rates from other studies. Results— The age-adjusted prevalence of 48.8/1000 Mohawk population was two times (95% CI 1.2–3.2) the U.S. rate. Although precise comparisons with Canadian studies are difficult because of differences in study design, rates for Quebec Mohawks aged 45–64 yr were similar. Conclusions— A high prevalence (21%) among New York Mohawk Indians &amp;lt;45 yr of age, compared with 17% of diabetic patients in that age-group in the U.S. population, means that complications resulting from diabetes will occur at a relatively young age, placing an increased burden on the health-care system with costs of patient care associated with diabetes increasing accordingly. The registry system is being used to gather information on the prevalence and incidence of diabetic complications and risk factors for developing diabetes. These data will be used to evaluate programs.
Blood fibrinogen as a biomarker of chronic obstructive pulmonary disease: Table 1
Authors: Annelyse Duvoix, Jenny Dickens, Imran Haq, David Mannino, Bruce Miller, Ruth Tal-Singer, David A Lomas
Journal: Thorax (2012)

<h3>Background</h3> Chronic obstructive pulmonary disease (COPD) is a multicomponent condition that is characterised by airflow obstruction that is not fully reversible and is a major global cause of morbidity and mortality. The most widely used marker of disease severity and progression is FEV<sub>1</sub>. However, FEV<sub>1</sub> correlates poorly with both symptoms and other measures of disease progression and thus there is an urgent need for other biological markers to better characterise individuals with COPD. Fibrinogen is an acute phase plasma protein that has emerged as a promising biomarker in COPD. Here we review the current clinical evidence linking fibrinogen with COPD and its associated co-morbidities and discuss its potential utility as a biomarker. <h3>Methods</h3> Searches for appropriate studies were undertaken on PubMed using search terms fibrinogen, COPD, emphysema, chronic bronchitis, FEV<sub>1</sub>, cardiovascular disease, exacerbation and mortality. <h3>Results</h3> There is strong evidence of an association between fibrinogen and the presence of COPD, the presence and frequency of exacerbations and with mortality. Fibrinogen is associated with disease severity but does not predict lung function decline, a measure used as a surrogate for disease activity. The role of fibrinogen in identifying inflammatory co morbidities, particularly cardiovascular disease, remains unclear. Fibrinogen is reduced by p38 mitogen-activated protein kinase inhibitors in individuals with stable disease and by oral corticosteroids during exacerbations. <h3>Conclusions</h3> Fibrinogen is likely to be a useful biomarker to stratify individuals with COPD into those with a high or low risk of future exacerbations and may identify those with a higher risk of mortality.
SOCS3 negatively regulates IL-6 signaling in vivo
Authors: Ben A Croker, Danielle L Krebs, Jian-Guo Zhang, Sam Wormald, Tracy A Willson, Edouard G Stanley, Lorraine Robb, Christopher J Greenhalgh, Irmgard Förster, Björn E Clausen, Nicos A Nicola, Donald Metcalf, Douglas J Hilton, Andrew W Roberts, Warren S Alexander
Journal: Nature Immunology (2003)
Necrosis Avidity: A Newly Discovered Feature of Hypericin and its Preclinical Applications in Necrosis Imaging
Authors: Binghu Jiang, Jichen Wang, Yicheng Ni, Feng Chen
Journal: Theranostics (2013)

Hypericin has been widely studied as a potent photosensitizer for photodynamic therapy in both preclinical and clinical settings. Recently, hypericin has also been discovered to have a specific avidity for necrotic tissue. This affinity is also observed in a series of radiolabeled derivatives of hypericin, including [(123)I]iodohypericin, [(124)I]iodohypericin, and [(131)I]iodohypericin. Hypericin, along with other necrosis-avid contrast agents, has been investigated for use in noninvasively targeting necrotic tissues in numerous disorders. Potential clinical applications of hypericin include the identification of acute myocardial infarction, evaluation of tissue viability, assessment of therapeutic responses to treatments, and interventional procedures for solid tumors. The mechanisms of necrosis avidity in hypericin remain to be fully elucidated, although several hypotheses have been suggested. In particular, it has been proposed that the necrosis avidity of hypericin is compound specific; for instance, cholesterol, phosphatidylserine, or phosphatidylethanolamine components in the phospholipid bilayer of cellular membranes may be the major targets for its observed selectivity. Further investigations are needed to identify the specific binding moiety that is responsible for the necrosis avidity of hypericin.
“Patchy-Tachy” Leads to False Positives for Recombination
Authors: Stephanie Sun, Ben J Evans, G Brian Golding
Journal: Molecular Biology and Evolution (2011)

Indirect tests have detected recombination in mitochondrial DNA (mtDNA) from many animal lineages, including mammals. However, it is possible that features of the molecular evolutionary process without recombination could be incorrectly inferred by indirect tests as being due to recombination. We have identified one such example, which we call "patchy-tachy" (PT), where different partitions of sequences evolve at different rates, that leads to an excess of false positives for recombination inferred by indirect tests. To explore this phenomena, we characterized the false positive rates of six widely used indirect tests for recombination using simulations of general models for mtDNA evolution with PT but without recombination. All tests produced 30-99% false positives for recombination, although the conditions that produced the maximal level of false positives differed between the tests. To evaluate the degree to which conditions that exacerbate false positives are found in published sequence data, we turned to 20 animal mtDNA data sets in which recombination is suggested by indirect tests. Using a model where different regions of the sequences were free to evolve at different rates in different lineages, we demonstrated that PT is prevalent in many data sets in which recombination was previously inferred using indirect tests. Taken together, our results argue that PT without recombination is a viable alternative explanation for detection of widespread recombination in animal mtDNA using indirect tests.
Visual Perception and Memory: A New View of Medial Temporal Lobe Function in Primates and Rodents
Authors: Elisabeth A. Murray, Timothy J. Bussey, Lisa M. Saksida
Journal: Annual Review of Neuroscience (2007)

The prevailing view of medial temporal lobe (MTL) function has two principal elements: first, that the MTL subserves memory but not perception, and second, that the many anatomically distinctive parts of the MTL function together in the service of declarative memory. Recent neuropsychological studies have, however, challenged both opinions. First, studies in rodents, nonhuman primates, and humans suggest that the perirhinal cortex represents information about objects for both mnemonic and perceptual purposes. Second, the idea that MTL components contribute to declarative memory in similar ways has also been contradicted. Whereas the perirhinal cortex plays an essential role in familiarity-based object recognition, the hippocampus contributes little, if at all, to this function. In both primates and rodents, the hippocampus contributes to the memory and perception of places and paths, whereas the perirhinal cortex does so for objects and the contents of scenes.
Reduced-dose craniospinal radiotherapy followed by tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk medulloblastoma
Authors: K. W. Sung, D. H. Lim, M. H. Son, S. H. Lee, K. H. Yoo, H. H. Koo, J. H. Kim, Y.-L. Suh, Y. S. Joung, H. J. Shin
Journal: Neuro-Oncology (2012)

We assessed the feasibility and effectiveness of reduced-dose craniospinal (CS) radiotherapy (RT) followed by tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) in reducing late adverse effects without jeopardizing survival among children with high-risk medulloblastoma (MB).From October 2005 through September 2010, twenty consecutive children aged >3 years with high-risk MB (presence of metastasis and/or postoperative residual tumor >1.5 cm(2)) were assigned to receive 2 cycles of pre-RT chemotherapy, CSRT (23.4 or 30.6 Gy) combined with local RT to the primary site (total 54.0 Gy), and 4 cycles of post-RT chemotherapy followed by tandem HDCT/autoSCT. Carboplatin-thiotepa-etoposide and cyclophosphamide-melphalan regimens were used for the first and second HDCT, respectively.Of 20 patients with high-risk MB, 17 had metastatic disease and 3 had a postoperative residual tumor >1.5 cm(2) without metastasis. The tumor relapsed/progressed in 4 patients, and 2 patients died of toxicities during the second HDCT/autoSCT. Therefore, 14 patients remained event-free at a median follow-up of 46 months (range, 23-82) from diagnosis. The probability of 5-year event-free survival was 70.0% ± 10.3% for all patients and 70.6% ± 11.1% for patients with metastases. Late adverse effects evaluated at a median of 36 months (range, 12-68) after tandem HDCT/autoSCT were acceptable.In children with high-risk MB, CSRT dose might be reduced when accompanied by tandem HDCT/autoSCT without jeopardizing survival. However, longer follow-up is needed to evaluate whether the benefits of reduced-dose CSRT outweigh the long-term risks of tandem HDCT/autoSCT.
The <i>SIL</i> Gene Is Essential for Mitotic Entry and Survival of Cancer Cells
Authors: Ayelet Erez, Asher Castiel, Luba Trakhtenbrot, Marina Perelman, Esther Rosenthal, Itamar Goldstein, Noa Stettner, Alon Harmelin, Hagit Eldar-Finkelman, Stefano Campaner, Ilan Kirsch, Shai Izraeli
Journal: Cancer Research (2007)

Although mitosis is a general physiologic process, cancer cells are unusually sensitive to mitotic inhibitors. Therefore, there is an interest in the identification of novel mitotic inhibitors. Here, we report the novel discovery of the SIL gene as a regulator of mitotic entry and cell survival. The SIL gene was cloned from leukemia-associated chromosomal translocation. It encodes a cytosolic protein with an unknown function and no homology to known proteins. Previously, we observed an increased expression of SIL in multiple cancers that correlated with the expression of mitotic spindle checkpoint genes and with increased metastatic potential. Here, we show that SIL is important for the transition from the G(2) to the M phases of the cell cycle. Inducible knockdown of SIL in cancer cells in vitro delayed entrance into mitosis, decreased activation of the CDK1 (CDC2)-cyclin B complex, and induced apoptosis in a p53-independent manner. SIL is also essential for the growth of tumor explants in mice. Thus, SIL is required for mitotic entry and cancer cell survival. Because increased expression of SIL has been noted in multiple types of cancers and correlates with metastatic spread, it may be a suitable target for novel anticancer therapy.
Active Focal Segmental Glomerulosclerosis Is Associated with Massive Oxidation of Plasma Albumin
Authors: Luca Musante, Giovanni Candiano, Andrea Petretto, Maurizio Bruschi, Nazzareno Dimasi, Gianluca Caridi, Barbara Pavone, Piero Del Boccio, Monica Galliano, Andrea Urbani, Francesco Scolari, Flavio Vincenti, Gian Marco Ghiggeri
Journal: Journal of the American Society of Nephrology (2007)

The basic mechanism for idiopathic FSGS still is obscure. Indirect evidence in humans and generation of FSGS by oxidants in experimental models suggest a role of free radicals. In vitro studies demonstrate a main role of plasma albumin as antioxidant, its modification representing a chemical marker of oxidative stress. With the use of complementary liquid chromatography electron spray ionization tandem mass spectrometry (LC-ESI-MS/MS) and biochemical methods, plasma albumin was characterized in 34 patients with FSGS; 18 had received a renal transplant, and 17 had IgM mesangial deposition. Patients with FSGS that was in remission or without recurrence after transplantation had normal plasma albumin, and the same occurred in patients with primary and secondary nephrites and with chronic renal failure. In contrast, patients with active FSGS or with posttransplantation recurrence had oxidized plasma albumin. This finding was based on the characterization of albumin Cys 34 with an mass-to-charge ratio of 511.71 in triple charge that was consistent with the formation of a cysteic acid carrying a sulfonic group (alb-SO3−). The exact mass of albumin was increased accordingly (+48 Da) for incorporation of three oxygen radicals. Direct titration of the free sulfhydryl group 34 of plasma albumin and electrophoretic titration curves confirmed loss of free sulfhydryl group and formation of a fast-moving isoform in all cases with disease activity. This is the first demonstration of in vivo plasma albumin oxidation that was obtained with an adequate structural approach. Albumin oxidation seems to be specific for FSGS, suggesting some pathogenetic implications. Free radical involvement in FSGS may lead to specific therapeutic interventions.