tbuckley/cabot-search huggingface dataset:
Phagocytosis and antigen presentation: a partnership initiated by Toll-like receptors
Authors: J M. Blander
Journal: Annals of the Rheumatic Diseases (2008)

Professional phagocytes play an important role in the clearance of microbial pathogens and apoptotic cells. Many receptors are involved in this process, some with signalling capabilities, some without. Increasing evidence now shows a previously unappreciated regulatory component to phagocytosis exerted by the concomitant engagement of signalling receptors. The engagement of Toll-like receptors (TLRs) during phagocytosis of microbial pathogens is the best characterised example. Here, a brief overview is presented of the findings that TLRs exert positive and phagosome autonomous control on both the kinetics and outcomes of phagosome maturation. Although phagosomes could mature in the absence of TLR signals, they did so at a slower constitutive rate. Engagement of TLRs from another phagosome or from the plasma membrane did not affect the constitutive maturation of phagosomes devoid of TLR ligands. This was also reflected in the superior ability of phagosomes carrying TLR ligands to contribute peptides to major histocompatibility complex (MHC) class II molecules. Thus, TLR control of antigen presentation favours the presentation of microbial antigens within the context of T-lymphocyte costimulatory molecule expression. This current work aims to identify whether TLRs exert similar control on the presentation of phagocytosed antigens within MHC class I molecules, a process referred to as cross-presentation.
Nitroglycerin Enhances the Ability of Dobutamine Stress Echocardiography to Detect Hibernating Myocardium
Authors: Lijie Ma, Lianglong Chen, Linda Gillam, David D Waters, Chunguang Chen
Journal: Circulation (1997)

Background A biphasic response of wall thickening with initial improvement and subsequent deterioration during dobutamine stress echocardiography (DSE) has been increasingly used for detection of hibernating myocardium. However, the improvement of wall thickening at low-dose DSE may be limited in hibernating myocardium by severe hypoperfusion. Nitroglycerin (NTG) improves myocardial perfusion, reduces oxygen demand, and may enhance low-dose dobutamine to improve wall thickening. Methods and Results A pig model of myocardial hibernation of 24 hours to 7 days was created through severe left anterior descending coronary artery stenosis with coronary flow reductions of ≈40%, producing severe regional left ventricular dysfunction but no infarction in seven pigs. Myocardial infarction was produced in five pigs with occlusion of the artery. DSE was performed with incremental doses with and without an NTG infusion of 50 to 100 μg/min. In the hibernating group, NTG alone improved wall thickening in the hibernating region modestly from 11.4±7.2% at baseline to 19.1±7.0%. The improvement was associated with increased regional coronary flow from 0.46±0.12 to 0.55±0.13 mL · beat −1 · 100 g myocardium −1 ( P &lt;.05). There was an additive effect of NTG to low-dose (2.5 to 5 μg · kg −1 · min −1 ) dobutamine on wall thickening in the hibernating region. The improvement of wall thickening of hibernating myocardium with NTG and dobutamine, from 23.7±11.1% to 31.1±8.9% ( P &lt;.001), was associated with an increase in regional coronary flow ( P &lt;.01). NTG did not prevent high doses of dobutamine from inducing deterioration of wall thickening in hibernating myocardium. In the infarcted group, no improvement in wall thickening was observed in infarcted regions during NTG infusion, dobutamine infusion, or the combination. Conclusions NTG enhances the improvement of wall thickening at low-dose dobutamine and does not prevent high-dose dobutamine from inducing ischemia in hibernating myocardium. Thus, NTG augments the biphasic response of wall thickening and improves the accuracy of DSE for detecting viable myocardium.
A two-phase study evaluating the relationship between Thimerosal-containing vaccine administration and the risk for an autism spectrum disorder diagnosis in the United States
Authors: David A Geier, Brian S Hooker, Janet K Kern, Paul G King, Lisa K Sykes, Mark R Geier
Journal: Translational Neurodegeneration (2013)

Autism spectrum disorder (ASD) is defined by standardized criteria of qualitative impairments in social interaction, qualitative impairments in communication, and restricted and stereotyped patterns of behavior, interests, and activities. A significant number of children diagnosed with ASD suffer a loss of previously-acquired skills, which is suggestive of neurodegeneration or a type of progressive encephalopathy with an etiological pathogenic basis occurring after birth. To date, the etiology of ASD remains under debate, however, many studies suggest toxicity, especially from mercury (Hg), in individuals diagnosed with an ASD. The present study evaluated concerns about the toxic effects of organic-Hg exposure from Thimerosal (49.55% Hg by weight) in childhood vaccines by conducting a two-phased (hypothesis generating/hypothesis testing) study with documented exposure to varying levels of Thimerosal from vaccinations. A hypothesis generating cohort study was undertaken to evaluate the relationship between exposure to organic-Hg from a Thimerosal-containing Diphtheria-Tetanus-acellular-Pertussis (DTaP) vaccine in comparison to a Thimerosal-free DTaP vaccine administered, from 1998 through 2000, for the risk of ASD as reported in the Vaccine Adverse Event Reporting System (VAERS) database (phase I). A hypothesis testing case–control study was undertaken to evaluate the relationship between organic-Hg exposure from Thimerosal-containing hepatitis B vaccines administered at specific intervals in the first six months of life among cases diagnosed with an ASD and controls born between 1991 through 1999 in the Vaccine Safety Datalink (VSD) database (phase II). In phase I, it was observed that there was a significantly increased risk ratio for the incidence of ASD reported following the Thimerosal-containing DTaP vaccine in comparison to the Thimerosal-free DTaP vaccine. In phase II, it was observed that cases diagnosed with an ASD were significantly more likely than controls to receive increased organic-Hg from Thimerosal-containing hepatitis B vaccine administered within the first, second, and sixth month of life. Routine childhood vaccination is an important public health tool to reduce the morbidity and mortality associated with infectious diseases, but the present study provides new epidemiological evidence supporting an association between increasing organic-Hg exposure from Thimerosal-containing childhood vaccines and the subsequent risk of an ASD diagnosis.
Heritability estimates provide a crumbling foundation
Authors: Scott F. Stoltenberg
Journal: Behavioral and Brain Sciences (1997)

When Genotype × Environment (G × E) interactions are present, heritability estimates are not interpretable. Mealey cites abundant evidence for G × E interactions in the etiology of sociopathy, thereby completely undermining estimates of the heritability of sociopathy which form the foundation of her model. Without proper evidence for a genetic basis of sociopathy, Mealey's sociobiological model collapses under its own great weight.
A note on methodology in linguistics
Authors: Robert Freidin
Journal: Behavioral and Brain Sciences (2009)

Abstract Evans &amp; Levinson's (E&amp;L's) critique of Universal Grammar fails because their methodology is flawed, as illustrated in their discussion of the Subjacency Condition. The lack of explicit analysis leads the authors to a false conclusion that is refuted by work published in this journal twenty years ago. They miss the point that unanalyzed data cannot disprove grammatical hypotheses.
Lip Abscess Associated With Isotretinoin Treatment of Acne Vulgaris
Authors: Kevin C. Huoh, Kay W. Chang
Journal: JAMA Dermatology (2013)

<h3>Importance</h3> Isotretinoin is frequently prescribed for the treatment of acne vulgaris. Among the numerous documented adverse effects, most common are xerostomia and cheilitis. Lip abscesses as a consequence of cheilitis present dramatically and may pose a diagnostic challenge. <h3>Observations</h3> We present a case of a 15-year-old boy with a severe lip abscess requiring incision and drainage and hospital admission for intravenous antibiotic treatment of methicillin-resistant<i>Staphylococcus aureus</i>. We discuss the pathophysiologic characteristics of isotretinoin therapy and the likely causative role that the medication played in the development of the lip abscess. <h3>Conclusions and Relevance</h3> Although rare, lip abscesses related to isotretinoin therapy present with substantial morbidity and should be promptly recognized. Misdiagnosis of mucositis and angioedema may delay appropriate therapy.
Use of 70-gene signature to predict prognosis of patients with node-negative breast cancer: a prospective community-based feasibility study (RASTER)
Authors: Jolien M Bueno-de-Mesquita, Wim H van Harten, Valesca P Retel, Laura J van 't Veer, Frits SAM van Dam, Kim Karsenberg, Kirsten FL Douma, Harm van Tinteren, Johannes L Peterse, Jelle Wesseling, Tin S Wu, Douwe Atsma, Emiel JT Rutgers, Guido Brink, Arno N Floore, Annuska M Glas, Rudi MH Roumen, Frank E Bellot, Cees van Krimpen, Sjoerd Rodenhuis, Marc J van de Vijver, Sabine C Linn
Journal: The Lancet Oncology (2007)
Pathogenesis and Consequences of Uniparental Disomy in Cancer
Authors: Hideki Makishima, Jaroslaw P. Maciejewski
Journal: Clinical Cancer Research (2011)

The systematic application of new genome-wide single nucleotide polymorphism arrays has demonstrated that somatically acquired regions of loss of heterozygosity without changes in copy number frequently occur in many types of cancer. Until recently, the ubiquity of this type of chromosomal defect had gone unrecognized because it cannot be detected by routine cytogenetic technologies. Random and recurrent patterns of copy-neutral loss of heterozygosity, also referred to as uniparental disomy, can be found in specific cancer types and probably contribute to clonal outgrowth owing to various mechanisms. In this review we explore the types, topography, genesis, pathophysiological consequences, and clinical implications of uniparental disomy.
From Genome to Drugs: Where Do We Stand?
Authors: C. Schmidt
Journal: JNCI Journal of the National Cancer Institute (2011)

Adecade has passed since scientists produced a rough draft of the human genome. Since then, modern genomics has produced just one new drug: a treatment for lupus called belimumab (Benlysta), which the U.S. Food and Drug Administration (FDA) approved in March. Whether that ’ s consistent with early, bullish predictions about what genomics might add to the drug arsenal is open to debate. Press coverage from the human genome ’ s early days was certainly optimistic. USA Today , for instance, quoted Francis Collins, M.D., Ph.D., now the director of the National Institutes of Health, who said that decoding the human genome was an “exhilarating moment in history . . . and a major step towards treating a host of diseases for which genomics offers the best hope of prevention and cure.” Fast forward to June of last year, when the New York Times essentially declared genomics a failure for what it was accomplishing for patients. Genomics had been a boon for basic science, wrote staff reporter Nicholas Wade, but it had “produced little for medicine,” largely because, he claimed, most of the disease genes identifi ed by sequencing were too rare to make practical drug targets.
Serum calcitonin-lowering effect of magnesium in patients with medullary carcinoma of the thyroid.
Authors: C Anast, L David, J Winnacker, R Glass, W Baskin, L Brubaker, T Burns
Journal: Journal of Clinical Investigation (1975)

The effect of magnesium chloride or magnesium sulfate infusion on circulating levels of immunoreactive calcitonin (iCT) was evaluated on nine occasions in three patients with metastatic medullary carcinoma of the thyroid. One patient was normocalcemic and had normal circulating levels of immunoreactive parathyroid hormone (iPTH), one patient was hypocalcemic and had surgical hypoparathyroidism, and one patient had mild to moderate hypercalcemia associated with bone metastases. The basal serum iPTH levels were undetectable in the latter two patients. In every instance magnesium administration produced a rapid and striking fall in circulating iCT and usually a detectable fall in serum calcium. During the hypermagnesemic state, serum iPTH fell from normal to undetectable in the patient with normal parathyroid function, while serum iPTH levels remained undetectable in the hypoparathyroid patient and in the patient with hypercalcemia associated with bone metastases. The results of these studies indicate that: (a) contrary to what has been reported in normal experimental animals, magnesium administration lowers circulating iCT in human subjects with thyroid medullary carcinoma and (b) the calcium-lowering effect produced by magnesium in patients with medullary carcinoma may, in part at least, be due to a redistribution of body calcium that is not mediated by the actions of either parathyroid hormone or clacitonin.
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Authors: G W Baker, J R Duncan
Journal: JNCI Journal of the National Cancer Institute (1983)

The effect of zinc on the growth of a transplantable DAB hepatoma in young male Wistar rats was determined. Both a zinc deficiency (less than 0.5 microgram/g feed) as well as high levels of dietary zinc (500 micrograms/g feed) significantly reduced tumor growth. Both high- and low-zinc diets resulted in reduced activity of the salvage pathway of thymidine synthesis as well as reduced 32PO4 incorporation into DNA and diminished DNA polymerase activity. Blockage of the de novo pathway of DNA synthesis by the folate antagonist methotrexate (MTX) resulted in greatly increased flux through the thymidine salvage pathway and increased DNA polymerase activity but decreased 32PO4 incorporation in the transplantable hepatomas in Wistar rats fed normal zinc diets (50 micrograms/g feed). MTX had the effect of reducing all these activities in the groups fed low- and high-zinc diets. These data suggested a site of action of zinc associated with the salvage pathway of thymidine synthesis.
Kindlin-2 Is an Essential Component of Intercalated Discs and Is Required for Vertebrate Cardiac Structure and Function
Authors: James J. Dowling, Elizabeth Gibbs, Mark Russell, Daniel Goldman, Jeremy Minarcik, Jeffrey A. Golden, Eva L. Feldman
Journal: Circulation Research (2008)

Integrins and proteins that associate with integrins are implicated in normal cardiac muscle function and development. Unc-112 is a cytoplasmic adaptor protein required for the proper establishment of integrin junctions in Caenorhabditis elegans muscle. A vertebrate homolog of unc-112, kindlin-2, is an integrin-binding protein that is expressed in cardiac muscle, but its function is unknown. We sought to understand the role of kindlin-2 in the development and function of the mouse and zebrafish heart. In the mouse, we found that kindlin-2 is highly expressed in the heart and is enriched at intercalated discs and costameres. Targeted disruption of the murine kindlin-2 gene resulted in embryonic lethality before cardiogenesis. To better assess the role of kindlin-2 in cardiac muscle development, we used morpholinos to knockdown the kindlin-2 homolog in zebrafish (z-kindlin-2), which resulted in severe abnormalities of heart development. Morphant hearts were hypoplastic and dysmorphic and exhibited significantly reduced ventricular contractility. Ultrastructural analysis of these hearts revealed disrupted intercalated disc formation and a failure in the attachment of myofibrils to membrane complexes. We conclude that kindlin-2 is an essential component of the intercalated disc, is necessary for cytoskeletal organization at sites of membrane attachment, and is required for vertebrate myocardial formation and function. These findings provide the first characterization of the in vivo functions of this novel and critical regulator of cardiogenesis.
Use of an objective measure of articular stiffness to record changes in finger joints after intra-articular injection of corticosteroid
Authors: P. S Helliwell
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVE</h3> (1) To measure objectively the subjective improvement in joint stiffness following intra-articular injections of corticosteroids, and (2) to record changes in joint stiffness in the first 24 hours after injection to look for changes in the physical properties of the joint that would be consistent with a crystal synovitis. <h3>METHODS</h3> The study population consisted of 15 patients having 17 metacarpophalangeal joints injected as part of their routine care. Measurements were taken before injection, at 24 hours, and after one week. Outcome variables included articular stiffness, strength, joint range of movement, and subjective scores. <h3>RESULTS</h3> At 24 hours, mean values for stiffness had increased (mean slope from 0.0085 to 0.0123 Nm degree<sup>-1</sup>; curve area from 0.1003 to 0.1555 units), but the increase was not significant. After one week a significant decrease in “elastic stiffness” had occurred (mean slope from 0.0085 to 0.0065 Nm degree<sup>-1</sup>; P = 0.025). Significant changes in grip, range of movement, and subjective scores were also found after one week (maximum grip from 75.3 to 85.9 N; flexion/extension range from 87.0 to 102.4 degrees; pain visual analogue scale (VAS) from 50 mm to 12 mm; stiffness VAS from 65 mm to 27 mm). <h3>CONCLUSIONS</h3> An early increase in joint stiffness in some patients following intra-articular corticosteroids is consistent with a transient synovitis. Symptoms of joint stiffness generally correlate with mechanical measures which provide a useful objective index of acute changes in joint pathophysiology.
Pharmacokinetics and Bioavailability of Injected Glucagon: Differences Between Intramuscular, Subcutaneous, and Intravenous Administration
Authors: Ingrid Mühlhauser, Jutta Koch, Michael Berger
Journal: Diabetes Care (1985)

Pharmacokinetics and bioavailability of 1 mg glucagon injected intramuscularly (i.m.), subcutaneously (s.c.), or intravenously (i. v.) were studied in 6 nondiabetic men rendered hypoglycemic by s.c. injection of 10 U regular insulin. At 90 min after the insulin injection, when blood glucose levels had fallen to a mean of 49 mg/dl, glucagon was administered. Ten minutes later plasma glucagon levels had risen from a mean of 246 to 3233 pg/ml (s.c. experiment) and from 250 to 2638 pg/ml (i.m. experiment). Accordingly, there was no difference in blood glucose behavior whether glucagon was injected s.c. or i.m. In the i.v. experiment, plasma glucagon levels were significantly higher during the first 15 min after the glucagon injection when compared with the other experiments. The initially high levels of plasma glucagon after i.v. administration were associated with a steeper rise of glycemia during the first 5 min after glucagon injection; the maximal increase of blood glucose was, however, not different when compared with the s.c. or i.m. route of glucagon administration. Thus, in case of severe hypoglycemia, therapeutically administered glucagon will be most efficient when injected i.v., but there is no difference between the i.m. and s.c. routes of administration with regard to the efficacy to increase blood glucose levels.
Acute Depletion of Endothelial β3-Integrin Transiently Inhibits Tumor Growth and Angiogenesis in Mice
Authors: Veronica Steri, Tim S. Ellison, Aleksander Maksym Gontarczyk, Katherine Weilbaecher, Jochen G. Schneider, Dylan Edwards, Marcus Fruttiger, Kairbaan M. Hodivala-Dilke, Stephen Douglas Robinson
Journal: Circulation Research (2013)

The dramatic upregulation of αvβ3-integrin that occurs in the vasculature during tumor growth has long suggested that the endothelial expression of this molecule is an ideal target for antiangiogenic therapy to treat cancer. This discovery led to the development of small-molecule inhibitors directed against αvβ3-integrin that are currently in clinical trials. In 2002, we reported that β3-integrin-knockout mice exhibit enhanced tumor growth and angiogenesis. However, as β3-integrin is expressed by a wide variety of cells, endothelial cell-specific contributions to tumor angiogenesis are muddied by the use of a global knockout of β3-integrin function.
Effects of positive end-expiratory pressure on regional distribution of tidal volume and recruitment in adult respiratory distress syndrome.
Authors: L Gattinoni, P Pelosi, S Crotti, F Valenza
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The distribution of tidal volume (VT) and recruitment was investigated by chest computed tomography (CT) in eight sedated-paralyzed patients with the adult respiratory distress syndrome (ARDS). A CT section was obtained in the supine position at 0, 5, 10, 15, and 20 cm H2O positive end-expiratory pressure (PEEP) and at the corresponding inspiratory plateau pressure (21 +/- 1.8, 26 +/- 1.4, 31 +/- 1.8, 38 +/- 2.1, and 46 +/- 3.2 cm H2O [mean +/- SE]), keeping VT constant. Each CT section was divided along its ventral-dorsal height into 10 equally spaced intervals (levels). Vi(insp) and Vi(exp) were defined as the gas volume for level i (i = 1 to 10) at end-inspiration and at end-expiration, respectively. The following variables were computed at each lung level: (1) distribution of CT section tidal volume (VTct), i.e., the fraction of VT that inflates a given lung level; (2) the plateau-induced and PEEP-induced recruitment, i.e., the amount of lung tissue previously collapsed that inflates at plateau pressure and at PEEP, respectively; (3) the reopening-collapsing tissue, i.e., the amount of lung tissue that regains inflation at plateau pressure and collapses at PEEP. With increasing PEEP from 0 to 20 cm H2O, the VTct distribution decreased significantly (p < 0.01) in the upper levels, did not change in the middle levels, and increased significantly (p < 0.01) in the lower levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Hepatotoxicity due to allyl alcohol in deermice depends on alcohol dehydrogenase
Authors: Steven A. Belinsky, Blair U. Bradford, Donald T. Forman, Edward B. Glassman, Michael R. Felder, Ronald G. Thurman
Journal: Hepatology (1985)

The role of alcohol dehydrogenase in the hepatic necrosis due to allyl alcohol was studied in two strains of the deermouse, Peromyscus maniculatus. Mice of the alcohol dehydrogenase–negative ( Adh N ) strain which lack alcohol dehydrogenase activity were resistant to allyl alcohol toxicity. In contrast, dose–dependent necrosis of periportal regions of the liver and increases in plasma levels of lactate dehydrogenase, sorbitol dehydrogenase and SGOT were observed in plasma from alcohol dehydrogenase–positive deermice ( Adh F ) 24 hr following administration of allyl alcohol (21 to 84 mg per kg). Half–maximal damage to periportal areas was observed with about 52 mg per kg allyl alcohol. Thus, these data demonstrate that metabolism of allyl alcohol to acrolein by alcohol dehydrogenase is obligatory for the hepatotoxicity of allyl alcohol.
Economic evaluation of taxane-based first-line chemotherapy in the treatment of patients with metastatic breast cancer in Greece: an analysis alongside a multicenter, randomized phase III clinical trial
Authors: N. Maniadakis, U. Dafni, V. Fragoulakis, I. Grimani, E. Galani, A. Fragkoulidi, G. Fountzilas
Journal: Annals of Oncology (2008)