tbuckley/cabot-search huggingface dataset:
Activation of Arterial Wall Dendritic Cells and Breakdown of Self-tolerance in Giant Cell Arteritis
Authors: Wei Ma-Krupa, Myung-Shin Jeon, Silvia Spoerl, Thomas F. Tedder, Jörg J. Goronzy, Cornelia M. Weyand
Journal: The Journal of Experimental Medicine (2004)

Giant cell arteritis (GCA) is a granulomatous and occlusive vasculitis that causes blindness, stroke, and aortic aneurysm. CD4+ T cells are selectively activated in the adventitia of affected arteries. In human GCA artery–severe combined immunodeficiency (SCID) mouse chimeras, depletion of CD83+ dendritic cells (DCs) abrogated vasculitis, suggesting that DCs are critical antigen-presenting cells in GCA. Healthy medium-size arteries possessed an indigenous population of DCs at the adventitia–media border. Adoptive T cell transfer into temporal artery–SCID mouse chimeras demonstrated that DCs in healthy arteries were functionally immature, but gained T cell stimulatory capacity after injection of lipopolysaccharide. In patients with polymyalgia rheumatica (PMR), a subclinical variant of GCA, adventitial DCs were mature and produced the chemokines CCL19 and CCL21, but vasculitic infiltrates were lacking. Human histocompatibility leukocyte antigen class II–matched healthy arteries, PMR arteries, and GCA arteries were coimplanted into SCID mice. Immature DCs in healthy arteries failed to stimulate T cells, but DCs in PMR arteries could attract, retain, and activate T cells that originated from the GCA lesions. We propose that in situ maturation of DCs in the adventitia is an early event in the pathogenesis of GCA. Activation of adventitial DCs initiates and maintains T cell responses in the artery and breaks tissue tolerance in the perivascular space.
Differences in hypervariable region 1 quasispecies of hepatitis C virus in human serum, peripheral blood mononuclear cells, and liver
Authors: Michiari Okuda, Keisuke Hino, Masaaki Korenaga, Yuhki Yamaguchi, Yoshiharu Katoh, Kiwamu Okita
Journal: Hepatology (1999)

Hepatitis C virus (HCV) has been reported to potentially replicate in peripheral blood mononuclear cells (PBMCs), but direct information on the pathogenic implication of HCV infection in PBMCs is still limited. To investigate this issue, we compared the complexity of HCV quasispecies in serum, PBMCs, and livers of 13 patients with type C chronic liver disease. Hypervariable region 1 (HVR 1) was amplified by reverse-transcription polymerase chain reaction (RT-PCR), and the PCR products were subcloned and sequenced. Considerable differences in the complexity of HVR 1 quasispecies were found in the serum, PBMCs, and liver in all patients, and the predominant sequences from each source were mutually different in 3 (23%) patients. An amino acid sequence unique to each source existed as well as a sequence common to serum and PBMCs, common to serum and livers, or common to PBMCs and liver. These results suggest infection of PBMCs by HCV, and that HCV in PBMCs may be differently exposed to host immunity from that in liver.
Redistribution of regional and organ blood volume and effect on cardiac function in relation to upright exercise intensity in healthy human subjects.
Authors: S D Flamm, J Taki, R Moore, S F Lewis, F Keech, F Maltais, M Ahmad, R Callahan, S Dragotakes, N Alpert
Journal: Circulation (1990)

To determine the effect of relative exercise intensity on organ blood volume and its relation to cardiac function, changes in relative blood volume and cardiac function were monitored with radionuclide techniques in 14 healthy volunteers. After labeling the subject's red cells with technetium 99m, we acquired data at rest, zero-load cycling, and at 50%, 75%, and 100% of maximal oxygen uptake. From rest to zero-load cycling, leg blood volume decreased 32 +/- 2% (mean +/- SEM), whereas relative end-diastolic blood volume increased 9.6 +/- 1.2%, and lung blood volume increased 18 +/- 2%, suggesting that the lungs may act as a blood volume buffer during periods of acutely increased venous return. With relative increasing exercise, leg blood volume stabilized, and then the blood volume in the abdominal organs decreased, further augmenting cardiopulmonary blood volume; leg blood volume and abdominal blood volume decreased by 23 +/- 2% and 19 +/- 2% from baseline, respectively, whereas thoracic blood volume increased 38 +/- 4%. In the abdomen, large decreases in blood volume were observed in the spleen (46 +/- 2%), kidney (24 +/- 4%), and liver (18 +/- 4%). In contrast, lung blood volume increased 50 +/- 4%, with the upper lung fields increasing more than the lower. Blood sampling revealed an increase in the hematocrit level by 4.3 +/- 0.4 units at peak exercise that paralleled the decrease in splenic blood volume (r2 = -0.64, p less than 0.001), suggesting a role for the spleen in augmenting cardiovascular performance by the release of concentrated red blood cells into general circulation. We conclude that upright exercise results in marked blood volume shifts from the legs and abdominal organs to the heart and lungs in a dynamic process correlating closely with oxygen consumption.
Elastic Support of the Lower Limbs in Hospital Patients
Authors: Elias A. Husni
Journal: JAMA (1970)

Elastic compression of the lower limb was critically evaluated in 105 hospital patients relative to reduction of the venous pool, effect upon venous hemodynamics, and the degree of compression commensurate with maximum reduction of venous stasis. Pressure studies and phlebograms were performed with and without knee-high elastic support of varying compression pressures. It was demonstrated that elastic support of 16 to 20 mm Hg effects significant reduction of the venous pool of the leg with improved venous return. The results of the study strongly suggest that knee-high elastic compression of the limb is effective in combating stasis in the deep veins as well as in the superficial varicose veins, and support its use when stasis is a predominant cause of phlebothrombosis in the confined patient.
Silencing of Elongation Factor-2 Kinase Potentiates the Effect of 2-Deoxy-<scp>d</scp>-Glucose against Human Glioma Cells through Blunting of Autophagy
Authors: Hao Wu, Hua Zhu, David X. Liu, Ting-Kuang Niu, Xingcong Ren, Rajesh Patel, William N. Hait, Jin-Ming Yang
Journal: Cancer Research (2009)

Abstract 2-Deoxy-d-glucose (2-DG), a synthetic glucose analogue that acts as a glycolytic inhibitor, is currently being evaluated in the clinic as an anticancer agent. In this study, we observed that treatment of human glioma cells with 2-DG activated autophagy, a highly conserved cellular response to metabolic stress and a catabolic process of self-digestion of intracellular organelles for energy use and survival in stressed cells. The induction of autophagy by 2-DG was associated with activation of elongation factor-2 kinase (eEF-2 kinase), a structurally and functionally unique enzyme that phosphorylates eEF-2, leading to loss of affinity of this elongation factor for the ribosome and to termination of protein elongation. We also showed that inhibition of eEF-2 kinase by RNA interference blunted the 2-DG–induced autophagic response, resulted in a greater reduction of cellular ATP contents, and increased the sensitivity of tumor cells to the cytotoxic effect of 2-DG. Furthermore, the blunted autophagy and enhanced 2-DG cytotoxicity were accompanied by augmentation of apoptosis in cells in which eEF-2 kinase expression was knocked down. The results of this study indicate that the energy stress and cytotoxicity caused by 2-DG can be accelerated by inhibition of eEF-2 kinase, and suggest that targeting eEF-2 kinase–regulated autophagic survival pathway may represent a novel approach to sensitizing cancer cells to glycolytic inhibitors. [Cancer Res 2009;69(6):2453–60]
Vascular Endothelial Growth Factor Is Necessary in the Development of Arteriosclerosis by Recruiting/Activating Monocytes in a Rat Model of Long-Term Inhibition of Nitric Oxide Synthesis
Authors: Qingwei Zhao, Kensuke Egashira, Shujiro Inoue, Makoto Usui, Shiro Kitamoto, Weihua Ni, Minako Ishibashi, Ken-ichi Hiasa, Toshihiro Ichiki, Masabumi Shibuya, Akira Takeshita
Journal: Circulation (2002)

It remains unclear whether vascular endothelial growth factor (VEGF) is a proarteriosclerotic or an antiarteriosclerotic factor. We recently reported that long-term inhibition of nitric oxide by administering Nomega-nitro-L-arginine methyl ester (L-NAME) induces coronary vascular inflammation and arteriosclerosis.We used this animal model to investigate the role of VEGF in arteriosclerosis. We blocked VEGF activity in vivo by transfecting with plasmid DNA encoding the murine soluble FLT-1 (sFLT-1) gene into thigh muscle. Soluble FLT-1 can suppress VEGF activity both by sequestering VEGF and by functioning as a dominant-negative inhibitor of VEGF receptors. We observed vascular inflammation associated with increased VEGF expression within 3 days of L-NAME administration, which was prevented by pretreatment with ACE inhibitor, angiotensin II receptor antagonist, or neutralizing monocyte chemoattractant protein-1 antibody. The sFLT-1 gene transfer attenuated the early vascular inflammation and prevented late arteriosclerosis. The sFLT-1 gene transfer also inhibited increased expression of monocyte chemoattractant protein-1 and transforming growth factor-beta, indicating creation of a positive feedback loop to cause arteriosclerosis.VEGF is necessary in the development of arteriosclerosis by mediating monocyte recruitment and activation in this model.
Relevance of Bone Marrow Cell Dose on Allogeneic Transplantation Outcomes for Patients With Acute Myeloid Leukemia in First Complete Remission: Results of a European Survey
Authors: Vanderson Rocha, Myriam Labopin, Eliane Gluckman, Ray Powles, William Arcese, Andrea Bacigalupo, Josy Reiffers, Arturo Iriondo, Olle Ringdén, Tapani Ruutu, Francesco Frassoni
Journal: Journal of Clinical Oncology (2002)

Many attempts have been made to improve the results of allogeneic bone marrow transplantation (alloBMT) for patients with acute myeloid leukemia (AML) in first complete remission (CR1). Bone marrow cell dose has been reported to be an important factor in alloBMT; however, its true impact on relapse incidence (RI), leukemia-free survival (LFS), and nonrelapse mortality (NRM) in a large cohort of patients is unknown.From January 1992 to December 1999, 572 bone marrow transplantation recipients reported to the European Blood and Marrow Transplantation (EBMT) registry underwent allografting from an HLA-identical sibling donor with an unmanipulated bone marrow for AML in CR1.The median number of nucleated cells (NCs) infused was 2.6 x 10(8)/kg. Estimated 5-year NRM, LFS, and RI for patients receiving more or less than 2.6 x 10(8) NCs/kg were, respectively, 18% +/- 5% v 30% +/- 5% (P =.001), 68% +/- 3% v 46% +/- 3% (P <.00001), and 14% +/- 4% v 24% +/- 5% (P =.004). The association of cell dose with the above outcomes was confirmed in multivariate analyses for NRM (relative risk [RR], 0.53; P =.0007), for LFS (RR, 0.53; P =.00008), and for RI (RR, 0.57; P =.02). The cell dose was also an important factor for neutrophil (RR, 0.76; P =.009) and platelet (RR, 0.77; P =.03) recoveries; however, it did not statistically influence the incidence of acute graft-versus-host disease.This study shows that marrow cell dose is one of the most important factors influencing relapse, NRM, and LFS after alloBMT for patients with AML in CR1. Therefore, increasing the marrow cell dose should substantially improve the survival of these patients.
Identifying Superficial, Muscle-Invasive, and Metastasizing Transitional Cell Carcinoma of the Bladder
Authors: Olga Modlich, Hans-Bernd Prisack, Gerald Pitschke, Uwe Ramp, Rolf Ackermann, Hans Bojar, Thomas A. Vögeli, Marc-Oliver Grimm
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Expression profiling by DNA microarray technology permits the identification of genes underlying clinical heterogeneity of bladder cancer and which might contribute to disease progression, thereby improving assessment of treatment and prediction of patient outcome. Experimental Design: Invasive (20) and superficial (22) human bladder tumors from 34 patients with known outcome regarding disease recurrence and progression were analyzed by filter-based cDNA arrays (Atlas Human Cancer 1.2; BD Biosciences Clontech) containing 1185 genes. For 9 genes, array data were confirmed using real-time reverse transcription-PCR. Additionally, Atlas array data were validated using Affymetrix GeneChip oligonucleotide arrays with 22,283 human gene fragments and expressed sequence tags sequences in a subset of three superficial and six invasive bladder tumors. Results: A two-way clustering algorithm using different subsets of gene expression data, including a subset of 41 genes validated by the oligonucleotide array (Affymetrix), classified tumor samples according to clinical outcome as superficial, invasive, or metastasizing. Furthermore, (a) a clonal origin of superficial tumors, (b) highly similar gene expression patterns in different areas of invasive tumors, and (c) an invasive-like pattern was observed in bladder mucosas derived from patients with locally advanced disease. Several gene clusters that characterized invasive or superficial tumors were identified. In superficial bladder tumors, increased mRNA levels of genes encoding transcription factors, molecules involved in protein synthesis and metabolism, and some proteins involved into cell cycle progression and differentiation were observed, whereas transcripts for immune, extracellular matrix, adhesion, peritumoral stroma and muscle tissue components, proliferation, and cell cycle controllers were up-regulated in invasive tumors. Conclusions: Gene expression profiling of human bladder cancers provides insight into the biology of bladder cancer progression and identifies patients with distinct clinical phenotypes.
Improved Arterial Compliance by a Novel Advanced Glycation End-Product Crosslink Breaker
Authors: David A. Kass, Edward P. Shapiro, Miho Kawaguchi, Anne R. Capriotti, Angelo Scuteri, Robert C. deGroof, Edward G. Lakatta
Journal: Circulation (2001)

Arterial stiffening with increased pulse pressure is a leading risk factor for cardiovascular disease in the elderly. We tested whether ALT-711, a novel nonenzymatic breaker of advanced glycation end-product crosslinks, selectively improves arterial compliance and lowers pulse pressure in older individuals with vascular stiffening.Nine US centers recruited and randomly assigned subjects with resting arterial pulse pressures >60 mm Hg and systolic pressures >140 mm Hg to once-daily ALT-711 (210 mg; n=62) or placebo (n=31) for 56 days. Preexisting antihypertensive treatment (90% of subjects) was continued during the study. Morning upright blood pressure, stroke volume, cardiac output, systemic vascular resistance, total arterial compliance, carotid-femoral pulse wave velocity, and drug tolerability were assessed. ALT-711 netted a greater decline in pulse pressures than placebo (-5.3 versus -0.6 mm Hg at day 56; P=0.034 for treatment effect by repeated-measures ANOVA). Systolic pressure declined in both groups, but diastolic pressure fell less with ALT-711 (P=0.056). Mean pressure declined similarly in both groups (-4 mm Hg; P<0.01 for each group, P=0.34 for treatment effect). Total arterial compliance rose 15% in ALT-711-treated subjects versus no change with placebo (P=0.015 versus ALT-711), an effect that did not depend on reduced mean pressure. Pulse wave velocity declined 8% with ALT-711 (P<0.05 at day 56, P=0.08 for treatment effect). Systemic arterial resistance, cardiac output, and heart rate did not significantly change in either group.ALT-711 improves total arterial compliance in aged humans with vascular stiffening, and it may provide a novel therapeutic approach for this abnormality, which occurs with aging, diabetes, and isolated systolic hypertension.
What are the most appropriate return-to-play guidelines for concussed child athletes?: Figure 1
Authors: L Purcell
Journal: British Journal of Sports Medicine (2009)

Objective: To examine concussion literature for specific guidelines regarding return to play (RTP) following sport-related concussion in child athletes. To make recommendations regarding the most appropriate RTP guidelines for child athletes following sport-related concussion. Design: A literature review of concussion literature. Intervention: A literature search was conducted using Medline and Embase databases from 1998 to 2008. More than 60 articles and two websites were reviewed. Results: There is a paucity of research on sport-related concussion in child athletes, particularly younger children (age 5–12 years). In particular, there is no research on RTP guidelines for child athletes following sport-related concussion. Child athletes take longer to recover from concussions than adults. Concussion symptoms may resolve before cognitive function has completely recovered. Concussion assessment and management in children can be confounded by their growth and development, as well as the lack of trained medical personnel involved with youth sports. There are no child-specific assessment tools for concussion. Conclusions: RTP decisions in children should be made cautiously and should be individualised. No concussed child athlete should be allowed to RTP the same day. Physical and cognitive rest is very important to allow for the resolution of concussion symptoms. Child athletes should remain symptom free for several days before starting a medically supervised stepwise exertion protocol. Further research is needed to elucidate the effects of concussion in children and to determine the most appropriate RTP guidelines. Child-specific concussion assessment tools need to be developed to improve concussion assessment and management in children.
Atherosclerosis
Authors: IRVINE H. PAGE
Journal: Circulation (1968)

The effectiveness of the research endeavor in atherogenesis is searchingly considered because neither how to prevent nor how to cure atherosclerosis is known, and there is no decision about what atherosclerosis looks like. In the overview one of the most serious problems is failure to see the whole problem. Systematic marshalling of detail is vital; yet there must be a longer look. The first broad suggestion is to curtail the divisive trends, view the blood vessels and heart as a whole, and declare unabashedly in favor of atherosclerosis as the prime interest no matter where it appears or under what guise. The time has come when those who study atherosclerosis and myocardial infarction should rethink their approach. Research excellence is the ability to select the few experiments most likely to get at the heart of the matter. An important question is, If the experiment is successful, will it contribute to the solution of the problems of atherogenesis? There is urgent need to reduce the amount of repetitive, almost trivial, investigation and to seek more creative approaches. Several problems are suggested as examples: the neural component, the atherogenic mosaic, and the inextricable association of atherosclerosis with myocardial infarction. Even such sacrosanct rights as how to do research are briefly considered. This all constitutes an apologia of the author's own failures in this pressingly important field.
Acute and chronic dose-response relationships for angiotensin, aldosterone, and arterial pressure at varying levels of sodium intake.
Authors: A W Cowley, R E McCaa
Journal: Circulation Research (1976)

We examined the acute and chronic dose-response relationships between intravenously infused angiotensin II (A II) and the resulting changes in arterial pressure and plasma aldosterone concentration at varying levels of sodium intake. Sequential analysis of plasma aldosterone at each A II infusion rate resulted in an acute dose-related increase in plasma aldosterone which was markedly attenuated after the first 24 hours of infusion, the final level being directly related to the dose of A II and inversely related to sodium intake. A II infused at 5,15, and 23 ng/kg per min was associated with an initial increase (2nd to 8th hour) in plasma aldosterone to 2,6, and 9 times control values, respectively, in dogs receiving 40 mEq Na+/day. But, after the 1st day, aldosterone averaged only 1, 1.7, and 3 times control values for the next 2 weeks at the same rates of A II infusion. Dogs receiving 120 mEq Na+/day during A II infusion exhibited only a transient increase in plasma aldosterone during the 1st day. Sustained hypertension developed over a period of a week at all doses of A II at normal and high sodium intake, but did not occur at any dose of A II in sodium-depleted dogs. Increasing sodium intake from 40 to 120 mEq/day resulted in higher levels of hypertension, 125% compared to 140% of ocntrol values for dogs infused with A II, 5.0 ng/kg per min. We conclude that primary angiotensin-induced hypertension need not be associated with increased levels of plasma aldosterone, which appears to remain elevated only with amounts of A II greater than those required to sustain a significant degree of hypertension.
Induced pluripotent stem cells from CINCA syndrome patients as a model for dissecting somatic mosaicism and drug discovery
Authors: Takayuki Tanaka, Kazutoshi Takahashi, Mayu Yamane, Shota Tomida, Saori Nakamura, Koichi Oshima, Akira Niwa, Ryuta Nishikomori, Naotomo Kambe, Hideki Hara, Masao Mitsuyama, Nobuhiro Morone, John E. Heuser, Takuya Yamamoto, Akira Watanabe, Aiko Sato-Otsubo, Seishi Ogawa, Isao Asaka, Toshio Heike, Shinya Yamanaka, Tatsutoshi Nakahata, Megumu K. Saito
Journal: Blood (2012)
Late and Prolonged Pseudoprogression in Glioblastoma After Treatment With Lomustine and Temozolomide
Authors: Moritz Stuplich, Dariusch R. Hadizadeh, Klaus Kuchelmeister, Jasmin Scorzin, Christian Filss, Karl-Josef Langen, Niklas Schäfer, Frederic Mack, Heinrich Schüller, Matthias Simon, Martin Glas, Torsten Pietsch, Horst Urbach, Ulrich Herrlinger
Journal: Journal of Clinical Oncology (2012)
Bronchodilator effect of nebulized sodium cromoglycate in children born prematurely
Authors: B Yuksel, A Greenough
Journal: European Respiratory Journal (1993)

We wished to determine whether nebulized sodium cromoglycate (SCG) has bronchodilator effects in very young children. In 18 children born prematurely and studied at a median of 15 months of age, thoracic gas volume (TGV) and airways resistance (Raw), were measured and hence specific airways conductance (sGaw) was calculated before (baseline) and after nebulized saline, and then after sodium cromoglycate. sGaw improved significantly in 10 infants after SCG, compared to only in two following saline. These preliminary results suggest that nebulized SCG may have an acute bronchodilator effect in some children born prematurely.