tbuckley/cabot-search huggingface dataset:
Contribution of lymphocyte function-associated-1/intercellular adhesion molecule-1 binding to the adhesion/signaling cascade of cytotoxic T lymphocyte activation.
Authors: B Ybarrondo, A M O'Rourke, A A Brian, M F Mescher
Journal: The Journal of Experimental Medicine (1994)

A rapid induction of adhesion to immobilized intercellular adhesion molecule (ICAM)-1 occurs when cytotoxic T lymphocytes (CTL) are stimulated with either soluble anti-T cell receptor (TCR) monoclonal antibodies (mAb) or with immobilized alloantigen, and this binding is blocked by the addition of anti-lymphocyte function-associated (LFA)-1 mAbs. Requirements for activating LFA-1 adhesion to ICAM-1 are similar to those found for induction of binding to immobilized fibronectin (FN), but distinct from those for activating CD8-mediated adhesion to class I major histocompatibility complex. A distinct role for LFA-1 in co-signaling for TCR-dependent degranulation could not be demonstrated. In contrast, both CD8 and the FN-binding integrin provide costimulatory signals for this response. Thus, if co-signaling via LFA-1 occurs, it clearly differs from that provided by CD8 or the FN-binding integrin. On the basis of antibody blocking effects, alloantigen-dependent activation of adhesion to ICAM-1 involves both the TCR and CD8. These results support a view of CTL activation as a cascade of adhesion and signaling events, with different coreceptors making distinct contributions.
High Frequency of Epidermal Growth Factor Receptor Mutations with Complex Patterns in Non–Small Cell Lung Cancers Related to Gefitinib Responsiveness in Taiwan
Authors: Shiu-Feng Huang, Hui-Ping Liu, Ling-Hui Li, Yuan-Chieh Ku, Yu-Ning Fu, Hsien-Yu Tsai, Ya-Ting Chen, Yung-Feng Lin, Wen-Cheng Chang, Han-Pin Kuo, Yi-Cheng Wu, Yi-Rong Chen, Shih-Feng Tsai
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Epidermal growth factor receptor (EGFR) mutations related to gefitinib responsiveness in non–small cell lung cancer have been found recently. Detection of EGFR mutations has become an important issue for therapeutic decision-making in non–small cell lung cancer. Experimental Design: Mutational analysis of the kinase domain of EGFR coding sequence was done on 101 fresh frozen tumor tissues from patients without prior gefitinib treatment and 16 paraffin-embedded tumor tissues from patients treated with gefitinib. Detection of phosphorylated EGFR by immunoblot was also done on frozen tumor tissues. Results: The 101 non–small cell lung cancer tumor specimens include 69 adenocarcinomas, 24 squamous cell carcinomas, and 8 other types of non–small cell lung cancers. Mutation(s) in the kinase domain (exon 18 to exon 21) of the EGFR gene were identified in 39 patients. All of the mutations occurred in adenocarcinoma, except one that was in an adenosquamous carcinoma. The mutation rate in adenocarcinoma was 55% (38 of 69). For the 16 patients treated with gefitinib, 7 of the 9 responders had EGFR mutations, and only 1 of the 7 nonresponders had mutations, which included a nonsense mutation. The mutations seem to be complex in that altogether 23 different mutations were observed, and 9 tumors carried 2 mutations. Conclusions: Data from our study would predict a higher gefitinib response rate in lung adenocarcinoma patients in Chinese and, possibly, other East Asian populations. The tight association with adenocarcinoma and the high frequency of mutations raise the possibility that EGFR mutations play an important role in the tumorigenesis of adenocarcinoma of lung, especially in East Asians.
Genomic polymorphisms provide prognostic information in intermediate-risk acute myeloblastic leukemia
Authors: Mariano Monzo, Salut Brunet, Alvaro Urbano-Ispizua, Alfons Navarro, Granada Perea, Jordi Esteve, Rosa Artells, Miquel Granell, Juan Berlanga, Josep M. Ribera, Javier Bueno, Andreu Llorente, Ramon Guardia, Mar Tormo, Pio Torres, Josep F. Nomdedéu, Emili Montserrat, Jordi Sierra
Journal: Blood (2006)
Simultaneous aortic and pulmonary artery aneurysms due to giant cell arteritis.
Authors: A R Dennison, R M Watkins, A J Gunning
Journal: Thorax (1985)

Programed Cell death (PD-1), encoded by Pdcd1, is an immune inhibitory receptor expressed on the surface of lymphocytes. Surface PD-1 expression is amongst its highest in a subset of CD4<sup>+</sup> T cells called T follicular helper cells (T<sub>FH</sub>). T<sub>FH</sub> cells are pivotal for optimal germinal center formation and subsequent generation of pathogen- and vaccine-induced antibodies by B cells. Despite the clear connection to human health, the majority of previous work has centered on elucidating the mechanisms surrounding murine Pdcd1 regulation. Surprisingly, there is almost nothing known about how human Pdcd1 (<b>hPdcd1</b>) is regulated! Here we seek to close this gap in knowledge by identifying the cis-, trans-, and epigenetic pathways that regulate hPdcd1 in T<sub>FH</sub> cells. To this end, human T<sub>FH</sub> cells were sourced from both discarded tonsil tissue as well as from a recently described model to generate ex vivo human T<sub>FH</sub> cells through treatment with the cytokines Activin A, IL-12 and TGFβ. RNA-sequencing demonstrated that ex vivo T<sub>FH</sub> cells exhibit characteristics of bona-fide tonsillar T<sub>FH</sub> cells, including increased expression of PD-1. Furthermore, ATAC-seq and H3K27<sup>Ac</sup> Hi-ChIP experiments revealed the presence of 7 conserved accessible regions within the hPdcd1 locus that exhibit unique looping characteristics and potential enhancer properties. Functionality of each regulatory element was further defined through promoter reporter assays. Additionally, PAGE-RANK analysis elucidated transcription factors that may play a role in the induction of hPdcd1 expression. Collectively, these findings begin to unearth the mechanisms that control hPdcd1, informing the design of future therapeutics aimed at precisely manipulating human PD-1 expression.
Extracellular Matrix Glycoprotein Biglycan Enhances Vascular Smooth Muscle Cell Proliferation and Migration
Authors: Ryoko Shimizu-Hirota, Hiroyuki Sasamura, Mari Kuroda, Emi Kobayashi, Matsuhiko Hayashi, Takao Saruta
Journal: Circulation Research (2004)

Proteoglycans are produced and secreted by vascular smooth muscle cells, but the pathophysiological role of these glycoproteins in the vasculature is an enigma. Because the small leucine-rich proteoglycan (SLRP) biglycan is overexpressed in arteriosclerotic lesions, we produced mice constitutively overexpressing biglycan in the vascular smooth muscle, in order to examine the effects on vascular pathology. In the aorta and renal vasculature, increased vascular proliferation was seen both in the basal state and after infusion of angiotensin II (Ang II) in the transgenic mice compared with wild-type controls. In addition, the combination of biglycan overexpression and Ang II infusion resulted in marked increases in vascular smooth muscle cell proliferation and migration in the coronary arteries, as well as increases in fibrosis surrounding the vessels. In vitro, biglycan caused an increase in thymidine incorporation and migration of vascular smooth muscle cells, whereas these parameters were unchanged or reduced in endothelial cells. Moreover, addition of biglycan resulted in an increase in cdk2 expression and decrease in p27 levels in the vascular smooth muscle cells. These results suggest that this extracellular matrix SLRP may be involved in the regulation of vascular smooth muscle growth and migration through cdk2- and p27-dependent pathways. Furthermore, changes in biglycan expression could be a factor influencing the susceptibility of arteries to vascular injury, and may play a direct role in the pathogenesis of vascular lesions.
Public Biobanks: Calculation and Recovery of Costs
Authors: Bruno Clément, Martin Yuille, Kurt Zaltoukal, Heinz-Erich Wichmann, Gabriele Anton, Barbara Parodi, Lukasz Kozera, Christian Bréchot, Paul Hofman, Georges Dagher
Journal: Science Translational Medicine (2014)

A group of experts aided development of a cost-related tool for biobank access prices and tested it in three partnership models.
Chelation of intracellular calcium prevents mesangial cell proliferative responsiveness.
Authors: C Whiteside, S Munk, X Zhou, T Miralem, D M Templeton
Journal: Journal of the American Society of Nephrology (1998)

Mesangial cell transformation into a proliferative phenotype, observed in many glomerular diseases, occurs in response to growth factors and cytokines. This study tests the hypothesis that intracellular calcium is necessary for stimulation of mesangial cell proliferative responsiveness to a variety of growth factors. Furthermore, these experiments tested whether nonspecific calcium entry via a calcium ionophore was sufficient to elicit the same response. Rat primary mesangial cells (passages 5 to 10) were growth-arrested for 48 h in 0.5% fetal bovine serum (FBS), then stimulated with 0.1 microM endothelin-1, 1.9 microM platelet-derived growth factor (PDGF)-BB, 0.5% FBS, or 0.1 microM ionomycin, with or without the intracellular calcium chelator 1,2-bis-(2-aminophenoxy)-ethane-N,N,N',N'-tetra-acetic acid (BAPTA). Calcium signaling was measured in Fura-2-loaded cells on coverslips by dual-wavelength spectrofluorometry and in Fluo-3-loaded cells by confocal fluorescence laser microscopy. [3H]-Thymidine incorporation was measured after 12 to 24 h of stimulation with each test agent. Expression of c-fos mRNA was analyzed by Northern blot. All test agents stimulated a significant increase in cytosolic and nuclear calcium, which were both effectively inhibited with BAPTA. All agents stimulated a significant increase in [3H]-thymidine incorporation and enhanced c-fos mRNA expression (no detectable c-fos mRNA was observed in quiescent cells). BAPTA prevented the enhanced [3H]-thymidine incorporation stimulated by endothelin-1 and PDGF, and partial inhibition of FBS-stimulated incorporation with BAPTA was observed. BAPTA inhibited c-fos expression observed in response to these agents. Phorbol ester induction of c-fos mRNA in the absence of raised cytosolic or nuclear calcium was also suppressed by BAPTA. Cell viability as measured by thiazolyl blue and trypan blue was not altered by BAPTA. It is concluded that normal regulation of intracellular calcium is necessary for mesangial cell proliferative responsiveness.
Enhancement of reactive oxygen species formation in stable and unstable asthmatic patients
Authors: I Vachier, P Chanez, C Le Doucen, M Damon, B Descomps, P Godard
Journal: European Respiratory Journal (1994)

There is increasing evidence to suggest that human blood polymorphonuclear neutrophils (PMNs) and monocytes play an important role in the inflammatory processes of asthma. In asthmatic patients, PMNs and monocytes were shown to be activated more than in healthy subjects. We investigated the capacity of these two cell populations to generate reactive oxygen species (ROS) in stable and unstable asthmatic patients. The two populations of asthmatic patients were identified by asthma activity, as expressed by clinical events occurring within 2 weeks prior to the study. Oxygen species formation was analysed for isolated purified PMNs and monocytes (Mos) by chemiluminescence (CL) using lucigenin and luminol as luminescent probes. CL was determined on nonstimulated and on phorbol myristate acetate (PMA)-stimulated cells. The stimulatability coefficient (PMA-stimulated/nonstimulated cell ratio) of each cell population was then calculated. Resting PMNs and Mos generated significantly greater amounts of ROS in stable asthmatic patients, and much more in unstable asthmatic patients, as compared to healthy subjects, both in lucigenin and luminol enhanced CL. Non O2.- ROS production from PMA-stimulated PMNs and Mos was identical in unstable asthmatic patients and in healthy subjects, whereas a significant decrease was observed in stable asthmatic patients, as assessed by luminol enhanced CL. PMA-stimulated cells showed no difference in O2.- generation, as assessed by lucigenin enhanced CL. However, the stimulatability coefficient of all asthmatic patients was always significantly lower than that of healthy subjects. These results suggest that there are differences in priming and stimulation of Ros production from PMNs and Mos between stable and unstable asthmatic patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Platelet lipoprotein interplay: trigger of foam cell formation and driver of atherosclerosis
Authors: D. Siegel-Axel, K. Daub, P. Seizer, S. Lindemann, M. Gawaz
Journal: Cardiovascular Research (2008)

In the last decade, it was recognized that platelets and lipoproteins play a pivotal role in both early and late atherogenesis. Beside cellular interactions of platelets with other blood cells and vascular cells, interactions with lipoproteins seem to be quite important. Lipoproteins are fundamental 'players' in atherogenesis since they change the properties of different cells involved in atherosclerosis and thrombosis. Several studies have already shown that low density lipoproteins (LDL) are involved in the initiation of platelet signalling pathways. Platelets of hypercholesterolemic patients show hyperaggregability in vitro and enhanced activity in vivo. This review elucidates the major aspects concerning how native and modified lipoproteins influence the activation and metabolic behaviour of platelets, and shows a new way by which platelet-mediated lipoprotein transfer might contribute to foam cell formation. In hyperlipidaemia, circulating platelets are activated. This is accompanied by increased platelet aggregation, platelet-leukocyte aggregate formation, and platelet-induced superoxide anion production. Furthermore, oxidized LDL induces monocyte adhesion to the endothelium, migration and proliferation of smooth muscle cells, injures cells, interferes with nitric oxide release, and promotes procoagulant properties of vascular cells. New data about platelet-mediated lipoprotein transport and consequent foam cell formation, however, provide proof of how platelets might contribute to atheromatous lesion formation.
Single cells in the visual system and images past
Authors: Glenn E. Meyer
Journal: Behavioral and Brain Sciences (2002)

Various techniques have attempted to localize imagery. However, early findings using single cell recordings of human receptive fields during imagery tasks have had little impact. Reports by Marg and his coworkers (1968) found no evidence for imagery in human Area 17, 18, and 19. Single cells from humans suggest later imagery-related activity in hippocampus, amygdala, entorhinal cortex, and parahippocampal gyrus.
Relation of Smoking With Total Mortality and Cardiovascular Events Among Patients With Diabetes Mellitus
Authors: An Pan, Yeli Wang, Mohammad Talaei, Frank B. Hu
Journal: Circulation (2015)

Background— The prevalence of smoking in diabetic patients remains high, and reliable quantification of the excess mortality and morbidity risks associated with smoking is important for diabetes management. We performed a systematic review and meta-analysis of prospective cohort studies to evaluate the relation of active smoking with risk of total mortality and cardiovascular events among diabetic patients. Methods and Results— We searched Medline and Embase databases through May 2015, and multivariate-adjusted relative risks were pooled by using random-effects models. A total of 89 cohort studies were included. The pooled adjusted relative risk (95% confidence interval) associated with smoking was 1.55 (1.46–1.64) for total mortality (48 studies with 1 132 700 participants and 109 966 deaths), and 1.49 (1.29–1.71) for cardiovascular mortality (13 studies with 37 550 participants and 3163 deaths). The pooled relative risk (95% confidence interval) was 1.44 (1.34–1.54) for total cardiovascular disease (16 studies), 1.51 (1.41–1.62) for coronary heart disease (21 studies), 1.54 (1.41–1.69) for stroke (15 studies), 2.15 (1.62–2.85) for peripheral arterial disease (3 studies), and 1.43 (1.19–1.72) for heart failure (4 studies). In comparison with never smokers, former smokers were at a moderately elevated risk of total mortality (1.19; 1.11–1.28), cardiovascular mortality (1.15; 1.00–1.32), cardiovascular disease (1.09; 1.05–1.13), and coronary heart disease (1.14; 1.00–1.30), but not for stroke (1.04; 0.87–1.23). Conclusions— Active smoking is associated with significantly increased risks of total mortality and cardiovascular events among diabetic patients, whereas smoking cessation is associated with reduced risks in comparison with current smoking. The findings provide strong evidence for the recommendation of quitting smoking among diabetic patients.
The problem of choice
Authors: Hassan R Naqvi, Shawn Mathur, David Covarrubias, Josephine A Curcio, Christian Schmidt
Journal: Molecular Cancer (2008)

Convictions are a driving force for actions. Considering that every individual has a different set of convictions and larger groups act once a consensus decision is reached, one can see that debate is an inherent exercise in decision-making. This requires a sustainably generated surplus to allow time for intellectual exchange, gathering of information and dissemination of findings. It is essential that the full spectrum of options remain treated equally. At the end of this process, a choice has to be made. Looking back at a later time point, a retrospective analysis sometimes reveals that the choice was neither completely free nor a truly conscious one. Leaving the issue of consequences of a once made decision aside, we wish to contribute to the debate of the problem of choice.
Observations on the mechanisms of glucosuria during glucose loads in normal and nondiabetic subjects
Authors: John J. McPhaul, John J. Simonaitis
Journal: Journal of Clinical Investigation (1968)

The study of 14 normal young men by glucose titration procedures has defined the magnitude of splay in this population, differing from previously reported data in its unexpected deviation from the line of theoretic unity high on the titration curve. Compared to these normal subjects, a group of glucosuric men could be divided into two subclasses, those with normal maximal rate of glucose reabsorption (Tm(G)) and those with subnormal Tm(G), both with comparably abnormal splay. Most consistent glucosurics fall into the latter group. Nephritic patients studied were not such a homogeneous group in terms of age and sex, but did manifest an abnormal splay during their titration curves in most cases. They also demonstrated a greater than normal reabsorptive rate of glucose per unit measured glomerular filtration rate. It is concluded that renal glucosuria must be defined not only in terms of the concept of Tm(G) but also by deviation of the glucose titration curve expressing an unusual degree of splay. The latter is presumed, as has been suggested by others, to be a characteristic of nonhomogeneity of glucose handling units in the kidney. This seems subject to exaggeration in the adaptations which accompany chronic renal disease.
Prognostic Significance of Cyclooxygenase-2 Overexpression in Glottic Cancer
Authors: Melanie K. Sackett, Isabelle Bairati, François Meyer, Édith Jobin, Sébastien Lussier, André Fortin, Michel Gélinas, Abdenour Nabid, François Brochet, Bernard Têtu
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Cyclooxygenase-2 (COX-2) overexpression has been associated with a poor prognosis in many cancers. However, the role of COX-2 overexpression in head and neck cancers remains undetermined. The objective of this study was to evaluate whether COX-2 is a prognostic factor in glottic cancer. Experimental Design: This study was part of a phase III placebo-controlled randomized trial evaluating the efficacy of α-tocopherol in reducing second primary cancers (SPC) in head and neck cancer patients. Immunohistochemical analyses were conducted on pretreatment biopsies of 301 patients with early-stage glottic cancer treated by radiotherapy. The median value of 50% of positive tumor cells was the cutoff point used to define COX-2 overexpression. Outcomes considered in the statistical analysis were recurrence, SPC, and death. The Cox proportional hazards model was used to estimate the hazard ratios (HR) and their 95% confidence intervals (95% CI). Results: The HR associated with COX-2 overexpression was 0.94 (95% CI, 0.55-1.62) for recurrence. The HR associated with SPC was 2.63 (95% CI, 1.32-5.23) for the first 3.5 years of follow-up and 0.55 (95% CI, 0.22-1.32) for the following 3.5 years. The HR associated with COX-2 overexpression was 1.57 (95% CI, 1.01-2.45) for overall mortality. Conclusions: COX-2 overexpression in glottic cancer was associated with increased overall mortality and an increased risk of SPC during the early follow-up period. Future studies are needed to explain observed effects on SPC. COX-2 expression may prove helpful in defining an individual patient's prognosis.
Stability of Olfactory Identification Deficits in Neuroleptic-Naive Patients With First-Episode Psychosis
Authors: Warrick J. Brewer, Christos Pantelis, Vicki Anderson, Dennis Velakoulis, Bruce Singh, David L. Copolov, Patrick D. McGorry
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Olfactory identification deficits and their relationship to negative symptoms in patients with schizophrenia were examined in patients with recent-onset psychosis, the majority of whom were neuroleptic naive. METHOD: Seventy-four inpatients with a first episode of psychosis (27 with schizophrenia or schizophreniform disorder, nine with schizoaffective disorder, 17 with affective psychoses, and 21 with other psychoses), 49 of whom had not received antipsychotic medication, were compared to 38 age- and gender-matched normal subjects. Olfactory identification ability was assessed with the University of Pennsylvania Smell Identification Test. Forty patients and 13 comparison subjects were reassessed at 6 months to examine whether olfactory deficits were specific to schizophrenia or schizophreniform disorder and were stable over time. RESULTS: At baseline, the patients had significant impairment in olfactory identification ability compared to the normal subjects. This difference persisted after controlling for gender, premorbid or current IQ, smoking history, cannabis use, or the effects of medication. Diagnostic subgroups did not differ in olfactory identification ability. The deficits remained stable at 6-month follow-up and were associated with negative symptoms at both time points. No relationship was found between olfactory identification ability and length of either untreated psychosis or illness prodrome. CONCLUSIONS: Impairment in olfactory identification ability was apparent from the outset of psychotic illness and was not specific to schizophrenia or schizophreniform disorder. No change in the degree of this deficit was found after patients were stabilized and had responded to medication. The deficit could not be explained by peripheral factors that might contribute to olfactory identification ability, suggesting that it reflects central mechanisms.