tbuckley/cabot-search huggingface dataset:
The Role of Platelet/Endothelial Cell Adhesion Molecule–1 (CD31) and CD38 Antigens in Marrow Microenvironmental Retention of Acute Myelogenous Leukemia Cells
Authors: Nathalie Gallay, Ludovic Anani, Adriana Lopez, Philippe Colombat, Christian Binet, Jorge Domenech, Babette B. Weksler, Fabio Malavasi, Olivier Herault
Journal: Cancer Research (2007)

Abstract In acute myelogenous leukemia (AML), leukemic cell-microenvironment interactions within various niches (stromal/osteoblastic or sinusoidal endothelial cell niches) have a role in leukemia cell survival and drug resistance. The AML leukemic cells express platelet/endothelial cell adhesion molecule–1 (CD31) and CD38, two adhesion molecules that could interact with microenvironmental elements, i.e., CD31 on the surface of marrow endothelial cells (CD31/CD31 and CD38/CD31 interactions) and hyaluronate (CD38/hyaluronate interactions). We report a physical association of these two antigens on the plasma membrane of myeloid leukemic cells. In this context, in vitro experiments done using interaction-blocking anti-CD31 and anti-CD38 monoclonal antibodies (CLB-HEC75 and OKT10, respectively) indicate that an excess of CD31 on the cell membrane of leukemic cells (CD31/CD38 MFI ratio &amp;gt;1) promotes a homotypic interaction with marrow endothelial cells, resulting in higher transendothelial migration. Conversely, an excess of CD38 (CD31/CD38 MFI ratio &amp;lt;1) allows leukemic cells to be entrapped within the bone marrow microenvironment through hyaluronate adhesion. The results obtained in vitro using fluorescence resonance energy transfer, co-capping, and co-immunoprecipitation experiments, and hyaluronate adhesion and transendothelial migration assays, are supported by immunophenotypic characterization of marrow leukemic cells from 78 AML patients on which CD38 expression levels were found to be positively correlated with those of CD31. Importantly, the excess of CD31 in those samples was associated with a higher peripheral WBC count. These findings indicate that bone marrow retention of AML cells depends on CD31 and CD38 coexpression levels. [Cancer Res 2007;67(18):8624–32]
Isolation and purification of large quantities of fresh human Kupffer cells, which are cytotoxic against colon carcinoma
Authors: Gijsbert Heuff, Arjan A. De Van Loosdrecht, Michiel G. H. Betjes, Robert H. J. Beelen, Sybren Meijer
Journal: Hepatology (1995)

A new rapid method is described for the isolation and purification of functional active human Kupffer cells without the need of in situ perfusion techniques. Liver wedge biopsies (3 to 5 g), obtained after laparotomy, were incubated with pronase under continuous pH registration. Human Kupffer cells were subsequently separated from other nonparenchymal cells by Nycodenz gradient centrifugation and purified by counterflow centrifugal elutriation. Kupffer cells, 1.7 +/- 0.4 x 10(6) per gram liver, were isolated with a purity of 95% +/- 3%. Cell-mediated cytotoxicity of Kupffer cells was assayed against a human colon carcinoma cell line (SW948). Kupffer cell cytotoxicity was 42% +/- 9% (mean +/- SD) at an effector-to-target cell ratio of 10 and significantly increased to 73 +/- 17% (P < .05) after activation of Kupffer cells with interferon-gamma. In conclusion, a reliable and relatively simple method is provided to isolate and purify fresh human Kupffer cells in large yields, which show spontaneous as well as gamma-interferon-induced cytotoxicity against a human colon carcinoma cell line.
Glucagon-like peptide 1 enhances glucose tolerance both by stimulation of insulin release and by increasing insulin-independent glucose disposal.
Authors: D A D'Alessio, S E Kahn, C R Leusner, J W Ensinck
Journal: Journal of Clinical Investigation (1994)

Glucagon-like peptide 1 [7-36 amide] (GLP-1) has been shown to enhance insulin secretion in healthy and type II diabetic humans, and to increase glucose disposal in type I diabetic patients. To further define its action on glucose kinetics, we studied six healthy subjects who received either GLP-1 (45 pmol/kg per h) or 150 mM saline on two mornings during which a modified intravenous glucose tolerance test was performed. Plasma insulin and glucose levels were analyzed using Bergman's minimal model of glucose kinetics to derive indices of insulin sensitivity (SI) and glucose effectiveness at basal insulin (SG), the latter a measure of glucose disposition independent of changes in insulin. In addition, basal insulin concentrations, the acute insulin response to glucose (AIRg), plasma glucagon levels, and the glucose disappearance constant (Kg) were measured on the days that subjects received GLP-1 or saline. Compared with saline infusions, GLP-1 increased the mean Kg from 1.61 +/- 0.20 to 2.65 +/- 0.25%/min (P = 0.022). The enhanced glucose disappearance seen with GLP-1 was in part the result of its insulinotropic effect, as indicated by a rise in AIRg from 240 +/- 48 to 400 +/- 78 pM (P = 0.013). However, there was also an increase in SG from 1.77 +/- 0.11 to 2.65 +/- 0.33 x 10(-2).min-1 (P = 0.038), which was accounted for primarily by insulin-independent processes, viz glucose effectiveness in the absence of insulin. There was no significant effect of GLP-1 on SI or basal insulin, and glucagon levels were not different during the glucose tolerance tests with or without GLP-1. Thus, GLP-1 improves glucose tolerance both through its insulinotropic action and by increasing glucose effectiveness. These findings suggest that GLP-1 has direct effects on tissues involved in glucose disposition. Furthermore, this peptide may be useful for studying the process of insulin-independent glucose disposal, and pharmacologic analogues may be beneficial for treating patients with diabetes mellitus.
Lipoprotein metabolism influenced by training-induced changes in human skeletal muscle.
Authors: B Kiens, H Lithell
Journal: Journal of Clinical Investigation (1989)

The influence of training-induced adaptations in skeletal muscle tissue on lipoprotein metabolism was investigated in six healthy men. The knee extensors were studied at rest and during exercise after 8 wk of dynamic exercise training of the knee extensors of one leg, while the other leg served as a control. The trained and nontrained thighs were investigated on different occasions. In the trained knee extensors, muscle (m) lipoprotein lipase activity (LPLA) was 70 +/- 29% higher compared with the nontrained (P less than 0.05), and correlated positively with the capillary density (r = 0.84). At rest there was a markedly higher arteriovenous (A-V) VLDL triacylglycerol (TG) difference over the trained thigh, averaging 55 mumol/liter (range 30-123), than over the nontrained, averaging 30 mumol/liter (4-72). In addition to the higher LPLA and VLDL-TG uptake in the trained thigh, a higher production of HDL cholesterol (C) and HDL2-C was also observed (P less than 0.05). Positive correlations between m-LPLA and A-V differences of VLDL-TG (r = 0.90; P less than 0.05) were observed only in the trained thigh. During exercise with the trained thigh the venous concentration of HDL2-C was invariably higher than the arterial, and after 110 min of exercise a production of 88 mumol/min (54-199) of HDL2-C was revealed. Even though a consistent degradation of VLDL-TG was not found during exercise, the total production of HDL-C across the trained and nontrained thigh, estimated from A-V differences times venous blood flow for the whole exercise period, correlated closely with the total estimated degradation of VLDL-TG (r = 0.91). At the end of 2 h of exercise m-LPLA did not differ from the preexercise value in either the nontrained or the trained muscle. We conclude that changes in the lipoprotein profile associated with endurance training to a large extent are explainable by training-induced adaptations in skeletal muscle tissue.
Where to now with Achilles tendon treatment?
Authors: Håkan Alfredson
Journal: British Journal of Sports Medicine (2011)

The chronic painful midportion Achilles tendon has been difficult to treat for years, and has on occasions ended the career of high-level athletes. Traditionally, when conservative treatments failed these athletes, surgery was instituted. Surgical treatment of midportion Achilles tendinosis consisted of a dorsal approach, with a central longitudinal tenotomy and excision of tendinosis tissue.1,–,3 This often required a long postoperative rehabilitation of 3–6 months before that athlete was allowed to retry full tendon-loading activity. The results of intra-tendinous surgery is known to be unpredictable.

With the introduction of painful eccentric training in the late 1990s,4 a high proportion of recreationally active athletes became pain-free, but the treatment was less successful for high-level …
The role of bronchodilator treatment in the prevention of exacerbations of COPD
Authors: Jadwiga A. Wedzicha, Marc Decramer, Terence A.R. Seemungal
Journal: European Respiratory Journal (2012)

Exacerbations of chronic obstructive pulmonary disease (COPD) are natural events in the progression of the disease, and are characterised by acute worsening of symptoms, especially dyspnoea. These heterogeneous events follow increased airway inflammation, often due to infection, and lead to decreased airflow and increased lung hyperinflation relative to stable COPD. Although exacerbation frequency generally increases as COPD progresses, some patients experience frequent exacerbations (≥2 per year) independently of disease severity. Exacerbations, especially frequent exacerbations, are associated with impaired health-related quality of life, reduced physical activity and poor disease prognosis. The cornerstone of pharmacotherapy for stable COPD is long-acting bronchodilators, including the long-acting β 2 -agonists (LABAs) and long-acting anti-muscarinic agents (LAMAs) alone or combined with inhaled corticosteroids (ICS). While ICS treatment can potentially reduce the risk of exacerbations, clinical studies have demonstrated the efficacy of LABAs and LAMAs in reducing COPD symptoms, primarily by reducing lung hyperinflation secondary to reduced airway resistance. Sustained reduction in lung hyperinflation may in turn lessen dyspnoea during an exacerbation. Indeed, recent studies suggest that bronchodilators may also reduce the incidence of, or prevent, exacerbations. Using data from recent studies, this review explores the evidence and possible mechanisms through which bronchodilators may prevent exacerbations.
Diffuse malignant pleural mesothelioma and asbestos exposure
Authors: F. Whitwell, R. M. Rawcliffe
Journal: Thorax (1971)

Pleural mesothelioma has been diagnosed in 52 patients in three hospitals on Merseyside between 1955 and 1970, 60% being diagnosed from operation specimens and the rest from postmortem tissues. Necropsies eventually held on nearly half the operation cases confirmed the diagnosis, giving a necropsy rate of 70% for the series. The morbid anatomy conformed to earlier descriptions except that widespread metastases were much commoner than has usually been described. Histological findings agreed with previous accounts of the tumour, except that, in our hands, special acid mucopolysaccharide staining was less reliable than Southgate9s mucicarmine, which was of value in differential diagnosis. Association with asbestos was confirmed from industrial histories in 80% of cases, the commonest industries involved being shipbuilding and repairing in men and sackware repairing in women. Lungs of industrial mesothelioma cases showed basal asbestosis in 17% and excessive asbestos bodies in almost all the rest. Quantitative comparison of asbestos bodies in lung smears from mesothelioma cases compared with lung smears from other Merseyside adults showed much higher counts in the mesothelioma cases. The interval from first exposure to asbestos until appearance of mesothelioma ranged between 13 and 63 years, with a mean of 42 years. We think the incidence of mesothelioma will continue to rise with the increased use of asbestos until about 40 years after adequate protective measures have been taken.
Rose Gardener's disease
Authors: Rogerio Rufino, Bruna Liete Marques, Claudia Henrique Costa
Journal: Thorax (2012)

A 32-year-old man worked as a subsistence farmer raising pigs and tending his small garden; he also kept cats and dogs. He reported fever, night sweats, weight loss of 10 kg over 3 months, haemoptysis and skin ulcers (figure 1). Radiography and chest CT scan (figure …
A systematic video analysis of National Hockey League (NHL) concussions, part I: who, when, where and what?
Authors: Michael G Hutchison, Paul Comper, Willem H Meeuwisse, Ruben J Echemendia
Journal: British Journal of Sports Medicine (2013)

Although there is a growing understanding of the consequences of concussions in hockey, very little is known about the precipitating factors associated with this type of injury.To describe player characteristics and situational factors associated with concussions in the National Hockey League (NHL).Case series of medically diagnosed concussions for regular season games over a 3.5-year period during the 2006-2010 seasons using an inclusive cohort of professional hockey players. Digital video records were coded and analysed using the Heads Up Checklist.Of 197 medically diagnosed concussions, 88% involved contact with an opponent. Forwards accounted for more concussions than expected compared with on-ice proportional representation (95% CI 60 to 73; p=0.04). Significantly more concussions occurred in the first period (47%) compared with the second and third periods (p=0.047), with the majority of concussions occurring in the defensive zone (45%). Approximately 47% of the concussions occurred in open ice, 53% occurred in the perimeter. Finally, 37% of the concussions involved injured players' heads contacting the boards or glass.This study describes several specific factors associated with concussions in the NHL, including period of the game, player position, body size, and specific locations on the ice and particular situations based on a player's position.
Formestane, a steroidal aromatase inhibitor after failure of non-steroidal aromatase inhibitors (anastrozole and letrozole): Is a clinical benefit still achievable?
Authors: P. Carlini, A. Frassoldati, S. De Marco, A. Casali, E.M. Ruggeri, M. Nardi, P. Papaldo, A. Fabi, F. Paoloni, F. Cognetti
Journal: Annals of Oncology (2001)
<i>An Introduction to the Mind in Health and Disease for Students and General Practitioners Interested in Mental Work.</i>By T. Waddelow Smith, F. R. C. S. (Eng.), Deputy Medical Superintendent of the City Mental Hospital, Nottingham; Member of the Medico-Psychological Association (<i>New York: Wm. Wood and Co., 1925.</i>)
Authors: Harry Stack Sullivan
Journal: American Journal of Psychiatry (1926)
Plasma Level of a Triggering Receptor Expressed on Myeloid Cells-1: Its Diagnostic Accuracy in Patients with Suspected Sepsis
Authors: Sébastien Gibot, Marie-Nathalie Kolopp-Sarda, Marie C. Béné, Aurélie Cravoisy, Bruno Levy, Gilbert C. Faure, Pierre-Edouard Bollaert
Journal: Annals of Internal Medicine (2004)

Background: Previous experimental studies have suggested that the triggering receptor expressed on myeloid cells-1 (TREM-1) is specifically upregulated in the presence of microbial products. Objective: To evaluate the diagnostic value of plasma levels of the soluble form of TREM-1 in patients admitted with clinical suspicion of infection. Design: Prospective, noninterventional study conducted between July and September 2003. Setting: Medical adult intensive care unit at a university hospital in France. Participants: 76 consecutive newly admitted patients who presented with clinically suspected infection and fulfilled at least 2 criteria of the systemic inflammatory response syndrome. Measurements: Sensitivity and specificity of plasma soluble TREM-1 levels at admission for the diagnosis of infection. Two independent intensivists blinded to the results of soluble TREM-1 assays retrospectively classified patients as having the systemic inflammatory response syndrome, sepsis, severe sepsis, or septic shock. Results: The systemic inflammatory response syndrome was diagnosed in 29 patients (38%), and sepsis, severe sepsis, or septic shock was diagnosed in the remaining 47 (62%). A plasma soluble TREM-1 level higher than 60 ng/mL was more accurate than any other clinical or laboratory finding for indicating infection (sensitivity, 96% [95% CI, 92% to 100%]; specificity, 89% [CI, 82% to 95%]; positive likelihood ratio, 8.6 [CI, 3.8 to 21.5]; negative likelihood ratio, 0.04 [CI, 0.01 to 0.2]). Limitations: The study did not enroll patients with mild infections not requiring intensive care unit hospitalization, patients older than 80 years of age, or patients who were immunocompromised. Conclusion: In newly admitted critically ill patients, measurement of plasma levels of soluble TREM-1 could help to rapidly identify those with infection.
Alzheimer's disease: synaptic dysfunction and Aβ
Authors: Ganesh M Shankar, Dominic M Walsh
Journal: Molecular Neurodegeneration (2009)

Synapse loss is an early and invariant feature of Alzheimer's disease (AD) and there is a strong correlation between the extent of synapse loss and the severity of dementia. Accordingly, it has been proposed that synapse loss underlies the memory impairment evident in the early phase of AD and that since plasticity is important for neuronal viability, persistent disruption of plasticity may account for the frank cell loss typical of later phases of the disease. Extensive multi-disciplinary research has implicated the amyloid β-protein (Aβ) in the aetiology of AD and here we review the evidence that non-fibrillar soluble forms of Aβ are mediators of synaptic compromise. We also discuss the possible mechanisms of Aβ synaptotoxicity and potential targets for therapeutic intervention.
Antiarrhythmic actions of the ATP-regulated K+ current activated by pinacidil.
Authors: W Spinelli, S Sorota, M Siegal, B F Hoffman
Journal: Circulation Research (1991)

We tested the hypothesis that a selective increase in membrane current, as contrasted with the decreases in currents caused by most antiarrhythmic agents, would be an effective antiarrhythmic intervention. We studied models of early afterdepolarizations (EADs), delayed afterdepolarizations (DADs), and abnormal automaticity in single canine ventricular myocytes using intracellular microelectrodes or patch electrodes. EADs were induced by injected current, Bay K 8644 (0.5-1 microM), or ketanserin (1.0 microM); DADs were induced by ouabain intoxication (2 x 10(-7) M); and abnormal automaticity was induced by exposure to barium (0.25 mM). To increase outward K+ current, we used pinacidil and the protein kinase C activator 4 beta-phorbol 12,13-dibutyrate (PDBu). Under control conditions, 10-100 microM pinacidil caused a concentration-dependent and reversible decrease in action potential duration and an increase in steady-state outward current; both effects were blocked by glibenclamide and thus presumably reflected changes in the ATP-regulated potassium current. Pinacidil increased the current required to induce EADs and abolished EADs caused by Bay K 8644 or ketanserin. After exposure of myocytes to ouabain, pinacidil caused a decrease in action potential duration and diminished or abolished DADs. Finally, pinacidil arrested abnormal automaticity caused by Ba2+. PDBu (30 nM) shortened action potential duration without altering plateau amplitude in some of the myocytes. In these cells the depolarizing current needed to produce an EAD was increased by over 70%; outward potassium current tails were also increased, an effect consistent with an increase of the repolarizing potassium current (IK). These findings show that each of the mechanisms for abnormal impulse generation can be effectively antagonized by an increase in outward current and suggest to us that selective augmentation of a repolarizing current, possibly IK, might be a reasonable antiarrhythmic intervention.
Soluble interleukin 6 receptor is raised in sleep‐related breathing disorder.
Authors: T Sathyamoorthy
Journal: Thorax (2007)

▴ Mehra R, Storfer-Isser A, Kirchner HL, et al . Soluble interleukin 6 receptor: a novel marker of moderate to severe sleep-related breathing disorder. Arch Intern Med2006;166:1725–31.

[OpenUrl][1][CrossRef][2][PubMed][3]



Cardiovascular disease (CVD) is increased in moderate to severe sleep-related breathing disorder (SRBD). Interleukin 6 (IL6) promotes atherogenesis and elevated levels occur in SRBD. Soluble IL6 receptor (sIL6R) exerts widespread effects compared with IL6 alone. The authors examined the relationship between SRBD severity, IL6 and sIL6R levels, and morning and evening variability …

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Mechanical Stress and the Induction of Lung Fibrosis via the Midkine Signaling Pathway
Authors: Rong Zhang, Ying Pan, Vito Fanelli, Sulong Wu, Alice Aili Luo, Diana Islam, Bing Han, Pu Mao, Mirna Ghazarian, Wenmei Zeng, Peter M. Spieth, Dingyan Wang, Julie Khang, Hongyin Mo, Xiaoqing Liu, Stefan Uhlig, Mingyao Liu, John Laffey, Arthur S. Slutsky, Yimin Li, Haibo Zhang
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Lung-protective ventilatory strategies have been widely used in patients with acute respiratory distress syndrome (ARDS), but the ARDS mortality rate remains unacceptably high and there is no proven pharmacologic therapy.Mechanical ventilation can induce oxidative stress and lung fibrosis, which may contribute to high dependency on ventilator support and increased ARDS mortality. We hypothesized that the novel cytokine, midkine (MK), which can be up-regulated in oxidative stress, plays a key role in the pathogenesis of ARDS-associated lung fibrosis.Blood samples were collected from 17 patients with ARDS and 10 healthy donors. Human lung epithelial cells were challenged with hydrogen chloride followed by mechanical stretch for 72 hours. Wild-type and MK gene-deficient (MK(-/-)) mice received two-hit injury of acid aspiration and mechanical ventilation, and were monitored for 14 days.Plasma concentrations of MK were higher in patients with ARDS than in healthy volunteers. Exposure to mechanical stretch of lung epithelial cells led to an epithelial-mesenchymal transition profile associated with increased expression of angiotensin-converting enzyme, which was attenuated by silencing MK, its receptor Notch2, or NADP reduced oxidase 1. An increase in collagen deposition and hydroxyproline level and a decrease in lung tissue compliance seen in wild-type mice were largely attenuated in MK(-/-) mice.Mechanical stretch can induce an epithelial-mesenchymal transition phenotype mediated by the MK-Notch2-angiotensin-converting enzyme signaling pathway, contributing to lung remodeling. The MK pathway is a potential therapeutic target in the context of ARDS-associated lung fibrosis.
Improved survival and reduced bleeding with low-molecular-weight heparin across all acute coronary syndrome subsets: findings from the global registry of acute coronary events
Authors: Werner Klein, Wilfried Kraxner, Ronald Hödis, Ph.Gabriel Steg, Andrzej Budaj, Dietrich Gulba, Frans Van de Werf, Immad Sadiq, Kami White, Keith A.A. Fox
Journal: Journal of the American College of Cardiology (2002)