tbuckley/cabot-search huggingface dataset:
CC-Chemokine Ligand 20/Macrophage Inflammatory Protein-3α and CC-Chemokine Receptor 6 Are Overexpressed in Myeloma Microenvironment Related to Osteolytic Bone Lesions
Authors: Nicola Giuliani, Gina Lisignoli, Simona Colla, Mirca Lazzaretti, Paola Storti, Cristina Mancini, Sabrina Bonomini, Cristina Manferdini, Katia Codeluppi, Andrea Facchini, Vittorio Rizzoli
Journal: Cancer Research (2008)

Abstract The expression of the chemokine CC-chemokine ligand 20 (CCL20)/macrophage inflammatory protein (MIP)-3α and its receptor CC-chemokine receptor 6 (CCR6) by multiple myeloma (MM) and microenvironment cells and their potential relationship with osteoclast (OC) formation and osteolytic bone lesions in MM patients was investigated in this study. First, we found that MM cells rarely produce CCL20/MIP-3α but up-regulate its production by bone marrow (BM) osteoprogenitor cells and osteoblasts in coculture with the involvement of soluble factors as interleukin-1β and tumor necrosis factor α. MM cells also stimulate both CCL20/MIP-3α and CCR6 expression by OCs in coculture. Thereafter, we showed that CCL20/MIP-3α significantly increases both the number of multinucleated tartrate-resistant acid phosphatase–positive OCs and receptor activator of nuclear factor-κB–positive OC progenitor cells similar to CCL3/MIP-1α. Finally, we found that blocking anti-CCL20/MIP-3α and anti-CCR6 antibodies significantly inhibits MM-induced OC formation. In vitro data were further expanded in vivo analyzing a total number of 64 MM patients. Significantly higher CCL20/MIP-3α levels were detected in MM patients versus monoclonal gammopathy of uncertain significance (MGUS) subjects and in MM osteolytic patients versus nonosteolytic ones. Moreover, a significant increase of CCL20/MIP-3α–positive osteoblasts in osteolytic MM patients compared with nonosteolytic ones was observed. Interestingly, no significant difference in BM CCL20/MIP-3α expression and level was observed between MGUS and nonosteolytic MM patients. Our data indicate that CCL20/MIP-3α and its receptor CCR6 are up-regulated in the bone microenvironment by MM cells and contribute to OC formation and osteolytic bone lesions in MM patients. [Cancer Res 2008;68(16):6840–50]
Non-apnoeic REM sleep induced nocturnal oxygen desaturation treated by nasal continuous positive airway pressure.
Authors: F Series, Y Cormier, J La Forge
Journal: Thorax (1989)

Non-apnoeic oxygen desaturation related to rapid eye movement (REM) sleep in a patient with hypothyroidism, obesity, respiratory failure, and cardiac failure was improved by treatment with nasal continuous positive airway pressure of 10 cm H2O.
Mucosal architecture of the small bowel in cases of psoriasis
Authors: R. E. Barry, P. R. Salmon, A. E. Read, R. P. Warin
Journal: Gut (1971)

Using a strictly defined grading system to eliminate subjective assessment of mucosal architecture, the jejunal mucosa from cases of extensive psoriasis has been shown to be significantly different from that of normal controls obtained both in life and at postmortem examination. The same changes, however, are shown to occur in patients who are ill and losing weight for reasons other than psoriasis. Diminshed lactose utilization, demonstrated in extensive psoriasis, supports the suggestion of a decreased mucosal surface area in this disease.
Association of a Common AKAP9 Variant With Breast Cancer Risk: A Collaborative Analysis
Authors: Bernd Frank, Miriam Wiestler, Silke Kropp, Kari Hemminki, Amanda B. Spurdle, Christian Sutter, Barbara Wappenschmidt, Xiaoqing Chen, Jonathan Beesley, John L. Hopper, Alfons Meindl, Marion Kiechle, Tracy Slanger, Peter Bugert, Rita K. Schmutzler, Claus R. Bartram, Dieter Flesch-Janys, Elke Mutschelknauss, Katie Ashton, Ramona Salazar, Emily Webb, Ute Hamann, Hiltrud Brauch, Christina Justenhoven, Yon-Dschun Ko, Thomas Brüning, Isabel dos Santos Silva, Nichola Johnson, Paul P. D. Pharoah, Alison M. Dunning, Karen A. Pooley, Jenny Chang-Claude, Douglas F. Easton, Julian Peto, Richard Houlston, Georgia Chenevix-Trench, Olivia Fletcher, Barbara Burwinkel
Journal: JNCI Journal of the National Cancer Institute (2008)

Data from several studies have suggested that polymorphisms in A-kinase anchoring proteins (AKAPs), which are key components of signal transduction, contribute to carcinogenesis. To evaluate the impact of AKAP variants on breast cancer risk, we genotyped six nonsynonymous single-nucleotide polymorphisms that were predicted to be deleterious and found two (M463I, 1389G>T and N2792S, 8375A>G) to be associated with an allele dose–dependent increase in risk of familial breast cancer in a German population. We extended the analysis of AKAP9 M463I, which is in strong linkage disequilibrium with AKAP9 N2792S, to 9523 breast cancer patients and 13770 healthy control subjects from seven independent European and Australian breast cancer studies. All statistical tests were two-sided. The collaborative analysis confirmed the association of M463I with increased breast cancer risk. Among all breast cancer patients, the combined adjusted odds ratio (OR) of breast cancer for individuals homozygous for the rare allele TT (frequency = 0.19) compared with GG homozygotes was 1.17 (95% confidence interval [CI] = 1.08 to 1.27, P = .0003), and the OR for TT homozygotes plus GT heterozygotes compared with GG homozygotes was 1.10 (95% CI = 1.04 to 1.17, P = .001). Among the combined subset of 2795 familial breast cancer patients, the respective ORs were 1.27 (95% CI = 1.12 to 1.45, P = .0003) and 1.16 (95% CI = 1.06 to 1.27, P = .001).
Reduced thrombin binding and aggregation in Bernard-Soulier platelets.
Authors: G A Jamieson, T Okumura
Journal: Journal of Clinical Investigation (1978)

Platelets from two patients with Bernard-Soulier disease showed a reduction in their ability to bind human thrombin. Thrombin binding studies in the high affinity range showed 1,500 sites for the Bernard-Soulier platelets as against 4,000 for normal controls. However, the dissociation constant was the same for both normals and patients (4.4 nM) indicating identical affinity for thrombin at the available sites. In the low affinity range, the Bernard-Soulier platelets showed 8,800 thrombin binding sites as against 24,000 for the controls, but again with identical values of Kd (37 nM). In addition, platelets from these Bernard-Soulier patients showed a decreased rate of aggregation with thrombin at both optimal (300 mU/ml) and suboptimal (60 and 120 mU/ml) thrombin concentrations. The decreased amount of thrombin which can bind to Bernard-Soulier platelets and the decrease in thrombin-induced aggregation may partly explain the hemostatic defect in these patients. In addition, the identical ratios of high affinity and low affinity binding sites in normals and in patients (0.37 and 0.36, and 0.36, respectively) supports the idea of a single class of binding sites for thrombin on the platelet surface.
Phosphodiesterase Type 5 Inhibitors for Pulmonary Arterial Hypertension
Authors: Stephen L. Archer, Evangelos D. Michelakis
Journal: New England Journal of Medicine (2009)

A 46-year-old-woman presents with exertional dyspnea and syncope and receives a diagnosis of idiopathic pulmonary arterial hypertension. Treatment with sildenafil is recommended. Sildenafil and tadalafil are phosphodiesterase type 5 inhibitors that ameliorate pulmonary arterial hypertension by increasing levels of cyclic guanosine monophosphate in the smooth-muscle cells of the pulmonary artery.
Allergic granulomatosis and angiitis (Churg-Strauss syndrome): response to 'pulse' intravenous cyclophosphamide.
Authors: C C Chow, E K Li, F M Lai
Journal: Annals of the Rheumatic Diseases (1989)

A 51 year old Chinese woman suffering from classical Churg-Strauss syndrome is presented. She deteriorated with acute pulmonary infiltrates resulting in hypoxaemic respiratory failure but responded dramatically with 'pulse' intravenous cyclophosphamide.
An in vitro beating heart model for long-term assessment of experimental therapeutics
Authors: Walter Habeler, Séverine Pouillot, Alexandra Plancheron, Michel Pucéat, Marc Peschanski, Christelle Monville
Journal: Cardiovascular Research (2008)

Within the framework of studies aiming at regenerative medicine for cardiovascular disease, we have developed an in vitro model to analyse human embryonic stem (ES) cell engraftment into the myocardium. This model is based on organotypic rat ventricular slices maintained in culture at the air–medium interface on semi-porous membranes. Survival and differentiation of human cardiomyocytes derived from ES cells were then assessed for several months. In addition, we observed that ventricular tissue slices not only exhibited normal histology, but also rhythmic contractions till the end of the experiments (up to 3 months). Similar results were obtained using ventricular slices obtained from two human foetuses at 8 and 9.5 weeks of age. Calcium transients were associated with the beating frequency, and the pattern was modulated in a dose-dependent manner by epinephrine. Our data suggest that the organotypic heart slice culture on semi-porous membranes is a relevant in vitro heart model for long-term histological and physiological studies.
Reduced Eukaryotic Initiation Factor 2Bε-Subunit Expression Suppresses the Transformed Phenotype of Cells Overexpressing the Protein
Authors: James W. Gallagher, Neil Kubica, Scot R. Kimball, Leonard S. Jefferson
Journal: Cancer Research (2008)

Eukaryotic initiation factor 2B (eIF2B), a five-subunit guanine nucleotide exchange factor, plays a key role in the regulation of mRNA translation. Expression of its epsilon-subunit is specifically up-regulated in certain conditions associated with increased cell growth. Therefore, the purpose of the present study was to examine the effect of repressing eIF2Bepsilon expression on growth rate, protein synthesis, and other characteristics of two tumorigenic cell lines that display up-regulated expression of the epsilon-subunit. Experiments were designed to compare spontaneously transformed fibroblasts to transformed mouse embryonic fibroblasts infected with a lentivirus containing a short hairpin RNA directed against eIF2Bepsilon. Cells expressing the short hairpin RNA displayed a reduction in eIF2Bepsilon abundance to 30% of the value observed in uninfected transformed mouse embryonic fibroblasts, with no change in the expression of any of the other four subunits. The repression of eIF2Bepsilon expression was accompanied by reductions in guanine nucleotide exchange factor activity and global rates of protein synthesis. Moreover, repressed eIF2Bepsilon expression led to marked reductions in cell growth rate in culture, colony formation in soft agar, and tumor progression in nude mice. Similar results were obtained in MCF-7 human breast cancer cells in which eIF2Bepsilon expression was repressed through transient transfection with a small interfering RNA directed against the epsilon-subunit. Overall, the results support a role for eIF2Bepsilon in the regulation of cell growth and suggest that it might represent a therapeutic target for the treatment of human cancer.
Pulmonary toxicity in hamsters of smoke particles from Kuwaiti oil fires.
Authors: J D Brain, N C Long, S F Wolfthal, T Dumyahn, D W Dockery
Journal: Environmental Health Perspectives (1998)

The Kuwaiti oil wells set on fire by retreating Iraqi troops at the end of the Persian Gulf War released complex particles, inorganic and organic gases, and hydrocarbons into the atmosphere, damaging the environment where many people live and work. In this study, we assessed the health effects of particles from the Kuwaiti oil fires by instilling hamsters intratracheally with particles (<3.5 microM in size) collected in Ahmadi, a residential area in Kuwait located downwind of hundreds of oil fires. Twenty-four hours after instillation, we performed bronchoalveolar lavage (BAL) to assess various indicators of pulmonary inflammation, including neutrophil and macrophage numbers; albumin, an index of air-blood barrier permeability; and activities of three enzymes: lactate dehydrogenase (LDH; an indicator of cell injury), myeloperoxidase (MPO; which indicates activation of neutrophils), and ss-N-acetylglucosaminidase (GLN; which is indicative of damage to macrophages or neutrophils). We compared the response of hamsters instilled with particles from Ahmadi to animals instilled with urban particles collected in St. Louis, Missouri. We also compared the Ahmadi particles against a highly fibrogenic positive control ([alpha]-quartz) and a relatively nontoxic negative control (iron oxide). When compared to hamsters instilled with particles from St. Louis, the animals treated with the Ahmadi particles had between 1.4- and 2.2-fold more neutrophils in their BAL fluids. The Ahmadi hamsters had more macrophages and lower MPO and LDH activities, but comparable albumin levels and GLN activities. Thus, the acute toxicity of the Ahmadi particles was roughly similar to that of urban particles collected in the United States, when identical masses were compared. However, the relatively higher concentrations of particles measured in Kuwait and Saudi Arabia during the oil fires (at times more than 16 times higher than the EPA standard) is of particular concern. In addition, since the long-term effects of exposure to these particles remains unknown, further studies are needed to fully assess the health effects of the Kuwaiti oil fires.
A review of intercostal chest drain (ICD) management in an intensive care unit (ICU)
Authors: Norman Main, Rajesh Yadavalli, Seher Zaidi, Lee Poole
Journal: European Respiratory Journal (2013)

Background:In 2008, The National Patient Safety Agency (UK) 1  published a report highlighting problems following ICD insertions. In response, the British Thoracic Society (BTS) issued guidance pertaining to consent, documentation and the procedure 2 . This study reviews current practice of ICD insertion and management in our ICU, to identify areas requiring development in relation to current BTS guidance.  Methods:Data was collected over a 1-year period for all ICU inpatients requiring chest drain insertion (n=52).  Results:The main indications for insertion were Pleural Effusion (44%), Pneumothorax (44%) and Haemothorax (10%). 71% of ICD’s were inserted by Specialty Residents and 12% by Radiologists. Consent was documented in only 50% and the procedure recorded in 81% of cases. Documentation regarding the size of the drain was done in 75% and removal in 62% of patients. Only 57% of drains inserted for pleural effusion were performed under Ultrasound guidance. 92% had a chest radiograph post procedure. Complications that occurred included drain repositioning (11%), lung contusion (4%) and desaturation post procedure (4%).  Conclusions:This study highlights the need to improve documentation of consent, and procedure details. Subsequently, we have commenced a training programme for doctors on our unit, to develop competence in ICD insertion in the Clinical Skills laboratory and in using ultrasound where indicated. Emphasis is also being placed on documentation and issues around consent.  References:   1 Rapid Response Report: Risks of chest drain insertion: NPSA/2008/RRR03   2 Guidance for the safe insertion of chest drains for pleural effusions in adults, following the NPSA Rapid Response Report. A BTS Statement.
Phase I Study of Intravenous Vascular Endothelial Growth Factor Trap, Aflibercept, in Patients With Advanced Solid Tumors
Authors: A. Craig Lockhart, Mace L. Rothenberg, Jakob Dupont, Wendy Cooper, Paul Chevalier, Lars Sternas, Giliane Buzenet, Elizabeth Koehler, Jeffrey A. Sosman, Lawrence H. Schwartz, David H. Gultekin, Jason A. Koutcher, Edwin F. Donnelly, Ric Andal, Isabelle Dancy, David R. Spriggs, William P. Tew
Journal: Journal of Clinical Oncology (2009)

Vascular endothelial growth factor (VEGF) Trap (aflibercept) is an angiogenesis inhibitor comprising portions of the extracellular domains of human VEGF receptors 1 and 2 fused to the Fc portion of human immunoglobulin G. This phase I study was designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of VEGF Trap administered intravenously (IV) every 2 weeks.Patients with refractory solid tumors or non-Hodgkin's lymphoma with adequate organ function were eligible. Pharmacokinetic/pharmacodynamic markers included measurement of plasma VEGF bound to VEGF Trap and free VEGF Trap. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was incorporated to measure the biologic effects of the drug on tumor vascularity and permeability.The study enrolled 47 patients at doses ranging from 0.3 to 7.0 mg/kg IV every 2 weeks. Dose-limiting toxicities were rectal ulceration and proteinuria at the 7.0 mg/kg dose. Other mechanism-specific toxicities included hypertension. On the basis of these observations and on pharmacokinetics, the recommended phase II dose of VEGF Trap as a single agent is 4 mg/kg every 2 weeks. Three RECIST (Response Evaluation Criteria in Solid Tumors) -defined partial responses were observed, one at the 3.0 mg/kg and two at the 7.0 mg/kg dose level. Maximum plasma concentration of free VEGF Trap increased proportionally with dose. Maximal VEGF-bound VEGF Trap complex levels were reached at doses > or = 2.0 mg/kg. Changes in volume transfer constant measured by DCE-MRI at baseline and at 24 hours after administration indicate a possible dose-related change in this pharmacodynamic marker.IV VEGF Trap was well tolerated at the dose levels tested. Pharmacodynamic and pharmacokinetic markers were indicative of VEGF blockade.
Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report
Authors: C. A. Akdis, M. Akdis, T. Bieber, C. Bindslev‐Jensen, M. Boguniewicz, P. Eigenmann, Q. Hamid, A. Kapp, D. Y. M. Leung, J. Lipozencic, T. A. Luger, A. Muraro, N. Novak, T. A. E. Platts‐Mills, L. Rosenwasser, A. Scheynius, F. E. R. Simons, J. Spergel, K. Turjanmaa, U. Wahn, S. Weidinger, T. Werfel, T. Zuberbier
Journal: Allergy (2006)

There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.
FDA approves implantable chip to access medical records
Authors: Janice Hopkins Tanne
Journal: BMJ (2004)

The US Food and Drug Administration has approved Verichip, an implantable radiofrequency identification device for patients, which would enable doctors to access their medical records.

Doctors hope that use of the device will result in be better treatment for patients in emergencies or when a patient is unconscious or lacks medical records. Some people have raised fears, however, that it could lead to infringements of patients' privacy.

The chip is the size of a grain of rice and is implanted under local anaesthesia beneath the patient's skin in the triceps area of the right arm, where it is invisible to the naked eye. It contains …
Differences in prostaglandin metabolism in cultured aortic and pulmonary arterial endothelial cells exposed to acute and chronic hypoxia.
Authors: H W Farber, H F Barnett
Journal: Circulation Research (1991)

In vivo, a marked difference in blood oxygen tension exists between the pulmonary artery and the aorta. Responses of vascular endothelial cells from these vessels to changes in ambient oxygen might be influenced by the oxygen tension to which they are continuously exposed in vivo or by their anatomic site. To explore this hypothesis, we initially studied the production of the cyclooxygenase metabolites prostacyclin and thromboxane in bovine aortic and main pulmonary arterial endothelial cells grown in 21% O2 and exposed to different degrees of acute hypoxia over a wide range of times. We found that short-term hypoxia (3% or 0% O2) rapidly and transiently activates the cyclooxygenase pathway in both cell types, with a more rapid response in bovine aortic endothelial cells. To determine whether culture in an oxygen tension similar to that to which main pulmonary arterial endothelial cells are exposed in vivo alters this response, we evaluated these cyclooxygenase metabolites in bovine aortic and main pulmonary arterial endothelial cells cultured long-term in 3% O2, both at baseline and after exposure to acute anoxia (0% O2). In both cell types, we found a decrease in prostacyclin and thromboxane synthesis at baseline and evidence of an increase in the Vmax of thromboxane synthetase following stimulation with exogenous arachidonic acid. In chronically hypoxic cells exposed to acute anoxia, there were marked differences in enzyme activity compared with that in endothelial cells maintained in 21% O2 with differences depending on the origin of the endothelial cells. In bovine aortic endothelial cells, production of neither cyclooxygenase metabolite increased; in bovine main pulmonary arterial endothelial cells, only thromboxane production increased, suggesting isolated activation of the cyclooxygenase-thromboxane synthetase pathway. These studies demonstrate that acute and chronic hypoxia have profound effects on endothelial cell cyclooxygenase metabolism and that these effects depend on the duration and degree of the hypoxic exposure and the vascular bed from which the endothelial cells are derived.
Diaphragm ultrasound as a predictor of successful extubation from mechanical ventilation
Authors: Ernest DiNino, Eric J Gartman, Jigme M Sethi, F Dennis McCool
Journal: Thorax (2013)

<h3>Introduction</h3> The purpose of this study was to evaluate if ultrasound derived measures of diaphragm thickening, rather than diaphragm motion, can be used to predict extubation success or failure. <h3>Methods</h3> Sixty-three mechanically ventilated patients were prospectively recruited. Diaphragm thickness (tdi) was measured in the zone of apposition of the diaphragm to the rib cage using a 7–10 MHz ultrasound transducer. The percent change in tdi between end-expiration and end-inspiration (Δtdi%) was calculated during either spontaneous breathing (SB) or pressure support (PS) weaning trials. A successful extubation was defined as SB for &gt;48 h following endotracheal tube removal. <h3>Results</h3> Of the 63 subjects studied, 27 patients were weaned with SB and 36 were weaned with PS. The combined sensitivity and specificity of Δtdi%≥30% for extubation success was 88% and 71%, respectively. The positive predictive value and negative predictive value were 91% and 63%, respectively. The area under the receiver operating characteristic curve was 0.79 for Δtdi%. <h3>Conclusions</h3> Ultrasound measures of diaphragm thickening in the zone of apposition may be useful to predict extubation success or failure during SB or PS trials.