tbuckley/cabot-search huggingface dataset:
Combined Blockade of Integrin-α4β1 Plus Cytokines SDF-1α or IL-1β Potently Inhibits Tumor Inflammation and Growth
Authors: Michael C. Schmid, Christie J. Avraamides, Philippe Foubert, Yuval Shaked, Sang Won Kang, Robert S. Kerbel, Judith A. Varner
Journal: Cancer Research (2011)

Tumor-associated macrophages promote tumor growth by stimulating angiogenesis and suppressing antitumor immunity. Thus, therapeutics that inhibit macrophage recruitment to tumors may provide new avenues for cancer therapy. In this study, we showed how chemoattractants stromal cell-derived growth factor 1 alpha (SDF-1α) and interleukin 1 beta (IL-1β) collaborate with myeloid cell integrin-α4β1 to promote tumor inflammation and growth. We found that SDF-1α and IL-1β are highly expressed in the microenvironments of murine lung, pancreatic, and breast tumors; surprisingly, SDF-1α was expressed only by tumor cells, whereas IL-1β was produced only by tumor-derived granulocytes and macrophages. In vivo, both factors directly recruited proangiogenic macrophages to tissues, whereas antagonists of both factors suppressed tumor inflammation, angiogenesis, and growth. Signals induced by IL-1β and SDF-1α promoted the interaction of talin and paxillin with the cytoplasmic tails of integrin-α4β1, thereby stimulating myeloid cell adhesion to endothelium in vitro and in vivo. Inhibition of integrin-α4β1, SDF-1α, or IL-1β was sufficient to block tumor inflammation and growth, and the combined blockade of these molecules greatly accentuated these effects. Furthermore, antagonists of integrin-α4β1 inhibited chemotherapy-induced tumor inflammation and acted synergistically with chemotherapeutic agents to suppress tumor inflammation and growth. These results show that targeting myeloid cell recruitment mechanisms can be an effective approach to suppress tumor progression.
Acute excited states and sudden death
Authors: D. Pounder, S. B Karch, B. G Stephens
Journal: BMJ (1998)

Editor—Farnham and Kennedy’s recent editorial on sudden death in patients with acute psychiatric illness1 who are being restrained does not reflect the forensic literature fairly. It omits evidence from key publications2,3 and twice misattributes statements to a paper that specifically excluded such deaths from the reported study.4

The current consensus on “restraint asphyxiation” is reflected in a guidance statement of the United States Department of Justice.5 Any person who is restrained prone has trouble breathing when pressure is applied to his or her back or when handcuffed and “hog tied,”2,3 and obesity exacerbates this. People’s natural reaction is to struggle more violently, which may be met with still more restraining force, resulting in greater oxygen deficiency and, in some cases, death. Risk factors include any condition, such as ischaemic heart disease or excited delirium,2 that increases susceptibility to cardiac arrhythmias, as well as intoxication with alcohol or drugs. 

Recommendations given to police officers on how to prevent such deaths include releasing people from the prone position as soon as they are handcuffed, not sitting on them, and never tying handcuffs to a leg or ankle restraint (hog tying).5 A form of hog tying restraint known as the police leg lock was prohibited in Denmark in 1994, after a campaign by the human rights organisation Amnesty International when an incident had left an 18 year old permanently brain damaged. There is evidence that restraint procedures that compromise respiratory movements are potentially dangerous, and this needs to be taken into account in any debate on their use in a healthcare setting.
Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials
Authors: G. C S Smith
Journal: BMJ (2003)

To determine whether parachutes are effective in preventing major trauma related to gravitational challenge.Systematic review of randomised controlled trials.Medline, Web of Science, Embase, and the Cochrane Library databases; appropriate internet sites and citation lists.Studies showing the effects of using a parachute during free fall.Death or major trauma, defined as an injury severity score > 15.We were unable to identify any randomised controlled trials of parachute intervention.As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind, randomised, placebo controlled, crossover trial of the parachute.
Calcium Signaling Mechanisms in T Lymphocytes
Authors: Richard S Lewis
Journal: Annual Review of Immunology (2001)

Elevation of intracellular free Ca 2+ is one of the key triggering signals for T-cell activation by antigen. A remarkable variety of Ca 2+ signals in T cells, ranging from infrequent spikes to sustained oscillations and plateaus, derives from the interactions of multiple Ca 2+ sources and sinks in the cell. Following engagement of the T cell receptor, intracellular channels (IP 3 and ryanodine receptors) release Ca 2+ from intracellular stores, and by depleting the stores trigger prolonged Ca 2+ influx through store-operated Ca 2+ (CRAC) channels in the plasma membrane. The amplitude and dynamics of the Ca 2+ signal are shaped by several mechanisms, including K + channels and membrane potential, slow modulation of the plasma membrane Ca 2+ -ATPase, and mitochondria that buffer Ca 2+ and prevent the inactivation of CRAC channels. Ca 2+ signals have a number of downstream targets occurring on multiple time scales. At short times, Ca 2+ signals help to stabilize contacts between T cells and antigen-presenting cells through changes in motility and cytoskeletal reorganization. Over periods of minutes to hours, the amplitude, duration, and kinetic signature of Ca 2+ signals increase the efficiency and specificity of gene activation events. The complexity of Ca 2+ signals contains a wealth of information that may help to instruct lymphocytes to choose between alternate fates in response to antigenic stimulation.
Quality of Life, Fertility Concerns, and Behavioral Health Outcomes in Younger Breast Cancer Survivors: A Systematic Review
Authors: J. Howard-Anderson, P. A. Ganz, J. E. Bower, A. L. Stanton
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundBreast cancer is the most common cancer in women younger than age 50 years. Cancer treatments in younger women may cause premature menopause, infertility, and negative psychosocial effects. In this systematic review, we examined three key domains of functioning that are particularly relevant for younger breast cancer survivors: health-related quality of life (QOL), menopausal symptoms and fertility concerns, and behavioral health outcomes.
Internalization of antibodies by endothelial cells via fibronectin implicating a novel mechanism in lupus nephritis
Authors: Hiroshi Fujii, Kimihiko Nakatani, Norimasa Arita, Mitsuko R. Ito, Miho Terada, Tatsuhiko Miyazaki, Minako Yoshida, Masao Ono, Takashi Fujiwara, Kan Saiga, Toshiyuki Ota, Haruo Ohtani, Martin Lockwood, Takeshi Sasaki, Masato Nose
Journal: Kidney International (2003)
Propranolol inhalation challenge in relation to histamine response in children with asthma.
Authors: J Gerritsen, G H Koeter, L T Vander Weele, K Knol
Journal: Thorax (1988)

The relation between airway responsiveness to propranolol and histamine was studied in 32 asthmatic children. Propranolol and histamine were given by nebuliser to a maximum dose of 16 mg/ml and 32 mg/ml respectively and the response was measured as the provocative concentration of agonist causing a 20% fall in FEV1 (PC20). A PC20 histamine value of less than 32 mg/ml was obtained in 24 of the 32 children, of whom 15 had a measurable PC20 propranolol (less than 16 mg/ml). In these 24 children the geometric mean PC20 histamine was 4.5 mg/ml and 14.4 mg/ml respectively in those with and without a measurable PC20 propranolol (p = 0.023). There was a linear relationship between histamine and propranolol PC20 values (r = 0.60), and between PC20 histamine and FEV1 % predicted (r = 0.43), but not between PC20 propranolol and FEV1 % predicted (r = 0.38). In an open time course study in 12 children with asthma recovery of FEV1 after inhaled propranolol was incomplete in seven of the children after 90 minutes. When inhaled propranolol was followed by inhaled ipratropium bromide in a further 11 children FEV1 had returned to baseline in all children after 60 minutes. Thus propranolol inhalation can be used in children with asthma to assess the contribution of the beta adrenergic system to the regulation of bronchial smooth muscle tone. The test has several disadvantages in comparison with histamine provocation-long duration, the prolonged action of propranolol, and the fact that only the children with substantial hyperreactivity to histamine react to propranolol.
EGFR/JIP-4/JNK2 Signaling Attenuates Cetuximab-Mediated Radiosensitization of Squamous Cell Carcinoma Cells
Authors: Iris Eke, Lydia Schneider, Claudia Förster, Daniel Zips, Leoni A. Kunz-Schughart, Nils Cordes
Journal: Cancer Research (2012)

EGF receptor (EGFR) promotes tumor growth as well as radio- and chemoresistance in various human malignancies including squamous cell carcinomas (SCC). In addition to deactivation of prosurvival signaling, cetuximab-mediated EGFR targeting might concomitantly induce self-attenuating signaling bypasses. Identification of such bypass mechanisms is key to improve the efficacy of targeted approaches. Here, we show great similarity of EGFR signaling and radiation survival in cetuximab-treated SCC cells grown in a more physiologic three-dimensional extracellular matrix and as tumor xenografts in contrast to conventional monolayer cell cultures. Using phosphoproteome arrays, we observed strong induction of JNK2 phosphorylation potentially resulting from cetuximab-inhibited EGFR through c-jun-NH(2)-kinase (JNK)-interacting protein-4 (JIP-4), which was identified using an immunoprecipitation-mass spectrometric approach. Inhibition of this signaling bypass by JIP-4 or JNK2 knockdown or pharmacologic JNK2 inhibition enhanced cetuximab efficacy and tumor cell radiosensitivity. Our findings add new facets to EGFR signaling and indicate signaling bypass possibilities of cancer cells to improve their survival on cetuximab treatment. By deactivation of cetuximab-self-attenuating JNK2-dependent signaling, the cytotoxicity, and radiosensitizing potential of cetuximab can be augmented.
Postoperative dose-dense sequential chemotherapy with epirubicin, followed by CMF with or without paclitaxel, in patients with high-risk operable breast cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group
Authors: G. Fountzilas, D. Skarlos, U. Dafni, H. Gogas, E. Briasoulis, D. Pectasides, C. Papadimitriou, C. Markopoulos, A. Polychronis, H.P. Kalofonos, V. Siafaka, P. Kosmidis, E. Timotheadou, D. Tsavdaridis, D. Bafaloukos, P. Papakostas, E. Razis, P. Makrantonakis, G. Aravantinos, C. Christodoulou, A.-M. Dimopoulos
Journal: Annals of Oncology (2005)
OPTIMOX1: A Randomized Study of FOLFOX4 or FOLFOX7 With Oxaliplatin in a Stop-and-Go Fashion in Advanced Colorectal Cancer—A GERCOR Study
Authors: Christophe Tournigand, Andres Cervantes, Arie Figer, Gérard Lledo, Michel Flesch, Marc Buyse, Laurent Mineur, Elisabeth Carola, Pierre-Luc Etienne, Fernando Rivera, Isabel Chirivella, Nathalie Perez-Staub, Christophe Louvet, Thierry André, Isabelle Tabah-Fisch, Aimery de Gramont
Journal: Journal of Clinical Oncology (2006)

In metastatic colorectal cancer, a combination of leucovorin (LV) and fluorouracil (FU) with oxaliplatin (FOLFOX) 4 is a standard first-line regimen. The cumulative neurotoxicity of oxaliplatin often requires therapy to be stopped in patients who are still responding. This study evaluates a new strategy of intermittent oxaliplatin treatment that is based on FOLFOX7, a simplified leucovorin and fluorouracil regimen with high-dose oxaliplatin.Previously untreated patients were randomly assigned to either FOLFOX4 administered every 2 weeks until progression (arm A) or FOLFOX7 for six cycles, maintenance without oxaliplatin for 12 cycles, and reintroduction of FOLFOX7 (arm B).Six hundred twenty patients were enrolled, including an exploratory cohort of 95 elderly or poor prognosis patients. Median progression-free survival and survival times were 9.0 and 19.3 months, respectively, in patients allocated to arm A compared with 8.7 and 21.2 months, respectively, in patients allocated to arm B (P = not significant). Response rates were 58.5% with arm A and 59.2% with arm B. National Cancer Institute Common Toxicity Criteria grade 3 or 4 toxicity was observed in 54.4% of the patients in arm A v 48.7% of patients in arm B. From cycle 7, fewer patients experienced grade 3 or 4 toxicity in arm B. Grade 3 sensory neuropathy was observed in 17.9% of the patients in arm A v 13.3% of patients in arm B (P = .12). In arm B, oxaliplatin was reintroduced in only 40.1% of the patients but achieved responses or stabilizations in 69.4% of these patients.Oxaliplatin can be safely stopped after six cycles in a FOLFOX regimen. Further study is needed to fully evaluate oxaliplatin reintroduction.
Accuracy of asthma treatment in schoolchildren in NSW, Australia
Authors: NA Paterson, JK Peat, CM Mellis, W Xuan, AJ Woolcock
Journal: European Respiratory Journal (1997)

Insufficient use of anti-inflammatory drugs, such as inhaled corticosteroids and cromoglycate, may contribute to the disease burden associated with asthma. Conversely, aggressive treatment of mild disease may result in avoidable costs and/or adverse drug effects. The aim of this study was to determine the relationship between asthma severity and inhaled corticosteroid/cromoglycate use in a large (n=4,909) random sample of children, aged 8-11 yrs, in NSW, Australia. Asthma and its treatment were assessed by questionnaire responses. Asthma, defined as diagnosis plus current wheeze, was present in 901 children (18% of the sample), of whom 225 (5%) had moderate asthma, defined as asthma plus additional symptoms (sleep disturbance), utilization (hospital, casualty), or disability (reduced activity, school absence). Use of inhaled corticosteroid/cromoglycate was reported by 636 children (13% of the sample). Determinants of use included: asthma diagnosis, current wheeze, and troublesome dry nocturnal cough. There was also a strong relationship between anti-inflammatory treatment and a multicomponent asthma severity score constructed for each child. Inhaled corticosteroids and/or cromoglycate were used by 56% of the children with asthma (24% daily) and by 76% of children with moderate asthma (42% daily). Undertreatment, defined as less than daily inhaled corticosteroids/cromoglycate in moderate asthma, was identified in 130 children (14% of those with asthma or 3% of the sample). Conversely, apparently aggressive treatment, defined as inhaled corticosteroid/cromoglycate use in children with persistent minimal symptoms (asthma severity score of less than 3) was identified in 101 children (2% of the sample). Although there were significant differences between regions in the choice of anti-inflammatory drugs and in the prevalence both of undertreatment and apparently aggressive treatment, there was no clear relationship to regional utilization of emergency and hospital services for asthma. Nevertheless, the frequency of undertreatment suggests an opportunity to reduce asthma morbidity by more consistent application of current therapeutic guidelines.
Obstructive and restrictive spirometric patterns: fixed cut-offs for FEV1/FEV6 and FEV6
Authors: J. Vandevoorde, S. Verbanck, D. Schuermans, J. Kartounian, W. Vincken
Journal: European Respiratory Journal (2006)

The purpose of this study was to determine fixed cut-off points for forced expiratory volume in one second (FEV(1))/FEV(6) and FEV(6) as an alternative for FEV(1)/forced vital capacity (FVC) and FVC in the detection of obstructive and restrictive spirometric patterns, respectively. For the study, a total of 11,676 spirometric examinations, which took place on Caucasian subjects aged between 20-80 yrs, were analysed. Receiver-operator characteristic curves were used to determine the FEV(1)/FEV(6) ratio and FEV(6) value that corresponded to the optimal combination of sensitivity and specificity, compared with the commonly used fixed cut-off term for FEV(1)/FVC and FVC. The data from the current study indicate that FEV(1)/ FEV(6) <73% and FEV(6) <82% predicted can be used as a valid alternative for the FEV(1)/FVC <70% and FVC <80% pred cut-off points for the detection of obstruction and restriction, respectively. The statistical analysis demonstrated very good, overall, agreement between the two categorisation schemes. For the spirometric diagnosis of airway obstruction (prevalence of 45.9%), FEV(1)/FEV(6) sensitivity and specificity were 94.4 and 93.3%, respectively; the positive and negative predictive values were 92.2 and 95.2%, respectively. For the spirometric detection of a restrictive pattern (prevalence of 14.9%), FEV(6) sensitivity and specificity were 95.9 and 98.6%, respectively; the positive and negative predictive values were 92.2 and 99.3%, respectively. This study demonstrates that forced expiratory volume in one second/forced expiratory volume in six seconds <73% and forced expiratory volume in six seconds <82% predicted, can be used as valid alternatives to forced expiratory volume in one second/forced vital capacity <70% and forced vital capacity <80% predicted, as fixed cut-off terms for the detection of an obstructive or restrictive spirometric pattern in adults.
A multicenter randomized controlled trial of recombinant interferon-α2b in patients with acute transfusion-associated hepatitis C
Authors: Pietro Lampertico, Mariagrazia Rumi, Raffaella Romeo, Antonio Craxi, Roberta Soffredini, Daniela Biassoni, Massimo Colombo
Journal: Hepatology (1994)

To assess whether interferon-alpha might prevent non-A, non-B hepatitis from becoming chronic, 45 consecutive patients with transfusion-associated hepatitis were enrolled in a randomized clinical trial. Thirty-eight patients had hepatitis C virus infection, and 7 had non-A, non-B, non-C hepatitis. Twenty-six patients (22 with HCV) were given 3 MU of recombinant interferon-alpha 2b three times a week for 12 wk, whereas 19 (16 with HCV) were not. Biochemical and virological parameters were monitored at regular intervals during an 18-mo follow-up. At the end of the 3-mo therapy, 16 (73%) patients with hepatitis C had normal serum ALT activity, compared with 7 (44%) who were not treated (NS). Fifty-three percent of the treated patients and none of the untreated patients had normal ALT levels and no HCV RNA (p = 0.0087). At the end of the 18-mo follow-up, 13 (59%) treated patients had normal ALT levels, compared with 6 (37%) untreated controls (NS). Thirty-nine percent had normal ALT and no HCV RNA, compared with none of the controls (p = 0.035). Four patients (22%) had had sustained complete responses to interferon, defined as normal ALT levels and no HCV RNA at the end of the 3-mo treatment period and the 18-mo follow-up period. All seven patients with non-A, non-B, non-C hepatitis, treated and untreated, recovered uneventfully from hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)
Electrophysiologic characteristics of Ebstein's anomaly of the tricuspid valve.
Authors: J A Kastor, B N Goldreyer, M E Josephson, J K Perloff, D L Scharf, J H Manchester, J C Shelburne, J W Hirshfeld
Journal: Circulation (1975)

Electrophysiologic characteristics of five patients with Ebstein's anomaly of the tricuspid valve were defined with studies using luminal intracardiac electrode catheters. The diagnosis was made in each case from clinical data and confirmed at cardiac catheterization by the presence of an atrialized right ventricular chamber with atrial mechanical activity and ventricular electrical activity. In three cases intra-right atrial conduction was prolonged (P-A intervals of 50, 50, and 65 msec), a finding which reflected the presence of a characteristically large right atrium. The bundle of His electrogram was recorded in its usual anatomical location. Atrioventricular nodal conduction was prolonged in only one case. Intra-His delay was observed in two cases (bundle of His duration of 30 and 30 msec). Infranodal conduction was prolonged in four cases with H-V intervals of 60, 65, 65, and 80 msec. The anatomical abnormalities were least severe in the only patient with a normal H-V interval (50 msec). The prolonged H-V interval was thought to result from stretching of the conduction system over the atrialized right ventricle (ARV). The late depolarization during the splintered R' of the electrocardiogram found during intracardiac mapping of the ARV in three patients confirms the theory that the ARV produces the "second QRS" typically seen in this anomaly. The ARV was particularly irritable, and ventricular fibrillation was produced in two patients during catheter manipulation in this area. In one case the ARV had a shorter refractory period than the body of the right ventricle. Re-entrant supraventricular tachycardia was induced in the only patient with Wolff-Parkinson-White syndrome. In addition to the previously recognized electrophysiologic features reconfirmed here, patients with Ebstein's anomaly of the tricuspid valve usually have: normal position of the bundle of His, prolonged intra- right atrial conduction, prolonged infranodal conduction, and irritable ARV with delayed activation.
HIV-1 Envelope gp41 Antibodies Can Originate from Terminal Ileum B Cells that Share Cross-Reactivity with Commensal Bacteria
Authors: Ashley M. Trama, M. Anthony Moody, S. Munir Alam, Frederick H. Jaeger, Bradley Lockwood, Robert Parks, Krissey E. Lloyd, Christina Stolarchuk, Richard Scearce, Andrew Foulger, Dawn J. Marshall, John F. Whitesides, Thomas L. Jeffries, Kevin Wiehe, Lynn Morris, Bronwen Lambson, Kelly Soderberg, Kwan-Ki Hwang, Georgia D. Tomaras, Nathan Vandergrift, Katherine J.L. Jackson, Krishna M. Roskin, Scott D. Boyd, Thomas B. Kepler, Hua-Xin Liao, Barton F. Haynes
Journal: Cell Host & Microbe (2014)
<i>Islet1</i> Derivatives in the Heart Are of Both Neural Crest and Second Heart Field Origin
Authors: Kurt A. Engleka, Lauren J. Manderfield, Rachael D. Brust, Li Li, Ashley Cohen, Susan M. Dymecki, Jonathan A. Epstein
Journal: Circulation Research (2012)

Islet1 (Isl1) has been proposed as a marker of cardiac progenitor cells derived from the second heart field and is utilized to identify and purify cardiac progenitors from murine and human specimens for ex vivo expansion. The use of Isl1 as a specific second heart field marker is dependent on its exclusion from other cardiac lineages such as neural crest.Determine whether Isl1 is expressed by cardiac neural crest.We used an intersectional fate-mapping system using the RC::FrePe allele, which reports dual Flpe and Cre recombination. Combining Isl1(Cre/+), a SHF driver, and Wnt1::Flpe, a neural crest driver, with Rc::FrePe reveals that some Isl1 derivatives in the cardiac outflow tract derive from Wnt1-expressing neural crest progenitors. In contrast, no overlap was observed between Wnt1-derived neural crest and an alternative second heart field driver, Mef2c-AHF-Cre.Isl1 is not restricted to second heart field progenitors in the developing heart but also labels cardiac neural crest. The intersection of Isl1 and Wnt1 lineages within the heart provides a caveat to using Isl1 as an exclusive second heart field cardiac progenitor marker and suggests that some Isl1-expressing progenitor cells derived from embryos, embryonic stem cultures, or induced pluripotent stem cultures may be of neural crest lineage.