tbuckley/cabot-search huggingface dataset:
<i>In Vivo</i> Programming of Tumor Antigen-Specific T Lymphocytes from Pluripotent Stem Cells to Promote Cancer Immunosurveillance
Authors: Fengyang Lei, Baohua Zhao, Rizwanul Haque, Xiaofang Xiong, Lynn Budgeon, Neil D. Christensen, Yuzhang Wu, Jianxun Song
Journal: Cancer Research (2011)

Abstract Adoptive T-cell immunotherapy has garnered wide attention, but its effective use is limited by the need of multiple ex vivo manipulations and infusions that are complex and expensive. In this study, we show how highly reactive antigen (Ag)-specific CTLs can be generated from induced pluripotent stem (iPS) cells to provide an unlimited source of functional CTLs for adoptive immunotherapy. iPS cell–derived T cells can offer the advantages of avoiding possible immune rejection and circumventing ethical and practical issues associated with other stem cell types. iPS cells can be differentiated into progenitor T cells in vitro by stimulation with the Notch ligand Delta-like 1 (DL1) overexpressed on bone marrow stromal cells, with complete maturation occurring upon adoptive transfer into Rag1-deficient mice. Here, we report that these iPS cells can be differentiated in vivo into functional CTLs after overexpression of MHC I-restricted Ag-specific T-cell receptors (TCR). In this study, we generated murine iPS cells genetically modified with ovalbumin (OVA)-specific and MHC-I restricted TCR (OT-I) by retrovirus-mediated transduction. After their adoptive transfer into recipient mice, the majority of OT-I/iPS cells underwent differentiation into CD8+ CTLs. TCR-transduced iPS cells developed in vivo responded in vitro to peptide stimulation by secreting interleukin 2 and IFN-γ. Most importantly, adoptive transfer of TCR-transduced iPS cells triggered infiltration of OVA-reactive CTLs into tumor tissues and protected animals from tumor challenge. Taken together, our findings offer proof of concept for a potentially more efficient approach to generate Ag-specific T lymphocytes for adoptive immunotherapy. Cancer Res; 71(14); 4742–7. ©2011 AACR.
Cell Distribution and Proliferation Pattern of a Transferable Acute Leukemia in Rats2
Authors: D. Hoelzer, W. Calvo, K.-D. Meyer-Hamme, E. B. Harriss
Journal: JNCI Journal of the National Cancer Institute (1973)

The pattern of colonization of an acute leukemia in rats, transferred by intravenous injection of leukemia cells, was investigated. The localization of leukemia cells and study of their proliferation in the early posttransfer stages were facilitated by labeling them in vitro with 3H-cytidine before transfer and subsequent autoradiography of sections. Immediately after injection, labeled cells were observed in the blood vessels of all organs studied. The earliest evidence of colonization was in the bone marrow and spleen. Proliferation of leukemia cells in these organscommenced within a few hours after injection. On the 3d day,deterioriation in the vascular structure of bone marrow and spleen occurred. Leukemia cells appeared in increasing numbers in the peripheral blood, and infiltration of liver, lung, lymph nodes, and thymus—only slight up to this time—became progressively more extensive. In the final stages, all organs were involved, with almost complete loss of normal architecture in bone marrow, spleen, thymus, and lymph nodes, whereas in the liver the normal architecture was maintained in large areas and the kidney became infiltrated only minimally. Although the cells transferred had already undergone neoplastic transformation, the observed growth pattern could reFlect some general aspects of the process of leukemic dissemination.
Bortezomib and gemcitabine in relapsed or refractory Hodgkin's lymphoma
Authors: J.H. Mendler, J. Kelly, S. Voci, D. Marquis, L. Rich, R.M. Rossi, S.H. Bernstein, C.T. Jordan, J. Liesveld, R.I. Fisher, J.W. Friedberg
Journal: Annals of Oncology (2008)
Occupational asthma in France: a 1-yr report of the Observatoire National de Asthmes Professionnels project
Authors: M.C. Kopferschmitt-Kubler, J. Ameille, E. Popin, A. Calastreng-Crinquand, D. Vervloet, M.C. Bayeux-Dunglas, G. Pauli
Journal: European Respiratory Journal (2002)

Observatoire National des Asthmes Professionnels (ONAP) was created in 1996 by two French professional societies to estimate the incidence of occupational asthma and to promote preventive measures against it. Occupational and chest physicians were asked to report newly diagnosed cases of work-related asthma and reactive airway dysfunction syndrome (RADS), the information collected included age, sex, occupation, suspected causal agents and diagnostic methods. In 1997, 82.3% of 559 cases reported (64% males, mean age 36±13 yrs) involved occupational asthma, 4.7% RADS and 12.7% atypical asthma syndromes. Incidence rates (expressed as number of cases per million workers) showed a regional variation that ranged from 4 to 73 (national mean: 25.7). The most frequently suspected agents were flour (23.3%), followed by isocyanates (16.6%), latex (7.5%), aldehydes (5.5%), and persulphates (4.1%). Occupations at risk were bakers (23.9%), healthcare workers (12%), painters (9.1%), hairdressers (5.2%), wood industry workers (4.8%) and cleaners (3.5%). These results are compared to those of other systems set up in Europe and North America. Because of the considerable bias inherent in a surveillance system based on voluntary, reporting, the number of occupational asthma cases reported is probably lower than the real incidence. Nevertheless, the French National Observatory for Occupational Asthma encourages physician awareness of occupational asthma and provides an estimate of its incidence and aetiologies in France.
A new instrument to assess physician skill at chest tube insertion: the TUBE-iCOMPT: Figure 1
Authors: Matthew R Salamonsen, Farzad Bashirzadeh, Alexander J Ritchie, Helen E Ward, David I K Fielding
Journal: Thorax (2014)

<h3></h3> Currently no tool exists to assess proceduralist skill at chest tube insertion. As inadequate doctor procedural competence has repeatedly been associated with adverse events, there is a need for a tool to assess procedural competence. <h3></h3> This study aims to develop and examine the validity of a tool to assess competency at insertion of a chest tube, using either the Seldinger technique or blunt dissection. <h3></h3> A 5-domain 100-point assessment tool was developed inline with British Thoracic Society guidelines and international consensus—the Chest Tube Insertion Competency Test (TUBE-iCOMPT). The instrument was used to assess chest tube insertion in mannequins and live patients. 29 participants (9 novices, 14 intermediate and 6 advanced) were tested by 2 blinded expert examiners on 2 occasions. The tool9s validity was examined by demonstrating: (1) stratification of participants according to expected level of expertise (analysis of variance), and (2) test-retest and intertester reliability (intraclass correlation coefficient). The intraclass correlation coefficient of repeated scores for the Seldinger technique and blunt dissection, were 0.92 and 0.91, respectively, for test-retest results, and 0.98 and 0.95, respectively, for intertester results. Clear stratification of scores according to participant experience was seen (p&lt;0.0001). There was no significant difference between scores obtained using mannequins or live patients. This study has validated the TUBE-iCOMPT, which could now be incorporated into chest tube insertion training programmes, providing a way to document acquisition of skill, guide individualised teaching, and assist with the assessment of the adequacy of clinician training.
Protein S–K196E mutation as a genetic risk factor for deep vein thrombosis in Japanese patients
Authors: Rina Kimura, Shigenori Honda, Tomio Kawasaki, Hajime Tsuji, Seiji Madoiwa, Yoichi Sakata, Tetsuhito Kojima, Mitsuru Murata, Kazuhiro Nishigami, Masaaki Chiku, Tokio Hayashi, Yoshihiro Kokubo, Akira Okayama, Hitonobu Tomoike, Yasuo Ikeda, Toshiyuki Miyata
Journal: Blood (2006)
Muscle insulin resistance resulting from impaired microvascular insulin sensitivity in Sprague Dawley rats
Authors: Dino Premilovac, Eloise A. Bradley, Huei L.H. Ng, Stephen M. Richards, Stephen Rattigan, Michelle A. Keske
Journal: Cardiovascular Research (2013)

Enhanced microvascular perfusion of skeletal muscle is important for nutrient exchange and contributes ∼40% insulin-mediated muscle glucose disposal. High fat-fed (36% fat wt./wt.) rats are a commonly used model of insulin-resistance that exhibit impairment of insulin-mediated microvascular recruitment and muscle glucose uptake, which is accompanied by myocyte insulin-resistance. Distinguishing the contribution of impaired microvascular recruitment and impaired insulin action in the myocyte to decreased muscle glucose uptake in these high-fat models is difficult. It is unclear whether microvascular and myocyte insulin-resistance develop simultaneously. To assess this, we used a rat diet model with a moderate increase (two-fold) in dietary fat. Sprague Dawley rats fed normal (4.8% fat wt./wt., 5FD) or high (9.0% fat wt./wt., 9FD) fat diets for 4 weeks were subject to euglycaemic hyperinsulinemic clamp (10 mU/min/kg insulin or saline) or isolated hindlimb perfusion (1.5 or 15 nM insulin or saline). Body weight, epididymal fat mass, and fasting plasma glucose were unaffected by diet. Fasting plasma insulin and non-esterified fatty acid concentrations were significantly elevated in 9FD. Glucose infusion rate and muscle glucose uptake were significantly impaired during insulin clamps in 9FD. Insulin-stimulated microvascular recruitment was significantly blunted in 9FD. Insulin-mediated muscle glucose uptake between 5FD and 9FD were not different during hindlimb perfusion. Impaired insulin-mediated muscle glucose uptake in vivo can be the direct result of reduced microvascular blood flow responses to insulin, and can result from small (two-fold) increases in dietary fat. Thus, microvascular insulin-resistance can occur independently to the development of myocyte insulin-resistance.
The infrapatellar fat pad of osteoarthritic patients has an inflammatory phenotype
Authors: I. Klein-Wieringa, M. Kloppenburg, Y. Bastiaansen-Jenniskens, E. Yusuf, J. Kwekkeboom, H. El-Bannoudi, R. Nelissen, A. Zuurmond, V. Stojanovic-Susulic, G. Van Osch, R. Toes, A. Ioan-Facsinay
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Obesity is a risk factor for the development of osteoarthritis (OA) in hands and knees. It has become apparent during the last years that adipose tissue can secrete different adipokines with powerful immunomodulatory effects. Because the infrapatellar fat pad (IFP) is an intra-articular organ in the vicinity of synovium and cartilage, the authors hypothesised that IFP-derived soluble factors could contribute to pathological processes in the knee joint. Therefore the authors have extensively compared the release of inflammatory mediators and characterised the adipocytes and immune cell infiltrate in IFP and Sc adipose tissue (ScAT). <h3>Materials and methods</h3> Paired IFP and ScAT samples were obtained from 27 primary OA patients. The stromal vascular cell fraction (SVF) was isolated and characterised by FACS. Cytokine and adipokine release in fat- and adipocyte-conditioned media was measured by luminex. <h3>Results</h3> IFP secreted higher levels of inflammatory mediators, like IL-6, adipsin, adiponectin and visfatin than ScAT. This could be due to differences in the phenotype of adipocytes or/and in composition and phenotype of the SVF cells. Indeed, a similar trend was seen for IL-6 and adipsin when adipocyte-conditioned media from IFP and ScAT were compared. Moreover, the SVF fraction of IFP contained more cells per gram tissue, a lower percentage of T cells and a higher percentage of mast cells than ScAT. In addition, IFP-derived T cells displayed a predominantly proinflammatory phenotype, while macrophages in IFP presented a mixed pro- and anti-inflammatory phenotype. Finally, tumour necrosis factor-α release by IFP was correlated with BMI, indicating BMI-related inflammatory changes in IFP. <h3>Conclusions</h3> The authors show profound differences in secreted inflammatory factors and immune cell composition between IFP and ScAT. These data indicate that IFP is qualitatively different from ScAT and IFP-derived soluble mediators could contribute to pathophysiological processes in the OA knee joint.
Permeability of connective tissue linings isolated from implanted capsules; implications for interstitial pressure measurements.
Authors: H J Granger, A E Taylor
Journal: Circulation Research (1975)

Quantification of the permeability of connective tissue linings isolated from implanted capsules was achieved by two types of experiments. The objective of the first type was to determine the restriction offered by the lining to diffusion of 125I-labeled human serum albumin. The restricted diffusion coefficient of albumin with respect to the connective tissue lining the luminal capsule surface (internal lining) averaged 3.0 times 10-7 plus or minus 0.4 times 10-7 cm2/sec in ten experiments indicating that the rate if migration of albumin across the structure was 35% of its free diffusion rate in water. In contrast, the albumin diffusion coefficient obtained for the abluminal (external) lining suggested that diffusion of albumin through this structure was 73% of the free diffusion rate in water. The objective of the second type of experiment was to determine solute reflection coefficients for inulin, serum albumin, and gamma-globulin with respect to the internal and external linings. For the internal lining, the reflection coefficients were: inulin 0.07, albumin0.23, and gamma-globulin 0.53. The external lining showed greater leakiness as evidenced by its lower reflection coefficient for a given molecule and its higher hydraulic conductivity. An equivalent pore calculation resulted in a calculated pore radius of 250-350 angstrom for the internal lining and a calculated pore radius of 500-600 angstrom for the external lining. The ineffectiveness of the leaky capsule lining in transmitting oncotic pressure suggests that under normal conditions the capsule measures interstitial hydrostatic pressure rather than oncotic pressure.
Protein Precoating of Elastomeric Tissue-Engineering Scaffolds Increased Cellularity, Enhanced Extracellular Matrix Protein Production, and Differentially Regulated the Phenotypes of Circulating Endothelial Progenitor Cells
Authors: Virna L. Sales, George C. Engelmayr, John A. Johnson, Jin Gao, Yadong Wang, Michael S. Sacks, John E. Mayer
Journal: Circulation (2007)

Optimal cell sources and scaffold-cell interactions remain unanswered questions for tissue engineering of heart valves. We assessed the effect of different protein precoatings on a single scaffold type (elastomeric poly (glycerol sebacate)) with a single cell source (endothelial progenitor cells).Elastomeric poly (glycerol sebacate) scaffolds were precoated with laminin, fibronectin, fibrin, collagen types I/III, or elastin. Characterized ovine peripheral blood endothelial progenitor cells were seeded onto scaffolds for 3 days followed by 14 days incubation. Endothelial progenitor cells were CD31+, vWF+, and alpha-SMA- before seeding confirmed by immunohistochemistry and immunoblotting. Both precoated and uncoated scaffolds demonstrated surface expression of CD31+ and vWF+, alpha-SMA+ cells and were found in the "interstitium" of the scaffold. Protein precoating of elastomeric poly (glycerol sebacate) scaffolds revealed significantly increased cellularity and altered the phenotypes of endothelial progenitor cells, which resulted in changes in cellular behavior and extracellular matrix production. Moreover, mechanical flexure testing demonstrated decreased effective stiffness of the seeded scaffolds compared with unseeded controls.Scaffold precoating with extracellular matrix proteins can allow more precise "engineering" of cellular behavior in the development of tissue engineering of heart valves constructs by altering extracellular matrix production and cell phenotype.
The power of context: reconceptualizing the placebo effect
Authors: Franklin G Miller, Ted J Kaptchuk
Journal: Journal of the Royal Society of Medicine (2008)

The placebo effect has received increasing scientific attention in recent years. Progress in translating knowledge about this phenomenon into improved outcomes for patients, however, is hampered by conceptual confusion and misleading terminology. In this article we diagnose what is wrong with the placebo concept and suggest ‘contextual healing’ as a fruitful alternative way of conceiving the placebo effect.
Association Between the Insulin-Like Growth Factor 2 Gene (<i>IGF2</i>) and Scores on the Eating Attitudes Test in Nonclinical Subjects: A Family-Based Study
Authors: Rachel Bachner-Melman, Ada H. Zohar, Lubov Nemanov, Uriel Heresco-Levy, Inga Gritsenko, Richard P. Ebstein
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: An interesting candidate gene for eating disorders is the gene for insulin-like growth factor 2 (IGF2). Located on chromosome 11p15.5, IGF2 is a member of the insulin family of polypeptide growth factors that is involved in development and growth. Consistent with its profile of metabolic actions, an association has been reported between a single nucleotide polymorphism (SNP) in the 3′ untranslated region of the IGF2 gene (ApaI) and body mass index. This investigation extended these studies and investigated the psychological and behavioral implications of this hormone's impact on metabolism and body composition. METHOD: The authors tested nonclinical subjects from 376 families for three IGF2 SNPs and for eating disorders, as reflected in scores on the 26-item Eating Attitudes Test, a self-report questionnaire widely used as a screening instrument. RESULTS: A highly significant association was observed between the IGF2 ApaI G allele and scores on the Eating Attitudes Test overall and each of its subscales (bulimia, dieting, and oral control). Additionally, a significant association was observed between this polymorphism and body mass index. CONCLUSIONS: The current finding that the IGF2 ApaI G polymorphism, which predisposes to weight gain, may also contribute to the pathology of eating disorders is intriguing. Neurotransmitter modulation of appetitive behavior is the focus of most hypotheses regarding the etiology of severe eating disorders. The current results to some measure challenge this view, and inborn metabolic tendencies to weight gain in some women may trigger constant dieting, which in predisposed individuals eventually leads to severe eating disorders.
Austrian Society of Gastroenterology and Hepatology (ÖGGH) - Guidelines on sedation and monitoring during gastrointestinal endoscopy
Authors: F. Schreiber,
Journal: Endoscopy (2007)

The increasing invasiveness of endoscopic examinations and interventions means that adequate sedation and appropriate patient monitoring are required. Overall, endoscopic interventions in the gastrointestinal tract are low risk, provided that they are performed in sufficient numbers by experienced personnel [1]. The risk of the examination or intervention depends primarily on the invasiveness and technical complexity of the procedure, but also on the patient's individual risk profile and the specific side-effect profile of the sedatives or anesthetics used. The overall rate of serious complications in gastroenterological examinations and interventions is between 1 in 1000 and 1 in 7500 [2].
Disruption of myofibrillar energy use: dual mechanisms that may contribute to postischemic dysfunction in stunned myocardium.
Authors: R A Greenfield, J L Swain
Journal: Circulation Research (1987)

The abnormalities in regional function produced by myocardial ischemia persist after the ischemic episode resolves. Since a close functional coupling exists between myofibrillar creatine kinase and myosin ATPase, a disruption of this coupling could adversely influence myocardial function and might provide a mechanism for the myocardial dysfunction observed. The purpose of the present study was to determine if an alteration in the activity of creatine kinase associated with the myofibril occurs in the postischemic period. Anesthetized open-chest dogs (n = 6) underwent coronary occlusion for 15 minutes, followed by reperfusion for 15 minutes. In reperfused myocardium, adenine nucleotide content was decreased (72 +/- 10% of nonischemic myocardium, p less than 0.05), documenting the presence of previous ischemia. The creatine phosphate content of reperfused myocardium returned to normal, indicating resumption of myocardial energy production. The creatine kinase activity of purified myofibrils isolated from reperfused myocardium was decreased by 17 +/- 7% compared to that of nonischemic myofibrils (p less than 0.03). In addition, the free adenosine diphosphate concentration in reperfused myocardium was calculated to be 96 microM and was less than the Km of adenosine diphosphate determined for myofibrillar creatine kinase (105 microM). The results suggest two putative mechanisms for disruption of energy use in postischemic myocardium: decreased creatine kinase activity associated with the myofibril, and limitation of substrate necessary for maximal creatine kinase activity.
US hospitals escape the worst of power failure
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

US hospitals coped well when the power went out. Elective surgery and outpatient clinics were cancelled in many hospitals across New York state as a result of the power blackout on 14 August. But most hospitals switched automatically to backup generators during the failure.

Electricity was lost in much of the northeastern area of the United States and southern Canada on a hot afternoon, affecting an estimated 50 million people for up to two days. The blackout knocked out mobile phones and also some landline telephones.

In New York city, the emergency medical service reportedly responded to 5000 calls, about 2000 more than usual. There were 80 000 calls to 911, the emergency telephone number. People were evacuated …
Targeted Deletion of <i>MKK4</i> in Cancer Cells: A Detrimental Phenotype Manifests as Decreased Experimental Metastasis and Suggests a Counterweight to the Evolution of Tumor-Suppressor Loss
Authors: Steven C. Cunningham, Eike Gallmeier, Tomas Hucl, David A. Dezentje, Eric S. Calhoun, Geppino Falco, Kotb Abdelmohsen, Myriam Gorospe, Scott E. Kern
Journal: Cancer Research (2006)

Abstract Tumor-suppressors have commanded attention due to the selection for their inactivating mutations in human tumors. However, relatively little is understood about the inverse, namely, that tumors do not select for a large proportion of seemingly favorable mutations in tumor-suppressor genes. This could be explained by a detrimental phenotype accruing in a cell type–specific manner to most cells experiencing a biallelic loss. For example, MKK4, a tumor suppressor gene distinguished by a remarkably consistent mutational rate across diverse tumor types and an unusually high rate of loss of heterozygosity, has the surprisingly low rate of genetic inactivation of only ∼5%. To explore this incongruity, we engineered a somatic gene knockout of MKK4 in human cancer cells. Although the null cells resembled the wild-type cells regarding in vitro viability and proliferation in plastic dishes, there was a marked difference in a more relevant in vivo model of experimental metastasis and tumorigenesis. MKK4−/− clones injected i.v. produced fewer lung metastases than syngeneic MKK4-competent cells (P = 0.0034). These findings show how cell type-specific detrimental phenotypes can offer a paradoxical and yet key counterweight to the selective advantage attained by cells as they experiment with genetic null states during tumorigenesis, the resultant balance then determining the observed biallelic mutation rate for a given tumor-suppressor gene. (Cancer Res 2006; 66(11): 5560-4)