tbuckley/cabot-search huggingface dataset:
Overexpression of histidine-rich Ca-binding protein protects against ischemia/reperfusion-induced cardiac injury
Authors: X ZHOU, G FAN, X REN, J WAGGONER, K GREGORY, G CHEN, W JONES, E KRANIAS
Journal: Cardiovascular Research (2007)

The histidine-rich Ca-binding protein (HRC) is a Ca-storage protein in cardiac sarcoplasmic reticulum. Recent transgenic studies revealed that this protein inhibits the maximal rates of sarcoplasmic reticulum Ca-transport, leading to cardiac dysfunction. In view of the role of sarcoplasmic reticulum Ca-cycling in myocardial ischemia/reperfusion injury, we designed this study to gain further insight into the role of HRC during ischemia/reperfusion.The transgenic mouse model with cardiac-specific overexpression of HRC was utilized and cardiac contractile parameters were assessed before and after ischemia/reperfusion injury by Langendorff perfusion. After a 20-min stabilization period, the hearts were subjected to 40 min of global ischemia, followed by 60 min of reperfusion. We found that although transgenic (TG) hearts showed depressed cardiac function (25%) compared to wild types (WTs) at baseline, they exhibited better recovery of left ventricular developed pressure (86.6+/-2.6% in TGs vs. 58.3+/-4.0% in WTs of pre-ischemic values, P<0.05) and higher rates of contraction and relaxation after ischemia/reperfusion than WTs. This improvement was accompanied by smaller infarcts (23.1+/-1.7% in TGs vs. 41.1+/-2.5% in WTs of infarct region-to-risk region ratio, P<0.05) and lower creatine kinase release. Notably, the extent of apoptotic cell death was significantly attenuated, as evidenced by decreased DNA fragmentation, upregulation of the antiapoptotic protein Bcl-2, and downregulation of the active caspases (3, 9 and 12) following ischemia/reperfusion in TG hearts, compared with WTs. Extension of these studies to an in vivo model of 30-min myocardial ischemia, via coronary artery occlusion, followed by 24-h reperfusion, showed that the infarct region-to-risk region ratio was 9+/-0.9% in TGs, compared with 20.4+/-2.9% in WTs (P<0.05).Our findings suggest that increased cardiac HRC expression protects against ischemia/reperfusion injury in the heart, resulting in improved recovery of function and reduced infarction.
Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women.
Authors: P Szulc, M C Chapuy, P J Meunier, P D Delmas
Journal: Journal of Clinical Investigation (1993)

1. Abbreviations used in this paper: GLA, -y-carboxyglutamic acid; OC, osteocalcin; similarly carbOC, carboxylated osteocalcin; ucOC, under- carboxylated osteocalcin; also, ucOC%, undercarboxylated
Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: results of a phase 1/2 study
Authors: Donna E. Reece, Ute Hegenbart, Vaishali Sanchorawala, Giampaolo Merlini, Giovanni Palladini, Joan Bladé, Jean-Paul Fermand, Hani Hassoun, Leonard Heffner, Robert A. Vescio, Kevin Liu, Christopher Enny, Dixie-Lee Esseltine, Helgi van de Velde, Andrew Cakana, Raymond L. Comenzo
Journal: Blood (2011)
Tissue of origin determines cancer-associated CpG island promoter hypermethylation patterns
Authors: Duncan Sproul, Robert R Kitchen, Colm E Nestor, J Michael Dixon, Andrew H Sims, David J Harrison, Bernard H Ramsahoye, Richard R Meehan
Journal: Genome biology (2012)

Abstract Background Aberrant CpG island promoter DNA hypermethylation is frequently observed in cancer and is believed to contribute to tumor progression by silencing the expression of tumor suppressor genes. Previously, we observed that promoter hypermethylation in breast cancer reflects cell lineage rather than tumor progression and occurs at genes that are already repressed in a lineage-specific manner. To investigate the generality of our observation we analyzed the methylation profiles of 1,154 cancers from 7 different tissue types. Results We find that 1,009 genes are prone to hypermethylation in these 7 types of cancer. Nearly half of these genes varied in their susceptibility to hypermethylation between different cancer types. We show that the expression status of hypermethylation prone genes in the originator tissue determines their propensity to become hypermethylated in cancer; specifically, genes that are normally repressed in a tissue are prone to hypermethylation in cancers derived from that tissue. We also show that the promoter regions of hypermethylation-prone genes are depleted of repetitive elements and that DNA sequence around the same promoters is evolutionarily conserved. We propose that these two characteristics reflect tissue-specific gene promoter architecture regulating the expression of these hypermethylation prone genes in normal tissues. Conclusions As aberrantly hypermethylated genes are already repressed in pre-cancerous tissue, we suggest that their hypermethylation does not directly contribute to cancer development via silencing. Instead aberrant hypermethylation reflects developmental history and the perturbation of epigenetic mechanisms maintaining these repressed promoters in a hypomethylated state in normal cells.
Smoking habits after laryngectomy.
Authors: S Himbury, R West
Journal: BMJ (1985)

Questionnaires envoyes a 248 malades apres laryngectomie pour cancer. Les reponses (171), anonymes, sont analysees. 40% des malades ont repris leurs habitudes de fumeurs, ce qui est peu par comparaison avec les cas de cancer du poumon. Cette difference s'explique peut-etre par le fait qu'apres laryngectomie la satisfaction est reduite, la fumee n'atteignant pas les poumons de la meme facon
A Closer Look at the Institutional Ethics Committee
Authors: Herman S. Wigodsky
Journal: JAMA (1986)

This 27-minute VHS TV film, accompanied by a seven-page viewer's guide and bibliography, evolved from a twoday conference on institutional ethics committees; it is somewhat disjointed because of apparent difficulties in editing. The film opens with a brief glimpse of an ongoing discussion in a simulated meeting of an institutional ethics committee, followed by a brief introduction by a commentator who appears in a number of sequences in the film. Four principal institutional ethics committee issues are discussed in the film: genesis, functions, decision-marking process, and unsettled issues. A part of the genesis or developmental background of institutional ethics committees is presented by the moderator and by John Paris, SJ, ethicist, College of Holy Cross. Functions of the committee are discussed briefly by Ellen Weiss, JD, general counsel, Boston Children's Hospital. A mock case is presented to a meeting of the simulated institutional ethics committee. The presenter, a physician on
A Clinical Comparison of Aerosol and Powder Administration of Beclomethasone Dipropionate in Childhood Asthma
Authors: H. Bisgaard, J. B. Andersen, N. Bach‐Mortensen, A. Bertelsen, B. Friis, B. C. Koch, P. Prahl, R. Wichmann, O. ØSterballe
Journal: Allergy (1984)

Forty children with childhood asthma were conducted through a double‐blind cross‐over study to compare the effect of 400 μg beclomethasone dipropionate administered as aerosol and powder (Rotacaps). Children with severe asthma derived more benefit from the steroid administered as aerosol judged from their peak (low performance in the morning, although neither evening peak flow nor symptom scores revealed any difference. It is concluded that the Rotacaps are an advantageous supplement to available medication for the treatment of asthmatic children, although it should be observed that, using equal amounts of BDP. powder administration seems less effective than aerosol.
Report LXXXIII: Some Experiments on Enterica, Scarlet Fever, and Measles in the Chimpanzee: [A Preliminary Communication.]
Authors: A. S. Grunbaum
Journal: BMJ (1904)

THE bacillus described by Eberth in i88o and isolated bv Gaffky. in I884 has been very generally accepted as the causal agent of enteric, fever, although it was not then possible to fulfil Koch's third postulate, and to produce with the bacillus lesions in ani-mals similar to those resulting from the disease in man.Additional evidence.wasforthcoming as-to the probable responsibility of the Eberth-Gaffky bacillus for en-
The effect of preserving antral innervation and of a pyloroplasty on gastric emptying after vagotomy in man
Authors: R. J. Clarke, J. Alexander-Williams
Journal: Gut (1973)

A prospective randomized trial of 40 duodenal ulcer patients is reviewed. The patients had one of four operations (selective vagotomy, proximal gastric vagotomy, selective vagotomy plus pyloroplasty, or proximal gastric vagotomy plus pyloroplasty). The gastric emptying of a hypertonic fluid meal was assessed before and three to four months after operation. Selective vagotomy without a drainage procedure results in gastric retention and should no longer be considered as a method of treatment for duodenal ulcer. Proximal gastric vagotomy without a drainage procedure does not lead to gastric retention. Initial gastric emptying is more rapid after proximal gastric vagotomy but the final emptying time is the same as before operation and this operation alters the pattern of gastric emptying less than the other operations. Pyloroplasty added to either selective or proximal gastric vagotomy results in loss of the normal regulation of gastric emptying, very rapid initial gastric emptying, and a significant increase in the incidence of `dumping9. It appears from these studies that `dumping9 is due to rapid gastric emptying and mainly due to the drainage procedure.
Staging of Pancreatic Carcinoma by Endoscopic Ultrasonography
Authors: K. Yasuda, H. Mukai, M. Nakajima, K. Kawai
Journal: Endoscopy (1993)

The ability of EUS to diagnose small pancreatic cancer is well known. In this study, we present our experience with EUS in the local staging of 29 patients with pancreatic carcinoma who underwent surgery. EUS was 79, 83 and 79 % accurate in determining anterior (including gastric), duodenal and retroperitoneal (vascular) invasion by the tumor. Ultrasonography (48, 39 and 55 %, respectively) and CT (38, 33 and 41 %, respectively) were less reliable. EUS was equal to angiography in diagnosing vascular involvement. EUS was more effective in detecting splenoportal infiltration (sensitivity 88 %, specificity 78 %) than arterial involvement (accuracy 50 %). EUS was also less reliable in determining the N stage (66 %) and in stage grouping (72 %). Although EUS is superior to ultrasonography and CT in the local staging of pancreatic carcinoma, further studies must show whether improved staging criteria will lead to better results.
289Pharmacologic rejuvenation of senescent human cardiac stem cells enhances myocardial repair
Authors: E Avolio, G Gianfranceschi, A Caragnano, E Athanasakis, R Katare, M Meloni, CA Beltrami, D Cesselli, P Madeddu, AP Beltrami
Journal: Cardiovascular Research (2014)

Purpose: Cellular senescence associated with ageing and disease hampers the functional properties of human c-Kit+ Cardiac Stem Cells (CSC) in vitro. Aim of the study was to identify molecular mechanisms associated with CSC senescence and to pharmacologically modulate this latter, at the aim to improve the therapeutic potential of CSC in vivo. Methods: c-Kit+ CSC were isolated from atrial specimens of end-stage failing hearts (E-CSC, n=20) and hearts donated for transplantation (D-CSC, n=14). D- and E-CSC were compared in vitro for the expression of senescence markers and secretome. The ability of CSC's secretome to protect rat adult cardiomyocytes (CM) in vitro from a simulated ischemia-reperfusion injury was analysed. 3 molecular signalling pathways associated with cell senescence were investigated. A 3-days pharmacologic treatment with a cocktail of 10nM Rapamycin and 0.5μM Resveratrol was employed to revert E-CSC senescence in vitro. The functional recovery of SCID-Beige mice infarcted hearts injected with Vehicle (n=17), D-CSC (n=17), E-CSC (n=18) or drug-conditioned-E-CSC (n=18) (300,000 cells/heart) was compared 14 days post-transplantation. Results: with respect to D-CSC, E-CSC show, in vitro, higher levels of senescence markers (p16, γH2AX), a blunted proliferation and a secretome strongly enriched in the pro-inflammatory IL-1β, unable to protect rat CM from apoptosis and senescence in vitro. Neutralisation of IL-1β restored E-CSC's secretome protective effect. At the molecular level, E-CSC are characterized by an hyper-activation of the canonical NFB pathway and of Caspase1, an increased activity of the TORC1 complex, an impairment of the authophagic flux and a reduction of AMPK, Akt and CREB activation. All these alterations could be successfully reverted employing a cocktail of Rapamycin and Resveratrol. The drug treatment reduced the fraction of senescent E-CSC and the amount of IL-1β secreted in vitro, thus restoring the protective effect on rat CM. Last, D-CSC but not E-CSC were able to enhance myocardial healing when injected in a mouse infarcted heart. However, the ex vivo preconditioning of E-CSC with Rapamycin and Resveratrol, prior to the in vivo transplantation, restored their reparative potential to D-CSC levels. Conclusions: we first demonstrate that senescent c-Kit+ CSC resident in human failing hearts display an impaired in vivo reparative ability; importantly, senescent CSC can be rejuvenated in vitro with a short pharmacologic conditioning, finally boosting the in vivo cardiac regeneration. These findings open new avenues to improve autologous CSC therapy in heart failure.
Circulating and Urinary Catecholamines in Pheochromocytoma
Authors: Emmanuel L. Bravo, Robert C. Tarazi, Ray W. Gifford, Bruce H. Stewart
Journal: New England Journal of Medicine (1979)

Three biochemical tests for the diagnosis of pheochromocytoma were evaluated in 24 patients with proved tumors and 40 patients whose clinical picture was suspect but who had no evidence of the disease. Measurement of resting, supine plasma catecholamines (by radioenzymatic assay) was more useful than either 24-hour urinary vanillyl-mandelic acid (VMA) or metanephrines or both. In only one of 23 patients with pheochromocytoma were plasma catecholamines within the range of those in patients without pheochromocytoma, as compared with urinary VMA in 11 of 22, urinary metanephrines in five of 22 and both metabolites in three of 22. These studies reaffirm the value of plasma catecholamines in the diagnosis of pheochromocytoma and indicate that urinary catecholamine metabolites are less useful. The poor correlation between the height of arterial pressure and circulating levels of catecholamines suggests that the regulation of arterial pressure in pheochromocytoma is complex. (N Engl J Med 301:682–686, 1979)
P01.02 * FIBROBLAST GROWTH FACTOR 4 CONTRIBUTES TO 3-DIMENSIONAL GROWTH OF HUMAN GLIOBLASTOMA
Authors: D. Lotsch, B. Englinger, J. Pichler, J. Hainfellner, C. Marosi, T. Czech, E. Knosp, J. Buchroithner, S. Spiegl-Kreinecker, W. Berger
Journal: Neuro-Oncology (2014)

Glioblastoma growth is driven by receptor tyrosine kinase (RTK)-mediated signals. One of the RTK systems recently coming into focus are the fibroblast growth factor (FGF) high-affinity receptors (FGFR1-FGFR4) due to mutation, overexpression or translocation in several cancer types. FGF/FGFR represents a complex signal network with essential functions in embryonic development, tissue homeostasis and wound healing but also for malignant transformation and growth as well as tumor neoangiogenesis and therapy failure. Several studies have suggested a role of FGFRs in human glioblastoma whereby the information on FGFR4 is sparse. Here we investigated whether FGFR4 as compared to FGFR1 blockade impacts on glioblastoma growth in vitro and in vivo. Both in human glioblastoma cell lines (N = 8) and primary cell cultures from clinical samples (N = 26) we found a widespread expression of several FGFs (e.g. FGF1, FGF2, and FGF5) but also a significant overexpression of FGFR1 and FGFR4 in distinct subgroups as compared to non-malignant brain primo cell cultures. Regarding FGFR1 mRNA, all glioma cell models investigated expressed in addition to the FGFR1-IIIb also the mesenchymal and more oncogenic FGFR1-IIIc splice variant. Application of the FGFR inhibitors (nintedanib, ponatinib) as well as expression of dominant-negative (dn) versions of FGFR1 and FGFR4 significantly reduced in vitro cell growth and clonogenicity in the tested glioma cell models whereby dnFGFR1 tended to be more efficient than dnFGFR4. Accordingly, both dominant-negative FGFRs induced significant apoptosis whereby the effects of dnFGFR1 were again significantly stronger. Surprisingly, the inhibitory effects on anchorage-independent growth in soft agar were opposite with significant mitigation by dnFGFR1 but almost complete blockade by dnFGFR4 in the majority of the glioblastoma models analysed. Additionally, neurosphere formation, indicative for the presence of glioma stem cells, was profoundly reduced by both dnFGFRs. Interestingly, FGFR4 belonged to those genes significantly overexpressed in the cancer stem cell compartment (N = 16; mRNA expression arrays of neurosphere versus adherent cell culture). Accordingly, growth of two out of three human glioblastoma xenografts analysed in SCID mice was completely inhibited by dnFGFR4 while only retarded by dnFGFR1. Summarizing our data substantiates a significant contribution of FGF/FGFR-mediated signals to different aspects of glioblastoma aggressiveness and suggests a particular role of FGFR4 in stemness and three-dimensional in vivo growth.
Treatment of Neuroblastoma Using the Fused Imaging Guided Radiotherapy (FIGURA) System
Authors: Eyal Fenig, Moshe Mishaeli, Rinat Yerushalmi, Zvi Bar Sever, Shifra Ash, Liora Kornreich, Itzak Yaniv, Adam Steinmetz
Journal: Clinical Nuclear Medicine (2006)

Purpose: The purpose of this study was to describe our department's experience with the fused imaging-guided radiotherapy (FIGURA) system for planning radiation treatment of high-risk neuroblastoma. Patients and Methods: Between 1999 and 2002, 11 patients received radiation therapy as consolidation after chemotherapy in 9 and for palliation in 2. Diagnostic metaiodobenzylguanidine (MIBG) imaging was used, which is specific for neuroblastoma, to identify the residual tumor, followed by computed tomography scanning in the radiation treatment position. The FIGURA software fused the images obtained by the 2 modalities and transferred the result to a 3-dimensional radiation treatment planning system. Radiation was delivered at a total dose of 25.2 Gy according to the FIGURA. Results: Five patients achieved complete remission and 2 partial remission; 3 were stabilized. One child with a highly rapid progressive course died of the disease. Conclusion: FIGURA is a new, feasible technique for defining target volumes. By using standard hospital equipment, it is possible to treat residual disease identified by sensitive metaiodobenzylguanidine imaging and localized with the anatomic computed tomography scan. Treating a more accurate target volume spares normal tissue and organs and minimizes side effects.
Primary Payer Status Is Associated With Mortality and Resource Utilization for Coronary Artery Bypass Grafting
Authors: Damien J. LaPar, George J. Stukenborg, Richard A. Guyer, Matthew L. Stone, Castigliano M. Bhamidipati, Christine L. Lau, Irving L. Kron, Gorav Ailawadi
Journal: Circulation (2012)

Background— Medicaid and uninsured populations are a significant focus of current healthcare reform. We hypothesized that outcomes after coronary artery bypass grafting (CABG) in the United States is dependent on primary payer status. Methods and Results— From 2003 to 2007, 1 250 619 isolated CABG operations were evaluated using the Nationwide Inpatient Sample (NIS) database. Patients were stratified by primary payer status: Medicare, Medicaid, uninsured, and private insurance. Hierarchical multiple regression models were applied to assess the effect of primary payer status on postoperative outcomes. Unadjusted mortality for Medicare (3.3%), Medicaid (2.4%), and uninsured (1.9%) patients were higher compared with private insurance patients (1.1%, P &lt;0.001). Unadjusted length of stay was longest for Medicaid patients (10.9±0.04 days) and shortest for private insurance patients (8.0±0.01 days, P &lt;0.001). Medicaid patients accrued the highest unadjusted total costs ($113 380±386, P &lt;0.001). Importantly, after controlling for patient risk factors, income, hospital features, and operative volume, Medicaid (odds ratio, 1.82; P &lt;0.001) and uninsured (odds ratio, 1.62; P &lt;0.001) payer status independently conferred the highest adjusted odds of in-hospital mortality. In addition, Medicaid payer status was associated with the longest adjusted length of stay and highest adjusted total costs ( P &lt;0.001). Conclusions— Medicaid and uninsured payer status confers increased risk adjusted in-hospital mortality for patients undergoing coronary artery bypass grafting operations. Medicaid was further associated with the greatest adjusted length of stay and total costs despite risk factors. Possible explanations include delays in access to care or disparate differences in health maintenance.
The T cell response of HLA-DR transgenic mice to human myelin basic protein and other antigens in the presence and absence of human CD4.
Authors: D M Altmann, D C Douek, A J Frater, C M Hetherington, H Inoko, J I Elliott
Journal: The Journal of Experimental Medicine (1995)

Analysis of HLA class II transgenic mice has progressed in recent years from analysis of single chain HLA class II transgenes with expression of mixed mouse/human heterodimers to double transgenic mice expressing normal human heterodimers. Previous studies have used either HLA transgenic mice in which there is a species-matched interaction with CD4 or mice which lack this interaction. Since both systems are reported to generate HLA-restricted responses, the matter of the requirement for species-matched CD4 remains unclear. We have generated triple transgenic mice expressing three human transgenes, DRA, DRB, and CD4, and compared HLA-restricted responses to peptide between human-CD4+ (Hu-CD4+) and Hu-CD4- littermates. We saw no difference between Hu-CD4+ and Hu-CD4- groups, supporting the notion that for some responses at least the requirement for species-matched CD4 may not be absolute. Evidence for positive selection of mouse T cell receptors in HLA-DR transgenic mice came both from the acquisition of new, HLA-restricted responses to various peptides and from an increased frequency of T cells using the TCR V beta 4 gene segment. An important goal with respect to the analysis of function in HLA transgenic mice is the clarification of mechanisms which underpin the recognition of self-antigens in human autoimmune disease. As a first step towards 'humanized' disease models in HLA transgenic mice, we analyzed the responses of HLA-DR transgenic mice to the human MPB 139-154 peptide which has been implicated as an epitope recognized by T cells of multiple sclerosis patients. We obtained T cell responses to this epitope in transgenic mice but not in nontransgenic controls. This study suggests that HLA transgenic mice will be valuable in the analysis of HLA-restricted T cell epitopes implicated in human disease and possibly in the design of new disease models.