tbuckley/cabot-search huggingface dataset:
Hyperoxygenation Effect on Cognitive Functioning in the Aged
Authors: Eleanor A. Jacobs, Peter M. Winter, Harry J. Alvis, S. Mouchly Small
Journal: New England Journal of Medicine (1969)

Thirteen elderly male patients with measured cognitive deficits were treated with 30 intermittent exposures to 100 per cent oxygen at 2.5 atmospheres absolute. Five controls, each exposed at the same time and manner as a paired experimental patient, breathed a low oxygen mixture that maintained essentially normal alveolar oxygen tension despite increased ambient pressure. Arterial samples for blood gas determinations were obtained from each patient during one of the early hyperbaric exposures. Analysis showed the expected large intra-exposure increase in arterial oxygen tension among the experimental subjects. Negligible changes in arterial oxygen tension were found among control patients. Post-treatment performance on psychological tests of cognitive functioning showed highly significant gains over pretreatment levels in experimental subjects, suggesting an improved performance that persisted beyond the temporary increase in arterial oxygen tension levels. Control patients showed no improvement in post-treatment cognitive functioning.
Enhanced Atrioventricular Conduction during Atrial Flutter after Intravenous Adenosine
Authors: Michael A. Brodsky, Byron J. Allen, James A. Grimes, Claudia Gold
Journal: New England Journal of Medicine (1994)

To the Editor: Adenosine is the treatment of choice for tachycardia with narrow QRS complexes involving the atrioventricular node as part of its reentrant circuit1. It has also been recommended as a diagnostic aid in determining the mechanism of other tachyarrhythmias, but there has been no thorough analysis of its risks and benefits for this use. We report an adverse event associated with adenosine administered for diagnostic purposes to a patient with atrial flutter. A 53-year-old man came for medical evaluation because of palpitations. An electrophysiologic study previously revealed normal atrioventricular-node function (second-degree atrioventricular nodal Wenckebach block occurred at . . .
Abstract P4-08-09: Targeting Thyroid Receptor b in Estrogen Receptor Negative Breast Cancer
Authors: G Gu, K Covington, Y Rechoum, B O'Malley, D Mangelsdorf, J Minna, P Webb, S Fuqua
Journal: Cancer Research (2012)

Abstract Background: The treatment of estrogen receptor (ER)-negative breast cancer (BC) is a major clinical problem due to the lack of useful therapeutic targets. Nuclear receptors (NRs) are potential targets in these patients because they regulate global transcriptional events and many already have agonists/antagonists available. Material and Methods: We used microarray analysis of 227 ER-negative tumors to identify NR targets, and performed hierarchical clustering using 41 NRs. Expressed receptors were scored using prediction analysis of microarrays (PAM) across clustered groups. Cell lines were matched to subtypes using previously described data (Neve et al. 2006). Candidate gene expression levels were confirmed by qRT-PCR using TaqMan probes. pGIPZ lentiviral vectors encoding shRNA were used to knockdownselected candidates. MTT and soft agar assays were used to measure chemosensitivity and growth following treatment with Docetaxel (Doc), Doxorubicin (Dox), or Cisplatin (Cis). Statistical analysis was performed using Red-R. Results: The 41 NRs clustered tumors into 5 groups. For each group we selected genes representing the highest ranked discriminators, and examined their effects in cell lines matching each groups' gene signature. Thyroid hormone receptor b (THRβ) was selected from group V. The expression levels of this receptor were confirmed by qRT-PCR and Western blot analysis. Knockdown of THRβ in ER-negative HCC2185 cells rendered cells more resistant to all chemotherapeutics by using MTT assay. Similar results were confirmed in ER-negative MDA-MB-453 and HCC202 cells. Knockdown of THRβ enhanced colony forming potential in anchorage-independent soft agar assays in MDA-MB-453 and HCC202 cells. Statistical analysis using clinical data from Sabatier et al. (BCRT 2011) showed that patients with low THRb have a worse clinical outcome. In order to translate these findings into the clinic, we treated cells with a specific THRβ agonists, GC-1 and KB-141. GC-1 inhibited cell growth in growth assays, and synergistic effects were observed when cells were treated with GC-1 and Docetaxel in combination. Re-expression of ERα protein was observed in ER-nagative cells lines after treatment with GC-1 and KB141, suggesting that modulation of THRβ may also extend hormonal therapy to this hormonally insensitive group of patients. Conclusion: Clinical targeting of NRs in ER-negative BCs is a novel strategy since receptors can be specifically targeted with ligands. Our data suggest that chemotherapy response in ER-negative patients overexpressing THRβ could be enhanced with a THRβ agonist. Similarly, functional re-activation of ERα by activating THRβ might extend hormonal therapies to these patients as well. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-08-09.
Generation of Metastatic Variants in Populations of Mutator and Aniplificator Mutants
Authors: J E Damen, A Y Tagger, A H Greenberg, J A Wright
Journal: JNCI Journal of the National Cancer Institute (1989)

Genetic instability has been hypothesized by P. C. Nowell and other investigators to be an important aspect of tumor progression that leads to the generation of metastatic variants. In this study we examined the rate of generation of metastatic variants in mutant cell lines having increased rates of spontaneous mutation and gene amplification. Parallel clonal populations of the spontaneous mutation rate mutant thy-49 and the gene amplification mutants YMP1 and YMP7 and their respective wild types were generated and grown to a critical population size. The number of metastatic variants in each clonal population was then determined following iv injection into nude mice. Lung tumors were scored 3-4 weeks after injection of cells, and the mean number per clonal population was determined. Analysis of the means with the Luria-Delbruck fluctuation test showed no significant differences in the rate of generation of metastatic variants produced in the genetically unstable lines compared to their normal counterparts. This study suggests that increased spontaneous mutation and gene amplification rates in mammalian cells are not sufficient on their own to increase the rate of generation of metastatic variants.
TCTAP A-164 Safety and Efficacy of Manual Aspiration Thrombectomy Combined with Transradial Coronary Intervention in the Patients with ST Segment Elevation Myocardial Infarction
Authors: Yukio Mizuguchi, Akihiko Takahashi, Sho Hashimoto, Takeshi Yamada, Norimasa Taniguchi, Shunsuke Nakajima, Tetsuya Hata
Journal: Journal of the American College of Cardiology (2016)
S138 Blood outgrowth endothelial cells isolated from patients with pulmonary arterial hypertension possess less caveolae and reduced cavin-2 expression
Authors: BJ Dunmore, G Howard, A Crosby, BJ Nichols, NW Morrell
Journal: Thorax (2013)

<h3></h3> Pulmonary arterial hypertension (PAH) is a progressive disease characterised by a marked elevation in pulmonary arterial pressure due to increased muscularisation and obliteration of small pulmonary arteries. The majority of heritable PAH cases are due to mutations in members of the transforming growth factor-β (TGFβ) receptor signalling pathway. Although predominantly associated with mutations in the bone morphogenetic protein type II receptor (BMPR-II) genetic variations causing disease have recently been identified in caveolin-1, the major component of caveolae generation. Caveolae are flask shaped invaginations in the plasma membrane that play an important role in many endothelial cell functions including vesicular trafficking and signalling. Correct caveolae formation in the lung has recently been shown to require serum deprivation protein response (SDPR), also known as cavin-2. Using blood outgrowth endothelial cells (BOECs) isolated from patients with PAH we sought to determine the expression of cavin-2 and caveolae formation. <h3>Methods</h3> Blood outgrowth endothelial cells (BOECs) were isolated from control subjects and individuals with PAH, including BMPR-II mutation and idiopathic patients. Following transmission electron microscopy (TEM) the number of caveolae and depth of invaginations were assessed in ten cells from each cell line. Protein expression of caveolin-1, cavin-1 and cavin-2 were assessed by western blotting. Caveolin-1 and cavin-2 knockout mice were assessed for right ventricular systolic pressure (RVSP) and right ventricular hypertrophy. <h3>Results</h3> Reduced caveolae and depth of invaginations were observed in idiopathic PAH patients and individuals with a BMPR-II mutation when compared to controls. Interestingly, an individual with a BMPR-II mutation without disease had similar levels to controls. Furthermore, cavin-2 protein expression was decreased in cells from individuals with pulmonary hypertension, but other caveolae components appeared unaffected. In the absence of a disease stimulus caveolin-1 and cavin-2 knockout mice did not develop pulmonary hypertension although slightly elevated RVSP was observed. <h3>Conclusions</h3> Our preliminary data suggests that caveolae formation is dysregulated in cells from individuals with pulmonary hypertension. In addition, reduced levels of cavin-2 could play a significant role in the decreased number of caveolae. Cavin-2 and caveolae generation could therefore be novel therapeutic targets for pulmonary hypertension.
An Epidemic of Pharyngitis Due to a Nonhemolytic Group A Streptococcus at Lowry Air Force Base
Authors: Leroy James, Robert B. McFarland
Journal: New England Journal of Medicine (1971)

A nonhemolytic Group A streptococcus caused a brief epidemic of pharyngitis at Lowry Air Force Base in May, 1968. Six cases of rheumatic fever followed the epidemic, and three of these patients had antibodies to the Type 18 epidemic strain. This organism can be recognized by its mucoid colonial form together with the absence of beta hemolysis.
Abstract 2153: Active PAK6 induces aneuploidy in breast cancer cells
Authors: Michael L. Lu
Journal: Cancer Research (2012)

Abstract The natural history of breast cancer remains largely undefined. More than 50% of the clinical specimen exhibits aneuploidy. Among these aneuploid cancers, 50% has chromosome copy number near tetraploid. The high incidence of aneupoidy in advanced breast cancer is thought to be a byproduct of chromosome mis-segregation resulting from mutations of checkpoint-regulating tumor suppressor genes associated with disease progression. However, new large-scale sequencing projects reveal that most tumors contain approximately 14-20 different mutant genes, suggesting that genomes and karyotypes of cancer cells are equally heterogeneous. This notion revives the old concept that aneuploidy resulting from chromosome mis-segregation or other similar mechanisms may play an active role leading to transformation and disease progression. A novel p21-activated kinase 6 (PAK6) was recently identified to be an androgen receptor (AR) and estrogen receptor (ER) interacting protein. An estrogen-stimulated PAK6 activation was observed in breast cancer BT474 cells. This activation is mediated by estrogen-stimulated activation of PKA. At the cellular level, active PAK6 promotes breast cancer MCF7 cell metastatic phenotypes including increased cell motility, matrigel invasion and soft agar growth. Further characterization of breast cancer MCF7 cells expressing PAK6 constitutive active mutant revealed an accumulation of cells with higher ploidy as compared to that of parental MCF7. Using a proteomic approach to determine the PAK6 downstream target, we identified that Cdt1, a DNA pre-replicative complex (pre-RC) subunit, is overexpressed in response to PAK6 activation. In eukaryotes, the expression and stability of Cdt1 are strictly regulated to ensure only one round of DNA replication in each cell cycle. Deregulated overexpression of Cdt1 has previously been demonstrated to induce aneuploidy and malignant transformation due to re-initiation of DNA replication within the same S-phase. The identification of Cdt1 overexpression in response to PAK6 activation provides a plausible mechanism for the observed accumulation of higher ploidy cells in MCF7 expressing active PAK6. These findings directly link the hormonal signals to the DNA replication process and maintenance of genomic integrity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2153. doi:1538-7445.AM2012-2153
ESTRATIFICACIÓN DEL RIESGO DE COLEDOCOLITIASIS. INFLUENCIA DE COLECISTITIS ASOCIADA. EXPERIENCIA DE UN CENTRO DE SEGUNDO NIVEL SIN COLANGIORRESONANCIA NI ECOENDOSCOPIA
Authors: A Huergo Fernández, F Fernández Cadenas, P Amor Martín, M Álvarez Posadilla, AI Milla Crespo, R Sánchez Fernández, F Pozo Fidalgo
Journal: Endoscopy (2013)

Introducción: El diagnóstico de coledocolitiasis se basa en pruebas de laboratorio e imagen, algunas no disponibles en todos los centros. Objetivo: Analizar la fiabilidad de estratificar el riesgo de coledocolitiasis basado en el algoritmo propuesto por la Sociedad Americana para Endoscopia Gastrointestinal respecto hallazgos en CPRE, valorando la influencia de colecistitis asociada. Material y Método: Se estudiaron retrospectivamente 106 CPREs realizadas en nuestro centro entre enero 2010 y junio 2013 por indicación de coledocolitiasis. Se estratificaron en tres grupos de riesgo: alto, medio y bajo. Los resultados fueron analizados respecto riesgo asignado, variables del algoritmo y colecistitis asociada. Resultados: Edad: 72,51 ± 15,89 años. Sexo: 60 mujeres (56,6%). 61 CPREs (57,5%) durante ingreso hospitalario. Bilirrubina: 3,6 ± 2,88; AST: 221,94 ± 233,56; ALT: 261,69 ± 231,17; FA: 252,04 ± 176,87 y GGT: 414,73 ± 402,09. Ecografía de abdomen: 104 casos (98,1%); 30 casos sin alteraciones (28,8%), 36 vía biliar dilatada (34,6%) y 38 coledocolitiasis (36,5%). Riesgo asignado: bajo: 1 caso (0,9%), interrmedio: 29 casos (27,4%) y alto: 76 casos (71,7%). Existían asociadas 24 colecistitis (22,6%). Canulación: 100 casos (94,3%), 12 tras precorte. 98 esfinterotomías (98%) y 2 esfinteroplastias. Coledocolitiasis confirmada en 57 casos (57%); 4 casos barro biliar (4%). Extracción completa contenido 91,6%. 89 casos sin complicaciones (84%); 9 hemorragias (8,5%), 5 diferidas, 3 perforaciones (2,8%) y 5 pancreatitis postCPRE (4,7%). No se confirmó asociación entre el riesgo asignado y la existencia de contenido en CPRE (p 0,150). Del resto de variables, solo la ecografía resultó predictiva de coledocolitiasis (p 0,00). Aunque la exclusión de los casos con colecistitis mejoró el resultado del riesgo asignado, éste no alcanzó significación estadística (p 0,076). Conclusiones: – La estratificación del riesgo de coledocolitiasis es una medida para toma de decisiones. – La precisión aumenta cuando la ecografía transabdominal apoya el diagnóstico. – La existencia de colecistitis asociada puede ser un factor de error en este algoritmo.
Abstract C37: Ensemble survival prediction for breast cancer using microarray data
Authors: Anupama Reddy, Shridar Ganesan, Gyan Bhanot
Journal: Cancer Research (2009)

Abstract We present an algorithm, “Ensemble Logical Analysis of Survival Data”, for predicting survival of cancer patients based on patterns identified on gene-expression microarray data. A pattern is defined as a combination of expression levels of multiple genes, associated with risk of mortality or metastasis of the tumor. We illustrate our method on several breast cancer microarray datasets, including 286 samples from a study of node negative untreated samples from Wang et al 2005, 347 primary invasive samples from Ivshina et al. 2006, and 255 early-stage samples who received Tamoxifen as adjuvant treatment from Loi et al. 2008. We use the recent molecular stratification of the breast cancers into eight robust subtypes: Luminals: (LA, LB1, LB2, LB3), Basal-like: (BA1, BA2) and Her2+: (Her2+I, Her2+NI) from Alexe et al. 2007 and identify patterns of genes which drive the disease within each of these molecular types. This is followed by an analysis of the genes seen most frequently in patterns to determine the pathways responsible for progression/metastasis/death for each subtype. At each event time point (event = death/recurrence/metastasis), we identify patterns that separate patients into high/low risk classes. Each pattern is then associated with a score defined as the integral of the Kaplan-Meier survival curve for the samples that satisfy the pattern. Pattern space is not disjoint and a sample can satisfy more than one pattern, even for a given time point. The average of the pattern scores for each patient across all time points defines a patient-specific survival score. All the above steps are computed using an ensemble method: two-thirds of the data is randomly selected, patterns are generated on this random subset, and patient scores are computed. This is repeated 100 times, and patient scores are aggregated over these 100 runs. We find that these aggregated scores correlate very well with actual survival in the Wang dataset (c-statistic: 86% for LA, 95% for LB1, 88% for LB3, 77% for Basals, and 80% for Her2+). High/low risk class assignment based on the median of the predicted survival score is highly significant (log-rank p-value: 0.01 for LA, 0.0004 for LB1, 0.00006 for LB3, 3.3×10−8 for Basals and 0.0003 for Her2+). The method that we propose is general and can be used for predicting survival for any cancer type. It can also be applied to RT-PCR data, single nucleotide polymorphisms, microRNA data and data on copy number variations. Finally, we show that our risk score is significantly superior to an Oncotype DXTM score inferred for the samples from the gene expression data. Citation Information: Cancer Res 2009;69(23 Suppl):C37.
FRI0238 The effect of rituximab on lipid levels in patients with rheumatoid arthritis
Authors: I. Kostoglou-Athanassiou, A. Tzanavari, D. Basdragianni, A. Papadaki, N. Dadiras, P. Athanassiou
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is known to be associated with cardiovascular comorbidity. In particular, patients with RA are known to be at increased for the development of atherosclerosis. Treatment with biological agents in RA may affect lipid levels. <h3>Objectives</h3> The aim was to study the effect of rituximab treatment on lipid levels in RA patients. <h3>Methods</h3> In a cohort of 20 patients with RA lipid levels were studied before, 6 and 12 months after treatment with the biological agent rituximab (2x1000 mg i.v. infusions 2 wks apart) at baseline, 6 and 12 months later. All patients fulfilled the 2010 ACR/EULAR criteria for RA. Total cholesterol, HDL, LDL cholesterol and triglyceride levels were measured at baseline, 6 and 12 months later. <h3>Results</h3> At baseline total cholesterol was 207.41±8.33 mg/dl (mean±SEM), 6 months and 12 months later increasing to 218.27±7.02 and 226.12±8.71 mg/dl, respectively (p&lt;0.001, Student's t test). At baseline HDL cholesterol was 59.17±3.31 mg/dl, 6 and 12 months later increasing to 66.05±3.49 and 58.81±3.04 mg/dl, respectively (p&lt;0.001). At baseline LDL cholesterol was 122.89±8.96 mg/dl, 6 and 12 months later increasing to 124.58±5.61 and 141.56±7.95 mg/dl, respectively (p&lt;0.001). At baseline triglyceride levels were 138.50±13.91 mg/dl, 6 and 12 months later decreasing to 122.55±10.52 and 118.65±9.91 mg/dl, respectively (p&lt;0.001). <h3>Conclusions</h3> Treatment with the biological agent rituximab in RA resulted in an increase in total cholesterol, paralleled by an increase in HDL cholesterol, LDL cholesterol, while triglyceride levels decreased. The adverse effect on total cholesterol levels may be counteracted by the parallel increase in HDL thus conferring a beneficial effect on the patients as far as cardiovascular risk is concerned. These findings have therapeutic implications as the effect of rituximab on lipid levels may render systematic treatment with statins necessary in rheumatoid arthritis. <b>Disclosure of Interest</b>: None Declared
Abstract 4511: The effect of obesity-related adipokines at diagnosis on breast cancer survival
Authors: Sang-Ah Lee, Dong-Young Noh, Ji-Yeob Choi, Sei-Hyun Ahn, Deahee Kang
Journal: Cancer Research (2012)

Abstract Background: Although a number of experimental studies have suggested the effect of obesity-related adipokines in breast cancer progression, limited numbers of epidemiological studies have examined the relationship between the adipokines and breast cancer survival. Patients and methods: Preoperative serum levels of obesity-related adipokines including leptin, adiponectine and hepatocyte growth factor (HGF) were measured in 370 breast cancer patients recruited between 2004 and 2007. We examined the association between those adipokines and disease-free survival (DFS) using Cox proportional hazard regression model. Results: There was no difference in age distribution, menopausal status, BMI, PR status, tumor size, and lymph node status between survivor and recurrence or death subjects. On the other hand, the TNM stage, ER status and histological grade were observed the association with breast cancer survival. Elevated adiponectin were associated with reduced DFS of breast cancer (P for trend = 0.047) with adjustment for age, ER/PR status, histological grade, nuclear grade and TNM stage among patient with less than 4 year survival time. There was no association of leptin and HGF with the breast cancer survival. Conclusions: Our study suggests that the elevated levels of adiponectine at diagnosis are associated with breast cancer survival, but the leptin and HGF level in blood not associated. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4511. doi:1538-7445.AM2012-4511
Single-step endoscopic ultrasonography-guided drainage of peripancreatic fluid collections with a single self-expandable metal stent and standard linear echoendoscope
Authors: M. Berzosa, S. Maheshwari, K. Patel, Y. Shaib
Journal: Endoscopy (2012)

Endoscopic ultrasonography (EUS)-guided drainage of peripancreatic fluid collections (PFCs) is a well described alternative to surgery or percutaneous drainage. However, it is limited by the requirement for a large working channel that allows multiple plastic stent placement, which is only commercially available on therapeutic linear echoendoscopes. Herein, we describe the drainage of PFCs with a single self-expandable metal stent (SEMS) using a single-step technique and standard linear echoendoscope. Seven cases were identified during a retrospective chart review, and included all patients who had undergone EUS-guided drainage of PFCs during a 6-month period. The mean age was 46 years (range 25 - 70 years) and all patients were symptomatic. The mean diameter of PFCs was 8 cm (range 4.1 - 12.5 cm). Previous percutaneous drainage had failed in three patients. A total of 10 PFCs were drained. Three patients had two cysts drained by the same stent and one patient had two separate procedures to drain two distinct cysts. The SEMS was in place for a mean of 13 weeks (range 4 - 34 weeks). Successful placement of SEMS was achieved in all seven cases. Patients were followed for a mean of 18 weeks (range 7 - 35 weeks), and symptom improvement was achieved in all cases. Complete resolution of PFC was achieved in 9 /10 cysts. No complications were encountered. Single-step EUS-guided drainage of PFCs using a single 10-mm SEMS and a standard linear echoendoscope appears to be a feasible endoscopic technique with excellent technical and clinical success rates.