tbuckley/cabot-search huggingface dataset:
Sensation of Inspiratory Difficulty during Inspiratory Threshold and Hyperinflationary Loadings
Authors: SHENG YAN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Dynamic hyperinflation loads the inspiratory muscles by increasing end-expiratory lung volume (EELV) and imposing intrinsic positive end-expiratory pressure (PEEPi), the latter behaving as an inspiratory threshold load (ITL). The aim of the current study was to examine how induced-inspiratory muscle fatigue affects the independent effects of the imposed ITL and increasing operating lung volume on the perceived inspiratory difficulty. Dynamic hyperinflation in healthy subjects was induced by positive end-expiratory pressure (PEEP). Increasing operating lung volume alone (without PEEPi) and increasing ITL alone (without change in EELV) were induced by continuous positive airway pressure (CPAP) and external ITL, respectively. Inspiratory difficulty was quantified by the modified Borg scale and analyzed by step forward multiple regression, using the imposed ITL, EELV, and end-inspiratory lung volume (EILV) as independent variables. When fresh, the first entered variable was the imposed ITL (r(2), 0.38). Adding EILV into the model increased r(2) to 0.67. After fatigue, the first entered variable became EILV (r(2), 0.50) and the second selected variable was the imposed ITL, which increased r(2) to 0.66. EELV was insignificant under both conditions. The coefficient of EILV increased significantly from 0.039 +/- 0.005 to 0.092 +/- 0.012 (% inspiratory capacity(-)(1)) after fatigue run (p < 0.001), whereas that of the imposed ITL did not change. It is concluded that in the experimental conditions studied, inspiratory muscle fatigue increased the importance of lung volume over that of inspiratory threshold load in determining the perceived inspiratory difficulty.
Abstract LB-517: EIF5A2, A downstream target of PI3K/Akt pathway, Is an adverse prognostic marker of melanoma patient survival by increasing cell invasion
Authors: Shahram Khosravi, Ronald P.C. Wong, Magdalena Martinka, Gang Li
Journal: Cancer Research (2012)

Abstract Human cutaneous melanoma is a life-threatening skin cancer due to its invasive nature and high metastatic potential, leading to poor prognosis for melanoma patients. However, the mechanisms for melanoma invasion and metastasis are poorly understood. Human eukaryotic translation initiation factor 5A2 (EIF5A2) has been shown to be associated with tumor progression in multiple types of cancers. We examined EIF5A2 expression in 459 melanocytic lesions at different stages using tissue microarray and immunohistochemistry and analyzed the correlations between EIF5A2 expression and clinicopathologic parameters and patient survival. We found that positive EIF5A2 staining was significantly increased in primary melanomas compared to dysplastic nevi (P=0.002), and further increased in metastatic melanomas (P=0.036). EIF5A2 expression was correlated with melanoma thickness (P=0.0004) and was inversely correlated with overall and disease-specific 5-year survival of primary (P=0.008 and 0.007, respectively), especially low-risk (≤2.0mm) melanoma patients (P=0.026 and 0.044, respectively). We also examined the correlation between EIF5A2 and p-Akt protein expression and their role in regulating melanoma cell invasion. Combining the TMA data sets for EIF5A2 and p-Akt, we found that positive EIF5A2 staining directly correlated with strong p-Akt expression (P=0.026). Additionally, overexpression of PTEN or inhibition of p-Akt or ILK significantly reduced EIF5A2 expression. EIF5A2 overexpression also increased melanoma cell invasion and MMP-2 activity. We for the first time showed that the expression of EIF5A2, a downstream target of PI3K/Akt pathway, is significantly increased during melanoma invasion and is inversely correlated with patient survival, suggesting that EIF5A2 may be used as a potential therapeutic target for melanoma. 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 LB-517. doi:1538-7445.AM2012-LB-517
Features of large granular lymphocytes (LGL) expansion following allogeneic stem cell transplantation: a long-term analysis
Authors: M Mohty, C Faucher, N Vey, C Chabannon, D Sainty, C Arnoulet, B Gaugler, JA Gastaut, D Maraninchi, D Olive, D Blaise
Journal: Leukemia (2002)
Abstract 5063: Signatures of Ral GTPase status define key clinicopathologic characteristics and outcomes in cancer
Authors: Steven C. Smith, Alexander S. Baras, Hong Wang, Charles R. Owens, Dan Theodorescu
Journal: Cancer Research (2010)

Abstract Ral GTPases, which include RalA and RalB, mediate essential phenotypes in model cancer systems; however, demonstration of the clinical relevance of these molecules has been lacking. To address this concern, we develop two types of gene expression signatures as surrogates for Ral GTPase status in tumors and characterize their nosologic and prognostic performance across several epithelial malignancies. Given Ral's well characterized role in regulating a variety of transcriptional pathways including AP1, NFkB, STAT3B, forkhead family members, and RREB1, the first type of signature is related to transcription downstream of RalA and RalB and was derived empirically from expression profiling of cells depleted of these molecules. This signature was then applied to human tumor gene expression data by using a nearest neighbor algorithm for classification. Consistent with prior findings of a role for these molecules in model surrogates of cancer progression(1,2), presence of the Ral transcriptional signature characterized the muscle invasive status of human bladder cancer (P&amp;lt;0.001), including prediction of subsequent development of invasion in non-invasive tumors (P&amp;lt;0.01). In prostate cancer, the signature characterized androgen independent status, and estrogen receptor status in human breast cancer, both datasets P&amp;lt;0.05. Supportive of a recent report of tumor suppressor function of Ral in a model of squamous cell cancer (3), the signature was inversely associated with stage in this tumor type. Secondly, we have assayed constitutively-active RalA and RalB mutants, finding that either induces accelerated experimental metastasis of UMUC3 bladder cancer cells in mice (logrank P=0.01), similar to results for other tumor types (4). This made us question whether signatures of metastasis from tumor profiling could be associated with differential Ral activation. We assayed the activation of RalA and RalB across 40 cell lines, then mapped individual tumor expression of metastatic genes to these cell lines in silico. Using this methodology to compare tumors to cell lines of known Ral activation, we found association of higher Ral activation with nodal metastasis in bladder cancer and with visceral metastasis in breast cancer, both P&amp;lt;0.05. Taken together, these findings begin to make the as yet missing clinical case for the Ral pathway in human tumors and call for aggressive investigation of therapies to interrupt this pathway. (1) Oxford, Cancer Res, 2005 (2) Lim, Curr Biol, 2006 (3) Sowalsky, Oncogene, 2009 (4) Yin, Mol Cell Biol, 2007 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5063.
Informative morphogenetic variants in patients with schizophrenia and alcohol-dependent patients: beyond the Waldrop Scale
Authors: M Trixler, T Tényi, G Csábi, G Szabó, K Méhes
Journal: American Journal of Psychiatry (1997)

The authors evaluated the presence or absence of informative morphogenetic variants in patients with schizophrenia compared with alcohol-dependent patients.Taking into consideration the criticisms of the Waldrop Scale, which was widely used until recently to define the presence of informative morphogenetic variants, the authors evaluated the presence or absence of 56 informative morphogenetic variants in 50 consecutively admitted patients with schizophrenia and 50 consecutively admitted alcohol-dependent patients. They made a distinction between minor malformations (those developing during organogenesis) and phenogenetic variants (those developing after organogenesis). A kappa index above 75% was considered reliable.Thirty-four of the 56 informative morphogenetic variants met the authors' reliability criterion. Patients with schizophrenia had significantly higher rates of three minor malformations (furrowed tongue, multiple buccal frenula, and hemangioma) and two phenogenetic variants (protruding auricle and large tongue).The results suggest that using finer distinction in the evaluation of informative morphogenetic variants in schizophrenia may open new perspectives in the research of the neurodevelopmental background of schizophrenia.
FRI0082 Development of impairment, disability, radiological damage, comorbidity and mortality over 20 years in rheumatoid arthritis patients
Authors: K. Eberhardt, M. Crnkic Kapetanovic, E. Lindqvist, J.-Å. Nilsson, T. Saxne, P.G. Pierre Geborek
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To study the development of impairment, disability, radiological damage, comorbidity and mortality over 20 years in a cohort followed prospectively from diagnosis. <h3>Methods</h3> 183 RA patients diagnosed between 1985 and 1989 were prospectively monitored according to a standardised protocol over 20 years. Treatments followed clinical practice. There were 115 (63%) women, mean (SD) age was 51 (12) years and symptom duration before inclusion was 11 (7) months. Impairment was measured by signals of functional impairment (SOFI), a 3-parts performance based index measuring hand, arm and leg function, disability by health assessment questionnaire (HAQ), joint damage by Larsen score of radiographs of hands and feet, comorbidity by Charlson Comorbidity Index (17 diagnoses each weighted by mortality risk). Comorbidity was ascertained by scrutinizing medical records which are linked to national census registers to ascertain vital status. Due to mortality, both per protocol and last observation carried forward (LOCF) techniques were used. LOCF was used from baseline for comorbity, and from 10 years for the other variables. Data are given as means and 95% CI. <h3>Results</h3> Impairment had a linear progression over the whole study period while disability progressed year 2-10 and then stabilised. Disease activity decreased year 1 and 2 and remained stable thereafter. Radiological damage progressed more rapidly year 1-5 and then gradually showed diminished progression rate. LOCF analyses did not change these analyses to any significant degree. Comorbidity increased the first 10 years but then stabilised in the per protocol analysis, but showed a steady increase over 20 years when using LOCF technique. <h3>Conclusions</h3> Impairment measured by SOFI is much more progressive in RA over 20 years in this cohort diagnosed in the late 1980ies, compared to disability measured by HAQ where progression levelled off after 10 years. Radiographic damage increased most rapidly during the first 5 years. Disease activity was high in the beginning but stabilised after 2 years. Comorbidity measured by Charlson index showed a linear progression over time when using LOCF but not when using per protocol analyses. None of the other variables seemed sensitive to mortality as LOCF did not markedly change the results. <h3>Disclosure of Interest</h3> None Declared
OBSTRUCTIVE SLEEP APNEA IS ASSOCIATED WITH VISIT-TO-VISIT VARIABILITY IN LOW DENSITY LIPOPROTEIN-CHOLESTEROL IN PATIENTS WITH CORONARY ARTERY DISEASE
Authors: Gavin Ng, Elaine Boey, Chris Frampton, Mark Richards, Tiong Cheng Yeo, Chi-Hang Lee
Journal: Journal of the American College of Cardiology (2016)
Case 26-2005
Authors: William D. Binder, Michael A. Fifer, Mary Etta King, James R. Stone
Journal: New England Journal of Medicine (2005)

A man, approximately 40 years of age, fell while jogging, losing consciousness and striking his head. Emergency-medical-services technicians found hypertension, tachycardia, and normal blood sugar and noted spontaneous arm movements. In the emergency department, a physical examination showed only a scalp laceration; computed tomography of the head showed no intracranial bleeding.
Rules on protecting people in social and behavioral studies need to be revised, says US panel
Authors: M. McCarthy
Journal: BMJ (2014)

Current rules governing research involving human participants in the United States should be revised to take into account the differences between risks posed by biomedical research and those posed by most social and behavioral research studies, says an expert panel convened by the National Research Council.

The council commissioned the panel to advise the Department of Health and Human Services, which is currently updating the Federal Policy for the Protection of Human Subjects, the regulation that governs human research in the US and that is often referred to as the “Common Rule.”

The revisions suggested by the panel would cover research typically conducted in such fields as anthropology, cognitive sciences, political science, psychology, social work, and health services research.

The study was supported by the Bill and Melinda Gates Foundation, the Alfred P Sloan Foundation, and the National Academy of Education. Susan Fiske, professor of psychology and public affairs at Princeton University, chaired the panel.

Unlike biomedical research, which can often pose a risk of physical harm …
Abstract 166: Elevated levels of serum fatty acid synthase (FAS) in patients with gastric carcinoma.
Authors: Tomoaki Ito, Koichi Sato, Hiroshi Maekawa, Takashi Tada, Mutsumi Sakurada, Hajime Orita, Kazunori Shimada, Ryo Wada, Masaaki Abe, Okio Hino, Yoshiaki Kajiyama
Journal: Cancer Research (2013)

Abstract Aim: Gastric cancer is the second leading cause of cancer mortality in the world. In East Asia especially, in countries such as China, Japan, and Korea, more than one million new cases are diagnosed each year. The need remains for biomarkers to detect early stage gastric cancer. Fatty acid synthase (FAS) is highly expressed in many human cancers, but the potential utility of measuring FAS for detection of gastric cancer has not been previously investigated. The aim of this study was to provide a preliminary assessment of serum FAS as a marker of gastric carcinoma. Materials and methods: Our study included 47 patients with gastric cancer (37 men and 10 women, aged 33-89 years) and 150 healthy subjects (113 men and 37 women, aged 33-83 years). Serum FAS levels were measured by ELISA and compared across the two groups of patients. Blood samples were collected from each cancer patient before treatment, and additionally, post-therapeutic samples were obtained from eleven of the patients with gastric cancer. Measurement data were analyzed using the Mann-Whitney test. P&amp;lt;0.05 was considered statistically significant. The receiver operator characteristic (ROC) curve was used to determine sensitivity and specificity values. Results: We found significantly higher levels of serum FAS in gastric cancer patients (95% confidence interval, 95% CI=30.37-52.46) than in healthy controls (95% CI=1.331-2.131), with elevated levels even in patients with early stage tumors. Using 5.5 ng/ml as the cut-off value, the sum of sensitivity (95.74%) and specificity (91.33%) was the highest, and the positive predictive values and negative predictive values were 77.59% and 98.56%, respectively (Area Under the Curve=0.9845, Standard Error=0.0084, 95% CI=0.9681-1.001). The pre-therapeutic FAS levels were greater than 5.5 ng/ml, and in 8 of 11 patients, the post- therapeutic serum FAS levels decreased to less than 5.5 ng/ml. Conclusion: Our results suggest that measuring serum FAS levels has strong potential to provide a biomarker for detection of gastric cancer with high sensitivity and high specificity. Citation Format: Tomoaki Ito, Koichi Sato, Hiroshi Maekawa, Takashi Tada, Mutsumi Sakurada, Hajime Orita, Kazunori Shimada, Ryo Wada, Masaaki Abe, Okio Hino, Yoshiaki Kajiyama. Elevated levels of serum fatty acid synthase (FAS) in patients with gastric carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 166. doi:10.1158/1538-7445.AM2013-166
Abnormal Proteins in the Cerebrospinal Fluid of Patients with Creutzfeldt–Jakob Disease
Authors: Michael G. Harrington, Carl R. Merril, David M. Asher, D. Carleton Gajdusek
Journal: New England Journal of Medicine (1986)

We studied more than 300 cerebrospinal fluid proteins from 21 patients with Creutzfeldt-Jakob disease. We also examined cerebrospinal fluid from 100 normal controls and more than 400 patients with various neurologic disorders other than Creutzfeldt-Jakob disease. Four abnormal proteins that were identified in the patients with Creutzfeldt-Jakob disease were absent in the normal persons. Two of these proteins (Mr [relative molecular mass], 40,000; pl [isoelectric point], 5.7 and Mr 40,000; pl 5.9) were also present in some patients with multiple sclerosis, herpes simplex encephalitis, schizophrenia, Parkinson's disease, or Guillain-Barré or Behçet's syndrome. Two proteins (Mr 26,000; pl 5.2 and Mr 29,000; pl 5.1) were present in all patients with Creutzfeldt-Jakob disease and in 5 of 10 patients with herpes simplex encephalitis, but in none of the other control groups. A subsequent blinded study of these cerebrospinal fluid proteins from patients with Creutzfeldt-Jakob disease, Alzheimer's disease, Huntington's disease, multi-infarct dementia, parkinsonism dementia of Guam, or the specific dementia of the acquired immunodeficiency syndrome resulted in the ability to distinguish all cases of Creutzfeldt-Jakob disease from the other types of dementia. Although the identity and origin of the abnormal spinal fluid proteins are not yet known, these preliminary results suggest that their presence may help in the diagnosis of Creutzfeldt-Jakob disease.
PERCUTANEOUS BALLOON MITRAL VALVULOPLASTY IN RHEUMATIC MITRAL STENOSIS WITH SUPRASYSTEMIC PULMONARY ARTERIAL HYPERTENSION
Authors: Rahul Bhoite, Girija R. Bhoite, Dayanand N. Bagdure, Santosh N. Ghalme, Sunil V. Sathe
Journal: Journal of the American College of Cardiology (2016)
Abstract 83: Differential regulation of PTEN in ERα positive and negative ovarian cancer cells during cisplatin induced apoptosis
Authors: Mohan Singh, Parvesh Chaudhry, Eric Asselin
Journal: Cancer Research (2012)

Abstract The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor is a central negative regulator of the PI3K/AKT signaling cascade and suppresses cell survival as well as cell proliferation. PTEN is found to be either inactivated or mutated in various human malignancies. In the present study we have investigated the regulation of PTEN levels during cisplatin induced apoptosis in estrogen receptor alpha (ERα) positive (OVCAR-3 and SKOV-3) and negative (A2780 and A270-CP) ovarian cancer cell lines. Cells were treated with 10μM cisplatin for 24hrs. Transcript and protein levels were analysed by reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting, respectively. The results showed that PTEN levels were significantly decreased in ERα-negative A2780 cells at both the transcript and protein levels; however, there was no change in PTEN levels in ERα-positive cells and cisplatin resistant cells (A2780-CP) in the presence of cisplatin. The decrease in PTEN was accompanied with an increase in the levels of Akt phosphorylation in A2780 cells. Cisplatin treatment induced the activation of caspase-3, -7, -8, -9 and cleavage of Parp in all the cell lines tested in the study except A2780-CP cells. In A2780 cells, restoration of PTEN levels was achieved upon pre-treatment with Z-VAD-fmk (caspase inhibitor) and not with MG132 (proteasome inhibitor), suggesting that, in addition to the regulation of PTEN at transcript level, caspases are also involved in the decrease of PTEN protein levels in A2780. The decrease in pro-apoptotic PTEN levels both at the transcriptional and post-translational levels and increase in survival factor pAkt in ERα-negative ovarian cancer cells suggest that cisplatin treatment could further exacerbates drug resistance in ERα-negative ovarian cancer cells. 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 83. doi:1538-7445.AM2012-83
The effect of macrophage and angiogenesis inhibition on the drug release and absorption from an intramuscular sustained-release paliperidone palmitate suspension
Authors: Nicolas Darville, Marjolein van Heerden, Dirk Mariën, Marc De Meulder, Stefaan Rossenu, An Vermeulen, An Vynckier, Sandra De Jonghe, Patrick Sterkens, Pieter Annaert, Guy Van den Mooter
Journal: Journal of Controlled Release (2016)
Abstract 4011: Evidence supporting a role of c-Myb in pancreatic cancer
Authors: Seema Singh, Sanjeev K. Srivastava, Arun Bhardwaj, Laurie B. Owen, William E. Grizzle, Ajay P. Singh
Journal: Cancer Research (2011)

Abstract The clinical outcome from pancreatic cancer has not improved over the years. This is, in part, due to not well understood disease mechanisms and consequently there is little progress made in developing intervention therapy. Many genetic alterations have been characterized in pancreatic cancer, of which some have been shown to be functionally relevant. In an earlier study, c-Myb was identified as a candidate oncogene in pancreatic cancer with gene amplification in a subset and overexpression in majority of pancreatic cancer tissues and cell lines. The role of c-Myb in pancreatic cancer, however, has not been defined so far. c-Myb is a cellular progenitor of v-Myb oncogenes, which encodes for a transcription factor and confers its oncogenic activity by regulating the expression of several target genes. To examine the functional role of c-Myb in pancreatic cancer, we silenced its expression in two pancreatic cancer cell lines (Panc1 and MiaPaCa) by stable transfection of a c-Myb-targeted short-hairpin RNA (shRNA)-expression plasmid. Silencing of c-Myb expression resulted in diminished growth and clonogenicity of pancreatic cancer cells. c-Myb knockdown pancreatic cancer cells were arrested at G1/S boundary of cell cycle, and exhibited enhanced apoptosis. Furthermore, we observed decreased migration and invasion in c-Myb silenced pancreatic cancer cells as compared to the control cells. Immunoblot analysis demonstrated gain of epithelial- and loss of mesenchymal- markers in c-Myb knockdown pancreatic cancer cells, thus indicating a reversal of epithelial to mesenchymal transition (EMT). We also observed noticeable changes in cell morphology and actin-organization upon silencing of c-Myb expression that were consistent with loss of mesenchymal features. Together, these findings provide first experimental evidence for a functional role of c-Myb in pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4011. doi:10.1158/1538-7445.AM2011-4011