tbuckley/cabot-search huggingface dataset:
Cell aggregation induces phosphorylation of PECAM-1 and Pyk2 and promotes tumor cell anchorage-independent growth
Authors: Xing Zhang, Li-hua Xu, Qiang Yu
Journal: Molecular Cancer (2010)

Apoptosis caused by inadequate or inappropriate cell-matrix interactions is defined as anoikis. Although transformed cells are known to be anoikis-resistant, the underlying mechanisms have not been well understood. We investigated the mechanisms of anoikis resistance of tumor cells.We observed that cell aggregation in suspension promoted cell survival and proliferation. We demonstrated a correlation between tumor cell aggregation in suspension and cell growth in soft agar. Analysis of tyrosine kinase-mediated cell survival and growth signaling pathways revealed increased levels of tyrosine-phosphorylation of PECAM-1 and Pyk2 in cell aggregates. We also showed that PECAM-1 and Pyk2 physically interact with each other, and that PECAM-1 carrying a deletion of exons 11-16 could no longer bind to Pyk2. Furthermore, RNA interference-mediated reduction of Pyk2 and PECAM-1 protein levels reduced cell aggregation and inhibited the growth of tumor cells in soft agar.The data demonstrated that Pyk2 and PECAM-1 were critical mediators of both anchorage-independent growth and anoikis resistance in tumor cells.
Incorporating Multidimensional Patient-Reported Outcomes of Symptom Severity, Functioning, and Quality of Life in the Individual Burden of Illness Index for Depression to Measure Treatment Impact and Recovery in MDD
Authors: Robert M. Cohen, Jared M. Greenberg, Waguih William IsHak
Journal: JAMA Psychiatry (2013)

The National Institute of Mental Health Affective Disorders Workgroup identified the assessment of an individual's burden of illness as an important need. The Individual Burden of Illness Index for Depression (IBI-D) metric was developed to meet this need.To assess the use of the IBI-D for multidimensional assessment of treatment efficacy for depressed patients.Complete data on depressive symptom severity, functioning, and quality of life (QOL) from depressed patients (N = 2280) at entry and exit of level 1 of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (12-week citalopram treatment) were used as the basis for calculating IBI-D and self-rating scale changes.Principal component analysis of patient responses at the end of level 1 of STAR*D yielded a single principal component, IBI-D, with a nearly identical eigenvector to that previously reported. While changes in symptom severity (Quick Inventory of Depressive Symptomatology-Self Report) accounted for only 50% of the variance in changes in QOL (Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form) and 47% of the variance in changes in functioning (Work and Social Adjustment Scale), changes in IBI-D captured 83% of the variance in changes in QOL and 80% in functioning, while also capturing 79% of the variance in change in symptom severity (Quick Inventory of Depressive Symptomatology-Self Report). Most importantly, the changes in IBI-D of the 36.6% of remitters who had abnormal QOL and/or functioning (mean [SD], 2.98 [0.35]) were significantly less than the changes in IBI-D of those who reported normal QOL and functioning (IBI-D = 1.97; t = 32.6; P < 10(-8)) with an effect size of a Cohen d of 2.58. In contrast, differences in symptom severity, while significant, had a Cohen d of only 0.78.Remission in depressed patients, as defined by a reduction in symptom severity, does not denote normal QOL or functioning. By incorporating multidimensional patient-reported outcomes, the IBI-D provides a single measure that adequately captures the full burden of illness in depression both prior to and following treatment; therefore, it offers a more accurate metric of recovery.clinicaltrials.gov Identifier: NCT00021528.
Neural Stimulation and Recording Electrodes
Authors: Stuart F. Cogan
Journal: Annual Review of Biomedical Engineering (2008)

Electrical stimulation of nerve tissue and recording of neural electrical activity are the basis of emerging prostheses and treatments for spinal cord injury, stroke, sensory deficits, and neurological disorders. An understanding of the electrochemical mechanisms underlying the behavior of neural stimulation and recording electrodes is important for the development of chronically implanted devices, particularly those employing large numbers of microelectrodes. For stimulation, materials that support charge injection by capacitive and faradaic mechanisms are available. These include titanium nitride, platinum, and iridium oxide, each with certain advantages and limitations. The use of charge-balanced waveforms and maximum electrochemical potential excursions as criteria for reversible charge injection with these electrode materials are described and critiqued. Techniques for characterizing electrochemical properties relevant to stimulation and recording are described with examples of differences in the in vitro and in vivo response of electrodes.
Cationic Albumin–Conjugated Pegylated Nanoparticles Allow Gene Delivery into Brain Tumors via Intravenous Administration
Authors: Wei Lu, Qing Sun, Jin Wan, Zhenjue She, Xin-Guo Jiang
Journal: Cancer Research (2006)

Abstract Patients with malignant gliomas have a poor prognosis because these tumors do not respond well to conventional treatments. Studies of glioma xenografts suggest that they may be amenable to gene therapy with cytotoxic genes, such as the proapoptotic Apo2 ligand/tumor necrosis factor–related apoptosis-inducing ligand (Apo2L/TRAIL). Gene therapy of gliomas ideally employs i.v. given vectors, thus excluding viral vectors as they cannot cross the brain microvascular endothelium or blood-brain barrier. Recently, we reported the synthesis of cationic albumin–conjugated pegylated nanoparticles (CBSA-NP) and showed their accumulation in mouse brain cells upon i.v. administration. In this study, plasmid pORF-hTRAIL (pDNA) was incorporated into CBSA-NP, and the resulting CBSA-NP-hTRAIL was evaluated as a nonviral vector for gene therapy of gliomas. Thirty minutes after transfection of C6 glioma cells, CBSA-NP-hTRAIL was internalized and mostly located in the cytoplasm, whereas NP-hTRAIL was entrapped in the endolysosomal compartment. At 6 and 48 hours after transfection, respectively, released pDNA was present in the nuclei and induced apoptosis. At 30 minutes after i.v. administration of CBSA-NP-hTRAIL to BALB/c mice bearing i.c. C6 gliomas, CBSA-NP-hTRAIL colocalized with glycoproteins in brain and tumor microvasculature and, via absorptive-mediated transcytosis, accumulated in tumor cells. At 24 and 48 hours after i.v. administration of CBSA-NP-hTRAIL, respectively, hTRAIL mRNA and protein were detected in normal brain and tumors. Furthermore, repeated i.v. injections of CBSA-NP-hTRAIL induced apoptosis in vivo and significantly delayed tumor growth. In summary, this study indicates that CBSA-NP-hTRAIL is a promising candidate for noninvasive gene therapy of malignant glioma. (Cancer Res 2006; 66(24): 11878-87)
The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer.
Authors: Magali Olivier, Anita Langer√∏d, Patrizia Carrieri, Jonas Bergh, Sigrid Klaar, Jorunn Eyfjord, Charles Theillet, Carmen Rodriguez, Rosette Lidereau, Ivan Bi√®che, Jennifer Varley, Yves Bignon, Nancy Uhrhammer, Robert Winqvist, Arja Jukkola-Vuorinen, Dieter Niederacher, Shunsuke Kato, Chikashi Ishioka, Pierre Hainaut, Anne-Lise B√∏rresen-Dale
Journal: Clinical Cancer Research (2006)

Abstract To investigate the clinical value of somatic TP53 mutations in breast cancer, we assembled clinical and molecular data on 1,794 women with primary breast cancer with long-term follow-up and whose tumor has been screened for mutation in exons 5 to 8 of TP53 by gene sequencing. TP53 mutations were more frequent in tumors of ductal and medullar types, aggressive phenotype (high grade, large size, node positive cases, and low hormone receptor content) and in women &amp;lt;60 years old. TP53 mutations within exons 5 to 8 conferred an elevated risk of breast cancer-specific death of 2.27 (relative risk &amp;gt;10 years; P &amp;lt; 0.0001) compared with patients with no such mutation. The prognostic value of TP53 mutation was independent of tumor size, node status, and hormone receptor content, confirming and reconciling previous findings in smaller series. Moreover, an interaction between TP53 mutation and progesterone receptor (PR) status was revealed, TP53 mutation combined with the absence of progesterone receptor being associated with the worst prognosis. Whereas previous studies have emphasized the fact that missense mutations in the DNA-binding motifs have a worse prognosis than missense mutations outside these motifs, we show that non-missense mutations have prognostic value similar to missense mutations in DNA-binding motifs. Nonetheless, specific missense mutants (codon 179 and R248W) seem to be associated with an even worse prognosis. These results, obtained on the largest series analyzed thus far, show that TP53 mutations identified by gene sequencing have an independent prognostic value in breast cancer and could have potential uses in clinical practice.
Reduction in hospital mortality by first day percutaneous coronary intervention for non-ST elevation myocardial infarction in diabetics: Result of the ACOS-registry
Authors: Anselm K. Gitt, Rudolf Schiele, Harm Wienbergen, Steffen Schneider, Tobias Heer, Uwe Zeymer, Martin G. Gottwik, Jochen Senges
Journal: Journal of the American College of Cardiology (2003)
Monocyte-mediated Tumoricidal Activity via the Tumor Necrosis Factor–related Cytokine, TRAIL
Authors: Thomas S. Griffith, Steven R. Wiley, Marek Z. Kubin, Lisa M. Sedger, Charles R. Maliszewski, Neil A. Fanger
Journal: The Journal of Experimental Medicine (1999)

TRAIL (tumor necrosis factor [TNF]-related apoptosis-inducing ligand) is a molecule that displays potent antitumor activity against selected targets. The results presented here demonstrate that human monocytes rapidly express TRAIL, but not Fas ligand or TNF, after activation with interferon (IFN)-gamma or -alpha and acquire the ability to kill tumor cells. Monocyte-mediated tumor cell apoptosis was TRAIL specific, as it could be inhibited with soluble TRAIL receptor. Moreover, IFN stimulation caused a concomitant loss of TRAIL receptor 2 expression, which coincides with monocyte acquisition of resistance to TRAIL-mediated apoptosis. These results define a novel mechanism of monocyte-induced cell cytotoxicity that requires TRAIL, and suggest that TRAIL is a key effector molecule in antitumor activity in vivo.
Health Plan Members' Views about Disclosure of Medical Errors
Authors: Kathleen M. Mazor, Steven R. Simon, Robert A. Yood, Brian C. Martinson, Margaret J. Gunter, George W. Reed, Jerry H. Gurwitz
Journal: Annals of Internal Medicine (2004)

Various authorities and national organizations encourage disclosing medical errors, but there is little information on how patients respond to disclosure.To examine how the type of error, severity of adverse clinical outcome, and level of disclosure affect patients' responses to error and disclosure.Mail questionnaire survey (8 versions were developed) varying 3 factors in a completely crossed, randomized, factorial design. Each questionnaire included a vignette describing 1) a medical error (failure to check for penicillin allergy or inadequate monitoring of antiepileptic medication); 2) an associated clinical outcome (life-threatening or less serious); and 3) a physician-patient dialogue, with either full disclosure (acceptance of responsibility and an apology) or nondisclosure (expression of regret without acceptance of responsibility or an apology).New England-based health plan.Random sample of 1500 adult members received the questionnaire, with a 66% response rate.Likelihood of changing physicians, likelihood of seeking legal advice, ratings of patient satisfaction, trust and emotional reaction in response to a vignette and dialogue, and views on medical error and disclosure.Full disclosure reduced the reported likelihood of changing physicians and increased patient satisfaction, trust, and positive emotional response. Full disclosure reduced the reported likelihood of seeking legal advice in only 1 error-and-outcome vignette. In the other vignettes, the percentage of patients indicating that they would seek legal advice was relatively high even with full disclosure. Almost all respondents (98.8%) wanted to be told of errors, most (83%) favored financial compensation if harm occurred, and few (12.7%) favored compensation if no harm occurred.Since the study was done in the context of a managed care plan in one geographic area, it could not assess whether the results are generalizable to other populations. In addition, it could not determine whether responses to the simulated situations used predict responses to real situations.Patients will probably respond more favorably to physicians who fully disclose medical errors than to physicians who are less forthright, but the specifics of the case and the severity of the clinical outcome also affect patients' responses. In some circumstances, the desire to seek legal advice may not diminish despite full disclosure.
Antioxidant treatment inhibits the development of intimal thickening after balloon injury of the aorta in hypercholesterolemic rabbits.
Authors: A Freyschuss, A Stiko-Rahm, J Swedenborg, P Henriksson, I Björkhem, L Berglund, J Nilsson
Journal: Journal of Clinical Investigation (1993)

The effect of the antioxidant butylated hydroxytoluene (BHT) on the accumulation of intimal smooth muscle cells (SMC) and development of intimal thickening after balloon catheter injury of the aorta were studied in rabbits with dietary-induced hyperlipidemia. Two sets of New Zealand White rabbits (eight rabbits in each group) were fed either 0.25% cholesterol or 0.25% cholesterol/1% BHT for a total of 6 wk. Serum lipid levels did not differ between the two groups. 3 wk after the start of the study, a balloon injury of the aorta was performed, after which the rabbits were kept on their respective diets for another 3 wk. After this period of time, the rabbits were killed and their aortas were investigated. The BHT-treated rabbits had only one fourth of the intimal thickness (P < 0.0001) and half the number of SMC/mm intima (P < 0.001), as compared to the rabbits fed only cholesterol. There was also a lower number of macrophages in the BHT-treated group. T lymphocytes were present in the intima of cholesterol-fed rabbits, whereas no such cells could be identified in the BHT-fed animals. There were significantly lower levels of autooxidation products of cholesterol (7-oxocholesterol, cholesterol-5,6-epoxide, and 7 beta-hydroxycholesterol) in the aortas of BHT-treated rabbits, P < 0.001. In conclusion, the antioxidant BHT effectively inhibited the accumulation of intimal SMC and the development of intimal thickening of the aorta in hypercholesterolemic rabbits after a balloon catheter-induced injury. These results indicate that antioxidants may modify intimal response to injury.
Increased Nitric Oxide Synthase-3 Expression in Kidneys of Deoxycorticosterone Acetate-Salt Hypertensive Rats
Authors: GRAHAM H. ALLCOCK, MIKA HUKKANEN, JULIA M. POLAK, JENNIFER S. POLLOCK, DAVID M. POLLOCK
Journal: Journal of the American Society of Nephrology (1999)

Abstract. In addition to its hemodynamic effects, nitric oxide (NO) may play a role in the renal tubular handling of sodium. Experiments were conducted to determine possible changes in renal nitric oxide synthase-3 (NOS3) expression in rats treated with deoxycorticosterone acetate (DOCA) and high salt. All rats were uninephrectomized, and either a placebo or DOCA pellet was implanted subcutaneously. Placebo-treated rats were then given tap water to drink ad libitum, and DOCA-treated rats received a 0.9% NaCl solution to drink. Once a week, rats were placed in metabolic cages so that a 24-h urine sample could be collected. After 3 wk, the animals were sacrificed and the kidneys removed and prepared for subsequent immunohistochemical or Western blot analysis. Urinary excretion of nitrate and nitrite (NOx) was measured to provide an indication of the intrarenal production of NO. DOCA-salt hypertensive rats exhibited increased urinary NOx excretion (2.43 ± 0.48 μmol NOx/mg creatinine) compared with the placebo control animals (1.17 ± 0.06 μmol NOx/mg creatinine). Western blot analysis revealed that NOS3 protein levels in both the cortex and medulla were greater in DOCA-salt rats compared with placebo-treated animals. Immunohistochemical analysis of kidneys revealed that NOS3 expression in placebo rats was localized in vascular endothelial cells with slight, but detectable, immunoreactivity in medullary collecting ducts. In DOCA-salt rats, a very large increase in the intensity of immunostaining was detected in tubular epithelia of the proximal tubule, thick ascending limb of Henle's loop, and cortical and medullary collecting duct; immunoreactivity in endothelial cells appeared unchanged. These data suggest that increased tubular expression of NOS3 is responsible, at least in part, for the increased renal production of NO in DOCA-salt hypertension, and are consistent with a role for NO in the renal tubular response to salt loading.
Ten-year stability and predictive validity of five bulimia-related indicators
Authors: T E Joiner, T F Heatherton, P K Keel
Journal: American Journal of Psychiatry (1997)

The authors examined the temporal stability and predictive utility of bulimic symptoms and related variables over the course of 10 years, from 1982 to 1992.The subjects were 459 women who were aged 18-22 years in 1982 and were surveyed in both 1982 and 1992. Each respondent completed five subscales of the Eating Disorders Inventory (bulimia, drive for thinness, maturity fears, perfectionism, and interpersonal distrust) and answered questions based on the DSM-III criteria for bulimia nervosa.The temporal stability of bulimic symptoms and related variables was relatively high. Bulimic status in 1982 conferred an approximately 15-fold increase in risk 10 years later. Drive for thinness and, to lesser degrees, maturity fears and perfectionism received support as long-term predictors of bulimic symptoms.Bulimic symptoms display high temporal stability and thus may affect long-term functioning and well-being. Later symptoms are related to scores on specific subscales of the Eating Disorders Inventory administered 10 years earlier. Assessment and therapy should be conducted accordingly.
MAGE-A, mMage-b, and MAGE-C Proteins Form Complexes with KAP1 and Suppress p53-Dependent Apoptosis in MAGE-Positive Cell Lines
Authors: Bing Yang, Sean M. O'Herrin, Jianqiang Wu, Shannon Reagan-Shaw, Yongsheng Ma, Kumar M.R. Bhat, Claudia Gravekamp, Vijayasaradhi Setaluri, Noel Peters, F. Michael Hoffmann, Hongzhuang Peng, Alexey V. Ivanov, Andrew J.G. Simpson, B. Jack Longley
Journal: Cancer Research (2007)

Abstract The MAGE-A, MAGE-B, and MAGE-C protein families comprise the class-I MAGE/cancer testes antigens, a group of highly homologous proteins whose expression is suppressed in all normal tissues except developing sperm. Aberrant expression of class I MAGE proteins occurs in melanomas and many other malignancies, and MAGE proteins have long been recognized as tumor-specific targets; however, their functions have largely been unknown. Here, we show that suppression of class I MAGE proteins induces apoptosis in the Hs-294T, A375, and S91 MAGE-positive melanoma cell lines and that members of all three families of MAGE class I proteins form complexes with KAP1, a scaffolding protein that is known as a corepressor of p53 expression and function. In addition to inducing apoptosis, MAGE suppression decreases KAP1 complexing with p53, increases immunoreactive and acetylated p53, and activates a p53 responsive reporter gene. Suppression of class I MAGE proteins also induces apoptosis in MAGE-A–positive, p53wt/wt parental HCT 116 colon cancer cells but not in a MAGE-A–positive HCT 116 p53−/− variant, indicating that MAGE suppression of apoptosis requires p53. Finally, treatment with MAGE-specific small interfering RNA suppresses S91 melanoma growth in vivo, in syngenic DBA2 mice. Thus, class I MAGE protein expression may suppress apoptosis by suppressing p53 and may actively contribute to the development of malignancies and by promoting tumor survival. Because the expression of class I MAGE proteins is limited in normal tissues, inhibition of MAGE antigen expression or function represents a novel and specific treatment for melanoma and diverse malignancies. [Cancer Res 2007;67(20):9954–62]
Determinants of altered quality of life in patients with sleep-related breathing disorders
Authors: E. Sforza, J.P. Janssens, T. Rochat, V. Ibanez
Journal: European Respiratory Journal (2003)

Recent reports have suggested that altered quality of life and well-being are reported by patients with sleep-related breathing disorders (SRBD). There seems to be no data available in the literature on factors underlying these behavioural consequences. In this study, health-related quality of life (HRQL) scores were examined in SRBD patients in order to establish which factors are implicated in these disturbances. The study group consisted of 130 patients: 49 snorers and 81 patients with obstructive sleep apnoea. The Medical Outcome Survey Short Form-36 questionnaire was administered the morning after the sleep study and scores for the eight dimension scores were obtained. Patient's data were compared to normative sex- and age-matched data. In comparison with normal values, scores for all HRQL dimensions were decreased in SRBD patients, with a greater impact on subscores for "vitality", "physical role", "social functioning", "mental health" and "role emotional" dimensions. While impairment in physical function was mostly influenced by sleep stage and obesity, subjective daytime sleepiness mainly affected the other dimensions. The authors conclude that the altered health-related quality of life of sleep-related breathing disorder patients is a multifactorial phenomenon depending on the interaction of sleep stages, daytime sleepiness and obesity, with no significant contribution of sleep fragmentation, hypoxaemia and apnoea recurrence.
Will Diabetes Save the Platelet Blockers?
Authors: Marc S. Sabatine, Eugene Braunwald
Journal: Circulation (2001)

ore than 30 000 patients have been enrolled in trials assessing the efficacy of glycoprotein (GP) IIb/IIIa inhibitors in unstable angina (UA) or non-ST-segment elevation MI (NSTEMI).The initial trials demonstrated that the use of a GP IIb/IIIa inhibitor resulted in a significant decrease in the rate of death or nonfatal myocardial infarction. 1,2More recently, however, the GP IIb/IIIa inhibitor with the best track record to date in the setting of percutaneous coronary intervention (PCI), abciximab, was tested in UA/NSTEMI in the Global Use of Strategies To Open occluded coronary arteries in Acute Coronary Syndromes (GUSTO IV-ACS) trial, which enrolled patients in whom PCI was not intended, and showed no benefit. 3These disappointing results may have been related to issues of dosing, patient selection, and trial design, but nevertheless, they have led to a reappraisal of the utility of GP IIb/IIIa inhibitors in UA/NSTEMI.
ANTI‐PANCREATIC, CELLULAR HYPERSENSITIVITY IN DIABETES MELLITUS. EXPERIMENTAL INDUCTION OF ANTI‐PANCREATIC, CELLULAR HYPERSENSITIVITY AND ASSOCIATED MORPHOLOGICAL B‐CELL CHANGES IN THE RAT
Authors: JØSRN NERUP, OLE ORTVED ANDERSEN, GUNNAR BENDIXEN, JØRN EGEBERG, JACOB E. POULSEN, MOGENS VILIEN, MIKKEL WESTRUP
Journal: Allergy (1973)
Noninvasive assessment of ejection intraventricular pressure gradients
Authors: Raquel Yotti, Javier Bermejo, J.Carlos Antoranz, José Luis Rojo-Álvarez, Carmen Allue, Jacobo Silva, M.Mar Desco, Mar Moreno, Miguel A. Garcı́a-Fernández
Journal: Journal of the American College of Cardiology (2004)