tbuckley/cabot-search huggingface dataset:
Overexpression of Tumor Vascular Endothelial Growth Factor A May Portend an Increased Likelihood of Progression in a Phase II Trial of Bevacizumab and Erlotinib in Resistant Ovarian Cancer
Authors: Setsuko K. Chambers, Mary C. Clouser, Amanda F. Baker, Denise J. Roe, Haiyan Cui, Molly A. Brewer, Kenneth D. Hatch, Michael S. Gordon, Mike F. Janicek, Jeffrey D. Isaacs, Alan N. Gordon, Raymond B. Nagle, Heather M. Wright, Janice L. Cohen, David S. Alberts
Journal: Clinical Cancer Research (2010)

Abstract Purpose: This phase II trial evaluated bevacizumab plus erlotinib in platinum-resistant ovarian cancer; exploratory biomarker analyses, including that of tumor vascular endothelial growth factor A (VEGF-A), were also done. Experimental Design: Forty heavily pretreated patients received erlotinib (150 mg/d orally) and bevacizumab (10 mg/kg i.v.) every 2 weeks until disease progression. Primary end points were objective response rate and response duration; secondary end points included progression-free survival (PFS), toxicity, and correlations between angiogenic protein levels, toxicity, and efficacy. Results: Grade 3 toxicities included skin rash (n = 6), diarrhea (n = 5), fatigue (n = 4), and hypertension (n = 3). Grade 4 toxicities were myocardial infarction (n = 1) and nasal septal perforation (n = 1). Only one grade 3 fistula and one grade 2 bowel perforation were observed. Nine (23.1%) of 39 evaluable patients had a response (median duration, 36.1+ weeks; one complete response), and 10 (25.6%) patients achieved stable disease, for a disease control rate of 49%. Median PFS was 4 months, and 6-month PFS was 30.8%. Biomarker analyses identified an association between tumor cell VEGF-A expression and progression (P = 0.03); for every 100-unit increase in the VEGF-A score, there was a 3.7-fold increase in the odds of progression (95% confidence interval, 1.1-16.6). Conclusions: Bevacizumab plus erlotinib in heavily pretreated ovarian cancer patients was clinically active and well tolerated. Erlotinib did not seem to contribute to efficacy. Our study raises the intriguing possibility that high levels of tumor cell VEGF-A, capable of both autocrine and paracrine interactions, are associated with resistance to bevacizumab, emphasizing the complexity of the tumor microenvironment. Clin Cancer Res; 16(21); 5320–8. ©2010 AACR.
Induced Sputum Cell Counts in Healthy Adults
Authors: JOSE BELDA, RICHARD LEIGH, KRISHNAN PARAMESWARAN, PAUL M. O'BYRNE, MALCOLM R. SEARS, FREDERICK E. HARGREAVE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Induced sputum cell counts provide a relatively noninvasive method to evaluate the presence, type, and degree of inflammation in the airways of the lungs. Their interpretation requires a knowledge of normal values from a healthy population. The objective was to examine the total and differential cell counts in induced sputum from a sample of healthy adults. A total of 118 healthy nonsmoking adults were studied. None had asthma or airflow obstruction (negative history, FEV1 ⩾ 80% predicted, ratio of FEV1 to vital capacity [FEV1/VC] ⩾ 80%, methacholine PC20 ⩾ 16 mg/ml). Forty-six were atopic. Sputum induction produced an adequate sample in 96 subjects [53 males, mean age (range) 36 (18 to 60) yr]. The expectorate was processed within 2 h; sputum was selected, treated with dithiothreitol, filtered, and examined in a hemocytometer for total cell count and viability and on Wright-stained cytospins for a differential cell count. The mean, median (90th percentile) total cell count was 4.1, 2.4 (9.7) × 106 cells/g and cell viability was 69.6, 72.0 (89.7)%. The proportions of eosinophils were 0.4, 0.0 (1.1)%, neutrophils 37.5, 36.7 (64.0)%, macrophages 58.8, 60.8 (86.1)%, lymphocytes 1.0, 0.5 (2.6)%, metachromatic cells 0.0, 0.0 (0.04)%, and bronchial epithelial cells 1.6, 0.3 (4.4)%, respectively. Female gender and atopy were associated with a significant elevation of eosinophils; mean difference between male/female was 0.3% (p = 0.043) and between atopic/nonatopic 0.4% (p = 0.024). This study has identified reference values for total and differential cell counts in induced sputum of healthy adults. Belda J, Leigh R, Parameswaran K, O'Byrne PM, Sears MR, Hargreave FE. Induced sputum cell counts in healthy adults.
Phase I and pharmacokinetic study of oral fludarabine phosphate in relapsed indolent B-cell non-Hodgkin's lymphoma
Authors: Y. Ogawa, T. Hotta, K. Tobinai, T. Watanabe, Y. Sasaki, H. Minami, Y. Morishima, M. Ogura, T. Seriu
Journal: Annals of Oncology (2005)
Clinical management and associated costs for moderate and severe Alzheimer’s disease in urban China: a Delphi panel study
Authors: Xin Yu, Shengdi Chen, Xiaochun Chen, Jianjun Jia, Chunhou Li, Cong Liu, Mondher Toumi, Dominique Milea
Journal: Translational Neurodegeneration (2015)

Healthcare resource utilisation for Alzheimer's disease (AD) in China is not well understood. This Delphi panel study aimed to describe the clinical management pathways for moderate and severe AD patients in urban China and to define the amount and cost of healthcare resources used.A panel of 11 experts was recruited from urban China to participate in two rounds of preparatory interviews. In the first round, 9 physicians specialised in dementia gave a qualitative description of the clinical management of AD patients. In the second round, 2 hospital administrators were asked about the cost of AD management and care. Results from the interviews were discussed by the experts in a Delphi panel meeting, where consensus was reached on quantitative aspects of AD management, including the rate of healthcare resource utilisation, the respective unit costs and caregiving time.Interviewees reported that mild AD is under-recognised in China; most patients are diagnosed with moderate to severe AD. Loss of independence and agitation/aggression are the main drivers for healthcare resource utilisation and contribute to a heavier caregiver burden. It was estimated that 70 % moderate AD patients are independent/non-aggressive at the time of diagnosis, 15 % are independent/aggressive, 10 % are dependent/non-aggressive, and 5 % are dependent/aggressive. Dependent/aggressive AD patients are more likely to be hospitalised (70-90 %) than accepted in a nursing home (0-20 %), while the opposite is true for dependent/non-aggressive patients (5-35 % for hospitalisation vs. 80 % for nursing home). Independent AD patients require 1-3 hours/day of caregiver time, while dependent patients can require up to 12-15 hours/day. Experts agreed that AD complicates the management of age-related comorbidities, found in 70-80 % of all AD patients, increasing the frequency and cost of hospitalisation.The Delphi panel approach was an efficient method of gathering data about the amount of healthcare resources used and associated costs for moderate and severe AD patients in urban China. The results of this study provide a useful source of information for decision makers to improve future healthcare policies and resource planning, as well as to perform economic evaluations of AD therapies.
Safety and Efficacy of Dose-Intensive Oral Vitamin A in Subjects with Sun-Damaged Skin
Authors: David Alberts, James Ranger-Moore, Janine Einspahr, Kathylynn Saboda, Paul Bozzo, Yun Liu, Xiao-chun Xu, Reuben Lotan, James Warneke, Stuart Salasche, Suzanne Stratton, Norman Levine, Rayna Goldman, Marcy Islas, Laura Duckett, Deborah Thompson, Peter Bartels
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Previously, we reported the results of a Phase III, placebo-controlled trial in 2,297 randomized participants with moderately severe actinic keratoses wherein 25,000 IU/day vitamin A caused a 32% risk reduction in squamous cell skin cancers. We hypothesized that dose escalation of vitamin A to 50,000 or 75,000 IU/day would be both safe and more efficacious in skin cancer chemoprevention. Experimental Design: One hundred and twenty-nine participants with severely sun-damaged skin on their lateral forearms were randomized to receive placebo or 25,000, 50,000, or 75,000 IU/day vitamin A for 12 months. The primary study end points were the clinical and laboratory safety of vitamin A, and the secondary end points included quantitative, karyometric image analysis and assessment of retinoid and rexinoid receptors in sun-damaged skin. Results: There were no significant differences in expected clinical and laboratory toxicities between the groups of participants randomized to placebo, 25,000 IU/day, 50,000 IU/day, and 75,000 IU/day. Karyometric features were computed from the basal cell layer of skin biopsies, and a total of 22,600 nuclei from 113 participants were examined, showing statistically significant, dose-response effects for vitamin A at the 25,000 and 50,000 IU/day doses. These karyometric changes correlated with increases in retinoic acid receptor α, retinoic acid receptor β, and retinoid X receptor α at the 50,000 IU/day vitamin A dose. Conclusions: The vitamin A doses of 50,000 and 75,000 IU/day for 1 year proved safe and equally more efficacious than the 25,000 IU/day dose and can be recommended for future skin cancer chemoprevention studies.
Endocardial Implantation of a Cardioverter-Defibrillator in a 13-Month-Old Child Affected by Long-QT Syndrome and Syndactyly
Authors: Maurizio Gasparini, Maurizio Lunati, Paola Galimberti, Raffaella Bloise, Iorio Fiore, Silvia G. Priori
Journal: Circulation (2004)
PKC-δ Promotes Renal Tubular Cell Apoptosis Associated with Proteinuria
Authors: Xiaoning Li, Navjotsingh Pabla, Qingqing Wei, Guie Dong, Robert O Messing, Cong-Yi Wang, Zheng Dong
Journal: Journal of the American Society of Nephrology (2010)

Proteinuria may contribute to progressive renal damage by inducing tubulointerstitial inflammation, fibrosis, and tubular cell injury and death, but the mechanisms underlying these pathologic changes remain largely unknown. Here, in a rat kidney proximal tubular cell line (RPTC), albumin induced apoptosis in a time- and dose-dependent manner. Caspase activation accompanied albumin-induced apoptosis, and general caspase inhibitors could suppress this activation. In addition, Bcl-2 transfection inhibited apoptosis and attenuated albumin-induced Bax translocation to mitochondria and cytochrome c release from the organelles, further confirming a role for the intrinsic pathway of apoptosis in albuminuria-associated tubular apoptosis. We observed phosphorylation and activation of PKC-delta early during treatment of RPTC cells with albumin. Rottlerin, a pharmacologic inhibitor of PKC-delta, suppressed albumin-induced Bax translocation, cytochrome c release, and apoptosis. Moreover, a dominant-negative mutant of PKC-delta blocked albumin-induced apoptosis in RPTC cells. In vivo, we observed activated PKC-delta in proteinuric kidneys of streptozotocin-induced diabetic mice and in kidneys after direct albumin overload. Notably, albumin overload induced apoptosis in renal tubules, which was less severe in PKC-delta-knockout mice. Taken together, these results suggest that activation of PKC-delta promotes tubular cell injury and death during albuminuria, broadening our understanding of the pathogenesis of progressive proteinuric kidney diseases.
Human Decidual Natural Killer Cells Are a Unique NK Cell Subset with Immunomodulatory Potential
Authors: Louise A. Koopman, Hernan D. Kopcow, Basya Rybalov, Jonathan E. Boyson, Jordan S. Orange, Frederick Schatz, Rachel Masch, Charles J. Lockwood, Asher D. Schachter, Peter J. Park, Jack L. Strominger
Journal: The Journal of Experimental Medicine (2003)

Natural killer cells constitute 50–90% of lymphocytes in human uterine decidua in early pregnancy. Here, CD56bright uterine decidual NK (dNK) cells were compared with the CD56bright and CD56dim peripheral NK cell subsets by microarray analysis, with verification of results by flow cytometry and RT-PCR. Among the ∼10,000 genes studied, 278 genes showed at least a threefold change with P ≤ 0.001 when comparing the dNK and peripheral NK cell subsets, most displaying increased expression in dNK cells. The largest number of these encoded surface proteins, including the unusual lectinlike receptors NKG2E and Ly-49L, several killer cell Ig-like receptors, the integrin subunits αD, αX, β1, and β5, and multiple tetraspanins (CD9, CD151, CD53, CD63, and TSPAN-5). Additionally, two secreted proteins, galectin-1 and progestagen-associated protein 14, known to have immunomodulatory functions, were selectively expressed in dNK cells.
Breast carcinoma cells re-express E-cadherin during mesenchymal to epithelial reverting transition
Authors: Yvonne L Chao, Christopher R Shepard, Alan Wells
Journal: Molecular Cancer (2010)

Abstract Background Epithelial to mesenchymal transition (EMT), implicated as a mechanism for tumor dissemination, is marked by loss of E-cadherin, disruption of cell adhesion, and induction of cell motility and invasion. In most intraductal breast carcinomas E-cadherin is regulated epigenetically via methylation of the promoter. E-cadherin expression is therefore dynamic and open to modulation by the microenvironment. In addition, it has been observed that metastatic foci commonly appear more differentiated than the primary tumor, suggesting that cancer cells may further undergo a mesenchymal to epithelial reverting transition (MErT) in the secondary organ environment following the EMT that allows for escape. Results We first examined E-cadherin expression in primary breast tumors and their corresponding metastases to liver, lung and brain and discovered that 62% (10/16) of cases showed increased E-cadherin expression in the metastases compared to the primaries. These observations led to the question of whether the positive metastatic foci arose from expansion of E-cadherin-positive cells or from MErT of originally E-cadherin-negative disseminated cells. Thus, we aimed to determine whether it was possible for the mesenchymal-like MDA-MB-231 breast cancer cells to undergo an MErT through the re-expression of E-cadherin, either through exogenous introduction or induction by the microenvironment. Ectopic expression of full-length E-cadherin in MDA-MB-231 cells resulted in a morphological and functional reversion of the epithelial phenotype, with even just the cytosolic domain of E-cadherin yielding a partial phenotype. Introduction of MDA-MB-231 cells or primary explants into a secondary organ environment simulated by a hepatocyte coculture system induced E-cadherin re-expression through passive loss of methylation of the promoter. Furthermore, detection of E-cadherin-positive metastatic foci following the spontaneous metastasis of MDA-MB-231 cells injected into the mammary fat pad of mice suggests that this re-expression is functional. Conclusions Our clinical observations and experimental data indicate that the secondary organ microenvironment can induce the re-expression of E-cadherin and consequently MErT. This phenotypic change is reflected in altered cell behavior and thus may be a critical step in cell survival at metastatic sites.
A Randomized, Controlled Trial of Cognitive Behavioral Social Skills Training for Middle-Aged and Older Outpatients With Chronic Schizophrenia
Authors: Eric Granholm, John R McQuaid, Fauzia Simjee McClure, Lisa A Auslander, Dimitri Perivoliotis, Paola Pedrelli, Thomas Patterson, Dilip V Jeste
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The number of older patients with chronic schizophrenia is increasing. There is a need for empirically validated psychotherapy interventions for these patients. Cognitive behavioral social skills training teaches cognitive and behavioral coping techniques, social functioning skills, problem solving, and compensatory aids for neurocognitive impairments. The authors compared treatment as usual with the combination of treatment as usual plus cognitive behavioral social skills training. METHOD: The randomized, controlled trial included 76 middle-aged and older outpatients with chronic schizophrenia, who were assigned to either treatment as usual or combined treatment. Cognitive behavioral social skills training was administered over 24 weekly group sessions. Blind raters assessed social functioning, psychotic and depressive symptoms, cognitive insight, and skill mastery. RESULTS: After treatment, the patients receiving combined treatment performed social functioning activities significantly more frequently than the patients in treatment as usual, although general skill at social functioning activities did not differ significantly. Patients receiving cognitive behavioral social skills training achieved significantly greater cognitive insight, indicating more objectivity in reappraising psychotic symptoms, and demonstrated greater skill mastery. The overall group effect was not significant for symptoms, but the greater increase in cognitive insight with combined treatment was significantly correlated with greater reduction in positive symptoms. CONCLUSIONS: With cognitive behavioral social skills training, middle-aged and older outpatients with chronic schizophrenia learned coping skills, evaluated anomalous experiences with more objectivity (achieved greater cognitive insight), and improved social functioning. Additional research is needed to determine whether cognitive insight mediates psychotic symptom change in cognitive behavior therapy for psychosis.
E2F-1 Overexpression in Cardiomyocytes Induces Downregulation of p21 <sup>CIP1</sup> and p27 <sup>KIP1</sup> and Release of Active Cyclin-Dependent Kinases in the Presence of Insulin-Like Growth Factor I
Authors: Rüdiger von Harsdorf, Ludger Hauck, Felix Mehrhof, Ursula Wegenka, M. Cristina Cardoso, Rainer Dietz
Journal: Circulation Research (1999)

Abstract —The heart is a postmitotic organ unable to regenerate after injury. The mechanisms controlling cell cycle arrest in cardiomyocytes are still unknown. Adenoviral delivery of E2F-1 to primary rat cardiomyocytes resulted in an increase in the expression of key cell cycle activators and apoptosis in &gt;90% of the cells. However, insulin-like growth factor I (IGF-I) rescued cardiomyocytes from E2F-1–induced apoptosis. Furthermore, overexpression of E2F-1 in the presence of IGF-I induced the specific downregulation of total p21 CIP1 and p27 KIP1 protein levels and their dissociation from cyclin-dependent kinases (cdks). In contrast, p16 INK4 and p57 KIP2 protein levels and their association with cdks remained unaltered. The dissociation of p21 CIP1 and p27 KIP1 from their cdk complexes correlated well with the activation of cdk2, cdk4, and cdk6 and the release from cell cycle arrest. Under these circumstances, the number of cardiomyocytes in S phase rose from 1.2% to 23%. These results indicate that IGF-I renders cardiomyocytes permissive for cell cycle reentry. Finally, the specific downregulation of p21 CIP1 and p27 KIP1 further suggests their key role in the maintenance of cell cycle arrest in cardiomyocytes.
FEMORAL ARTERY PERCUTANEOUS REVASCULARIZATION FOR PATIENTS WITH CRITICAL LIMB ISCHEMIA: OUTCOMES COMPARED TO PATIENTS WITH CLAUDICATION OVER 2.5 YEARS
Authors: Thomas M. Todoran, Gerard Connors, Brian A. Engleson, Piotr S. Sobieszczyk, Andrew C. Eisenhauer, Scott Kinlay
Journal: Journal of the American College of Cardiology (2011)
Variable arrangement of 5S ribosomal genes within the ribosomal DNA repeats of arthropods.
Authors: G Drouin, J M Sévigny, I A McLaren, J D Hofman, W F Doolittle
Journal: Molecular Biology and Evolution (1992)

The polymerase chain reaction and hybridization to genomic blots were used to investigate whether the previously observed inclusion of 5S ribosomal RNA genes in the 28S-18S ribosomal DNA intergenic regions of some crustacean species (copepods) could also be detected in other arthropods. Such an arrangement was found not only in other calanoid copepod species but also in a cirriped, an euphausid, and a spider. It is interesting that species from two different calanoid copepod genera do not have this type of arrangement. We conclude that the inclusion of 5S ribosomal RNA genes within the ribosomal DNA repeats has probably occurred repeatedly during the evolution of arthropod species and that the mechanism(s) responsible for these insertions could also be responsible for their loss.
Functional assessment of beta adrenoceptor subtypes in human colonic circular and longitudinal (taenia coli) smooth muscle
Authors: L Manara
Journal: Gut (2000)

<h3>BACKGROUND AND AIMS</h3> The subtype and species related heterogeneity of β adrenoceptors prompted a functional reappraisal of these molecular targets of motility inhibition in the human colon. <h3>METHODS</h3> Relaxation of muscle strips was measured in vitro. <h3>RESULTS</h3> The following agonists had decreasing relaxing potency (effective concentration range 10<sup>−8</sup>–10<sup>−4</sup> mol/l): (−)isoprenaline (non-selective), terbutaline (β<sub>2</sub> selective), CGP 12177 (β<sub>3</sub> selective, also β<sub>1</sub>, β<sub>2</sub>antagonist), and SR 58611A (β<sub>3</sub> selective). Isoprenaline and terbutaline were more potent on circular than taenia strips; CGP 12177 and SR 58611A weakly and partially relaxed taenia but had little effect on circular strips. The potency of isoprenaline on circular strips was greatly reduced by the β<sub>1</sub> selective antagonist CGP 20712 (10<sup>−7</sup> mol/l), and less so by ICI 118551 (10<sup>−7</sup> mol/l, β<sub>2</sub> selective). CGP 20712 and ICI 118551 together (both 3×10<sup>-6</sup> mol/l) had no effect on taenia relaxation by SR 58611A and rendered isoprenaline and terbutaline virtually inactive on circular strips, although not on taenia, which was relaxed at higher than control concentrations and maximally by isoprenaline. Propranolol, a β<sub>1</sub>, β<sub>2</sub> non-selective antagonist, at high concentrations (10<sup>-5</sup> mol/l) prevented taenia relaxation by CGP 12177 and SR 58611A; its quantitative antagonism of isoprenaline (in common with that of CGP 12177 used as an antagonist) was competitive in circular strips but not on taenia. <h3>CONCLUSIONS</h3> β<sub>1</sub>, β<sub>2</sub>, and β<sub>3</sub> adrenoceptors are functionally detectable in the human colon; agonist stimulation of any one type relaxed taenia but only isoprenaline was fully effective at the β<sub>3</sub> subtype.
Identification of Typical Left Bundle Branch Block Contraction by Strain Echocardiography Is Additive to Electrocardiography in Prediction of Long-Term Outcome After Cardiac Resynchronization Therapy
Authors: Niels Risum, Bhupendar Tayal, Thomas F. Hansen, Niels E. Bruun, Magnus T. Jensen, Trine K. Lauridsen, Samir Saba, Joseph Kisslo, John Gorcsan, Peter Sogaard
Journal: Journal of the American College of Cardiology (2015)