tbuckley/cabot-search huggingface dataset:
Exploring the Biomechanical Properties of Brain Malignancies and Their Pathologic Determinants <i>In Vivo</i> with Magnetic Resonance Elastography
Authors: Yann Jamin, Jessica K.R. Boult, Jin Li, Sergey Popov, Philippe Garteiser, Jose L. Ulloa, Craig Cummings, Gary Box, Suzanne A. Eccles, Chris Jones, John C. Waterton, Jeffrey C. Bamber, Ralph Sinkus, Simon P. Robinson
Journal: Cancer Research (2015)

Malignant tumors are typically associated with altered rigidity relative to normal host tissue. Magnetic resonance elastography (MRE) enables the noninvasive quantitation of the mechanical properties of deep-seated tissue following application of an external vibrational mechanical stress to that tissue. In this preclinical study, we used MRE to quantify (kPa) the elasticity modulus Gd and viscosity modulus Gl of three intracranially implanted glioma and breast metastatic tumor models. In all these brain tumors, we found a notable softness characterized by lower elasticity and viscosity than normal brain parenchyma, enabling their detection on Gd and Gl parametric maps. The most circumscribed tumor (U-87 MG glioma) was the stiffest, whereas the most infiltrative tumor (MDA-MB-231 metastatic breast carcinoma) was the softest. Tumor cell density and microvessel density correlated significantly and positively with elasticity and viscosity, whereas there was no association with the extent of collagen deposition or myelin fiber entrapment. In conclusion, although malignant tumors tend to exhibit increased rigidity, intracranial tumors presented as remarkably softer than normal brain parenchyma. Our findings reinforce the case for MRE use in diagnosing and staging brain malignancies, based on the association of different tumor phenotypes with different mechanical properties.
Factors Related to Response to Intermittent Treatment of <i>Mycobacterium avium</i> Complex Lung Disease
Authors: Phung K. Lam, David E. Griffith, Timothy R. Aksamit, Stephen J. Ruoss, Stuart M. Garay, Charles L. Daley, Antonino Catanzaro
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with substantial morbidity, and standard daily multidrug therapy is difficult to tolerate.Objectives: To characterize response to a three-times-weekly (TIW) regimen of clarithromycin, ethambutol, and rifampin.Methods: A 1-yr prospective noncomparative trial of TIW treatment was conducted during 2000–2003 in 17 U.S. cities. Participants were 91 HIV-negative adults, diagnosed with moderate to severe MAC-PD, who originally participated in a trial of an inhaled IFN-γ treatment. Improvement in sputum culture, high-resolution computed tomography (HRCT), and symptoms were assessed.Results: Treatment response rates (and median response times) were 44% (2 mo or longer) for culture, 60% (5.5–11.5 mo) for HRCT, and 53% (8.5 mo) for symptoms. Having noncavitary, compared with cavitary, disease increased culture response by 4.0 times (95% confidence interval [CI], 1.7–9.2) and HRCT response by 4.9 times (95% CI, 1.9–13.0). Culture response was 1.5 times (95% CI, 1.1–2.2) higher for older subjects and 2.2 times (95% CI, 1.0–4.7) higher for previously untreated subjects. Being smear-negative increased culture response by 2.3 times (95% CI, 1.1–5.2) but decreased HRCT response by 4.4 times (95% CI, 1.7–11.5). Increasing ethambutol use by 5 mo increased culture response by 1.5 times (95% CI, 1.0–2.1) but decreased symptom response. Not having chronic obstructive pulmonary disease, bronchiectasis, or poor lung function increased symptom response by 1.9 to 3.9 times.Conclusions: TIW therapy was less effective for MAC-PD patients with cavitary disease and a history of chronic obstructive pulmonary disease, bronchiectasis, or previous treatment for MAC-PD. Further research is needed to study the long-term outcomes of TIW treatment.
Risk of Cardiovascular Disease Events in Patients With Type 2 Diabetes Prescribed the Glucagon-Like Peptide 1 (GLP-1) Receptor Agonist Exenatide Twice Daily or Other Glucose-Lowering Therapies
Authors: Jennie H. Best, Byron J. Hoogwerf, William H. Herman, Elise M. Pelletier, Daniel B. Smith, Made Wenten, Mohamed A. Hussein
Journal: Diabetes Care (2010)

OBJECTIVE To test the hypothesis that exenatide twice daily reduces the relative incidence of cardiovascular disease (CVD) events among patients with type 2 diabetes compared with other glucose-lowering agent(s). RESEARCH DESIGN AND METHODS A retrospective database analysis was performed of the LifeLink database of medical and pharmaceutical insurance claims for June 2005 through March 2009. Patients with no history in the preceding 9 months of myocardial infarction, ischemic stroke, or coronary revascularization procedure were assigned to the exenatide-initiated or non–exenatide-initiated cohorts based on the first new prescription filled and reassigned if exenatide was prescribed or discontinued. Incident CVD events (myocardial infarction, ischemic stroke, or coronary revascularization procedure) were identified by ICD-9-CM diagnosis codes. Patient outcomes were adjusted for differences in clinical and demographic characteristics and compared using propensity score–weighted discrete time survival analysis with time-varying exposure to exenatide. RESULTS A total of 39,275 patients with type 2 diabetes were treated with exenatide twice daily, and 381,218 patients were treated with other glucose-lowering therapies. Patients who initiated exenatide were more likely to have prior ischemic heart disease, obesity, hyperlipidemia, hypertension, and/or other comorbidities at baseline. Exenatide-treated patients were less likely to have a CVD event than non–exenatide-treated patients (hazard ratio 0.81; 95% CI 0.68–0.95; P = 0.01) and lower rates of CVD-related hospitalization (0.88; 0.79–0.98; P = 0.02) and all-cause hospitalization (0.94; 0.91–0.97; P &amp;lt; 0.001). CONCLUSIONS Exenatide twice-daily treatment was associated with a lower risk of CVD events and hospitalizations than treatment with other glucose-lowering therapies.
Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs.
Authors: S Banai, M T Jaklitsch, M Shou, D F Lazarous, M Scheinowitz, S Biro, S E Epstein, E F Unger
Journal: Circulation (1994)

BACKGROUND Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that is angiogenic in vitro and in vivo. It has been hypothesized that VEGF plays a role in myocardial collateral formation; however, the effects of VEGF on collateral flow to ischemic myocardium are unknown. METHODS AND RESULTS We studied the effect of VEGF on collateral blood flow in dogs subjected to gradual occlusion of the left circumflex coronary artery (LCx). Beginning 10 days after placement of an LCx-constricting device, VEGF 45 micrograms (n = 9) or saline (n = 12) was administered daily via an indwelling catheter in the distal LCx, at a point just beyond the occlusion. Treatment was maintained for 28 days. Collateral blood flow was determined with microspheres 7 days before treatment, immediately before treatment (day 0), and 7, 14, 21, and 28 days into the treatment period. Collateral blood flow was quantified during chromonar-induced maximal vasodilation and expressed as a collateral zone/normal zone (CZ/NZ) ratio. Treatment with VEGF was associated with a 40% increase in collateral blood flow (final CZ/NZ blood flow ratios of 0.49 +/- 0.06 and 0.35 +/- 0.02 in the VEGF-treated and control groups, respectively, P = .0037) as well as an 89% increase in the numerical density of intramyocardial distribution vessels (&gt; 20 microns diameter) in the CZ (6.6 +/- 1.4 versus 3.5 +/- 0.7 vessels/mm2 in VEGF-treated and control dogs, respectively, P &lt; .05). CONCLUSIONS We conclude that intracoronary VEGF enhances the development of small coronary arteries supplying ischemic myocardium, resulting in marked augmentation of maximal collateral blood flow delivery. These results demonstrate the feasibility of pharmacological enhancement of collateral growth and suggest a new therapeutic approach for the treatment of myocardial ischemia.
Anaerobic heat production by the heart.
Authors: W A Neill, W E Huckabee
Journal: Journal of Clinical Investigation (1966)

02 60% sat. 2 (beat) Control Art.02 37% sat.Control Art.02 31% sat. 3 (fib) Control Art.O2 22% sat.Art.O2 20% sat.Art.O2 13% sat.
Inhibition of diet-induced atheroma formation in transgenic mice expressing apolipoprotein E in the arterial wall.
Authors: H Shimano, J Ohsuga, M Shimada, Y Namba, T Gotoda, K Harada, M Katsuki, Y Yazaki, N Yamada
Journal: Journal of Clinical Investigation (1995)

Apolipoprotein E (apoE) plays a crucial role in lipoprotein metabolism both in plasma and in peripheral tissues. To test whether apoE in the vascular wall has a direct and local effect on atherogenesis, we established transgenic mice expressing human apoE under control of H2 Ld promoter. Studies on mRNA levels and immunohistochemistry demonstrated that this line was characterized by high expression of human apoE in the arterial wall while its expression was relatively low in other tissues as compared with the respective endogenous expression of mouse apoE. They showed no difference in plasma cholesterol levels and lipoprotein profile from controls when fed both normal and atherogenic diets. However, after 24 wk of an atherogenic diet, the formation of fatty streak lesions in proximal aorta was markedly inhibited in transgenic mice as compared with controls. Both lesion area and esterified cholesterol content were < 30% of those in controls. In a tissue cholesterol labeling study with 3H-cholesterol, the specific activity of aorta cholesterol was much less in transgenic mice, suggesting that apoE enhances cholesterol efflux from the aortic wall into plasma. Thus, apoE has anti-atherogenic action which is mediated via enhancing reverse cholesterol transport from arterial wall.
The Sleep Apnea Syndromes
Authors: C Guilleminault, A Tilkian, W C Dement
Journal: Annual Review of Medicine (1976)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Evaluation of next generation sequencing platforms for population targeted sequencing studies
Authors: Olivier Harismendy, Pauline C Ng, Robert L Strausberg, Xiaoyun Wang, Timothy B Stockwell, Karen Y Beeson, Nicholas J Schork, Sarah S Murray, Eric J Topol, Samuel Levy, Kelly A Frazer
Journal: Genome biology (2009)

Abstract Background Next generation sequencing (NGS) platforms are currently being utilized for targeted sequencing of candidate genes or genomic intervals to perform sequence-based association studies. To evaluate these platforms for this application, we analyzed human sequence generated by the Roche 454, Illumina GA, and the ABI SOLiD technologies for the same 260 kb in four individuals. Results Local sequence characteristics contribute to systematic variability in sequence coverage (&gt;100-fold difference in per-base coverage), resulting in patterns for each NGS technology that are highly correlated between samples. A comparison of the base calls to 88 kb of overlapping ABI 3730xL Sanger sequence generated for the same samples showed that the NGS platforms all have high sensitivity, identifying &gt;95% of variant sites. At high coverage, depth base calling errors are systematic, resulting from local sequence contexts; as the coverage is lowered additional 'random sampling' errors in base calling occur. Conclusions Our study provides important insights into systematic biases and data variability that need to be considered when utilizing NGS platforms for population targeted sequencing studies.
Three dose regimens of fulvestrant in postmenopausal Japanese women with advanced breast cancer: results from a double-blind, phase II comparative study (FINDER1)
Authors: S. Ohno, Y. Rai, H. Iwata, N. Yamamoto, M. Yoshida, H. Iwase, N. Masuda, S. Nakamura, H. Taniguchi, S. Kamigaki, S. Noguchi
Journal: Annals of Oncology (2010)
Randomized Pharmacokinetic and Pharmacodynamic Study of Docetaxel: Dosing Based on Body-Surface Area Compared With Individualized Dosing Based on Cytochrome P450 Activity Estimated Using a Urinary Metabolite of Exogenous Cortisol
Authors: Noboru Yamamoto, Tomohide Tamura, Haruyasu Murakami, Tatsu Shimoyama, Hiroshi Nokihara, Yutaka Ueda, Ikuo Sekine, Hideo Kunitoh, Yuichiro Ohe, Tetsuro Kodama, Mikiko Shimizu, Kazuto Nishio, Naoki Ishizuka, Nagahiro Saijo
Journal: Journal of Clinical Oncology (2005)

Docetaxel is metabolized by cytochrome P450 (CYP3A4) enzyme, and the area under the concentration-time curve (AUC) is correlated with neutropenia. We developed a novel method for estimating the interpatient variability of CYP3A4 activity by the urinary metabolite of exogenous cortisol (6-beta-hydroxycortisol [6-beta-OHF]). This study was designed to assess whether the application of our method to individualized dosing could decrease pharmacokinetic (PK) and pharmacodynamic (PD) variability compared with body-surface area (BSA) -based dosing.Fifty-nine patients with advanced non-small-cell lung cancer were randomly assigned to either the BSA-based arm or individualized arm. In the BSA-based arm, 60 mg/m(2) of docetaxel was administered. In the individualized arm, individualized doses of docetaxel were calculated from the estimated clearance (estimated clearance = 31.177 + [7.655 x 10(-4) x total 6-beta-OHF] - [4.02 x alpha-1 acid glycoprotein] - [0.172 x AST] - [0.125 x age]) and the target AUC of 2.66 mg/L . h.In the individualized arm, individualized doses of docetaxel ranged from 37.4 to 76.4 mg/m(2) (mean, 58.1 mg/m(2)). The mean AUC and standard deviation (SD) were 2.71 (range, 2.02 to 3.40 mg/L . h) and 0.40 mg/L . h in the BSA-based arm, and 2.64 (range, 2.15 to 3.07 mg/L . h) and 0.22 mg/L . h in the individualized arm, respectively. The SD of the AUC was significantly smaller in the individualized arm than in the BSA-based arm (P < .01). The percentage decrease in absolute neutrophil count (ANC) averaged 87.1% (range, 59.0 to 97.7%; SD, 8.7) in the BSA-based arm, and 87.4% (range, 78.0 to 97.2%; SD, 6.1) in the individualized arm, suggesting that the interpatient variability in percent decrease in ANC was slightly smaller in the individualized arm.The individualized dosing method based on the total amount of urinary 6-beta-OHF after cortisol administration can decrease PK variability of docetaxel.
Cerebrovascular disease in The Count of Monte Cristo
Authors: J. Goodwin
Journal: Journal of the Royal Society of Medicine (2003)

Dr Williams has written a most interesting analysis of cerebrovascular disease as depicted in Dumas' The Count of Monte Cristo (August 2003, JRSM1). In the case of Abbe Faria, Dumas portrays an old man who had three successive episodes of cerebral apoplexy with effusion that resulted in hemiplegia, probably referring to intracerebral haemorrhages, the last of which was fatal. Faria's father had died in exactly the same way after three episodes of cerebral apoplexy. Dr Williams mentions Osler-Rendu-Weber syndrome and Sturge-Weber syndrome as inheritable causes of recurrent cerebral haemorrhage. I would like to suggest adding cerebral amyloid angiopathy to that differential diagnosis since it is an autosomal dominant hereditary cause of recurrent lobar cerebral haemorrhage.
CD11b facilitates the development of peripheral tolerance by suppressing Th17 differentiation
Authors: Driss Ehirchiou, Ying Xiong, Guangwu Xu, Wanjun Chen, Yufang Shi, Li Zhang
Journal: The Journal of Experimental Medicine (2007)

Antigen-induced immune suppression, like T cell activation, requires antigen-presenting cells (APCs); however, the role of APCs in mediating these opposing effects is not well understood, especially in vivo. We report that genetic inactivation of CD11b, which is a CD18 subfamily of integrin receptors that is highly expressed on APCs, abolishes orally induced peripheral immune tolerance (oral tolerance) without compromising APC maturation or antigen-specific immune activation. The defective oral tolerance in CD11b−/− mice can be restored by adoptive transfer of wild-type APCs. CD11b deficiency leads to enhanced interleukin (IL) 6 production by APCs, which subsequently promotes preferential differentiation of naive T cells to T helper 17 (Th17) cells, which are a T cell lineage characterized by their production of IL-17. Consequently, antigen feeding and immunization of CD11b−/− mice results in significant production of IL-17 within the draining lymph nodes that interferes with the establishment of oral tolerance. Together, we conclude that CD11b facilitates oral tolerance by suppressing Th17 immune differentiation.
Predicting patient attitudes to asthma medication.
Authors: L M Osman, I T Russell, J A Friend, J S Legge, J G Douglas
Journal: Thorax (1993)

BACKGROUND--Studies of patient attitudes to asthma and its control have focused on crisis action, and little attention has been paid to attitudes to regular preventive medication. It is not clear whether attitudes to regular medication are related to the degree of distress or interference with life perceived by patients as being caused by their asthma. For this reason this study examined how far dislike of medication related to dislike of other aspects of interference of asthma with daily life. METHODS--Three hundred and ninety one patients were surveyed with a questionnaire which assessed their dislike of the interference of asthma with their physical, social, and emotional functioning, together with dislike of regular asthma medication. A response was received from 320 patients (82%). RESULTS--Four attitude clusters were identified. Recorded in descending factor order, these were (1) dislike of asthma medication, (2) dislike of disability, (3) dislike of public life interference, and (4) dislike of social and emotional interference. The attitude clusters were not related: in particular, dislike of asthma medication could not be predicted from other dislikes, or from asthma best function ratio (ratio of best recorded peak expiratory flow rate in the previous year to predicted value), age, or sex. The most significant predictors of the patients9 dislike of taking their own inhaled steroid were (1) dislike of using bronchodilator, (2) dislike of steroids generally, and (3) dislike of taking medicine every day. CONCLUSIONS--Patient attitudes to regular asthma medication are not related to general anxieties and dislikes about asthma, nor to the potential for asthma control as judged by the best function ratio. Patients were not always consistent in their attitude to inhaled steroids in general, nor to their own named inhaled steroid in particular. A general cluster of antimedication attitudes existed, independent of whether the medication was for prophylaxis or relief. Attitudes to asthma medication may be helpful in predicting patient behaviour.
MSC-based VEGF gene therapy in rat myocardial infarction model using facial amphipathic bile acid-conjugated polyethyleneimine
Authors: Hyung-Ho Moon, Min Kyung Joo, Hyejung Mok, Minhyung Lee, Ki-Chul Hwang, Sung Wan Kim, Ji Hoon Jeong, Donghoon Choi, Sun Hwa Kim
Journal: Biomaterials (2013)
1184 EXTRACORPOREAL LIVER SUPPORT WITH THE MOLECULAR ADSORBENT RECIRCULATING SYSTEM (MARS) IN PATIENTS WITH ACUTE-ON-CHRONIC LIVER FAILURE (AOCLF). THE RELIEF TRIAL
Authors: R. Bañnares, F. Nevens, F.S. Larsen, R. Jalan, A. Albillos, M. Dollinger
Journal: Journal of Hepatology (2010)
VEGFR2 induces c-Src signaling and vascular permeability in vivo via the adaptor protein TSAd
Authors: Zuyue Sun, Xiujuan Li, Sara Massena, Simone Kutschera, Narendra Padhan, Laura Gualandi, Vibeke Sundvold-Gjerstad, Karin Gustafsson, Wing Wen Choy, Guangxiang Zang, My Quach, Leif Jansson, Mia Phillipson, Md Ruhul Abid, Anne Spurkland, Lena Claesson-Welsh
Journal: The Journal of Experimental Medicine (2012)

Regulation of vascular endothelial (VE) growth factor (VEGF)–induced permeability is critical in physiological and pathological processes. We show that tyrosine phosphorylation of VEGF receptor 2 (VEGFR2) at Y951 facilitates binding of VEGFR2 to the Rous sarcoma (Src) homology 2-domain of T cell–specific adaptor (TSAd), which in turn regulates VEGF-induced activation of the c-Src tyrosine kinase and vascular permeability. c-Src was activated in vivo and in vitro in a VEGF/TSAd-dependent manner, and was regulated via increased phosphorylation at pY418 and reduced phosphorylation at pY527. Tsad silencing blocked VEGF-induced c-Src activation, but did not affect pathways involving phospholipase Cγ, extracellular regulated kinase, and endothelial nitric oxide. VEGF-induced rearrangement of VE–cadherin–positive junctions in endothelial cells isolated from mouse lungs, or in mouse cremaster vessels, was dependent on TSAd expression, and TSAd formed a complex with VE-cadherin, VEGFR2, and c-Src at endothelial junctions. Vessels in tsad−/− mice showed undisturbed flow and pressure, but impaired VEGF-induced permeability, as measured by extravasation of Evans blue, dextran, and microspheres in the skin and the trachea. Histamine-induced extravasation was not affected by TSAd deficiency. We conclude that TSAd is required for VEGF-induced, c-Src-mediated regulation of endothelial cell junctions and for vascular permeability.
Unraveling the mind
Authors: Philip Gerrans
Journal: Behavioral and Brain Sciences (2013)

A radical interpretation of the predictive coding approach suggests that the mind is "seamless" - that is, that cancellation of error signals can propagate smoothly from highest to lowest levels of the control hierarchy, dissolving a distinction between belief and perception. Delusions of alien control provide a test case. Close examination suggests that while they are evidence of predictive coding within the cortex, they are not evidence for the seamless interpretation.
Decreased High–Molecular Weight Adiponectin–to–Total Adiponectin Ratio in Sera Is Associated With Insulin Resistance in Japanese Metabolically Obese, Normal-Weight Men With Normal Glucose Tolerance
Authors: Akira Katsuki, Mina Suematsu, Esteban C. Gabazza, Shuichi Murashima, Kaname Nakatani, Kenji Togashi, Yutaka Yano, Yashuhiro Sumida
Journal: Diabetes Care (2006)

Adiponectin is a key regulator of insulin resistance. Recent studies on multimer formation in human blood have demonstrated that high–molecular weight (HMW) adiponectin is the active form of the protein (1–3). Recently, Hara et al. (3) demonstrated that the ratio of HMW adiponectin to total adiponetin (HMWR) in systemic circulation is useful for the prediction of insulin resistance and metabolic syndrome.

Metabolically obese, normal-weight (MONW) subjects (BMI <25 kg/m2) are characterized by excess visceral fat area (VFA; ≥100 cm2 by abdominal computed tomography scanning) and insulin resistance (4–6). In addition, we previously demonstrated that the …