tbuckley/cabot-search huggingface dataset:
Radio-deoxynucleoside Analogs used for Imaging <i>tk</i> Expression in a Transgenic Mouse Model of Induced Hepatocellular Carcinoma
Authors: Haibin Tian, Xincheng Lu, Hong Guo, David Corn, Joseph Molter, Bingcheng Wang, Guangbin Luo, Zhenghong Lee
Journal: Theranostics (2012)

Purpose: A group of radiolabeled thymidine analogs were developed as radio-tracers for imaging herpes viral thymidine kinase (HSV1-tk) or its variants used as reporter gene.A transgenic mouse model was created to express tk upon liver injury or naturally occurring hepatocellular carcinoma (HCC).The purpose of this study was to use this unique animal model for initial testing with radio-labeled thymidine analogs, mainly a pair of newly emerging nucleoside analogs, D-FMAU and L-FMAU.Methods: A transgeneic mouse model was created by putting a fused reporter gene system, firefly luciferase (luc) and HSV1-tk, under the control of mouse alpha fetoprotein (Afp) promoter.Initial multimodal imaging, which was consisted of bioluminescent imaging (BLI) and planar gamma scintigraphy with [ 125 I]-FIAU, was used for examining the model creation in the new born and liver injury in the adult mice.Carcinogen diethylnitrosamine (DEN) was then administrated to induce HCC in these knock-in mice such that microPET imaging could be used to track the activity of Afp promoter during tumor development and progression by imaging tk expression first with [ 18 F]-FHBG.Dynamic PET scans with D-[ 18 F]-FMAU and L-[ 18 F]-FMAU were then performed to evaluate this pair of relatively new tracers.Cells were derived from these liver tumors for uptake assays using H-3 labeled version of PET tracers.Results: The mouse model with dual reporters: HSV1-tk and luc placed under the transcriptional control of an endogenous Afp promoter was used for imaging studies.The expression of the Afp gene was highly specific in proliferative hepatocytes, in regenerative liver, and in developing fetal liver, and thus provided an excellent indicator for liver injury and cancer development in adult mice.Both D-FMAU and L-FMAU showed stable liver tumor uptake where the tk gene was expressed under the Afp promoter.The performance of this pair of tracers was slightly different in terms of signal-to-background ratio as well as tracer clearance.Conclusion: The newly created knock-in mouse model was used to demonstrate the use of the dual-reporter genes driven by well-characterized cancer-specific transcriptional units in conjunction with in vivo imaging as a paradigm in studying naturally occurring cancer in live animals.While BLI is suitable for small animal imaging with luc expression, PET with L-FMAU seemed be the choice for liver injury or liver cancer imaging with this animal model for future investigations.
Posttraumatic Pleural-Fluid and Blood Eosinophilia
Authors: U. Nanda Kumar
Journal: JAMA (1975)

THE FIRST case, to our knowledge, of simultaneous pleural-fluid and blood eosinophilia following chest trauma was recently reported by Beekman et al.<sup>1</sup>We report a similar case. <h3>Report of a Case</h3> A 68-year-old man fell and injured the left side of his chest. Six weeks later he was admitted to the Veterans Hospital, Wood, because of persistent chest pain unrelieved by a combination of aspirin and caffeine (Anacin). Past medical history was unremarkable except for a diagnosis of pharyngoesophageal (Zenker) diverticulum. He had no history of pleurisy or allergies and had been well before the accident. On examination he was afebrile, but there was swelling and tenderness over the lateral aspect of the left lower chest. Dullness on percussion and diminished breath sounds were noted in the left infrascapular and infra-axillary areas. Chest roentgenogram (Figure) showed blunting of the left costophrenic angle, and decubitus film confirmed the presence of
Recruitment of Gr-1+ monocytes is essential for control of acute toxoplasmosis
Authors: Paul M. Robben, Marie LaRegina, William A. Kuziel, L. David Sibley
Journal: The Journal of Experimental Medicine (2005)

Circulating murine monocytes comprise two largely exclusive subpopulations that are responsible for seeding normal tissues (Gr-1-/CCR2-/CX3CR1high) or responding to sites of inflammation (Gr-1+/CCR2+/CX3CR1lo). Gr-1+ monocytes are recruited to the site of infection during the early stages of immune response to the intracellular pathogen Toxoplasma gondii. A murine model of toxoplasmosis was thus used to examine the importance of Gr-1+ monocytes in the control of disseminated parasitic infection in vivo. The recruitment of Gr-1+ monocytes was intimately associated with the ability to suppress early parasite replication at the site of inoculation. Infection of CCR2-/- and MCP-1-/- mice with typically nonlethal, low doses of T. gondii resulted in the abrogated recruitment of Gr-1+ monocytes. The failure to recruit Gr-1+ monocytes resulted in greatly enhanced mortality despite the induction of normal Th1 cell responses leading to high levels of IL-12, TNF-alpha, and IFN-gamma. The profound susceptibility of CCR2-/- mice establishes Gr-1+ monocytes as necessary effector cells in the resistance to acute toxoplasmosis and suggests that the CCR2-dependent recruitment of Gr-1+ monocytes may be an important general mechanism for resistance to intracellular pathogens.
Global Gene Expression Profiling of Pleural Mesotheliomas: Overexpression of Aurora Kinases and <i>P16/CDKN2A</i> Deletion as Prognostic Factors and Critical Evaluation of Microarray-Based Prognostic Prediction
Authors: Fernando López-Ríos, Shannon Chuai, Raja Flores, Shigeki Shimizu, Takatoshi Ohno, Kazuhiko Wakahara, Peter B. Illei, Sanaa Hussain, Lee Krug, Maureen F. Zakowski, Valerie Rusch, Adam B. Olshen, Marc Ladanyi
Journal: Cancer Research (2006)

Most gene expression profiling studies of mesothelioma have been based on relatively small sample numbers, limiting their statistical power. We did Affymetrix U133A microarray analysis on 99 pleural mesotheliomas, in which multivariate analysis showed advanced-stage, sarcomatous histology and P16/CDKN2A homozygous deletion to be significant independent adverse prognostic factors. Comparison of the expression profiles of epithelioid versus sarcomatous mesotheliomas identified many genes significantly overexpressed among the former, including previously unrecognized ones, such as uroplakins and kallikrein 11, both confirmed by immunohistochemistry. Examination of the gene expression correlates of survival showed that more aggressive mesotheliomas expressed higher levels of Aurora kinases A and B and functionally related genes involved in mitosis and cell cycle control. Independent confirmation of the negative effect of Aurora kinase B was obtained by immunohistochemistry in a separate patient cohort. A role for Aurora kinases in the aggressive behavior of mesotheliomas is of potential clinical interest because of the recent development of small-molecule inhibitors. We then used our data to develop microarray-based predictors of 1 year survival; these achieved a maximal accuracy of 68% in cross-validation. However, this was inferior to prognostic prediction based on standard clinicopathologic variables and P16/CDNK2A status (accuracy, 73%), and adding the microarray model to the latter did not improve overall accuracy. Finally, we evaluated three recently published microarray-based outcome prediction models, but their accuracies ranged from 63% to 67%, consistently lower than reported. Gene expression profiling of mesotheliomas is an important discovery tool, but its power in clinical prognostication has been overestimated.
P122 The use of impulse oscillometry (IOS) to study fractal scaling and sample entropy in airway resistance time series in severe asthma
Authors: I. Umar, D. Desai, S. Corkill, M. Shelley, A. Singapuri, C. Brightling, S. Siddiqui
Journal: Thorax (2010)

<h3>Introduction</h3> Severe asthma affects airway calibre and can be monitored using IOS. Sample entropy (SampEn) is a measure of complexity and is defined as the probability that sequences of patterns (template size) in time series which are initially closely related, that is, within a fraction of the standard deviation (tolerance level) of the time-series remain so within subsequent time frames. Fractal scaling is a measure of self similarity and scale invariance measured in a time-series and quantifies the memory found within as a consequence. We hypothesised that fractal scaling and SampEn will be useful in characterising severe asthma. <h3>Methods</h3> 66 GINAstage 4–5 severe asthmatics (Mean(Sem) age; 54.1(1.4), Sex M:F; 31:35, post-bronchodilator FEV<sub>1</sub>% predicted; 81.02 (2.7)%) and 27 Controls (Mean(Sem) age; 48.4(2.2), Sex M:F;9:18, post-bronchodilator FEV<sub>1</sub>% predicted; 108.2 (2.8)%) were recruited. Impulse oscillometry was performed at 5–35 Hz, with impulses triggered every 0.2 s for 150 s, at baseline and 15 min after 400 mcg inhaled salbutamol. Detrended fluctuation analysis was used to derive the fractal scaling exponent α<sub>1</sub>. SampEn was derived using a custom program. SampEn and α<sub>1</sub> were both obtained from airway resistance at 10 Hz over the 150 s time-series. Triplicate measurements of 150 s were repeated in 18 randomly selected asthmatics from our cohort after 6 months. <h3>Results</h3> SampEn was significantly increased compared to controls (Abstract P122 Table 1) and correlated significantly with exacerbation frequency from the previous 12 months (Asthma Baseline- p=0.007, rs=0.3; Post-Bronchodilator- p=0.009, rs=0.3). Fractal scaling was also found to be present in airway resistance in severe asthma (α<sub>1</sub>=0.94 (0.03)) and showed an inverse relationship with SampEn (p=0.0352, r=−0.4). Increased SampEn was associated with worse ACQ scores (p=0.027, rs=0.3) and lower AQLQ scores (p=0.023, rs=−0.2). SampEn measurements were repeatable (an Intra-class correlation of 0.74) in the triplicate series. In keeping with other studies, airway resistance was significantly increased in severe asthma. <h3>Conclusions</h3> SampEn a measure of complexity is (1) increased in severe asthma (2) a repeatable measure (3) associated with a lower quality of life and exacerbation frequency. The ability of this technique to monitor asthma stability and to predict future exacerbations by stochastic modelling needs to be explored.
Effects of Troglitazone in Young First-Degree Relatives of Patients With Type 2 Diabetes
Authors: Klaus Levin, Ole Hother-Nielsen, Jan Erik Henriksen, Henning Beck-Nielsen
Journal: Diabetes Care (2004)

OBJECTIVE—Insulin resistance is a key characteristic of first-degree relatives of patients with type 2 diabetes. We therefore treated young, glucose-tolerant relatives with the insulin action enhancer troglitazone in order to determine the effects on insulin sensitivity, glucose metabolism, and glycogen synthase activity. RESEARCH DESIGN AND METHODS—Relatives were randomized in a double-blind manner and treated for 12 weeks with either 200 mg troglitazone or placebo. Before and after treatment, an oral glucose tolerance test (OGTT) and a euglycemic-hyperinsulinemic clamp (40 mU · m−2 · min−1) were performed, including 3-3H glucose infusion, glycolytic flux calculations, indirect calorimetry, and muscle biopsies. RESULTS—Twelve relatives received troglitazone and 12 placebo (aged 30.8 ± 2.0 vs. 30.3 ± 1.6 years, BMI 29.6 ± 0.8 vs. 30.5 ± 1.3 kg/m2; means ± SE). Area under the curve (AUC) for plasma glucose at the second OGTT was unchanged after troglitazone. In contrast, troglitazone reduced fasting (from 70.3 ± 6.9 to 52.2 ± 5.8 vs. 73.6 ± 11.0 to 73.3 ± 6.5 pmol/l, P &amp;lt; 0.02) and AUC plasma insulin (mean [CI] from 335.7 [230.9–488.1] to 277.4 [179.4–428.8] vs. 313.8 [218.2–451.2] to 353.9 [208.3–601.3] pmol/l, P &amp;lt; 0.05). Additionally, fasting plasma triglycerides were reduced by troglitazone (from 1.86 ± 0.33 to 1.38 ± 0.27 vs. 2.22 ± 0.44 to 2.35 ± 0.46 mmol/l, P &amp;lt; 0.01). Insulin-stimulated glucose disposal increased in the troglitazone group (from 208.3 ± 23.7 to 263.5 ± 30.4 vs. 197.1 ± 20.0 to 200.8 ± 20.8 mg · m−2 · min−1, P &amp;lt; 0.02) mainly due to increased glucose storage (from 99.9 ± 17.9 to 146.0 ± 25.3 vs. 87.1 ± 16.7 to 87.9 ± 15.7 mg · m−2 · min−1, P &amp;lt; 0.02), which took place without altering insulin-stimulated glycogen synthase activity. CONCLUSIONS—In glucose-tolerant first-degree relatives, treatment with troglitazone improved insulin sensitivity almost 50%, primarily due to increased glucose storage. It is suggested that the use of insulin action enhancers can be especially valuable in this group of subjects with a known high risk for developing type 2 diabetes.
Clinicopathologic characteristics of primary bronchial cancer metastasizing to the brain
Authors: Eszter Podmaniczky, Katalin Fabian, Gyorgy Losonczy, Judit Moldvay
Journal: European Respiratory Journal (2011)

Brain metastasis is one of the most important factors influencing the quality of life in lung cancer patients with metastatic disease.  We analyzed the clinicopathological data of 163 lung cancer patients with brain metastasis (96 men, 67 women). The brain metastasis was diagnosed either by CT (n=119) or MRI (n=44). The lung cancer was diagnosed according to bronchoscopy, surgical resection VATS biopsy or transtoracic needle biopsy. The lung tumor was diagnosed cytologically in 43 cases, and histologically in 120 cases.  The histological distribution was the following: 67 adenocarcinomas, 43 small cell lung cancers, 22 squamous cell cancers, 12 anaplastic carcinomas,1 adenosquamous carcinoma, 2 atypical carcinoid tumors and 16 malignant tumors.  At the time of diagnosis 24% of our patients were operable, while in 98 cases (63.6%) the desease were already at stage IV.  Central tumors were found in 64.3%, and peripheral in 35.7%. In 103 cases (64%) the tumor was in the right lung. The upper lobe was concerned in 92 cases (56.4%). There were 58 tumors in the right upper lobe, and 34 in the left upper lobe. 20 tumors were in the right lower lobe, 9 in the left lower lobe,11 in the middle lobe.  When compared small cell lung cancer to adenocarcinoma, the proportion of early metastasis (  Brain metastasis was observed most frequently in adenocarcinomas localized to the upper lobes, and among them the proportion of early metastasis was very high. According to our results, especially in case of upper lobe adenocarcinoma, the exclusion of intracranial metastasis by brain MRI is highly desirable before surgical resection of lung cancer.
Noradrenaline turnover and metabolism in myocardium following aortic constriction in rats
Authors: P. K Ganguly, G. R Sherwood
Journal: Cardiovascular Research (1991)

Study objective — The aim was to provide meaningful information on the function of the sympathetic system soon after an increased pressure overload on the heart. Design — Noradrenaline storage, turnover, uptake, and synthesis were investigated at 3, 14, and 28 d after aortic banding in rats. Sham operated rats without aortic banding were used as control group. Experimental material — Left ventricle, spleen, and kidney from male Sprague-Dawley rats (175-200 g) were used in this study. Measurements and main results — Cardiac noradrenaline concentration was decreased at 3 d and 28 d after banding and increased at 14 d; left ventricular mass was increased from 14 d onwards. The rate of change in the specific activity of myocardial noradrenaline (noradrenaline turnover) as well as dopamine β hydroxylase, an enzyme for noradrenaline synthesis, was unaltered at 3 d, increased at 14 d, and decreased at 28 d after aortic banding. Myocardial [3H]noradrenaline uptake, on the other hand, was decreased at all time points studied. The changes observed in the myocardium at day 14 were specific since noradrenaline turnover rate was unaltered in other peripheral organs such as spleen and kidney. Furthermore, after ganglionic blockade with pentolinium, both sham operated control and banded animals had identical, low noradrenaline turnover rate constants, and significant restoration of cardiac weight and noradrenaline stores was observed in the hearts from banded animals. Conclusions — Noradrenaline turnover and metabolism are altered soon after imposing increased workload on heart. Whether or not the changes in the sympathetic activity are a prerequisites for hypertrophy still remains to be seen.
Suppression of Inhibitor of Differentiation 2, a Target of Mutant p53, Is Required for Gain-of-Function Mutations
Authors: Wensheng Yan, Gang Liu, Ariane Scoumanne, Xinbin Chen
Journal: Cancer Research (2008)

Abstract Overexpression of mutant p53 is a common theme in human tumors, suggesting a tumor-promoting gain-of-function for mutant p53. To elucidate whether and how mutant p53 acquires its gain-of-function, mutant p53 is inducibly knocked down in the SW480 colon cancer cell line, which contains mutant p53(R273H/P309S), and the MIA PaCa-2 pancreatic cancer cell line, which contains mutant p53(R248W). We found that knockdown of mutant p53 markedly inhibits cell proliferation. In addition, knockdown of mutant p53 sensitizes tumor cells to growth suppression by various chemotherapeutic drugs. To determine whether a gene involved in cell growth and survival is regulated by mutant p53, gene expression profiling analysis was performed and showed that the expression level of Id2, a member of the inhibitor of differentiation (Id) family, was markedly increased upon knockdown of mutant p53. To confirm this, Northern blot analysis was performed and showed that the expression level of Id2 was regulated by various mutant p53s in multiple cell lines. In addition, we found that the Id2 promoter is responsive to mutant but not wild-type p53, and mutant p53 binds to the Id2 promoter. Consistent with these observations, expression of endogenous Id2 was found to be inhibited by exogenous mutant p53 in p53-null HCT116 cells. Finally, we showed that knockdown of Id2 can restore the proliferative potential of tumor cells inhibited by withdrawal of mutant p53. Together, these findings suggest that one mechanism by which mutant p53 acquires its gain-of-function is through the inhibition of Id2 expression. [Cancer Res 2008;68(16):6789–96]
Alterations in Atrial Electrophysiology and Tissue Structure in a Canine Model of Chronic Atrial Dilatation Due to Mitral Regurgitation
Authors: Sander Verheule, Emily Wilson, Thomas Everett, Sujata Shanbhag, Catherine Golden, Jeffrey Olgin
Journal: Circulation (2003)

Background— Clinically, chronic atrial dilatation is associated with an increased incidence of atrial fibrillation (AF), but the underlying mechanism is not clear. We have investigated atrial electrophysiology and tissue structure in a canine model of chronic atrial dilatation due to mitral regurgitation (MR). Methods and Results— Thirteen control and 19 MR dogs (1 month after partial mitral valve avulsion) were studied. Dogs in the MR group were monitored using echocardiography and Holter recording. In open-chest follow-up experiments, electrode arrays were placed on the atria to investigate conduction patterns, effective refractory periods, and inducibility of AF. Alterations in tissue structure and ultrastructure were assessed in atrial tissue samples. At follow-up, left atrial length in MR dogs was 4.09±0.45 cm, compared with 3.25±0.28 at baseline ( P &lt;0.01), corresponding to a volume of 205±61% of baseline. At follow-up, no differences in atrial conduction pattern and conduction velocities were noted between control and MR dogs. Effective refractory periods were increased homogeneously throughout the left and right atrium. Sustained AF (&gt;1 hour) was inducible in 10 of 19 MR dogs and none of 13 control dogs ( P &lt;0.01). In the dilated MR left atrium, areas of increased interstitial fibrosis and chronic inflammation were accompanied by increased glycogen ultrastructurally. Conclusions— Chronic atrial dilatation in the absence of overt heart failure leads to an increased vulnerability to AF that is not based on a decrease in wavelength.
Quality Indicators and Monitoring of Mental Health Services: What Do Frontline Providers Think?
Authors: Marcia Valenstein, Allison Mitchinson, David L. Ronis, Jeffrey A. Alexander, Sonia A. Duffy, Thomas J. Craig, Kristen Lawton Barry
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Many health care organizations are giving feedback to mental health care providers about their performance on quality indicators. Mental health care providers may be more likely to respond to this feedback if they believe the indicators are meaningful and within their "sphere of influence." The authors surveyed frontline mental health care providers to elicit their perceptions of widely used indicators for quality monitoring in mental health services. METHOD: The survey was distributed to a stratified, random sample of 1,094 eligible mental health care providers at 52 Department of Veterans Affairs facilities; 684 (63%) returned the survey. The survey elicited perceptions of 21 widely used indicators in five quality domains (access, utilization, satisfaction, process, and outcomes). The data were analyzed with descriptive and multivariate methods. RESULTS: Most mental health care providers (65%) felt that feedback about these widely used indicators would be valuable in efforts to improve care; however, only 38% felt able to influence performance related to these monitors and just 13% were willing to accept incentives/risk for their performance. Providers were most positive about satisfaction monitors and preferentially included satisfaction, access, and process monitors in performance sets to measure overall quality. Despite providers' relatively positive views of monitors, 41% felt that monitoring programs did not assist them in improving care. Providers cited numerous barriers to improving care processes. CONCLUSIONS: Mental health care providers may be more receptive to monitoring efforts if satisfaction, access, and process monitors are emphasized. However, providers' views of monitoring programs appear to be less affected by concerns about specific monitors than by concerns about the accuracy of quality measurement and barriers to changing care processes.
Public policy for the poor? A randomised assessment of the Mexican universal health insurance programme
Authors: Gary King, Emmanuela Gakidou, Kosuke Imai, Jason Lakin, Ryan T Moore, Clayton Nall, Nirmala Ravishankar, Manett Vargas, Martha María Téllez-Rojo, Juan Eugenio Hernández Ávila, Mauricio Hernández Ávila, Héctor Hernández Llamas
Journal: The Lancet (2009)
The NT‐proBNP assay identifies very elderly nursing home residents suffering from pre‐clinical heart failure
Authors: Roberto Valle, Nadia Aspromonte, Sabrina Barro, Cristina Canali, Emanuele Carbonieri, Vincenzo Ceci, Maura Chinellato, Giovanni Gallo, Prospero Giovinazzo, Roberto Ricci, Loredano Milani
Journal: European Journal of Heart Failure (2004)