tbuckley/cabot-search huggingface dataset:
LOX-1 deletion alters signals of myocardial remodeling immediately after ischemia–reperfusion
Authors: C HU, A DANDAPAT, J CHEN, Y FUJITA, N INOUE, Y KAWASE, K JISHAGE, H SUZUKI, T SAWAMURA, J MEHTA
Journal: Cardiovascular Research (2007)

Chronic ischemia is associated with alterations in genes that result in myocardial remodeling. An important biochemical basis of cardiac remodeling is generation of reactive oxygen species (ROS). A few studies have suggested that acute ischemia triggers signals for remodeling. We examined the hypothesis that targeted deletion of lectin-like oxidized-LDL receptor (LOX-1) may inhibit signals related to cardiac remodeling.We generated LOX-1 knockout (KO) mice on C57BL/6 (wild-type mice) background, and subjected wild-type and KO mice to ischemia-reperfusion (I-R). The wild-type mice developed a marked reduction in left ventricular systolic pressure and +/-dp/dt(max) and an increase in left ventricular end-diastolic pressure following I-R, and this change was much less in the LOX-1 KO mice, indicating preservation of left ventricular function with LOX-1 deletion. There was evidence for marked oxidative stress (NADPH oxidase expression, malondialdehyde and 8-isoprostane) following I-R in the wild-type mice, much less so in the LOX-1 KO mice (P<0.01). In concert, collagen deposition (Masson's trichrome and Picro-sirius red staining) increased dramatically in the wild-type mice, but only half as much in the LOX-1 KO mice (P<0.01). Collagen staining data was corroborated with procollagen-I expression. Further, fibronectin and osteopontin expression increased in the wild-type mice, but to a much smaller extent in the LOX-1 KO mice (P<0.01).These findings provide compelling evidence that LOX-1 is a key modulator of cardiac remodeling which starts immediately following I-R.
Weekly paclitaxel as first-line chemotherapy in elderly advanced breast cancer patients: a phase II study of the Gruppo Italiano di Oncologia Geriatrica (GIOGer)
Authors: L. Del Mastro, F. Perrone, L. Repetto, L. Manzione, V. Zagonel, L. Fratino, D. Marenco, M. Venturini, E. Maggi, C. Bighin, T. Catzeddu, A. Venturino, R. Rosso
Journal: Annals of Oncology (2005)
Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Domenico Corrado, Mark S. Link, Hugh Calkins
Journal: New England Journal of Medicine (2017)

Arrhythmogenic right ventricular cardiomyopathy is a heritable heart-muscle disorder that causes progressive replacement of right ventricular myocardium by fibrofatty tissue. Mutations in genes encoding desmosomal proteins play a key role in the pathogenesis of the disease.
An unusual abdominal mass
Authors: P Grimison
Journal: Gut (2005)

Background: The role of intestinal transporter regulation in optimising nutrient absorption has been studied extensively in rodent and cell line models but not in human subjects.Aims: The aim of the present study was to investigate the response in vivo of zinc transporters in the human enterocyte to dietary zinc supplementation.Subjects: Eighteen patients who had previously undergone ileostomy, all free of any symptoms of inflammatory bowel disease.Methods: Subjects took a daily zinc supplement of 25 mg for 14 days in a double blind, placebo controlled, crossover trial.The effect of the supplement on expression in ileal biopsies of the zinc transporters SLC30A1, SLC30A4, SLC30A5, SLC39A1, SLC39A4, and metallothionein was measured by reverse transcription-polymerase chain reaction RT-PCR.Expression of SLC30A1, SLC30A5, and SLC39A4 was also examined by immunoblotting.Results: The zinc supplement reduced SLC30A1 mRNA (1.4-fold) together with SLC30A1, SLC30A5, and SLC39A4 protein (1.8-fold, 3.7-fold, and to undetectable levels, respectively) in ileal mucosa and increased metallothionein mRNA (1.7-fold).The supplement had no effect on expression of SLC30A4 or SLC39A1 mRNA.Localisation of SLC30A5 at the apical human enterocyte/colonocyte membrane and also at the apical membrane of Caco-2 cells was demonstrated by immunohistochemistry. Commensurate with these observations in zinc supplemented human subjects, SLC30A1, SLC30A5, and SLC39A4 mRNA and protein were reduced in Caco-2 cells cultured at 200 mM compared with 100 mM zinc.Conclusions: These observations indicate that, in response to variations in dietary zinc intakes, regulated expression of plasma membrane zinc transporters in the human intestine contributes to maintenance of zinc status.
Automated quantitative coronary arteriography: morphologic and physiologic validation in vivo of a rapid digital angiographic method.
Authors: G B Mancini, S B Simon, M J McGillem, M T LeFree, H Z Friedman, R A Vogel
Journal: Circulation (1987)

Quantitative coronary arteriography has been shown to be useful in assessing the extent of coronary disease, its functional significance, and its response to therapeutic interventions. Most current methods rely either on hand-drawn arterial contours or automatic edge-detection algorithms applied to 35 mm cineangiograms. To assess the performance in vivo of a new, fully automatic, rapid coronary quantitation program, dogs were instrumented with precision-drilled, plastic cylinders to create intraluminal stenoses in the left anterior descending and/or circumflex arteries, as well as with high-fidelity micromanometers and electromagnetic flow probes. Stenosis diameters ranged from 0.83 to 1.83 mm. Biplane, on-line, digital coronary angiograms and cineangiograms were recorded during standard selective coronary arteriography in the closed-chest preparation. The on-line digital images were analyzed in nonsubtracted and subtracted modes. Cineangiograms were digitized to allow coronary quantitation by the same computer program. There was an excellent correlation between known and measured minimal diameter stenoses (r = .87 to .98, SEE = 0.09 to 0.24 mm). Interobserver and intraobserver variability analysis showed high reproducibility (r = .90 to .97, SEE = 0.12 to 0.23 mm). The best results in both analyses were achieved by nonsubtracted digital imaging and the worst by cineradiography. Measures of percent diameter stenosis, percent area stenosis (geometric and videometric), and absolute minimal cross-sectional area (geometric and videometric) were all significantly correlated with independent measures of actual coronary flow reserve. This study provides direct anatomic and physiologic validation in vivo of a new and rapid coronary quantitation method suitable for analysis of both digital angiograms and cineangiograms.
Prevention of injury in karate.
Authors: H V Johannsen, F O Noerregaard
Journal: British Journal of Sports Medicine (1988)

The purpose of the study was to analyse the effect of knuckle protection on the type and incidence of injuries in traditional karate contests. Knuckle protection was mandatory at the Danish karate championships 1983 and 1986 (290 matches, 0.26 injuries per match), and prohibited at the championships 1984 and 1985 (620 matches, 0.25 injuries per match). Head injuries were more common in the tournaments where fist pads were used. The incidences of transitory psychomotor disturbances following blows to the head were comparable. The severity of head injuries, however, decreased; minor head injuries dominated when fist pads were used (66%, compared with 44% without fist pads, p less than 0.01) and there were fewer lacerations and fractures. Injuries to the fingers or hands were also fewer--1.3% compared with 11% without protection (p less than 0.01). The use of fist pads reduced considerably the number of injuries requiring treatment (from 42% to 16%, p less than 0.01). In conclusion; fist pads offer some protection against injuries, especially to the hands, but additional measures are needed.
Dual Targeting of mTOR and Aurora-A Kinase for the Treatment of Uterine Leiomyosarcoma
Authors: Kari J. Brewer Savannah, Elizabeth G. Demicco, Kristelle Lusby, Markus PH. Ghadimi, Roman Belousov, Eric Young, Yiqun Zhang, Kai-Lieh Huang, Alexander J. Lazar, Kelly K. Hunt, Raphael E. Pollock, Chad J. Creighton, Matthew L. Anderson, Dina Lev
Journal: Clinical Cancer Research (2012)

Abstract Purpose: The significance of mTOR activation in uterine leiomyosarcoma (ULMS) and its potential as a therapeutic target were investigated. Furthermore, given that effective therapies likely require combination mTOR blockade with inhibition of other targets, coupled with recent observations suggesting that Aurora-A kinase (Aurk-A) deregulations commonly occur in ULMS, the preclinical impact of dually targeting both pathways was evaluated. Experimental Design: Immunohistochemical staining was used to evaluate expression of activated mTOR components in a large (&amp;gt;200 samples) ULMS tissue microarray. Effects of mTOR blockade (using rapamycin) and Aurk-A inhibition (using MLN8237) alone and in combination on human ULMS cell growth, cell-cycle progression, and apoptosis were assessed in cellular assays. Drug interactions were determined via combination index analyses. The antitumor effects of inhibitors alone or in combination were evaluated in vivo. Results: Enhanced mTOR activation was seen in human ULMS samples. Increased pS6RP and p4EBP1 expression correlated with disease progression; p4EBP1 was found to be an independent prognosticator of patient outcome. Rapamycin inhibited growth and cell-cycle progression of ULMS cell strains/lines in culture. However, only a cytostatic effect on tumor growth was found in vivo. Combining rapamycin with MLN8237 profoundly (and synergistically) abrogated ULMS cells' growth in culture; interestingly, these effects were seen only when MLN8237 was preadministered. This novel therapeutic combination and scheduling regimen resulted in marked tumor growth inhibition in vivo. Conclusions: mTOR and Aurk-A pathways are commonly deregulated in ULMS. Preclinical data support further exploration of dual mTOR and Aurk-A therapeutic blockade for human ULMS. Clin Cancer Res; 18(17); 4633–45. ©2012 AACR.
A new method for measuring aerosol nebulizer output using radioactive tracers
Authors: AA Gatnash, ST Chandler, CK Connolly
Journal: European Respiratory Journal (1998)

Reproducibility and comparability of bronchial challenge tests depends critically on accurate assessment of nebulizer output. Evaporation during nebulization means that simple weighing is inaccurate, overestimating the delivered dose of active ingredient. We wanted to quantify this effect in the context of intermittent nebulization, using a dosimeter as used in bronchial provocation tests. Output of three types of nebulizer, from the MEFAR dosimeter, was measured by radioactive tracer, using a standard solution of technetium-99m-pertechnetate (1.5 kBq x mL(-1)) in 4 mL of normal saline. The aerosol was impacted by suction onto a microfilter, and the radioactivity measured. Nebulizers were weighed before and after nebulization. Ratio of nebulized volume calculated from the radioactivity on the filter, to the total volume loss by weight, was expressed as nebulized ratio. The effect on output of two concentrations of methacholine, two tracers of different weights, and change in temperature, were assessed. Nebulized ratio varied between 44.1-71.6%. Results were more consistent within the same type of nebulizer than between different makes. Neither changes in molar concentration nor molecular weight affected nebulizer output or nebulized ratio. Mean nebulized ratio was 58.5%, showing that calibration by weighing, overestimates the delivered dose by a factor of approximately two. Measuring radioactivity eluted from a microfilter, onto which nebulized output had been impacted proved to be a satisfactory method of calibration.
Cancer screening in the United States, 2014: A review of current American Cancer Society guidelines and current issues in cancer screening
Authors: Robert A. Smith, Deana Manassaram-Baptiste, Durado Brooks, Vilma Cokkinides, Mary Doroshenk, Debbie Saslow, Richard C. Wender, Otis W. Brawley
Journal: CA A Cancer Journal for Clinicians (2014)

Answer questions and earn CME/CNE Each year the American Cancer Society publishes a summary of its guidelines for early cancer detection, a report on data and trends in cancer screening rates, and select issues related to cancer screening. In this issue of the journal, we summarize current American Cancer Society cancer screening guidelines. In addition, the latest data on the use of cancer screening from the National Health Interview Survey is described, as are several issues related to screening coverage under the Patient Protection and Affordable Care Act, including the expansion of the Medicaid program.
A Mouse Model of Angiotensin II Slow Pressor Response
Authors: Noritaka Kawada, Enyu Imai, Alexsander Karber, William J. Welch, Christopher S. Wilcox
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. The slow pressor response to prolonged infusions of angiotensin II (AngII) entails a delayed rise in BP. This study investigated the hypothesis that the response depends on the generation of oxidative stress. The BP and renal functional response of mice to graded doses (200, 400, and 1000 ng · kg−1 · min−1) of subcutaneously infused AngII was studied. The SBP of conscious mice increased by day 3 at AngII1000 but showed a delayed rise by days 9 to 13 (slow pressor response) at the lower rates of AngII infusion. By day 13, there was a graded increase in SBP with the rate of AngII infusion (Vehicle, −2.6 ± 2.6%; AngII200, +14.1 ± 5.0%; AngII400, +31.9 ± 1.9%; AngII1000, +43.2 ± 5.5%). The MAP measured under anesthesia rose significantly (P < 0.001) with AngII400 at 14 d (Vehicle, 85 ± 2 mmHg; AngII400, 100 ± 3 mmHg). When studied at day 6, the MAP of AngII400 rats was not elevated (88 ± 2 mmHg; NS versus vehicle), yet the GFR was higher (1.05 ± 0.05 versus 1.25 ± 0.05 ml · min−1 · g−1; P < 0.05) accompanied by an increase in the filtration fraction (FF) (28.8 ± 1.2 versus 37.2 ± 0.8%; P < 0.001). From day 6 through day 14, the MAP had increased (P < 0.01) in AngII400, accompanied by a significant reduction in GFR to 1.05 ± 0.04 ml · min−1 · g−1 (P < 0.01) and elevation of renal vascular resistance (RVR) (day 6 versus day 14, 15.3 ± 0.6 versus 19.2 ± 1.2 mmHg · ml−1 · min−1 · g−1; P < 0.05). Renal excretion of 8-iso PGF2α was increased in AngII400 group at day 12 (2.52 ± 0.35 versus 5.85 ± 0.78 pg · day−1; P < 0.01). The permeant superoxide dismutase mimetic tempol reduced the effects of AngII400 on the SBP (−1.7 ± 5.8%; P < 0.01), the MAP (87 ± 4 mmHg; P < 0.01), and the RVR (15.2 ± 0.5 mmHg · ml−1 · min−1 · g−1; P < 0.05) at day 14 and the renal 8-iso PGF2α excretion (3.53 ± 0.71 pg · d−1; P < 0.05) at day 12. It is concluded that the AngII infused mouse is a valid model for the slow pressor response. There is an early rise in GFR and FF, consistent with increased postglomerular vascular resistance and a late rise in RVR with a fall in GFR, consistent with increased preglomerular vascular resistance that is accompanied by a rise in BP. There is evidence of increased oxidative stress that is implicated in the increase in the BP and RVR in this model.
Effect of insulin on system A amino acid transport in human skeletal muscle.
Authors: R C Bonadonna, M P Saccomani, C Cobelli, R A DeFronzo
Journal: Journal of Clinical Investigation (1993)

Transmembrane transport of neutral amino acids in skeletal muscle is mediated by at least four different systems (system A, ASC, L, and Nm), and may be an important target for insulin's effects on amino acid and protein metabolism. We have measured net amino acid exchanges and fractional rates of inward (k(in), min-1) and outward (kout, min-1) transmembrane transport of 2-methylaminoisobutyric acid (MeAIB, a nonmetabolizable amino acid analogue, specific for system A amino acid transport) in forearm deep tissues (skeletal muscle), by combining the forearm perfusion technique and a novel dual tracer ([1-H3]-D-mannitol and 2-[1-14C]-methylaminoisobutyric acid) approach for measuring in vivo the activity of system A amino acid transport. Seven healthy lean subjects were studied. After a baseline period, insulin was infused into the brachial artery to achieve local physiologic hyperinsulinemia (76 +/- 8 microU/ml vs 6.4 +/- 1.6 microU/ml in the basal period, P < 0.01) without affecting systemic hormone and substrate concentrations. Insulin switched forearm amino acid exchange from a net output (-2,630 +/- 1,100 nmol/min per kig of forearm tissue) to a net uptake (1,610 +/- 600 nmol/min per kg, P < 0.01 vs baseline). Phenylalanine and tyrosine balances simultaneously shifted from a net output (-146 +/- 47 and -173 +/- 34 nmol/min per kg, respectively) to a zero balance (16.3 +/- 51 for phenylalanine and 15.5 +/- 14.3 nmol/min per kg for tyrosine, P < 0.01 vs baseline for both), showing that protein synthesis and breakdown were in equilibrium during hyperinsulinemia. Net negative balances of alanine, methionine, glycine, threonine and asparagine (typical substrates for system A amino acid transport) also were decreased by insulin, whereas serine (another substrate for system A transport) shifted from a zero balance to net uptake. Insulin increased k(in) of MeAIB from a basal value of 11.8.10(-2) +/- 1.7.10(-2).min-1 to 13.7.10(-2) +/- 2.2.10(-2).min-1 (P < 0.02 vs the postabsorptive value), whereas kout was unchanged. We conclude that physiologic hyperinsulinemia stimulates the activity of system A amino acid transport in human skeletal muscle, and that this effect may play a role in determining the overall concomitant response of muscle amino acid/protein metabolism to insulin.
The first annual EULAR Congress
Authors: L. B A VAN DE PUTTE
Journal: Annals of the Rheumatic Diseases (2000)

The June 2000 congress in Nice is the first annual Congress of the European League against Rheumatism (EULAR ) . Until now congresses have been organised once every four years, with smaller sized symposia in between. Another change this year concerns the journal of EULAR. In January 2000 the Annals of the Rheumatic Diseases …
T cell-T cell killing is induced by specific epitopes: evidence for an apoptotic mechanism.
Authors: D J Moss, S R Burrows, G D Baxter, M F Lavin
Journal: The Journal of Experimental Medicine (1991)

Epstein-Barr virus-specific cytotoxic T lymphocyte clones were shown to be an effective target for their own lysis when incubated in the presence of their specific epitopes but not in the presence of irrelevant epitopes. The mode of cell killing appeared to be by apoptosis and was prevented by previously described inhibitors of the process. Degranulation, as measured by serine esterase activity, was involved in this form of T cell-T cell killing. This is the first report of T cell-T cell killing by apoptosis and is only observed in the presence of a specific epitope. This result may be of significance in the use of peptide-based vaccines.
A “Bone” Fide Predictor of Metastasis? Predicting Breast Cancer Metastasis to Bone
Authors: Scott L. Kominsky, Nancy E. Davidson
Journal: Journal of Clinical Oncology (2006)

Bone is the most common site of breast cancer metastasis, with bone metastasis occurring in the majority of women with stage IV disease. These patients may experience marked morbidity with pain, decreased mobility, neurologic compromise, and/or pathologic fractures. Although the primary treatment for metastasis is systemic therapy directed at the underlying neoplasm, recent advances in therapy have led to the development of agents tailored to the treatment of bone metastasis including radiopharmaceuticals (eg, strontium-89 chloride) and bisphosphonates (eg, zoledronate or pamidronate). These agents localize predominantly to skeletal areas of high bone turnover like metastatic sites, thereby limiting systemic exposure, but their use is not without toxicity. The administration of bone-targeted radiopharmaceuticals has been associated with painful flare responses and myelosuppres
Apolipoprotein A-IV Predicts Progression of Chronic Kidney Disease
Authors: Eva Boes, Danilo Fliser, Eberhard Ritz, Paul König, Karl Lhotta, Johannes F.E. Mann, Gerhard A. Müller, Ulrich Neyer, Werner Riegel, Peter Riegler, Florian Kronenberg
Journal: Journal of the American Society of Nephrology (2005)

It has not been established firmly whether dyslipidemia contributes independently to the progression of kidney disease. Lipid and lipoprotein parameters, including levels of total, HDL, and LDL cholesterol; triglycerides; lipoprotein(a); apolipoprotein A-IV; and the apolipoprotein E and A-IV polymorphisms, were assessed in 177 patients who had mostly mild to moderate renal insufficiency and were followed prospectively for up to 7 yr. Progression of kidney disease was defined as doubling of baseline serum creatinine and/or terminal renal failure necessitating renal replacement therapy. In univariate analysis, patients who reached a progression end point (n = 65) were significantly older and had higher serum creatinine and proteinuria as well as lower GFR and hemoglobin levels. In addition, baseline apolipoprotein A-IV and triglyceride concentrations were higher and HDL cholesterol levels were lower. Multivariate Cox regression analysis revealed that baseline GFR (hazard ratio 0.714; 95% confidence interval [CI] 0.627 to 0.814 for an increment of 10 ml/min per 1.73 m(2); P < 0.0001) and serum apolipoprotein A-IV concentrations (hazard ratio 1.062; 95% CI 1.018 to 1.108 for an increment of 1 mg/dl; P = 0.006) were significant predictors of disease progression. Patients with apolipoprotein A-IV levels above the median had a significantly faster progression (P < 0.0001), and their mean follow-up time to a progression end point was 53.7 mo (95% CI 47.6 to 59.8) as compared with 70.0 mo (95% CI 64.6 to 75.4) in patients with apolipoprotein A-IV levels below the median. For the apolipoprotein E polymorphism, only the genotype epsilon2/epsilon4 was associated with an increased risk for progression. In summary, this prospective study in patients with nondiabetic primary kidney disease demonstrated that apolipoprotein A-IV concentration is a novel independent predictor of progression.
Genomic analysis of heat-shock factor targets in Drosophila.
Authors: Ian Birch-Machin, Shan Gao, David Huen, Richard McGirr, Robert AH White, Steven Russell
Journal: Genome biology (2005)

Abstract We have used a chromatin immunoprecipitation-microarray (ChIP-array) approach to investigate the in vivo targets of heat-shock factor (Hsf) in Drosophila embryos. We show that this method identifies Hsf target sites with high fidelity and resolution. Using cDNA arrays in a genomic search for Hsf targets, we identified 141 genes with highly significant ChIP enrichment. This study firmly establishes the potential of ChIP-array for whole-genome transcription factor target mapping in vivo using intact whole organisms.
Figures on screening for Down's syndrome are inaccurate
Authors: A. Kennard, E. Alberman, M. Gill
Journal: BMJ (1996)

Tuberculosis Research Unit for the streptomycin trial,4 which subsequently (from 1948) served as a model for randomisation in many later randomised controlled trials?Or is it because the results of the patulin trial were negative and those of the streptomycin trial made medical history?I have previously quoted Bradford Hill's re- collection that his statistical, and my medical, experiences in this field converged when we pre- pared for the streptomycin project.56The patulin trial certainly influenced my thinking.Yet, so far as I am aware, the literature on the modem clinical trial contains no recognition of this trial, despite its many deserving features.Should not this omission be rectified?