tbuckley/cabot-search huggingface dataset:
Effect of Platelet-Derived Growth Factor Receptor-α and -β Blockade on Flow-Induced Neointimal Formation in Endothelialized Baboon Vascular Grafts
Authors: Mark G. Davies, Erik L. Owens, David P. Mason, Holly Lea, P. Kiet Tran, Selina Vergel, Suzanne A. Hawkins, Charles E. Hart, Alexander W. Clowes
Journal: Circulation Research (2000)

Abstract —The growth of neointima and neointimal smooth muscle cells in baboon polytetrafluoroethylene grafts is regulated by blood flow. Because neointimal smooth muscle cells express both platelet-derived growth factor receptor-α and -β (PDGFR-α and -β), we designed this study to test the hypothesis that inhibiting either PDGFR-α or PDGFR-β with a specific mouse/human chimeric antibody will modulate flow-induced neointimal formation. Bilateral aortoiliac grafts and distal femoral arteriovenous fistulae were placed in 17 baboons. After 8 weeks, 1 arteriovenous fistulae was ligated, normalizing flow through the ipsilateral graft while maintaining high flow in the contralateral graft. The experimental groups received a blocking antibody to PDGFR-α (Ab-PDGFR-α; 10 mg/kg; n=5) or PDGFR-β (Ab-PDGFR-β; 10 mg/kg; n=6) by pulsed intravenous administration 30 minutes before ligation and at 4, 8, 15, and 22 days after ligation. Controls received carrier medium alone (n=8). Serum antibody concentrations were followed. Grafts were harvested after 28 days and analyzed by videomorphometry. Serum Ab-PDGFR-α concentrations fell rapidly after day 7 to 0, whereas serum Ab-PDGFR-β concentrations were maintained at the target levels (&gt;50 μg/mL). Compared with controls (3.7±0.3), the ratio of the intimal areas (normalized flow/high flow) was significantly reduced in Ab-PDGFR-β (1.2±0.2, P &lt;0.01) but not in Ab-PDGFR-α (2.2±0.4). Ab-PDGFR-α decreased significantly the overall smooth muscle cell nuclear density of the neointima ( P &lt;0.01) compared with either the control or Ab-PDGFR-β treated groups. PDGFR-β is necessary for flow-induced neointimal formation in prosthetic grafts. Targeting PDGFR-β may be an effective pharmacological strategy for suppressing graft neointimal development.
Molecular-Scale Tools for Studying Mechanotransduction
Authors: Andrew S. LaCroix, Katheryn E. Rothenberg, Brenton D. Hoffman
Journal: Annual Review of Biomedical Engineering (2015)

Mechanical stimuli are known to be potent regulators of the form and function of cells and organisms. Although biological regulation has classically been understood in terms of principles from solution biochemistry, advancements in many fields have led to the development of a suite of techniques that are able to reveal the interplay between mechanical loading and changes in the biochemical properties of proteins in systems ranging from single molecules to living organisms. Here, we review these techniques and highlight the emergence of a new molecular-scale understanding of the mechanisms mediating the detection and response of cells to mechanical stimuli, a process termed mechanotransduction. Specifically, we focus on the role of subcellular adhesion structures in sensing the stiffness of the surrounding environment because this process is pertinent to applications in tissue engineering as well the onset of several mechanosensitive disease states, including cancer.
BMI/BCI Modeling and Signal Processing
Authors: José C. Principe, Dennis J. McFarland
Journal: Brain-Computer Interfaces (2008)

Due to the large differences in the biophysical characteristics between multi-microelectrode array and EEG/ECoG recordings, this report treats them separately. The signal processing modalities required to spatially resolve, extract features, and interpret intent depend on the selection of recording modality, which includes electroencephalography (EEG), electrocorticography (ECoG), local field potentials (LFPs), and single-neuron action potential recordings (single units).
Increased risk of virologic failure to the first antiretroviral regimen in HIV-infected migrants compared to natives: data from the ICONA cohort
Authors: A. Saracino, P. Lorenzini, S. Lo Caputo, E. Girardi, F. Castelli, P. Bonfanti, S. Rusconi, P. Caramello, N. Abrescia, C. Mussini, L. Monno, A. d’Arminio Monforte, M. Moroni, M. Andreoni, G. Angarano, A. Antinori, A. d’Arminio Monforte, F. Castelli, R. Cauda, G. Di Perri, M. Galli, R. Iardino, G. Ippolito, A. Lazzarin, C.F. Perno, F. von Schloesser, P. Viale, A. Castagna, F. Ceccherini-Silberstein, A. Cozzi-Lepri, E. Girardi, S. Lo Caputo, C. Mussini, M. Puoti, A. Ammassari, C. Balotta, P. Bonfanti, S. Bonora, M. Borderi, M.R. Capobianchi, A. Cingolani, P. Cinque, A. De Luca, A. Di Biagio, N. Gianotti, A. Gori, G. Guaraldi, G. Lapadula, M. Lichtner, G. Madeddu, F. Maggiolo, G. Marchetti, S. Marcotullio, L. Monno, E. Quiros Roldan, S. Rusconi, A. Saracino, P. Cicconi, I. Fanti, L. Galli, P. Lorenzini, M. Shanyinda, A. Tavelli, A. Giacometti, A. Costantini, S. Mazzoccato, C. Santoro, C. Suardi, E. Vanino, G. Verucchi, C. Minardi, T. Quirino, C. Abeli, P.E. Manconi, P. Piano, J. Vecchiet, K. Falasca, L. Sighinolfi, D. Segala, F. Mazzotta, G. Cassola, C. Viscoli, A. Alessandrini, R. Piscopo, G. Mazzarello, C. Mastroianni, V. Belvisi, I. Caramma, A. Chiodera, A.P. Castelli, G. Rizzardini, A.L. Ridolfo, R. Piolini, S. Salpietro, L. Carenzi, M.C. Moioli, C. Tincati, C. Puzzolante, N. Abrescia, A. Chirianni, G. Borgia, M.G. Guida, M. Gargiulo, I. Gentile, R. Orlando, F. Baldelli, D. Francisci, G. Parruti, T. Ursini, G. Magnani, M.A. Ursitti, V. Vullo, A. d’Avino, L. Gallo, E. Nicastri, R. Acinapura, M. Capozzi, R. Libertone, G. Tebano, M. Zaccarelli, F. Viviani, L. Sasset, M.S. Mura, B. Rossetti, P. Caramello, G. Di Perri, G.C. Orofino, M. Sciandra, M. Bassetti, A. Londero, G. Pellizzer, V. Manfrin
Journal: Clinical Microbiology and Infection (2015)
Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease?
Authors: W C Little, M Constantinescu, R J Applegate, M A Kutcher, M T Burrows, F R Kahl, W P Santamore
Journal: Circulation (1988)

To help determine if coronary angiography can predict the site of a future coronary occlusion that will produce a myocardial infarction, the coronary angiograms of 42 consecutive patients who had undergone coronary angiography both before and up to a month after suffering an acute myocardial infarction were evaluated. Twenty-nine patients had a newly occluded coronary artery. Twenty-five of these 29 patients had at least one artery with a greater than 50% stenosis on the initial angiogram. However, in 19 of 29 (66%) patients, the artery that subsequently occluded had less than a 50% stenosis on the first angiogram, and in 28 of 29 (97%), the stenosis was less than 70%. In every patient, at least some irregularity of the coronary wall was present on the first angiogram at the site of the subsequent coronary obstruction. In only 10 of the 29 (34%) did the infarction occur due to occlusion of the artery that previously contained the most severe stenosis. Furthermore, no correlation existed between the severity of the initial coronary stenosis and the time from the first catheterization until the infarction (r2 = 0.0005, p = NS). These data suggest that assessment of the angiographic severity of coronary stenosis may be inadequate to accurately predict the time or location of a subsequent coronary occlusion that will produce a myocardial infarction.
Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL)
Authors: Jeanette Lundin, Eva Kimby, Magnus Björkholm, Per-Anders Broliden, Fredrik Celsing, Viktoria Hjalmar, Lars Möllgård, Peppy Rebello, Geoff Hale, Herman Waldmann, Håkan Mellstedt, Anders Österborg
Journal: Blood (2002)
Backward estimation of exposure to organochlorines using repeated measurements.
Authors: Wilfried Karmaus, Christopher Fussman, Jyotsna Muttineni, Xiaobei Zhu
Journal: Environmental Health Perspectives (2004)

Great Lakes sport-caught fish are contaminated with various organochlorines (OCs) such as polychlorinated biphenyls (PCBs). Through consumption of these fish, humans are subject to continuing levels of OC contamination. To assess potential adverse effects of past exposure, we compared three different backward extrapolation models. The data originated from OC determinations in a cohort of anglers and their families. Repeated PCB measurements collected in the 1970s, 1980s, and 1990s were used when testing the backward extrapolations. We applied a simple and a complex decay model based on assumptions used in previous studies; a third was a regression model incorporating markers of OC intake and loss. These techniques provided past exposure estimates. Intraclass correlation coefficients (ICCs) were calculated comparing measured and estimated PCB values. ICC values for the regression model equations were 0.77 and 0.89; ICC values for the simple and complex decay models were significantly lower, with ranges of 0.07-0.45 and -0.14-0.69, respectively. Plots showing trends of OC concentrations in fish and humans indicate comparable increases and decreases of PCB in fish and humans, with fish concentrations peaking approximately 10 years before that in humans. Our findings suggest that one should be cautious when using simple backward extrapolation techniques to estimate OC exposure in situations involving changing environmental exposures. Whenever repeated measurements are available, regression analyses seem to produce more accurate backward estimations of exposure.
Nm23-H1 Suppresses Tumor Cell Motility by Down-regulating the Lysophosphatidic Acid Receptor <i>EDG2</i>
Authors: Christine E. Horak, Jong Heun Lee, Abdel G. Elkahloun, Mathieu Boissan, Sylvie Dumont, Tara K. Maga, Sandrine Arnaud-Dabernat, Diane Palmieri, William G. Stetler-Stevenson, Marie-Lise Lacombe, Paul S. Meltzer, Patricia S. Steeg
Journal: Cancer Research (2007)

Abstract Exogenous overexpression of the metastasis suppressor gene Nm23-H1 reduces the metastatic potential of multiple types of cancer cells and suppresses in vitro tumor cell motility and invasion. Mutational analysis of Nm23-H1 revealed that substitution mutants P96S and S120G did not inhibit motility and invasion. To elucidate the molecular mechanism of Nm23-H1 motility suppression, expression microarray analysis of an MDA-MB-435 cancer cell line overexpressing wild-type Nm23-H1 was done and cross-compared with expression profiles from lines expressing the P96S and S120G mutants. Nine genes, MET, PTN, SMO, FZD1, L1CAM, MMP2, NETO2, CTGF, and EDG2, were down-regulated by wild-type but not by mutant Nm23-H1 expression. Reduced expression of these genes coincident with elevated Nm23-H1 expression was observed in human breast tumor cohorts, a panel of breast carcinoma cell lines, and hepatocellular carcinomas from control versus Nm23-M1 knockout mice. The functional significance of the down-regulated genes was assessed by transfection and in vitro motility assays. Only EDG2 overexpression significantly restored motility to Nm23-H1–suppressed cancer cells, enhancing motility by 60-fold in these cells. In addition, silencing EDG2 expression with small interfering RNA reduced the motile phenotype of metastatic breast cancer cells. These data suggest that Nm23-H1 suppresses metastasis, at least in part, through down-regulation of EDG2 expression. [Cancer Res 2007;67(15):7238–46]
Development of lung radiological findings of cystic fibrosis patients under 6 years old
Authors: Cassio Ibiapina, Jesiana Pedrosa, Cristina Alvim, Paulo Camargos
Journal: European Respiratory Journal (2013)

Introduction  :  The pulmonary evaluation in children with Cystic fibrosis (CF) under 6 years old is limited and based on chest radiography. Neonatal screening (NS) is important for early diagnosis, however there are few studies on its impact on the progression of pulmonary infection-inflamation cycle.   Objective : To evaluate development of radiological changes of CF in patients under 6 years old through Brasfield score and analyze its differences according to pulmonary colonization with  Pseudomonas aeruginosa  (PA) and  Staphylococcus aureus  sensitive to oxacilin (OSSA) and with the diagnose form, if by NS or not.   Methods : It is a cross-sectional study that evaluated 254 chest radiographs of 67 patients who had done airway cultures as part of routine care. Statistical analysis was based on Kruskal Wallis test and with a significance level of 5%.   Results  :  Approximately 35,8% of the radiographs showed Brasfield score below 21 points, compatible with potentially irreversible lung disease, and from four years old the average score was below this value. According to the increasing children ages, it has increased the average severity of linear opacities and nodular cystic lesions. NS was related to less severe radiographic changes. The cronic colonization by PA was associated with greater severity of radiographic findings.   Conclusions : Radiographic evaluation of the chest was able to show the first lung changes of CF and identified the age group from which the changes became more pronounced. NS and prevention methods for chronic infection with PA seems to exert a protective effect on progression of lung disease in CF.
Depressive Symptomatology in Obese Adults With Type II Diabetes
Authors: Rena R Wing, Marsha D Marcus, Elaine H Blair, Leonard H Epstein, Lisa R Burton
Journal: Diabetes Care (1990)

This study compared depressive symptomatology in 32 obese subjects with type II (non-insulin-dependent) diabetes (16 men, 16 women) and their obese nondiabetic spouses. All subjects completed the Beck Depression Inventory (BDI) before participation in a behavioral weight-loss program. Diabetic subjects reported significantly more depressive symptomatology than their overweight nondiabetic spouses (10.6 ± 6.4 vs. 7.5 ± 6.2, P &amp;lt; 0.04). Diabetic subjects scored higher than their spouses on 15 of 20 BDI items, with significant differences in feelings of being punished, perceived appearance, and interest in sex. Mean BDI score in the diabetic spouses was similar to that observed in the first 123 diabetic subjects to enter the weight-loss program (BDI 11.2 ± 6.9). Further studies are needed to determine whether diabetic subjects differ from age-, sex-, and weight-matched nondiabetic individuals in clinical depression and depressive symptomatology.
Local Changes in GC/AT Substitution Biases and in Crossover Frequencies on Drosophila Chromosomes
Authors: T Takano-Shimizu
Journal: Molecular Biology and Evolution (2001)

I present here evidence of remarkable local changes in GC/AT substitution biases and in crossover frequencies on Drosophila chromosomes. The substitution pattern at 10 loci in the telomeric region of the X chromosome was studied for four species of the Drosophila melanogaster species subgroup. Drosophila orena and Drosophila erecta are clearly the most closely related species pair (the erecta complex) among the four species studied; however, the overall data at the 10 loci revealed a clear dichotomy in the silent substitution patterns between the AT-biased- substitution melanogaster and erecta lineages and the GC-biased-substitution yakuba and orena lineages, suggesting two or more independent changes in GC/AT substitution biases. More importantly, the results indicated a between- loci heterogeneity in GC/AT substitution bias in this small region independently in the yakuba and orena lineages. Indeed, silent substitutions in the orena lineage were significantly biased toward G and C at the consecutive yellow, lethal of scute, and asense loci, but they were significantly biased toward A and T at sta. The substitution bias toward G and C was centered in different areas in yakuba (significantly biased at EG:165H7.3, EG:171D11.2, and suppressor of sable). The similar silent substitution patterns in coding and noncoding regions, furthermore, suggested mutational biases as a cause of the substitution biases. On the other hand, previous study reveals that Drosophila yakuba has about 20-fold higher crossover frequencies in the telomeric region of the X chromosome than does D. melanogaster; this study revealed that the total genetic map length of the yakuba X chromosome was only about 1.5 times as large as that of melanogaster and that the map length of the X-telomeric y-sta region did not differ between Drosophila yakuba and D. erecta. Taken together, the data strongly suggested that an approximately 20- fold reduction in the X-telomeric crossover frequencies occurred in the ancestral population of D. melanogaster after the melanogaster-yakuba divergence but before the melanogaster-simulans divergence.
Clinical Factors Associated With Merkel Cell Polyomavirus Infection in Merkel Cell Carcinoma
Authors: Harri Sihto, Heli Kukko, Virve Koljonen, Risto Sankila, Tom Böhling, Heikki Joensuu
Journal: JNCI Journal of the National Cancer Institute (2009)

Merkel cell carcinoma is a rare malignancy of the skin. Integration of Merkel cell polyomavirus (MCPyV) DNA to the tumor genome is frequent in these cancers. The clinical consequences of MCPyV infection are unknown.We analyzed formalin-fixed paraffin-embedded Merkel cell carcinoma tissue samples from 114 of 207 patients diagnosed with Merkel cell carcinoma in Finland from 1979 to 2004 for the presence of MCPyV DNA with the use of polymerase chain reaction (PCR), quantitative PCR, and DNA sequencing and examined associations between tumor MCPyV DNA status and histopathologic factors and survival. The median follow-up time after Merkel cell carcinoma diagnosis for subjects who were alive was 9.9 years (range = 4.9-21.9 years). All P values are two-sided.MCPyV DNA was present in 91 carcinomas (79.8%). Compared with MCPyV DNA-negative cancers, MCPyV DNA-positive cancers were more often located in a limb (40.7% vs 8.7%, P = .015) and less frequent in patients who had regional nodal metastases at diagnosis (6.6% vs 21.7%, P = .043). Patients with MCPyV DNA-positive tumors had better overall survival than those with MCPyV DNA-negative tumors (5-year survival: 45.0% vs 13.0%, respectively; P < .001, two-sided log-rank test).MCPyV infection is associated with clinical outcomes in patients with Merkel cell carcinoma. These findings lend support to the hypothesis that viral infection is frequently associated with the pathogenesis of Merkel cell carcinoma.
Una Rachel Finnegan
Authors: R. H. O. Finnegan
Journal: BMJ (2014)

Una Rachel Finnegan’s attitude to medicine and society was greatly influenced not only by her undergraduate studies in Newcastle, but also by her intercalated year in Edinburgh studying for her master’s degree in medical anthropology, which she passed with merit. Her love of life and the outdoors was nurtured in her native Northern Ireland, especially the Causeway Coast and the Donegal Hills, …
Longitudinal Diffusion Tensor Magnetic Resonance Imaging Study of Radiation-Induced White Matter Damage in a Rat Model
Authors: Silun Wang, Ed X. Wu, Deqiang Qiu, Lucullus H.T. Leung, Ho-Fai Lau, Pek-Lan Khong
Journal: Cancer Research (2009)

Radiation-induced white matter (WM) damage is a major side effect of whole brain irradiation among childhood cancer survivors. We evaluate longitudinally the diffusion characteristics of the late radiation-induced WM damage in a rat model after 25 and 30 Gy irradiation to the hemibrain at 8 time points from 2 to 48 weeks postradiation. We hypothesize that diffusion tensor magnetic resonance imaging (DTI) indices including fractional anisotropy (FA), trace, axial diffusivity (lambda(//)), and radial diffusivity (lambda( perpendicular)) can accurately detect and monitor the histopathologic changes of radiation-induced WM damage, measured at the EC, and that these changes are dose and time dependent. Results showed a progressive reduction of FA, which was driven by reduction in lambda(//) from 4 to 40 weeks postradiation, and an increase in lambda( perpendicular) with return to baseline in lambda(//) at 48 weeks postradiation. Histologic evaluation of irradiated WM showed reactive astrogliosis from 4 weeks postradiation with reversal at 36 weeks, and demyelination, axonal degeneration, and necrosis at 48 weeks postradiation. Moreover, changes in lambda(//) correlated with reactive astrogliosis (P < 0.01) and lambda( perpendicular) correlated with demyelination (P < 0.01). Higher radiation dose (30 Gy) induced earlier and more severe histologic changes than lower radiation dose (25 Gy), and these differences were reflected by the magnitude of changes in lambda(//) and lambda( perpendicular). DTI indices reflected the histopathologic changes of WM damage and our results support the use of DTI as a biomarker to noninvasively monitor radiation-induced WM damage.
Implications of Phase Variation of a Gene (<i>pgtA</i>) Encoding a Pilin Galactosyl Transferase in Gonococcal Pathogenesis
Authors: Asesh Banerjee, Rong Wang, Sherry L. Supernavage, Salil K. Ghosh, James Parker, Nisha F. Ganesh, Peng G. Wang, Sunita Gulati, Peter A. Rice
Journal: The Journal of Experimental Medicine (2002)

The pilin glycoprotein (PilE) is the main building block of the pilus of Neisseria gonorrhoeae (gonococcus [GC]). GC pilin is known to carry a disaccharide O-glycan, which has an αGal attached to the O-linked GlcNAc by a 1–3 glycosidic bond. In this report, we describe the cloning and characterization of the GC gene, pilus glycosyl transferase A (pgtA), which encodes the galactosyl transferase that catalyzes the synthesis of this Gal–GlcNAc bond of pilin glycan. A homopolymeric tract of Gs (poly-G) is present in the pgtA gene of many GC strains, and this pgtA with poly-G can undergo phase variation (Pv). However, in many other GC, pgtA lacks the poly-G and is expressed constitutively without Pv. Furthermore, by screening a large number of clinical isolates, a significant correlation was observed between the presence of poly-G in pgtA and the dissemination of GC infection. Poly-G was found in pgtA in all (24 out of 24) of the isolates from patients with disseminated gonococcal infection (DGI). In contrast, for the vast majority (20 out of 28) of GC isolated from uncomplicated gonorrhea (UG) patients, pgtA lacked the poly-G. These results indicate that Pv of pgtA is likely to be involved in the conversion of UG to DGI.