tbuckley/cabot-search huggingface dataset:
The Invasion and Reproductive Toxicity of QDs-Transferrin Bioconjugates on Preantral Follicle <i>in vitro</i>
Authors: Gaixia Xu, Suxia Lin, Wing-Cheung Law, Indrajit Roy, Xiaotan Lin, Shujiang Mei, Hanwu Ma, Siping Chen, Hanben Niu, Xiaomei Wang
Journal: Theranostics (2012)

The toxicity of QD has been extensively studied over the past decade. However, the potential toxicity of QDs impedes its use for clinical research. In this work, we established a preantral follicle in vitro culture system to investigate the effects of QD-Transferrin (QDs-Tf) bioconjugates on follicle development and oocyte maturation. The preantral follicles were cultured and exposed to CdTe/ZnTe QDs-Tf bioconjugates with various concentrations and the reproductive toxicity was assessed at different time points post-treatment. The invasion of QDs-Tf for oocytes was verified by laser scanning confocal microscope. Steroid production was evaluated by immunoassay. C-band Giemsa staining was performed to observe the chromosome abnormality of oocytes. The results showed that the QDs-Tf bioconjugates could permeate into granulosa cells and theca cells, but not into oocyte. There are no obvious changes of oocyte diameter, the mucification of cumulus-oocyte-complexes and the occurrence of aneulpoidy as compared with the control group. However, delay in the antrum formation and decrease in the ratio of oocytes with first polar body were observed in QDs-Tf-treated groups. The matured oocytes with first polar body decreased significantly by ~16% (from 79.6±10 % to 63±2.9 %) when the concentration of QDs-Tf bioconjugates exceeded 2.89 nmol·L(-1) (P < 0.05). Our results implied that the CdTe/ZnTe QDs-Tf bioconjugates were reproductive toxic for follicle development, and thus also revealed that this in vitro culture system of preantral follicle is a highly sensitive tool for study on the reproductive toxicity of nanoparticles.
Chronic non-bacterial osteomyelitis in children
Authors: H J Girschick
Journal: Annals of the Rheumatic Diseases (2005)

Chronic recurrent multifocal osteomyelitis (CRMO) in children is a chronic non-suppurative inflammation involving multiple sites. Some children affected by chronic non-bacterial osteomyelitis (CNO) do not have multiple lesions or a recurrent course.To characterise the long term outcome of children with the full spectrum of CNO.30 children diagnosed with CNO were followed up for a mean of 5.6 years and their disease assessed using a clinical score, multiple imaging, and a diagnostic biopsy, including extensive microbial analysis.9 patients had unifocal non-relapsing disease, 3 unifocal lesions with relapses, 9 multifocal lesions without relapses, and 9 multifocal lesions with relapses (CRMO). Granulocytes were present significantly more often in CRMO than in unifocal and non-recurrent lesions. Pustulosis was more common in multifocal cases regardless of recurrence. Mean duration of treatment in 15 children with a single occurrence was 9.2 months. Naproxen treatment was generally effective. Naproxen treatment in 12 patients with relapses lasted 25 months. However, 7 of these were not effectively treated with naproxen alone. Five were treated with oral glucocorticoids for 27 days in addition to naproxen, which induced remission in four, lasting for at least 1.5 years. Longitudinal growth of affected bones was not altered, except for the development of hyperostosis.CNO is a spectrum of inflammatory conditions, with CRMO being the most severe. Most children with CNO have a favourable outcome of the disease. Oral glucocorticoids may be necessary in severe recurrent cases.
Platelet-Derived Growth Factor Promotes the Expression of Peroxisome Proliferator-Activated Receptor γ in Vascular Smooth Muscle Cells by a Phosphatidylinositol 3-Kinase/Akt Signaling Pathway
Authors: Mingui Fu, Xiaojun Zhu, Qian Wang, Jifeng Zhang, Qing Song, Hui Zheng, Wataru Ogawa, Jie Du, Yuqing E. Chen
Journal: Circulation Research (2001)

Vascular diseases such as atherosclerosis are characterized by abnormal accumulation of vascular smooth muscle cells (VSMCs) within the intimal lining. The intimal VSMCs exhibit an increased expression of peroxisome proliferator-activated receptor γ (PPARγ), and the administration of pharmacological PPARγ agonists attenuates vascular lesion formation. The factors that regulate PPARγ expression in the vasculature are poorly defined. Here we report that platelet-derived growth factor (PDGF) upregulates PPARγ by the phosphatidylinositol 3-kinase (PI3-kinase)/Akt signaling pathway. Using Northern-blotting and Western-blotting analyses, we observed that the levels of PPARγ mRNA and protein were increased by 2- to 3.5-fold in human aortic smooth muscle cells (HASMCs) treated with PDGF (20 ng/mL). This was abolished by preincubation of HASMCs with a PI3-kinase inhibitor (LY294002, 50 μmol/L), and partially inhibited by a MEK1 inhibitor (U0126, 10 μmol/L), but not affected by a p38 kinase inhibitor (SB202190, 10 μmol/L). In addition, overexpression of the dominant-negative p85 subunit of PI3-kinase or Akt proteins blocked the PDGF-induced PPARγ expression. Taken together, our results suggest that PDGF induces PPARγ expression in VSMCs by a PI3-kinase/Akt signaling pathway. The characterization of factors and signaling pathways that modulate PPARγ expression in VSMCs may have important implications for understanding the pathogenesis of vascular diseases.
Phase II trial of 7 days on/7 days off temozolmide for recurrent high-grade glioma
Authors: S. J. Han, J. D. Rolston, A. M. Molinaro, J. L. Clarke, M. D. Prados, S. M. Chang, M. S. Berger, A. DeSilva, N. A. Butowski
Journal: Neuro-Oncology (2014)

A phase II trial was performed to evaluate the efficacy of a dose-dense, 7 days on/7 days off schedule of temozolomide for patients with recurrent high-grade gliomas (HGG).Sixty patients with recurrent HGG received temozolomide at 150 mg/m(2)/day on days 1-7 and days 15-21 during each 4-week cycle. The primary endpoint was 6-month progression-free survival (PFS-6), with a secondary endpoint of overall survival (OS). A further exploratory objective included the investigation of whether methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter within tumor tissue predicted outcomes.Among patients with glioblastoma (n = 40), PFS-6 was 10% (95% CI, 3%-24%) with median OS of 21.6 weeks (95% CI, 16.9-30.6 weeks). PFS-6 for grade III glioma patients (n = 20) was 50% (95% CI, 27%-73%), and median OS was 100.6 weeks (95% CI, 67 weeks to not reached). There were trends towards longer PFS and OS with MGMT promoter methylation (log-rank test; P = .06 for PFS; P = .07 for OS). Additionally, bevacizumab-naïve glioblastoma patients had significantly longer PFS and OS (median PFS was 8.07 weeks [95% CI, 8 weeks to not reached] vs 7.57 weeks [95% CI, 7.29-8.29 weeks], log-rank test, P < .001; median OS was 62 weeks [26.1 weeks to not reached] vs 18.2 weeks [13.9-27.3 weeks], log-rank test, P < .001).The dose-dense temozolomide regimen was well tolerated, although it has no significant activity in this population. Clinical trials.gov identified. NCT00619112 (available at http://clinicaltrials.gov/ct2/show/NCT00619112).
Investigation of Coronary Venous Anatomy by Retrograde Venography in Patients With Malignant Ventricular Tachycardia
Authors: Eckhard Meisel, Dietrich Pfeiffer, Lothar Engelmann, Jürgen Tebbenjohanns, Bernd Schubert, Stephen Hahn, Eckart Fleck, Christian Butter
Journal: Circulation (2001)

Background The coronary venous system is increasingly used for left ventricular or biventricular pacing in patients with severe heart failure. The present study investigated the structure of the coronary veins in patients presenting with structural heart disease and malignant ventricular tachyarrhythmias. The availability of veins for possible lead placement was assessed. Methods and Results The number, relative size, and location of coronary veins were evaluated by retrograde venography in 129 patients undergoing cardioverter-defibrillator implantation. Detailed x-ray image analysis was performed in 86 patients, for whom optimal coronary sinus occlusion and vein visualization was achieved. The anterior interventricular vein and the middle cardiac vein were visible in 85 (99%) of 86 patients and in 86 (100%) of 86 patients, respectively. Between these 2 veins, at least 1 additional prominent vein was visible in 85 (99%) of 86 patients. Just 1 vein was present in 44 (51%) of 86 patients. Two veins were observed in 40 (46%) of 86 patients, and &gt;2 veins were visualized in 2 (2%) of 86 patients. Venous anatomy allowed positioning of a 0.014-in guidewire in a coronary vein in 115 (93%) of 124 patients. Conclusions The presence, diameter, angulation, and tortuosity of veins as visualized by retrograde venography determine their acceptability for the placement of a lead in a predetermined location. Despite the considerable variability of the coronary venous system among patients, a lateral vessel for lead introduction was available in 82%, and a posterior or lateral vessel was available in 99% of individuals within a patient population that could potentially benefit from a lead on the left ventricle.
Inhaled lysine acetylsalicylate (L-ASA) attenuates the bronchoconstrictor response to adenosine 5'-monophosphate (AMP) in asthmatic subjects
Authors: N Crimi, R Polosa, S Magri, G Prosperini, VL Milazzo, G Santonocito, A Mistretta
Journal: European Respiratory Journal (1995)

When administered by inhalation, adenosine 5'-monophosphate (AMP) provokes dose-related bronchoconstriction in asthmatic subjects by a mechanism believed to involve mast cell mediator release. However, little is known of the change in airway responsiveness to AMP after cyclo-oxygenase blockade. The aim of this study was to investigate the effect of the potent cyclo-oxygenase inhibitor, lysine acetylsalicylate (L-ASA) administered by inhalation, on AMP-induced bronchoconstriction in a group of nine asthmatic subjects. The subjects studied attended the laboratory on six separate occasions to receive nebulized L-ASA (solution of 90 mg.ml-1) or matched placebo (glycine solution, 30 mg.ml-1) 15 min prior to bronchoprovocation tests with AMP, histamine and methacholine in a randomized, double-blind order. Changes in airway calibre were followed as forced expiratory volume in one second (FEV1) and agonist responsiveness was expressed as the provocative concentration causing a 20% fall in FEV1 from baseline (PC20). Administration of both L-ASA and glycine solution caused a small but significant acute fall in FEV1 from baseline, which returned to normal within 15 min. When compared to placebo, inhaled L-ASA reduced the airway responsiveness to AMP in all the subjects studied, the geometric mean (range) values for PC20 AMP increasing significantly from 36.3 (7.9-250.5) to 101.8 (27.2-1300) mg.ml-1 after placebo and L-ASA, respectively. Moreover, nebulized L-ASA induced a small but significant reduction in airway responsiveness to histamine, the geometric mean (range) PC20 values for histamine increasing from 2.77 (1.05-5.49) to 4.36 (1.69-11.24) mg.ml-1 after placebo and L-ASA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Assessment of symptomatic response as predictor of<i>Helicobacter pylori</i> status following eradication therapy in patients with ulcer
Authors: K E L McColl, A El-Nujumi, L S Murray, E M El-Omar, A Dickson, A W Kelman, T E Hilditch
Journal: Gut (1998)

Background — Helicobacter pylori eradication therapy is routinely used for treating patients with peptic ulcer disease. Aims —To assess the value of symptomatic response to H pylori eradication therapy as a marker of post-treatment H pylori status. Patients and methods —One hundred and nine dyspeptic patients with active duodenal or gastric ulceration associated with H pylori infection had their symptoms measured by a validated questionnaire before and three months following H pylori eradication therapy. The symptomatic response was compared with post-treatment H pylori status as determined by the 14 C urea breath test. Results —An eradication rate of 84% was achieved. Of the 92 patients eradicated of H pylori , 47% experienced complete or near complete resolution of dyspepsia. Of the 17 patients in whom the infection was not eradicated, only one (6%) experienced resolution of dyspepsia. Resolution of dyspepsia was therefore a powerful predictor of eradication of H pylori with a predictive value of 98%. In contrast, persistence of dyspepsia was a weak predictor of persisting infection with a predictive value of only 25%. Excluding patients with endoscopic evidence of coexisting oesophagitis and/or retrosternal discomfort or reflux at initial presentation did not increase the predictive value of persisting dyspepsia for persisting infection. Conclusions —Complete resolution of dyspeptic symptoms is a powerful predictor of eradication of H pylori infection in ulcer patients. Persistence of symptoms is a weak predictor of persisting infection and patients with persisting dyspepsia must have their H pylori status rechecked to guide future management.
The sirtuin SIRT6 blocks IGF-Akt signaling and development of cardiac hypertrophy by targeting c-Jun
Authors: Nagalingam R Sundaresan, Prabhakaran Vasudevan, Lei Zhong, Gene Kim, Sadhana Samant, Vishwas Parekh, Vinodkumar B Pillai, P V Ravindra, Madhu Gupta, Valluvan Jeevanandam, John M Cunningham, Chu-Xia Deng, David B Lombard, Raul Mostoslavsky, Mahesh P Gupta
Journal: Nature Medicine (2012)
Protection of Rat Cardiomyocytes Against Simulated Ischemia and Reoxygenation by Treatment With Protein Kinase C Activator
Authors: Y. V. Ladilov, C. Balser, H. M. Piper
Journal: Circulation Research (1998)

Abstract —The aim of this study was to investigate whether treatment with the protein kinase C (PKC) agonist 1,2-dioctanoyl- sn -glycerol (1,2DOG ) can protect isolated adult Wistar rat cardiomyocytes against simulated ischemia and reoxygenation. Cytosolic Ca 2+ (assessed by fura 2 fluorescence), pH i (assessed by BCECF fluorescence), and cell length were measured during 80 minutes of simulated ischemia (anoxia, pH o 6.4) and 20 minutes of reoxygenation (pH o 7.4) and compared between control cells and cells treated with 20 μmol/L 1,2DOG before anoxia (10-minute treatment and 10-minute washout), before and during anoxia (two-step treatment), or only during anoxia. Treatment before anoxia attenuated rigor contracture but did not influence anoxic Ca 2+ overload. In contrast, two-step treatment before and during anoxia accelerated rigor contracture but reduced the rate of anoxic Ca 2+ accumulation. During reoxygenation, control cells developed irreversible hypercontracture (reduction of cell length to 43±2% of the initial cell length, n=62), which was accompanied by spontaneous oscillations of cytosolic Ca 2+ (19.6±1.6 per minute). Two-step treatment with 1,2DOG before and during anoxia significantly reduced hypercontracture (reduction of cell length to 60±2%, P &lt;.01 versus control, n=41) and suppressed spontaneous Ca 2+ oscillations (2.8±0.9 per minute, P &lt;.01 versus control). These effects could not be reproduced by treatment with 1,2DOG before anoxia or during anoxia or by a two-step treatment with the PKC-inactive 1,3-dioctanoyl- sn -glycerol and were fully abolished with 1 μmol/L bisindolylmaleimide (PKC inhibitor). We conclude that a two-step activation of PKC before and during anoxia is required for effective protection of cardiomyocytes against anoxic Ca 2+ overload and reoxygenation-induced hypercontracture.
IP-10, a -C-X-C- chemokine, elicits a potent thymus-dependent antitumor response in vivo.
Authors: A D Luster, P Leder
Journal: The Journal of Experimental Medicine (1993)

IP-10 is a member of the -C-X-C-chemokine superfamily of proinflammatory cytokines whose secretion is induced by interferon gamma (IFN-gamma) and lipopolysaccharide (LPS). To date no function has been described for IP-10. We have genetically engineered tumor cells to secrete high levels of murine IP-10 and demonstrate that while IP-10 has no effect on the growth of these tumor cells in culture, it elicits a powerful host-mediated antitumor effect in vivo. The IP-10 antitumor response is T lymphocyte dependent, non-cell autonomous, and appears to be mediated by the recruitment of an inflammatory infiltrate composed of lymphocytes, neutrophils, and monocytes. These results document an important biologic property of IP-10 and raise the possibility that some of the T cell-directed effects of IFN-gamma and LPS may be mediated by this chemokine.
RMA/S cells present endogenously synthesized cytosolic proteins to class I-restricted cytotoxic T lymphocytes.
Authors: F Esquivel, J Yewdell, J Bennink
Journal: The Journal of Experimental Medicine (1992)

RMA/S is a mutant cell line with decreased cell surface expression of major histocompatibility complex class I molecules that has been reported to be deficient in presenting endogenously synthesized influenza virus nucleoprotein (NP) to cytotoxic T lymphocytes (CTL). In the present study we show that RMA/S cells can present vesicular stomatitis virus nucleocapsid protein, and, under some conditions, NP, to Kb-and Db-restricted CTL, respectively. Antigen presentation results from processing of cytosolic pools of endogenously synthesized proteins, and not the binding to cell surface class I molecules of antigenic peptides present in the virus inoculum or released from infected cells. Antigen processing of RMA/S differs, however, from processing by wild-type cells in requiring greater amounts of antigen, longer times to assemble or transport class I-peptide complexes, and in being more sensitive to blocking by anti-CD8 antibody. Thus, the antigen processing deficit in RMA/S cells is of a partial rather than absolute nature.
Awareness during anaesthesia.
Authors: N. S. Faithfull
Journal: BMJ (1969)

in which the subject of awareness during anaesthesia was discussed.Out of a total of 1,328 cases that I have recently anaesthetized, five cases have volunteered details of their operative experience indicating awareness.Three of these cases received nitrous-oxide-oxygen and relaxant anaesthesia-two out of a total of 25 caesarean sections and one case of multiple injuries.
New techniques to create and verify continuity of long RF lesions in patients with atrial fibrillation
Authors: C. Pappone, M. Rillo, F. Lamberti, M.L. Loricchio, P. Mazzone, T. Russo, S. Bianchi, G. Vicedomini, S.B. Haim, S.L. Chierchia
Journal: Journal of the American College of Cardiology (1998)
Catalogues of mammalian long noncoding RNAs: modest conservation and incompleteness
Authors: Ana C Marques, Chris P Ponting
Journal: Genome biology (2009)

Abstract Background Despite increasing interest in the noncoding fraction of transcriptomes, the number, species-conservation and functions, if any, of many non-protein-coding transcripts remain to be discovered. Two extensive long intergenic noncoding RNA (ncRNA) transcript catalogues are now available for mouse: over 3,000 macroRNAs identified by cDNA sequencing, and 1,600 long intergenic noncoding RNA (lincRNA) intervals that are predicted from chromatin-state maps. Previously we showed that macroRNAs tend to be more highly conserved than putatively neutral sequence, although only 5% of bases are predicted as constrained. By contrast, over a thousand lincRNAs were reported as being highly conserved. This apparent difference may account for the surprisingly small fraction (11%) of transcripts that are represented in both catalogues. Here we sought to resolve the reported discrepancy between the evolutionary rates for these two sets. Results Our analyses reveal lincRNA and macroRNA exon sequences to be subject to the same relatively low degree of sequence constraint. Nonetheless, our observations are consistent with the functionality of a fraction of ncRNA in these sets, with up to a quarter of ncRNA exons having evolved significantly slower than neighboring neutral sequence. The more tissue-specific macroRNAs are enriched in predicted RNA secondary structures and thus may often act in trans , whereas the more highly and broadly expressed lincRNAs appear more likely to act in the cis -regulation of adjacent transcription factor genes. Conclusions Taken together, our results indicate that each of the two ncRNA catalogues unevenly and lightly samples the true, much larger, ncRNA repertoire of the mouse.
VEGF-C gene therapy augments postnatal lymphangiogenesis and ameliorates secondary lymphedema
Authors: Young-sup Yoon, Toshinori Murayama, Edwin Gravereaux, Tengiz Tkebuchava, Marcy Silver, Cynthia Curry, Andrea Wecker, Rudolf Kirchmair, Chun Song Hu, Marianne Kearney, Alan Ashare, David G. Jackson, Hajime Kubo, Jeffrey M. Isner, Douglas W. Losordo
Journal: Journal of Clinical Investigation (2003)

Although lymphedema is a common clinical condition, treatment for this disabling condition remains limited and largely ineffective. Recently, it has been reported that overexpression of VEGF-C correlates with increased lymphatic vessel growth (lymphangiogenesis). However, the effect of VEGF-C–induced lymphangiogenesis on lymphedema has yet to be demonstrated. Here we investigated the impact of local transfer of naked plasmid DNA encoding human VEGF-C (phVEGF-C) on two animal models of lymphedema: one in the rabbit ear and the other in the mouse tail. In a rabbit model, following local phVEGF-C gene transfer, VEGFR-3 expression was significantly increased. This gene transfer led to a decrease in thickness and volume of lymphedema, improvement of lymphatic function demonstrated by serial lymphoscintigraphy, and finally, attenuation of the fibrofatty changes of the skin, the final consequences of lymphedema. The favorable effect of phVEGF-C on lymphedema was reconfirmed in a mouse tail model. Immunohistochemical analysis using lymphatic-specific markers: VEGFR-3, lymphatic endothelial hyaluronan receptor-1, together with the proliferation marker Ki-67 Ab revealed that phVEGF-C transfection potently induced new lymphatic vessel growth. This study, we believe for the first time, documents that gene transfer of phVEGF-C resolves lymphedema through direct augmentation of lymphangiogenesis. This novel therapeutic strategy may merit clinical investigation in patients with lymphedema.