tbuckley/cabot-search huggingface dataset:
Applied Anatomic Site Study of Palatal Anchorage Implants Using Cone Beam Computed Tomography
Authors: Ren‐fa Lai, Hui Zou, Wei‐dong Kong, Wei Lin
Journal: International Journal of Oral Science (2010)

The purpose of this study was to conduct quantitative research on bone height and bone mineral density of palatal implant sites for implantation, and to provide reference sites for safe and stable palatal implants. Three‐dimensional reformatting images were reconstructed by cone beam computed tomography (CBCT) in 34 patients, aged 18 to 35 years, using EZ Implant software. Bone height was measured at 20 sites of interest on the palate. Bone mineral density was measured at the 10 sites with the highest implantation rate, classified using K‐mean cluster analysis based on bone height and bone mineral density. According to the cluster analysis, 10 sites were classified into three clusters. Significant differences in bone height and bone mineral density were detected between these three clusters (P<0.05). The greatest bone height was obtained in cluster 2, followed by cluster 1 and cluster 3. The highest bone mineral density was found in cluster 3, followed by cluster 1 and cluster 2. CBCT plays an important role in pre‐surgical treatment planning. CBCT is helpful in identifying safe and stable implantation sites for palatal anchorage.
Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry study
Authors: Karim Ladha, Marcos F Vidal Melo, Duncan J McLean, Jonathan P Wanderer, Stephanie D Grabitz, Tobias Kurth, Matthias Eikermann
Journal: BMJ (2015)

<b>Objective</b> To evaluate the effects of intraoperative protective ventilation on major postoperative respiratory complications and to define safe intraoperative mechanical ventilator settings that do not translate into an increased risk of postoperative respiratory complications. <b>Design</b> Hospital based registry study. <b>Setting</b> Academic tertiary care hospital and two affiliated community hospitals in Massachusetts, United States. <b>Participants</b> 69 265 consecutively enrolled patients over the age of 18 who underwent a non-cardiac surgical procedure between January 2007 and August 2014 and required general anesthesia with endotracheal intubation. <b>Interventions</b> Protective ventilation, defined as a median positive end expiratory pressure (PEEP) of 5 cmH<sub>2</sub>O or more, a median tidal volume of less than 10 mL/kg of predicted body weight, and a median plateau pressure of less than 30 cmH<sub>2</sub>O. <b>Main outcome measure</b> Composite outcome of major respiratory complications, including pulmonary edema, respiratory failure, pneumonia, and re-intubation. <b>Results</b> Of the 69 265 enrolled patients 34 800 (50.2%) received protective ventilation and 34 465 (49.8%) received non-protective ventilation intraoperatively. Protective ventilation was associated with a decreased risk of postoperative respiratory complications in multivariable regression (adjusted odds ratio 0.90, 95% confidence interval 0.82 to 0.98, P=0.013). The results were similar in the propensity score matched cohort (odds ratio 0.89, 95% confidence interval 0.83 to 0.97, P=0.004). A PEEP of 5 cmH<sub>2</sub>O and median plateau pressures of 16 cmH<sub>2</sub>O or less were associated with the lowest risk of postoperative respiratory complications. <b>Conclusions</b> Intraoperative protective ventilation was associated with a decreased risk of postoperative respiratory complications. A PEEP of 5 cmH<sub>2</sub>O and a plateau pressure of 16 cmH<sub>2</sub>O or less were identified as protective mechanical ventilator settings. These findings suggest that protective thresholds differ for intraoperative ventilation in patients with normal lungs compared with those used for patients with acute lung injury.
Acetyl-11-Keto-β-Boswellic Acid Inhibits Prostate Tumor Growth by Suppressing Vascular Endothelial Growth Factor Receptor 2–Mediated Angiogenesis
Authors: Xiufeng Pang, Zhengfang Yi, Xiaoli Zhang, Bokyung Sung, Weijing Qu, Xiaoyuan Lian, Bharat B. Aggarwal, Mingyao Liu
Journal: Cancer Research (2009)

The role of angiogenesis in tumor growth and metastasis is well established. Identification of a small molecule that blocks tumor angiogenesis and is safe and affordable has been a challenge in drug development. In this study, we showed that acetyl-11-keto-beta-boswellic acid (AKBA), an active component from an Ayurvedic medicinal plant (Boswellia serrata), could strongly inhibit tumor angiogenesis. AKBA suppressed tumor growth in the human prostate tumor xenograft mice treated daily (10 mg/kg AKBA) after solid tumors reached approximately 100 mm(3) (n = 5). The inhibitory effect of AKBA on tumor growth was well correlated with suppression of angiogenesis. When examined for the molecular mechanism, we found that AKBA significantly inhibited blood vessel formation in the Matrigel plug assay in mice and effectively suppressed vascular endothelial growth factor (VEGF)-induced microvessel sprouting in rat aortic ring assay ex vivo. Furthermore, AKBA inhibited VEGF-induced cell proliferation, chemotactic motility, and the formation of capillary-like structures from primary cultured human umbilical vascular endothelial cells in a dose-dependent manner. Western blot analysis and in vitro kinase assay revealed that AKBA suppressed VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR2) kinase (KDR/Flk-1) with IC(50) of 1.68 micromol/L. Specifically, AKBA suppressed the downstream protein kinases of VEGFR2, including Src family kinase, focal adhesion kinase, extracellular signal-related kinase, AKT, mammalian target of rapamycin, and ribosomal protein S6 kinase. Our findings suggest that AKBA potently inhibits human prostate tumor growth through inhibition of angiogenesis induced by VEGFR2 signaling pathways.
Oncogenic transcription factors: cornerstones of inflammation-linked pancreatic carcinogenesis
Authors: Sandra Baumgart, Volker Ellenrieder, Martin E Fernandez-Zapico
Journal: Gut (2011)

Transcription factors are proteins that regulate gene expression by modulating the synthesis of messenger RNA. Since this process is often one dominant control point in the production of many proteins, transcription factors represent the key regulators of numerous cellular functions, including proliferation, differentiation and apoptosis. Pancreatic cancer progression is characterised by activation of inflammatory signalling pathways converging on a limited set of transcription factors that fine-tune gene expression patterns contributing to the growth and maintenance of these tumours. Thus strategies targeting these transcriptional networks activated in pancreatic cancer cells could block the effects of upstream inflammatory responses participating in pancreatic tumorigenesis. The authors review this field of research and summarise current strategies for targeting oncogenic transcription factors and their activating signalling networks in the treatment of pancreatic cancer.
Fetal Stromal–Dependent Paracrine and Intracrine Vascular Endothelial Growth Factor-A/Vascular Endothelial Growth Factor Receptor-1 Signaling Promotes Proliferation and Motility of Human Primary Myeloma Cells
Authors: Loïc Vincent, David K. Jin, Matthias A. Karajannis, Koji Shido, Andrea T. Hooper, William K. Rashbaum, Bronislaw Pytowski, Yan Wu, Daniel J. Hicklin, Zhenping Zhu, Peter Bohlen, Ruben Niesvizky, Shahin Rafii
Journal: Cancer Research (2005)

Abstract Induction of neoangiogenesis plays an important role in the pathogenesis of multiple myeloma. However, the mechanism by which expression of vascular endothelial growth factor (VEGF)-A and its receptors modulate the interaction of multiple myeloma cells with stromal cells is not known. Here, we describe a novel in vitro coculture system using fetal bone stromal cells as a feeder layer, which facilitates the survival and growth of human primary multiple myeloma cells. We show that stromal-dependent paracrine VEGF-A signaling promotes proliferation of human primary multiple myeloma cells. Primary multiple myeloma cells only expressed functional VEGF receptor (VEGFR)-1, but not VEGFR-2 or VEGFR-3. VEGFR-1 expression was detected in the cytoplasm and the nuclei of proliferating multiple myeloma cells. Inhibition of VEGFR-1 abrogated multiple myeloma cell proliferation and motility, suggesting that the functional interaction of VEGF-A with its cognate receptor is essential for the growth of primary multiple myeloma cells. Collectively, our results suggest that stromal-dependent paracrine and intracrine VEGF-A/VEGFR-1 signaling contributes to human primary multiple myeloma cell growth and therefore, VEGFR-1 blockade is a potential therapeutic strategy for the treatment of multiple myeloma.
The Raf Inhibitor BAY 43-9006 (Sorafenib) Induces Caspase-Independent Apoptosis in Melanoma Cells
Authors: David J. Panka, Wei Wang, Michael B. Atkins, James W. Mier
Journal: Cancer Research (2006)

Abstract Mitogen-activated protein kinase (MAPK) is activated in the majority of melanomas, and its activity is essential for cell survival. In this report, we examined the effects of a novel raf inhibitor BAY 43-9006 on melanoma cell viability and intracellular signaling and found that it induces apoptosis through a caspase-independent mechanism. At concentrations that suppress extracellular signal-regulated kinase (ERK) phosphorylation, BAY 43-9006 dephosphorylates Bad on Ser75 and Ser99, activates Bak and Bax, and reduces the mitochondrial transmembrane potential. BAY 43-9006 (sorafenib) down-modulates the levels of Bcl-2 and Bcl-XL in a MAPK-independent manner in A2058 and SKMEL5 melanoma cells but not in the more resistant A375 cells. Of the three lines tested, only A375 cells were rescued from BAY 43-9006–induced apoptosis by knocking down Bad. BAY 43-9006 induced poly(ADP-ribose) polymerase cleavage and the mitochondrial release of cytochrome c and SMAC. However, the pan-caspase inhibitor Z-VAD-fmk had only a modest protective effect against the drug, suggesting that BAY 43-9006–induced apoptosis is largely caspase independent. BAY 43-9006 but not the MAP/ERK kinase inhibitors PD98059 or U0126 induced the nuclear translocation of apoptosis-inducing factor (AIF) in A2058 and SKMEL5 cells, and the introduction of a small interfering RNA (siRNA) for AIF partially protected these cells from BAY 43-9006–induced apoptosis. The AIF siRNA had little effect in A375 cells, in which drug-induced AIF release was negligible. These data indicate that in sensitive cell lines, BAY 43-9006–induced apoptosis is independent of Bad dephosphorylation and caspase activation and largely mediated through the nuclear translocation of AIF. (Cancer Res 2006; 66(3): 1611-9)
Tau-Hsp70 interaction on the single molecule level
Authors: Franziska Kundel, Magnus Kjaergaard, Sarah Shammas, Sophie Jackson, David Klenerman
Journal: Molecular Neurodegeneration (2013)

Background As the protein quality control centre of the cell molecular chaperones tightly regulate amyloid proteins and seem to alleviate their cytotoxicity. However, the precise mechanism of this interplay and how its modification leads to disease remain elusive. Particularly oligomeric species of amyloid proteins have emerged as the most important mediators of neurotoxicity in neurodegenerative diseases. However, these oligomers are exceedingly hard to characterize as they are transient, heterogeneous and rare relative to the monomeric and fibrillar states. We have developed single molecule FRET techniques for the time-resolved detection and characterisation of oligomeric species [1-3]. Here, we characterise the oligomers evolving during the aggregation of a tau variant carrying the Δ280K mutation associated with some forms of frontotemporal dementia. Further, we study the interaction of these oligomers with the intracellular chaperone Hsp70 which has previously been identified as a key regulator of tau turnover.
Thoracic gas volume at functional residual capacity measured with an integrated-flow plethysmograph in infants and young children
Authors: F Marchal, C Duvivier, R Peslin, P Haouzi, JP Crance
Journal: European Respiratory Journal (1991)

Thoracic gas volume (TGV) was measured with an integrated flow plethysmograph in 15 infants aged 2-34 months. End-expiratory (TGVe) and end-inspiratory (TGVi) airway occlusions were compared, after correction of TGV for the occluded volume above functional residual capacity (FRC). The relationship between pressure at the airway opening (Pao) and volume displaced from the box during airway occlusion (Vg) was studied numerically by: 1) an algorithm including a correction for the drift of Vg and linear regression analysis (LR); and 2) Fourier analysis of the signals (FFT). TGVe was significantly higher than TGVi (256 vs 237 ml, 20.4 (square root of residual variance; p less than 0.002). The correlation coefficient of the Pao-Vg relationship was slightly but significantly higher for TGVi than for TGVe: 0.9968 (0.9937-0.9995) vs 0.9947 (0.9840-0.9990) (means and range). No difference was observed between LR and FFT, although the intra-individual coefficient of variation was lower for LR than FFT: 5.2% (1.6-11.3) vs 7.9% (1.9-21.0) (means and range). Model simulations suggested that the difference between TGVe and TGVi could be mainly attributed to gas compression in the instrumental deadspace and upper airway wall motion and/or to uneven distribution of alveolar and pleural pressure associated with chest wall distortion.
Colitis complicating chronic granulomatous disease. A clinicopathological case report.
Authors: J M Sloan, C H Cameron, R J Maxwell, D R McCluskey, J S Collins
Journal: Gut (1996)

BACKGROUND--This report concerns a female patient now aged 24 years, diagnosed at the age of 7 years as suffering from chronic granulomatous disease. At age 20 she developed diarrhoea accompanied by rectal bleeding. Endoscopy showed extensive colitis. She failed to respond to medical treatment and underwent total colectomy two years later. AIMS--To discuss the histological changes in the colon in chronic granulomatous disease. RESULTS--There was extensive mucosal inflammation throughout colon and rectum resembling ulcerative colitis. In addition characteristic large pigmented macrophages were distributed in the basal mucosa and superficial submucosa. Similar cells accompanied by granulomata were present in mesenteric lymph nodes. CONCLUSIONS--Colitis is an unusual clinical manifestation of chronic granulomatous disease but the presence and characteristic distribution of such pigmented macrophages in colonic biopsy in children and young adults may suggest the diagnosis.
Phase 2 trial of radiation plus high-dose tamoxifen for glioblastoma multiforme: RTOG protocol BR-00211
Authors: H Ian Robins, M Won, Wendy F Seiferheld, Christopher J Schultz, Ali K Choucair, David G Brachman, William F Demas, Minesh P Mehta
Journal: Neuro-Oncology (2006)

Preclinical studies support the concept that inhibition of protein kinase C (PKC) by tamoxifen (TAM) should provide both antineoplastic effects and radiosensitization. High-dose TAM (80 mg/m2 p.o. daily in divided doses) was given with and after conventional radiotherapy (XRT) to inhibit PKC-mediated signaling, which is known to be enhanced in glioblastoma (GBM). Seventy-seven patients were accrued between December 2000 and December 2001; two were ineligible and not included in the efficacy results. Pretreatment characteristics of the patients included the following: 52% were less than 60 years of age, 39% had a Zubrod score of 0, 70% had minor or no neurological symptoms, and 65% were Radiation Therapy Oncology Group-recursive partition analysis (RPA) class III and IV. Eighty-six percent of patients achieved acceptable dosing of TAM. Notable toxicity included late radiation grade 3 in two patients and thromboembolic events in 16 patients (two grade 2, 10 grade 3, three grade 4, and one grade 5), for an incidence of 20.8% (which is lower than expected, based on the literature for deep vein thrombophlebitis in GBM patients not receiving TAM). Median survival time (MST) was 9.7 months as compared (by three different statistical methodologies) to the historical GBM control database of 1457 RPA class III, IV, and V drug/XRT-treated patients. After controlling for RPA class IV, the MST was 11.3 months, which compares to the historical RPA control of 11.3 months (P = 0.37). The results obtained do not exhibit a substantial advance over those of previous studies with various XRT/drug doublets, including BCNU. However, as TAM does not have significant overlapping toxicities with most other drugs, its testing in a combined modality approach with other medications may be justified in future clinical trials. Historically, the incidence of thromboembolic events in GBM patients is approximately 30%. The lower-than-expected incidence seen here has also been observed in other high-dose TAM GBM studies. We speculate that TAM inhibited the PKC-mediated phosphorylation of coagulation factors.
Interleukin 4 is localized to and released by human mast cells.
Authors: P Bradding, I H Feather, P H Howarth, R Mueller, J A Roberts, K Britten, J P Bews, T C Hunt, Y Okayama, C H Heusser
Journal: The Journal of Experimental Medicine (1992)

Recent attention has focused on the T helper type 2 (Th2) lymphocyte as a source of interleukin 4 (IL-4) in allergic disease. However, Th2 cells themselves require a pulse of IL-4 to initiate this synthesis. Here we provide immunohistochemical evidence of IL-4 localization to human mast cells of the skin and respiratory tract, and demonstrate that immunoglobulin E-dependent stimulation of purified human lung mast cells leads to the rapid release of IL-4 into the extracellular environment. We propose that mast cell activation in an allergic response provides a rapid and local pulse of IL-4 into the local environment essential for the triggering of T lymphocytes into sustained IL-4 production and to initiate inflammatory cell accumulation and activation.
Vibrational analysis of bioprosthetic heart valve leaflets using numerical models: effects of leaflet stiffening, calcification, and perforation.
Authors: M S Hamid, H N Sabbah, P D Stein
Journal: Circulation Research (1987)

The fundamental natural frequency of the closed cusps of porcine bioprosthetic valves, fabricated from the normal leaflets of pig aortic valves, was estimated using a finite element model. Both normal and stiffened leaflets were considered in the vibrational analysis. The effects of conditions that simulated degeneration, such as stiffening, central perforation, a tear, calcium deposits in the commissural attachments, and combinations of these were determined. The primary frequency of vibration of the normal leaflets was within the range of the dominant frequency of the heart sounds determined clinically by spectral analysis of the recorded phonocardiogram. If only one leaflet was stiffened or calcified, there was only a marginal change of frequency. With stiffening and calcification of the commissures of all 3 leaflets, the frequency of vibration increased. Introduction of a tear in a single leaflet of a stiffened and calcified valve markedly reduced the fundamental frequency. In view of the relation between the frequency content of heart sounds and the frequency of valve vibration, this mathematical simulation establishes a possible basis for the observation of a varying dominant frequency of heart sounds in patients with bioprosthetic valves that are in the process of degenerating.
Risk assessment of left ventricular systolic dysfunction in primary care: cross sectional study evaluating a range of diagnostic tests
Authors: O. W. Nielsen
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objectives:</b> To assess the probability of left ventricular systolic dysfunction without echocardiography in patients from general practice. <b>Design:</b> Cross sectional study using multivariate regression models to examine the relation between clinical variables and left ventricular systolic dysfunction as determined by echocardiography. <b>Setting:</b> Three general practices in Copenhagen. <b>Subjects:</b> 2158 patients aged &gt;40 years were screened by questionnaires and case record reviews; 357 patients with past or present signs or symptoms of heart disease were identified, of whom 126 were eligible for and consented to examination. <b>Main outcome measures:</b> Clinical variables that were significantly (P&lt;0.05) related to ejection fraction 0.45 and their predictive value for left ventricular systolic dysfunction. <b>Results:</b> 15 patients (12%) had left ventricular systolic dysfunction. The prevalence was significantly related to three questions: does the electrocardiogram have Q waves, left bundle branch block, or ST-T segment changes? (P=0.012); is resting supine heart rate greater than the simultaneous diastolic blood pressure? (P=0.002); and is plasma N-terminal atrial natriuretic peptide&gt;0.8 nmol/l? (P=0.040)? Only one of 60 patients with a normal electrocardiogram had systolic dysfunction (2%, 95% confidence interval 0% to 9%) regardless of response to the other two questions. The risk of dysfunction was appreciable in patients with a yes answer to two or three questions (50%, 27% to 73%). <b>Conclusions:</b> A normal electrocardiogram implies a low risk of left ventricular systolic dysfunction. Patients can be identified for echocardiography on the basis of an abnormal electrocardiogram combined with increased natriuretic peptide concentration or a heart rate greater than diastolic blood pressure, or both. <h3>Key messages</h3> Early treatment of left ventricular systolic dysfunction reduces morbidity, but diagnosis relies on echocardiography This study examines methods for assessing the risk of left ventricular systolic dysfunction in patients from primary care with past or present signs or symptoms of heart disease Risk can be assessed by three factors: QRS or ST-T changes in the electrocardiogram; increased plasma concentration of N-terminal atrial natriuretic peptide; and tachycardia (supine resting heart rate&gt;diastolic blood pressure) Risk of systolic dysfunction was very low in patients with normal electrocardiographic results Risk was high in patients who had an abnormal electrocardiogram in combination with at least one other abnormal result