tbuckley/cabot-search huggingface dataset:
Abstract 216: Effects on Anti-Inflammatory Agent on Neurologic Recovery for Asphyxial Cardiac Arrest in Rats
Authors: Taeyun Kim, Joong Eui Rhee, Kyuseok Kim, You Hwan Jo, Gwang Pil Im, Jin Hee Lee
Journal: Circulation (2010)

Background: Rewarming after therapeutic hypothermia for comatose survivor of cardiac arrest, is essential step. However, some studies reported that neurological status was deteriorated during rewarming phase. We hypothesized that the administration of anti-inflammatory agent would reduce the neurological damages. Objective: We assessed the hypothesis that the administration of anti-inflammatory agent during rewarming phase would reduce the neurological damages in asphyxial cardiac arrest model treated with therapeutic hypothermia. Methods: Forty adult male Sprague-Dawley rats were assigned at random to 4 groups: normothermia (NT, maintaining a body temperature of 36–38°C); normothermia and administration of dexamethasone during rewarming phase (NT+D); hypothermia (HT, maintaining a body temperature of 30–32°C); hypothermia and administration of dexamethasone during rewarming phase (HT+D). Rats were chemically paralyzed with intravenous vecuronium and the ventilator was disconnected for producing complete ...
Abstract 9389: Histone Deacetylase 4 Causes Vascular Inflammation and Mediates Development of Hypertension in Spontaneous Hypertensive Rats
Authors: Tatsuya Usui, Muneyoshi Okada, Wataru Mizuno, Mayuko Oda, Natsuki Ide, Yukio Hara, Hideyuki Yamawaki
Journal: Circulation (2011)

Histone deacetylases (HDAC)s are transcription factors which play important roles on structural remodeling of chromatin. It is recently clarified that HDAC4 mediates heart failure and vascular smooth muscle cells (SMCs) hypertrophy. Moreover our recent study demonstrated that HDAC4 protein increases in mesenteric artery from spontaneous hypertensive rats (SHR) compared with Wistar Kyoto rats (WKY). Vascular inflammation is essential for pathogenesis of hypertension. We therefore examined whether HDAC4 affects on vascular inflammatory responses and mediates hypertensive vascular diseases. Protein expression (n=6-7, P&lt;0.01) and activity (n=3-5, P&lt;0.01) of HDAC4 in rat mesenteric arterial SMCs were increased by TNF-α (10 ng/ml, 1-3 h). An HDACs inhibitor, trichostatin A (TSA) (10 μM, pretreatment for 30 min), inhibited TNF (10 ng/ml, 24 h)-induced vascular cell adhesion molecule (VCAM)-1 expression (n=4, P&lt;0.01). TSA also inhibited TNF (20 min)-induced phosphorylation of NF-κB (n=4, P&lt;0.01). HDAC4 siRNA inhibited TNF-induced VCAM-1 (n=3-6, P&lt;0.01), monocyte adhesion (n=6, P&lt;0.05), phosphorylation (n=3-6, P&lt;0.05) and transcriptional activity (n=4-5, P&lt;0.05) of NF-κB. Furthermore, HDAC4 siRNA inhibited TNF-induced reactive oxygen species (ROS) production (n=4, P&lt;0.01). In vivo study, blood pressure (n=4, P&lt;0.05), ROS production (n=2) and VCAM-1 expression (n=4) in isolated mesenteric artery were increased in SHR compared with WKY, which were prevented by a long-term TSA treatment to SHR (100, 500 μg/kg/day, 3 weeks). In isolated mesenteric artery, the increased angiotensin II-induced contraction in SHR was reversed by a TSA treatment (n=4-6, P&lt;0.01). The endothelium-dependent relaxation induced by acetylcholine in SHR was augmented by TSA (n=6-8, P&lt;0.01). The present results indicate that in vascular SMCs TNF-induced HDAC4 mediates vascular inflammation via VCAM-1 induction through ROS-dependent NF-κB activation. It is also suggested that pro-inflammatory effects as well as hypercontractile effects of HDAC4 may mediate the development of hypertension in SHR. Our results may imply that HDAC4 is a promising important target for drug therapy against essential hypertension.
Histopathological Evidence of Lymph Node Metastasis in Papillary Thyroid Carcinoma
Authors: Nuray Can, Ebru Tastekin, Filiz Ozyilmaz, Yavuz Atakan Sezer, Sibel Guldiken, Necdet Sut, Nurtac Sarikas, Fulya Oz Puyan, Beril Guler, Semra Ayturk, Mehmet Celik
Journal: Endocrine Pathology (2015)
Expression of Epidermal Growth Factor Receptor (EGF-R) and Erb-B2 (HER 2/NEU) in Glioblastoma (GEM): Prognosttc Relevance
Authors: E. M. Hiesiger, R. L. Hayes, L. Thoron, G. N. Budzilovich, D. M. Pierz, A. Wise, J. Ransohoff
Journal: Neuro-Oncology (1991)

Archival material from 17 untreated primary adult GEMs were analyzed retrospectively using immunocytochemistry for the expression of EGF-R and ErbB2. Patients were divided into long term survivors (LTS) (N=10, median survival >4 yrs) and short term survivors (STS) (N=7, median survival 61 wks, mean ± SEM time to recurrence 22 ± 3 wks). There were no biologically significant differences between the groups in terms of age, post-operative Karnofsky status, or post-operative treatment (standard cranial radiation and chemotherapy). 6/7 of the STS had >90% of tumor resected compared with 6/10 of the LTS. All STS underwent debulking reoperation at suspected recurrence, confirming tumor regrowth as the cause of death in all STS. Histologically diagnostic paraffin sections were stained with monoclonal antibodies to EGF-R and ErbB2. Tumor staining was scored as 1 to 3: scant/ negative; ≦25% but <75% positive, or ≦75% positive. Scores of 2 and 3 were considered positve (+). Each tumor section was scored for positivity by 3 independent observers, blinded as to patient's name and history. There was general concordance between all three observers. All LTS were EGF-R negative/ scant and 7/10 were ErbB2 negative/scant. 4/7 STS were EGF-R+, 5/7 were ErbB2+, and 4/7 were positive for both proteins. Recurrrent tumors in STS had increased expression of EGF-R in 4/7 of cases and of ErbB2 in 7/7 cases over the pretreatment baseline. EGF-R negativity correlated best with long term survival, while ErbB2 positivity better predicted short term survival. Increased growth factor expression appears to be associated with aggressive clinical behavior and treatment resistance.
Abstract 9148: Inhibition of Endothelial Senescence Ameliorates Insulin Resistance of Obese Mice
Authors: Masataka Yokoyama, Tohru Minamino, Sho Okada, Kaoru Tateno, Junji Moriya, Ippei Shimizu, Aika Nojima, Takashi Ito, Yoko Ogasawara, Issei Komuro, Yoshio Kobayashi
Journal: Circulation (2011)

Various stimuli can induce irreversible cell growth arrest, termed cellular senescence. This response is controlled by negative regulators of the cell cycle such as p53. Accumulating evidence suggests a potential relationship between cellular senescence and age-associated diseases including type 2 diabetes. Here we show a crucial role for endothelial p53 in the regulation of insulin resistance. We found that treatment of endothelial cells with high glucose and palmitate synergistically increased p53 expression. Consistent with the in vitro results, endothelial expression of p53 was markedly up-regulated when the mice were fed a high-calorie diet, suggesting that excessive calorie intake promotes endothelial senescence. To investigate the role of endothelial p53 in type 2 diabetes, we analyzed metabolic parameters in endothelial cell-specific p53 conditional knockout (ECp53CKO) mice on a high-calorie diet. In spite of no difference in dietary intake, ECp53CKO mice had a significantly smaller weight and less fat accumulation than control mice. Moreover, ECp53CKO mice showed better insulin sensitivity and glucose tolerance than control littermates. ECp53CKO mice demonstrated a significant increase in oxygen consumption and had a higher core body temperature compared with control mice. Next we considered some assumed mechanisms of relationship between endothelial cell p53 expression and metabolic disorders. As a result, we found that ECp53CKO mice had higher glucose uptake in skeletal muscles than control. These results indicate that inhibition of endothelial senescence ameliorates insulin resistance by increasing energy consumption via glucose uptake and suggest that endothelial p53 will be a novel therapeutic target for type 2 diabetes.
Assessment of mother and fetus in labour
Authors: O. Olsen, P. Steer
Journal: BMJ (1999)

Editor—In its advice for authors1 of ABCs the BMJstates that “there are now many ... good systematic reviews” and that “we would like ... evidence for key statements.” But is this advice always followed?

My concern was raised by Steer’s article on assessment of the mother and fetus in labour in the ABC of labour care, in which electronic fetal heart rate monitoring is discussed.2 No systematic reviews are listed in the key references. The systematic reviews published by the Cochrane Collaboration show no apparent benefit in terms of neonatal outcome.3,4 This is not mentioned in the ABC; rather it is stated that electronic fetal heart rate monitoring has had a “bad press,” and it is suggested that this could be due “to a false expectation that it could reveal all about fetal condition during labour.” A more straightforward explanation might be that it adds no benefits beyond intermittent auscultation but is expensive, increases the risk of caesarean section, and promotes a false need for centralisation of births.

More specifically, a box lists some “accepted indications for continuous electronic fetal heart rate monitoring in labour,” including labour before 34 weeks. It is not clear why and by whom these indications are accepted. The inclusion of this indication is especially odd as a trial that focused on premature infants showed a large and significant increase in cerebral palsy (relative risk 2.5) among babies monitored electronically, and no benefits.5 Is the list of indications exclusively opinion based and sometimes contrary to firm evidence or does some evidence exist to support it? If it is opinion based I suggest that the table of accepted indications is revised before the ABC of Labour Care is published as a book and that thorough explanations are given if any of the advice is against firm evidence.
Abstract 16499: Quantitative Assessment of Mitral Valve Geometry in Patients with Degenerative Aortic Stenosis Using Real-Time 3D Transesophageal Echocardiography
Authors: Kyoko Otani, Masaaki Takeuchi, Kyoko Kaku, Nobuhiko Haruki, Hidetoshi yoshitani, Roberto M Lang, Yutaka Otsuji
Journal: Circulation (2010)
National screening programme for diabetic retinopathy
Authors: S. Prasad, H. Swindlehurst, L. G Clearkin, R. Broughton
Journal: BMJ (2001)

Editor—We have concerns about the National Screening Committee's recommendations for a risk reduction programme for diabetic retinopathy, in which digital photography is the screening method of choice.1 The gold standard for fundus examination is slit lamp biomicroscopy performed by an experienced ophthalmologist; this is the standard on which treatment decisions are made. The same technique used by other trained professionals in a screening environment duplicates the gold standard.

Slit lamp biomicroscopy has advantages over fundus photography. It offers a stereoscopic view, thereby detecting diffuse macular oedema that is missed by photography. The entire post-equatorial retina can be examined with this technique, whereas even seven-field photography misses about 17% of the retina.2

The technical failure rate of photography is high and has been reported to be 14.4%, compared with only 2.2% for ophthalmoscopy in the same group.3 In our district the technical failure rate of slit lamp biomicroscopy is 0.2%.4 Over-reading by trained graders has been reported in studies of photographic screening.2 One study looked at the performance of retina specialists compared with a standardised reading centre and found an overall agreement of only 74%, concluding that there was a significant discrepancy in concordance.5

The main reason for choosing digital photography seems to be the ease of audit, with no need for repeat examinations. However, the high technical failure rate of photography means that more re-examinations will be needed with this technique; a 5-10% re-examination rate for audit purposes in an ophthalmoscopic screening system compares favourably with a 15% re-examination rate because of technical failure in a photographic screening system.3,4

We also have concerns about the cost of the different screening systems. A new national training infrastructure will be needed to provide accredited training for photographic screeners, whereas integrating retinopathy screening skills into the training of optometrists would be fairly easy. Thus training and accreditation costs would be lower for screening by optometrists.

The main cost of this screening is the fee paid to the optometrists. The national committee estimates this at £20, but in our district it is £15. This alone would reduce the overall cost by £60 000 a year for a programme that had 12 000 primary screen events a year. Most optometrists already have the necessary equipment, and thus the cost of new equipment for screening would be unlikely to be great.
Early Detection of Lung Cancer with Meso Tetra (4-Carboxyphenyl) Porphyrin-Labeled Sputum
Authors: Lara Patriquin, Daniel T. Merrick, David Hill, Richard G. Holcomb, Madeleine E. Lemieux, Gordon Bennett, Bijal Karia, Vivienne I. Rebel, Thomas Bauer
Journal: Journal of Thoracic Oncology (2015)

Early detection of lung cancer in high-risk individuals reduces mortality. Low-dose spiral computed tomography (LDCT) is the current standard but suffers from an exceedingly high false-positive rate (>96%) leading to unnecessary and potentially dangerous procedures. We, therefore, set out to develop a simple, noninvasive, and quantitative assay to detect lung cancer.This proof-of-concept study evaluated the sensitivity/specificity of the CyPath Early Lung Cancer Detection Assay to correctly classify LDCT-confirmed cohorts of high-risk control (n = 102) and cancer (n = 26) subjects. Fluorescence intensity parameters of red fluorescent cells (RFCs) from tetra (4-carboxyphenyl) porphyrin (TCPP)-labeled lung sputum samples and subjects' baseline characteristics were assessed for their predictive power by multivariable logistic regression. A receiver operating characteristic curve was constructed to evaluate the sensitivity/specificity of the CyPath assay.RFCs were detectable in cancer subjects more often than in high-risk ones (p = 0.015), and their characteristics differed between cohorts. Two independent predictors of cancer were the mean of RFC average fluorescence intensity/area per subject (p < 0.001) and years smoked (p = 0.003). The CyPath-based classifier had an overall accuracy of 81% in the test population; false-positive rate of 40% and negative predictive value of 83%.The tetra (4-carboxyphenyl) porphyrin -based CyPath assay correctly classified study participants into cancer or high-risk cohorts with considerable accuracy. Optimizing sputum collection, sample reading, and refining the classifier should improve sensitivity and specificity. The CyPath assay thus has the potential to complement LDCT screening or serve as a stand-alone approach for early lung cancer detection.
Abstract 8779: Effect of Cathepsin a Inhibition on Cardiac Function and Remodeling in Rats with Heart Failure Induced by Ischemia and Long-Term Reperfusion
Authors: Wolfgang Linz, Thomas Hübschle, Georg Horstick, Paulus Wohlfahrt, Hans-Paul Juretschke, Dominik Linz, Claudia Neumann-Haefelin, Hartmut Rütten, Sven Ruf, Thorsten Sadowski
Journal: Circulation (2011)

Introduction: Cathepsin A (CathA) is a lysosomal carboxypeptidase involved in the cardiac metabolism of various peptide hormones. Its expression is significantly upregulated in the border zone after myocardial infarction (MI) in rats. Affymetrix profiling in MI patients revealed a similar regulation. Method: Male Wistar rats were randomized in: (1) Sham-OP, (2) I/R-Placebo (I/R=30min ischemia/reperfusion of the left coronary artery), (3) I/R-ramipril (RA 1 mg/kg/d p.o.), (4) I/R - CathA Inhibitor SAR1 (SAR1 30 mg/kg/d p.o.). After 9 weeks of treatment a magnetic resonance imaging (MRI)-investigation was done. Thereafter, left ventricles (LV) were fixed for histological evaluation and gene expression analysis by Taqman PCR. Brain natriuretic peptide (BNP) was measured in serum by ELISA. Results: Inhibition of CathA with SAR1 attenuated left ventricular (LV) remodeling observed after I/R without altering blood pressure. MRI analysis revealed preserved ventricular wall geometry in infarcted and non-infarcted regions. Global parameters such as ejection fraction, cardiac output, stroke volume, end-diastolic volume, end-systolic volume and left ventricle peak filling rate were significantly improved during dobutamin stress when compared to placebo treated I/R-rats. Especially the regional parameters such as wall motion and systolic wall thickness were improved in the infarcted area and even normalized in the non-infarcted area in SAR-treated I/R-rats. In contrast, RA treatment did not prevent the adverse remodeling. In all parameters SAR1 was clearly superior to RA. Histological investigations confirmed the beneficial effects of SAR1 treatment and serum levels of BNP were significantly reduced in SAR1 treated animals. LV gene expression of TGFβ, ANP, collagen type III and CD14 was decreased by ramipril and SAR1 treatment. Conclusion: We identified hitherto unknown functions of CathA in cardiac disease. Especially the dramatic improvement in LV wall geometry after inhibition of CathA with SAR1 makes this enzyme a highly promising target for the treatment of post-MI heart failure patients. SAR1 has the potential to introduce a new treatment option for patients with acute MI to further preserve myocardial function on top of standard treatment.
Abstract 19865: Rem-GTPase Regulates Cardiac Myocyte L-type Calcium Current
Authors: Carmen Kiper, Janos Magyar, Shawn Crump, Douglas A Andres, Jonathan Satin
Journal: Circulation (2010)

The L-type calcium channels (LTCC) are critical for maintaining Ca2+-homeostasis. In turn, Ca2+-homeostasis is critical for cardiac myocyte growth. In heterologous expression studies, the RGK-class...
Abstract 5779: Quantification of Right Ventricular Dyssynchrony in Acute Pulmonary Embolism and Right Ventricular Pressure Overload Using Speckle-Tracking Strain Imaging
Authors: Emiyo Ogawa, Kaoru Dohi, Katsuya Onishi, Takeshi Takamura, Hiroshi Nakajima, Masaki Tanabe, Satoshi Ota, Hiroya Tamada, Norikazu Yamada, Masatoshi Miyahara, Mashio Nakamura, Masaaki Ito
Journal: Circulation (2008)

Acute right ventricular (RV) pressure overload can alter RV systolic synchronicity associated with RV expansion and wall motion abnormalities in patinets with acute pulmonary thrombo-embolism (APTE). Twenty patients with massive or sub-massive APTE (mean age 57 ± 18 years, estimated peak systolic pulmonary pressure 51 ± 16mmHg) had echocardiography with speckle-tracking strain imaging on admission. RV dyssynchrony was defined as the time difference from earliest to latest peak strain among 6-sites (basal septum, mid septum, apical septum, apical free wall, mid free wall, basal free wall) form apical 4-chamber view using speckle-tracking longitudinal strain imaging. All intervals were corrected for heart rate (corrected interval = measured interval/(RR interval) 1/2 ). Twenty normal subjects (Control: mean age 58 ± 10 years) were also assessed RV function and synchronicity for comparison. APTE had significantly low RV fractional area change (29 ± 10%* vs. 50 ± 7%), low global RV strain (−13 ± 4%* vs. −25 ± 3%), and large RV dyssynchorny (220 ± 103msec* vs. 78 ± 39msec) compared with Control (*p&lt;0.05 vs. Control). After hemodynamic recovery from acute RV pressure overload by primary thrombolysis and/or anticoagulation therapy, both global RV strain and dyssynchrony were improved (−18 ± 4%† and 130 ± 53msec†, †p&lt;0.05 vs. APTE on admission, respectively). Acute RV pressure overload induced reversible RV systolic dyssynchrony associated with RV systolic dysfunction in patients with APTE.
Abstract 5539: Tenascin-c Has a Protective Role During the Development of Abdominal Aortic Aneurysm
Authors: Taizo Kimura, Koichi Yoshimura, Hiroki Aoki, Yasuhiro Ikeda, Kyoko Imanaka-Yoshida, Toshimichi Yoshida, Kimikazu Hamano, Michiaki Hiroe, Kazutaka Aonuma, Masunori Matsuzaki
Journal: Circulation (2009)

Abdominal aortic aneurysm (AAA) is an important healthcare problem for which non-surgical treatment is not available. Recently we reported that c-Jun N-terminal kinase-targeted pharmacotherapy can cause the regression of AAA by regulating inflammation and abnormal metabolism of extracellular matrix (ECM). To realize the pharmacotherapy, it is essential to develop the therapeutic biomarker that is involved in the pathogenesis and reflects the disease activity of AAA. We previously reported that tenascin-C (TN-C), an ECM protein, is an appropriate biomarker and can be used for the bioimaging of the inflammatory sites in several inflammatory diseases such as myocarditis. In this study, we tested if TN-C is a suitable biomarker for AAA. The tissue expression of TN-C was highest in human AAA with the diameter of 45–55 mm, the phase when AAA starts to progress rapidly. TN-C expression in individual aneurysms was highest at the transitional zone between normal and aneurysmal tissue where inflammatory process is most active. In mouse model of AAA induced by periaortic application of CaCl2, TN-C expression increased 4 to 6 weeks after the CaCl2 treatment that coincided with the rapid progression of AAA. Next, we examined if TN-C is involved in the pathogenesis of AAA by creating mouse model with periaortic application of CaCl2 followed by continuous infusion of angiotensin II in wild type (WT) and TN-C knockout (KO) mice. Surprisingly, 5 out of 15 TN-C KO mice developed large suprarenal aneurysms, while none of 14 WT mice did. Histologically, TN-C KO mice showed much more severe inflammation and destruction of elastic lamellae compared to WT. This may be because TN-C-deficient vascular smooth muscle cells express much higher cathepsin S, an elastolytic protease, and inflammatory mediators such as pentraxin 3. These results indicate that TN-C is expressed at the active lesion of AAA and critically involved in the pathogenesis by protecting aorta against tissue destruction. Because serum TN-C reflects the severity of inflammation and is also suitable for bioimaging in various inflammatory diseases, current study suggests that TN-C is an excellent candidate for the therapeutic biomarker and a potential therapeutic target for AAA.