tbuckley/cabot-search huggingface dataset:
A5.18 BMP2 requires TGF-BETA to induce osteophytes during experimental osteoarthritis
Authors: E N Blaney Davidson, E L Vitters, A B Blom, A P M van Caam, M B Bennink, W B van den Berg, F A J van de Loo, P M van der Kraan
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Osteophytes are a major hallmark of osteoarthritis (OA). Both TGF-beta and BMP2 can induce osteophytes in murine knee joints. We demonstrated that TGF-beta could induce chondrogenesis in mesenchymal stem cells when BMPs were inhibited but not vice versa. This suggested that BMP2 might require a trigger like TGF-beta to induce initial stages of chondrogenesis. Therefore, we investigated whether BMP2 was still able to induce osteophyte formation in experimental OA when TGF-beta activity was blocked. <h3>Materials and Methods</h3> We made a unique transgenic mouse (Col2a1-rtTA-BMP2) expressing BMP2 under control of the Col2a1 promoter, only when exposed to doxycycline (dox) which results in only chondrocytes producing BMP2. These mice were fed dox-food up to 8 weeks to investigate BMP2 effects on osteophyte formation. We induced the DMM-model and investigated whether BMP2 augmented osteophyte formation. We combined the DMM-model with intra-articular injection of an adenovirus overexpressing TGF-beta-inhibitor LAP with or without dox. Knee joints were isolated 4 weeks after DMM for histology. <h3>Results</h3> There was no significant difference in osteophyte formation between dox and non-dox treated Col2a1-rtTA-BMP2 mice. However, dox treatment increased the number of osteophytes (8.0) during DMM compared to DMM non-dox (4.25). These "new" osteophytes were Iarger than DMM-induced osteophytes. The lack of osteophytes by dox compared to DMM + dox implied that DMM provided a trigger enabling BMP2-induced osteophyte formation. To investigate whether TGF-beta was that trigger, we injected Ad-LAP one day after DMM-induction. Without TGF-beta, BMP2 no longer augmented the number of osteophytes during DMM. Strikingly, inhibition of TGF-beta significantly reduced the pace of osteophyte formation.. This was completely abolished by the presence of BMP2 restoring the speed of osteophyte formation and maturation. <h3>Conclusions</h3> Our data show that BMP2 is capable of inducing osteophyte formation, but is dependent on an additional trigger to achieve this, as present in OA. In OA conditions, BMP2 can severely aggravate osteophyte formation, both in number and size. However, when TGF-beta is blocked BMP2 is no longer capable of aggravating osteophyte formation during DMM. Strikingly, early inhibition of TGF-beta during OA impaired the speed of osteophyte formation, which could be compensated by the presence of BMP2. Our data show for the first time that BMP2 is dependent on TGF-beta to induce de novo osteophyte formation. This provides novel insight into the mechanism behind osteophyte formation and provides clues for future therapeutic application for osteophyte formation in OA.
Association of Herpesvirus Infections with T-Lymphocyte-Subset Alterations, Glomerulopathy, and Opportunistic Infections after Renal Transplantation
Authors: Robert T. Schooley, Martin S. Hirsch, Robert B. Colvin, A. Benedict Cosimi, Nina E. Tolkoff-Rubin, Robert T. McCluskey, Robert C. Burton, Paul S. Russell, John T. Herrin, Francis L. Delmonico, Janis V. Giorgi, Werner Henle, Robert H. Rubin
Journal: New England Journal of Medicine (1983)

We studied the interrelation among herpes-virus infections, T-lymphocyte subsets, opportunistic infections, and renal histopathology in 28 recipients of renal allografts. All primary or reactivated herpesvirus infections occurring in the first three months after transplantation in recipients of cadaveric grafts accompanied persistent inversions in the ratio of OKT4 (helper/inducer) to OKT8 (cytotoxic/suppressor) lymphocytes. In the less heavily immunosuppressed recipients of organs of living related donors, these inversions were seen only in association with clinically apparent cytomegalovirus infections. Five of seven opportunistic infections occurred in patients with OKT4/OKT8 ratios of less than 1.0. Biopsy specimens from patients with renal dysfunction occurring in association with a low OKT4/OKT8 ratio frequently revealed glomerular damage rather than acute cellular rejection. Monitoring of T-lymphocyte subsets provides early evidence of herpesvirus infections and identifies patients at increased risk for opportunistic infection after renal transplantation.
Living conditions in Iraq: 10 years after the US-led invasion
Authors: S Rawaf, S Hassounah, E Dubois, B Abdalrahman, M Raheem, H Jamil, A Majeed
Journal: Journal of the Royal Society of Medicine (2014)

In the early 1980s, Iraq was a middle-income and rapidly developing country with a well-developed health system. A few decades later - after wars, sanctions and a violent sectarian upsurge - child and maternal health indicators have deteriorated, its poverty headcount index is at 22.9% and diseases such as cholera have remerged. Today Iraq is beset by chronic political deadlock and a complexity of economic challenges; accordingly, all aspects of life are suffering, including health. Irrespective of the monumental investment to improve components of the health system, via national and international efforts, the health status of the population can only advance through resounding and synergistic effort in other aspects of life affecting health: the social determinants of health.
Acute Treatment of Hypercalcemia with Furosemide
Authors: W. N. Suki, J. J. Yium, M. Von Minden, C. Saller-Hebert, G. Eknoyan, M. Martinez-Maldonado
Journal: New England Journal of Medicine (1970)

Eight patients with serum calcium values ranging between 12.3 and 18.4 mg per 100 ml were treated with large doses of furosemide intravenously. Their urinary losses of water, sodium and potassium were measured and carefully replaced. Serum calcium was reduced to normal in three patients and to near normal in another three. In the remaining two patients serum calcium fell from 18.4 to 14.6, and from 18.0 to 14.8 mg per 100 ml. The mean fall in serum calcium was 3.1 mg, with a range of 2.3 to 3.8 mg per 100 ml. The decrease was the consequence of the excretion of 0.7 to 2.7 g of calcium in the period of diuresis. Magnesium losses were considerable and had to be replaced. This method of treatment appears safe in patients with compromised cardiac reserve, and effective even in patients with moderate renal insufficiency. The careful replacement of water and electrolyte losses (sodium, potassium and magnesium), however, is essential if this therapy is to be safe.
P442Chrysin alleviates isoproterenol-induced myocardial infarction in diabetic rats through modulation of PPAR-gamma
Authors: N Rani, S Bharti, D S Arya
Journal: Cardiovascular Research (2014)

Purpose: Chrysin (5,7-dihydroxylflavone), an agonist of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been shown to possess antioxidant and anti-inflammatory properties. Here, we investigated whether chrysin (60 mg/kg/day) can improve the pathophysiology of myocardial infarction in diabetes partially through the PPAR-gamma pathway by assessing a variety of indices, e.g., hemodynamic, biochemical, histoarchitectural changes, and apoptosis. Methods: Diabetes was induced by a single dose of streptozotocin (70 mg/kg, i.p.). Diabetic rats received either chrysin (60 mg/kg/day, orally), PPAR-gamma antagonist GW9662 (1 mg/kg/day, i.p.) or both for 28 days with concurrent administration of isoproterenol (85 mg/kg, SC) on days 27th and 28th. Results: Compared with diabetic controls, diabetic rats with myocardial infarction exhibited altered hemodynamic profiles (MAP, LVEDP, ±LVdP/dtmax) and reduction in the activities of creatine kinase-MB isoenzyme, lactate dehydrogenase, superoxide dismutase, catalase, and glutathione level along with increased level of malondialdehyde. Further, diabetic animals with myocardial infarction exhibited increased myonecrosis, edema, and apoptotic cell death. Treatment with chrysin significantly improved the redox status of the myocardium with subsequent cardiac functional recovery. However, significant effects were lowered in animals treated with chrysin plus GW9662. Chrysin markedly inhibited Bax expression, TUNEL-positive cells, and increased Bcl2 expression. Moreover, down-regulated PPAR-gamma expression in myocardial infarcted diabetic hearts was also increased by chrysin. Conclusion: Chrysin improves myocardial infarction in diabetic rats through a pathway involving PPAR- gamma.
CIRCULATING INTERMEDIATE CD14++CD16+ MONOCYTES ARE INCREASED IN PATIENTS WITH ATRIAL FIBRILLATION AND REFLECT FUNCTIONAL REMODELING OF LEFT ATRIUM
Authors: Atsushi Suzuki, Koji Fukuzawa, Tomoya Yamashita, Akihiro Yoshida, Naoto Sasaki, Takuo Emoto, Asumi Takei, Ryudo Fujiwara, Tomoyuki Nakanishi, Soichiro Yamashita, Akinori Matsumoto, Hiroki Konishi, Hirotoshi Ichibori, Nobutaka Inoue, Ken-ichi Hirata
Journal: Journal of the American College of Cardiology (2015)
EFFECTIVE ORIFICE AREA REFERENCE VALUES WITH THE DIFFERENT SIZES OF THE SAPIEN 3 BALLOON-EXPANDING TRANSCATHETER AORTIC VALVE
Authors: Brandon S. Oberweis, Nadira Hamid, Omar Khalique, Isaac George, Tamim Nazif, Torsten Vahl, Jonathon White, Susheel Kodali, Martin Leon, Rebecca Hahn
Journal: Journal of the American College of Cardiology (2016)
The Intermediate Coronary Syndrome
Authors: Stephen J. Fischl, Michael V. Herman, Richard Gorlin
Journal: New England Journal of Medicine (1973)

In 23 patients with the intermediate coronary syndrome hypertension and an increased heart rate were common during pain. Clinical signs of acute left ventricular failure appeared in 1/3 of the patients. Electrocardiograms uniformly showed ST-segment changes or T-wave inversion or both. Coronary angiography revealed lesions similar to those seen during the chronic stage of coronary disease in all but one patient. Collateralization, however, occurred less frequently than expected. Left ventriculography exhibited only moderately abnormal function. Of 20 patients treated by beta-adrenergic blockade with propranolol 17 had prompt relief of pain, with lowering of blood pressure and heart rate. Seven patients with acute left ventricular failure showed clinical resolution during blockade. Fourteen patients eventually underwent revascularization surgery. Effective and safe treatment with beta-adrenergic blockade thus seems possible for most patients with the intermediate coronary syndrome. Revascularization surgery may then be considered on an elective basis. (N Engl J Med 288:1193–1198, 1973)
Review of John H. Evans,<i>The History and Future of Medical Ethics: A Sociological View</i>
Authors: Joseph J. Fins
Journal: The American Journal of Bioethics (2013)

It has been said that a good book reads you. And so it is with John H. Evans's The History and Future of Bioethics: A Sociological View. As a physician-ethicist I was fascinated by this sociologica...
Abstract 2929: Predictors of survival in never-smokers with non-small cell lung cancer: A large-scale, two-phase genetic study
Authors: Xia Pu, Yuanqing Ye, Margaret R. Spitz, Liang Wang, Jian Gu, Scott M. Lippman, Michelle AT Hildebrandt, Waun K. Hong, John D. Minna, Jack A. Roth, Ping Yang, Xifeng Wu
Journal: Cancer Research (2012)

Abstract Lung cancer in never-smokers is increasingly recognized as distinct from that in ever-smokers owing to substantial differences in etiology, clinical characteristics, and prognosis. Therefore, we aimed to identify prognostic markers specific for lung cancer in never-smokers in a two-stage study. First, 11,930 single-nucleotide polymorphisms (SNPs) in 904 inflammation-related genes were genotyped, and their associations with overall survival in 411 never-smokers with lung cancer at The University of Texas MD Anderson Cancer Center were analyzed. Next, fast-track validation of the top 37 SNPs in 311 never-smokers with lung cancer at Mayo Clinic was performed. Three SNPs (interleukin 17 receptor A:rs879576, bone morphogenetic protein 8A:rs698141, and spleen tyrosine kinase:rs290229) were validated (p&amp;lt;0.05), and two more SNPs (CD74:rs1056400 and CD38:rs10805347) were borderline significant (p=0.08) in the Mayo Clinic population. In combined analysis of the MD Anderson and Mayo Clinic patients, IL17RA:rs879576 resulted in a 40% reduction in the risk of death (p=4.1 × 10−5 [p=0.61, heterogeneity test]). We successfully validated a survival tree created in MD Anderson population based on gene-gene interactions in the Mayo Clinic population. This survival tree stratified patients into subsets with significantly different risks of death: patients at MD Anderson with the rs1056400_GG/rs698141_GA+AA genotype had a 2.32-fold higher risk of death (p=1.72 × 10−5) and 9-month shorter median survival time (MST) (p=4.5 × 10−4, log-rank test) than did those with the rs1056400_GG/rs698141_GG or rs1056400_GA+AA genotype in the discovery phase. Also, the patients at Mayo Clinic with the former genotype had an approximately twofold higher risk of death (p=0.02) and a strikingly shorter (by 26 months) MST (p=0.029, log-rank test) than did those with the latter genotype in the validation phase. We evaluated these five SNPs in 996 ever-smokers and found no significant associations. To our knowledge, this is the first study to systematically evaluate the associations of genetic variations in major inflammation-related genes with outcome of lung cancer in never-smokers. It provides strong evidence that inflammation-related genetic variations can affect clinical outcomes in these patients, which may lead to significant biological insight into these outcomes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2929. doi:1538-7445.AM2012-2929
AB0288 Rheumatoid Arthritis Impact Disease (RAID) among Moroccan Patients
Authors: S. El Kabbaj, F. Allali, L. Medrare, I. Benslama, T. Lakhdar, A. Ngeuleu, H. Rkain, N. Hajjaj Hassouni
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Score distributions and associations between the RAID score and RA demographic and disease related variables were examined in rheumatoid arthritis (RA) patients. <h3>Methods</h3> 103 patients diagnosed were enrolled in the study. Disease activity was assessed through the Disease Activity Score (DAS) 28 scale. quality of life was evaluated with The EQ-5D, and Health Assessment Questionnaire (HAQ) was completed by all patients. Pain and fatigue were evaluated with pain Visual analogic scale (VAS) and fatigue VAS respectively. The Rheumatoid Arthritis Impact disease (RAID) was used for the evaluation of the impact of rheumatoid arthritis. <h3>Results</h3> The mean RAID was 3,78±2,15. The distribution of the RAID: 32% had a score between 0 and 2, and 13.5% between 7 and 10. In univariate analysis the RAID score correlated with pain (r=0,79; IC95% (0,05-0,06); p&lt;0,001), fatigue (r=0,80; IC95% (2,2-3,7); p&lt;0,001), morning stiffness (r=0.53; IC95% (0,017-0,03); p&lt;0.001), DAS28 (r=0.75; IC95% (0,7-1); p&lt;0.001), HAQ (r=0,75; IC95% (1,7-2,4); p&lt;0,001), EQ-5D (r= -0,72; IC95% (-4,7_-3,2) p&lt;0.001). After multivariate analysis the pain (r=0,15; IC95% (0,01-0,35); p&lt;0,001), fatigue (r=0,18; IC95% (0,17-1,2); p&lt;0,01), DAS28 (r=0,26; IC95% (0,2-0,3); p&lt;0,001), HAQ (r=0,2; IC95% (0,18-0,9); p&lt;0,01) and EQ-5D (r= -0,26; IC95% (-1,9_-0,4); p=0,001) still strongly associated with RAID. <h3>Conclusions</h3> This study suggested that RAID associated with disease activity, functional capacity, Pain, fatigue and EQ-5D. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4863
Abstract P422: Dissociation between Changes in Cardiorespiratory Fitness and Cardiometabolic Risk Profile in Response to Exercise in Abdominally Obese Adults
Authors: Andrea Brennan, Miu Lam, Robert Hudson, Robert Ross
Journal: Circulation (2013)

Cardiorespiratory fitness (CRF) is a strong, independent predictor of morbidity and mortality. Although the majority of adults who increase daily physical activity experience an increase in CRF (VO2 peak), about 10-15% of participants do not increase CRF despite participating in a standardized exercise program. In this study we sought to determine whether exercise combined with a healthy diet was associated with a corresponding improvement in cardiometabolic risk factors despite the absence of change in CRF. We studied 59 sedentary, abdominally obese (waist circumference: 104.6 ± 8.5cm) adults who participated in 3 (women) or 4 (men) months of supervised aerobic exercise. CRF was measured using a standard treadmill test. Cardiometabolic risk factors included fasting triglycerides, total cholesterol, HDL-C, LDL-C, insulin, glucose, systolic and diastolic blood pressure. Participants were asked to exercise 7 days per week for the time required to expend 500 kcals per session for women, and 700 kcals for men. The intensity of exercise was self-selected and ranged between 65-90% of VO2 peak. Men and women were combined for all analyses. To examine the relationship between corresponding changes in cardiometabolic risk factors and CRF, participants were divided into tertiles based on mean change in CRF. A linear trend test was used to characterize the change in cardiometabolic risk factors across CRF change tertiles. The volume (energy expenditure (kcal)) and intensity (%VO2 peak) of exercise performed across tertiles of change in CRF was not different (P&gt;0.10). As expected a significant linear trend across tertiles was observed for change in CRF (P&lt;0.001), however, the mean change in CRF within the lowest tertile was not significant (P&gt;0.10). Without exception, no linear trend was observed for the change in cardiometabolic risk factors across tertiles of change in CRF (P&gt;0.10). This was also true for change in waist circumference and visceral fat (P&gt;0.10). Regression analysis using the total sample confirmed that, with the exception of glucose, the change score for each cardiometabolic risk factor was not related to the change in CRF (P&gt;0.10). Our findings suggest that in abdominally obese adults, improvement in cardiometabolic risk profile is not associated with change in CRF and that increasing physical activity combined with a healthful diet is associated with substantial health benefit in the absence of change in CRF.
Abstract 5684: B-catenin-dependent and independent changes in gene expression induced by sphingolipids
Authors: Hui Zhou, Eva M. Schmelz
Journal: Cancer Research (2010)

Abstract Dietary supplementation with sphingolipids inhibits colon tumorigenesis in carcinogen-treated CF1 mice and in multiple intestinal neoplasia (Min) mice that produce intestinal tumors spontaneously. In both cancer models the regulation of β-catenin by sphingolipid metabolites is an important early event. Stabilization and nuclear translocation of β-catenin and its interaction with T-cell factor (TCF)/lymphoid enhancer factor (LEF) play important roles to activate the transcription of genes associated with cancer development and progression. Sphingosine and ceramides, major digestion products of complex sphingolipids in the diet, down-regulate β-catenin transcriptional activity in a dose- and time-dependent manner. Our data indicate that sphingosine and ceramides suppress SW480 human colon cancer cell growth in a concentration-dependent manner. In the present study, we investigated the dependency of sphingosine- and ceramide-induced changes in gene expression on β-catenin transcriptional activity by comparing control and β-catenin siRNA treated cells. We observed changes in the expression of genes involved in signal transduction, transcription factors, cell cycle control and DNA damage repair, cell adhesion, cell invasion and metastasis, angiogenesis, and apoptosis and cell senescence. Most genes were regulated by all metabolites; however, some genes were only targeted by specific metabolites. Furthermore, only a small number of genes regulated by the sphingolipid metabolites relied completely on the activation of the β-catenin transcriptional activity. Further experiments are currently being performed to confirm the function of β-catenin on the regulation of these genes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5684.
Treatment of Late Infantile Metachromatic Leukodystrophy by Bone Marrow Transplantation
Authors: William Krivit, Elsa Shapiro, William Kennedy, Meryl Lipton, Lawrence Lockman, Stephen Smith, C. Gail Summers, David A. Wenger, Michael Y. Tsai, Norma K.C. Ramsay, John H. Kersey, Jeffrey K. Yao, Edward Kaye
Journal: New England Journal of Medicine (1990)

METACHROMATIC leukodystrophy of the late infantile type, an autosomal recessive inherited disorder caused by a deficiency of arylsulfatase A activity, is characterized by progressive mental regression, loss of speech, quadriparesis, peripheral neuropathy, and death within a few years of onset.1 We describe a 10-year-old girl with metachromatic leukodystrophy in whom neurophysiologic function and sulfatide metabolism had improved after she received a bone marrow transplant five years before. These results may encourage the use of bone marrow transplantation in other patients with metachromatic leukodystrophy early in the course of the disease, when the degree of central nervous system impairment and the . . .
1007 CONTRAST-ENHANCED ULTRASOUND (CEUS) VERSUS VOLUME-PERFUSION-COMPUTED-TOMOGRAPHY (VPCT) FOR DETECTION OF HEPATOCELLULAR CARCINOMA (HCC) AND EARLY RESPONSE EVALUATION OF TRANSARTERIAL CHEMOEMBOLISATION (TACE)
Authors: M. Horger, K. Brechtel, M. Schulze, D. Spira, M. Bitzer, U. Lauer, S. Kaufmann
Journal: Journal of Hepatology (2012)
Circulating T follicular helper cells with increased function during chronic graft-versus-host disease
Authors: Edouard Forcade, Haesook T. Kim, Corey Cutler, Kathy Wang, Ana C. Alho, Sarah Nikiforow, Vincent T. Ho, John Koreth, Philippe Armand, Edwin P. Alyea, Bruce R. Blazar, Robert J. Soiffer, Joseph H. Antin, Jerome Ritz
Journal: Blood (2016)
BI-29 * VARIANT ANALYSIS OF PRIMARY AND RECURRENT GLIOBLASTOMA USING ION AMPLISEQTM COMPREHENSIVE CANCER PANEL AND WHOLE EXOME SEQUENCING
Authors: S. Virk, R. Gibson, J. Barnholtz-Sloan, M. Quinones-Mateu
Journal: Neuro-Oncology (2014)

BACKGROUND: Glioblastoma is the most deadly and frequently occurring adult primary brain tumor. The characterization of genetic variants and molecular signatures in glioblastoma is heavily reliant upon genomic sequencing. The availability of rapid and economical sequencing platforms is necessary for the widespread adoption of high-throughput sequencing in the clinical environment. METHODS: Utilizing patient matched triplet samples consisting of normal blood and snap-frozen primary and recurrent glioblastoma tumor samples from the Ohio Brain Tumor Study, we compared whole exome sequencing data from TCGA to sequencing data obtained from Ion AmpliSeqTM Comprehensive Cancer Panel (CCP). RESULTS: As we anticipated, the number of variants identified from the exome sequencing data (n = 619) was greater than those identified from the Ion AmpliSeqTM CCP data (n = 22). Surprisingly, there were only six variants common across both data sets. In addition, none of the variants from the Ion AmpliSeqTM CCP data were shared across patient samples. CONCLUSIONS: Our pilot results suggest disparities in both the number and category of mutations identified from analysis of data generated from the Ion AmpliSeqTM CCP and whole exome sequencing. Future studies are needed to elucidate the nature of these differences and to determine the clinical relevance of variants that may be associated with glioblastoma recurrence and response to treatment. High-throughput sequencing based cancer panels may be improved by the development of brain tumor specific panels.