tbuckley/cabot-search huggingface dataset:
Abstract 2609: Mitochondrial Oxidative Stress Promotes Failure of the Pressure-Loaded Infant Right Ventricle
Authors: Huamei He, Dimitrios N Poutias, Kazuo Kitahori, Mistuhiro Kawata, Patrick Campbell, Douglas B Cowan, Ingeborg Friehs, Pedro J del Nido, Francis X McGowan
Journal: Circulation (2008)

Background: Right ventricular hypertrophy (RVH) and failure induced by chronic RV pressure overload is a major problem in congenital heart disease. We have previously shown that mitochondrial (Mito) damage accompanied load-induced infant RV failure. Here we assessed Mito electron transport chain(ETC) dysfunction and Mito oxidative stress in the transition of infant RVH to failure. Methods : Newborn rabbits underwent pulmonary artery banding (or sham) causing stable RV pressure load (~40 mmHg) and RVH by 2 weeks; RV contractile function (echocardiography) was preserved for ~4 weeks, followed by failure onset at ~8 weeks. Thus, RV free wall was assayed at 3, 4 and 8 weeks for ETC enzyme activities, high energy phosphates, Mito GSH/GSSH ratio (index of Mito ROS scavenging) , Mito 8-hydroxy-2-deoxyguanosine (8-OHdG, oxidative Mito DNA damage), Mito protein carbonyls (oxidative Mito protein damage) and Mito ultrastructure (electron microscopy). Results: By 4 weeks (RVH, preserved function), Mito 8-OHdG and protein carbonyl markedly increased, accompanied by decreased complex I and III activity. At 8 weeks (early failure), there were further increases in Mito 8-OHdG and protein carbonyls, significantly decreased GSH/GSSG ratio, further loss of complex I and III, and decreased activities of complexes IV and V; ATP content and ATP/ADP ratio were also significantly reduced. In parallel the number of abnormal disrupted RV mitochondria increased markedly. Conclusion: Pressure-load of the infant RV rapidly induces Mito oxidative stress. Due to the limited Mito scavenging and repair systems, this results in a cycle of Mito DNA and protein damage, progressive loss of ETC enzyme activity and further oxidative stress, as well as loss of functional mitochondria. This load-induced oxidative stress may be a therapeutic target to preserve RV function and oxidative metabolism and prevent the transition of RVH to RV failure. Changes in banded and sham-operated hearts after surgery
Greater left cerebral hemispheric metabolism in bulimia assessed by positron emission tomography
Authors: J C Wu, J Hagman, M S Buchsbaum, B Blinder, M Derrfler, W Y Tai, E Hazlett, N Sicotte
Journal: American Journal of Psychiatry (1990)

Eight women with bulimia and eight age- and sex-matched normal control subjects were studied with positron emission tomography using [18F]-fluorodeoxyglucose (FDG) as a tracer of brain metabolic rate. Subjects performed a visual vigilance task during FDG uptake. In control subjects, the metabolic rate was higher in the right hemisphere than in the left, but patients with bulimia did not have this normal asymmetry. Lower metabolic rates in the basal ganglia, found in studies of depressed subjects, and higher rates in the basal ganglia, reported in a study of anorexia nervosa, were not found. This is consistent with the suggestion that bulimia is a diagnostic grouping distinct from these disorders.
Patients With Glanzmann Thrombasthenia Lacking Platelet Glycoprotein α <sub>IIb</sub> β <sub>3</sub> (GPIIb/IIIa) and α <sub>v</sub> β <sub>3</sub> Receptors Are Not Protected From Atherosclerosis
Authors: O. Shpilberg, I. Rabi, K. Schiller, R. Walden, D. Harats, K.S. Tyrrell, B. Coller, U. Seligsohn
Journal: Circulation (2002)

Background — Platelets have been suggested to play a role in the early development of atherosclerosis. As one test of this hypothesis, we assessed whether patients with Glanzmann thrombasthenia who lack platelet glycoprotein α IIb β 3 (GPIIb/IIIa) complexes or both α IIb β 3 and the more ubiquitous α v β 3 cell membrane complexes are protected from development of atherosclerosis. Methods and Results — Seven patients with Glanzmann thrombasthenia, 45 to 66 years of age, underwent bilateral carotid artery ultrasonography and screening for risk factors of atherosclerosis. Findings consistent with early atherosclerosis evaluated by measurement of intima-media thickness and presence of atherosclerotic plaques were observed in 6 of the 7 patients. Intima-media thickness values higher than the 75th and 90th percentiles of age- and sex-matched white control subjects of the Atherosclerosis Risk in Communities (ARIC) study were observed in 30 and 8 of 56 carotid artery measurements, respectively. Five of the 6 patients with signs consistent with early atherosclerosis lacked both α IIb β 3 and α v β 3 complexes and 1 only lacked α IIb β 3 . Conclusions — Glanzmann thrombasthenia does not protect affected individuals from development of atherosclerosis.
Tumor-specific Immunity to Transplanted Dibenz[a,h]-anthracene-induced Sarcomas
Authors: Richmond T. Prehn
Journal: Cancer Research (1960)

Summary  Subcutaneous fibrosarcomas were induced in inbred mice by the implantation of glycerol-moistened crystals of dibenz[ a,h ]anthracene. Eleven dibenz[ a,h ]anthracene-induced sarcomas were investigated. The data demonstrate that the temporary growth of these tumors in other mice of the same inbred strain often produced a tumorspecific immunity to subsequent challenge inoculations of the same tumor. Normal tissues from the very mouse in which an antigenic tumor arose failed either to induce the immunity or to respond to it. The results are similar to previous findings with 3-methylcholanthrene-induced fibrosarcomas and therefore suggest that tumor-specific antigenicity may be a general property of fibrosarcomas induced by the aromatic hydrocarbons in mice.
Circulating fibrocytes in pulmonary arterial hypertension
Authors: Natalia Gambaryan, Montani David, Girerd Barbara, Huertas Alice, Sylvia Cohen-Kaminsky, Humbert Marc, Frederic Perros
Journal: European Respiratory Journal (2011)

Bone marrow-derived progenitor cells have been shown to participate in angiogenesis, vascular repair and tissue remodelling in pulmonary arterial hypertension (PAH). A unique subpopulation of peripheral blood mononuclear cells (PBMC), termed fibrocytes, has been demonstrated to develop myofibroblasic phenotype and contribute to the vascular remodelling process in hypoxic models of PAH. To extend these studies, we tested the hypothesis that circulating fibrocytes contribute to human PAH and examined their possible role as predictors of activity and progression of disease.  18 patients with idiopathic and familial PAH and 20 healthy control subjects were studied. Circulating fibrocytes, identified as CD11b+CD34+vimentin+ cells and membrane CD11b expression were quantified by flow cytometry. The in vitro differentiation capacity of PBMC to fibrocytes was quantified.  We observed a slight decrease in the percentage but not in the number of circulating fibrocytes in the blood of PAH patients, compared with healthy control subjects (0.67±0.015% in control subjects vs 0.22±0.04% in PAH patients, p  Our data suggest that a more detailed analysis of circulating fibrocyte function and activation is needed in PAH patients.
Uptake and metabolism of safingol in human neuroblastoma and leukemia cell lines
Authors: Hongtao Wang, Guo-Ying Kong, C. Patrick Reynolds, Barry J. Maurer
Journal: Cancer Research (2004)

2980   We reported that safingol (L-threo-dihydrosphingosine), the isomer of dihydrosphingosine, synergized multi-log fenretinide(4-HPR) cytotoxicity in a variety of types of solid tumor and leukemia cell lines in vitro. Safingol has a short plasma half-life in vivo. The mechanism of safingol synergistically increasing 4-HPR cytotoxicity is unknown. It has been reported that safingol inhibits protein kinase C activity, and DL-threo-dihydrosphingosine inhibits sphingosine kinase. As it has been mainly assayed in platelets, or cell extracts, or using short-term (minutes) drug exposure, its significance is unclear. To clarify the uptake and metabolism of safingol in human cancer/leukemia cells not only help us to understand the mechanism of safingol cytotoxicity, but also is a crucial step for design of an effective safingol administration strategy. Using tritium-labeled safingol as tracer, we studied the uptake and metabolism of safingol in human neuroblastoma cell line CHLA-90 and leukemia cell line MOLT-4. Safingol and its metabolites were analyzed by (high performance) thin-layer chromatography and liquid scintillation counting, cell viability were measured using DIMSCAN analysis. After 4 hrs incubation with 1 μM or 3 μM safingol, CHLA-90 cells uptake 59% and 38%, MOLT-4 cells uptake 72% and 59% of safingol, respectively. For the washout experiments, CHLA-90 or MOLT-4 cells were preincubated with 6 μM safingol for 2 hrs, then free safingol was washed away and fresh medium was added. Four hrs after washout, there was 50% and 70% free cellular safingol left in CHLA-90 cells and MOLT-4 cells, respectively. Twenty-four hrs after washout, only 15% and 21% free cellular safingol left in CHLA-90 cells and MOLT-4 cells, respectively. Lipids analysis showed that Safingol was N-acylated to form unsaturated L-threo-dihydroceramide and L-threo-dihydrosphingomyelin. No safingol-derived glucosylceramide was detected. Most of the cellular safingol was converted to L-threo-dihydrosphingomylelin in CHLA-90 cells, and to L-threo-dihydroceramide in MOLT-4 cells at 24 hrs after washout. Short chain L-threo-dihydroceramide (C2, C6 and C8) did not synergistically increase 4-HPR cytotoxicity in CHLA-90 and MOLT-4 cells. We conclude that 1). Safingol is uptoken very quickly by CHLA-90 and MOLT-4 cells; 2). High levels of free safingol exist in human cancer/leukemia cell for up to 4 hrs; 3). Most of safingol uptoken is converted to L-threo-sphingomyelin by CHLA-90 cells, and to L-threo-dihydroceramide by MOLT-4 cells; 4). No detectable glucosylceramide is formed from safingol; 5). Safingol cytotoxicity is decreased after converted to L-threo-dighydroceramide. This study has provided crucial information for design an effective strategy to administrate safingol for in vivo study, and for clarification of the mechanism of safingol synergizing 4-HPR cytotoxicity in human cancer/leukemia cells.
TREATMENT OF LUPUS ERYTHEMATOSUS WITH CHLOROQUINE..
Authors: JORGEN V. CHRISTIANSEN
Journal: British Journal of Dermatology (1957)

Journal Article TREATMENT OF LUPUS ERYTHEMATOSUS WITH CHLOROQUINE.: Therapeutic Results and a Comparison of the Value of Chloroquine and Mepacrine. Get access JØRGEN V. CHRISTIANSEN JØRGEN V. CHRISTIANSEN Department of Dermatology, the Finsen Institute, Copenhagen. (Director: Professor Poul V. Marcussen, M.D.) Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 69, Issue 5, 1 May 1957, Pages 157–168, https://doi.org/10.1111/j.1365-2133.1957.tb13249.x Published: 01 May 1957
FK506 (Tacrolimus) monotherapy for prevention of graft-versus-host disease after histocompatible sibling allogenic bone marrow transplantation
Authors: JW Fay, JR Wingard, JH Antin, RH Collins, LA Pineiro, BR Blazar, R Saral, BE Bierer, D Przepiorka, WE Fitzsimmons, RM Maher, DJ Weisdorf
Journal: Blood (1996)
The Effect of Coenzyme Q 10 on Morbidity and Mortality in Chronic Heart Failure
Authors: Svend A. Mortensen, Franklin Rosenfeldt, Adarsh Kumar, Peter Dolliner, Krzysztof J. Filipiak, Daniel Pella, Urban Alehagen, Günter Steurer, Gian P. Littarru
Journal: JACC Heart Failure (2014)
A role for MLH3 in hereditary nonpolyposis colorectal cancer
Authors: Ying Wu, Maran J.W. Berends, Rolf H. Sijmons, Rob G.J. Mensink, Edwin Verlind, Krista A. Kooi, Tineke van der Sluis, Claudia Kempinga, Ate G.J. van der Zee, Harry Hollema, Charles H.C.M. Buys, Jan H. Kleibeuker, Robert M.W. Hofstra
Journal: Nature Genetics (2001)
Impaired IL-20 expression in lung cancer contributes to high levels of COX-2/PGE2 and angiogenesis
Authors: Nathalie Heuze-Vourc’h, Ming Liu, Harnisha Dalwadi, Felicita E. Baratelli, Li Zhu, Lee Goodglick, Jake Solomon, Lauren Winter, Mehis Pold, Ruben Ramirez, Jerry W. Shay, John D. Minna, Steven M. Dubinett
Journal: Cancer Research (2005)

4642  >Background: Up-regulation of the inducible nitric oxide synthase (iNOS) and the cycloxygenase-2 enzyme (COX-2) have been reported to play a role in the process of carcinogenesis and angiogenesis. The aim of this study is to evaluate the possible correlation between iNOS, COX-2 and angiogenesis in ovarian serous carcinoma (OSC) Methods: We identified 118 patients with high-grade, advanced stage OSC from our database. Clinical data including patients’ and tumor characteristics and overall survival were collected. Two to 3 paraffin blocks were stained by immunohistochemistry (IHC) with antibodies to COX-2, VEGF and iNOS. For all three markers both intensity and percentage of positive cells were evaluated to give an overall score. Statistical analysis included Chi-square testing to evaluate the correlation between the various markers and the Kaplan-Meier method to evaluate survival Results: Up-regulation of all three markers was noted in a significant number of the cases. The frequencies of overexpression of the specific markers in the study population were: 49% for iNOS, 69% for COX-2 and 77% for VEGF. High iNOS expression strongly correlated with high expression of COX-2 and VEGF. In fact, 98.3% of tumors with high iNOS expression exhibited high COX-2 expression and 98.1% exhibited high VEGF expression. The median survival of patients with high iNOS expressing tumors was 637 days compared to 1107 days for those with low iNOS expressors; this difference did not reach statistical significance Conclusion: High expression of iNOS is noted in a significant number of OSC tumors. This high expression is associated with high expression of COX-2 and VEGF. This suggests a significant role for iNOS in the process of ovarian carcinogenesis and tumor angiogenesis and warrants further investigation
Abstract 3878: Glucagon-Like Peptide-1 Metabolite Protects the Myocardium Against Ischemia-Reperfusion Injury in Diabetes Mellitus
Authors: Susheel Gundewar, John W Elrod, John W Calvert, Xuelaing Du, Diane Edelstein, David J Lefer, Michael Brownlee
Journal: Circulation (2008)

Background: Glucagon-Like Peptide-1 (GLP-1) is an incretin hormone with potent plasma glucose lowering actions that is rapidly degraded by the enzyme Dipeptidyl Peptidase-IV to GLP-1(9 –36) amide . GLP-1(9 –36) amide (GLP1dp) has previously been viewed to be biologically inactive. However, our laboratory has demonstrated that GLP1dp inhibits hyperglycemia-induced production of oxidant species and prevents the inactivation of both eNOS and prostacyclin synthase in cells and diabetic animals. We investigated the effects of GLP1dp in two in vivo diabetic murine models of myocardial ischemia-reperfusion (MI-R) injury. Methods: Diabetic (db/db and STZ-diabetic) mice were treated with 2.4 μg/day of GLP1dp via Alzet pump for 7 days and subjected to 45 min of left coronary artery occlusion and 2 hr of R. At 2 hr of R, hearts were excised and evaluated for infarct (INF) size. Results: Diabetic (db/db) and STZ-diabetic mice treated with GLP1dp exhibited a 37% and 33% reduction in myocardial infarct size following MI-R respectively. Additionally, GLP1dp significantly reduced oxidative stress in the myocardium of these mice. Both models of diabetic mice (db/db and STZ-diabetic) exhibited elevated baseline blood glucose (BG) values of 386 ± 25 and 435 ± 15 mg/dl respectively. After 7 days of GLP1dp therapy, db/db mice exhibited a 48% reduction in BG values. In contrast, no reduction in BG was observed in the STZ-diabetic mice. Conclusion : Administration of GLP1dp peptide confers cardioprotection in diabetic mice by attenuating the extent of oxidant-mediated injury following MI-R. The cardioprotective actions of GLP1dp appear to be independent of any effects on blood glucose.
Effects of Thioacetamide on Metabolism of Proteins of Normal and Regenerating Liver
Authors: Masami Muramatsu, Harris Busch
Journal: Cancer Research (1962)

Summary  Within 24 hours after injection of thioacetamide, there was an increase in labeling of all proteins in the liver as measured by isotope uptake one hour after the intravenous injection of 10 µc. of l-lysine-U-C 14 . The greatest increase in uptake of isotope was found in the histones, whereas the smallest increase in uptake of the labeled amino acid was found in the microsomal proteins. After 9 days of treatment with thioacetamide, the uptake of isotope of l-lysine-U-C 14  was significantly increased only in the proteins of the cytoplasmic sap and the histones. As found by others, there was a marked decrease in the content of microsomal proteins and a relative increase in the content of the proteins of the cytoplasmic sap in the livers of rats treated with thioacetamide. At 24 hours after partial hepatectomy, there was a relatively equal increase in the labeling of all proteins, with the exception of the histones in which the increase in labeling was greater than that found in other fractions; there was a relative increase in labeling of mitochondrial proteins and a relative decrease in labeling of proteins of the cytoplasmic sap.  These data suggest that one difference between the biosynthetic activities of the regenerating liver and the liver of animals treated with thioacetamide is that in the former the uptake of amino acids into the mitochondrial proteins increases, whereas in the latter there is increase in the uptake of amino acids into the protein of cytoplasmic sap. This latter result more closely resembles the changes found in neoplastic cells.
Relationship of dissociation to self-mutilation and childhood abuse in borderline personality disorder
Authors: B S Brodsky, M Cloitre, R A Dulit
Journal: American Journal of Psychiatry (1995)

This study sought to document the prevalence of dissociative experiences in adult female inpatients with borderline personality disorder and to explore the relationship between dissociation, self-mutilation, and childhood abuse history.A treatment history interview, the Dissociative Experiences Scale, the Sexual Experiences Questionnaire, and the Hamilton Depression Rating Scale were administered to 60 consecutively admitted female inpatients with borderline personality disorder as diagnosed by the Structured Clinical Interview for DSM-III-R Personality Disorders.Fifty percent of the subjects had a score of 15 or more on the Dissociative Experiences Scale, indicating pathological levels of dissociation. Fifty-two percent reported a history of self-mutilation, and 60% reported a history of childhood physical and/or sexual abuse. The subjects who dissociated were more likely than those who did not to self-mutilate and to report childhood abuse. They also had higher levels of current depressive symptoms and psychiatric treatment. Multiple regression analysis demonstrated that each of these variables predicted dissociation when each of the others was controlled for, and that self-mutilation was the most powerful predictor of dissociation.Female inpatients with borderline personality disorder who dissociate may represent a sizable subgroup of patients with the disorder who are at especially high risk for self-mutilation, childhood abuse, depression, and utilization of psychiatric treatment. The strong correlation between dissociation and self-mutilation independent of childhood abuse history should alert clinicians to address these symptoms first while exercising caution in attributing them to a history of abuse.
Abstract 1911: NF-κB mediated CD47 upregulation promotes sorafenib resistance and its blockade synergizes the effect of sorafenib in hepatocellular carcinoma
Authors: Jessica Lo, Eunice Yuen Ting Lau, Irene Oi Lin Ng, Terence Kin Wah Lee
Journal: Cancer Research (2014)

Abstract Sorafenib, a multikinase inhibitor, is currently used as the normative treatment for advanced hepatocellular carcinoma (HCC). It can prolong survival for a few months however sorafenib insensitivity and resistance often develops in tumors hence a better understanding of resistance mechanisms is urgently needed. Tumor-initiating cells (T-ICs) have recently been implicated in the cause of treatment resistance. Recently, our group found that CD47 is preferentially expressed in liver T-ICs, which suggests a possibility of targeting CD47 in order to evade sorafenib resistance via elimination of liver T-ICs. To test this hypothesis, we have successfully developed sorafenib-resistant clones in HCC cell lines (BEL7402 and Huh-7 cells) and in vivo using patient-derived xenograft (PDTX #1) by continuous exposure to sorafenib. We found that sorafenib-resistant clones showed enhanced T-IC properties such as self-renewal, tumorigenicity and invasiveness, which is also accompanied by an increase in CD47 expression. We found increased NF-κB activation in sorafenib resistant clones indicated by upregulated levels of phosphorylated p65 and IkBα which is consistent to the bioinformatics analysis showing two putative NF-κB binding sites on the CD47 promoter. In addition, CD47 expression was found to be decreased upon treatment of NF-κB inhibitor IMD-0354 and increased upon treatment of TNF-α. These results suggested that NF-κB mediated CD47 upregulation promotes sorafenib resistance in HCC. To further confirm the role of CD47 in sorafenib resistance, we knocked down CD47 expression in CD47-high expressing HCC cells. Through annexin V staining, we found that knockdown of CD47 sensitized Huh-7 and MHCC-97L to sorafenib treatment at 10µM and 20µM respectively. Using patient derived xenograft model (PDTX #8) to investigate the effect of different treatment regimens, we found that mice treated with daily administration of sorafenib (100mg/Kg) showed tumor volume reduction by 3-fold upon 30 days of treatment and a similar effect was found in mice treated daily with and anti-CD47 antibody (500mg/Kg). Interestingly, sorafenib combined with anti-CD47 antibody exhibited maximal effect on tumor suppression. All in all, regulation of CD47 by NF-κB may enable the promotion of sorafenib resistance and anti-CD47 antibody in co-treatment with sorafenib may serve as a novel therapeutic regimen for the treatment of advanced stage HCC. Citation Format: Jessica Lo, Eunice Yuen Ting Lau, Irene Oi Lin Ng, Terence Kin Wah Lee. NF-κB mediated CD47 upregulation promotes sorafenib resistance and its blockade synergizes the effect of sorafenib in hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1911. doi:10.1158/1538-7445.AM2014-1911