tbuckley/cabot-search huggingface dataset:
Abstract 3980: Pre-clinical evaluation of a novel DNA crosslinking agent, Ureidomustin (BO-1055) in pediatric sarcomas
Authors: Srikanth R. Ambati, Elissa W. Wong, Benet Pera, Elizabeth Peguero, Eloisi Caldas Lopes, Jin-Jer Chen, Jae-Hung Shieh, Tsann-Long Su, Malcolm A. Moore
Journal: Cancer Research (2014)

Abstract DNA crosslinking agents continue to be an important part of chemotherapy for pediatric sarcomas. We tested potent analogues of phenyl N-mustard-benzene conjugates in several tumor models. In this work, we compared the efficacy of a novel water-soluble DNA alkylating agent, Ureidomustin (BO-1055) in Ewing sarcoma, rhabdomyosarcoma, osteosarcoma, desmoplastic small round cell tumor (DSRCT) cell lines and early cultures derived from primary patient samples. We tested its toxicity in normal human cells in vitro including the proliferation of mesenchymal stromal cells, bone marrow-derived endothelial cells and purified cord blood CD34+ cells in colony-forming assay (for hematopoietic progenitor cells) and in cobblestone area forming assay (for hematopoietic stem cells). We performed cell viability, cytotoxicity and caspase activation assays in a dose-dependent and time-dependent manner. We also performed apoptosis, cell cycle analyses using flow cytometry, immunoblot analysis and in vivo experiments in nude mice using Ewing sarcoma (A673) cell line transduced with GFP/luciferase for bioimaging. We evaluated cardiotoxicity in the HL-1 cardiomyocyte line in vitro and noted a 227 fold less cytotoxicity using BO-1055 compared to Doxorubicin. Based on MTD testing in nude mice, we used 30mg/kg q2d for 5 doses after tumors reached 75-100mm3 and were detected on luciferase bioimaging. Our results indicated that BO-1055 has a significant therapeutic window in its activity (mean IC50±SD μM) for rhabdomyosarcoma (0.16±0.11), Ewing sarcoma (0.48±0.29) and DSRCT (3.07±0.94) but not for osteosarcoma (IC50&amp;gt;10μM). The mean IC50 in benign cells was &amp;gt;10μM. Treatment with BO-1055 resulted in G2 arrest and activation of caspases 3 and 7 in a dose dependent manner. A673 xenografts were significantly inhibited by BO-1055 compared to the control mice injected with vehicle, based on mean fluorescence intensity and size of the tumors. Our results suggest that BO-1055 has potent activity against Ewing sarcoma and rhabdomyosarcoma and presents a strong rationale for further development as a therapeutic agent. Citation Format: Srikanth R. Ambati, Elissa WP Wong, Benet Pera, Elizabeth Peguero, Eloisi Caldas Lopes, Jin-Jer Chen, Jae-Hung Shieh, Tsann-Long Su, Malcolm AS Moore. Pre-clinical evaluation of a novel DNA crosslinking agent, Ureidomustin (BO-1055) in pediatric sarcomas. [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 3980. doi:10.1158/1538-7445.AM2014-3980
Plaque radiotherapy for large posterior uveal melanomas (≥8-mm thick) in 354 consecutive patients 11Presented in part at the annual meeting of the American Academy of Ophthalmology, October 2002.
Authors: Carol L Shields, Masood Naseripour, Jacqueline Cater, Jerry A Shields, Hakan Demirci, Asraf Youseff, Jorge Freire
Journal: Ophthalmology (2002)
Toxic epidermal necrolysis.
Authors: A. V. Ratnam
Journal: British Journal of Dermatology (1978)

Journal Article Toxic epidermal necrolysis: FIVE CASE REPORTS OF UNUSUAL PRESENTATION IN ZAMBIANS Get access A. V. RATNAM A. V. RATNAM Department of Dermatology, University Teaching Hospital, Private Bag R. W. I., Lusaka, Zambia Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 99, Issue 3, 1 September 1978, Pages 271–277, https://doi.org/10.1111/j.1365-2133.1978.tb01996.x Published: 01 September 1978
HIV Researchers Air New FindingsBrew It or Chew It? Military Seeks Ways to CaffeinateMillennial Influenza VaccineFDA May Get Welcome New Funds in Its BudgetMISCELLANEA MEDICAHIV Researchers Air New FindingsBrew It or Chew It? Military Seeks Ways to CaffeinateMillennial Influenza VaccineFDA May Get Welcome New Funds in Its BudgetMISCELLANEA MEDICA
Authors: J Stephenson
Journal: JAMA (1999)

CHICAGO—Researchers are detecting signs that the immune systems of HIVinfected patients treated with highly active antiretroviral therapy (HAART) can be at least partly restored—although many questions remain about how fully the battered immune system can be healed. The recovering immune system, an increasing awareness of the importance of the key immune cells in controlling infection, and concerns about drug-resistant HIV were among the issues that took center stage at the Sixth Conference on Retroviruses and Opportunistic Infections held here last month.
Abstract MP59: Revisiting Heritability Accounting For Common Environmental Effects And Maternal Inheritance
Authors: Chunyu Liu, Josée Dupuis, Martin G Larson, L. Adrienne Cupples, Jose M M Ordovas, Ramachandran S Vasan, James Meigs, Paul F Jacques, Danial Levy
Journal: Circulation (2014)

Background: Heritability measures the proportion of phenotypic variation attributable to genetic factors. Reliable heritability estimates are used to determine the necessary sample size and power for subsequent genetic studies of susceptibility genes. In addition to a shared nuclear genetic component, common environmental factors and maternal or mitochondrial inheritance may have strong effects on some phenotypes. Failure to account for necessary variance components may give rise to biased heritability estimates. Aims: Our primary goal was to investigate how heritability estimates are biased in the presence of common environmental or/and maternal effects. The second goal was to estimate mitochondrial inheritance for a number of common phenotypes. Methods: We employed variance component methods to account for additional variance components using both simulated and Framingham Heart Study (FHS) pedigree data to revisit heritability estimates in the presence of common environmental and maternal effects. Results: Using both simulated families and actual FHS extended pedigrees, we demonstrated that heritability is greatly overestimated when key variance components are not properly accounted for. The inflation in heritability ranged from 9% to 214% across several anthropometric, metabolic and life-style phenotypes when we compared models that consider correct variance components and simple models that only consider familial relationships (Table 1). Maternal inheritance was observed in most phenotypes investigated. The estimated maternal inheritance ranged from ~1 to 5%, which is considerable because the mitochondrial genome is about the size of an average gene. Conclusion/Discussion: We systematically investigated the influence of common environmental effects and maternal inheritance in heritability estimates using extended pedigrees. Our findings may explain, in part, the missing heritability for some traits and may facilitate further collaborations in the genetic study of mitochondrial DNA in disease susceptibility for common phenotypes.
Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene
Authors: Hidetoshi Date, Osamu Onodera, Hajime Tanaka, Kiyoshi Iwabuchi, Kazutoshi Uekawa, Shuichi Igarashi, Ryoko Koike, Tadashi Hiroi, Tatsuhiko Yuasa, Yutaka Awaya, Tetsuo Sakai, Tatsuya Takahashi, Hideki Nagatomo, Yoshiki Sekijima, Izumi Kawachi, Yoshihisa Takiyama, Masatoyo Nishizawa, Nobuyoshi Fukuhara, Kayoko Saito, Sumio Sugano, Shoji Tsuji
Journal: Nature Genetics (2001)
Familial Link Seen in Obstructive Sleep Apnea
Authors: Lynne Lamberg
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Mutations at the mitochondrial DNA polymerase (POLG) locus associated with male infertility
Authors: Anja T. Rovio, David R. Marchington, Susanne Donat, Hans-Christian Schuppe, Josef Abel, Ellen Fritsche, David J. Elliott, Pekka Laippala, Arja L. Ahola, David McNay, Robert F. Harrison, Barbara Hughes, Thomas Barrett, David M.D. Bailey, Denise Mehmet, Anne M. Jequier, Tim B. Hargreave, Shu-Huei Kao, James M. Cummins, David E. Barton, Howard J. Cooke, Yau-Huei Wei, Lars Wichmann, Joanna Poulton, Howard T. Jacobs
Journal: Nature Genetics (2001)
Abstract 5582: Safety and Efficacy of Rivaroxaban in Prevention of Venous Thromboembolism in Patients Undergoing Elective Major Orthopedic Surgery: A Meta-Analysis of Randomized Controlled Trials
Authors: Umesh U Tamhane, Pascal Meier, Guido Knapp, Hitinder S Gurm
Journal: Circulation (2009)

Background: Venous thromboembolism is a significant cause of morbidity and mortality after major orthopedic surgery. Recent clinical trials comparing enoxaparin with rivaroxaban, a novel oral factor Xa inhibitor for thromboprophylaxis were not adequately powered to detect differences in low frequency clinical outcomes. We evaluated the impact of rivaroxaban in prevention of deep venous thrombosis (DVT) and pulmonary embolism (PE) compared to enoxaparin in patients undergoing elective total knee replacement (TKR) or total hip replacement (THR). Methods: Eight randomized trials (n=13398 patients) comparing rivaroxaban (10 mg/day) with enoxaparin therapy were included. Summary odds ratios for DVT, PE, deaths, major bleeding and cardiovascular events were calculated using random-effects models. Results: Rivaroxaban therapy was associated with a significant reduction in DVT (Odds ratio [OR] 0.49, 95% CI 0.33 – 0.75, p = 0.001). There was no significant difference in the incidence of PE (OR 0.90, 95% CI 0.30 –2.77, p = 0.86), deaths (OR 0.66, 95% CI 0.27–1.65, p = 0.38) or cardiovascular events (OR 0.91, 95% CI 0.50 –1.65, p = 0.76) during follow up for rivaroxaban compared to enoxaparin in THR and TKR populations. Major bleeding (OR 1.56, 95% CI 0.86 –2.83, p = 0.15) was also not significantly different between the two regimens. Conclusion: Rivaroxaban as a fixed once daily anticoagulant may be a more effective agent compared to enoxaparin for thromboprophylaxis in patients undergoing major orthopedic surgery.
A Practical Handbook of Joint Fluid Analysis.
Authors: Robert A. Gatter, H. Ralph Schumacher
Journal: Annals of Internal Medicine (1984)

A guide to the use of joint fluid analysis and its application for the clinician and technician. New to this edition are a chapter on physiology and pathophysiology of synovial fluid, an appendix featuring lab standards for synovianalysis, and increased depiction of joint aspiration sites.
PERICARDIAL COELOMIC CYST SIMULATING CHRONIC PERICARDIAL EFFUSION: REPORT OF A CASE
Authors: F S GERBASI
Journal: Annals of Internal Medicine (1954)

Case Reports1 October 1954PERICARDIAL COELOMIC CYST SIMULATING CHRONIC PERICARDIAL EFFUSION: REPORT OF A CASEFRANCIS S. GERBASI, M.D.FRANCIS S. GERBASI, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-41-4-828 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAlthough pericardial cysts are relatively rare, recent medical literature has contained several excellent reports1, 2, 3 concerning the etiology, pathology, diagnosis and treatment of these anomalies. An extensive review of the publications on this subject, however, shows that cysts of such size, configuration and location as to be confused with chronic pericarditis with effusion are exceedingly rare. Inasmuch as the cyst herein reported was difficult to differentiate from pericardial effusion and appears to be the largest coelomic cyst ever described, it is felt that it may be of interest.CASE REPORTA 34 year old white woman was admitted to...Bibliography1. LillieMcDonaldClagett IWRJTO: Pericardial coelomic cysts and pericardial diverticula, J. Thoracic Surg. 20: 494, 1950. CrossrefGoogle Scholar2. Lambert AV: Etiology of thin-walled thoracic cysts, J. Thoracic Surg. 10: 1-7, 1940. CrossrefGoogle Scholar3. ForseeBlake JHHA: Pericardial coelomic cyst, Surgery 31: 753-760, 1952. MedlineGoogle Scholar4. Davis CL: Development of the human heart from its first appearance to the stage found in embryos of twenty paired somites, Contrib. Embryol. 19: 247-287, 1927. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Long Beach, California*Received for publication November 6, 1953.From the Department of Surgery, University of Michigan School of Medicine, Ann Arbor, Michigan. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byNeoplasmen des MediastinumsMediastinumA Clinical Appraisal of Thymic Lesions and Anterior Mediastinal LymphomataRoentgenography of pericardial diseaseErkrankungen des PerikardPericardial Coelomic Cysts 1 October 1954Volume 41, Issue 4Page: 828-836KeywordsEtiologySurgery ePublished: 1 December 2008 Issue Published: 1 October 1954 PDF downloadLoading ...
Selective enrichment of transduced cells for gene therapy of an inherited immune deficiency, chronic granulomatous disease
Authors: Olga Ujhelly, Judit Cervenak, Csilla Laczka Ozvegy, Manuel Grez, Balazs Sarkadi, Katalin Nemet
Journal: Molecular Therapy (2004)

Stem cell based gene therapy is a promising tool for the treatment of inherited haematopoietic disorders, such as the X-linked chronic granulomatous disease (X-CGD). However, the relatively low number of gene-modified cells and their fast disappearance from the patients requires an in vivo selective enrichment of the graft cells expressing the therapeutic gene. In this study we applied the cDNA of a substrate mutant variant of the human multidrug-resistance ABC half-transporter, BCRP/MXR/ABCG2. The relatively small size of this cDNA is a potential advantage for gene therapy application.
99. Long-Term Expression of Soluble TNFR:Fc Protein Following Multiple Administrations of AAV-TNFR:Fc Vector Pseudotyped with Capsids of Alternate Serotypes
Authors: Thomas J. Conlon, Travis L. Cossette, Terence R. Flotte
Journal: Molecular Therapy (2004)

The use of recombinant adeno-associated serotype (rAAV2) as a vector for the liver has been hindered by the relatively low efficiency of stable transduction of hepatocytes (approximately 5%). Alpha-1 antitrypsin(AAT) deficiency is a common single gene disorder in which a mutation in the AAT gene (PI*Z) leads to misfolding of the protein, loss of the protective antiprotease effect of AAT for the lungs and a toxic effect on the hepatocyte where it is produced. Therefore, optimal therapy for AAT deficiency will require a high percentage of hepatocyte transduction in order to be effective for both liver and lung disease. Recently, rAAV genomes have been successfully pseudotyped with capsids from novel serotypes (eg. rAAV7 and AAV8), and AAV8 was shown to be quite efficient for hepatic transduction (Gao et al. PNAS 2002; 99:11854-59). We hypothesized that upon portal vein injection to target hepatocytes, serotype 8 would better transduce target cells and therefore express AAT in both a greater percentage of cells and in greater overall amounts. 1 × 1010 particle doses of serotypes 1, 2, 5 and 8 vectors carrying the human alpha-1-antitrypsin (hAAT) gene were injected in C57Bl/6 female mice at six weeks of age. Circulating hAAT in mouse serum was measured by a human-specific sandwich ELISA. RESULTS: In the serotype comparison studies, rAAV8 vectors express significantly sooner after injection than serotypes 1 or 5. This was demonstrated in samples from 1 week post-injection where serotypes 1 and 5 had no detectable hAAT expression, while the rAAV8 group had a mean level of 574 ug/ml and the rAAV2 group had a mean level of 2 ug/ml hAAT. By week 3, rAAV8 injected animals had circulating hAAT levels 30 times higher than AAV2(607 ug/ml versus 22 ug/ml). Subsequently, a dose escalation study was performed with doses of 1 × 109, 1×1010 and 1×1011 particles of the rAAV8-hAAT vector. At three weeks post-portal vein injection, the animals showed a clear dose-response with mean serum levels of 917, 7,065 and 806,449 ng/ml, respectively in the three groups. These results confirm the impression that rAAV8 may be a more promising gene vector for therapy of liver disorders. Further studies will be necessary to quantify the percent transduction of hepatocytes with rAAV8 and the functional effect in a liver disease model, as well as to evaluate the safety and biodistribution of the rAAV8-hAAT vector.
Abstract 1666: Suppression of cyclooxygenase-2 by dual-specificity phosphatase-2 ameilorates cancer malignancy
Authors: Yo-Hua Li, Shih-Chieh Lin, Shaw-Jenq Tsai
Journal: Cancer Research (2014)

Abstract Aberrant production of cyclooxygenase-2 (COX-2) and COX-2-derived prostaglandin E2 (PGE2) have been demonstrated to contribute to tumor development and malignancy in many human cancers. However, the initiating factor responsible for maintaining high levels of COX-2 expression during cancer development remains enigmatic. We hypothesize that aberrant expression of COX-2 in cancer cells is initiated by hypoxia, a common phenomenon occurs in very early stage during cancer development. Herein, we present data demonstrating that levels of COX-2 in cancer cells are induced by hypoxia in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. Intriguingly, HIF-1α does not directly induce COX-2 promoter activity. In contrast, induction of COX-2 expression is mediated by HIF-1α-induced downregulation of dual specificity phosphatase-2 (DUSP-2), a MAPK-specific phosphatase. Forced expression of DUSP2 reduces the levels of COX-2, while knockdown of DUSP2 induces COX-2 expression in cancer cells. Moreover, depletion of DUSP2 also induces the expression of microsomal prostaglandin E synthase (mPGES) and consequently increases the production of PGE2. Further study reveals that re-induction of DUSP2 abolishes hypoxia-induced COX-2 expression and PGE2 production. To test the hypothesis that COX-2 mediates loss-of-DUSP2-induced tumorigenesis, a selective COX-2 inhibitor, NS-398, was used to block the function of COX-2 in the DUSP2-knockdown xenograft mouse model. Knockdown of DUSP2 markedly enhances tumor growth while treatment with NS-398 reverses loss-of-DUSP2-induced tumor development in vivo. Taken together, our data indicate that DUSP2, a negative regulator of COX-2, plays a critical tumor suppressive role and hypoxia, a common stress during cancer development, suppresses DUSP2 to initiate COX-2 overexpression and promote cancer progression. Our findings suggest that preventing DUSP2 from hypoxia-mediated downregulation or re-induction of DUSP2 during cancer development may represent a potential approach for cancer therapy. Citation Format: Yo-Hua Li, Shih-Chieh Lin, Shaw-Jenq Tsai. Suppression of cyclooxygenase-2 by dual-specificity phosphatase-2 ameilorates cancer malignancy. [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 1666. doi:10.1158/1538-7445.AM2014-1666
Abstract 3554: Gene and miRNA expression networks specific to never smoker lung adenocarcinoma
Authors: Rebecca Kusko, Carly Garrison, Teresa Wang, Josh Campbell, Joseph Perez-Rogers, Lingqi Luo, Jennifer Beane, Gang Liu, Humam Kadara, Steven Belinsky, Marc E. Lenburg, Avrum Spira
Journal: Cancer Research (2014)

Abstract While smoking is well recognized as a major risk factor for lung cancer, there is a growing incidence of lung cancer in never smokers which is in turn the fifth leading cause of cancer-related death worldwide. Never smokers (NS) who develop lung cancer exhibit disparate profiles of somatic mutations and clinical responses to targeted therapy relative to lung cancer arising in current or former “ever” smokers (ES), suggesting that ES and NS lung cancer arise through distinct molecular processes. We therefore sought to characterize mRNA and miRNA expression differences specific to NS adenocarcinoma (AdC) to gain insights into the molecular differences underlying NS and ES AdC carcinogenesis. Total RNA was isolated from matched pairs of lung AdC tumor and adjacent histologically normal tissue obtained from 22 subjects (8 NS, 14 ES). Large and small RNA libraries were sequenced on the Illumina HiSeq 2000. Tumor-specific gene and miRNA expression differences between NS and ES were identified using linear mixed-effects ANOVA. MiRConnx was used to construct miRNA-mRNA networks. We identified 120 mRNA and 15 miRNA whose expression was modified uniquely in NS lung AdC. In the predicted miRNA-mRNA regulatory network, additional analysis pinpointed modulation of the development and cellular metabolism canonical pathway within genes connected to several of the differentially expressed miRNA (GATHER, p&amp;lt;0.001). Several of the differentially expressed mRNA and miRNA were validated by qRT-PCR in samples from an independent cohort. In summary, the construction of a miRNA-mRNA regulatory network has enabled us to identify molecular alterations that may be specific to NS lung AdC. Ultimately, these findings may serve to broaden the landscape of personalized therapeutic and treatment options by identifying targetable molecular interactions and therapeutic drug candidates for lung AdC in never smokers. Citation Format: Rebecca Kusko, Carly Garrison, Teresa Wang, Josh Campbell, Joseph Perez-Rogers, Lingqi Luo, Jennifer Beane, Gang Liu, Humam Kadara, Steven Belinsky, Marc E. Lenburg, Avrum Spira. Gene and miRNA expression networks specific to never smoker lung adenocarcinoma. [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 3554. doi:10.1158/1538-7445.AM2014-3554