tbuckley/cabot-search huggingface dataset:
Abstract 3270: Hemodynamic and Prognostic Implications of Net Atrioventricular Compliance in Patients with Mitral Stenosis: Exercise Echocardiographic Study
Authors: Hyung-Kwan Kim, Sung-A Chang, Jin-Shik Park, Hyun-Jae Kang, Bon-Kwon Koo, Sang-Hyun Kim, In-Ho Chae, Dae-Won Sohn, Byung-Hee Oh, Young-Bae Park, Yun-Shik Choi, Yong-Jin Kim
Journal: Circulation (2007)

Background-On the basis of the close association of left atrial(LA) compliance with pulmonary hypertension in patients with mitral stenosis(MS), we hypothesized that 1) Doppler-derived net atrioven...
Abstract IA31: Combining targeted therapy and immune checkpoint blockade to improve responses
Authors: Jennifer A. Wargo
Journal: Cancer Research (2015)

Abstract There have been significant advances in treatment of metastatic melanoma over the past several years through the use of targeted therapy and immune checkpoint blockade. Oncogenic mutations in the BRAF gene occur in over half of melanoma tumors, and treatment with agents targeting this mutation results in objective responses in the majority of patients. However significant limitations exist as responses are not durable, with the majority of patients progressing on therapy within 6-10 months. Another area of significant progress involves the use of immune checkpoint blockade, such as with monoclonal antibodies blocking CTLA-4 and the PD-1 pathway. In contrast, treatment of patients with immune checkpoint inhibitors results in a lower response rate than those observed with targeted therapy, but ones that tend to be more durable. With these advances, we are posed with therapeutic dilemmas with regard to timing and sequence of therapy. Namely, there is significant debate as to whether to begin treatment with targeted therapy versus immune checkpoint blockade upfront, and at which point to change treatment strategy. There is growing evidence of potential synergy in combining treatment with BRAF-targeted therapy and immune checkpoint blockade, and this concept is being empirically tested in clinical trials. There a strong scientific rationale for combining these therapies, as treatment with BRAF inhibitors is associated with increased immunogenicity of melanoma tumors within 2 weeks of therapy - with increased melanoma antigens and CD8+ T cell infiltrate, and decreased immunosuppressive cytokines and VEGF. BRAF inhibitors may also directly activate T cells through paradoxical activation of the MAPK pathway. However there is a concurrent increase in expression of immunomodulatory molecules (such as PD-L1) within 2 weeks of therapy which is likely related to T cell infiltrate, though also suggest a possible immune mechanism of resistance. Clinical trials and studies in murine models are currently underway to explore synergy between these therapies, and insights gained will be discussed herein. It is becoming increasingly apparent that complexities exist regarding appropriate timing and sequence in these combination strategies to optimize responses and minimize toxicity. Ultimately, ideal approaches using combined BRAF-targeted therapy and immune checkpoint blockade will be built on a deep understanding of the molecular and immune effects of each of these therapies in isolation, as well as in combination. Citation Format: Jennifer A. Wargo. Combining targeted therapy and immune checkpoint blockade to improve responses. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr IA31.
Targeted gene knockout mediated by triple helix forming oligonucleotides
Authors: Alokes Majumdar, Alexander Khorlin, Natalia Dyatkina, F.-L. Michael Lin, James Powell, Jilan Liu, Zhizhong Fei, Yuri Khripine, Kyoichi A. Watanabe, Jay George, Peter M. Glazer, Michael M. Seidman
Journal: Nature Genetics (1998)
Treatment of Sarin Exposure
Authors: Amir Krivoy, Ido Layish, Eran Rotman, Yoav Yehezkelli
Journal: JAMA (2004)

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
"New Look" Reflects Changing Style of Patient Safety EnhancementLearning Lessons From True-life School Trauma"New Look" Reflects Changing Style of Patient Safety EnhancementLearning Lessons From True-life School Trauma
Authors: D F Phillips
Journal: JAMA (1999)

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
556. Another Hepatic Control Region for Sustained Expression of Human Factor IX in the Mouse Liver
Authors: Ji Eun Lee, Hong Sung Kim, Keun Sik Kim, Eun Jung Kim, Jong Chul Kim, In Ho Song, Yong Serk Park
Journal: Molecular Therapy (2005)

For long-term gene expression mediated by plasmid vectors, the plasmids should remain stable in the episomal state with transcriptional and post-transcriptional activities inside nucleus. There was an important report that a hepatic control region (referred to HCR I) maintained plasmids in the stable episomal state in nucleus, preventing loss of plasmids. Furthermore, the HCR has an enhancer activity, thus leading to high expression of transgenes in hepatic cells. There is another hepatic control region, called the second hepatic control region (referred to HCR II). In this research, we have tried to compare the functional activities of HCR I and HCR II in hepatic transgene expression. Their sequences in the functional region have 85% homology. We constructed the plasmid vector containing HCR II and encoding human factor IX (pBS-HCRII-IX), that was compared with the plasmid containing HCR I (pBSHCRHPI-IXA, provided by Dr. Miao, U. Wa). Several other plasmids containing HCR I and HCR II (pBS-HCRI-HCRII-IX and pBS-HCRII-HCRI-IX) were also constructed. These four different plasmids were administered to mice by the hydrodynamic method. There was no significant differences among the expression levels of human factor IX by the four different vectors for 3 months; about 1.2 mg/ml (24% of the normal level) on day 1 and about 0.2 mg/ml (4% of the normal level) on day 85. Also, blood clotting activities of human factor IX produced by the four vectors were similar among each other for the same period of time. Meanwhile, the factor IX level induced by a control plasmid (pAAVCMV-hFIX) without HCR was drastically diminished in 72 hours. Interestingly, the significant amount of anti-human factor IX antibody was detected in the mice treated with the control plasmid, but not in the mice treated with the plasmids containing HCR. At this moment, we have not seen any functional differences among the four different plasmids containing HCR. Further analysis of human factor IX expression and blood coagulation in hemophilia B mice treated with the HCR-containing plasmids for a longer period of time will give us a better understanding about HCR functions in hepatic transgene expression.
The REVEAL Study
Authors: Tatsuro Ishibashi, Xiaoxin Li, Adrian Koh, Timothy Y.Y. Lai, Fenq-Lih Lee, Won-Ki Lee, Zhizhong Ma, Masahito Ohji, Nikolle Tan, Sung Bok Cha, Jila Shamsazar, C. Lillian Yau
Journal: Ophthalmology (2015)
Volatile N-nitrosamine formation after intake of nitrate at the ADI level in combination with an amine-rich diet.
Authors: I T Vermeer, D M Pachen, J W Dallinga, J C Kleinjans, J M van Maanen
Journal: Environmental Health Perspectives (1998)

Formation of nitrite from ingested nitrate can result in several adverse health effects and implies a genotoxic risk as a consequence of endogenous formation of carcinogenic N-nitroso compounds. We studied the formation of volatile N-nitrosamines after intake of nitrate at the acceptable daily intake (ADI) level in combination with a fish meal rich in amines as nitrosatable precursors. Twenty-five volunteers consumed this meal during 7 consecutive days; a diet low in nitrate was consumed during 1 week before and 1 week after the test week. Nitrate intake at the ADI level resulted in a significant rise in mean salivary nitrate and nitrite concentrations. Mean urinary nitrate excretion increased from 76 mg/24 hr in the first control week to 194 and 165 mg/24 hr in the test week, followed by a decline to 77 mg/24 hr in the second control week. The urine samples were analyzed for volatile N-nitrosamines, and both N-nitrosodimethylamine (NDMA) and N-nitrosopiperidine (NPIP) were detected in the samples. Mean urinary NDMA excretion significantly increased from 287 ng/24 hr in the control week to 871 and 640 ng/24 hr in the test week and declined to 383 ng/24 hr in the second control week. Excretion of NPIP was not directly related to the nitrate intake and composition of the diet. Nitrate excretion and NDMA excretion were significantly correlated, as well as salivary nitrate and nitrite concentration and NDMA excretion. We conclude that nitrate intake at the ADI level in combination with a fish meal containing nitrosatable precursors increases NDMA excretion in urine and thus demonstrates increased formation of carcinogenic N-nitrosamines.
Increased Risk of Cardiovascular Events Associated with TKI Treatment in Chronic Phase Chronic Myeloid Leukemia. Data from Swedish Population-Based Registries
Authors: Torsten Dahlén, Gustaf Edgren, Martin Höglund, Mats Lambe, Magnus Björkholm, Fredrik Sandin, Anders Själander, Johan Richter, Lotta Ohm, Magnus Bäck, Leif Stenke
Journal: Blood (2014)
CARDIOVASCULAR COMPLICATIONS OF PAGET'S DISEASE: A CASE REPORT
Authors: S ALPERT
Journal: Annals of Internal Medicine (1958)

Case Reports1 April 1958CARDIOVASCULAR COMPLICATIONS OF PAGET'S DISEASE: A CASE REPORTSAMUEL ALPERT, M.D., F.A.C.P.SAMUEL ALPERT, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-48-4-871 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPaget's disease is one of the most frequently encountered bone disorders, and the emphasis in the voluminous literature on the subject has been on the osseous changes. Less well known, and until relatively recent years rarely recorded, are the cardiovascular complications, of which the following case is a graphic example.CASE REPORTThe patient was a 29 year old male of Italian extraction in whom Paget's disease had first been diagnosed 11 years before, when he was treated for a spontaneous fracture of the elbow. The diagnosis was subsequently confirmed by a bone biopsy. The course of the bone disease...Bibliography1. Wagner M: Report of a case of Paget's disease in an 18 year old male, with review of literature, Wisconsin M. J. 46: 1098, 1947. MedlineGoogle Scholar2. Paget J: On a form of chronic inflammation of bones (osteitis deformans), Med.-Chir. Tr. London 60: 37, 1877. CrossrefMedlineGoogle Scholar3. SornbergerSmedal CFML: Cardiovascular changes in Paget's disease, Circulation 6: 711-726 (Nov.) 1952. CrossrefMedlineGoogle Scholar4. Moore S: Osteitis deformans, Am. J. Roentgenol. 10: 507, 1923. Google Scholar5. EdholmMcMichael OGJ: Heart failure and bone blood flow in osteitis deformans, Clin. Sc. 5: 249, 1945. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Received for publication August 15, 1956.From the New York Regional Office, Veterans Administration, New York, N. Y.Requests for reprints should be addressed to Samuel Alpert, M.D., Chief, Medical Unit, Veterans Administration Regional Office, 252 Seventh Avenue, New York 1, N. Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe clinical relevance of radiologically revealed Paget's disease of bone (osteitis deformans)Paget’s DiseaseClinical Entities with Both Vascular and Orthopedic ComponentsDie Pagetsche KnochenerkrankungAbsence of Anatomic Arteriovenous Shunts in Paget's Disease of Bone 1 April 1958Volume 48, Issue 4Page: 871-876KeywordsBiopsyBoneCardiovascular diseasesDyspneaElbowPhosphatases ePublished: 1 December 2008 Issue Published: 1 April 1958 PDF downloadLoading ...
A large radial artery false aneurysm after repeated arterial punctures, causing compartment syndrome of the forearm
Authors: Miltiadis I. Matsagas, Michael Mitsis, Christos Rigopoulos, Vasiliki Theodossiou, Vasilios Koulouras, Konstantinos Polyzoidis, Angelos M. Kappas
Journal: Intensive Care Medicine (2003)
Abstract 619: Selective estrogen mimics for the treatment of tamoxifen-resistant breast cancer
Authors: Mary Ellen Molloy, Bethany Perez White, Huiping Zhao, Bradley T. Michalsen, Hitisha K. Patel, Jiong Zhao, Rui Xiong, Marton I. Siklos, Gregory R.J. Thatcher, Debra A. Tonetti
Journal: Cancer Research (2014)

Abstract Endocrine-resistant breast cancer, whether de novo or acquired, is a major clinical obstacle. Although recent clinical trials have demonstrated the efficacy of 17β-estradiol (E2) or diethylstilbestrol (DES) following exhaustive use of antiestrogens, E2 treatment is associated with major side effects such as an increased risk of other gynecological cancers, deterring the clinical community from adopting it as a treatment strategy. Our lab has previously shown that Protein kinase C alpha (PKCα) overexpression predicts tamoxifen (TAM) resistance in the clinic (Tonetti DA et al., Br J Cancer. 2003) and may also predict a positive response to an estrogenic therapy (Chisamore MJ et al., Clinical Cancer Research. 2001). Further, the ectopic overexpression of PKCα in T47D breast cancer cells, led to a TAM-resistant, E2-inhibited phenotype in vivo which was accompanied by the translocation of estrogen receptor alpha (ERα) to extranuclear sites (Perez White B et al., Molecular Cancer. 2013). The purpose of this study was to identify novel selective estrogen mimics (SEMs), which could achieve the positive therapeutic effects of E2 treatment in TAM-resistant breast cancers, while minimizing the side effects. In vitro screening identified two SEMs, BTC and TTC-352, which displayed estrogenic activity in breast cancer cell lines. BTC and TTC-352 treatment resulted in significant tumor regression in two xenograft models of TAM-resistant, PKCα-overexpressing breast cancer. Similar to E2, T47D:A18/PKCα tumor regression was accompanied by translocation of ERα to extranuclear sites, possibly defining a mechanism through which these SEMs initiate tumor regression. SEM treatment, however, did not result in growth of parental, TAM-sensitive xenograft tumors. Endometrial thickening, caused by both E2 and TAM, is directly associated with gynecological carcinogenesis and uterine cancer. Interestingly, SEM treatment did not increase uterine weight in mice suggesting negligible hormonal stimulation in gynecological tissues. Both BTC and TTC-352 resulted in regression of two TAM-resistant breast cancer models, while displaying enhanced safety compared to E2 and TAM. These data suggest that further development of SEMs targeted to TAM-resistant breast cancer is a feasible therapeutic strategy. Citation Format: Mary Ellen Molloy, Bethany Perez White, Huiping Zhao, Bradley T. Michalsen, Hitisha K. Patel, Jiong Zhao, Rui Xiong, Marton I. Siklos, Gregory R.J. Thatcher, Debra A. Tonetti. Selective estrogen mimics for the treatment of tamoxifen-resistant breast cancer. [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 619. doi:10.1158/1538-7445.AM2014-619
Some Inhibitors of Deamination of 9-β-d-Arabinofuranosyladenine and 9-β-d-Xylofuranosyladenine by Blood and Neoplasms of Experimental Animals and Humans
Authors: Ryozo Koshiura, G. A. LePage
Journal: Cancer Research (1968)

Earlier studies concerning the relationship between adenosine deaminase and the response of ascites tumors in mice to analogs of adenosine were extended to subcutaneous mouse tumors. A tumor with relatively high adenosine deaminase activity, Sarcoma 180, was relatively unresponsive to 9-β-d-arabinofuranosyladenine (Ara-A) and 9-β-d-xylofuranosyladenine (Xyl-A). Tumors with lower deaminase content, Carcinoma 1025 and Ridgeway osteogenic sarcoma, were more responsive. Loss of Xyl-A and Ara-A due to deamination in mouse blood was studied under the influence of inhibitors. Several nucleosides were good inhibitors in vitro but had no useful effects in vivo . Agents preventing entry of the deaminase substrates into blood cells were effective in vivo . The most prolonged effects were obtained with 4-ethanolisopropanolamino-2-7-di(2′-methylmorpholino)-6-phenylpteridine.

Levels of adenosine deaminase in the blood of mice, rats, monkeys, and humans were determined. A survey was also made of adenosine deaminase levels in 41 human tumor samples.
Abstract 17478: Relationship Between Temporal Distribution of Coronary Artery Disease Progression and Subsequent Consequences in Patients With Acute Coronary Syndromes
Authors: Tatsuya Nakachi, Hidekuni Kirigaya, Daiki Gyotoku, Naoki Iinuma, Nao Ishii, Yuko Miki, Kohei Iguchi, Kazuki Fukui, Satoshi Umemura, Kazuo Kimura
Journal: Circulation (2014)

Background:  Recent reports have shown that the late consequences of presentation with ACS has been underestimated. The relationship between temporal distribution of clinically silent progression of coronary artery disease and subsequent consequences with ACS is unclear.   Methods:  We studied 217 patients (182 men, 64 ± 10 years) with ACS undergoing percutaneous coronary intervention (PCI) for culprit lesion during initial hospitalization. All patients underwent serial coronary angiograms (CAGs) immediately before PCI, and at 8 ± 2 months and 60 ± 10 months after presentation. Coronary artery disease progression (CP) was defined as an increase >= 15 % in stenosis severity of lesion in nonculprit artery between 2 serial CAGs. The relationship of CP between each of 2 serial CAGs and subsequent clinical events after final CAG was examined. Major adverse cardiac events (MACEs) were defined as death, myocardial infarction, unstable angina, heart failure, and ischemic stroke.   Results:  During median follow-up duration after final CAG of 48 months, 54 MACEs (10 death, 7 myocardial infarction, 17 unstable angina, 15 heart failure, 5 ischemic stroke) were observed. Kaplan-Meier curves demonstrated a significant difference in event-free survival according to CP between each of 2 serial CAGs (Fig.). Cox regression analysis revealed that CP between first and second CAGs (OR 2.34, 95% CI 1.37 to 4.00, p=0.002), CP between second and final CAGs (OR 2.82, 95% CI 1.65 to 4.80, p   Conclusion:  Both of CP in the early phase (0 - 8 months) and CP in the late phase (8 - 60 months) during the 5 years after ACS were independently associated with the subsequent clinical event. This may indicate prognostic significance of the persistency of the widespread coronary disease activity following presentation in patients with ACS undergoing PCI.
Abstract 682: Identification of HSP90 inhibitor sensitizers through pooled RNA interference screen
Authors: Yaoyu Chen, Jinyun Chen, Alice Loo, Margaret Mclaughlin, Raymond Pagliarini, Wenlai Zhou
Journal: Cancer Research (2014)

Abstract Key words: HSF1, cancer cells, HSP90 inhibitor, Melanoma, HCC, DEDD2. The molecular chaperone heat shock protein 90 (HSP90) facilitates the appropriate folding of various oncogenic proteins and is necessary for the survival of some cancer cells. HSP90 is therefore an attractive drug target, but the efficacy of HSP90 inhibitor may be limited by HSP90 inhibition induced feedback mechanisms. To identify genes that modulate the efficacy of HSP90 inhibition on tumor cell growth, we performed a large-scale RNA interference (RNAi) genetic screen with a collection of short hairpin RNA (shRNA) vectors targeting 1,000 human genes in A375. A barcoding technique was used to identify genes whose suppression caused resistance or sensitivity to two separate concentrations of NVP-AUY922. 163 and 360 shRNA constructs were significantly depleted form either low- or high-dose NVP-AUY922 treated samples (FDR&amp;lt;=0.15). Among those shRNA hits, 84 hits (including 81 genes) were common shRNA hits as shown in Venn diagram and sensitizing genes or rescuing genes were also shown. Among of these shRNA hits, HSF1 and heat shock protein 90 alpha, class B member 1(HSP90AB1) knockdown scored as the most top sensitizers to HSP90 inhibition in A375 cells, and are known to regulate the cell response to heat shock conditions, which may reflect the potential feedback mechanism of HSP90 inhibition. Taking together, HSF1 is identified as a sensitizer of HSP90 inhibitor through pooled shRNA screening. A striking combinational effect was observed when HSF1 knockdown plus with HSP90 inhibitors treatment in various cancer cell lines: A375, A2058 and HCT116 and tumor mouse models. Interestingly, HSF1 is highly expressed in hepatocellular carcinoma (HCC) patient samples and HCC is sensitive to combinational treatment, indicating a potential indication for the combinational treatment. To understand the mechanism of the combinational effect, we identified that a HSF1-target gene DEDD2 is involved in attenuating the effect of HSP90 inhibitors. Thus, the transcriptional activities of HSF1 induced by HSP90 inhibitors provide a feedback mechanism of limiting the HSP90 inhibitor's activity, and targeting HSF1 may provide a new avenue to enhance HSP90 inhibitors activity in human cancers. Citation Format: Yaoyu Chen, Jinyun Chen, Alice Loo, Margaret Mclaughlin, Raymond Pagliarini, Wenlai Zhou. Identification of HSP90 inhibitor sensitizers through pooled RNA interference screen. [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 682. doi:10.1158/1538-7445.AM2014-682