tbuckley/cabot-search huggingface dataset:
Activity of the NEDD8-specific inhibitor MLN 4924 in multiple myeloma and Waldenström's macroglobulinemia, and effect on miRNA expression.
Authors: D. W. McMillin, Z. R. Hunter, J. Delmore, P. Smith, A. Birner, P. G. Richardson, K. C. Anderson, S. P. Treon, C. S. Mitsiades
Journal: Journal of Clinical Oncology (2010)

8110 Background: Bortezomib is an effective treatment for both multiple myeloma (MM) and Waldenström Macroglobulinemia (WM), whose activity is attributed to blocking elimination of ubiquitin tagged regulatory proteins by the proteasome. The NEDD8-inhibitor MLN4924 is a novel agent which demonstrates selective inhibition of the ubiquitin pathway and may offer a more targeted approach to MM and WM therapy. Methods: A panel of human MM and WM cell lines were tested for their in vitro response to MLN 4924 using MTT colorimetric survival assays. MM and WM cell lines tested exhibited dose and time dependent decrease of their viability upon exposure to MLN4924 (IC50= 25-150 nM for 72hrs). Results: A longitudinal assessment of viability of MM1S (MM) and BCWM1 (WM) cells during a 72-hr incubation with MLN4924 (500nM) showed commitment to death <48hrs. This result, coupled with the observation that normal donor peripheral blood mononuclear cells (PBMCs) an dHS-5 stromal cells were less sensitive (IC50 >1,000 nM) than the MM or WM cell lines tested, suggest that this compound exhibits a rapid and more tumor-selective effect at clinically relevant conditions. We also evaluated primary MM (CD138+) and WM (CD19+) patient bone marrow cells, and observed sub-μ M activity by MLN 4924. In addition, we tested a series of combinations of MLN4924 with dexamethasone, doxorubicin and bortezomib in MM1S and BCWM1 cells lines and observed at least additive activity with MLN 4924. Longitudinal miRNA profiling revealed up-regulation of 181c, a modulator of Akt activity, and 361-5p at 24 and 36 hours in both cell lines indicating a cell line independent miRNA regulatory response to MLN4924. Conclusions: MLN4924 induces cell killing at sub-μ M concentrations for both MM and WM cells with significantly higher sensitivity of tumor cells compared to normal tissues, and exhibits selective miRNA regulation. These studies provide the framework for the clinical investigation of MLN 4924 in MM and WM. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium Millennium Millennium Millennium
Prospective validation of ‘Allergy-Control-SCORETM’: a novel symptom-medication score for clinical trials
Authors: D. Häfner, K. Reich, P. M. Matricardi, H. Meyer, J. Kettner, A. Narkus
Journal: Allergy (2011)

To cite this article: Häfner D, Reich K, Matricardi PM, Meyer H, Kettner J, Narkus A. Prospective validation of 'Allergy-Control-SCORETM': a novel symptom–medication score for clinical trials. Allergy 2011; 66: 629–636 Abstract Background: Combined symptom and medication scores (SMS) are recommended as primary endpoints in clinical trials. Several SMS have been created, but none has been formally validated. Objective: To evaluate the validity of the 'Allergy-Control-SCORE© (ACS)', a novel instrument to assess patient's allergy severity by recording symptoms and rescue medication. Methods: One hundred and twenty-one consenting subjects (age 18–65 year), including 81 patients with allergic rhino-conjunctivitis and/or asthma and 40 healthy controls, participated in the study. They recorded daily nasal, eye, and lung symptoms using a 4-point scale (none, mild, moderate, and severe) and use of anti-symptomatic medication. Pollen counts were monitored during the study period. Symptom and medication scores values were compared to global allergy severity, quality of life, and allergy-related medical consultations. Feasibility was tested through a questionnaire on comprehensibility, easiness of use, and completeness. Retest reliability was assessed by testing consistency, in relation to pollen exposure, and for values recorded during each of 2 consecutive weeks. Results: Convergent reliability analysis indicated a highly significant correlation between ACS© and global allergy severity (P < 0.0001), quality of life (P < 0.0001), and allergy-related medical consultations (P < 0.0001). Scores were highly related to pollen counts. Allergy-Control-SCORE© showed a good retest reliability (r = 0.81; P < 0.0001) and discriminated extremely well between patients with allergy and healthy controls (6.1 ± 4.8 vs 0.2 ± 0.5; t = 10.82; P < 0.0001) with a sensitivity of 97% and a specificity of 87%. Study participants evaluated the feasibility of the SMS as excellent. Conclusions: Allergy-Control-SCORE© is a valid and reliable instrument to assess allergy severity in clinical trials and observational studies of respiratory allergic diseases.
Presence of Heat Shock Protein 72 in Cardiomyocytes After Heat Stress
Authors: R.N.M. Cornelussen, F.A. van Nieuwenhoven, L.H.E.H. Snoeckx, A.A. Knowlton
Journal: Circulation (2001)

To the Editor:It is well-known that prior in vivo heat stress induces the synthesis of heat shock protein (HSP) 72 in the rat heart, but the precise content in the various cell-types has not yet been measured.It is therefore of great importance to conduct experiments as performed in the paper by Leger et al. 1 However, the overall conclusion that heat pretreatment does not lead to HSP72 synthesis in cardiomyocytes is unjustified.In addition, the statement that blood vessels play a primary role in the heat shock-induced cardioprotection is preliminary.The double-labeling experiments of Leger et al, 1 staining HSP72, as well as HSP27, clearly indicates the presence of both proteins in the same area, which the authors define as cardiomyocytes in the case of HSP27.Indeed, other studies indicate that cardiomyocytes do overexpress HSP72 after stress: cardiomyocytes of intact hearts are capable of overexpressing HSP72 after heat treatment. 2Although the increase of HSP72 normalized for protein content was lower in cardiomyocytes than in endothelial cells, the absolute HSP72 amount was 3 times higher in the cardiomyocyte than in the endothelial cell pool.Furthermore, isolated cardiomyocytes increase their synthesis of HSP72 either after heat shock or hypoxia. 3Lastly, in cardiomyocytes, an enhanced HSP72 presence has been documented immunohistochemically after ischemia/reperfusion, after application of a nitric oxide donor, and after aortic stenosis. 4,5Because of the similar response against various stresses, it is conceivable that heat pretreatment should provoke enhanced HSP72 synthesis in cardiomyocytes.The authors should have verified the relative HSP72 amounts in cardiomyocyte and endothelial cell fractions and the endothelial specific HSP72 expression.The authors' statement that the beneficial effects of heat pretreatment on ischemia/reperfusion tolerance are almost exclusively due to the HSP72-induction in endothelial cells is premature.To prove this hypothesis, transgenic mice overexpressing HSP72 exclusively in endothelial cells should be generated and tested for ischemia/ reperfusion tolerance.Furthermore, we do not know to what extent the increased functional recovery of the heat-pretreated hearts after ischemia/reperfusion is dependent on its absolute HSP72 content.Experiments specifically blocking the increase in HSP72-synthesis in cardiomyocytes after heat treatment would help to understand the contribution of HSP72 synthesis in these cells leading to enhanced ischemia and reperfusion tolerance. 3n our opinion, the conclusions of Leger and coworkers should be substantiated by experiments, providing exclusive evidence that heat shock-induced enhanced HSP72 expression in the endothelial cell compartment, and not in the cardiomyocyte, is responsible for the improved ischemia/reperfusion tolerance of the heart.
Abstract 591: LKB1 regulates COX-2 transcription via CRTCs dependent pathway
Authors: Chunxia Cao, Ruli Gao, Min Zhang, Zirong Chen, Lizi Wu, Maria Zajac Kaye, Frederic Kaye
Journal: Cancer Research (2014)

Abstract Inactivation of the liver kinase B1 (LKB1) gene by somatic mutation is a common event in lung adenocarcinoma. LKB1 was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome (PJS) and up regulation of cyclooxygenase-2 (COX-2) was detected in a significant percentage of human PJS polyps. In addition, COX-2 has been proposed as a therapeutic target for lung cancer although clinical trial using COX-2 inhibitors have been disappointing. In the current study, we identified a novel LKB1/CRTC/COX-2 molecular pathway in human lung cancer cells and provided new information for clinical use of COX-2 inhibitors. The Kaye lab cloned the CREB-regulated transcription co-activators (CRTCs) and showed aberrant phosphorylation and activation of CRTC1 exclusively in non-small cell lung cancer (NSCLC) samples carrying LKB1 null mutations. We have now demonstrated that CRTC directly regulates COX-2 expression via evolutionarily conserved CRE sites within the promoter. In addition, we observed that ectopic expression of LKB1 resulted in nuclear export of phosphorylated CRTC with attenuation of COX-2 expression. Alternatively, LKB1 knock-down results in CRTC activation and promotes COX-2 expression in NSCLC cells. Importantly, LKB1 null lung cancer cells were preferentially sensitive to COX-2 inhibitors. In summary, our data defines a CRTCs-mediated transcriptional regulatory mechanism for COX-2 activity in cancer and proposes a possible clinical application of COX-2 inhibitors in patients with lung tumors carrying somatic LKB1 null mutations. Citation Format: Chunxia Cao, Ruli Gao, Min Zhang, Zirong Chen, Lizi Wu, Maria Zajac Kaye, Frederic Kaye. LKB1 regulates COX-2 transcription via CRTCs dependent pathway. [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 591. doi:10.1158/1538-7445.AM2014-591
Abstract 15201: A Novel Prostacyclin Agonist, Ono1301(R), Improves the Cardiac Function Through Reverse Cytoskeletal Protein in Dilated Cardiomyopathic Hamster; a Promising Regenerative Therapy for Failing Heart
Authors: Kazuhiko Ishimaru, Shigeru Miyagawa, Satsuki Fukushima, Atsuhiro Saito, Yukiko Imanishi, Haruki Ide, Masaki Taira, Takayoshi Ueno, Yoshiki Sakai, Yoshiki Sawa
Journal: Circulation (2011)

Background: Aberrations in cytoskeletal proteins of myocyte have been suggested to play an important role in progression of left ventricular (LV) remodeling in dilated cardiomyopathy (DCM). ONO1301...
The 1-131 Rose Bengal Excretion Test Is Not Dead
Authors: VINCENT F. ANTICO, PAUL DENHARTOG, JUDITH M. ASH, DAVID L. GILDAY, SYLVAIN HOULE
Journal: Clinical Nuclear Medicine (1985)

One hundred and thirty I-131 Rose Bengal Excretion Studies (RBI) were performed on 84 patients over nine years. In 90% (56/60) of cases with biliary atresia, the 72-hour RBI was less than or equal to 7%. In only 12.5% (3/24) of cases with neonatal hepatitis was the 72-hour RBI less than or equal to 7%. The accuracy of the test was 91% with a specificity of 88%. Thirty patients later were studied following a Kasai procedure. The RBI test reliably predicted the patency of the anastomosis. The authors conclude that the 72-hour RBI is a reliable test in the diagnosis of biliary atresia and in the documentation of biliary patency following surgery, provided adequate care is taken in stool collection and measurement.
CLINICAL DIAGNOSIS OF AMYLOIDOSIS
Authors: H J Senn, H J Heiniger, H Bürki, U Rieder
Journal: JAMA (1963)

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
In Vitro and in Vivo Enhancement of Ganciclovir-Mediated Bystander Cytotoxicity with Gemcitabine
Authors: Paul D. Boucher, Donna S. Shewach
Journal: Molecular Therapy (2005)

To improve bystander cell killing with HSV-TK/GCV, we have utilized dFdCyd to reduce endogenous dGTP, which competes with GCVTP for incorporation into DNA. In this study we demonstrate the ability of dFdCyd to enhance GCV-mediated bystander cytotoxicity in cultured SW620 human colon carcinoma cells as well as in a murine xenograft model. In vitro, dFdCyd reduced cellular dGTP levels and produced a fourfold increase in the GCVTP:dGTP ratio. This elevated GCVTP:dGTP ratio resulted in a twofold increase in GCVMP incorporation into DNA in bystander cells cocultured with HSV-TK-expressing cells. The combination of GCV and dFdCyd was determined to be synergistic by isobologram analysis of bystander cytotoxicity. Tumors in mice treated with GCV and dFdCyd exhibited a significant growth delay requiring 40 days to obtain ∼10 times their initial size compared to tumors in PBS- or single-drug-treated animals, which grew rapidly, increasing to a similar size in just 19 to 24 days. In addition, complete tumor regression was observed only in animals treated with both drugs. Furthermore, dFdCyd alone or in combination with GCV produced no evidence of toxicity or significant weight loss. These data suggest that dFdCyd may improve the clinical efficacy of HSV-TK/GCV gene therapies.
Lowering Homocysteine With B Vitamins in Patients With Coronary Artery Disease
Authors: Gian Paolo Rossi, Teresa Maria Seccia, Achille C Pessina
Journal: JAMA (2008)

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
Abstract 74: Cardiopulmonary Resuscitation Quality Assessed by Electrocardiography Signal Processing Using Hilbert-Huang Transform Correlates Well with Accelerometer
Authors: Huang-Fu Yeh, Chiao-Hao Lee, Lian-Yu Lin, Wen-Chu Chiang, Patrick C Ko, Eric H Chou, Kah-Meng Chong, Men Tzung Lo, Joar Eilevstjønn, Helge Mykelbust, Matthew H Ma
Journal: Circulation (2011)

Objectives High quality cardiopulmonary resuscitation (CPR) is paramount to patient outcomes in cardiac arrests (CA). Methods to assess CPR quality using widely available data should be explored. This study was aimed to compare CPR quality assessed by surface ECG signal processing vs. accelerometer. Methods Adult patients with CA receiving CPR in the emergency department of a tertiary university hospital, from Dec 2010 to March 2011 were included. CPR was monitored continuously by recording the surface ECG signals and sternal displacement via an accelerometer. CPR quality parameters including total compression numbers, no flow time (pause &gt; 1.5 sec), total flow time (time with pause &lt; 1.5 sec) and average compression rate for up to the first 10 min of CPR were obtained by 1) ECG signal processing algorithm using empirical mode decomposition via Hilbert-Huang Transform (ECG-HHT) and 2) sternal displacement recorded by an accelerometer (ACCEL). Results CPR sessions of 9 CA (6 males, mean age 79.9 years) were analyzed. Compared to ACCEL, ECG-HHT showed lower total compressions, higher no flow time, and lower total flow time. There are good correlations between ECG-HHT vs. ACCEL in total compression numbers (R=0.95) and total flow time (R=0.97). Conclusions ECG-HHT correlates well with ACCEL in certain CPR quality parameters and may be used to assess CPR quality through widely available ECG data.
Abstract IA22: The immunobiology of the melanoma tumor microenvironment and efficacy of immunotherapies
Authors: Thomas F. Gajewski
Journal: Cancer Research (2015)

Abstract Two major categories of melanoma metastases have been observed based on gene expression profiling and confirmatory assays. One subgroup of patients has an inflamed phenotype that includes expression of chemokines, T cell markers, and other immunoregulatory factors. In contrast, the other major subset lacks this phenotype and appears to display immune “exclusion”. The optimal immunotherapeutic interventions may be distinct in these two global subsets. The T cell-inflamed tumor microenvironment subset shows the highest expression of negative regulatory factors, including PD-L1, IDO, and FoxP3+ Tregs, and evidence for T cell-intrinsic anergy has also emerged aided by a recently defined functional role of EGR2. In addition, the mechanism of induction of these inhibitory mechanisms has been elucidated—PD-L1 and IDO are induced by IFN-γ, and Tregs are largely recruited by the chemokine CCL22, both being produced by activated CD8+ effector T cells. Preclinical experiments have confirmed a critical role for each of these mechanisms in limiting anti-tumor T cell efficacy in vivo, giving candidate treatment strategies for translation back into the clinic. These include anti-PD-1/PD-L1 mAbs, IDO inhibitors, and approaches to deplete CD25+ Tregs and/or reverse anergy. The presence of multiple inhibitory mechanisms in the same tumor microenvironment argues that combination therapies may be advantageous. Preclinical data have indicated synergy between anti-CTLA-4 +/- anti-PD-L1 +/- IDO inhibition. The mechanism of synergy is striking, as it correlates with a marked improvement of IL-2 production and proliferation of tumor-infiltrating CD8+ T cells. Clinical translation of these combination immunotherapies is promising and ongoing. In contrast to the T cell-inflamed melanomas, a new paradigm may be needed to promote de novo inflammation in cases of the non-T cell-infiltrated tumor microenvironment. Natural innate immune sensing of tumors appears to occur via the host STING pathway, type I IFN production, and cross-priming of T cells via CD8α+ DCs. New strategies are being developed to engage or mimic this pathway as a therapeutic endeavor. The molecular mechanisms that mediate the presence or absence of the T cell-inflamed tumor microenvironment in patients are being elucidated and should open up additional new treatment approaches. Citation Format: Thomas F. Gajewski. The immunobiology of the melanoma tumor microenvironment and efficacy of immunotherapies. [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 IA22.
Abstract 15849: Impacts of Coexistence of Metabolic Syndrome and Chronic Kidney Disease on Serum Heart-Type Fatty Acid-Binding Protein Levels in General Population
Authors: Toshiaki Tamabuchi, Tetsu Watanabe, Harutoshi Tamura, Satoshi Nishiyama, Takanori Arimoto, Hiroki Takahashi, Tetsuro Shishido, Takehiko Miyashita, Joji Nitobe, Yoko Shibata, Tsuneo Konta, Sumio Kawata, Takeo Kato, Isao Kubota
Journal: Circulation (2010)

Serum heart-type fatty acid-binding protein (H-FABP) has been widely used as a marker of ongoing myocardial damage. Recent reports showed additive interaction of metabolic syndrome (MetS) and chron...
BUCKLING OF THE RIGHT COMMON CAROTID ARTERY IN HYPERTENSION
Authors: R. Arrillaga Torrens, Bayard T. Horton
Journal: Annals of Internal Medicine (1938)

Article1 November 1938BUCKLING OF THE RIGHT COMMON CAROTID ARTERY IN HYPERTENSIONR. ARRILLAGA TORRENS, M.D., BAYARD T. HORTON, M.D., F.A.C.P.R. ARRILLAGA TORRENS, M.D.Search for more papers by this author, BAYARD T. HORTON, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-12-5-688 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn 1925, Brown and Rowntree described a characteristic buckling of the right common carotid artery which is present in some severe cases of hypertension. A review of the literature1, 2, 5revealed that such limited recognition has so far been accorded this sign that it seemed opportune to call attention to its frequent occurrence in cases of hypertension and to the mistakes in diagnosis often caused by its non-recognition. We are also reporting two new cases in which buckling of the right common carotid artery occurred. These cases were observed in a study of 48 consecutive hospital cases of white...References1. BEARDWOOD JT: Right-sided carotid pulsation in hypertension, Med. Clin. N. Am., 1931, xiv, 989-992. Google Scholar2. BOLOTIN MT: Right carotid and other pulsations in essential hypertension, Med. Jr. and Rec., 1933, cxxxvii, 419-420. Google Scholar3. BROWNROWNTREE GELG: Right-sided carotid pulsations in cases of severe hypertension, Jr. Am. Med. Assoc., 1925, lxxxiv, 1016-1019. CrossrefGoogle Scholar4. CARMEL AG: An inquiry into the phylogenetic basis of the flexuous arteria carotis interna of man (the arteriae carotides of the seal), Anat. Rec., 1928, xxxix, 343-347. CrossrefGoogle Scholar5. HOLST JE: Pulsation in right carotid artery in arterial hypertension, Hospitalstid., 1934, lxxvii, 79-84. Google Scholar6. MONIZ E: La palpation des carotides comme élément de diagnostic de l'artériosclérose cérébrale, Rév. Neurol., 1930, ii, 48-51. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Rochester, Minnesota*Submitted for publication December 30, 1937. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byArtery buckling stimulates cell proliferation and NF-κB signalingThe tortuous or kinked carotid artery: Pathogenesis and clinical considerations. A historical reviewDysphagia Caused by Elongation and Tortuosity of the Common Carotid ArteryTHE KINKED CAROTID ARTERY THAT SIMULATES ANEURYSM 1 November 1938Volume 12, Issue 5Page: 688-691KeywordsArteriesCommon carotid arteriesHypertension Issue Published: 1 November 1938 PDF downloadLoading ...