tbuckley/cabot-search huggingface dataset:
Abstract 5661: Nanoparticle based combinatorial siRNA therapy against human hepatocellular carcinoma (HCC) .
Authors: Thomas Decaens, Valentina M. Factor, Iva Kulic, Jesper B. Andersen, Daekwan Seo, Yun-Han Lee, Adam D. Judge, Elizabeth A. Conner, Ian MacLachlan, Snorri S. Thorgeirsson
Journal: Cancer Research (2013)

Abstract Background: We have previously demonstrated the therapeutic effect of lipid nanoparticles (LNP) loaded with single siRNA targeting CSN5 and WEE1 against human HCC in mouse models. Aim: To test the benefit of a combinatorial versus single siRNA therapy in mouse models of human HCC and to identify molecular mechanism(s) involved in therapeutic response by extensive microarray analyses. Materials and Methods: LNP formulations of chemically modified siRNAs targeting CSN5 and WEE1 were produced by Tekmira® Pharmaceuticals. SCID-beige mice were used for subcutaneous (Hep3B) and intra-hepatic (Huh7-luciferase) tumor transplantation. Mice with established tumors were treated intravenously with 4 mg/kg single agent siRNA or 2 mg/kg + 2 mg/kg siCSN5:siWEE1 siRNA co-encapsulated in the same LNP. Tumors were assayed following 1 to 9 injected doses. Tumor progression in the Huh7 orthotopic model was monitored by bioluminescence imaging and metastases were evaluated at endpoint. Results: Significant target silencing was observed in tumors after single or repeat administration with no antagonism between siRNAs occurring in the CSN5:WEE1 combination. We observed significant inhibition of tumor growth and metastases in mice treated with active siRNAs compared to LNP containing a non-targeting control sequence. Potency was not lost with siCSN5:siWEE1 LNP, where the concentration of each siRNA is halved in combination, relative to the most efficacious single agent. Data from preliminary microarray analyses demonstrate a strong transcriptome difference between each treatment group. Conclusion: We demonstrate a clear efficacy of a LNP based combinatorial siRNA therapy in human mouse models of HCC. Overall this therapy led to a significant decrease of tumor size induced by mRNA inhibition Citation Format: Thomas Decaens, Valentina M. Factor, Iva Kulic, Jesper B. Andersen, Daekwan Seo, Yun-Han Lee, Adam D. Judge, Elizabeth A. Conner, Ian MacLachlan, Snorri S. Thorgeirsson. Nanoparticle based combinatorial siRNA therapy against human hepatocellular carcinoma (HCC) . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5661. doi:10.1158/1538-7445.AM2013-5661
Adding to the Effectiveness of Intravenous Tissue Plasminogen Activator for Treating Acute Stroke
Authors: James C. Grotta
Journal: Circulation (2003)

ntravenous tissue plasminogen activator (rt-PA) remains the only approved therapy for acute ischemic stroke with demonstrated effectiveness in phase 3 clinical trials. 1 Unfortunately, the utilization of this treatment is limited by a 6% risk of symptomatic brain hemorrhage 2 and a brief 3-hour time window of efficacy from symptom onset to treatment. 3Furthermore, its effectiveness is limited for several reasons; intravenously administered rt-PA often fails to lyse large clots, 4,5 arteries reocclude in about a third of cases, 5 flow may remain stagnant in the microcirculation despite clot lysis, 6,7 and cellular injury may continue despite reperfusion.
External Chemical Messengers
Authors: Harry Wiener
Journal: JAMA (1966)

<h3>To the Editor:—</h3> The following statements are odd facts, hard to fit into any general body of knowledge. All have appeared inThe Journalin 1966. Humans emit substances which attract mosquitoes. The composition of sweat fluctuates with the menstrual cycle. In the presence of catatonia, the physician should feel like a man standing before a half-trained tiger. The tendency to gout is the tendency to the executive suite. There may be some connection between neuropsychiatric disease and artistic creativity. I want to outline a hypothesis which may account for these odd facts, and many others. This out
Imaging the Intracranial Complications of Hemophilus Influenzae Meningitis
Authors: J R STY, R J STARSHAK, H M SWICK, M J CHUSID
Journal: Clinical Nuclear Medicine (1981)

Computed tomography (CT) and radionuclide imaging of the central nervous system (CNS) are important modalities in both the diagnosis and management of CNS complications from Hemophilus influenzae meningitis. Both examinations are sensitive indicators of CNS abnormalities associated with bacterial meningeal infections and are important determinants of the therapy and ultimate prognosis of such complications. Representative findings from CT and radionuclide imaging of children with complications from H. influenzae infection of the meninges are presented.
Comparative fates of intravenously and orally administered aldosterone: evidence for extrahepatic formation of acid-hydrolyzable conjugate in man.
Authors: T Bledsoe, G W Liddle, A Riondel, D P Island, D Bloomfield, B Sinclair-Smith
Journal: Journal of Clinical Investigation (1966)

It is well established that the liver is a major site of metabolic inactivation of aldosterone.In 1962 Coppage, Island, Cooner, and Liddle (2) reported that the human liver was capable of con- verting aldosterone both to its acid-hydrolyzable conjugate (AHC) 1 and to tetrahydroaldosterone.The same study also demonstrated that aldosterone was almost completely inactivated during a single passage through the normal liver.More recent studies by Luetscher and associates (4) have indi- cated that the normal liver extracts about 97%o of the aldosterone delivered to it by the arterial circulation, and the studies of Bougas and co-work- ers (5, 6) have indicated that in subjects with minimal cardiac dysfunction the rate of splanchnic clearance of aldosterone amounts to about 89%o of the hepatic blood flow.The fact that the liver metabolizes almost all of the aldosterone presented to it does not imply that the liver is the only site of metabolism of aldoster- one.Sandor and Lanthier (7) observed that kid- ney slices could convert aldosterone to AHC.From their analyses of hepatic and peripheral ve- nous plasma after the continuous infusion of triti- ated aldosterone into human subjects, Bougas and co-workers (5, 6) calculated the extrasplanchnic clearance rate of aldosterone to be approximately *
Undocumented HIV Infection
Authors: Arthur S. Harrow
Journal: Annals of Internal Medicine (1995)

Letters15 September 1995Undocumented HIV InfectionArthur S. Harrow, MDArthur S. Harrow, MDHenrico County Jail; Richmond, VA 23294Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-6-199509150-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read with interest the recent article by Craven and coworkers [1] regarding patients claiming undocumented human immunodeficiency virus (HIV)-positive status. As the medical director at a county jail, I had the opportunity to evaluate several such patients during the past 6 years. All announced their serologic status on registration at the jail, before any medical evaluation. All were reluctant to reveal details of their history, and none would submit to confirmatory testing at our facility.Several common factors were identified. First, each patient demanded a private cell. Second, each demanded narcotic medications. Third, each insisted on ...References1. Craven DE, Steger KA, La Chapelle R, Allen DM. Factitious HIV infection: the importance of documenting infection. Ann Intern Med. 1994; 121:763-6. Google Scholar Author, Article, and Disclosure InformationAffiliations: Henrico County Jail; Richmond, VA 23294 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByConfirmation of self-report of HIV testing among a cohort of pregnant women 15 September 1995Volume 123, Issue 6Page: 470KeywordsHIVHIV infections Issue Published: 15 September 1995 CopyrightCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Birth month and sensitization to house dust mites in asthmatic children
Authors: Y. Yoo, J. Yu, H. Kang, D. K. Kim, Y. Y. Koh, C. K. Kim
Journal: Allergy (2005)

Background: Early exposure to high quantities of allergen has an important role in the incidence of atopic sensitization. In fact, subjects sensitized to house dust mites (HDMs) have a significantly higher proportion of births in the season when HDMs are most abundant. Objective: The aim of this study was to investigate whether birth month patterns differ for asthmatic patients sensitized only to HDMs and for those sensitized to HDMs and other allergen(s). Methods: Among 2225 patients with asthma, aged 10–16 years, 1642 sensitized to HDMs were identified by skin prick testing. This group was composed of patients sensitized only to HDMs ( n = 715) and patients sensitized to HDMs and other allergen(s) ( n = 927). The birth month distributions of the group of HDM‐sensitive asthmatics or its subgroups were compared with that of a reference population (total live births in the same years as the studied subjects). The risk ratio of a given birth month in relation to all the other months was calculated as an odds ratio (OR) with the corresponding 95% confidence interval (CI). Results: A significant difference in birth month distribution was observed for HDM‐sensitive asthmatics ( χ 2 = 23.6, P = 0.015), with higher rates of birth in August (OR: 1.23, 95% CI: 1.04–1.46) and September (1.24, 1.04–1.46). When the two subgroups were analyzed separately, significantly more births were noted in August (1.34, 1.06–1.71) and September (1.34, 1.05–1.70) for those sensitized only to HDMs, whereas no such birth month preference was observed for those sensitized to HDMs and other allergen(s). Conclusions: The HDM‐positive asthmatics showed a greater proportion of births in August and September, which correspond to high HDM exposure. However, this birth month pattern was evident in asthmatic‐sensitive only to HDMs, but was not observed in those sensitive to HDMs and other allergen(s).
INTENSIVE TREATMENT OF BACK-WARD PATIENTS—A CONTROLLED PILOT STUDY
Authors: E. F. GALIONI, F. H. ADAMS, F. F. TALLMAN
Journal: American Journal of Psychiatry (1953)

The indication of this study is that a common integrated treatment program by means of a team approach in an atmosphere of therapeutic optimism can be a potent factor in the rehabilitation of increasing numbers of the so-called chronic patient. By itself, however, it will be doomed to failure if these initial results cannot be followed by the combined efforts of the hospital and the community in combating the "Rip Van Winkle" effects observed in patients hospitalized for many years.
What Are the Implications for Childhood Pneumonia of Successfully Introducing Hib and Pneumococcal Vaccines in Developing Countries?
Authors: J. Anthony G Scott, Mike English
Journal: PLoS Medicine (2008)

Points • In developing countries, pneumococcus and H. influenzae type b are the dominant causes of severe pneumonia in children, and introduction of conjugate vaccines against these diseases could reduce the global burden of severe pneumonia by about half.
Upregulation of PD-L1 by EGFR Activation Mediates the Immune Escape in EGFR-Driven NSCLC: Implication for Optional Immune Targeted Therapy for NSCLC Patients with EGFR Mutation
Authors: Nan Chen, Wenfeng Fang, Jianhua Zhan, Shaodong Hong, Yanna Tang, Shiyang Kang, Yaxiong Zhang, Xiaobo He, Ting Zhou, Tao Qin, Yan Huang, Xianping Yi, Li Zhang
Journal: Journal of Thoracic Oncology (2015)

IntroductionEpidermal growth factor receptor (EGFR) mutation status was reported to be associated with programmed death-ligand 1 (PD-L1) expression. However, the molecular mechanism of PD-L1 regulation by EGFR activation and the potential clinical significance of blocking PD-1/PD-L1 in EGFR-mutant non–small-cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs) were largely unknown.MethodsWestern blot, real-time polymerase chain reaction, immunofluorescence, and flow cytometry were employed to explore the association between PD-L1 and EGFR activation. Then, we used EGFR-TKIs and downstream pathways inhibitors to clarify the detailed signaling pathway involved in PD-L1 regulation. Cell apoptosis, viability, and enzyme-linked immunosorbent assay test were used to study the immune suppression by EGFR activation and immune reactivation by EGFR-TKIs and/or PD-1 blocking in tumor cells and human peripheral blood mononuclear cells coculture system.ResultsWe found that EGFR activation by EGF stimulation, exon-19 deletions, and L858R mutation could induce PD-L1 expression. EGFR activation upregulated PD-L1 through p-ERK1/2/p-c-Jun but not through p-AKT/p-S6 pathway. PD-L1 mediated by EGFR activation could induce the apoptosis of T cells through PD-L1/PD-1 axis in tumor cells and peripheral blood mononuclear cells coculture system. Inhibiting EGFR by EGFR-TKIs could free the inhibition of T cells and enhance the production of interferon-γ. Synergistic tumor cell killing effects were not observed with EGFR-TKIs and anti-PD-1 antibody combination treatment in coculture system.ConclusionsOur results imply that EGFR-TKIs could not only directly inhibit tumor cell viability but also indirectly enhance antitumor immunity through the downregulation of PD-L1. Anti-PD-1/PD-L1 antibodies could be an optional therapy for EGFR-TKI sensitive patients, especially for EGFR-TKIs resistant NSCLC patients with EGFR mutation. Combination of EGFR-TKIs and anti-PD-1/PD-L1 antibodies treatment in NSCLC is not supported by the current study but warrant more studies to move into clinical practice.
DNA damage associated with ultrastructural alterations in rat myocardium after loud noise exposure.
Authors: Paola Lenzi, Giada Frenzilli, Marco Gesi, Michela Ferrucci, Gloria Lazzeri, Francesco Fornai, Marco Nigro
Journal: Environmental Health Perspectives (2003)

Noise exposure causes changes at different levels in human organs, particularly the cardiovascular system, where it is responsible for increasing heart rate, peripheral vascular resistance, and blood pressure. In this study, we evaluated the effect of noise exposure on DNA integrity and ultrastructure of rat cardiomyocytes. The exposure to loud noise (100 dBA) for 12 hr caused a significant increase of DNA damage, accompanied by swelling of mitochondrial membranes, dilution of the matrix, and cristolysis. These alterations were concomitant with increased in situ noradrenaline levels and utilization. Genetic and ultrastructural alterations did not decrease 24 hr after the cessation of the stimulus. An elevated oxyradical generation, possibly related to altered sympathetic innervation, is hypothesized as responsible for the induction and persistence of noise-induced cellular damage.
False-Positive Restaging PET Scans Involving the Spleen in Two Patients With Aggressive Non-Hodgkin Lymphoma
Authors: Clyde D. Ford, Frank Gabor, Ross Morgan, Bashar Dabbas
Journal: Clinical Nuclear Medicine (2006)

We report 2 patients with aggressive non-Hodgkin lymphoma who had positive restaging PET scans limited to the spleen and no significant uptake in nodal areas of previously known disease. Examination of the resected spleens from both patients revealed extensive inflammation surrounding necrotic tumor with no evidence of viable lymphoma or active infection. It is suggested that close observation of such patients for evidence of progressive disease may be considered as opposed to immediate intervention.
Maternal T cells limit engraftment after in utero hematopoietic cell transplantation in mice
Authors: Amar Nijagal, Marta Wegorzewska, Erin Jarvis, Tom Le, Qizhi Tang, Tippi C. MacKenzie
Journal: Journal of Clinical Investigation (2011)

Transplantation of allogeneic stem cells into the early gestational fetus, a treatment termed in utero hematopoietic cell transplantation (IUHCTx), could potentially overcome the limitations of bone marrow transplants, including graft rejection and the chronic immunosuppression required to prevent rejection. However, clinical use of IUHCTx has been hampered by poor engraftment, possibly due to a host immune response against the graft. Since the fetal immune system is relatively immature, we hypothesized that maternal cells trafficking into the fetus may pose the true barrier to effective IUHCTx. Here, we have demonstrated that there is macrochimerism of maternal leukocytes in the blood of unmanipulated mouse fetuses, with substantial increases in T cell trafficking after IUHCTx. To determine the contribution of these maternal lymphocytes to rejection after IUHCTx, we bred T and/or B cell–deficient mothers to wild-type fathers and performed allogeneic IUHCTx into the immunocompetent fetuses. There was a marked improvement in engraftment if the mother lacked T cells but not B cells, indicating that maternal T cells are the main barrier to engraftment. Furthermore, when the graft was matched to the mother, there was no difference in engraftment between syngeneic and allogeneic fetal recipients. Our study suggests that the clinical success of IUHCTx may be improved by transplanting cells matched to the mother.
CD40: an upstream master switch for endothelial cell activation uncovered by RNAi-coupled transcriptional profiling
Authors: Raquel Pluvinet, Rut Olivar, Jerzy Krupinski, Inmaculada Herrero-Fresneda, Anna Luque, Joan Torras, Josep M. Cruzado, Josep M. Grinyó, Lauro Sumoy, Josep M. Aran
Journal: Blood (2008)
Abdominal Aortic Aneurysms
Authors: Sandor A. Friedman
Journal: JAMA (1967)

Of 100 patients who underwent elective resection of abdominal aortic aneurysms, most had been asymptomatic, but about one third had had symptoms referable to the aneurysms. In 19% of the cases, the aneurysms were found on roentgenograms taken for other reasons. There was high prevalence of other cardiovascular abnormalities. Peripheral arterial occlusion and myocardial infarction were the most serious complications in the survivors and occurred only in patients who had prior evidence of arterial occlusion. In particular, patients with angina and peripheral arterial occlusion had the greatest incidence of complications. The surgical mortality was 4%. The bleak outlook for patients with aneurysm which is not corrected by operation makes it necessary that this diagnosis not be overlooked in the general examination of patients.
Mucus’ Effects on Inflammation May Be Used to Treat Gut Diseases
Authors: Tracy Hampton
Journal: JAMA (2013)

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 2212: Urinary biomarkers of catechins in relation to risk of hepatocellular carcinoma in the Shanghai Cohort Study
Authors: Joyce Y. Huang, Lesley M. Butler, Renwei Wang, Chung S. Yang, Jian-Min Yuan, Yu-Tang Gao
Journal: Cancer Research (2014)

Abstract Background: Catechins from tea and non-tea sources are potential anti-carcinogenic compounds with potent antioxidant properties. Data supporting an effect of specific catechins on the risk of hepatocellular carcinoma (HCC) in humans are sparse. We examined the association between urinary biomarkers of catechins and their metabolites and risk of HCC. Methods: A nested case-control study of HCC (221 cases and 1072 matched controls) was conducted within the Shanghai Cohort Study, a cohort of 18,244 men who were enrolled in 1986-1989. Specific catechins and their metabolites including epicatechin (EC), epigallocatechin (EGC), 4′-O-methyl-epigallocatechin (4′-MeEGC), (-)-5-(3′, 4′, 5′-trihydroxyphenyl)-gamma-valerolactone (M4), and (-)-5-(3′, 4′-dihydroxyphenyl)-gamma-valerolactone (M6) were quantified in urine samples collected from study subjects at enrollment. Logistic regression methods were used to calculate odds ratios (OR) and 95% confidence intervals (CI) with adjustment for established risk factors for HCC, including hepatitis B surface antigen (HBsAg) serology status, self-reported physician-diagnosed cirrhosis, cigarette smoking, and alcohol drinking. Results: Compared with men who had no detectable EC, men with detectable levels of urinary EC had a statistically significant lower risk of HCC (OR=0.64; 95% CI: 0.45, 0.92). The inverse association between EC and HCC risk was not modified by smoking, alcohol intake or HBsAg/cirrhosis status. This inverse EC-HCC association strengthened in analyses restricted to cases that were diagnosed 10 or more years after specimen collection (OR=0.40; 95% CI: 0.22, 0.71). There was no association between urinary levels of EGC or other catechin metabolites and HCC risk. Conclusion: In our study population green tea is the sole source of dietary EGC while the major sources of EC include green tea, as well as apples, black grapes, soybeans, and broad beans. Thus, the findings of the present study support the notion that consumption of fruits and legumes may have a beneficial effect on HCC risk. Experimental studies are warranted to elucidate the biologic mechanisms of EC in hepatocarcinogenesis. Citation Format: Joyce Y. Huang, Lesley M. Butler, Renwei Wang, Chung S. Yang, Jian-Min Yuan, Yu-Tang Gao. Urinary biomarkers of catechins in relation to risk of hepatocellular carcinoma in the Shanghai Cohort Study. [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 2212. doi:10.1158/1538-7445.AM2014-2212
Gynecology and Obstetrics: A Longitudinal Approach
Authors: Dave E. David
Journal: JAMA (1994)

<i>Gynecology and Obstetrics</i>could easily have been subtitled "A Chronological Approach," as it cleverly takes the reader from embryologic development and genetics in the early chapters through pediatric gynecology, puberty, and the reproductive years, ending in the postmenopausal years, senescense, disability, and death. This format supplants the conventional separation between obstetric and gynecologic chapters. The keenly edited 61-chapter compilation makes for easy reading, accented
A CASE OF RELAPSING NON-SUPPURATIVE NODULAR PANNICULITIS, SHOWING PHAGOCYTOSIS OF SUBCUTANEOUS FAT-CELLS BY MACROPHAGES.*
Authors: F. PARKES WEBER
Journal: British Journal of Dermatology (1925)

Journal Article A CASE OF RELAPSING NON‐SUPPURATIVE NODULAR PANNICULITIS, SHOWING PHAGOCYTOSIS OF SUBCUTANEOUS FAT‐CELLS BY MACROPHAGES. Get access F. PARKES WEBER, M.A., M.D., F.R.C.P. F. PARKES WEBER, M.A., M.D., F.R.C.P. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 37, Issue 7, 1 July 1925, Pages 301–311, https://doi.org/10.1111/j.1365-2133.1925.tb10003.x Published: 01 July 1925