tbuckley/cabot-search huggingface dataset:
Abstract 5489: The IVECT™ method, a versatile micelle for the delivery of chemotherapeutic drugs
Authors: Jonathan Rios-Doria, Adam Carie, Gregoire Cardoen, Kevin Sill
Journal: Cancer Research (2010)

Abstract The development of new therapeutic agents has dramatically improved the quality of life and survival rate of patients suffering from a variety of disorders. However, drug delivery innovations are required to further improve the success rate of these treatments because approximately 40% of the newly discovered, promising small molecule therapeutics have poor aqueous solubility and cannot be delivered systemically. Rationally-designed, nanoscopic drug carriers offer a promising approach to achieving these goals due to their inherent ability to overcome multiple biological barriers. Ideally, a drug delivery system will not only be stable to systemic administration, but also be versatile enough to encapsulate a diverse range of molecules leading to decreased developmental and regulatory hurdles. These goals were the driving force behind the development of Intezyne's IVECT™ Method, which is based on tri-block copolymer micelle technology; spherical nano-sized drug carriers formed by the assembly of amphiphilic block copolymers in water. This modular drug delivery platform can be tailored to accommodate a wide range of drugs, biologics or diagnostics, improve post-administration stability, vary the micelle size, control the release of the therapeutic, and target specific diseased cells based on active targeting strategies. The purpose of this study is to demonstrate encapsulation of a variety of chemotherapeutics utilizing one polymer system, and show that crosslinked micelles have improved pharmacokinetic and toxicology profiles compared to the free drugs in animal models. To this end, formulations of gemcitabine, paclitaxel, doxorubicin and SN-38 were prepared and characterized for nanoparticle size distribution by DLS and active drug weight loading by HPLC. All micelles were 30-80 nm in size with weight loadings of between 2 and 10 %. PK data from cannulated rats demonstrated significant improvement in the CMax and AUC for encapsulated crosslinked formulations, compared to the free drugs. Toxicity profiling in CD-1 mice demonstrated that the polymer alone was very safe, as an MTD was not reachable, and that the crosslinked encapsulated formulations were tolerated at significantly higher doses compared to the free drugs. In conclusion, we have demonstrated that Intezyne's IVECT™ Method is extremely versatile and results in significant improvements in the overall pharmacology of chemotherapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5489.
Hematopoietic Stem Cell Mobilization–Associated Granulocytosis Severely Worsens Acute Renal Failure
Authors: Florian To[Combining Diaeresis]gel, Jorge Isaac, Christof Westenfelder
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Acute renal failure (ARF), resulting from ischemic or toxic insults, remains a major health care problem because of its grave prognosis and the limited effectiveness of available treatment modalities. On the basis of the recent demonstration that hematopoietic stem cells can differentiate into renal cells and the authors' observation here that ARF results in a rise in peripheral CD34+ cells, the authors tested whether a further increase in circulating stem cell numbers, induced by their mobilization from the bone marrow, would improve renal function and outcome in mice with ischemic ARF. Unexpected, it was found that the boosting of peripheral stem cell numbers failed to exert any renoprotective effects but rather was associated both with greatly increased severity of renal failure and mortality. Because identical ischemic injury in neutropenic mice resulted in milder renal insufficiency and significantly reduced mortality, it was deduced that the adverse effects of pharmacologic stem cell mobilization are primarily mediated by the concomitant induction of marked granulocytosis. In this manner, high numbers of activated granulocytes seem to obscure the potential renoprotective and positive survival effects of pluripotent hematopoietic stem cells, mediated by both their injurious renal and systemic actions. The data strongly argue against the clinical use of granulocytosis-inducing hematopoietic stem cell mobilization protocols for the prevention or treatment of ischemic ARF. Additional caution with this regimen may be warranted in patients with underlying renal insufficiency and those who develop renal insufficiency while undergoing stem cell mobilization in preparation for an autologous bone marrow transplant.
FDA Tries to Catch Up on Food Safety
Authors: Rebecca Voelker
Journal: JAMA (2010)

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
Metastasis of Malignant Melanoma to Common Biliary Duct Demonstrated With F-18 FDG PET/CT
Authors: Yasemin Sanli, Gozde Ozkan, Gulcin Yegen, Cuneyt Turkmen, Ayse Mudun
Journal: Clinical Nuclear Medicine (2011)

Malignant melanoma is well known for its propensity to spread to unpredictable sites. F-18 FDG PET can highlight metastases at unusual sites that may be missed with conventional imaging modalities. In this study, we present the case of a 57-year-old male patient who was referred to our department for PET/CT imaging because of metabolic characterization of the lesion located in distal common biliary duct and biopsied as malignant melanoma. His PET/CT images revealed a hypermetabolic lesion at the mentioned site. Interestingly, his images also showed mild FDG accumulation on right frontoparietal skin, and the biopsy of this lesion was also reported as malignant melanoma.
Abstract 2113: Programmed cell death 4 (PDCD4) regulates apoptotic resistance of human gliomas
Authors: Urszula Liwak, Lindsay Jordan, Martin Holcik
Journal: Cancer Research (2011)

Abstract Glioblastoma multiforme (GBM) is the most prevalent form of tumors of the central nervous system with an average survival rate of less than one year. Given the location and characteristics of GBM only limited treatment options are available, thus understanding the mechanisms of GBM formation or progression may lead to the development of novel treatment options. Strikingly, a common feature of GBM is the loss of expression of the tumor suppressor programmed cell death gene 4 (PDCD4), which correlates with a poor prognosis. Through both transcriptional and translational regulation, PDCD4 has been shown to regulate many proteins within the cell, although the precise mechanism of target selection is not known. We have hypothesised that silencing of PDCD4 in glioblastomas leads to an altered expression of apoptosis-regulating proteins resulting in the suppression of apoptotic signals and enhanced chemo-resistance of glioblastomas. Indeed, we show that low levels of PDCD4 correlate with an increase in the anti-apoptotic XIAP and Bcl-xL proteins, and decrease in pro-apoptotic Apaf-1. Importantly, these proteins are regulated at the level of protein synthesis through the internal ribosome entry sites (IRESs) in the 5’ untranslated region (UTR) of their respective mRNAs. IRES elements allow for translation to occur through a cap-independent mechanism during times of cellular stress when global translation is attenuated. We further show that PDCD4 regulates the activity of Bcl-xL, XIAP and Apaf-1 IRES and is therefore an IRES specific translational regulator. We further dissect the signalling pathways that regulate PDCD4 levels and show that activation of S6K2 results in the proteolytic degradation of PDCD4 and concomitant upregulation of XIAP and Bcl-xL, and downregulation of Apaf-1 levels. Importantly, reintroduction of PDCD4 into glioblastoma cell lines results in a reduction in both XIAP and Bcl-xL protein levels and enhanced cell death. In summary, our work provides a novel role for PDCD4 as a translational regulator of XIAP, Bcl-xL and Apaf-1, as well as a mechanistic understanding into the regulation of PDCD4 expression. Our research offers insight into the biology of glioblastomas in the hopes that we can identify new pathways as novel targets for anticancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2113. doi:10.1158/1538-7445.AM2011-2113
Small-bowel endoscopy
Authors: Claudia Diaz-Tobar, Lucia Fry, Klaus Mönkemüller
Journal: Endoscopy (2014)

Endoscopy Essentials Reviews in the Endoscopy Essentials series cite publications from the past year which, in the authors’ opinion, reflect the state-of-the-art in endoscopy. Alongside a short summary of each paper, authors explain why they consider their selected articles to be of importance.
Abstract 666: Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer.
Authors: Semra Demokan, Alice Y. Chuang, Kavita M. Pattani, David Sidransky, Wayne Koch, Joseph A. Califano
Journal: Cancer Research (2013)

Abstract Purpose: Methylation of CpG islands in the promoter region of genes acts as a significant mechanism of epigenetic gene silencing in head and neck cancer. In this study, we assessed the utility of epigenetic alterations of a panel of twelve genes (NOL4, IRX1, SLC5A8, LRRC3B, FUSSEL18, EBF3, GBX2, HMX2, SEPT9, ALX3, SOCS3, LHX6) previously reported. Experimental Design: In this study we investigated methylation of the 12 gene promoters via a candidate gene approach. After the initial screening of methylated CpG islands on the promoter regions by bisulfite sequencing using salivary rinse samples, only two genes had methylated CpG dinucleotides on their promoter regions in tumor samples and absence of methylated CpGs were found in normal salivary rinse samples after bisulfite modification and bisulfite sequencing. We then performed quantitative methylation specific PCR (Q-MSP) on 16 salivary rinse and 14 normal mucosal samples from healthy people and 33 HNSCC tumor samples for two genes selected. Results: After validation with QMSP, one gene, nucleolar protein 4 (NOL4), was highly methylated (91%) in tumor samples and unmethylated in normal salivary rinse samples and minimally methylated in normal mucosal samples demonstrating cancer specific methylation in HNSCC tissues. Although iroquois homeobox 1 (IRX1) gene was observed as methylated in normal mucosal and salivary rinse samples, indeed, the methylation values of these normal samples were very low (less than 10%). Conclusions: We identified NOL4, as a highly specific promoter methylated gene was associated with HNSCC. IRX1 which may have a potential as a biomarker for HNSCC and should also be assessed in a larger cohort. Citation Format: Semra Demokan, Alice Y. Chuang, Kavita M. Pattani, David Sidransky, Wayne Koch, Joseph A. Califano. Validation of nucleolar protein 4 as a novel methylated tumor suppressor gene in head and neck cancer. [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 666. doi:10.1158/1538-7445.AM2013-666
Globin gene expression in erythroid human fetal liver cells.
Authors: T J Ley, K A Maloney, J I Gordon, A L Schwartz
Journal: Journal of Clinical Investigation (1989)

We measured steady-state levels of the human globin mRNAs in liver samples from several mid-gestational fetuses. RNA from the epsilon, gamma, beta, zeta, theta, and alpha globin genes were present in fetal liver samples isolated from 10-25-wk embryos. The abundance of all human globin mRNAs declined in older fetuses, presumably because of a gradual reduction in the proportion of erythroid precursors in the liver as development proceeds. The gamma:beta globin mRNA ratio in 10-18-wk fetal erythroblasts was 6-7:1, and in adult erythroid bone marrow the ratio was 0.02:1. In fetal liver samples, the relative abundance of epsilon transcripts was less than 1% that of gamma, and zeta transcripts less than 5% that of alpha. Embryonic transcripts declined in abundance during late fetal development and were not detected in newborn liver or adult erythroid bone marrow. theta globin mRNA also represented a minor species (less than 1% that of alpha) in fetal liver samples, but in contrast to the embryonic mRNAs, was most abundant in adult marrow samples obtained from patients with erythroid hyperplasia. These results support the hypothesis that globin protein levels are regulated by the relative amounts of each globin mRNA at various stages of erythropoietic development.
The addicted human brain: insights from imaging studies
Authors: Nora D. Volkow, Joanna S. Fowler, Gene-Jack Wang
Journal: Journal of Clinical Investigation (2003)

tributes to an inability to inhibit the drive to seek and consume the drug and results in compulsive drug intake.This model has implications for therapy, for it suggests a multi-prong approach that targets strategies to decrease the rewarding properties of drugs, to enhance the rewarding properties of alternative reinforcers, to interfere with conditioned-learned associations, and to strengthen cognitive control in the treatment of drug addiction.
Not So Popular Psychiatry
Authors: P. Birchenall, P. Tuddenham
Journal: BMJ (1973)

The principal role of the consultant psychiatrist must be to bestow therapeutic skill on other workers (including general practitioners, social workers, health visitors, and ward nurses).This is not only dictated by arithmetic-it also offers the only hope for prevention.Mr. Bury is right to insist that psychiatry become more effective, but he should be warned not to expect it (or psychiatrists) to become popular; for it deals with the nost unpopular of human feelings.-I am, etc.,
Prostatic Obstruction and Inguinal Hernia
Authors: H. M. Grant
Journal: BMJ (1952)

<h3>Abstract</h3> One of the hallmark behaviors of social groups is division of labour, where different group members become specialized to carry out complementary tasks. By dividing labour, cooperative groups of individuals increase their efficiency, thereby raising group fitness even if these specialized behaviors reduce the fitness of individual group members. Here we provide evidence that antibiotic production in colonies of the multicellular bacterium <i>Streptomyces coelicolor</i> is coordinated by a division of labour. We show that <i>S. coelicolor</i> colonies are genetically heterogenous due to massive amplifications and deletions to the chromosome. Cells with gross chromosomal changes produce an increased diversity of secondary metabolites and secrete significantly more antibiotics; however, these changes come at the cost of dramatically reduced individual fitness, providing direct evidence for a trade-off between secondary metabolite production and fitness. Finally, we show that colonies containing mixtures of mutant strains and their parents produce significantly more antibiotics, while colony-wide spore production remains unchanged. Our work demonstrates that by generating mutants that are specialized to hyper-produce antibiotics, streptomycetes reduce the colony-wide fitness costs of secreted secondary metabolites while maximizing the yield and diversity of these products.
BLOOD VESSEL VISUALIZATION
Authors: JOHN B. CARNETT
Journal: JAMA (1927)

About eighteen months ago, one of us was confronted with the problem of differentiating, in a patient with a chronic toe ulcer, a very early thrombo-angiitis obliterans from a trophic or other disturbance. In this connection, it was thought that if the vessels could be visualized by means of a proper opaque substance, their condition would enable one to make an early diagnosis with the ultimate view of treatment before severe vessel alteration precluded all hope of cure. Besides, such visualization ought to be helpful in various disturbances of the vessels such as embolism, aneurysm and gangrenes, to determine the extent of the obliterative process.  Accordingly, experimental work was undertaken to determine whether or not visualization of the vessels was possible in the living subject. Sodium iodide, potassium bismuth tartrate, and dominal x (a German compound), which was advised by Dr. Pfahler, gave unsatisfactory roentgenologic films in animals. Shortly after
Deciphering the Impact of Common Genetic Variation on Lung Cancer Risk: A Genome-Wide Association Study
Authors: Peter Broderick, Yufei Wang, Jayaram Vijayakrishnan, Athena Matakidou, Margaret R. Spitz, Timothy Eisen, Christopher I. Amos, Richard S. Houlston
Journal: Cancer Research (2009)

To explore the impact of common variation on the risk of developing lung cancer, we conducted a two-phase genome-wide association (GWA) study. In phase 1, we compared the genotypes of 511,919 tagging single nucleotide polymorphisms (SNP) in 1,952 cases and 1,438 controls; in phase 2, 30,568 SNPs were genotyped in 2,465 cases and 3,005 controls. SNP selection was based on best supported P values from phase 1 and two other GWA studies of lung cancer. In the combined analysis of phases 1 and 2, the strongest associations identified were defined by SNPs mapping to 15q25.1 (rs12914385; P = 3.19 x 10(-16)), 5p15.33 (rs4975616; P = 6.66 x 10(-7)), and 6p21.33 (rs3117582; P = 9.13 x 10(-7)). Variation at 15q25.1, but not 5p15.33 or 6p21.33, was strongly associated with smoking behavior with risk alleles correlated to higher consumption. Variation at 5p15.33 was shown to significantly influence induction of lung cancer histology. Pooling data from the four series provided 21,620 genotypes for 7,560 cases and 8,205 controls. A meta-analysis provided increased support that variation at 15q25.1 (rs8034191; P = 3.24 x 10(-26)), 5p15.33 (rs4975616; P = 2.99 x 10(-9)), and 6p21.33 (rs3117582; P = 4.46 x 10(-10)) influences lung cancer risk. The next best-supported associations were attained at 15q15.2 (rs748404: P = 1.08 x 10(-6)) and 10q23.31 (rs1926203; P = 1.28 x 10(-6)). These data indicate few common variants account for 1% of the excess familial risk underscoring the necessity of having additional large sample series for gene discovery.
De subitaneis mortibus. XXIII. Rheumatoid arthritis and ankylosing spondylitis.
Authors: T N James
Journal: Circulation (1977)

The conduction system of the heart was carefully examined at necropsy in two cases of rheumatoid arthritis and one of ankylosing spondylitis. All three patients had cardiac electrical instability and two fo the three died suddenly. The electrophysiological abnormalities of the three patients included paroxysmal atrial fibrillation in the first case, sustained atrial fibrillation with complete heart block and escape atrioventricular (A-V) junctional rhythm in the second case, and progressively increasing heart block eventually became complete in the third case. The sinus node exhibited extensive focal degeneration with and without associated inflammation in all three hearts, but the sinus node artery was not remarkably abnormal in any of these. All three hearts had important focal degenerative disease in the A-V node and His bundle, and in each of these there was marked narrowing of the local nutrient arteries, amounting to virtual occlusion in two hearts. The probable relationship of these postmortem histological findings to the electrocardiographic disturbances in each patient is discussed. Abnormalities in the cardiac conduction system of the hearts of these three patients are compared to ones previously reported for disseminated lupus erythematosus, polyarteritis nodosa, and scleroderma heart disease.
The relationships between exposure dose and response in induction and elicitation of contact hypersensitivity in humans
Authors: P.S. Friedmann
Journal: British Journal of Dermatology (2007)

Like all physiological systems, the human immune system exhibits dose–response relationships in its reactions. The strength of sensitization is related to the potency of the immunogen and the dose that reaches the immune system. In skin, as sensitizing dose per unit area (μg cm−2) is increased on a log scale, there is a sigmoid dose–response curve for subsequent reactivity. Similarly, the response to elicitation shows a classical sigmoid response to increasing challenge dose, with the dose per unit area again being the determinant. There is a clear inverse correlation between the strength of sensitization and the subsequent dose of antigen to which an individual will respond. This is reflected in the different challenge systems used to diagnose the existence of allergic contact sensitization to a given allergen. The occluded patch test aims to use the highest concentration possible to detect the weakest degrees of allergy, whereas the repeated open application test uses much lower concentrations similar to those encountered in real life, applied repeatedly but without occlusion, to assess clinical relevance. Many authors have attempted to use the lowest concentrations to which rare, highly sensitized individuals can react to define the concentrations which might be free of risk in terms of inducing allergic sensitization. However, it is clear that the dose–response relationships for induction of sensitivity by repeated low‐dose exposures must be carefully defined in future studies. This article reviews the dose–response relationships of human contact sensitization.
INTERACTION BETWEEN ROSUVASTATIN AND HIGH SENSITIVITY C-REACTIVE PROTEIN ON PROGRESSION OF AORTIC STENOSIS
Authors: Kwan-Leung Chan, Andy Ni, James Tam, Randall Sochowski, Jean G. Dumesnil, John P. Giannoccaro, John Jue, A. Shekhar Pandey, Cam Joyner, Koon Teo
Journal: Journal of the American College of Cardiology (2010)