tbuckley/cabot-search huggingface dataset:
Cellular and molecular toxicity of lead in bone.
Authors: J G Pounds, G J Long, J F Rosen
Journal: Environmental Health Perspectives (1991)

To fully understand the significance of bone as a target tissue of lead toxicity, as well as a reservoir of systemic lead, it is necessary to define the effects of lead on the cellular components of bone. Skeletal development and the regulation of skeletal mass are ultimately determined by the four different types of cells: osteoblasts, lining cells, osteoclasts, and osteocytes. These cells, which line and penetrate the mineralized matrix, are responsible for matrix formation, mineralization, and bone resorption, under the control of both systemic and local factors. Systemic components of regulation include parathyroid hormone, 1,25-dihydroxyvitamin D3, and calcitonin: local regulators include numerous cytokines and growth factors. Lead intoxication directly and indirectly alters many aspects of bone cell function. First, lead may indirectly alter bone cell function through changes in the circulating levels of those hormones, particularly 1,25-dihydroxyvitamin D3, which modulate bone cell function. These hormonal changes have been well established in clinical studies, although the functional significance remains to be established. Second, lead may directly alter bone cell function by perturbing the ability of bone cells to respond to hormonal regulation. For example, the 1,25-dihydroxyvitamin D3-stimulated synthesis of osteocalcin, a calcium-binding protein synthesized by osteoblastic bone cells, is inhibited by low levels of lead. Impaired osteocalcin production may inhibit new bone formation, as well as the functional coupling of osteoblasts and osteoclasts. Third, lead may impair the ability of cells to synthesize or secrete other components of the bone matrix, such as collagen or bone sialoproteins (osteopontin). Finally, lead may directly effect or substitute for calcium in the active sites of the calcium messenger system, resulting in loss of physiological regulation. The effects of lead on the recruitment and differentiation of bone cells remains to be established. Compartmental analysis indicates that the kinetic distribution and behavior of intracellular lead in osteoblasts and osteoclasts is similar to several other cell types. Many of the toxic effects of lead on bone cell function may be produced by perturbation of the calcium and cAMP messenger systems in these cells.
T Cell Receptor Recognition Motifs Govern Immune Escape Patterns in Acute SIV Infection
Authors: David A. Price, Sadie M. West, Michael R. Betts, Laura E. Ruff, Jason M. Brenchley, David R. Ambrozak, Yvette Edghill-Smith, Marcelo J. Kuroda, Derek Bogdan, Kevin Kunstman, Norman L. Letvin, Genoveffa Franchini, Steven M. Wolinsky, Richard A. Koup, Daniel C. Douek
Journal: Immunity (2004)
Randomized Trial of Cutting Balloon Compared With High-Pressure Angioplasty for the Treatment of Resistant Pulmonary Artery Stenosis
Authors: Lisa Bergersen, Kimberlee Gauvreau, Henri Justino, Alan Nugent, Jonathon Rome, Jacqueline Kreutzer, John Rhodes, David Nykanen, Evan Zahn, Larry Latson, Phillip Moore, James Lock, Kathy Jenkins
Journal: Circulation (2011)

Background— We sought to determine the safety and efficacy of Cutting Balloon therapy (CB) compared with conventional high-pressure balloon therapy (HPB) for the treatment of pulmonary artery stenosis. Methods and Results— This prospective, randomized, multicenter, investigational device exemption trial compared CB with HPB. Patient eligibility was determined at the precatheterization assessment; vessel eligibility was determined at catheterization. In all vessels, low-pressure balloon dilation to 8 atm was performed, and if it was not successful, the vessel was randomized to CB or HPB. The primary efficacy outcome was percent change in minimum lumen diameter. A core laboratory performed all vessel measurements and angiographic assessment of vessel damage. The primary safety outcome was any serious adverse event attributable to vessel dilation as assessed by the Data and Safety Monitoring Board. Seventy-three patients from 8 institutions were enrolled between 2004 and 2008. In these patients, 72 vessels responded to low-pressure balloon dilation. Of the 173 vessels that met eligibility criteria, 107 were randomized to CB and 66 to HPB. In randomized vessels, CB therapy was associated with greater percent increase in lumen diameter (85% versus 52%; P =0.004). After crossover was introduced, 26 of 47 vessels treated with HPB underwent CB therapy and experienced an additional 48% increase in lumen diameter; the final diameter after CB was 99% greater than the initial diameter. There were no serious adverse events related to treatment in a study vessel. Conclusion— CB therapy for pulmonary artery stenosis not responsive to low-pressure balloon is more effective than HPB therapy and has an equivalent safety profile.
Metabolic remodelling in human heart failure
Authors: H. Tuunanen, J. Knuuti
Journal: Cardiovascular Research (2011)

In addition to the typical abnormalities in myocardial structure and function, it is well established that the cardiac metabolism is abnormal in patients with heart failure (HF). Insulin resistance is a common co-morbidity in HF patients and also modulates cardiac metabolism in HF. The notion that an altered myocardial metabolism may contribute to the disease pathogenesis and optimizing it may serve therapeutic purposes underscores the importance of identifying the metabolic characteristics of HF patients. In this paper, the literature on the metabolic changes in human HF is reviewed, and the effects of metabolic modulators on patients with HF are discussed.
A Pseudoepidemic due to Atypical Mycobacteria in a Hospital Water Supply
Authors: Terry M. Stine
Journal: JAMA (1987)

We describe a pseudoepidemic due to atypical mycobacteria contaminating the water used by a pathology laboratory and bronchoscopy suite on two floors of the same hospital building. Inspection of laboratory procedures revealed that contamination occurred during specimen processing in pathology and while obtaining the bronchoscopic specimens.<i>Mycobacterium gordonae, Mycobacterium avium</i>complex, and<i>Mycobacterium scrofulaceum</i>were identified. During an eight-month period, a total of 22 (31%) of 70 patients with positive acid-fast smears had either an illness inconsistent with tuberculosis or a known alternate diagnosis. Control was easily obtained by insertion of a 0.2-μm polymer filter into the outflow tubing of our pathology tap water-deionizing unit and the tap water source in the bronchoscopy suite. The pseudoepidemic led to additional diagnostic-therapeutic intervention, but no patient experienced delay in appropriate diagnosis. Pseudoepidemics due to atypical mycobacteria will likely be of increased importance in institutions providing care to patients with acquired immunodeficiency syndrome. (<i>JAMA</i>1987;258:809-811)
A Predictive Model Identifies Patients Most Likely to Have Inadequate Bowel Preparation for Colonoscopy
Authors: Cesare Hassan, Lorenzo Fuccio, Mario Bruno, Nico Pagano, Cristiano Spada, Silvia Carrara, Chiara Giordanino, Emanuele Rondonotti, Gabriele Curcio, Pietro Dulbecco, Carlo Fabbri, Domenico Della Casa, Stefania Maiero, Adriana Simone, Federico Iacopini, Giuseppe Feliciangeli, Gianpiero Manes, Antonio Rinaldi, Angelo Zullo, Francesca Rogai, Alessandro Repici
Journal: Clinical Gastroenterology and Hepatology (2012)
US medical association reaches agreement with sacked editor
Authors: J. H. Tanne
Journal: BMJ (1999)

The American Medical Association (AMA) has reached a settlement with Dr George Lundberg, avoiding a possible lawsuit by him.

Dr Lundberg was fired last month as editor of JAMA (the journal of the American Medical Association) because he “fast tracked” the publication of a paper-which indicated that university students in the United States did not think that oral sex was “real sex”-in the midst of the impeachment trial of President Clinton.

In a bland …
Novel mutations in the folliculin gene associated with spontaneous pneumothorax
Authors: B. A. Frohlich, C. Zeitz, G. Matyas, H. Alkadhi, C. Tuor, W. Berger, E. W. Russi
Journal: European Respiratory Journal (2008)

Spontaneous pneumothorax is mostly sporadic but may also occur in families with genetic disorders, such as Birt–Hogg–Dubé syndrome, which is caused by mutations in the folliculin (<i>FLCN</i>) gene. The aim of the present study was to investigate the presence and type of mutation in a Swiss pedigree and in a sporadic case. Clinical examination, lung function tests and high-resolution computed tomography were performed. All coding exons and flanking intronic regions of <i>FLCN</i> were amplified by PCR and directly sequenced. The amount of <i>FLCN</i> transcripts was determined by quantitative real-time RT-PCR. Two novel mutations in <i>FLCN</i> were identified. Three investigated family members with a history of at least one spontaneous pneumothorax were heterozygous for a single nucleotide substitution (c.779G&gt;A) that leads to a premature stop codon (p.W260X). Quantitative real-time RT-PCR revealed a reduction of <i>FLCN</i> transcripts from the patient compared with an unaffected family member. DNA from the sporadic case carried a heterozygous missense mutation (c.394G&gt;A). Lung function of this patient was normal and computed tomography showed similar bilateral cysts, as observed in the two members of the unrelated Swiss family. Mutations in the folliculin gene are associated with cystic lung lesions in an otherwise morphological normal lung and predispose to spontaneous pneumothorax.
Treatment of Plantar Warts With Elastoplast and Podophyllin
Authors: D. A. Duthie, D. I. McCallum
Journal: BMJ (1951)

Nine fatal cases of acute suprarenal insufficiency occurring in pregnancy are described in which death was apparently due to acute suprarenal insufficiency.The history of these cases was similar to that described in similar conditions in non-pregnant patients by other authors.The symptoms of these patients were classified into four groups as described by Arnaud (1900), Lavenson (1908), and Simpson (1937).The predisposing factors in the cases described appeared to be obstetric shock, pre-eclamptic toxaemia, or late vomit- ing of pregnancy.In some cases the pathological lesion was thrombosis of the central veins without destruction of the gland substance, and it is suggested that in these cases the lesion may not be irreparable.
Vorinostat inhibits STAT6-mediated TH2 cytokine and TARC production and induces cell death in Hodgkin lymphoma cell lines
Authors: Daniela Buglio, Georgios V. Georgakis, Shino Hanabuchi, Kazuhiko Arima, Noor M. Khaskhely, Yong-Jun Liu, Anas Younes
Journal: Blood (2008)
Mdm2 inhibitor Nutlin-3a induces p53-mediated apoptosis by transcription-dependent and transcription-independent mechanisms and may overcome Atm-mediated resistance to fludarabine in chronic lymphocytic leukemia
Authors: Kensuke Kojima, Marina Konopleva, Teresa McQueen, Susan O'Brien, William Plunkett, Michael Andreeff
Journal: Blood (2006)
Preconception-initiated, low-dose aspirin did not increase live birth after 1 or 2 pregnancy losses
Authors: Joel G. Ray
Journal: Annals of Internal Medicine (2014)

ACP Journal Club16 September 2014Preconception-initiated, low-dose aspirin did not increase live birth after 1 or 2 pregnancy lossesJoel G. Ray, MD, MScJoel G. Ray, MD, MScSt. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada (J.G.R.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-161-6-201409160-02013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationSchisterman EF, Silver RM, Lesher LL, et al. Preconception low-dose aspirin and pregnancy outcomes: results from the EAGeR randomised trial. Lancet. 2014;384:29-36. https://pubmed.ncbi.nlm.nih.gov/24702835Clinical Impact RatingsGIM/FP/GP: Reference1 Kaandorp SP, Goddijn M, van der Post JA, et al. Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. N Engl J Med. 2010;362:1586-96. [PMID: 20335572] Google Scholar Author, Article, and Disclosure InformationAuthors: Joel G. Ray, MD, MScAffiliations: St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada (J.G.R.)This article was published at Annals.org on 2 September 2014. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 16 September 2014Volume 161, Issue 6Page: JC13KeywordsAspirinBirthBirth ratesChild healthHuman chorionic gonadotropinMenstrual cyclePregnancyRelative riskResearch fundingTermination of pregnancy ePublished: 16 September 2014 Issue Published: 16 September 2014 Copyright & PermissionsCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Uptake of Tc-99m HMDP in an Abdominal Aortic Aneurysm
Authors: TSUNEO HIRANO, HIDENORI OTAKE, KOICHRO MAEDA
Journal: Clinical Nuclear Medicine (1992)

A 79-year-old woman with a 12-week history of right hip fracture had three-phase bone scintigraphy. A moderate dilatation of the lower abdominal aorta was incidentally noted on blood-flow and blood pool images. On delayed static images a mildly increased uptake of radiotracer was seen in a thrombotic abdominal aortic aneurysm, confirmed by a plain abdominal radiograph and contrast-enhanced abdominal CT images.
NEW NEEDLE FOR INTRAVENOUS INJECTIONS
Authors: J. L. Wollheim
Journal: JAMA (1924)

In presenting this needle, I am fully aware that intravenous injections of arsphenamin or other medicament are usually given with all sorts of needles, and mostly with the straight ones. However, I have had so much satisfaction from the needle here described that I believe the few minutes necessary to study it will be well spent. This needle is of the bayonet shape, with the bevel down and with a flat hub. The bayonet shape prevents rotation on the point as an axis. It also acts to make a concentric syringe, eccentric. The bevel, by being down, prevents to some extent the piercing of the posterior wall of the vein, and I believe this is very important. The flat hub also prevents rotation on a longitudinal axis. It is made by Becton, Dickinson &amp; Co. of iridioplatinum. It can be passed through the flame if plugged with blood or other
Nuclear Threat: What About the Russians?
Authors: F. R. Sennewald
Journal: JAMA (1985)

<h3>To the Editor.—</h3> Let me offer the following comments on Dr Grey Dimond's<sup>1</sup>plans endorsed by the Editor to exchange 250,000 students as hostages with the Soviet Union to assuage his fears of an atomic attack. It is one thing to package this idea as a means to promote understanding and friendship and, therefore, peace between our nations. It would serve as a demonstration of our openness and goodwill and would expose the hypocrisy of their peace-and-friendship propaganda, since it is an offer that the Soviets cannot possibly accept. It is quite another matter to indulge in self-delusion that the Soviets are really worried enough about the likelihood of a US-initiated first strike to open their doors to a quarter million unruly US teenagers who would probably destroy the system from within. Or do you suppose that our kids, if you could catch them before they escape to Canada,
Comparison of the effects of loratadine and astemizole in the treatment of children with seasonal allergic rhinoconjunctivitis
Authors: A. L. Boner, C. Richeili, C. Castellani, E. Marchesi, A. Andreoli
Journal: Allergy (1992)

The efficacy and safety of a once‐daily dose of loratadine 10 mg (5 mg in patients whose body weight was ≤ 30 kg) and astemizole 2 mg/10 kg body weight o.d. were compared in a 14‐day third‐party blind study. Forty‐one children (30 boys and 11 girls, aged 6–14 years) with seasonal allergic rhinoconjunctivitis entered the study. The pollen count was monitored throughout the study. A significant improvement (p &lt; 0.01) in allergy symptoms was observed from the third day for both drugs; there was no significant difference between drugs, although loratadine led to a greater reduction in symptoms. In the astemizole group, the apparently rapid onset of drug action might by explained by reduced pollen exposure. Therapeutic response was excellent/good in 83.3% and 58.8% of the loratadine and astemizole groups, respectively. The results reported by the patients/parents were similar. Nine of the children on astemizole and four children on loratadine complained of side effects; three patients in the astemizole group were withdrawn from treatment because of adverse effects. No abnormal changes in lab values were observed in either group.
Lower in vitro lymphoproliferative responses to tetanus toxoid at 1 year in infants who are atopic at 3 years
Authors: F.I. Smillie, E.C. McKie, A.J. Elderfield, R.B. Gore, P. Kissen, G. Tavernier, F.Y. Patel, P.D. Arkwright, I. Hutchinson, A. Custovic, A. Woodcock
Journal: Journal of Allergy and Clinical Immunology (2003)
Abstract 1671: A genome-wide RNA interference screen identifies autophagy mediators with therapeutic implications in chronic myeloid leukemia.
Authors: Zhi Sheng, Sujuan Guo, Susan Murphy, Hanne Varmark, Amy Virbasius, Michael Green
Journal: Cancer Research (2013)

Abstract Autophagy plays a critical role in cancer formation and therapeutic resistance. However, little is known about how autophagy is regulated in cancer and how it mediates therapeutic resistance. Here we elect to use chronic myeloid leukemia (CML) as a cancer model to study autophagy in that it is driven by a single onco-protein BCR-ABL, whose activity can be selectively blocked by imatinib a front-line treatment for CML. Moreover, imatinib resistance frequently occurs in CML patients. Thus, unraveling autophagy regulation in CML and its role in overcoming imatinib resistance has substantial therapeutic benefits not only for CML but also for other cancers that can be treated by imatinib. In this report, we performed a genome-wide RNA interference screen in K562 human CML cells using monodansylcadaverine (MDC) that marks autolysosomes followed by fluorescence-activated cell sorting to label and isolate autophagic cells. We have identified 336 candidate genes, knockdown of which significantly increased MDC fluorescence. Our further validation utilized Cyto-IDTM Green dye that selectively stains autophagy vacuoles and quantitative RT-PCR that measures knockdown efficiency of shRNAs. We have uncovered a set of genes acting as autophagy mediators in K562 cells. To study their role in imatinib resistance, we measured the effect of imatinib in combination with the knocking down of autophagy mediators. Our results showed that the shRNA of VAMP7, a pivotal factor in vesicle transportation, substantially sensitized K562 cells to imatinib. Intriguingly, our further work revealed that depletion of VAMP7 blocked the activity of key autophagy suppressors AKT and mTOR, suggesting that VAMP7 and perhaps other autophagy mediators regulate imatinib sensitivity through signaling pathways that inhibit autophagy. In conclusion, a set of genes revealed by a genome-wide RNA interference screen mediates autophagy in CML cells and, more importantly, some of these genes render CML cells resistant to imatinib thereby becoming appealing drug targets. Citation Format: Zhi Sheng, Sujuan Guo, Susan Murphy, Hanne Varmark, Amy Virbasius, Michael Green. A genome-wide RNA interference screen identifies autophagy mediators with therapeutic implications in chronic myeloid leukemia. [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 1671. doi:10.1158/1538-7445.AM2013-1671
VINCENT'S ANGINA
Authors: Sam N. Key
Journal: JAMA (1927)

<h3>To the Editor:</h3> —Dr. Joseph Colt Bloodgood's timely article (The Journal, April 9, page 1142), so full of practical observations and suggestions, should stimulate more interest in oral lesions due to Vincent's angina. I agree with him that this disease is on the increase. It is my further observation that in the tonsillar type of the disease the young male adult is more frequently attacked. As laryngologist for the students' health service of the University of Texas, I find Vincent's angina of the tonsils becoming more frequent each year among the male students. This condition also obtains in my private practice, though to lesser extent. Children and elderly people appear to have tonsillar involvement with Vincent's angina much less frequently. Why in the tonsillar type of this disease is the young adult, particularly the male, more susceptible? In elderly persons, probably the fibrosed tonsil is not the type that harbors
NT-09 * CO-DELIVERY OF siRNA AND CHEMOTHERAPY; A NEW APPROACH FOR GBM TREATMENT USING A NANOCARRIERS SYSTEM
Authors: Z. R. Cohen, N. Peshes-Yeloz, A. Voll, Z. Zibly, D. Peer
Journal: Neuro-Oncology (2014)

Over the past decade, progress in genomics and proteomics has paved the way for identifying promising macromolecular therapeutics including small RNAs, peptides and proteins. Still, the vast majority of leading drugs candidates for the treatment of CNS diseases is ineffective, mainly due to restricted passages across the BBB. Nanoparticles packaging of therapy is of particular interest for its potential to treat brain tumors, due to their ability to transport drugs through the BBB, while improving the performance of drugs by decreasing systemic and local toxicity. We chose GBM known for its poor prognosis, as a model for brain tumors. In our model we used a novel cluster-based nanoparticles termed Gagomers (GAGs) as our delivery system. GAGs are coated with the glycosamine glycan hyaluronan and can therefore bind to a specific CD44 variants expressed on tumor cells. We found that GAGs can successfully bind to both cultured cells and neurosphers (stem cells) of GBM patients and to GBM cell lines. In vitro, GAGs loaded with Kif-11 siRNA, dramatically reduced the expression of Kif11 mRNA in GBM cell lines, suggesting it can efficiently target GBM and reduce the expression of specific genes. Additionally, GAGs loaded with Doxorubicin (DXR) induced higher rates of GBM elimination than free DXR. As a next step, we examined GAGs' ability to bind specifically and efficiently to GBM cell lines in-vivo. U87 cell lines were stereotactically injected into the brains of SCID-NOD mice. Following tumor inoculation and growth mice underwent convection with GAGs loaded with Cy5 siRNA. only U87 cells were labeled with Cy5 suggesting that local treatment with GAGs can efficiently target GBM cells in-vivo. Our future plans are to examine the activity of GAGs co-entrapping siRNA and DXR on human GBM cell lines in-vitro and in-vivo. This strategy may ultimately become a novel therapeutic modality to treat GBM.
Twelve-Year Experience of Radioactive Iodine Uptake in Hyperthyroid Patients
Authors: Fred W. Flickinger
Journal: JAMA (1979)

To the Editor.—  Recent communications inThe Journal, an article by Wong and Schultz (238:1741, 1977) and a letter by Sostre (239:1035, 1978), have summarized data suggesting that the radioactive iodine uptake (RAIU) in normal persons declined during the 20 years from 1957 to 1977.  Hooper and Caplan (238:411, 1977) indicate that increased dietary iodine content may be the cause of decreasing RAIU values in hyperthyroid patients as well as in normal persons. They found a notable change in hyperthyroid patients with toxic nodular goiter. However, they did not find an appreciable change in the RAIU values for patients with Graves' disease between 1970 and 1976.  Between 1965 and 1977 we treated 466 patients for hyperthyroidism using radioactive iodine. During these years we found that the 24-hour RAIU values for hyperthyroid patients remained essentially unchanged, between 45% and 55% (Figure), within the usually accepted hyperthyroid range. Of these 466 patients,