tbuckley/cabot-search huggingface dataset:
Abstract 5464: Genotoxicity of multi-walled carbon nanotubes at occupationally relevant doses
Authors: Linda M. Sargent, Steven H. Reynolds, David Lowry, Michael L. Kashon, Stanley A. Benkovic, Jeffery L. Salisbury, Ann F. Hubbs, Shih-Houng Young, Katelyn J. Siegrist, Michael J. Keane, John Mastovich, Kristin Bunker, Jacqueline Sturgeon, Lorenzo Cena, Cerasela-Zoica Dinu
Journal: Cancer Research (2012)

Abstract Carbon nanotubes represent a creative alternative for applications in medicine as therapeutic vectors, imaging and controlled release of active molecules. Although the low density and small size of carbon nanotubes makes respiratory exposures to workers likely during the production or use of commercial products, the potential genotoxicity of multi-walled carbon nanotubes has not been investigated. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to single-walled carbon nanotubes (SWCNT). In order to investigate whether genetic damage was unique to SWCNT, we examined mitotic spindle aberrations following dosing of cells to multi-walled carbon nanotubes (MWCNT) at concentrations anticipated in the workplace. Immortalized and primary respiratory epithelial cells were exposed to 0.024, 0.24, 2.4, and 24μg/cm2 carbon nanotubes. The minimal dose of MWCNT considered for this research was based on the permissible exposure limit for particles with an aerodynamic diameter of less than 5 microns (Occupation Safety and Health Administration). MWCNT induced a dose response of disrupted centrosomes, mitotic spindles and aneuploid chromosome number. The data further showed that monopolar mitotic spindles comprised 95% of the disrupted mitoses. The monopolar phenotype of the disrupted mitotic spindles is in sharp contrast to the multi-polar spindle of SWCNT-induced disruption. Three-dimensional reconstructions showed carbon nanotubes integrated with the microtubules, the DNA and within the centrosome structure. The lower doses did not cause cytotoxicity or apoptosis 24 hours after exposure; however, after 72 hours, significant cytotoxicity was observed in the MWCNT-exposed cells. Disruption of the centrosome is common in many solid tumors including lung cancer. The resulting aneuploidy is a key event in the progression of cancer and is correlated with tumor stage. Our results demonstrate significant disruption of the mitotic spindle by MWCNT at occupationally relevant doses. These results suggest caution should be used in the handling and processing of carbon nanotubes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5464. doi:1538-7445.AM2012-5464
CXCR6 Induces Prostate Cancer Progression by the AKT/Mammalian Target of Rapamycin Signaling Pathway
Authors: Jianhua Wang, Yi Lu, Jingchen Wang, Alisa E. Koch, Jian Zhang, Russell S. Taichman
Journal: Cancer Research (2008)

Abstract Previous studies show that the chemokine CXCL16 and its receptor CXCR6 are likely to contribute to prostate cancer (PCa). In this investigation, the role of the CXCR6 receptor in PCa was further explored. CXCR6 protein expression was examined using high-density tissue microarrays and immunohistochemistry. Expression of CXCR6 showed strong epithelial staining that correlated with Gleason score. In vitro and in vivo studies in PCa cell lines suggested that alterations in CXCR6 expression were associated with invasive activities and tumor growth. In addition, CXCR6 expression was able to regulate expression of the proangiogenic factors interleukin (IL)-8 or vascular endothelial growth factor (VEGF), which are likely to participate in the regulation of tumor angiogenesis. Finally, we found that CXCL16 signaling induced the activation of Akt, p70S6K, and eukaryotic initiation factor 4E binding protein 1 included in mammalian target of rapamycin (mTOR) pathways, which are located downstream of Akt. Furthermore, rapamycin not only drastically inhibited CXCL16-induced PCa cell invasion and growth but reduced secretion of IL-8 or VEGF levels and inhibited expression of other CXCR6 targets including CD44 and matrix metalloproteinase 3 in PCa cells. Together, our data shows for the first time that the CXCR6/AKT/mTOR pathway plays a central role in the development of PCa. Blocking the CXCR6/AKT/mTOR signaling pathway may prove beneficial to prevent metastasis and provide a more effective therapeutic strategy for PCa. [Cancer Res 2008;68(24):10367–76]
Induced CD4+ forkhead box protein–positive T cells inhibit mast cell function and established contact hypersensitivity through TGF-β1
Authors: Wenru Su, Huimin Fan, Maogen Chen, Julie Wang, David Brand, Xiaoshun He, Valerie Quesniaux, Bernhard Ryffel, Ling Zhu, Dan Liang, Song Guo Zheng
Journal: Journal of Allergy and Clinical Immunology (2012)
NEW, THIRD CLASS OF AMYLOID FIBRIL PROTEIN
Authors: G. Husby, J. B. Natvig, K. Sletten
Journal: The Journal of Experimental Medicine (1974)

An unusual protein AR was isolated from the amyloid fibril preparation derived from a patient with primary amyloidosis. Protein AR was unique in its antigenicity, and revealed no structural identity with any known amyloid proteins or with immunoglobulin chains or fragments. Thus a new third class of amyloid fibril proteins besides the immunoglobulin light-chain variable region fragments and the nonimmunoglobulin protein AS, has been characterized. A component antigenically related to protein AR was found in the serum of the patient.
Airway epithelial SPDEF integrates goblet cell differentiation and pulmonary Th2 inflammation
Authors: Priya Rajavelu, Gang Chen, Yan Xu, Joseph A. Kitzmiller, Thomas R. Korfhagen, Jeffrey A. Whitsett
Journal: Journal of Clinical Investigation (2015)

Epithelial cells that line the conducting airways provide the initial barrier and innate immune responses to the abundant particles, microbes, and allergens that are inhaled throughout life. The transcription factors SPDEF and FOXA3 are both selectively expressed in epithelial cells lining the conducting airways, where they regulate goblet cell differentiation and mucus production. Moreover, these transcription factors are upregulated in chronic lung disorders, including asthma. Here, we show that expression of SPDEF or FOXA3 in airway epithelial cells in neonatal mice caused goblet cell differentiation, spontaneous eosinophilic inflammation, and airway hyperresponsiveness to methacholine. SPDEF expression promoted DC recruitment and activation in association with induction of Il33, Csf2, thymic stromal lymphopoietin (Tslp), and Ccl20 transcripts. Increased Il4, Il13, Ccl17, and Il25 expression was accompanied by recruitment of Th2 lymphocytes, group 2 innate lymphoid cells, and eosinophils to the lung. SPDEF was required for goblet cell differentiation and pulmonary Th2 inflammation in response to house dust mite (HDM) extract, as both were decreased in neonatal and adult Spdef–/– mice compared with control animals. Together, our results indicate that SPDEF causes goblet cell differentiation and Th2 inflammation during postnatal development and is required for goblet cell metaplasia and normal Th2 inflammatory responses to HDM aeroallergen.
Are tobacco subsidies a misuse of public funds?
Authors: L. Joossens, M. Raw
Journal: BMJ (1996)

The European Union spends about 1000m ecu (800m pounds, $1240m) a year subsidizing tobacco production but only about 1.55m ecu (1.2m pounds, $1.85m) on smoking prevention. The subsidies, part of the common agricultural policy, were originally intended to encourage farmers to grow commercially valued varieties of tobacco and thus reduce imports. But they also aimed to guarantee farmers' income, a goal in direct conflict with the first. The policy has failed to adapt production to demand or reduce imports, since most tobacco grown in the union has little commercial value. Reforms introduced in 1992 have had limited impact on expenditure, and data produced as a result of the reforms show that it would be much cheaper to give farmers direct income support than to subsidize them growing tobacco. Tobacco subsidies should be abolished and more should be spent on smoking prevention.
Infantile eczema
Authors: KEITH MUSGROVE, JOHN K. MORGAN
Journal: British Journal of Dermatology (1976)

A 15-17 year follow-up study was conducted on ninety-nine patients who had suffered from infantile eczema. The persistance of the eczema and the occurrence of related conditions were noted. The persistence of eczema was shown to be greater in those patients with a positive family history of eczema and in those who had developed asthma or hay-fever. An attempt was made to see if the persistence of eczema was affected by the position of the child in the family, and some factors provoking relapses were noted. The patients were also questioned with regard to their achievements in academic examinations, and to their social, artistic and sporting activities. The results showed a success rate in examinations not significantly higher than average. It was not possible to show if there is a particular type of atopic personality. There was no constant characteristic in social or artistic patterns. The group as a whole were normal at the milestones of early development, i.e. walking, talking and reading, and also normal with regard to weight and height.
Identification of an extracellular plasmin binding protein from nephritogenic streptococci.
Authors: R Poon-King, J Bannan, A Viteri, G Cu, J B Zabriskie
Journal: The Journal of Experimental Medicine (1993)

Examination of the extracellular products of nephritis(+) and nephritis(-) group A streptococci revealed the presence of a 46-kD protein secreted by nephritogenic strains that binds to human plasmin. Immunological data revealed that this protein, called nephritis plasmin binding protein (NPBP), is not related to group A streptokinase nor to a recently described streptococcal dehydrogenase protein. The binding of human plasmin to this protein can be blocked by epsilon-amino caproic acid, indicating the importance of lysine groups in the binding process. Mutanolysin extracts of cell walls from these nephritogenic strains probed with anti-NPBP antibody were negative for cell wall-bound NPBP. Serological data with acute poststreptococcal glomerulonephritis (APSGN) and acute rheumatic fever sera indicated that the protein reacts preferentially with APSGN sera. Amino acid sequence analysis and immunological reactivity suggest NPBP is the streptococcal pyrogenic exotoxin B precursor, also previously described as zymogen (streptococcal proteinase precursor). The secretion of both group A streptokinase and a secreted plasmin binding protein in the same nephritogenic strain raises an intriguing hypothesis of the mechanisms of action of this protein in APSGN.
THE RELATIONSHIP OF POLYMORPHONUCLEAR LEUKOCYTES TO INFERTILITY IN UTERI CONTAINING FOREIGN BODIES
Authors: Earl L. Parr, Russell W. Schaedler, James G. Hirsch
Journal: The Journal of Experimental Medicine (1967)

A chronic infiltration of polymorphonuclear leukocytes was invariably found in the infertile regions of uteri containing foreign bodies in conventional rats, germfree rats, mice, and rabbits. Polymorphonuclear leukocytes were never found in the fertile regions of these uteri. A foreign body in the uterus of the rat, and probably also the mouse, was associated with a bacterial infection which spread the inflammatory response throughout the horn containing the foreign body, and in the mouse occasionally into the control horn as well. No bacteria could be cultured from the rabbit uterine horn containing a foreign body. In the germfree rat, both the infiltration of polymorphonuclear leukocytes into the uterus and fertility were significantly different from that observed in the conventional rat. Whereas in the conventional rat the inflammation and infertility extended along the entire length of the uterine horn containing a small foreign body, in the germfree rat the inflammation and infertility were closely correlated to the position of the foreign body. As judged by measurements of lysozyme in the uterine lumens of rats and rabbits, polymorphonuclear leukocytes released their contents into solution in the uterine lumen. It is concluded that some substance derived from polymorphonuclear leukocytes may exert toxic effects on fertilized ova or on spermatozoa and thus be responsible for the infertility of uteri containing foreign bodies.
Changes in Glomerular Kidney Function Among HIV-1<b>–</b>Uninfected Men and Women Receiving Emtricitabine<b>–</b>Tenofovir Disoproxil Fumarate Preexposure Prophylaxis
Authors: Kenneth K. Mugwanya, Christina Wyatt, Connie Celum, Deborah Donnell, Nelly R. Mugo, Jordan Tappero, James Kiarie, Allan Ronald, Jared M. Baeten
Journal: JAMA Internal Medicine (2014)

<h3>Importance</h3> Tenofovir disoproxil fumarate (TDF) use has been associated with declines in the estimated glomerular filtration rate (eGFR) when used as part of antiretroviral treatment by persons with human immunodeficiency virus (HIV) type 1, but limited data are available for risk when used as preexposure prophylaxis (PrEP) for HIV-1 prevention. <h3>Objective</h3> To determine whether TDF-based PrEP causes eGFR decline in HIV-1<b>–</b>uninfected adults. <h3>Design, Setting, and Participants</h3> A per-protocol safety analysis of changes in eGFR in the Partners PrEP Study, a randomized, placebo-controlled trial of daily oral TDF and emtricitabine (FTC)-TDF PrEP among heterosexual HIV-1<b>–</b>uninfected members of serodiscordant couples in Kenya and Uganda. The trial was conducted from 2008 to 2012. <h3>Main Outcomes and Measures</h3> Predefined outcomes of this analysis were mean eGFR change and a 25% or greater eGFR decline from baseline. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. <h3>Results</h3> Of 4640 participants in the once-daily TDF (n = 1548), FTC-TDF (n = 1545), or placebo (n = 1547) groups, 63% were men. At enrollment, median age was 35 years (range, 18-64 years), and mean eGFR was 130 mL/min/1.73 m<sup>2</sup>. During a median follow-up of 18 months (interquartile range 12-27 months), mean within-group eGFR change from baseline was +0.14 mL/min/1.73 m<sup>2</sup>for TDF, −0.22 mL/min/1.73 m<sup>2</sup>for FTC-TDF, and +1.37 mL/min/1.73 m<sup>2</sup>for placebo, translating into average declines in eGFR attributable to PrEP vs placebo of −1.23 mL/min/1.73 m<sup>2</sup>(95% CI, −2.06 to −0.40;<i>P</i> = .004) for TDF and −1.59 mL/min/1.73 m<sup>2</sup>(95% CI, −2.44 to −0.74;<i>P</i> &lt; .001) for FTC-TDF. The difference in mean eGFR between PrEP and placebo appeared by 1 month after randomization, was stable through 12 months, and then appeared to wane thereafter. The respective proportions of persons who developed a confirmed 25% or greater eGFR decline from baseline by 12 and 24 months was 1.3% and 1.8% for TDF and 1.2% and 2.5% for FTC-TDF, and these frequencies were not statistically different from the confirmed decline in the placebo group (0.9% and 1.3% by 12 and 24 months, respectively). <h3>Conclusions and Relevance</h3> In this large randomized, placebo-controlled trial among heterosexual persons, with median follow-up of 18 months and maximum follow-up of 36 months, daily oral TDF-based PrEP resulted in a small but nonprogressive decline in eGFR that was not accompanied by a substantial increase in the risk of clinically relevant (≥25%) eGFR decline. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00557245
Rubella Immunization Risks
Authors: John Evrard
Journal: JAMA (1971)

<h3>To the Editor.—</h3> In LETTERS (<b>217</b>:697, 1971), Sever commented on the risk of conception within 60 days after delivery of a previous pregnancy. The data as expressed were ambiguous, at least to me. I assume that during the time span involved, 53,000 women were pregnant, and that 7,507 had a second pregnancy. It would seem to me that most of the 53,000 were at the risk of a second pregnancy (unless they died or were sterilized in the interim) and that 53,000 should have been the denominator rather than the 7,507 in the calculation of the percentage who conceived within 60 days. Thus, the percentage would be 0.8% rather than 5.6%.
Amphotericin B in Cryptococcal Meningitis
Authors: GEORGE A. SAROSI
Journal: Annals of Internal Medicine (1969)

Thirty-one patients with proved cryptococcal meningitis were treated with intravenous amphotericin B, and almost half had intrathecal therapy as well. The case fatality ratio during initial treatment was 9 of 31, or 29%. Outcome of the initial therapy tended to he worse, although not significantly so, in those patients who were older and had coexisting disease. Four of the 22 surviving patients relapsed from 6 weeks to 29 months after the completion of initial therapy. Three of the four patients who relapsed died from cryptococcal meningitis in spite of a second course of therapy. Two additional patients, apparently cured of cryptococcal meningitis, died of other causes shortly after the completion of initial therapy. The remaining 17 patients have now been followed from 2 to 12 years (average 7½ years). Only four have significant neurological residuals, but none require custodial care. Frequent follow-up examinations, including examinations of the spinal fluid, are recommended for at least 3 years to recognize all relapses early. This study is in agreement with other reports supporting the effectiveness of amphotericin B in the treatment of cryptococcal meningitis.
Myopia and Dental Caries
Authors: Joseph H. Goldstein
Journal: JAMA (1971)

<h3>To the Editor.—</h3> The cause of myopia remains unknown. Dunphy<sup>1</sup>has recently reviewed the various theories, identifying the systemic as well as local factors which might play a role in the development of myopia. Although some evidence was presented to support the belief that myopia may be part of a generalized anomaly, no definite conclusion could be made. Stocker noted that "Kuschel went so far as to claim a relation between flatfoot and myopia as a sign of weakness of all supporting tissue."<sup>2</sup>Other authors have provided evidence for its relation to a generalized diseased process. Pemberton and coworkers noted myopia in all affected members in a patient with Ehlers-Danlos syndrome.<sup>3</sup>They suggested that myopia was one of many signs of a generalized collagen disorder. Allen and co-workers<sup>4</sup>noted myopia in 10 of 12 eyes of patients with Marfan's syndrome. Johnson and co-workers,<sup>5</sup>in reporting
Inhibition of intracerebral glioblastoma growth by targeting the insulin-like growth factor 1 receptor involves different context-dependent mechanisms
Authors: Martin Zamykal, Tobias Martens, Jakob Matschke, Hauke S. Günther, Annegret Kathagen, Alexander Schulte, Regina Peters, Manfred Westphal, Katrin Lamszus
Journal: Neuro-Oncology (2014)

Signaling by insulin-like growth factor 1 receptor (IGF-1R) can contribute to the formation and progression of many diverse tumor types, including glioblastoma. We investigated the effect of the IGF-1R blocking antibody IMC-A12 on glioblastoma growth in different in vivo models. U87 cells were chosen to establish rapidly growing, angiogenesis-dependent tumors in the brains of nude mice, and the GS-12 cell line was used to generate highly invasive tumors. IMC-A12 was administered using convection-enhanced local delivery. Tumor parameters were quantified histologically, and the functional relevance of IGF-1R activation was analyzed in vitro. IMC-A12 treatment inhibited the growth of U87 and GS-12 tumors by 75% and 50%, respectively. In GS-12 tumors, the invasive tumor extension and proliferation rate were significantly reduced by IMC-A12 treatment, while apoptosis was increased. In IMC-A12–treated U87 tumors, intratumoral vascularization was markedly decreased, and tumor cell proliferation was moderately reduced. Flow cytometry showed that <2% of U87 cells but >85% of GS-12 cells expressed IGF-1R. Activation of IGF-1R by IGF-1 and IGF-2 in GS-12 cells was blocked by IMC-A12. Both ligands stimulated GS-12 cell proliferation, and IGF-2 also stimulated migration. IMC-A12 inhibited these stimulatory effects and increased apoptosis. In U87 cells, stimulation with either ligand had no functional effect. IGF-1R blockade can inhibit glioblastoma growth by different mechanisms, including direct effects on the tumor cells as well as indirect anti-angiogenic effects. Hence, blocking IGF-1R may be useful to target both the highly proliferative, angiogenesis-dependent glioblastoma core component as well as the infiltrative periphery.
Data and Safety Monitoring Boards
Authors: Paul W. Armstrong, Robert M. Califf
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
Incidence of therapy-related myeloid neoplasia after initial therapy for chronic lymphocytic leukemia with fludarabine-cyclophosphamide versus fludarabine: long-term follow-up of US Intergroup Study E2997
Authors: Mitchell R. Smith, Donna Neuberg, Ian W. Flinn, Michael R. Grever, Hillard M. Lazarus, Jacob M. Rowe, Gordon Dewald, John M. Bennett, Elisabeth M. Paietta, John C. Byrd, Mohamad A. Hussein, Frederick R. Appelbaum, Richard A. Larson, Mark R. Litzow, Martin S. Tallman
Journal: Blood (2011)
Disorders of Bone and Mineral Metabolism
Authors: Lila A. Wallis
Journal: JAMA (1993)

<i>Disorders of Bone and Mineral Metabolism</i>is a giant book of 1118 pages. The two editors take a justified pride in their successorship to Fuller Albright and Edward Reifenstein's<i>The Parathyroid Glands and Metabolic Bone Disease</i>. The present volume is much more than an "incomplete summary of studies on calcium metabolism"—the description given by Albright and Reifenstein of their work.<i>Disorders of Bone and Mineral Metabolism</i>has veritable encyclopedic dimensions and depth; it is a fundamental resource and reference source. The editors of this scholarly work and the chapter authors are acknowledged leaders in the field and respected investigators and teachers. The sheer magnitude of handling and coordinating the creative efforts of 71 contributors is an ambitious undertaking. Deserving of special praise is the uniform system of, for the most part, excellent, easily understood diagrams and captions. How was the diversity of sources overcome? This unified system shows a strong