tbuckley/cabot-search huggingface dataset:
Recurrent Ovarian Cancer
Authors: Thomas J. Herzog
Journal: Clinical Cancer Research (2004)

Abstract Ovarian cancer is increasingly recognized as a chronic disease whose treatment is often characterized by administration of multiple, sequential active agents, each of which may or may not be accompanied by a tumor response. Despite the large proportion of patients who relapse and undergo longer-term treatment, the question of optimal treatment duration has not been fully addressed to date. For patients who progress on therapy, the answer is straightforward: they are switched to another active agent, presumably having a different mechanism of action from previous therapies with, ideally, limited overlapping toxicities. However, for patients who remain in partial response or who have stable disease, the answer is less apparent and less clear. The majority of oncologists believe that treatment beyond 6 cycles of a given therapy does not provide any additional benefit to patients. There are some data to support that treatment strategy. However, with the advent of new, less toxic agents, treatment to progression should be further explored. Agents that are potentially well suited for extended treatment intervals may include such properties as absence of cumulative toxicity, non–cross-resistance, positive benefit on quality of life, and convenient schedule. A number of active agents in ovarian cancer (platinum, paclitaxel, topotecan, liposomal doxorubicin, docetaxel, gemcitabine, and etoposide) will be reviewed in the context of what is known about cumulative toxicity, potential adverse effects on patients’ quality of life, and evidence addressing the potential benefits of longer-term treatment.
Eosinophils and resistance to Trichinella spiralis.
Authors: D I Grove, A A Mahmoud, K S Warren
Journal: The Journal of Experimental Medicine (1977)

Mice infected with Trichinella spiralis were depleted of eosinophils by repeated administration of rabbit anti-mouse eosinophil serum. There was no effect on the spontaneous expulsion of adult worms from the small intestines, but the numbers of larvae in the muscles were almost doubled. It is concluded that eosinophils contribute to resistance to the systemic phase of trichinosis.
FOLFIRI Plus Cetuximab Versus Folfiri Plus Bevacizumab as First-Line Treatment of KRAS-Wildtype Metastatic Colorectal Cancer: German AIO Study Krk-0306 (FIRE-3)
Authors: Dominik Modest, Ludwig Fischer von Weikersthal, Sebastian Stintzing, Thomas Decker, Alexander Kiani, Ursula Vehling-Kaiser, Salah-Eddin Al Batran, Tobias Heintges, Christian Lerchenmüller, Christoph Kahl, Gernot Seipelt, Frank Kullmann, Martina Stauch, Werner Scheithauer, Jörg Hielscher, Michael Scholz, Sebastian Müller, Britta Schäfer, Andreas Jung, Volker Heinemann
Journal: Annals of Oncology (2013)
Distribution of cell surface glycoprotein CD9 (P24) antigen on megakaryocyte lineage leukemias and cell lines
Authors: Nobutaka Imamura, Deodatus M. Mtasiwa, Hiromi Ota, Tominari Inada, Atsushi Kuramoto
Journal: American Journal of Hematology (1990)

We herein describe CD9 (p24) antigen as existing on the cell surface of megakaryocyte lineage leukemias as well as megakaryocytic leukemia cell line, MEG-01 and HEL, by means of fluorescence-activated cell sorter (FACS IV) with a panel of monoclonal antibodies (Mabs). We found CD9 antigen expression on the cell surface of megakaryoblastic leukemias as well as MEG-01 and HEL cells. Furthermore, CD9 antigen expression increased while culturing these cells with phorbol esters, and was also found in the cytoplasm by means of indirect immunofluorescence test. These findings clearly showed that CD9 antigen exists on the cell surface of megakaryocytic cells which are capable of synthesizing the CD9.
Intravenous Thrombolytic Therapy for Acute Ischemic Stroke
Authors: Lawrence R. Wechsler
Journal: New England Journal of Medicine (2011)

An 81-year-old man presents to the ER with an acute ischemic stroke; IV thrombolytic therapy is recommended. Administered as a therapeutic agent within 4.5 hours after stroke, tissue plasminogen activator has been shown to improve neurologic outcomes.
Podoplanin requires sialylated O-glycans for stable expression on lymphatic endothelial cells and for interaction with platelets
Authors: Yanfang Pan, Tadayuki Yago, Jianxin Fu, Brett Herzog, J. Michael McDaniel, Padmaja Mehta-D’Souza, Xiaofeng Cai, Changgeng Ruan, Rodger P. McEver, Christopher West, Kesheng Dai, Hong Chen, Lijun Xia
Journal: Blood (2014)
Immunosuppression prolongs adenoviral mediated transgene expression in cardiac allograft transplantation
Authors: J Yap
Journal: Cardiovascular Research (1997)

Background: The immune response to adenoviral vectors used in gene transfer limits the duration of transgene expression and thus poses a potential limitation to their effectiveness for gene therapy. The need for immunosuppression in transplantation may modify this immune response and facilitate prolonged transgene expression. This study hypothesizes that in the setting of heart transplantation, the use of routine immunosuppression will prolong adenoviral-mediated transgene expression. Methods and results: In a model of rat heterotopic abdominal heart transplantation, 350 μl of viral solution (1×109 pfu/ml) was infused into the coronary arteries of donor hearts at the time of procurement. The duration of transgene expression was examined following (a) syngeneic transplantation in non-immunosuppressed animals (group A); (b) syngeneic transplantation in immunosuppressed animals (group B); and (c) allogeneic transplantation in immunosuppressed animals (group C). After transplantation donor hearts were studied at: 1, 4, 8 and 12 weeks. Transgene expression was assessed by histochemical staining of tissue cross sections for β-galactosidase activity. In the non-immunosuppressed syngeneic group (group A), transgene expression had largely disappeared by 4 weeks, whereas in both the immunosuppressed syngeneic (group B) and immunosuppressed allogeneic (group C) animals expression of the reporter gene persisted for the 12 weeks of the study, although the level of expression decreased significantly over time. Conclusions: This study demonstrates that transgene expression using adenoviral vectors is prolonged by immunosuppression in the heart transplantation setting.
DC-SIGN–ICAM-2 interaction mediates dendritic cell trafficking
Authors: Teunis B. H. Geijtenbeek, Daniëlle J. E. B. Krooshoop, Diederik A. Bleijs, Sandra J. van Vliet, Gerard C. F. van Duijnhoven, Valentine Grabovsky, Ronen Alon, Carl G. Figdor, Yvette van Kooyk
Journal: Nature Immunology (2000)
Contribution of Multidrug Resistance Protein 2 (MRP2/ABCC2) to the Renal Excretion of p-aminohippurate (PAH) and Identification of MRP4 (ABCC4) as a Novel PAH Transporter
Authors: Pascal H.E. Smeets, Re[Combining Acute Accent]mon A.M.H. van Aubel, Alfons C. Wouterse, Jeroen J.M.W. van den Heuvel, Frans G.M. Russel
Journal: Journal of the American Society of Nephrology (2004)

<i>p</i>-Aminohippurate (PAH) is the classical substrate used in the characterization of organic anion transport in renal proximal tubular cells. Although basolateral transporters for PAH uptake from blood into the cell have been well characterized, there is still little knowledge on the apical urinary efflux transporters. The multidrug resistance protein 2 (MRP2/ABCC2) is localized to the apical membrane and mediates ATP-dependent PAH transport, but its contribution to urinary PAH excretion is not known. In this report, we show that renal excretion of PAH in isolated perfused kidneys from wild-type and Mrp2-deficient (TR<sup>−</sup>) rats is not significantly different. Uptake of [<sup>14</sup>C]PAH in membrane vesicles expressing two different MRP2 clones isolated from Sf9 and MDCKII cells exhibited a low affinity for PAH (Sf9, 5 ± 2 mM; MDCKII, 2.1 ± 0.6 mM). Human MRP4 (ABCC4), which has recently been localized to the apical membrane, expressed in Sf9 cells had a much higher affinity for PAH (K<sub>m</sub> = 160 ± 50 μM). Various inhibitors of MRP2-mediated PAH transport also inhibited MRP4. Probenecid stimulated MRP2 at low concentrations but had no effect on MRP4; but at high probenecid concentrations, both MRP2 and MRP4 were inhibited. Sulfinpyrazone only stimulated MRP2, but inhibited MRP4. Real-time PCR and Western blot analysis showed that renal cortical expression of MRP4 is approximately fivefold higher as compared with MRP2. MRP4 is a novel PAH transporter that has higher affinity for PAH and is expressed more highly in kidney than MRP2, and may therefore be more important in renal PAH excretion.
<i>In vivo</i> Switching of Human Melanoma Cells between Proliferative and Invasive States
Authors: Keith S. Hoek, Ossia M. Eichhoff, Natalie C. Schlegel, Udo Döbbeling, Nikita Kobert, Leo Schaerer, Silvio Hemmi, Reinhard Dummer
Journal: Cancer Research (2008)

Abstract Metastatic melanoma represents a complex and heterogeneous disease for which there are no therapies to improve patient survival. Recent expression profiling of melanoma cell lines identified two transcription signatures, respectively, corresponding with proliferative and invasive cellular phenotypes. A model derived from these findings predicts that in vivo melanoma cells may switch between these states. Here, DNA microarray–characterized cell lines were subjected to in vitro characterization before s.c. injection into immunocompromised mice. Tumor growth rates were measured and postexcision samples were assessed by immunohistochemistry to identify invasive and proliferative signature cells. In vitro tests showed that proliferative signature melanoma cells are faster growing but less motile than invasive signature cells. In vivo proliferative signature cells initiated tumor growth in 14 ± 3 days postinjection. By comparison, invasive signature cells required a significantly longer (P &amp;lt; 0.001) period of 59 ± 11 days. Immunohistochemistry showed that regardless of the seed cell signature, tumors showed evidence for both proliferative and invasive cell types. Furthermore, proliferative signature cell types were detected most frequently in the peripheral margin of growing tumors. These data indicate that melanoma cells undergo transcriptional signature switching in vivo likely regulated by local microenvironmental conditions. Our findings challenge previous models of melanoma progression that evoke one-way changes in gene expression. We present a new model for melanoma progression that accounts for transcription signature plasticity and provides a more rational context for explaining observed melanoma biology. [Cancer Res 2008;68(3):650–6]
Sex differences in mortality in patients with COPD
Authors: J. P. de Torres, C. G. Cote, M. V. López, C. Casanova, O. Díaz, J. M. Marin, V. Pinto-Plata, M. M. de Oca, H. Nekach, L. J. Dordelly, A. Aguirre-Jaime, B. R. Celli
Journal: European Respiratory Journal (2008)

Little is known about survival and clinical prognostic factors in females with chronic obstructive pulmonary disease (COPD). The aim of the present study was to determine the survival difference between males and females with COPD and to compare the value of the different prognostic factors for the disease. In total, 265 females and 272 males with COPD matched at baseline by BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) and American Thoracic Society/European Respiratory Society/Global Initiative of Chronic Obstructive Lung Disease criteria were prospectively followed. Demographics, lung function, St George's Respiratory Questionnaire, BODE index, the components of the BODE index and comorbidity were determined. Survival was documented and sex differences were determined using Kaplan-Meier analysis. The strength of the association of the studied variables with mortality was determined using multivariate and receiver operating curves analysis. All-cause (40 versus 18%) and respiratory mortality (24 versus 10%) were higher in males than females. Multivariate analysis identified the BODE index in females and the BODE index and Charlson comorbidity score in males as the best predictors of mortality. The area under the curve of the BODE index was a better predictor of mortality than the forced expiratory volume in one second for both sexes. At similar chronic obstructive pulmonary disease severity by BODE index and forced expiratory volume in one second, females have significantly better survival than males. For both sexes the BODE index is a better predictor of survival than the forced expiratory volume in one second.
Patients' and family members' views on how clinicians enact and how they should enact incident disclosure: the "100 patient stories" qualitative study
Authors: R. Iedema, S. Allen, K. Britton, D. Piper, A. Baker, C. Grbich, A. Allan, L. Jones, A. Tuckett, A. Williams, E. Manias, T. H. Gallagher
Journal: BMJ (2011)

<b>Objectives</b> To investigate patients' and family members' perceptions and experiences of disclosure of healthcare incidents and to derive principles of effective disclosure. <b>Design</b> Retrospective qualitative study based on 100 semi-structured, in depth interviews with patients and family members. <b>Setting</b> Nationwide multisite survey across Australia. <b>Participants</b> 39 patients and 80 family members who were involved in high severity healthcare incidents (leading to death, permanent disability, or long term harm) and incident disclosure. Recruitment was via national newspapers (43%), health services where the incidents occurred (28%), two internet marketing companies (27%), and consumer organisations (2%). <b>Main outcome measures</b> Participants' recurrent experiences and concerns expressed in interviews. <b>Results</b> Most patients and family members felt that the health service incident disclosure rarely met their needs and expectations. They expected better preparation for incident disclosure, more shared dialogue about what went wrong, more follow-up support, input into when the time was ripe for closure, and more information about subsequent improvement in process. This analysis provided the basis for the formulation of a set of principles of effective incident disclosure. <b>Conclusions</b> Despite growing prominence of open disclosure, discussion about healthcare incidents still falls short of patient and family member expectations. Healthcare organisations and providers should strengthen their efforts to meet patients' (and family members') needs and expectations.
Parental psychological distress during pregnancy and wheezing in preschool children: The Generation R Study
Authors: Mònica Guxens, Agnes M.M. Sonnenschein–van der Voort, Henning Tiemeier, Albert Hofman, Jordi Sunyer, Johan C. de Jongste, Vincent W.V. Jaddoe, Liesbeth Duijts
Journal: Journal of Allergy and Clinical Immunology (2013)
Reactivating aberrantly hypermethylated p15 gene in leukemic T cells by a phenylhexyl isothiocyanate mediated inter-active mechanism on DNA and chromatin
Authors: Shaohong Jiang, Xudong Ma, Yiqun Huang, Yunlu Xu, Ruiji Zheng, Jen-Wei Chiao
Journal: Journal of Hematology & Oncology (2010)

Abstract Background We have previously demonstrated that phenylhexyl isothiocyanate (PHI), a synthetic isothiocyanate, inhibits histone deacetylases and remodels chromatins to induce growth arrest in HL-60 myeloid leukemia cells in a concentration-dependent manner. Methods To investigate the effect of PHI, a novel histone deacetylases inhibitor (HDACi), on demethylation and activation of transcription of p15 in acute lymphoid leukemia cell line Molt-4, and to further decipher the potential mechanism of demethylation, DNA sequencing and modified methylation specific PCR (MSP) were used to screen p15 -M and p15 -U mRNA after Molt-4 cells were treated with PHI, 5-Aza and TSA. DNA methyltransferase 1 (DNMT1), 3A (DNMT3A), 3B (DNMT3B) and p15 mRNA were measured by RT-PCR. P15 protein, acetylated histone H3 and histone H4 were detected by Western Blot. Results The gene p15 in Molt-4 cells was hypermethylated and inactive. Hypermethylation of gene p15 was attenuated and p15 gene was activated de novo after 5 days exposure to PHI in a concentration-dependent manner. DNMT1 and DNMT3B were inhibited by PHI (P &lt; 0.05). Alteration of DNMT3A was not significant at those concentrations. Acetylated histone H3 and histone H4 were accumulated markedly after exposure to PHI. Conclusion PHI could induce both DNA demethylation and acetylated H3 and H4 accumulation in Molt-4 cells. Hypermethylation of gene p15 was reversed and p15 transcription could be reactivated de novo by PHI.
Adverse Cognitive Effects of Medications
Authors: Noll L. Campbell, Malaz A. Boustani
Journal: JAMA Internal Medicine (2015)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Common genetic variation in the promoter of the human apo CIII gene abolishes regulation by insulin and may contribute to hypertriglyceridemia.
Authors: W W Li, M M Dammerman, J D Smith, S Metzger, J L Breslow, T Leff
Journal: Journal of Clinical Investigation (1995)

Overexpression of plasma apolipoprotein CIII (apo CIII) causes hypertriglyceridemia in transgenic mice.A geneti- cally variant form of the human apo CIII promoter, con- taining five single base pair changes, has been shown to be associated with severe hypertriglyceridemia in a patient population.In animals and in cultured cells the apo CIII gene is transcriptionally downregulated by insulin.In this study we demonstrate that, unlike the wild-type promoter, the variant promoter was defective in its response to insulin treatment, remaining constitutively active at all concentra- tions of insulin.The loss of insulin regulation was mapped to polymorphic sites at -482 and -455, which fall within a previously identified insulin response element.Loss of insu- lin regulation could result in overexpression of the apo CIII gene and contribute to the development of hypertriglyceridemia.The variant apo Cm promoter is common in the human population and may represent a major contributing factor to the development of hypertriglyceridemia. (
Microalbuminuria is associated with impaired brachial artery, flow-mediated vasodilation in elderly individuals without and with diabetes: Further evidence for a link between microalbuminuria and endothelial dysfunction—The Hoorn Study
Authors: Coen D.A. Stehouwer, Ronald M.A. Henry, Jacqueline M. Dekker, Giel Nijpels, Robert J. Heine, Lex M. Bouter
Journal: Kidney International (2004)
STUDIES ON NORMAL AND IMMUNE LYMPHOCYTE TRANSFER REACTIONS IN GUINEA PIGS, WITH SPECIAL REFERENCE TO THE CELLULAR CONTRIBUTION OF THE HOST
Authors: Siraik Zakarian, R. E. Billingham
Journal: The Journal of Experimental Medicine (1972)

Using guinea pigs of strains 2 and 13 and their F(1) hybrids as experimental subjects, various lines of evidence have been obtained that in this species, as in all others tested, the only significant cellular antigens with which donor lymphocytes engage when normal and immune lymphocyte reactions are incited are radiosensitive leukocytes. Constitutive cells of the skin are unimportant. (a) The intensities of these reactions in irradiated subjects are dependent upon the peripheral leukocyte concentration. When this falls below a certain threshold no reactions are incitable. (b) Highly leukopenic animals are capable of developing immune lymphocyte transfer (ILT) reactions if normal lymphoid cells of their own genetic constitution are mixed with the putative attacking donor cells, as "supplementing antigen," before inoculation. (c) Radiation-chimeric strain 13 animals having F(1) hybrid leukocytes in their bloodstream give typical ILT reactions when challenged intradermally with strain 13 anti-2 node cells. Exposure of strain 2 animals to 600 R does not prevent their becoming actively immunized if, 24 hr later, they are injected intradermally with strain 13 lymphocytes. However, this sensitization, revealed by the host's capacity to give delayed hypersensitivity reactions, wanes as leukopenia progresses. On the basis of this and other findings it is argued that the flare-up stage of the NLT reaction in preirradiated hosts is mainly an expression of host sensitivity against the transferred alien cells. Two unexpected observations have been made in the course of this study: (a) F(1) hybrid animals developed what appeared to be a strong delayed hypersensitivity after intradermal inoculation with parental strain lymphoid cells or antigenic extracts prepared from them. (b) If strain 13 guinea pigs which had been sensitized against strain 2 tissue antigens by intradermal injection of lymphocytes 7 days beforehand were inoculated intravenously with strain 2 antigenic extract a significant proportion of the animals developed severe delayed necrotizing reactions, recall flares, at some or all of the healed skin inoculation sites.
The effect of combined IL10 siRNA and CpG ODN as pathogen-mimicking microparticles on Th1/Th2 cytokine balance in dendritic cells and protective immunity against B cell lymphoma
Authors: Pallab Pradhan, Hong Qin, Jardin A. Leleux, Dongho Gwak, Ippei Sakamaki, Larry W. Kwak, Krishnendu Roy
Journal: Biomaterials (2014)
Delivery of siRNA by MRI-visible nanovehicles to overcome drug resistance in MCF-7/ADR human breast cancer cells
Authors: Gan Lin, Wencheng Zhu, Li Yang, Jun Wu, Bingbing Lin, Ye Xu, Zhuzhong Cheng, Chunchao Xia, Qiyong Gong, Bin Song, Hua Ai
Journal: Biomaterials (2014)