tbuckley/cabot-search huggingface dataset:
High breast milk levels of polychlorinated biphenyls (PCBs) among four women living adjacent to a PCB-contaminated waste site.
Authors: S A Korrick, L Altshul
Journal: Environmental Health Perspectives (1998)

As a consequence of contamination by effluents from local electronics manufacturing facilities, the New Bedford Harbor and estuary in southeastern Massachusetts is among the sites in the United States that are considered the most highly contaminated by polychlorinated biphenyls (PCBs). Since 1993, measures of intrauterine PCB exposure have been obtained for a sample of New Bedford area infants. Among 122 mother-infant pairs, we identified four milk samples with total PCB levels that were significantly higher than the rest, with estimated total PCBs ranging from 1,100 to 2,400 ng/g milk fat compared with an overall mean of 320 ng/g milk fat for the 122 women. The congener profile and history of one case was consistent with past occupational PCB exposures. Otherwise, the source of PCB exposures in these cases was difficult to specify. Environmental exposures including those from fish consumption were likely, whereas residence adjacent to a PCB-contaminated site was considered an unlikely exposure source. In all four cases, the infants were full-term, healthy newborns. Because the developing nervous system is believed to be particularly susceptible to PCBs (for example, prenatal PCB exposures have been associated with prematurity, decrements in birth weight and gestation time, and behavioral and developmental deficits in later infancy and childhood, including decrements in IQ), it is critical to ascertain if breast-feeding is a health risk for the women's infants. Despite the potential for large postnatal PCB exposures via breast milk, there is limited evidence of significant developmental toxicity associated with the transmission of moderate PCB concentrations through breast milk. Breast-feeding is associated with substantial health benefits including better cognitive skills among breast-fed compared with formula-fed infants. We conclude, based on evidence from other studies, that the benefits of breast-feeding probably outweigh any risk from PCB exposures via breast milk among the four New Bedford infants. In this case report, PCB analysis of breast milk and infant cord serum was a research tool. PCB analysis of milk is rarely done clinically, in part because it is difficult to use the results of such analyses to predict health risks. Substantial effort is needed to achieve a better understanding of the clinical and public health significance of PCB exposures, particularly among potentially susceptible groups such as infants and children. Such efforts are critical to improving the clinical and public health management of widespread and ongoing population exposures to PCBs.
Mechanisms of α-adrenergic potentiation of ventricular arrhythmias in dogs with inherited arrhythmic sudden death
Authors: E Sosunov
Journal: Cardiovascular Research (2004)

Objective: In German shepherd dogs having inherited arrhythmias and sudden death, pause-dependent arrhythmias are triggered by early afterdepolarizations (EADs) originating from left ventricular (LV) Purkinje fibers (PF). Heterogeneity of LV repolarization provides the arrhythmogenic substrate. To elucidate the mechanisms whereby α-adrenergic stimulation exacerbates these arrhythmias we tested the effects of phenylephrine on both arrhythmogenic trigger and substrate. Methods and results: We used microelectrode techniques to record action potentials from LV and right ventricular (RV) PF and from midmyocardial sections of anteroseptal, anterobasal and posterobasal LV wall of unafflicted and afflicted dogs. EADs occurred spontaneously in 8 of 12 LV PF and in no RV PF from afflicted dogs and in no PF from unafflicted dogs. In LV PF from afflicted dogs, phenylephrine (10−9–10−5 M) concentration-dependently decreased membrane potential, induced abnormal automaticity at membrane potentials from −65 to −45 mV in 6 LV PF and potentiated EADs in another 6. To determine the mechanisms of membrane depolarization we studied phenylephrine effects on IK1 in voltage-clamped single LV and RV PF cells from afflicted dogs. In LV PF, phenylephrine (10−5 M) reduced IK1 over the range of −120 to −40 mV and had no effects on RV PF. Regional heterogeneity of LV repolarization was observed in afflicted dogs only. Phenylephrine had no effects on repolarization in either group. Conclusion(s): α-adrenergic stimulation exacerbates arrhythmias in afflicted dogs by increasing the arrhythmogenic trigger while leaving the substrate unchanged. Decrease in IK1 contributes importantly to α-adrenergic effects on LV PF.
SMYD3 Promotes Cancer Invasion by Epigenetic Upregulation of the Metalloproteinase <i>MMP-9</i>
Authors: Alicia M. Cock-Rada, Souhila Medjkane, Natacha Janski, Nadhir Yousfi, Martine Perichon, Marie Chaussepied, Johanna Chluba, Gordon Langsley, Jonathan B. Weitzman
Journal: Cancer Research (2011)

Abstract Upregulation of the matrix metalloproteinase (MMP)–9 plays a central role in tumor progression and metastasis by stimulating cell migration, tumor invasion, and angiogenesis. To gain insights into MMP-9 expression, we investigated its epigenetic control in a reversible model of cancer that is initiated by infection with intracellular Theileria parasites. Gene induction by parasite infection was associated with trimethylation of histone H3K4 (H3K4me3) at the MMP-9 promoter. Notably, we found that the H3K4 methyltransferase SMYD3 was the only histone methyltransferase upregulated upon infection. SMYD3 is overexpressed in many types of cancer cells, but its contributions to malignant pathophysiology are unclear. We found that overexpression of SMYD3 was sufficient to induce MMP-9 expression in transformed leukocytes and fibrosarcoma cells and that proinflammatory phorbol esters further enhanced this effect. Furthermore, SMYD3 was sufficient to increase cell migration associated with MMP-9 expression. In contrast, RNA interference–mediated knockdown of SMYD3 decreased H3K4me3 modification of the MMP-9 promoter, reduced MMP-9 expression, and reduced tumor cell proliferation. Furthermore, SMYD3 knockdown also reduced cellular invasion in a zebrafish xenograft model of cancer. Together, our results define SMYD3 as an important new regulator of MMP-9 transcription, and they provide a molecular link between SMYD3 overexpression and metastatic cancer progression. Cancer Res; 72(3); 810–20. ©2011 AACR.
Phase I trial of intravenous aviscumine (rViscumin) in patients with solid tumors: a study of the European Organization for Research and Treatment of Cancer New Drug Development Group
Authors: P. Schöffski, S. Riggert, P. Fumoleau, M. Campone, O. Bolte, S. Marreaud, D. Lacombe, B. Baron, M. Herold, H. Zwierzina, K. Wilhelm-Ogunbiyi, H. Lentzen, C. Twelves
Journal: Annals of Oncology (2004)
Attention-based maintenance of speech forms in memory: The case of verbal transformations
Authors: Christian Abry, Marc Sato, Jean-Luc Schwartz, Hélène Loevenbruck, Marie-Agnès Cathiard
Journal: Behavioral and Brain Sciences (2003)

One of the fundamental questions raised by Ruchkin, Grafman, Cameron, and Berndt's (Ruchkin et al.'s) interpretation of no distinct specialized neural networks for short-term storage buffers and long-term memory systems, is that of the link between perception and memory processes. In this framework, we take the opportunity in this commentary to discuss a specific working memory task involving percept formation, temporary retention, auditory imagery, and the attention-based maintenance of information, that is, the verbal transformation effect.
Mitochondrial Targets of Drug Toxicity
Authors: K. B. Wallace, A. A. Starkov
Journal: The Annual Review of Pharmacology and Toxicology (2000)

Mitochondria have long been recognized as the generators of energy for the cell. Like any other power source, however, mitochondria are highly vulnerable to inhibition or uncoupling of the energy harnessing process and run a high risk for catastrophic damage to the cell. The exquisite structural and functional characteristics of mitochondria provide a number of primary targets for xenobiotic-induced bioenergetic failure. They also provide opportunities for selective delivery of drugs to the mitochondrion. In light of the large number of natural, commercial, pharmaceutical, and environmental chemicals that manifest their toxicity by interfering with mitochondrial bioenergetics, it is important to understand the underlying mechanisms. The significance is further underscored by the recent identification of bioenergetic control points for cell replication and differentiation and the realization that mitochondria play a determinant role in cell signaling and apoptotic modes of cell death.
Antibody-Drug Conjugates for the Treatment of Non–Hodgkin's Lymphoma: Target and Linker-Drug Selection
Authors: Andrew G. Polson, Jill Calemine-Fenaux, Pamela Chan, Wesley Chang, Erin Christensen, Suzanna Clark, Frederic J. de Sauvage, Dan Eaton, Kristi Elkins, J. Michael Elliott, Gretchen Frantz, Reina N. Fuji, Alane Gray, Kristin Harden, Gladys S. Ingle, Noelyn M. Kljavin, Hartmut Koeppen, Christopher Nelson, Saileta Prabhu, Helga Raab, Sarajane Ross, Jean-Philippe Stephan, Suzie J. Scales, Susan D. Spencer, Richard Vandlen, Bernd Wranik, Shang-Fan Yu, Bing Zheng, Allen Ebens
Journal: Cancer Research (2009)

Antibody-drug conjugates (ADC), potent cytotoxic drugs covalently linked to antibodies via chemical linkers, provide a means to increase the effectiveness of chemotherapy by targeting the drug to neoplastic cells while reducing side effects. Here, we systematically examine the potential targets and linker-drug combinations that could provide an optimal ADC for the treatment for non-Hodgkin's lymphoma. We identified seven antigens (CD19, CD20, CD21, CD22, CD72, CD79b, and CD180) for potential treatment of non-Hodgkin's lymphoma with ADCs. ADCs with cleavable linkers mediated in vivo efficacy via all these targets; ADCs with uncleavable linkers were only effective when targeted to CD22 and CD79b. In target-independent safety studies in rats, the uncleavable linker ADCs showed reduced toxicity, presumably due to the reduced release of free drug or other toxic metabolites into the circulation. Thus, our data suggest that ADCs with cleavable linkers work on a broad range of targets, and for specific targets, ADCs with uncleavable linkers provide a promising opportunity to improve the therapeutic window for ADCs in humans.
Specificity, Ly phenotype, and H-2 compatibility requirements of effector cells in delayed-type hypersensitivity responses to murine influenza virus infection.
Authors: K N Leung, G L Ada, I F McKenzie
Journal: The Journal of Experimental Medicine (1980)

Delayed-type hypersensitivity (DTH) to infectious and to noninfectious (UV-irradiated) influenza A viral preparations was measured in mice by the increase in footpad swelling 24 h after injection of the eliciting virus. DTH mice sensitized with noninfectious virus was elicited only by virus that shared hemagglutinin specificity with the sensitizing virus, whereas footpad injection of a given A-strain virus (A/WSN) could elicit DTH in mice sensitized with a variety of infectious A-strain viruses, including some not sharing hemagglutinin or neuraminidase specificities. The effector T cells generated in mice sensitized with either form of virus were sensitive to anti-Ly 1.1 serum and complement, but not to anti-Ly 2.1 serum and complement. Adoptive transfer of DTH was H-2 restricted. With spleen cells from mice sensitized subcutaneously with either infectious or noninfectious virus, sharing of the IA region was both necessary and sufficient for successful transfer to occur. Cells recovered from infected mouse lungs, and secondary effector cells generated in vitro transferred DTH if injected into the footpad with the eliciting virus. The effector cells had the Ly 1 phenotype, and, in both cases, the cells were I restricted. These results contrast with earlier findings that transfer of DTH to lymphocytic choriomeningitis virus infection required K- or D-region sharing between donor and recipient. Thus, the earlier hypothesis that multiplying infectious agents such as viruses would "alter" K- or D-coded, rather than I-coded, structures is not generally correct.
Assessment of 18F-fluorodeoxyglucose dual-head gamma camera in asbestos lung diseases
Authors: B. Melloni, J. Monteil, F. Vincent, F. Bertin, S. Gaillard, T. Ducloux, S. Verbeke, A. Maubon, J-C. Vandroux, F. Bonnaud
Journal: European Respiratory Journal (2004)

The purpose of this study was to evaluate the performance of 18 F-fluorodeoxyglucose ( 18 FDG) imaging via coincidence detection emission tomography (CDET) in identifying malignant lesions in subjects exposed to asbestos. A total of 30 patients exposed to asbestos underwent 18 FDG-CDET between January 2000 and June 2003. A CDET scan of the thorax and abdomen was performed 60 min after injection of 18 FDG in fasting patients, and results were obtained in slices in three axes. The CDET results were compared to those from computed tomography (CT), and pleural or surgical biopsy in patients with positive 18 FDG-CDET results. All primary malignant mesotheliomas accumulated 18 FDG (n=6), and, in two patients, CDET findings were superior to those of CT, allowing early detection. In two cases, lung carcinomas with malignant pleural effusion were also detected. There were five false positive CDET results: three unilateral pleural thickening, one rounded atelectasis, and one benign lung nodule. All patients with pleural plaques showed no significant 18 FDG uptake. Malignant diseases were detected by 18 FDG-CDET imaging with a sensitivity of 89% and specificity of 71%. Coincidence detection emission tomography can identify malignant mesothelioma in selected subjects exposed to asbestos. Coincidence detection emission tomography appears to be a useful noninvasive method for the follow-up of subjects with exposure risk of asbestosis.
Cell Trafficking of Endothelial Progenitor Cells in Tumor Progression
Authors: Pilar de la Puente, Barbara Muz, Feda Azab, Abdel Kareem Azab
Journal: Clinical Cancer Research (2013)

Blood vessel formation plays an essential role in many physiologic and pathologic processes, including normal tissue growth and healing, as well as tumor progression. Endothelial progenitor cells (EPC) are a subtype of stem cells with high proliferative potential that are capable of differentiating into mature endothelial cells, thus contributing to neovascularization in tumors. In response to tumor-secreted cytokines, EPCs mobilize from the bone marrow to the peripheral blood, home to the tumor site, and differentiate to mature endothelial cells and secrete proangiogenic factors to facilitate vascularization of tumors. In this review, we summarize the expression of surface markers, cytokines, receptors, adhesion molecules, proteases, and cell signaling mechanisms involved in the different steps (mobilization, homing, and differentiation) of EPC trafficking from the bone marrow to the tumor site. Understanding the biologic mechanisms of EPC cell trafficking opens a window for new therapeutic targets in cancer.
Dietary intake of acrylamide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
Authors: M. Obón-Santacana, N. Slimani, L. Lujan-Barroso, N. Travier, G. Hallmans, H. Freisling, P. Ferrari, M.C. Boutron-Ruault, A. Racine, F. Clavel, C. Saieva, V. Pala, R. Tumino, A. Mattiello, P. Vineis, M. Argüelles, E. Ardanaz, P. Amiano, C. Navarro, M.J. Sánchez, E. Molina Montes, T. Key, K.-T. Khaw, N. Wareham, P.H. Peeters, A. Trichopoulou, C. Bamia, D. Trichopoulos, H. Boeing, R. Kaaks, V. Katzke, W. Ye, M. Sund, U. Ericson, E. Wirfält, K. Overvad, A. Tjønneland, A. Olsen, G. Skeie, L.A. Åsli, E. Weiderpass, E. Riboli, H.B. Bueno-de-Mesquita, E.J. Duell
Journal: Annals of Oncology (2013)
Chromosomal translocations joining LCK and TCRB loci in human T cell leukemia.
Authors: B Tycko, S D Smith, J Sklar
Journal: The Journal of Experimental Medicine (1991)

A case of T lymphoblastic leukemia (T-ALL) showing t(1;7)(p34;q34) as the sole karyotypic abnormality was investigated at the molecular level. Screening of a phage library of tumor DNA with a probe for the beta T cell receptor gene (TCRB), which maps to chromosomal band 7q34, resulted in the isolation of a clone containing DNA spanning the translocation breakpoint of the der(1) chromosome. This clone contained chromosome 1 DNA juxtaposed upstream of a D beta-J beta joint. Cloning of the corresponding germline region of chromosome 1 resulted in the isolation of a phage containing the breakpoint from the reciprocal, der(7), product, which showed chromosome 1 DNA joined downstream to a V beta segment. Comparison of germline and translocation clones demonstrated that breakage of chromosome 1 had occurred at the border of a tandem repeat of Alu sequences. To search for transcripts from DNA near the breakpoint, a chromosomal walk was initiated along chromosome 1. A probe consisting of chromosome 1 DNA from 24-30 kb upstream of the breakpoint hybridized to a transcript derived from the gene encoding the lymphocyte-specific tyrosine kinase p56lck, previously mapped to chromosomal band 1p34. The nonrandom nature of the breakpoints in this case was confirmed by the analysis of a second independent case of T-ALL containing a t(1;7) translocation, which was also found to show breakage within the LCK locus. The chromosomal breakpoint in the first case was localized 2 kb upstream of the lck upstream promoter and first nontranslated exon, while the breakpoint of the second case lay between the two alternative lck promoters, upstream of the second exon. Relative to normal thymus and activated T cells, levels of lck mRNA were greatly elevated in the first case and moderately elevated in the second. The existence of these translocations raises the possibility that alterations in the promoter region of the LCK locus may play a role in human cancer.
Randomised controlled trial of physiotherapy compared with advice for low back pain
Authors: Helen Frost, Sarah E Lamb, Helen A Doll, Patricia Taffe Carver, Sarah Stewart-Brown
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To measure the effectiveness of routine physiotherapy compared with an assessment session and advice from a physiotherapist for patients with low back pain. <b>Design</b> Pragmatic, multicentre, randomised controlled trial. <b>Setting</b> Seven British NHS physiotherapy departments. <b>Participants</b> 286 patients with low back pain of more than six weeks9 duration. <b>Intervention</b> Routine physiotherapy or advice on remaining active from a physiotherapist. Both groups received an advice book. <b>Main outcome measures</b> Primary outcome was scores on the Oswestry disability index at 12 months. Secondary outcomes were scores on the Oswestry disability index (two and six months), scores on the Roland and Morris disability questionnaire and SF-36 (2, 6 and 12 months), and patient perceived benefit from treatment (2, 6, and 12 months). <b>Results</b> 200 of 286 patients (70%) provided follow up information at 12 months. Patients in the therapy group reported enhanced perceptions of benefit, but there was no evidence of a long term effect of physiotherapy in either disease specific or generic outcome measures (mean difference in change in Oswestry disability index scores at 12 months −1.0%, 95% confidence interval −3.7% to 1.6%). The most common treatments were low velocity spinal joint mobilisation techniques (72%, 104 of 144 patients) and lumbar spine mobility and abdominal strengthening exercises (94%, 136 patients). <b>Conclusions</b> Routine physiotherapy seemed to be no more effective than one session of assessment and advice from a physiotherapist.
Accountability Measures — Using Measurement to Promote Quality Improvement
Authors: Mark R. Chassin, Jerod M. Loeb, Stephen P. Schmaltz, Robert M. Wachter
Journal: New England Journal of Medicine (2010)

The authors argue that quality measures in health care should be based on strong evidence that a care process directly improves outcomes, should capture the actual performance of a process, should address a process proximate to the desired outcome, and should not have unintended adverse consequences.
Control of Immune Responses by Naturally Arising CD4+ Regulatory T Cells That Express Toll-like Receptors
Authors: Shimon Sakaguchi
Journal: The Journal of Experimental Medicine (2003)

It is a key issue in immunology to understand how the immune system discriminates between self- and nonself, inhibiting autoimmune responses but allowing the host to mount immune responses against invading microbes ([1][1]–[3][2]). This is due to the fact that once antigen-specific lymphocytes are
Genetic Heterogeneity of the c-K-ras Locus in Colorectal Adenomas but not in Adenocarcinomas
Authors: D. Shibata, J. Schaeffer, Z.-H. Li, G. Capella, M. Perucho
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Genetic Heterogeneity of the c-K-ras Locus in Colorectal Adenomas but not in Adenocarcinomas Get access Darryl Shibata, Darryl Shibata Department of Pathology, University of Southern California School of MedicineLos Angeles, Calif Correspondence to: Darryl Shibata, M.D., 1200 N. State St., #736, Los Angeles, CA 90033. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jim Schaeffer, Jim Schaeffer California Institute of Biological ResearchLa Jolla, Calif Search for other works by this author on: Oxford Academic PubMed Google Scholar Zhi-Hua Li, Zhi-Hua Li Department of Pathology, University of Southern California School of MedicineLos Angeles, Calif Search for other works by this author on: Oxford Academic PubMed Google Scholar Gabriel Capella, Gabriel Capella California Institute of Biological ResearchLa Jolla, Calif Search for other works by this author on: Oxford Academic PubMed Google Scholar Manuel Perucho Manuel Perucho California Institute of Biological ResearchLa Jolla, Calif * See "Notes" section following "References." Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 13, 7 July 1993, Pages 1058–1063, https://doi.org/10.1093/jnci/85.13.1058 Published: 07 July 1993 Article history Received: 11 January 1993 Revision received: 29 March 1993 Accepted: 06 April 1993 Published: 07 July 1993
Expression of different members of the Ly-49 gene family defines distinct natural killer cell subsets and cell adhesion properties.
Authors: J Brennan, D Mager, W Jefferies, F Takei
Journal: The Journal of Experimental Medicine (1994)

The murine Ly-49 antigen belongs to a family of type II transmembrane molecules containing lectin-like domains. The original member of this family, Ly-49A, has been demonstrated to be expressed by a subpopulation of natural killer (NK) cells, bind certain class I major histocompatibility complexes (MHC), and act as a negative regulator of lytic activity. The expression patterns and functional activities of the other Ly-49s, however, is unknown. We extended the study of this family by isolating cDNAs encoding two new Ly-49 molecules. The reactivity of these and previously identified Ly-49 molecules with NK antibodies was tested in a COS cell expression system. YE1/32 and YE1/48 bound Ly-49A specifically, and 5E6 reacted only with Ly-49C. Three-color flow cytometric analysis demonstrated Ly-49A and Ly-49C expression defines complex, but distinct subsets within NK1.1+ cells. Some NK1.1-CD3+ as well as NK1.1-CD3- cells expressing Ly-49A or C were also detected. Analysis of MHC congenic strains of mice demonstrated that YE1/32+ and YE1/48+ NK cells are not deleted, as has been shown with the Ly-49A mAb A1. Furthermore, COS cells transfected with Ly-49A bound H-2d and H-2k cell lines, whereas Ly-49C transfectants bound H-2d, H-2k, H-2b, and H-2s. The antibodies 5E6 and 34-1-2S (anti-class I MHC) inhibited the binding of Ly-49C to an H-2s cell line. These results imply that the NK cell antigens Ly-49A and C bind to different repertoires of class I MHC molecules.