tbuckley/cabot-search huggingface dataset:
Fusion Cell Vaccination of Patients with Metastatic Breast and Renal Cancer Induces Immunological and Clinical Responses
Authors: David Avigan, Baldev Vasir, Jianlin Gong, Virginia Borges, Zekui Wu, Lynne Uhl, Michael Atkins, James Mier, David McDermott, Therese Smith, Nancy Giallambardo, Carolyn Stone, Kim Schadt, Jennifer Dolgoff, Jean-Claude Tetreault, Marisa Villarroel, Donald Kufe
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Dendritic cells (DCs) are potent antigen-presenting cells that are uniquely capable of inducing tumor-specific immune responses. We have conducted a Phase I trial in which patients with metastatic breast and renal cancer were treated with a vaccine prepared by fusing autologous tumor and DCs. Experimental Design: Accessible tumor tissue was disrupted into single cell suspensions. Autologous DCs were prepared from adherent peripheral blood mononuclear cells that were obtained by leukapheresis and cultured in granulocyte macrophage colony-stimulating factor, interleukin 4, and autologous plasma. Tumor cells and DCs were cocultured in the presence of polyethylene glycol to generate the fusions. Fusion cells were quantified by determining the percentage of cells that coexpress tumor and DC markers. Patients were vaccinated with fusion cells at 3-week intervals and assessed weekly for toxicity, and tumor response was assessed at 1, 3, and 6 months after completion of vaccination. Results: The vaccine was generated for 32 patients. Twenty-three patients were vaccinated with 1 × 105 to 4 × 106 fusion cells. Fusion cells coexpressed tumor and DC antigens and stimulated allogeneic T-cell proliferation. There was no significant treatment-related toxicity and no clinical evidence of autoimmunity. In a subset of patients, vaccination resulted in an increased percentage of CD4 and CD8+ T cells expressing intracellular IFN-γ in response to in vitro exposure to tumor lysate. Two patients with breast cancer exhibited disease regressions, including a near complete response of a large chest wall mass. Five patients with renal carcinoma and one patient with breast cancer had disease stabilization. Conclusions: Our findings demonstrate that fusion cell vaccination of patients with metastatic breast and renal cancer is a feasible, nontoxic approach associated with the induction of immunological and clinical antitumor responses.
Acute Pseudogout Simulating Septic Arthritis
Authors: N. James Doll
Journal: JAMA (1979)

SINCE the original descriptions of pseudogout by McCarty et al<sup>1</sup>and Zitnan and Sitaj,<sup>2</sup>several patterns of arthritis have been described: (1) intermittent attacks of acute inflammatory arthritis that subside completely between attacks; (2) continuous acute attacks that usually involve more than one joint and may involve symmetrical joints; (3) chronic arthritis with superimposed acute attacks; and (4) chronic arthritis without acute attacks.<sup>3</sup>Rarely, pseudogout may be seen with clinical and laboratory findings suggestive of acute septic arthritis. We report here a case of acute pseudogout simulating septic arthritis in an elderly woman. <h3>Report of a Case</h3> An 82-year-old woman was admitted to the medical service with a diagnosis of septic arthritis of her left knee. She had a history of osteoarthritis and had fallen two days prior to admission without injury to her knee. Pertinent physical findings included a temperature of 38.7<sup>°</sup>C and a
Change in Level of Physical Activity and Risk of All-Cause Mortality or Reinfarction
Authors: Lyn Steffen-Batey, Milton Z. Nichaman, David C. Goff, Ralph F. Frankowski, Craig L. Hanis, David J. Ramsey, Darwin R. Labarthe
Journal: Circulation (2000)

Background —The role of physical activity (PA) in reducing the risk of all-cause mortality or reinfarction after a first myocardial infarction (MI) remains unresolved, particularly for minority populations. The association between change in level of PA and risk of death or reinfarction was studied in 406 Mexican American and non-Hispanic white women and men who survived a first MI. Methods and Results —MI patients were interviewed at baseline and annually thereafter about PA, medical history, and risk factors of coronary heart disease. Change in level of PA after the index MI was categorized as (1) sedentary, no change (referent group), (2) decreased activity, (3) increased activity, and (4) active, no change. Over a 7-year period, the relative risk (95% CI) of death was as follows: 0.21 (0.10 to 0.44) for the active, no change group; 0.11 (0.03 to 0.46) for the increased activity group; and 0.49 (0.26 to 0.90) for the decreased activity group. The relative risk of reinfarction was as follows: 0.40 (0.24 to 0.66) for the active, no change group; 0.22 (0.09 to 0.50) for the increased activity group; and 0.93 (0.59 to 1.42) for the decreased activity group. Conclusions —These findings are consistent with a beneficial role of PA for Mexican American and non-Hispanic white women and men who survive a first MI and have practical implications for the management of MI survivors.
Mucous membrane pemphigoid: management of advanced ocular disease with intravenous cyclophosphamide and amniotic membrane transplantation
Authors: P.D. Yesudian, S. Armstrong, J.I. Cawood, R.B. Allan, S.S. Mendelsohn, S.B. Kaye
Journal: British Journal of Dermatology (2005)

Journal Article Mucous membrane pemphigoid: management of advanced ocular disease with intravenous cyclophosphamide and amniotic membrane transplantation Get access P.D. Yesudian, P.D. Yesudian Departments of Dermatology, Ophthalmology Search for other works by this author on: Oxford Academic Google Scholar S. Armstrong, S. Armstrong Departments of Dermatology, Ophthalmology Search for other works by this author on: Oxford Academic Google Scholar J.I. Cawood, J.I. Cawood Maxillofacial Surgery, Countess of Chester Hospital, Chester CH2 1UL, U.K Search for other works by this author on: Oxford Academic Google Scholar R.B. Allan, R.B. Allan Unit of Oral Medicine, Liverpool University Dental Hospital, Liverpool, U.K Search for other works by this author on: Oxford Academic Google Scholar S.S. Mendelsohn, S.S. Mendelsohn Departments of Dermatology, Ophthalmology Search for other works by this author on: Oxford Academic Google Scholar S.B. Kaye S.B. Kaye St Paul's Eye Unit, Royal Liverpool University Hospital, Liverpool, U.K. E‐mail: Paul.Yesudian@coch.nhs.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 3, 1 September 2005, Pages 692–694, https://doi.org/10.1111/j.1365-2133.2005.06826.x Published: 01 September 2005
Preclinical Studies of Vorinostat (Suberoylanilide Hydroxamic Acid) Combined with Cytosine Arabinoside and Etoposide for Treatment of Acute Leukemias
Authors: Ken Shiozawa, Takeo Nakanishi, Ming Tan, Hong-Bin Fang, Wen-chyi Wang, Martin J. Edelman, David Carlton, Ivana Gojo, Edward A. Sausville, Douglas D. Ross
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Vorinostat [suberoylanilide hydroxamic acid (SAHA)] is a potent histone deacetylase inhibitor with promising clinical efficacy as an anticancer agent. In this preclinical study, we evaluated combining cytosine arabinoside [1-β-d-arabinofuranosylcytosine (ara-C)] and/or etoposide with vorinostat for use in the treatment of acute leukemias. Experimental Design: Cell survival was examined in vitro in HL-60 human myeloid leukemia cells and K562 myeloid blast crisis chronic myelogenous leukemia cells, using the 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt and/or fluorescein diacetate/propidium iodide assays. Drug interactions were analyzed by the combination index method (CalcuSyn) and by a novel statistical method that we developed (SynStat). Cell cycle phase distribution was measured by flow cytometry. Results: Cytotoxic antagonism resulted when vorinostat was combined concomitantly with ara-C; however, when vorinostat was given first followed by a drug-free interval before ara-C treatment, this sequential combination was mostly synergistic. Etoposide combined with vorinostat was additive to synergistic, and the synergism became more pronounced when etoposide was given after vorinostat. Cell cycle analyses revealed that the sequence-dependent interaction of vorinostat and ara-C or etoposide reflected the arrest of cells in G1 or G2 phase during vorinostat treatment and recovery into S phase after removal of vorinostat. Conclusions: These findings using two independent methods to assess drug combination effects provide a preclinical rationale for phase I trials of the sequential combination of vorinostat followed by ara-C and etoposide in patients with advanced or refractory leukemias. CalcuSyn findings were concordant with those of SynStat, validating the use of the latter in analyzing drug interactions.
Septin: a factor in plasma that opsonizes lipopolysaccharide-bearing particles for recognition by CD14 on phagocytes.
Authors: S D Wright, R A Ramos, M Patel, D S Miller
Journal: The Journal of Experimental Medicine (1992)

We have previously reported that lipopolysaccharide (LPS) binding protein (LBP) opsonizes endotoxin (LPS) for recognition by CD14 on phagocytes. Here we show that normal human plasma contains high titers of an activity that also binds LPS (Re, 595) and mediates recognition by CD14. Opsonization of LPS-coated particles with plasma enables the particles to be bound by phagocytes. Further, opsonization with plasma also enables subnanogram-per-milliliter concentrations of LPS to induce dramatic alterations in the function of leukocyte integrins on polymorphonuclear leukocytes and to induce secretion of tumor necrosis factor by monocytes, suggesting that opsonization by factors in plasma may be important in responses of cells to endotoxin. The opsonic activity in plasma appears distinct from LBP since it is not blocked by neutralizing antibodies against LBP. Surprisingly, the opsonic activity of plasma is not present in a single protein species, but at least two species must be combined to observe activity. Further, the opsonic activity of plasma for LPS is blocked by addition of protease inhibitors, suggesting that proteolytic activity or activities are required for opsonization. These properties are suggestive of the action of a protease cascade, but opsonic activity of plasma is not affected by blockade or depletion of either the complement or clotting cascades. We propose the name "septin" to describe this novel LPS-opsonizing activity in plasma.
Time-dependent increase in risk of hospitalisation with infection among Swedish RA patients treated with TNF antagonists
Authors: J. Askling, C M. Fored, L. Brandt, E. Baecklund, L. Bertilsson, N. Feltelius, L. Coster, P. Geborek, L. T Jacobsson, S. Lindblad, J. Lysholm, S. Rantapaa-Dahlqvist, T. Saxne, R. F van Vollenhoven, L. Klareskog
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> The degree to which treatment with tumour necrosis factor (TNF) antagonists may be associated with increased risks for serious infections is unclear. An observational cohort study was performed using prospectively collected data from the Swedish Biologics Register (ARTIS) and other national Swedish registers. <h3>Methods:</h3> First, in the ARTIS, all 4167 rheumatoid arthritis (RA) patients starting TNF antagonist treatment between 1999 and 2003 were identified. Secondly, in the Swedish Inpatient Register, all individuals hospitalised for any reason and who also carried a diagnosis of RA, between 1964 and 2003 (n = 44 946 of whom 2692 also occurred in ARTIS), were identified. Thirdly, in the Swedish Inpatient Register, all hospitalisations listing an infection between 1999 and 2003 were identified. By cross-referencing these three data sets, RRs for hospitalisation with infection associated with TNF antagonist treatment were calculated within the cohort of 44 946 RA patients, using Cox regression taking sex, age, geography, co-morbidity and use of inpatient care into account. <h3>Results:</h3> Among the 4167 patients treated with TNF antagonists, 367 hospitalisations with infections occurred during 7776 person-years. Within the cohort of 44 496 RA patients, the RR for infection associated with TNF antagonists was 1.43 (95% CI 1.18 to 1.73) during the first year of treatment, 1.15 (95% CI 0.88 to 1.51) during the second year of treatment, and 0.82 (95% CI 0.62 to 1.08) for subjects remaining on their first TNF antagonist treatment after 2 years. <h3>Conclusion:</h3> Treatment with TNF antagonists may be associated with a small to moderate increase in risk of hospitalisation with infection, which disappears with increasing treatment duration.
Reduced thromboxane biosynthesis in carriers of toll-like receptor 4 polymorphisms in vivo
Authors: Paola Patrignani, Concetta Di Febbo, Stefania Tacconelli, Valeria Moretta, Giovanna Baccante, Maria G. Sciulli, Emanuela Ricciotti, Marta L. Capone, Ivana Antonucci, Maria D. Guglielmi, Liborio Stuppia, Ettore Porreca
Journal: Blood (2006)
Cytokines and Sodium Induce Protein Kinase A–Dependent Cell-Surface Na,K-ATPase Recruitment via Dissociation of NF-κB/IκB/Protein Kinase A Catalytic Subunit Complex in Collecting Duct Principal Cells
Authors: Manlio Vinciguerra, Udo Hasler, David Mordasini, Martine Roussel, Maria Capovilla, Eric Ogier-Denis, Alain Vandewalle, Pierre-Yves Martin, Eric Feraille
Journal: Journal of the American Society of Nephrology (2005)

Collecting duct (CD) principal cells are exposed to large physiologic variations of apical Na+ influx as a result of variations of Na+ intake and extrarenal losses. It was shown previously that increasing intracellular [Na+] induces recruitment of Na,K-ATPase to the cell surface in a protein kinase A (PKA)-dependent manner in both native and cultured renal CD principal cells. As described previously in response to cytokines in nonrenal cells, PKA activation in response to increased intracellular [Na+] was independent of cAMP and required proteasomal activity. With the use of cultured mpkCCDcL4 cells as a model of CD principal cells, whether cytokines and increased intracellular [Na+] share a common signaling pathway leading to cell-surface Na,K-ATPase recruitment was investigated. Results showed that two potent inducers of NF-κB, LPS and TNF-α, enhance Na+ transport and induce cell-surface Na,K-ATPase recruitment in mpkCCDcL4 cells via cAMP-independent PKA activation. In addition, increased intracellular [Na+] after selective plasma membrane permeabilization by a low concentration of the Na+ ionophore amphotericin B (1 μg/ml) induced dissociation of the PKA catalytic subunit from p65–NF-κB and IκBα. Moreover, inhibitors of NF-κB/IκB dissociation prevented both Na+-dependent stimulation of PKA activity and cell-surface Na,K-ATPase recruitment. Altogether, these results revealed the presence of a novel Na+-dependent intracellular signaling pathway leading to Na,K-ATPase cell-surface recruitment via dissociation of the PKA catalytic subunit from a macromolecular complex that contains NF-κB and IκBα in CD epithelial cells.
The prevalence and clinical significance of sonographic tendon abnormalities in asymptomatic ballet dancers: a 24-month longitudinal study
Authors: Jules Comin, Jill L Cook, Peter Malliaras, Moira McCormack, Michelle Calleja, Andrew Clarke, David Connell
Journal: British Journal of Sports Medicine (2012)

Sonographic abnormalities of the achilles and patellar tendons are common findings in athletes, and tendinopathy is a common cause of pain and disability in athletes. However, it is unclear whether the sonographic changes are pathological or adaptive, or if they predict future injury. We undertook a cohort study to determine what sonographic features of the achilles and patellar tendons are consistent with changes as a result of ballet training, and which may be predictive of future development of disabling tendon symptoms.The achilles and patellar tendons of 79 (35 male, 44 female) professional ballet dancers (members of the English Royal Ballet) were examined with ultrasound, measuring proximal and distal tendon diameters and assessing for the presence of hypoechoic change, intratendon defects, calcification and neovascularity. All subjects were followed for 24 months for the development of patellar tendon or achilles-related pain or injury severe enough to require time off from dancing.Sonographic abnormalities were common among dancers, both male and female, and in both achilles and patellar tendons. Disabling tendon-related symptoms developed in 10 dancers and 14 tendons: 7 achilles (3 right, 4 left) and 7 patellar (2 right, 5 left). The presence of moderate or severe hypoechoic defects was weakly predictive for the development of future disabling tendon symptoms (p=0.0381); there was no correlation between any of the other sonographic abnormalities and the development of symptoms. There was no relationship between achilles or patellar tendons' diameter, either proximal or distal, with an increased likelihood of developing tendon-related disability.The presence of sonographic abnormalities is common in ballet dancers, but only the presence of focal hypoechoic changes predicts the development of future tendon-related disability. This suggests that screening of asymptomatic individuals may be of use in identifying those who are at higher risk of developing tendon-related disability, which may in turn allow targeted modifications of training or other preventative regimens.
Coincident Kaposi sarcoma and T‐cell lymphoma in a patient with the Wiskott‐Aldrich syndrome
Authors: Neal J. Meropol, David Hicks, John J. Brooks, Katherine A. Siminovitch, Neil O. Fishman, Jeffrey A. Kant, Joel S. Bennett
Journal: American Journal of Hematology (1992)

Abstract A 24 year old male with a history of eczema, recurrent mild infections, and thrombocytopenia consistent with the Wiskott‐Aldrich syndrome (WAS) presented with a mediastinal mass, generalized lymphadenopathy, splenomegaly, and severe thrombocytopenia. Studies of immune function including immunoglobulin levels and T‐cell subsets were normal. Furthermore, his T lymphocytes proliferated normally in response to phytohemagglutinin, concanavalin A, and the combination of neuraminidase/galactose oxidase. However, their proliferative responses to anti‐CD43 antibody and periodate were diminished, consistent with the clinical diagnosis of WAS. An initial inguinal lymph node biopsy surprisingly revealed Kaposi sarcoma. However, following splenctomy to increase the platelet count, biopsy of the mediastinal mass revealed T‐cell large cell lymphoma. Studies of biopsied tissue for the presence of Epstein‐Barr virus and cytomegalovirus were negative, as were studies of blood, including the polymerase chain reaction, for the presence of the human immunodeficiency virus (HIV). This is the first report of Kaposi sarcoma arising in a patient with a congenital immunodeficiency syndrome. Although Kaposi sarcoma can arise in the face of the severe immunosuppression that follows allograft transplantation and in patients infected with HIV, we postulate that longevity in the face of mild immunosuppression was the major factor in the development of Kaposi sarcoma in this patient. © 1992 Wiley‐Liss, Inc.
Heat produced by rabbit papillary muscle during anoxia and reoxygenation.
Authors: D L Dietrich, G Elzinga
Journal: Circulation Research (1993)

Resting heat rate was measured in superfused rabbit papillary muscles at 20 degrees C during 40 minutes of anoxia and subsequent reoxygenation. To reveal the nature of the reactions underlying energy output under such conditions, the data obtained were compared with values predicted from data on chemical change. Before and after the anoxic period, muscles were stimulated at 0.2 Hz, during which time the contraction-related heat rate was measured. During anoxia, muscles were kept at rest or stimulated at 1 Hz. Stimulation was switched off intermittently to determine resting heat rate. Before anoxia, resting heat rate was 8.7 +/- 1.1 (mean +/- SEM) mW.g dry wt-1. During anoxia, it decreased to 38% and 50% of the preanoxic level in resting and stimulated muscles, respectively (P &lt; .05). In resting muscles, heat rate increased with reoxygenation in approximately 10 to 15 minutes to 1.3 times the preanoxic level, whereas this was 3.7 times in stimulated muscles. Resting heat rate returned within 65 (resting muscles) or 150 (stimulated muscles) minutes to the baseline. The ratio of force- and contraction-related heat rate, ie, the economy of contraction, was not different before and after anoxia. We estimated that the heat produced by muscles during anoxia was not different from the heat to be expected from the hydrolysis of creatine phosphate, the breakdown of nucleotides, and the formation of lactate. The overshoot in resting heat during reoxygenation of resting muscles could be accounted for by the resynthesis of the energy store. The much larger overshoot in resting heat of stimulated muscles was due to the contracture. The finding that the economy of contraction was not altered by anoxia and reoxygenation suggests that both sarcoplasmic reticulum Ca(2+)-ATPase and myofibrillar ATPase are depressed by anoxia and that the enhancement of cytosolic calcium transients with reoxygenation, reported in other studies on papillary muscle, results from reduced binding of calcium rather than from enhanced release.
Evolutionary History of the Most Speciose Mammals: Molecular Phylogeny of Muroid Rodents
Authors: J Michaux, A Reyes, F Catzeflis
Journal: Molecular Biology and Evolution (2001)

Phylogenetic relationships between 32 species of rodents representing 14 subfamilies of Muridae and four subfamilies of Dipodidae were studied using sequences of the nuclear protein-coding genes Lecithin Cholesterol Acyl Transferase (LCAT) and von Willebrand Factor (vWF). An examination of some evolutionary properties of each data matrix indicates that the two genes are rather complementary, with lower rates of nonsynonymous substitutions for LCAT. Both markers exhibit a wide range of GC3 percentages (55%–89%), with several taxa above 70% GC3 for vWF, which indicates that those exonic regions might belong to the richest class of isochores. The primary sequence data apparently harbor few saturations, except for transitions on third codon positions for vWF, as indicated by comparisons of observed and expected pairwise values of substitutions. Phylogenetic trees based on 1,962 nucleotidic sites from the two genes indicate that the 14 Muridae subfamilies are organized into five major lineages. An early isolation leads to the clade uniting the fossorial Spalacinae and semifossorial Rhizomyinae with a strong robustness. The second lineage includes a series of African taxa representing nesomyines, dendromurines, cricetomyines, and the sole living member of mystromyines. The third one comprises only the mouselike hamster Calomyscus. The fourth clade represents the cricetines, myospalacines, sigmodontines, and arvicolines, whereas the fifth one comprises four “traditional” subfamilies (Gerbillinae, Murinae, Otomyinae, and Acomyinae). Within these groups, we confirm the monophyly of almost all studied subfamilies, namely, Spalacinae, Rhizomyinae, Nesomyinae, Cricetomyinae, Arvicolinae, Sigmodontinae, Cricetinae, Gerbillinae, Acomyinae, and Murinae. Finally, we present evidence that the sister group of Acomyinae is Gerbillinae, and we confirm a nested position of Myospalacinae within Cricetinae and Otomyinae within Murinae. From a biogeographical point of view, the five main lineages spread and radiated from Asia with different degrees of success: the first three groups are now represented by a limited number of species and genera localized in some regions, whereas the last two groups radiated in a large variety of species and genera dispersed all over the world.