tbuckley/cabot-search huggingface dataset:
Brief Report: Patients With Primary Sjögren's Syndrome Who Are Positive for Autoantibodies to Tripartite Motif-Containing Protein 38 Show Greater Disease Severity
Authors: Nina Wolska, Paulina Rybakowska, Astrid Rasmussen, Michael Brown, Courtney Montgomery, Arkadiusz Klopocki, Kiely Grundahl, Robert H. Scofield, Lida Radfar, Donald U. Stone, Juan M. Anaya, John A. Ice, Christopher J. Lessard, David M. Lewis, Nelson L. Rhodus, Rajaram Gopalakrishnan, Andrew J. W. Huang, Pamela J. Hughes, Michael D. Rohrer, Michael H. Weisman, Swamy Venuturupalli, Joel M. Guthridge, Judith A. James, Kathy L. Sivils, Harini Bagavant, Umesh S. Deshmukh
Journal: Arthritis & Rheumatology (2015)

Objective Autoantibodies reactive with Ro52 (tripartite motif−containing protein 21 [TRIM21]) are detected in 70% of patients with primary Sjögren's syndrome (SS). TRIM21 belongs to a 34‐member C‐IV family of TRIM proteins. Although autoantibodies against other TRIM proteins within the C‐IV family have been detected in the sera of patients with primary SS, their clinical relevance remains unclear. This study was undertaken to investigate the frequency of anti‐TRIM38 in patients with primary SS and evaluate its association with various clinical measures of the disease. Methods Serum samples from patients with primary SS (n = 235) and controls (n = 50) were analyzed for reactivity with in vitro−transcribed and −translated 35 S‐methionine−labeled TRIM38 protein. The associations of anti‐TRIM38 with various laboratory and clinical measures of primary SS were evaluated. Reactivity of anti‐TRIM38 with different structural domains of TRIM38 was analyzed. Affinity‐purified anti‐TRIM38 antibodies were used to immunoprecipitate TRIM21. Results TRIM38‐reactive autoantibodies were detected in the sera of 24 of the 235 patients with primary SS and 2 of the 50 controls. Anti‐TRIM38 positivity was significantly associated with the presence of anti‐Ro60, anti‐Ro52, anti‐La, rheumatoid factor, and hypergammaglobulinemia. Clinically, anti‐TRIM38 was associated with significantly higher ocular surface staining scores, lower Schirmer's test scores, and minor labial salivary gland biopsy focus scores of ≥3.0. Anti‐TRIM38 antibodies mainly recognized the cortactin‐binding protein 2 (CortBP‐2; amino acids 128–238) and the B30.2/SPRY (amino acids 268–465) domains on TRIM38. Affinity‐purified antibodies to TRIM38–CortBP‐2 and TRIM38–B30.2/SPRY domains reacted with TRIM21. Conclusion Our data demonstrate that anti‐TRIM38 specificity arising in a subset of patients with primary SS is associated with increased severity of the disease.
Post-embryonic Hourglass Patterns Mark Ontogenetic Transitions in Plant Development
Authors: Hajk-Georg Drost, Julia Bellstädt, Diarmuid S Ó'Maoiléidigh, Anderson T Silva, Alexander Gabel, Claus Weinholdt, Patrick T Ryan, Bas J W Dekkers, Leónie Bentsink, Henk W M Hilhorst, Wilco Ligterink, Frank Wellmer, Ivo Grosse, Marcel Quint
Journal: Molecular Biology and Evolution (2016)

The historic developmental hourglass concept depicts the convergence of animal embryos to a common form during the phylotypic period. Recently, it has been shown that a transcriptomic hourglass is associated with this morphological pattern, consistent with the idea of underlying selective constraints due to intense molecular interactions during body plan establishment. Although plants do not exhibit a morphological hourglass during embryogenesis, a transcriptomic hourglass has nevertheless been identified in the model plant Arabidopsis thaliana Here, we investigated whether plant hourglass patterns are also found postembryonically. We found that the two main phase changes during the life cycle of Arabidopsis, from embryonic to vegetative and from vegetative to reproductive development, are associated with transcriptomic hourglass patterns. In contrast, flower development, a process dominated by organ formation, is not. This suggests that plant hourglass patterns are decoupled from organogenesis and body plan establishment. Instead, they may reflect general transitions through organizational checkpoints.
Comparison of the Carcinogenic Effectiveness of &lt;italic&gt;N&lt;/italic&gt;-Nitrosobis(2-hydroxypropyl)amine, &lt;italic&gt;N&lt;/italic&gt;-Nitrosobis(2-oxopropyl)amine, &lt;italic&gt;N&lt;/italic&gt;-Nitroso(2-hydroxypropyl) (2-oxopropyl)amine, and &lt;italic&gt;N&lt;/italic&gt;-Nitroso-2,6-dimethylmorpholine in Syrian Hamsters&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: W Lijinsky, J E Saavedra, G L Knutsen, R M Kovatch
Journal: JNCI Journal of the National Cancer Institute (1984)

For examination of metabolic interrelationships in carcinogenesis between N-nitroso-2,6-dimethylmorpholine, N-nitrosobis(2-oxopropyl)amine (CAS: 60599-38-4), N-nitrosobis(2-hydroxypropyl)amine (CAS: 53609-64-6), and N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine, each was given to a separate group of 20 female Syrian golden hamsters by gavage. All four compounds induced tumors of the pancreatic duct and lung tumors, but the incidences varied from one compound to another. In addition, N-nitrosobis(2-oxopropyl)amine and N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine induced many hepatocellular and cholangiocellular neoplasms, which the other two compounds did not. On the basis of short time to death with tumors and the relatively low total dose administered, N-nitrosobis(2-oxopropyl) amine appeared to be the most potent carcinogen in the hamster among the four. N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine was next in potency but was considerably weaker than N-nitrosobis(2-oxopropyl)amine. N-Nitroso-2,6-dimethylmorpholine, which was similar in potency to N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine, however, did not induce a significant incidence of liver tumors of any type; and N-nitrosobis(2-hydroxypropyl) amine was considerably less potent than the other three compounds. These results did not support the opinion of N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine as the proximate carcinogenic metabolite of all three compounds in the Syrian hamster but instead suggested that these compounds might have acted through formation of different and yet unknown carcinogenic intermediates.
Phase I trial of recombinant interferon gamma in cancer patients.
Authors: S Vadhan-Raj, A Al-Katib, R Bhalla, L Pelus, C F Nathan, S A Sherwin, H F Oettgen, S E Krown
Journal: Journal of Clinical Oncology (1986)

Interferon gamma (IFN-gamma) is a lymphokine with potent in vitro effects on cell growth and immune function. We have investigated the effects of rIFN-gamma (sp act approximately 2 X 10(7) U/mg, purity greater than 99%) in 16 evaluable patients with advanced malignancy in a phase 1 trial. Patients were treated with six-hour intravenous (IV) infusions daily, five days a week for 2 weeks. After a 2-week rest period, the IV treatment cycle was repeated. Responders were maintained on repeated IV treatment cycles or daily intramuscular (IM) injections. Patients were entered at fixed dose levels of 0.1, 0.5, or 1.0 mg/m2/d. The maximum safely tolerated dose was 0.5 mg/m2. The most common side effects were constitutional symptoms, including fever, chills, fatigue, and myalgias. Reversible and transient increases in hepatic transaminase and decrease in granulocyte counts were seen. Treatment was associated with a dose-dependent increase in serum levels of beta 2 microglobulin. Partial responses (PRs) were observed in one patient with Hodgkin's disease and one patient with chronic lymphocytic leukemia. Fairly constant levels of serum IFN were found at four and six hours during infusion, followed by a rapid decline within one to two hours. We conclude that rIFN-gamma can be safely administered by a six-hour IV infusion and that it can induce in vivo some of the biologic effects reported in in vitro studies.
Japanese encephalitis among three U.S. travelers returning from Asia, 2003-2008.
Authors: J. Bakken, D. Neitzel, L. Taylor, R. Civen, L. L. Plawner, S. McKiernan, J. S. Duchin, R. Baer, N. Marsden-haug, S. Thamthitiwat, H. C. Baggett, G. L. Campbell, A. Griggs, A. J. Panella, J. Laven, O. Kosoy, R. S. Lanciotti, J. E. Staples, M. Fischer, M. Duffy
Journal: MMWR Morbidity and Mortality Weekly Report (2009)
Susceptibility of Tumor Cells in Different Phases of the Mitotic Cycle to the Effect of Immune Lymphocytes
Authors: Natasha V. Leneva, George J. Svet-Moldavsky
Journal: JNCI Journal of the National Cancer Institute (1974)

The cytotoxic effect of immune lymphocytes against synchronized L cells was studied. This effect occurred after the addition of immune lymphocytes to the target cells only at the beginning of the G1 phase. Target cells in the early G1 phase were destroyed during 30 minutes of interaction with immune lymphocytes. The addition of immune lymphocytes to the target cells 3 hours after the beginning of the G1 phase, as well as their addition to the target cells in the S, G2, and M phases, induced cytotoxicity neither during 30 minutes nor throughout any of these phases. The addition of immune lymphocytes to the synchronized target cells in all phases of the mitotic cycle, except the early G1 phase, led to the same cytotoxic effect as in the unsynchronized L cells. The high susceptibility of the early G1 phase to the effect of immune lymphocytes showed a special physiologic state of cells in this phase, designated as G1/α. It is assumed that the cytotoxic effect of immune lymphocytes against unsynchronized L cells is easily detected after 48 hours and depends on the passage of each cell through the G1/α phase in contact with immune iymphocytes.
Molecular monitoring of minimal residual disease in patients in long-term complete remission after allogeneic stem cell transplantation for multiple myeloma
Authors: Michele Cavo, Carolina Terragna, Giovanni Martinelli, Sonia Ronconi, Elena Zamagni, Patrizia Tosi, Roberto M. Lemoli, Monica Benni, Giorgio Pagliani, Giuseppe Bandini, Sante Tura
Journal: Blood (2000)
Can endosheath technology open primary care doors to Barrett’s esophagus screening by transnasal endoscopy?
Authors: Prasad Iyer, Amitabh Chak
Journal: Endoscopy (2016)

Articles on esophageal adenocarcinoma (EAC) generally begin with statistics regarding its alarming rise in recent decades [1]. Despite the ease with which Barrett's esophagus, the precursor of EAC, can be identified at endoscopy, there has been little progress in prevention or early detection of EAC. The limitations of current guidelines that hesitatingly recommend sedated esophagogastroduodenoscopy (EGD) in patients with symptoms of gastroesophageal reflux disease (GERD), multiple risk factors, or alarm symptoms are self-evident. A strategy based on symptoms will fail to detect Barrett's esophagus in asymptomatic individuals and will also fail in those with well-controlled symptoms. Unless we can improve screening for Barrett's esophagus, the status quo will not change, with fewer than 5 % of EACs detected early as part of Barrett's surveillance programs [2]. Promising ablative endoscopic therapies for dysplastic Barrett's esophagus [3] [4] will also have little impact, and the 5-year survival for EACs will remain a dismal 18 % [1] unless we develop effective alternatives to sedated EGD for identifying Barrett's esophagus in the general population.
Phase I Clinical and Pharmacokinetic Study of Bcl-2 Antisense Oligonucleotide Therapy in Patients With Non-Hodgkin’s Lymphoma
Authors: Justin S. Waters, Andrew Webb, David Cunningham, Paul A. Clarke, Florence Raynaud, Francesca di Stefano, Finbarr E. Cotter
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To evaluate the pharmacokinetics and toxicity of an antisense oligonucleotide targeting bcl-2 in patients with non-Hodgkin’s lymphoma (NHL) and to determine efficacy using clinical and biologic end points. PATIENTS AND METHODS: Twenty-one patients with Bcl-2–positive relapsed NHL received a 14-day subcutaneous infusion of G3139, an 18-mer phosphorothioate oligonucleotide complementary to the first six codons of the bcl-2 open reading frame. Plasma pharmacokinetics were measured by anion exchange high-performance liquid chromatography. Response was assessed by computed tomography. Changes in Bcl-2 expression were measured by fluorescence-activated cell sorting of patients’ tumor samples. RESULTS: Eight cohorts of patients received doses between 4.6 and 195.8 mg/m 2 /d. No significant systemic toxicity was seen at doses up to 110.4 mg/m 2 /d. All patients displayed skin inflammation at the subcutaneous infusion site. Dose-limiting toxicities were thrombocytopenia, hypotension, fever, and asthenia. The maximum-tolerated dose was 147.2 mg/m 2 /d. Plasma levels of G3139 equivalent to the efficacious plasma concentration in in vivo models were produced with doses above 36.8 mg/m 2 /d. Plasma levels associated with dose-limiting toxicity were greater than 4 μg/mL. By standard criteria, there was one complete response, 2 minor responses, nine cases of stable disease, and nine cases of progressive disease. Bcl-2 protein was reduced in seven of 16 assessable patients. This reduction occurred in tumor cells derived from lymph nodes in two patients and from peripheral blood or bone marrow mononuclear cell populations in the remaining five patients. CONCLUSION: Bcl-2 antisense therapy is feasible and shows potential for antitumor activity in NHL. Downregulation of Bcl-2 protein suggests a specific antisense mechanism.
Adjuvant tamoxifen in early-stage breast cancer: effects on intercurrent morbidity and mortality.
Authors: T Fornander, L E Rutqvist, B Cedermark, U Glas, A Mattsson, L Skoog, A Somell, T Theve, N Wilking, J Askergren
Journal: Journal of Clinical Oncology (1991)

Intercurrent mortality and the pattern of inpatient hospital care was studied among 1,846 postmenopausal patients included in the Stockholm randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no adjuvant endocrine therapy. The median follow-up time was 54 months (range, 2 to 123 months). The patients were matched to the Swedish National Registry of Causes of Death and a computerized register covering about 95% of all hospital admissions in Stockholm County. There was no significant difference in the pattern of intercurrent mortality among the tamoxifen and control patients. The total number of hospital admissions was similar in both groups, but the tamoxifen patients were admitted significantly less frequently because of immunologic diseases (relative risk [RR] = 0.4; 95% confidence interval [CI], 0.2 to 0.9). Admissions because of thrombotic diseases were slightly, but not significantly, more frequent among the tamoxifen patients (RR = 1.2; 95% [CI], 0.6 to 2.3). The risk of hospital stay for benign gynecologic diseases other than prolapse or uterine bleeding was increased in the tamoxifen group (RR = 3.2; 95% CI, 1.2 to 8.6). No significant differences were found for diseases related to arteriosclerosis or osteoporosis. The study confirms and extends previous reports, which have shown that tamoxifen has few and usually mild side effects. However, the current results should be judged cautiously because of the relatively short median follow-up time (4.5 years) and the limitation of data in detecting morbidity that does not necessarily result in hospitalization.
Impact of infertility treatment in patients with previous history of borderline ovarian tumors: Results of a multicenter study
Authors: A. Fortin, P. Morice, A. Thoury, C. Yazbeck, S. Camatte, D. Atallah, Y. Zafrani, C. Dhainaut, P. Madelenat
Journal: Journal of Clinical Oncology (2006)

5055 Background: The use of infertility drugs (ID) in infertile patients treated conservatively for ovarian malignancies remains theoretically contraindicated. Few recent case reports seem to suggest that ID could be used in patients treated for a borderline ovarian tumors (BOT). The aim of this multicenter retrospective study was to report the outcomes of the largest series of patients with a previous history of a BOT who underwent the use of ID. Methods: A multicenter retrospective study was conducted among centers which participate in the French National Register on In Vitro Fertilization registry to evaluate the outcomes of patients with a previous history of a BOT treated with ID. Four criteria were defined to select cases: 1. Histologic confirmation of BOT, 2. The use of a conservative surgery, 3. The use of ID and 4. A follow-up ≥ 12 months after the end of infertility treatment. Results: Thirty cases fulfilled inclusion criteria. Infertility therapy began in November 1989. Disease stages were: I (n = 20), II /III with noninvasive implants (n = 8) and unknown in 2 cases. The mean number of cycles of ovarian induction per patient was 2.6 (range,1–10). After a median follow-up of 42 months after infertility treatment, 4 recurrences were observed (all of them were borderline tumors on a remaining ovary treated by surgery alone). All patients are currently disease-free. Thirteen patients have since become pregnant. The median interval between treatment of the BOT and the use of ID is shorter in patients who relapsed compared to patients who did not (5 versus 29 months; p=.07). Conclusions: These results suggest that infertility drugs could be safely used in patients who experience infertility after conservative management of an early-stage BOT. A minimal interval should be respected between treatment of the ovarian tumor and the use of infertility drugs in order to decrease the risk of recurrence. No significant financial relationships to disclose.
Screening for Impaired Visual Acuity in Older Adults
Authors: Albert L. Siu, Kirsten Bibbins-Domingo, David C. Grossman, Linda Ciofu Baumann, Karina W. Davidson, Mark Ebell, Francisco A. R. García, Matthew Gillman, Jessica Herzstein, Alex R. Kemper, Alex H. Krist, Ann E. Kurth, Douglas K. Owens, William R. Phillips, Maureen G. Phipps, Michael P. Pignone
Journal: JAMA (2016)

POPULATION This recommendation applies to asymptomatic adults 65 years or older who do not present to their primary care clinician with vision problems.RECOMMENDATION The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in older adults.(I statement)
Methotrexate selectively targets human proinflammatory macrophages through a thymidylate synthase/p53 axis
Authors: Cristina Municio, Blanca Soler Palacios, Lizbeth Estrada-Capetillo, Alberto Benguria, Ana Dopazo, Elena García-Lorenzo, Salvador Fernández-Arroyo, Jorge Joven, María Eugenia Miranda-Carús, Isidoro González-Álvaro, Amaya Puig-Kröger
Journal: Annals of the Rheumatic Diseases (2016)

Methotrexate (MTX) functions as an antiproliferative agent in cancer and an anti-inflammatory drug in rheumatoid arthritis (RA). Although macrophages critically contribute to RA pathology, their response to MTX remains unknown. As a means to identify MTX response markers, we have explored its transcriptional effect on macrophages polarised by GM-CSF (GM-MØ) or M-CSF (M-MØ), which resemble proinflammatory and anti-inflammatory macrophages found in RA and normal joints, respectively.The transcriptomic profile of both human macrophage subtypes exposed to 50 nM of MTX under long-term and short-term schedules were determined using gene expression microarrays, and validated through quantitative real time PCR and ELISA. The molecular pathway involved in macrophage MTX-responsiveness was determined through pharmacological, siRNA-mediated knockdown approaches, metabolomics for polyglutamylated-MTX detection, western blot, and immunofluorescence on RA and normal joints.MTX exclusively modulated gene expression in proinflammatory GM-MØ, where it influenced the expression of 757 genes and induced CCL20 and LIF at the mRNA and protein levels. Pharmacological and siRNA-mediated approaches indicated that macrophage subset-specific MTX responsiveness correlates with thymidylate synthase (TS) expression, as proinflammatory TS+ GM-MØ are susceptible to MTX, whereas anti-inflammatory TSlow/- M-MØ and monocytes are refractory to MTX. Furthermore, p53 activity was found to mediate the TS-dependent MTX-responsiveness of proinflammatory TS+ GM-MØ. Importantly, TS and p53 were found to be expressed by CD163+/TNFα+ GM-CSF-polarised macrophages from RA joints but not from normal synovium.Macrophage response to MTX is polarisation-dependent and determined by the TS-p53 axis. CCL20 and LIF constitute novel macrophage markers for MTX responsiveness in vitro.
Nanomaterial-dependent immunoregulation of dendritic cells and its effects on biological activities of contraceptive nanovaccines
Authors: Pingping Xu, Shuai Tang, Luping Jiang, Lihua Yang, Dinglin Zhang, Shibin Feng, Tingting Zhao, Yajun Dong, Wei He, Ruibing Wang, Jianxiang Zhang, Zhiqing Liang
Journal: Journal of Controlled Release (2016)
Aptamers as Therapeutics
Authors: Shahid M. Nimjee, Rebekah R. White, Richard C. Becker, Bruce A. Sullenger
Journal: The Annual Review of Pharmacology and Toxicology (2017)

Aptamers are single-stranded nucleic acid molecules that bind to and inhibit proteins and are commonly produced by systematic evolution of ligands by exponential enrichment (SELEX). Aptamers undergo extensive pharmacological revision, which alters affinity, specificity, and therapeutic half-life, tailoring each drug for a specific clinical need. The first therapeutic aptamer was described 25 years ago. Thus far, one aptamer has been approved for clinical use, and numerous others are in preclinical or clinical development. This review presents a short history of aptamers and SELEX, describes their pharmacological development and optimization, and reviews potential treatment of diseases including visual disorders, thrombosis, and cancer.