tbuckley/cabot-search huggingface dataset:
Effects of frequent ultrasound during pregnancy.
Authors: David James, Peter Twining, MartinJ. Whittle, Roland Zimmermann, Gundula Hebisch, Renate Huch, Albert Huch, G.H.A. Visser, J.I.P. de Vries, Ejh Mulder, IaP Ververs, H.P. van Geijn, JohnP. Newnham, SharonF. Evans, ConA. Michael, FionaJ. Stanley, LouisI. Landau
Journal: The Lancet (1993)
Preexposure Prophylaxis for HIV Infection among African Women
Authors: Lut Van Damme, Amy Corneli, Khatija Ahmed, Kawango Agot, Johan Lombaard, Saidi Kapiga, Mookho Malahleha, Fredrick Owino, Rachel Manongi, Jacob Onyango, Lucky Temu, Modie Constance Monedi, Paul Mak'Oketch, Mankalimeng Makanda, Ilse Reblin, Shumani Elsie Makatu, Lisa Saylor, Haddie Kiernan, Stella Kirkendale, Christina Wong, Robert Grant, Angela Kashuba, Kavita Nanda, Justin Mandala, Katrien Fransen, Jennifer Deese, Tania Crucitti, Timothy D. Mastro, Douglas Taylor
Journal: New England Journal of Medicine (2012)

Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus (HIV) infection in some trials but not in others.In this randomized, double-blind, placebo-controlled trial, we assigned 2120 HIV-negative women in Kenya, South Africa, and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or placebo once daily. The primary objective was to assess the effectiveness of TDF-FTC in preventing HIV acquisition and to evaluate safety.HIV infections occurred in 33 women in the TDF-FTC group (incidence rate, 4.7 per 100 person-years) and in 35 in the placebo group (incidence rate, 5.0 per 100 person-years), for an estimated hazard ratio in the TDF-FTC group of 0.94 (95% confidence interval, 0.59 to 1.52; P=0.81). The proportions of women with nausea, vomiting, or elevated alanine aminotransferase levels were significantly higher in the TDF-FTC group (P=0.04, P<0.001, and P=0.03, respectively). Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF-FTC group (4.7%) than in the placebo group (3.0%, P=0.051). Less than 40% of the HIV-uninfected women in the TDF-FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion. The study was stopped early, on April 18, 2011, because of lack of efficacy.Prophylaxis with TDF-FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects, as compared with placebo. Despite substantial counseling efforts, drug adherence appeared to be low. (Supported by the U.S. Agency for International Development and others; FEM-PrEP ClinicalTrials.gov number, NCT00625404.).
Mast Cell–Mediated Stimulation of Angiogenesis
Authors: Igor Feoktistov, Sergey Ryzhov, Anna E. Goldstein, Italo Biaggioni
Journal: Circulation Research (2003)

Adenosine is released during tissue injury, ischemia and tumor growth, and promotes angiogenesis. Because mast cells accumulate in the proximity of new blood vessel development, we examined if they may contribute to adenosine-induced angiogenesis. We found that HMC-1 human mast cells express A2A, A2B, and A3 adenosine receptors. The adenosine agonist NECA (100 micromol/L) increased interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and angiopoietin-2 mRNA expression. NECA-induced secretion of IL-8 and VEGF was verified by ELISA. A2B receptors mediate VEGF and IL-8 secretion because neither CGS21680 (selective A2A agonist) nor IB-MECA (selective A3 agonist) produced this effect, and it was inhibited by the selective A2B antagonist IPDX but not by the selective A2A antagonist SCH58261 or the selective A3 antagonist MRS1191. In contrast, the selective A3 agonist IB-MECA (EC50 1 nmol/L) stimulated angiopoietin-2 expression. Conditioned media from NECA-activated HMC-1 stimulated human umbilical vein endothelial cell proliferation and migration, and induced capillary tube formation. Capillary formation induced by mast cell-conditioned media was maximal if both HMC-1 A2B and A3 receptors were activated, whereas activation of A2B receptor alone was less effective. Thus, adenosine A2B and A3 receptors act in a functional cooperative fashion to promote angiogenesis by a paracrine mechanism involving the differential expression and secretion of angiogenic factors from human mast cells.
Evidence That the Human X Chromosome Is Enriched for Male-Specific but not Female-Specific Genes
Authors: M. J. Lercher
Journal: Molecular Biology and Evolution (2003)

There is increasing evidence that X chromosomes have an unusual complement of genes, especially genes that have sex-specific expression. However, whereas in worm and fly the X chromosome has a dearth of male-specific genes, in mice genes that are uniquely expressed in spermatogonia are especially abundant on the X chromosome. Is this latter enrichment true for nongermline, male-specific genes in mammals, and is it found also for female-specific genes? Here, using SAGE data, we show (1) that tissue-specific genes tend to be more abundant on the human X chromosome, (2) that, controlling for this effect, genes expressed exclusively in prostate are enriched on the human X chromosome, and (3) that genes expressed exclusively in mammary gland and ovary are not so enriched. This we propose is consistent with Rice's model of the evolution of sexually antagonistic alleles.
VEGF: a critical player in neurodegeneration
Authors: Erik Storkebaum, Peter Carmeliet
Journal: Journal of Clinical Investigation (2004)

VEGF is a prototype angiogenic factor, but recent evidence indicates that this growth factor also has direct effects on neural cells. Abnormal regulation of VEGF expression has now been implicated in several neurodegenerative disorders, including motoneuron degeneration. This has stimulated an increasing interest in assessing the therapeutic potential of VEGF as a neuroprotective agent for such neurodegenerative disorders.
Occult hepatitis B infection in blood donors from South East Asia: molecular characterisation and potential mechanisms of occurrence
Authors: Daniel Candotti, C Kit Lin, Dalila Belkhiri, Tasanee Sakuldamrongpanich, Subhajit Biswas, Sujen Lin, Diana Teo, Yasmin Ayob, Jean-Pierre Allain
Journal: Gut (2012)

To investigate the molecular basis of occult hepatitis B virus (HBV) infection (OBI) in Asian blood donors.OBI donors from Hong Kong, Malaysia, Singapore, Taiwan and Thailand were tested for HBV serological markers, and strains were molecularly characterised.Among 138 confirmed OBI carriers (median age 47 years), HBV genotypes B and C were dominant (60% and 34%, respectively) in agreement with the genotype distribution in chronically infected donors in the region. Viral load ranged between unquantifiable and 3670 IU/ml (median 11 IU/ml). Eleven per cent of OBIs showed an unusual anti-HBs-only serological profile without evidence of past vaccination for most of these individuals. Occult HBV strains showed a higher genetic diversity than strains from matched hepatitis B surface antigen (HBsAg)+ donors, irrespective of genotype. No unique genetic signature or evidence of reduced replication competence was found. Mutations in the vicinity of the pre-S2/S splice donor site were common in OBI(B) (44%) and OBI(C) (36%) strains. S regions from four OBI cases were transfected in HuH7 cells. Results showed limited HBsAg secretion and suggested that mutations disrupting the splice donor site structure may affect pre-S2/S mRNA splicing.There is indirect evidence that incomplete immune control is involved in the occurrence of OBI in Asian blood donors infected with genotypes B and C as observed in Europe with genotype A2 but to a lower extent than with genotype D. A post-transcriptional mechanism may play a role in HBsAg expression in some OBIs irrespective of HBV genotype.
The Role of Body-on-a-Chip Devices in Drug and Toxicity Studies
Authors: M.B. Esch, T.L. King, M.L. Shuler
Journal: Annual Review of Biomedical Engineering (2011)

High-quality, in vitro screening tools are essential in identifying promising compounds during drug development. Tests with currently used cell-based assays provide an indication of a compound's potential therapeutic benefits to the target tissue, but not to the whole body. Data obtained with animal models often cannot be extrapolated to humans. Multicompartment microfluidic-based devices, particularly those that are physical representations of physiologically based pharmacokinetic (PBPK) models, may contribute to improving the drug development process. These scaled-down devices, termed micro cell culture analogs (μCCAs) or body-on-a-chip devices, can simulate multitissue interactions under near-physiological fluid flow conditions and with realistic tissue-to-tissue size ratios. Because the device can be used with both animal and human cells, it can facilitate cross-species extrapolation. Used in conjunction with PBPK models, the devices permit an estimation of effective concentrations that can be used for studies with animal models or predict the human response. The devices also provide a means for relatively high-throughput screening of drug combinations and, when utilized with a patient's tissue sample, an opportunity for individualized medicine. Here we review efforts made toward the development of microfabricated cell culture systems and give examples that demonstrate their potential use in drug development, such as identifying synergistic drug interactions as well as simulating multiorgan metabolic interactions. In addition to their use in drug development, the devices also can be used to estimate the toxicity of chemicals as occupational hazards and environmental contaminants.
The Origin and Evolution of Porcine Reproductive and Respiratory Syndrome Viruses
Authors: Kousuke Hanada, Yoshiyuki Suzuki, Takashi Nakane, Osamu Hirose, Takashi Gojobori
Journal: Molecular Biology and Evolution (2005)

Porcine reproductive and respiratory syndrome viruses (PRRSV) are divided into North American and European types, which show about 40% difference in their amino acid sequences. The divergence time of these two types has been estimated to be about 1980 from epidemiological data. This suggested that PRRSV have evolved at a higher evolutionary rate (order of 10−2/site/year) compared with other RNA viruses of 10−3 to 10−5/site/year. Here, to test the evolutionary history of PRRSV speculated by the epidemiological background, we estimated the divergence time and evolutionary rate of PRRSV with molecular evolutionary analysis. Estimated divergence time (1972–1988) corresponded well to that estimated by the epidemiological data, and the evolutionary rate (4.71–9.8) × 10−2 of PRRSV was indeed the highest among RNA viruses so far reported. Furthermore, we inferred important sites for the adaptation in order to examine how PRRSV have adapted to swine since they emerged. The adaptive sites were located not only in the epitopes related to immunity but also in the transmembrane regions including a signal peptide. In particular, the adaptive sites in the transmembrane regions were considered to affect compatibility to the host cell membrane. We conclude that PRRSV were transmitted from another host species to swine in about 1980 and have adapted to swine by altering the transmembrane regions.
Precision of 3.0 Tesla quantitative magnetic resonance imaging of cartilage morphology in a multicentre clinical trial
Authors: F Eckstein, R J Buck, D Burstein, H C Charles, J Crim, M Hudelmaier, D J Hunter, G Hutchins, C Jackson, V B. Kraus, N E Lane, T M Link, L S Majumdar, S Mazzuca, P V Prasad, T J Schnitzer, M S Taljanovic, A Vaz, B Wyman, M-P H. Le Graverand
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> Quantitative MRI (qMRI) of cartilage morphology is a promising tool for disease-modifying osteoarthritis drug (DMOAD) development. Recent studies at single sites have indicated that measurements at 3.0 Tesla (T) are more reproducible (precise) than those at 1.5 T. Precision errors and stability in multicentre studies with imaging equipment from various vendors have, however, not yet been evaluated. <h3>Methods:</h3> A total of 158 female participants (97 Kellgren and Lawrence grade (KLG) 0, 31 KLG 2 and 30 KLG 3) were imaged at 7 clinical centres using Siemens Magnetom Trio and GE Signa Excite magnets. Double oblique coronal acquisitions were obtained at baseline and at 3 months, using water excitation spoiled gradient echo sequences (1.0×0.31×0.31 mm<sup>3</sup> resolution). Segmentation of femorotibial cartilage morphology was performed using proprietary software (Chondrometrics GmbH, Ainring, Germany). <h3>Results:</h3> The precision error (root mean square coefficient of variation (RMS CV)%) for cartilage thickness/volume measurements ranged from 2.1%/2.4% (medial tibia) to 2.9%/3.3% (lateral weight-bearing femoral condyle) across all participants. No significant differences in precision errors were observed between KLGs, imaging sites, or scanner manufacturers/types. Mean differences between baseline and 3 months ranged from &lt;0.1% (non-significant) in the medial to 0.94% (p&lt;0.01) in the lateral femorotibial compartment, and were 0.33% (p&lt;0.02) for the total femorotibial subchondral bone area. <h3>Conclusions:</h3> qMRI performed at 3.0 T provides highly reproducible measurements of cartilage morphology in multicentre clinical trials with equipment from different vendors. The technology thus appears sufficiently robust to be recommended for large-scale multicentre trials.
Abstract 2513: Anti-tumor therapeutic effects in mice treated with Listeria monocytogenes (Lm)-LLO immunotherapy in combination with PD-L1
Authors: Poonam Molli, Anu Wallecha
Journal: Cancer Research (2015)

Abstract Published reports have shown that Listeria monocytogenes (Lm) LLO immunotherapies can be combined with different cytotoxic modalities such as radiation, chemotherapy or immunotherapy for treatment of cancer. In a recent study, the combination of Lm-LLO immunotherapy (ADXS11-001) with an anti-PD-1 antibody significantly inhibited tumor growth and prolonged survival in animals. The combined treatment significantly increased the generation of antigen-specific immune responses in the periphery, and the infiltration of CD8 T cells into the tumor. These findings demonstrated that Lm-LLO immunotherapy combined with blocking of the PD-1/PD-L1 interaction was a feasible approach. The expression of PD-L1 by tumor cells serves as a protective function that can lead to suppression of tumor-infiltrating effector lymphocytes, thus allowing tumors to escape immune surveillance. We hypothesized that the combination of an Lm-LLO immunotherapy with an anti-PD-L1 antibody may potentially increase the therapeutic efficacy of either single agent alone and may be translatable to the clinical setting. To evaluate this hypothesis, a tumor regression study was initiated in a mouse model where established tumors were treated with ADXS11-001, PD-L1 antibody or combination ADXS11-001/PD-L1 antibody and tumor growth was monitored. In addition to tumor regression, serum samples were collected at different timepoints post-treatment to evaluate the changes in expression of various cytokines and chemokines using mouse inflammation map (Myriad RBM). The initial results indicated that the combination of ADXS11-001 and PD-L1 was better at controlling tumor growth kinetics than the single agent treatments. Serum cytokine analysis indicated treatment-related differences in the kinetics of cytokines and chemokines induced after single agent or combination treatments during different days of the study. Currently, we are evaluating the anti-tumor effects and immune responses generated in the periphery as well as in the tumor microenvironment. The results of this study will provide further insight as to the anti-tumor potential of combination of Lm-LLO immunotherapies with PD-1/PD-L1 specific antibodies. Citation Format: Poonam Molli, Anu Wallecha. Anti-tumor therapeutic effects in mice treated with Listeria monocytogenes (Lm)-LLO immunotherapy in combination with PD-L1. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2513. doi:10.1158/1538-7445.AM2015-2513
ROENTGEN RAY INTOXICATION
Authors: S. L. Warren, G. H. Whipple
Journal: The Journal of Experimental Medicine (1922)

Roentgen radiation of the thorax (abdomen shielded) in dogs, even with large doses (up to 512 milliampere minutes), gives no clinical evidence of intoxication. There may be a transient leucopenia and a slight rise in urinary nitrogen. Roentgen radiation of the abdomen (thorax shielded) in dogs, with a dose of 350 milliampere minutes, will almost certainly cause a fatal intoxication. Smaller doses may be survived but usually with signs of gastrointestinal intoxication. This lethal intoxication due to abdominal radiation presents a remarkably uniform clinical and anatomical picture. There is a latent period of 24 to 36 hours, during which the dog is perfectly normal clinically. The 2nd day usually shows the beginning of diarrhea and perhaps some vomitus. The 3rd and 4th days show progressive intoxication with increasing vomiting and bloody diarrhea until the dog becomes stuporous. Death is almost always on the 4th day. Anatomically the only lesions of significance are to be found in the small intestine. The epithelium of the crypts and villi shows more or less complete necrosis, and this condition may involve almost all of the small intestine. The epithelium may vanish completely except for a few cells here and there which have escaped and are often found in mitosis, probably an effort at repair and regeneration. We are forced to the conclusion that this remarkable injury of the epithelium of the small intestine is responsible for the various abnormal reactions and final lethal intoxication which follow a unit dose of Roentgen radiation over the abdomen of a normal dog. This sensitiveness of the intestinal epithelium to x-rays is not appreciated and should be given proper consideration in clinical work.
Immunophenotypic studies in cutaneous T-cell lymphomas: clinical implications
Authors: E. RALFKIAER, A. WOLLF-SNEEDORFF, K. THOMSEN, G.L. VEJLSGAARD
Journal: British Journal of Dermatology (1993)

Examination of biopsies from 62 patients with, or suspected of having cutaneous T-cell lymphoma (CTCL) revealed 24 cases in which the neoplastic cells expressed aberrant or suppressor T-cell phenotypes. The clinical records of these patients were reviewed in an attempt to establish whether recognition of these phenotypes has any clinical implications. Twelve patients had mycosis fungoides (MF) with plaques (n = 4) or tumours (n = 8), four had Sézary syndrome, and eight had large-cell lymphomas of pleomorphic (n = 6) or anaplastic subtype (n = 2). Most of the large-cell lymphomas behaved aggressively, as might have been expected from their cytological appearance. Aggressive courses were also seen in Sézary syndrome, and in tumour lesions of MF, whereas the behaviour in cases of plaque lesions was indolent. Again, this might have been anticipated from the clinical staging and routine histological examination. It is suggested that the expression of aberrant or suppressor T-cell phenotypes in CTCL is not of independent prognostic significance, but that the stage and histology are more important. This issue is an important topic for a prospective analysis.
Metronomic Chemotherapy Enhances Antitumor Effects of Cancer Vaccine by Depleting Regulatory T Lymphocytes and Inhibiting Tumor Angiogenesis
Authors: Chi-An Chen, Chih-Ming Ho, Ming-Cheng Chang, Wei-Zun Sun, Yu-Li Chen, Ying-Cheng Chiang, Ming-Hong Syu, Chang-Yao Hsieh, Wen-Fang Cheng
Journal: Molecular Therapy (2010)

Although cancer vaccines are emerging as innovative methods for cancer treatment, these alone have limited potential for treating measurable tumor burden. Thus, the importance of identifying anticancer strategies with greater potency is necessary. The chimeric DNA vaccine CTGF/E7 (connective tissue growth factor linked to the tumor antigen human papillomavirus 16 E7) generates potent E7-specific immunity and antitumor effects. We tested immune-modulating doses of chemotherapy in combination with the CTGF/E7 DNA vaccine to treat existing tumors in mice. Metronomic low doses of paclitaxel, not the maximal tolerable dose, are synergistic with the antigen-specific DNA vaccine. Paclitaxel, given in metronomic sequence with the CTGF/E7 DNA vaccine enhanced the vaccine's potential to delay tumor growth and decreased metastatic tumors in vivo better than the CTGF/E7 DNA vaccine alone. The two possible mechanisms of metronomic paclitaxel chemotherapy are the depletion of regulatory T cells and the inhibition of tumor angiogenesis rather than direct cancer cell cytolytic effects. Results indicate that combination treatment of metronomic chemotherapy and antigen-specific DNA vaccine can induce more potent antigen-specific immune responses and antitumor effects. This provides an immunologic basis for further testing in cancer patients. Although cancer vaccines are emerging as innovative methods for cancer treatment, these alone have limited potential for treating measurable tumor burden. Thus, the importance of identifying anticancer strategies with greater potency is necessary. The chimeric DNA vaccine CTGF/E7 (connective tissue growth factor linked to the tumor antigen human papillomavirus 16 E7) generates potent E7-specific immunity and antitumor effects. We tested immune-modulating doses of chemotherapy in combination with the CTGF/E7 DNA vaccine to treat existing tumors in mice. Metronomic low doses of paclitaxel, not the maximal tolerable dose, are synergistic with the antigen-specific DNA vaccine. Paclitaxel, given in metronomic sequence with the CTGF/E7 DNA vaccine enhanced the vaccine's potential to delay tumor growth and decreased metastatic tumors in vivo better than the CTGF/E7 DNA vaccine alone. The two possible mechanisms of metronomic paclitaxel chemotherapy are the depletion of regulatory T cells and the inhibition of tumor angiogenesis rather than direct cancer cell cytolytic effects. Results indicate that combination treatment of metronomic chemotherapy and antigen-specific DNA vaccine can induce more potent antigen-specific immune responses and antitumor effects. This provides an immunologic basis for further testing in cancer patients.
IS SPOTTY CALCIFICATION REVEALED BY GRAY SCALE INTRAVASCULAR ULTRASOUND REALLY VULNERABLE? A VIRTUAL HISTOLOGY INTRAVASCULAR ULTRASOUND STUDY
Authors: Hideo Amano, Kenji Wagatsuma, Mikihito Toda, Hideo Nii, Yasuto Uchida, Jyunichi Yamazaki
Journal: Journal of the American College of Cardiology (2010)