tbuckley/cabot-search huggingface dataset:
T Cell-Mediated Autoimmune Disease Due to Low-Affinity Crossreactivity to Common Microbial Peptides
Authors: Maria Harkiolaki, Samantha L. Holmes, Pia Svendsen, Jon W. Gregersen, Lise T. Jensen, Roisin McMahon, Manuel A. Friese, Gijs van Boxel, Ruth Etzensperger, John S. Tzartos, Kamil Kranc, Sarah Sainsbury, Karl Harlos, Elizabeth D. Mellins, Jackie Palace, Margaret M. Esiri, P. Anton van der Merwe, E. Yvonne Jones, Lars Fugger
Journal: Immunity (2009)
Pneumococcal meningitis and endophthalmitis in a newborn
Authors: M. I. Weintraub
Journal: JAMA (1972)

To the Editor.—  Keyes et al recently reported an association between meningococcemia and endocervical infection in two patients and remarked on the uniqueness of this association. 1 We encountered a case in which a relatively asymptomatic pneumococcal infection of the endocervical area of a mother led to fatal pneumococcal meningitis in a live born infant who remained asymptomatic until 5 days of age.  Report of a Case.—  A 5-day-old female infant was born at term via low forceps delivery to a 23-year-old primigravida who had had an uneventful pregnancy except for mild preeclampsia. The child, with an initial apgar core of 3, required suction and oxygen, but within five minutes the respirations were normal. She received silver nitrate prophylaxis to the eyes, and on day 4 the child was discharged as a healthy newborn. The mother was disturbed by the foul odor of the vaginal discharge, but was afebrile and
Trauma with Progressive Muscular Atrophy
Authors: G. E. F. Sutton
Journal: BMJ (1938)

We know little indeed about the aetiology of progressive muscular atrophy, but its association with trauma in a small percentage of cases has been described by eminent Continental neurologists during the past decade.Thus Alajouanine, Gopcevitch, and Meillaud (1930) gave an account of an interesting case of post-traumatic muscular atrophy, with an illuminating discussion on the subject.These authors divide such atrophies into different groups.
HCV Activates Protein Kinase R and Attenuates Interferon-Induced MHC Class I Expression to Circumvent CD8+ T-Cell Responses
Authors: Wonseok Kang, P.S. Sung, S.-H. Park, S. Yoon, D.-Y. Chang, S. Kim, K.H. Han, J.K. Kim, B. Rehermann, Y.-J. Chwae, E.-C. Shin
Journal: Clinical Gastroenterology and Hepatology (2014)
Fibroblast Growth Factor 2 Restrains Ras-Driven Proliferation of Malignant Cells by Triggering RhoA-Mediated Senescence
Authors: Érico T. Costa, Fábio L. Forti, Tatiana G.F. Matos, Alexandre Dermargos, Fábio Nakano, Jacqueline Salotti, Kátia M. Rocha, Paula F. Asprino, Celina K. Yoshihara, Marianna M. Koga, Hugo A. Armelin
Journal: Cancer Research (2008)

Abstract Fibroblast growth factor 2 (FGF2) is considered to be a bona fide oncogenic factor, although results from our group and others call this into question. Here, we report that exogenous recombinant FGF2 irreversibly inhibits proliferation by inducing senescence in Ras-dependent malignant mouse cells, but not in immortalized nontumorigenic cell lines. We report the following findings in K-Ras–dependent malignant Y1 adrenocortical cells and H-Ras V12–transformed BALB-3T3 fibroblasts: (a) FGF2 inhibits clonal growth and tumor onset in nude and immunocompetent BALB/c mice, (b) FGF2 irreversibly blocks the cell cycle, and (c) FGF2 induces the senescence-associated β-galactosidase with no accompanying signs of apoptosis or necrosis. The tyrosine kinase inhibitor PD173074 completely protected malignant cells from FGF2. In Y1 adrenal cells, reducing the constitutively high levels of K-Ras-GTP using the dominant-negative RasN17 mutant made cells resistant to FGF2 cytotoxicity. In addition, transfection of the dominant-negative RhoA-N19 into either Y1 or 3T3-B61 malignant cell lines yielded stable clonal transfectants that were unable to activate RhoA and were resistant to the FGF2 stress response. We conclude that in Ras-dependent malignant cells, FGF2 interacts with its cognate receptors to trigger a senescence-like process involving RhoA-GTP. Surprisingly, attempts to select FGF2-resistant cells from the Y1 and 3T3-B61 cell lines yielded only rare clones that (a) had lost the overexpressed ras oncogene, (b) were dependent on FGF2 for proliferation, and (c) were poorly tumorigenic. Thus, FGF2 exerted a strong negative selection that Ras-dependent malignant cells could rarely overcome. [Cancer Res 2008;68(15):6215–23]
Suppression of silent ischemia by metoprolol without alteration of morning increase of platelet aggregability in patients with stable coronary artery disease.
Authors: S N Willich, S Pohjola-Sintonen, S J Bhatia, T L Shook, G H Tofler, J E Muller, D G Curtis, G H Williams, P H Stone
Journal: Circulation (1989)

To determine the effect of metoprolol on silent ischemia and platelet aggregability, 10 patients with coronary artery disease were studied with a randomized, double-blind, placebo-controlled, crossover trial. Patients were treated with metoprolol (200 mg b.i.d.) or placebo for 1 week and then received the alternate therapy. Two days before the end of each treatment period, platelet aggregability was studied for 24 hours, and a 48-hour ambulatory electrocardiogram was obtained. Compared with placebo, metoprolol significantly decreased the total number (from 26 to 4, p less than 0.1) and duration (from 735 to 84 minutes, p less than 0.01) of silent ischemic episodes. This decrease was accompanied by a decrease in the mean blood pressure (from 127/81 to 118/71 mm Hg, p less than 0.01) and the mean heart rate (from 70 to 54 beats/min, p less than 0.01). The incidence of silent ischemic episodes in the morning was significantly higher in untreated patients than in treated patients. The few episodes observed during metoprolol treatment occurred at the same time as the peak incidence observed during placebo treatment. During placebo treatment, platelet aggregability increased from 6:00 to 9:00 AM as reflected by a decrease in the threshold concentrations of ADP and epinephrine required to induce biphasic platelet aggregation (from 4.8 +/- 0.8 to 2.6 +/- 0.4 microM, p less than 0.02; and from 7.3 +/- 2.3 to 1.8 +/- 0.9 microM, respectively, p less than 0.02). Metoprolol did not alter the basal level nor blunt the morning increase of platelet aggregability.(ABSTRACT TRUNCATED AT 250 WORDS)
Evaluation of the American Stop Smoking Intervention Study (ASSIST): A Report of Outcomes
Authors: F. A. Stillman
Journal: JNCI Journal of the National Cancer Institute (2003)

The National Cancer Institute funded an 8-year, nonrandomized demonstration project for tobacco prevention and control, the American Stop Smoking Intervention Study (ASSIST). To evaluate ASSIST, we compared changes in adult smoking prevalence, per capita cigarette consumption, and tobacco control policies between the 17 ASSIST states and the 33 non-ASSIST states and the District of Columbia.The strength of tobacco control index was used to measure state-level program elements directed at tobacco control, and the initial outcomes index (IOI) was used to measure states' tobacco control policy outcomes. Prevalence data were obtained from the Tobacco Use Supplement to the Current Population Survey, and consumption data were obtained from the Tobacco Institute's bimonthly sales figures for cigarette packs moved from wholesale warehouses. Two-stage regression and mixed-effects linear modeling were used to analyze the various outcomes. Statistical analyses for testing individual regression coefficients were one-sided.ASSIST states had a greater decrease in adult smoking prevalence than non-ASSIST states, with an adjusted difference of -0.63% (P =.049). Per capita cigarette consumption was not statistically significantly different between ASSIST and non-ASSIST states. However, an increase in the IOI of a state from the 25th to the 75th percentile was associated with a reduction in per capita cigarette consumption by 0.57 packs per person per month. State IOI was also inversely, albeit not statistically significantly, associated with smoking prevalence (regression coefficient = -0.11;P =.06).The reduction in adult smoking prevalence associated with ASSIST could have translated into approximately 278 700 fewer smokers nationwide if all states had implemented ASSIST. Investment in building state-level tobacco control capacity and promoting changes in tobacco control policies are effective strategies for reducing tobacco use.
Correlation of Cytotoxicity With Elimination of lodine-125 From Nude Mice Inoculated With Prelabeled Human Melanoma Cells2
Authors: Arnold Lockshin, Beppino C. Giovanella, Carlos Quian, John T. Mendoza, Dana M. Vardeman, John S. Stehlin
Journal: JNCI Journal of the National Cancer Institute (1984)

BRO human melanoma cells were prelabeled in vitro with [125I]5-iodo-2′-deoxyuridine ([125I]Idllrd) and inoculated into NIH-II nude mice ip, im, sc, or iv. Saline or diphtheria toxin (DT), which is selectively toxic to human cells compared to those of mice, was injected, and the loss of 125I from the animals was monitored daily with a whole-body gamma scintillation detector. For most of the inoculation sites DT accelerated the rate of 125I excretion and in all cases was cytotoxic for the inoculated cells as determined by host survival or measurement of visible tumor growth. Differences between the rates of 125I loss for DT-treated mice compared to untreated mice were most evident for cells inoculated ip or im. These results indicate that [125I]ldUrd prelabeling of human tumor cells inoculated in nude mice offers a rapid method for determination of cytotoxicity in vivo.
Modulation of Telomerase Promoter Tumor Selectivity in the Context of Oncolytic Adenoviruses
Authors: Alan E. Bilsland, Andrew Merron, Georges Vassaux, W. Nicol Keith
Journal: Cancer Research (2007)

Abstract The telomerase RNA (hTR) and reverse transcriptase (hTERT) promoters are active in most cancer cells, but not in normal cells, and are useful for transcriptional targeting in gene therapy models. Telomerase-specific conditionally replicating adenoviruses (CRAd) are attractive vectors because they should selectively lyse tumor cells. Here, we compare CRAds, in which either the hTR or hTERT promoter controls expression of the adenovirus E1A gene. In replication-defective reporter adenoviruses, the hTR promoter was up to 57-fold stronger in cancer cells than normal cells and up to 49-fold stronger than hTERT. In normal cells, hTERT promoter activity was essentially absent. Doses of telomerase-specific CRAds between 1.8 and 28 infectious units per cell efficiently killed cancer cells, but normal cells required higher doses. However, CRAd DNA replication and E1A expression were detected in both cancer and normal cells. Overall, tumor specificity of the CRAds was limited compared with nonreplicating vectors. Surprisingly, both CRAds expressed similar E1A levels and functional behavior, despite known differentials between hTR and hTERT promoter activities, suggesting that the promoters are deregulated. Rapid amplification of cDNA ends analysis of hTR-/hTERT-E1A transcripts ruled out cryptic transcription from the vector backbone. Blocking E1A translation partially restored the hTR-/hTERT-E1A mRNA differential, evidencing feedback regulation by E1A. [Cancer Res 2007;67(3):1299–307]
Anterior segment optical coherence tomography
Authors: Marcus Ang, Mani Baskaran, René M. Werkmeister, Jacqueline Chua, Doreen Schmidl, Valentin Aranha dos Santos, Gerhard Garhöfer, Jodhbir S. Mehta, Leopold Schmetterer
Journal: Progress in Retinal and Eye Research (2018)

Optical coherence tomography (OCT) provides non-contact, rapid in vivo imaging of ocular structures, and has become a key part of evaluating the anterior segment of the eye. Over the years, improvements to technology have increased the speed of capture and resolution of images, leading to the increasing impact of anterior segment OCT imaging on clinical practice. In this review, we summarize the historical development of anterior segment OCT, and provide an update on the research and clinical applications of imaging the ocular surface, cornea, anterior chamber structures, aqueous outflow system, and most recently anterior segment vessels. We also describe advancements in anterior segment OCT technology that have improved understanding with greater detail, such as tear film in dry eye disease evaluation, intra-operative real-time imaging for anterior segment surgery, and aqueous outflow with angle assessment for glaucoma. Improvements to image processing and software have also improved the ease and utility of interpreting anterior segment OCT images in everyday clinical practice. Future developments include refinement of assessing vascular networks for the anterior segment, in vivo ultra-high resolution anterior segment optical coherence tomography with histology-like detail, en-face image with 3-dimensional reconstruction as well as functional extensions of the technique.
Lysolecithin: A factor in the pathogenesis of gastric ulceration?
Authors: A. G. Johnson, S. J. McDermott
Journal: Gut (1974)

Lysolecithin is formed when pancreatic juice and bile mix in the duodenum. Lysolecithin concentrations have been measured in intermittent samples of night gastric juice from patients with gastric ulcers and duodenal ulcers and in normal controls. In gastric ulcer patients, the mean of the peak concentrations (444 μg/ml) and mean of concentrations in all samples (199 μg/ml) were significantly higher than in controls (34 μg/ml and 18 μg/ml respectively). Duodenal ulcer patients had normal or moderately raised values. The levels in gastric ulcer patients were as high as those which have been found experimentally to cause severe damage to the gastric mucosal barrier, and it is concluded that lysolecithin may be as important, or more important, than bile salts in the destruction of the gastric mucosal barrier and therefore in the aetiology of gastric ulcer.
Quality of Life, Physical Disability, and Respiratory Impairment in Duchenne Muscular Dystrophy
Authors: Malcolm Kohler, Christian F. Clarenbach, Lukas Böni, Thomas Brack, Erich W. Russi, Konrad E. Bloch
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Duchenne muscular dystrophy (DMD) leads to progressive, generalized paresis, and to respiratory failure in the second decade of life. The assumption that severe physical disability precludes an acceptable quality of life is common, but has not been specifically evaluated in DMD.The purpose of this study was to investigate the quality of life in relation to physical disability, pulmonary function, and the need for assisted ventilation in DMD.In 35 patients with DMD, aged 8-33 yr, we assessed physical disability by a score ranging from 9 (no disability) to 80 (complete dependence on care and technical aids), pulmonary function, and health-related quality of life by Short-Form 36 of the medical outcome questionnaire.All patients required a wheelchair and help for dressing and eating. Fourteen patients were on long-term noninvasive positive-pressure ventilation. In ventilated patients, mean +/- SD FVC was 12 +/- 10 % predicted, and the physical disability score was 65 +/- 7. Corresponding values in spontaneously breathing patients were 48 +/- 25 % predicted, and 51 +/- 7, respectively (p < 0.05 for both comparisons between groups). Short-Form 36 physical function scores were massively reduced in both groups (1 +/- 2, and 0 +/- 0, respectively), but vitality, role-emotional, social function, and mental health scores were nearly normal (67-98), and did not differ between groups.Quality of life in DMD is not correlated with physical impairment nor the need for noninvasive positive-pressure ventilation. The surprisingly high quality of life experienced by these severely disabled patients should be taken into consideration when therapeutic decisions are made.
Sentinel Lymph Node Biopsy for Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Joint Clinical Practice Guideline
Authors: Sandra L. Wong, Charles M. Balch, Patricia Hurley, Sanjiv S. Agarwala, Timothy J. Akhurst, Alistair Cochran, Janice N. Cormier, Mark Gorman, Theodore Y. Kim, Kelly M. McMasters, R. Dirk Noyes, Lynn M. Schuchter, Matias E. Valsecchi, Donald L. Weaver, Gary H. Lyman
Journal: Journal of Clinical Oncology (2012)

The American Society of Clinical Oncology (ASCO) and Society of Surgical Oncology (SSO) sought to provide an evidence-based guideline on the use of lymphatic mapping and sentinel lymph node (SLN) biopsy in staging patients with newly diagnosed melanoma.A comprehensive systematic review of the literature published from January 1990 through August 2011 was completed using MEDLINE and EMBASE. Abstracts from ASCO and SSO annual meetings were included in the evidence review. An Expert Panel was convened to review the evidence and develop guideline recommendations.Seventy-three studies met full eligibility criteria. The evidence review demonstrated that SLN biopsy is an acceptable method for lymph node staging of most patients with newly diagnosed melanoma.SLN biopsy is recommended for patients with intermediate-thickness melanomas (Breslow thickness, 1 to 4 mm) of any anatomic site; use of SLN biopsy in this population provides accurate staging. Although there are few studies focusing on patients with thick melanomas (T4; Breslow thickness, > 4 mm), SLN biopsy may be recommended for staging purposes and to facilitate regional disease control. There is insufficient evidence to support routine SLN biopsy for patients with thin melanomas (T1; Breslow thickness, < 1 mm), although it may be considered in selected patients with high-risk features when staging benefits outweigh risks of the procedure. Completion lymph node dissection (CLND) is recommended for all patients with a positive SLN biopsy and achieves good regional disease control. Whether CLND after a positive SLN biopsy improves survival is the subject of the ongoing Multicenter Selective Lymphadenectomy Trial II.
Hormonal stimulation of erythropoietin production and erythropoiesis in anephric sheep fetuses.
Authors: E D Zanjani, M Banisadre
Journal: Journal of Clinical Investigation (1979)

The effect of testosterone (DT) and thyroxin (L-T4) on erythropoiesis and erythropoietin (Ep) production was studied in control and nephrectomized sheep fetuses beginning at about 100 d of gestation. Fetuses were given injections of either 1.2 mg/d x 13 of L-T4, 12 mg, once every 5 d x 3 of DT or the vehicle alone. Fetal plasma samples for Ep determinations were obtained before and at intervals after the start of the treatment. Reticulocyte and hematocrit levels, and the percent erythrocyte-59Fe uptake values were used to assess erythropoiesis in each fetus. No Ep was detected in plasmas of control fetuses, while significant amounts of Ep were present in plasma obtained from DT- and L-T4-treated intact fetuses. Bilateral nephrectomy did not diminish the Ep response to DT and L-T4. In both intact and nephrectomized fetuses, treatment with DT resulted in the production of significantly greater amounts of Ep than L-T4. The rise in Ep in all groups was accompanied by increases in reticulocytes (2.2 +/- 0.2% vs L-T4:8.1 +/- 0.4% and DT:7.6 +/- 0.7%), percent erythrocyte-59Fe uptake (20.5 +/- 2.9% vs. L-T4:36.7 +/- 3.8% and DT:39.1 +/- 4.0%) and hematocrit (31.2 +/- 2% vs. L-T4:41.8 +/- 3% and DT:48.6 +/- 4.2%). The enhanced erythropoiesis in all groups of nephrectomized fetuses was dependent upon the presence of Ep, because the administration of anti-Ep to these fetuses resulted in the suppression of erythropoiesis in all three groups. These data demonstrate that (a) DT and L-T4 are effective promoters of extrarenal Ep production, thereby enhancing erythropoiesis in intact and nephrectomized fetuses; (b) DT is a stronger stimulus of extrarenal Ep formation than L-T4; and (c) Ep is required for the expression of the erythropoietic effects of L-T4 and DT.
CD47 in the Tumor Microenvironment Limits Cooperation between Antitumor T-cell Immunity and Radiotherapy
Authors: David R. Soto-Pantoja, Masaki Terabe, Arunima Ghosh, Lisa A. Ridnour, William G. DeGraff, David A. Wink, Jay A. Berzofsky, David D. Roberts
Journal: Cancer Research (2014)

Abstract Although significant advances in radiotherapy have increased its effectiveness in many cancer settings, general strategies to widen the therapeutic window between normal tissue toxicity and malignant tumor destruction would still offer great value. CD47 blockade has been found to confer radioprotection to normal tissues while enhancing tumor radiosensitivity. Here, we report that CD47 blockade directly enhances tumor immunosurveillance by CD8+ T cells. Combining CD47 blockade with irradiation did not affect fibrosarcoma growth in T cell–deficient mice, whereas adoptive transfer of tumor-specific CD8+ T cells restored combinatorial efficacy. Furthermore, ablation of CD8+ T cells abolished radiotherapeutic response in immunocompetent syngeneic hosts. CD47 blockade in either target cells or effector cells was sufficient to enhance antigen-dependent CD8+ CTL-mediated tumor cell killing in vitro. In CD47-deficient syngeneic hosts, engrafted B16 melanomas were 50% more sensitive to irradiation, establishing that CD47 expression in the microenvironment was sufficient to limit tumor radiosensitivity. Mechanistic investigations revealed increased tumor infiltration by cytotoxic CD8+ T cells in a CD47-deficient microenvironment, with an associated increase in T cell–dependent intratumoral expression of granzyme B. Correspondingly, an inverse correlation between CD8+ T-cell infiltration and CD47 expression was observed in human melanomas. Our findings establish that blocking CD47 in the context of radiotherapy enhances antitumor immunity by directly stimulating CD8+ cytotoxic T cells, with the potential to increase curative responses. Cancer Res; 74(23); 6771–83. ©2014 AACR.
Evaluation of Cancer Tests of 1,3-Butadiene Using Internal Dose, Genotoxic Potency, and a Multiplicative Risk Model
Authors: Charlotta Fred, Margareta Törnqvist, Fredrik Granath
Journal: Cancer Research (2008)

Abstract In cancer tests with 1,3-butadiene (BD), the mouse is much more sensitive than the rat. This is considered to be related to the metabolism of BD to the epoxide metabolites, 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane, and 1,2-epoxy-3,4-butanediol. This study evaluates whether the large difference in outcome in cancer tests with BD could be predicted quantitatively on the basis of the concentration over time in blood (AUC) of the epoxide metabolites, their mutagenic potency, and a multiplicative cancer risk model, which has earlier been used for ionizing radiation. Published data on hemoglobin adduct levels from inhalation experiments with BD were used for the estimation of the AUC of the epoxide metabolites in the cancer tests. The estimated AUC of the epoxides were then weighed together to a total genotoxic dose, by using the relative genotoxic potency of the respective epoxide inferred from in vitro hprt mutation assays using EB as standard. The tumor incidences predicted with the risk model on the basis of the total genotoxic dose correlated well with the earlier observed tumor incidences in the cancer tests. The total genotoxic dose that leads to a doubling of the tumor incidences was estimated to be the same in both species, 9 to 10 mmol/L×h EB-equivalents. The study validates the applicability of the multiplicative cancer risk model to genotoxic chemicals. Furthermore, according to this evaluation, different epoxide metabolites are predominating cancer-initiating agents in the cancer tests with BD, the diepoxide in the mouse, and the monoepoxides in the rat. [Cancer Res 2008;68(19):8014–21]