tbuckley/cabot-search huggingface dataset:
Inhibition of human endothelial cell proliferation by gold compounds.
Authors: T Matsubara, M Ziff
Journal: Journal of Clinical Investigation (1987)

Neovascularization has a role in the propagation of rheumatoid synovitis because the spread of mononuclear cell infiltration and the growth of pannus are dependent on the growth of new blood vessels. Growth of such vessels requires local endothelial cell (EC) proliferation. Inhibition of synovial EC proliferation, therefore, would have the potential to diminish rheumatoid inflammation. We have, therefore, studied the effects of gold sodium thiomalate (GST), auranofin, and gold chloride on the proliferation of human umbilical vein EC. GST suppressed both basal and EC growth factor-induced tritiated thymidine incorporation into EC in a dose-dependent fashion. Inhibition was observed with concentrations as low as 1 microgram/ml GST, 5 micrograms/ml gold chloride, and 0.1 microgram/ml auranofin, levels attainable in blood and synovium of patients. These results suggest that gold compounds have an antiangiogenic effect. The low concentrations inhibiting EC proliferation suggest that gold compounds may suppress rheumatoid synovitis by reducing the number of small blood vessels available for mononuclear cell infiltration and synovial tissue proliferation.
Single Injection of Naked Plasmid Encoding Hepatocyte Growth Factor Prevents Cell Death and Ameliorates Acute Renal Failure in Mice
Authors: Chunsun Dai, Junwei Yang, Youhua Liu
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Hepatocyte growth factor (HGF) is a pleiotrophic factor that plays an important role in tissue repair and regeneration after injury. The expression of both HGF and its c-met receptor genes is rapidly upregulated after acute renal injury induced by folic acid. In this study, the role of exogenous HGF in preventing acute renal failure by systemic administration of naked plasmid containing human HGF cDNA driven under the cytomegalovirus promoter (pCMV-HGF) was examined in mice. Intravenous injection of pCMV-HGF plasmid produced substantial levels of human HGF protein in mouse kidneys. Simultaneous injection of HGF plasmid DNA significantly ameliorated renal dysfunctions and accelerated recovery from the acute injury induced by folic acid. Of interest, preadministration of HGF plasmid 24 h before folic acid injection dramatically protected renal epithelial cells from both apoptotic and necrotic death and preserved the structural and functional integrity of renal tubules. Expression of HGF transgene activated protein kinase B/Akt kinase and preserved prosurvival Bcl-xL protein expression in vivo. These results indicate that a single, intravenous injection of naked plasmid containing HGF gene not only promotes renal regeneration after injury but also protects tubular epithelial cells from the initial injury and cell death in the first place. These data suggest that HGF gene therapy may provide a new avenue for exploring a novel therapeutic strategy for clinical acute renal failure.
Effect of Improved Glycemic Control on Health Care Costs and Utilization
Authors: E H Wagner, N Sandhu, K M Newton, D K McCulloch, S D Ramsey, L C Grothaus
Journal: JAMA (2001)

Because of the additional costs associated with improving diabetes management, there is interest in whether improved glycemic control leads to reductions in health care costs, and, if so, when such cost savings occur.To determine whether sustained improvements in hemoglobin A(1c) (HbA(1c)) levels among diabetic patients are followed by reductions in health care utilization and costs.Historical cohort study conducted in 1992-1997 in a staff-model health maintenance organization (HMO) in western Washington State.All diabetic patients aged 18 years or older who were continuously enrolled between January 1992 and March 1996 and had HbA(1c) measured at least once per year in 1992-1994 (n = 4744). Patients whose HbA(1c) decreased 1% or more between 1992 and 1993 and sustained the decline through 1994 were considered to be improved (n = 732). All others were classified as unimproved (n = 4012).Total health care costs, percentage hospitalized, and number of primary care and specialty visits among the improved vs unimproved cohorts in 1992-1997.Diabetic patients whose HbA(1c) measurements improved were similar demographically to those whose levels did not improve but had higher baseline HbA(1c) measurements (10.0% vs 7.7%; P<.001). Mean total health care costs were $685 to $950 less each year in the improved cohort for 1994 (P =.09), 1995 (P =.003), 1996 (P =.002), and 1997 (P =.01). Cost savings in the improved cohort were statistically significant only among those with the highest baseline HbA(1c) levels (>/=10%) for these years but appeared to be unaffected by presence of complications at baseline. Beginning in the year following improvement (1994), utilization was consistently lower in the improved cohort, reaching statistical significance for primary care visits in 1994 (P =.001), 1995 (P<.001), 1996 (P =.005), and 1997 (P =.004) and for specialty visits in 1997 (P =.02). Differences in hospitalization rates were not statistically significant in any year.Our data suggest that a sustained reduction in HbA(1c) level among adult diabetic patients is associated with significant cost savings within 1 to 2 years of improvement.
Clinical and serological differences between systemic lupus erythematosus patients with antibodies to Ro versus patients with antibodies to Ro and La.
Authors: C A Wasicek, M Reichlin
Journal: Journal of Clinical Investigation (1982)

Among 55 systemic lupus erythematosus patients having antibodies to Ro and/or La, two major groups were distinguished by titration of sera in counterimmunoelectrophoresis. The first group (30 patients) had antibodies to Ro alone. This was associated with a high incidence of antibodies to DNA (77%) and serious renal disease (53%). The second group (23 patients) had antibodies to Ro and La, and this was associated with a lower incidence of antibodies to DNA (30%) and a very low incidence of nephritis (9%). In this group a phenomenon of linkage of anti- Ro and anti-La titers was observed. Additionally two patients with only anti-La were found. Neither had clinically apparent renal disease. Thus, systemic lupus erythematosus patients with anti-Ro fall into two subgroups that differ considerably in their prevalence of anti-DNA and serious renal disease.
Generation of Tumor-associated Cytotoxic T Lymphocytes Requires Interleukin 4 from CD8+ T Cells
Authors: Thomas Schüler, Thomas Kammertoens, Susanne Preiss, Pierre Debs, Nancy Noben-Trauth, Thomas Blankenstein
Journal: The Journal of Experimental Medicine (2001)

Activation of tumor-associated CD8+ cytotoxic T lymphocytes (CTLs) often requires antigen representation, e.g., by dendritic cells (DCs), and CD4+ T cell help. Previously, we showed that CTL-mediated tumor immunity required interleukin 4 (IL-4) during the immunization but not effector phase. To determine the source and target cells of IL-4, we performed adoptive T cell transfers using CD4+ and CD8+ T cells from IL-4−/− and IL-4R−/− mice and analyzed CTL generation. Even though necessary for CTL generation, CD4+ T cells did not need to express IL-4 or IL-4R. Surprisingly, CTL generation required IL-4 but not IL-4R expression by CD8+ T cells. As IL-4 (a) was expressed by naive CD8+ T cells within 24 h after antigen encounter, (b) IL-4 induced DC maturation, and (c) CTL development was impaired in T cell–reconstituted IL-4R−/− mice, CD8+ T cell–derived IL-4 appears to act on DCs. We conclude that CD4+ and CD8+ T cells provide different signals for DC activation during CTL generation.
Phase II Trial of Ixabepilone, an Epothilone B Analog, in Patients With Metastatic Breast Cancer Previously Untreated With Taxanes
Authors: Neelima Denduluri, Jennifer A. Low, James J. Lee, Arlene W. Berman, Janice M. Walshe, Ujala Vatas, Catherine K. Chow, Seth M. Steinberg, Sherry X. Yang, Sandra M. Swain
Journal: Journal of Clinical Oncology (2007)

Ixabepilone is an epothilone B analog that binds to microtubules and results in microtubule stabilization and mitotic arrest. Ixabepilone was evaluated for efficacy and safety in a phase II clinical trial for women with metastatic breast cancer.Patients were eligible if they had not previously received treatment with a taxane and had measurable metastatic breast cancer. Ixabepilone was administered at 6 mg/m(2)/d intravenously days 1 through 5 every 3 weeks until unacceptable toxicity or disease progression. Patients underwent pretreatment and post-treatment tumor biopsies, and tissues were analyzed for acetylated alpha-tubulin, tau-1, and p53 expression when possible.Twenty-three patients received 210 cycles with a median of eight cycles (range, two to 22 cycles) per patient. Thirteen patients (57%; exact 95% CI, 34.5% to 76.8%) had partial responses, six patients (26%) had stable disease, and four patients (17%) had progressive disease. Median time to progression and duration of response were 5.5 and 5.6 months, respectively. Four patients required dose reductions for neutropenia, neuropathy, or fatigue. Grade 3 or 4 toxicities included neutropenia (22%), fatigue (13%), anorexia (9%), and motor neuropathy (4%). Thirty-nine percent of patients experienced grade 1, 13% experienced grade 2, and none experienced grade 3/4 sensory neuropathy. The six patients with paired biopsies all had increases in tumor alpha-tubulin acetylation after treatment. Baseline or cycle 2 acetylated alpha-tubulin, tau-1, or p53 expression did not correlate with clinical response.Women with metastatic breast cancer previously untreated with taxanes have a meaningful durable response to single-agent ixabepilone therapy. Minimal hematologic toxicity and no grade 3 sensory neuropathy were noted.
Abstract 4273: Circulating human prostate cancer cells from an orthotopic mouse model rapidly captured by immunomagnetic beads and imaged by GFP expression
Authors: Katarina Kolostova, Daniela Pinterova, Robert M. Hoffman, Vladimir Bobek
Journal: Cancer Research (2011)

Abstract Circulating tumor cells (CTC) are potential precursors of metastasis. They are also of use in diagnosing malignancy and for prognostic purposes. Our laboratory has previously isolated CTC from orthotopic nude mouse models of human prostate cancer cells where the PC-3 cancer cells express green fluorescent protein (GFP). It was found that only orthotopic tumors produced CTC and not subcutaneous tumors, which may explain why orthotopic tumors metastasize and subcutaneous tumors do not. However, in this previous study, CTC were observed only after culture. In the present study, using the GFP-expressing PC-3 orthotopic model and immunomagnetic beads coated with anti-EpCAM and anti-PSMA, GFP-expressing CTC were isolated within 15 minutes and were readily visualized by GFP fluorescence. The immunomagnetic-bead-captured GFP-expressing PC-3 CTC could be immediately placed in 3-dimensional sponge cell culture where they proliferated. The combination of GFP-expression and immunomagnetic beads is very powerful method to obtain CTC for either immediate analysis or for biological characterization in vivo or 3-dimensional culture. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4273. doi:10.1158/1538-7445.AM2011-4273
A Reiterative Method for Calculating the Early Bactericidal Activity of Antituberculosis Drugs
Authors: Stephen H. Gillespie, Roland D. Gosling, Bambos M. Charalambous
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Studies of early bactericidal activity (EBA) are important in the rapid evaluation of new antituberculosis drugs. Historically, these have concentrated on the log fall in the viable count in sputum during the first 48 hours of therapy. In this paper, we provide a mathematical model that suggests that the viable count in sputum follows an exponential decay curve with the equation V = S + Me−kt (where V is the viable count, M the population of bacteria susceptible to the test drug, S the population susceptible only to sterilizing agents, t the day of sputum collection as related to start of therapy, k the rate constant for the bacteria killed each day, and e the Napierian constant). We demonstrate that data from clinical trials fits the exponential decay model. We propose that future EBA studies should be performed by measuring daily quantitative counts for at least 5 days. We also propose that the comparison of the early bactericidal activity of antituberculosis drugs should be evaluated using the time taken to reduce the viable count by 50% (vt50). A further reiterative refinement following a rule set based on statistically the best fit to the exponential decay model is described that will allow investigators to identify anomalous results and thus enhance the accuracy in measuring early bactericidal activity.
Unrelated stem cell transplantation in multiple myeloma after a reduced-intensity conditioning with pretransplantation antithymocyte globulin is highly effective with low transplantation-related mortality
Authors: Nicolaus Kröger, Herbert Gottfried Sayer, Rainer Schwerdtfeger, Michael Kiehl, Arnon Nagler, Helmut Renges, Tatjana Zabelina, Boris Fehse, Francis Ayuk, Georg Wittkowsky, Norbert Schmitz, Axel Rolf Zander
Journal: Blood (2002)
Spontaneous near closure of coronary artery fistula.
Authors: S J Shubrooks, C Z Naggar
Journal: Circulation (1978)

An asymptomatic 14-year-old male was found at cardiac catheterization to have a coronary artery fistula involving a vessel originating from the left main coronary artery and terminating in the right heart. Chest X-ray and electrocardiogram were within normal limits and shunt flow was too small to be detected by oximetry although a large vessel was seen angiographically. One year later, the previously loud continuous murmur had disappeared and repeat catheterization demonstrated near closure of the fistula. This is the first report documenting the spontaneous closure of a coronary artery fistula.
A Hydrophobic Dye‐Encapsulated Nano‐Hybrid as an Efficient Fluorescent Probe for Living Cell Imaging
Authors: Shu Chang, Xumeng Wu, Yongsheng Li, Dechao Niu, Zhi Ma, Wenru Zhao, Jinlou Gu, Wenjie Dong, Feng Ding, Weihong Zhu, Jianlin Shi
Journal: Advanced Healthcare Materials (2012)

Water-soluble [email protected] ([email protected]) with extraordinarily enhanced fluorescent performance were fabricated by encapsulating the hydrophobic dye molecules into the core of the hybrid nanospheres based on the self-assembly of amphiphilic block copolymers followed by shell cross-linking using 3-mercaptopropyltrimethoxy-silane. The [email protected] are 50 nm in size, are monodispersed in aqueous solution and have a quantum yield enhanced by 30 times. Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Downregulation of E-Cadherin enhances proliferation of head and neck cancer through transcriptional regulation of EGFR
Authors: Dongsheng Wang, Ling Su, Donghai Huang, Hongzheng Zhang, Dong M Shin, Zhuo G Chen
Journal: Molecular Cancer (2011)

Epidermal growth factor receptor (EGFR) has been reported to downregulate E-cadherin (E-cad); however, whether the downregulation of E-cad has any effect on EGFR expression has not been elucidated. Our previous studies have found an inverse correlation between EGFR and E-cad expression in tissue specimens of squamous cell carcinoma of the head and neck (SCCHN). To understand the biological mechanisms underlying this clinical observation, we knocked down E-cad expression utilizing E-cad siRNA in four SCCHN cell lines.It was observed that downregulation of E-cad upregulated EGFR expression compared with control siRNA-transfected cells after 72 hours. Cellular membrane localization of EGFR was also increased. Consequently, downstream signaling molecules of the EGFR signaling pathway, p-AKT, and p-ERK, were increased at 72 hours after the transfection with E-cad siRNA. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed EGFR mRNA was upregulated by E-cad siRNA as early as 24 hours. In addition, RT-PCR revealed this upregulation was due to the increase of EGFR mRNA stability, but not protein stability. Sulforhodamine B (SRB) assay indicated growth of E-cad knocked down cells was enhanced up to 2-fold more than that of control siRNA-transfected cells at 72-hours post-transfection. The effect of E-cad reduction on cell proliferation was blocked by treating the E-cad siRNA-transfected cells with 1 μM of the EGFR-specific tyrosine kinase inhibitor erlotinib.Our results suggest for the first time that reduction of E-cad results in upregulation of EGFR transcriptionally. It also suggests that loss of E-cad may induce proliferation of SCCHN by activating EGFR and its downstream signaling pathways.
Disseminated tuberculosis prognosis
Authors: Haifa Zaibi, Zied Moatemri, Amir Sellami, Salsebil Dabboussi, Alaeddine Eljery, Samira Mhamdi, Eya Tangour, Chiraz Aichaouia, Mohsen Khadhraoui, Rezieg Cheikh
Journal: European Respiratory Journal (2013)

Although disseminated tuberculosis DTB is uncommon, particularly in immunocompetent patients, its prognosis remains poor, needing earlier diagnosis and treatment.  The aim of the present study is to describe clinical profile and outcome of patients diagnosed to have DTB.  DTB accounted for 7.6% (n=7) of all cases of tuberculosis TB admitted in our pulmonary department of military hospital of Tunis (n=92) during period between 2007 and 2012. Mean age was 25.7 years. Mean diagnosis delay was 117 vs 68 days in non DTB. The most common presenting symptoms were: weight loss (100%), night sweats (85%) and fever (66.6%). Extrathoracic symptoms suggestive of the organs involved were hemiplegia (n=1), lameness (n=1) and chronic diarrhea (n=2). Associated miliary pulmonary tuberculosis was found in 60%. Positive acid-fast bacilli and M. tuberculosis cultures were seen in 4 of 10 affected sites. Caseating granulomas were identified in 4 patients and 8 sites. The most common extra-pulmonary organs involved were liver (28.5%), bowel (28.5%) and bone (28.5%), followed by splenic, gastric, peritoneal, haematopoietic, cerebral, meningitis, laryngeal and tongue TB in one case each one. Serious complications occurred in 3 patients; with respiratory failure and cerebral stroke in one case, medullar compression in the second and hemophagocytic syndrome with multi organ failure in the last. Disease outcome under antiTB therapy was favourable in 5 cases and fatal in one case, with persistent neurological sequelae in the other case.  TB should be considered in any dragging infectious table, especially in endemic countries such us our. Extrathoracic locations are usually deceptive, causing delays in diagnosis and treatment of DTB and therefore a worse prognosis.
Utility of an improved model of amyloid-beta (Aβ1-42) toxicity in Caenorhabditis elegans for drug screening for Alzheimer’s disease
Authors: Gawain McColl, Blaine R Roberts, Tara L Pukala, Vijaya B Kenche, Christine M Roberts, Christopher D Link, Timothy M Ryan, Colin L Masters, Kevin J Barnham, Ashley I Bush, Robert A Cherny
Journal: Molecular Neurodegeneration (2012)

The definitive indicator of Alzheimer's disease (AD) pathology is the profuse accumulation of amyloid-ß (Aß) within the brain. Various in vitro and cell-based models have been proposed for high throughput drug screening for potential therapeutic benefit in diseases of protein misfolding. Caenorhabditis elegans offers a convenient in vivo system for examination of Aß accumulation and toxicity in a complex multicellular organism. Ease of culturing and a short life cycle make this animal model well suited to rapid screening of candidate compounds.We have generated a new transgenic strain of C. elegans that expresses full length Aß₁₋₄₂. This strain differs from existing Aß models that predominantly express amino-truncated Aß₃₋₄₂. The Aß₁₋₄₂ is expressed in body wall muscle cells, where it oligomerizes, aggregates and results in severe, and fully penetrant, age progressive-paralysis. The in vivo accumulation of Aß₁₋₄₂ also stains positive for amyloid dyes, consistent with in vivo fibril formation. The utility of this model for identification of potential protective compounds was examined using the investigational Alzheimer's therapeutic PBT2, shown to be neuroprotective in mouse models of AD and significantly improve cognition in AD patients. We observed that treatment with PBT2 provided rapid and significant protection against the Aß-induced toxicity in C. elegans.This C. elegans model of full length Aß₁₋₄₂ expression can now be adopted for use in screens to rapidly identify and assist in development of potential therapeutics and to study underlying toxic mechanism(s) of Aß.
Reclaiming the name ‘bronchiectasis’
Authors: James D Chalmers, J Stuart Elborn
Journal: Thorax (2015)

The beginning of wisdom is to call things by their proper name — Confucius, The Analects of Confucius 

Diseases should be defined by what they are, not by what they are not. The way we classify and name things has a significant impact on our behaviour and on our perception of their importance.1 Here we argue that clinicians and researchers should stop using the term ‘non-cystic fibrosis’ bronchiectasis to describe this common and disabling disease.

Diseases are classified by putting patients into groups based on similarities so that we can better understand natural history, epidemiology and treatment. The International Classification of Diseases (ICD) provides a common language for reporting and monitoring diseases. This allows clinicians and researchers to compare and share data in a consistent and standard way—between hospitals, regions and countries and over periods of time. It facilitates the collection and storage of data for analysis and evidence-based decision-making.2 Bronchiectasis is a recognised code in ICD-10, J47.

Bronchiectasis is a pathological description of abnormal, usually permanent dilation of the bronchi which may be a feature of a wide range of clinical disorders. These include severe infections (including bacteria, viral and fungal diseases), immune deficiencies, autoimmune disorders, channelopathies, ciliary disorders and hypersensitivity reactions. Despite the heterogeneity in aetiology, 50%–70% of adults are typically classified as idiopathic and postinfective.2 ,3

Data on the epidemiology of bronchiectasis show a progressive increase in reported morbidity. Hospitalisations are increasing in the USA at a rate of 2%–3% per year, and in Europe, data show an average increase in age-adjusted incidence of 2.9% per year in Germany, …