tbuckley/cabot-search huggingface dataset:
* LNA-Modified oligonucleotides targeting mRNA of dicer in pegylated colloidal nanoparticles with linked ABS against CD44 eradicate esophageal cancer stem cells (ECSC) by induction of PCD after inhibition of oncomir machinery
Authors: J. Giannios
Journal: Gut (2011)

<h3>Introduction</h3> Metastatic oesophageal squamous cell Ca (ESCC) is incurable due to chemoresistance caused by cancer stem cells due to overexpression of oncomirs which upregulate oncogenes and hypermethylation in CpG islands which inactivates tumour suppressor genes. <h3>Methods</h3> We obtained metastatic ESCC and CSCs from patients and we injected them in xenograft animal models which were treated with LNA oligonucleotides targeting DICER where the 29-oxygen is bridged to the 49 position via a methylene linker leading to formation of a rigid bicycle locked into a C3 endo (RNA) sugar conformation encapsulated in PEG colloidal nanoparticles with linked Abs targeting CD44. Microarray, RT-PCR, IHC, flow cytometry, MTT, BrdU, TUNEL and TEM were used. <h3>Results</h3> There was inhibition of Dicer RNAIII endonuclease which blocked exportin5 cleavage blocking formation of mature oncogenic miRNA segments. This inhibition of oncomirs led to silencing of oncogenes such as transcription factors, apoptotic inhibitors, chromatin modifiers, growth factors (tyrosine kinases-integral membrane proteins), signal transducers (cytoplasmic regulators, membrane associated G-proteins, GTPase exchange factors and serine/threonine kinases). Dicer silencing led to inhibition of angiogenesis, invasion, metastasis, ESCC and CSC proliferation by inhibiting stem cell pathways Bmi-1, Notch, SHH and Wnt. There was inhibition of hypermethylation of CpG islands reactivating apoptotic tumour suppressor genes inducing irreversible D2 stage of type I PCD/apoptosis which led to a bystander killing effect. BrdU and MTT exhibited inhibition of DNA synthesis and metabolic activity of ESCC and CSCs. <h3>Conclusion</h3> Silencing of DICER exerted a synergistic apoptotic effect by activation of tumour suppressor genes after demethylation and inhibition of oncomirs and linked oncogenes leading to eradication of chemoresistant CSCs and ESCCs.
A phase II Hoosier Oncology Group study of vinorelbine and estramustine phosphate in hormone-refractory prostate cancer
Authors: C.J. Sweeney, F.J. Monaco, S.-H. Jung, M.J. Wasielewski, J. Picus, R.H. Ansari, W.M. Dugan, L.H. Einhorn
Journal: Annals of Oncology (2002)
Differential Regulation of Constitutive Major Histocompatibility Complex Class I Expression in T and B Lymphocytes
Authors: Chien-Kuo Lee, Ramon Gimeno, David E. Levy
Journal: The Journal of Experimental Medicine (1999)

Major histocompatibility complex (MHC) class I antigens are constitutively expressed yet highly induced by interferon (IFN) during inflammation. We found that not only IFN-induced but also normal basal expression of MHC I required IFN receptors and signal transducer and activator of transcription (STAT)1, providing genetic evidence for continuous IFN signaling. Surprisingly, an IFN-independent requirement for STAT1 was also found, specifically in T lymphocytes, where MHC class I expression was not fully accounted for by IFN signaling. This IFN-independent pathway maintained tyrosine phosphorylation of STAT1 in T but not B lymphocytes even in the absence of IFN receptors. Interestingly, interleukin (IL)-7 selectively activated STAT1 and induced MHC class I in mature T but not B cells. These loss of function studies demonstrate an essential role of endogenous IFN and activated STAT1 for constitutive MHC class I expression in normal mice and define IL-7–dependent but IFN-independent regulation of STAT1 restricted to T lymphocytes.
French women to have PIP breast implants removed for free
Authors: A. O'Dowd
Journal: BMJ (2011)

All 30 000 women in France who had Poly Implant Prosthese (PIP) breast implants have been recommended by their government to have them removed at no cost as a “preventive” measure.

In the UK, however, the drug regulatory body the Medicines and Healthcare Products Regulatory Agency said it stood by its earlier advice to the 40 000 UK women who had the implants, that there was no evidence to support routine removal.

The company PIP went into administration last year and use of its implants was banned after concerns that it may have used non-medical grade silicon to make the implants.

Fresh fears of the dangers of having the implants surfaced recently in the …
Ochronotic osteoarthropathy in a mouse model of alkaptonuria, and its inhibition by nitisinone
Authors: Andrew J Preston, Craig M Keenan, Hazel Sutherland, Peter J Wilson, Brenda Wlodarski, Adam M Taylor, Dominic P Williams, Lakshminarayan R Ranganath, James A Gallagher, Jonathan C Jarvis
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Alkaptonuria (AKU) is a rare metabolic disease caused by deficiency of homogentisate 1,2 dioxygenase, an enzyme involved in tyrosine catabolism, resulting in increased circulating homogentisic acid (HGA). Over time HGA is progressively deposited as a polymer (termed ochronotic pigment) in collagenous tissues, especially the cartilages of weight bearing joints, leading to severe joint disease. <h3>Objectives</h3> To characterise blood biochemistry and arthropathy in the AKU mouse model (<i>Hgd−/−</i>). To examine the therapeutic effect of long-term treatment with nitisinone, a potent inhibitor of the enzyme that produces HGA. <h3>Methods</h3> Lifetime levels of plasma HGA from AKU mice were measured by high-performance liquid chromatography (HPLC). Histological sections of the knee joint were examined for pigmentation. The effect of nitisinone treatment in both tissues was examined. <h3>Results</h3> Mean (±SE) plasma HGA levels were 3- to 4-fold higher (0.148±0.019 mM) than those recorded in human AKU. Chondrocyte pigmentation within the articular cartilage was first observed at 15 weeks, and found to increase steadily with mouse age. Nitisinone treatment reduced plasma HGA in AKU mice throughout their lifetime, and completely prevented pigment deposition. <h3>Conclusions</h3> The AKU mouse was established as a model of both the plasma biochemistry of AKU and its associated arthropathy. Early-stage treatment of AKU patients with nitisinone could prevent the development of associated joint arthropathies. The cellular pathology of ochronosis in AKU mice is identical to that observed in early human ochronosis and thus is a model in which the early stages of joint pathology can be studied and novel interventions evaluated.
Palliative Care and the Aggressiveness of End-of-Life Care in Patients With Advanced Pancreatic Cancer
Authors: Raymond W. Jang, Monika K. Krzyzanowska, Camilla Zimmermann, Nathan Taback, Shabbir M. H. Alibhai
Journal: JNCI Journal of the National Cancer Institute (2015)

We examined the impact of palliative care (PC) on aggressiveness of end-of-life care for patients with advanced pancreatic cancer. Measures of aggressive care included chemotherapy within 14 days of death; and at least one intensive care unit (ICU) admission, more than one emergency department (ED) visit, and more than one hospitalization, all within 30 days of death. A retrospective population-based cohort study using administrative data was conducted in patients with advanced pancreatic cancer from 2005 to 2010 in Ontario, Canada. Multivariable logistic regression was performed with the above measures of aggressive care as the outcomes of interest and PC as the main exposure, adjusting for covariables. Secondary analyses examined intensity of PC as the main exposure defined in two ways: 1) absolute number of PC visits before the outcome of interest (0, 1, 2, 3+ visits) and 2) monthly rate of PC visits. The cohort included 5381 patients (median survival 75 days); 2816 (52.3%) had received a PC consultation. PC consultation was associated with decreased use of chemotherapy near death (odds ratio [OR] = 0.34, 95% confidence interval [CI] = 0.25 to 0.46); lower risk of ICU admission: OR = 0.12, 95% CI = 0.08 to 0.18; multiple ED visits: OR = 0.19, 95% CI = 0.16 to 0.23; multiple hospitalizations near death: OR = 0.24, 95% CI = 0.19 to 0.31). A per-unit increase in the monthly rate of PC visits was associated with lower odds of aggressive care for all four outcomes. PC consultation and a higher intensity of PC were associated with less aggressive care near death in patients with advanced pancreatic cancer.
17-β Estradiol Positively Correlates With IL-17A+ CCR6+ Memory CD4+ T Cells In Patients With Severe Asthma
Authors: Dawn C. Newcomb Baker, Jacqueline-Yvonne Cephus, Emily W. Langley, Amy S. Feldman, Nanalene Frey, Kristen Cooper, John M. Fahrenholz, R. Stokes Peebles
Journal: Journal of Allergy and Clinical Immunology (2014)
Low-dose theophylline modulates T-lymphocyte activation in allergen-challenged asthmatics
Authors: ZH Jaffar, P Sullivan, C Page, J Costello
Journal: European Respiratory Journal (1996)

Theophylline has been shown by several investigators to attenuate the late asthmatic response (LAR) to inhaled allergen, suggesting that it has anti-inflammatory or immunomodulatory properties. We have, therefore, undertaken a double-blind, placebo-controlled study to examine the effects of low-dose theophylline on bronchoalveolar lavage (BAL) and blood T-lymphocyte profile and activation in asthmatics following antigen challenge and the development of a LAR. Peripheral blood and BAL samples were obtained from 17 subjects with mild atopic asthma before and after 6 weeks of treatment with either oral theophylline or placebo. The mean serum theophylline concentration achieved was 6.6 micrograms.mL-1, which is below the currently accepted therapeutic range. Following theophylline therapy, there was a significant decrease in the number of BAL lymphocytes compared to placebo. On flow cytometric analysis of BAL cells, a significant loss of CD3+ T-lymphocytes, comprising both CD4+ and CD8+ subsets, was demonstrated. Moreover, there was a decrease in the number of BAL CD4+ T-cells expressing the activation marker very late activation antigen-1 (VLA-1), and an apparent reduction in human leucocyte antigen-DR (HLA-DR). Correspondingly, this was accompanied in the blood by an elevation in the proportion of activated CD4+ T-lymphocytes, in particular those expressing HLA-DR. These findings provide further evidence that theophylline has an anti-inflammatory action in asthma.
P39 Nutritional assessments in COPD: the respiratory nurse perspective on current practice across the UK
Authors: J. Annandale, C. Kelly, R. Sherrington
Journal: Thorax (2011)

<h3>Background</h3> Low body mass index (BMI) and weight loss are associated with a poorer prognosis for patients with COPD but are potentially reversible.1 Nutritional assessments should be key part of patient management and respiratory nurses are in a good position to undertake these. Guidelines1 recommend referral to a dietician for those patients with an abnormal BMI (&lt;20 or &gt;25) and those with a low BMI given nutritional supplements. <h3>Methodology</h3> An electronic survey using closed ended questions was emailed to 533 respiratory nurses in the UK. 177 responses (33%) were returned from across primary, secondary and community sectors. Those nurses not managing COPD patients were asked not to respond. <h3>Results</h3> 88% reported using weight and BMI to assess patients, with 85% undertaking an assessment at least once or twice year. Only 32% used any further screening tool. 94% of nurses have access to a dietician and 85% of nurses are able to refer directly, but highlight long waiting times. Despite this, 54% refer less than half of patients they identify with an ongoing nutritional problem. 16% are unable to get nutritional supplements for their patients but, where available, 96% had access to a range of supplements. Reasons cited were the need for a dietician referral first and GPs reluctance to prescribe supplements. 65% reported not having any specific criteria for referral to a dietician and 87% felt a specific simple practical tool would help manage this group of patients. 42% felt overall that malnourished patients were managed poorly in their area (see Abstract P39 table 1). <h3>Discussion</h3> Respiratory nurses conduct nutritional assessments with COPD patients and the majority appear to have access to a dietician. Yet, despite this, referral to specialist dietetic services is low. This may be due to perceived lack of dietician services or long waiting times. Improved awareness, education and training among respiratory nurses regarding nutritional assessment together with improved access to dietetic services would seem to be priorities for the future in order to meet current recomendations.1
The masculinization of the fetus during pregnancy due to inhalation of diesel exhaust.
Authors: N Watanabe, M Kurita
Journal: Environmental Health Perspectives (2001)

This study was conducted to determine the impact of diesel exhaust inhalation on the fetus. Seventy-two pregnant rats and 18 nonpregnant rats were divided into three groups: a group exposed to total diesel engine exhaust containing 5.63 mg/m(3) particulate matter, 4.10 ppm nitrogen dioxide, and 8.10 ppm nitrogen oxide; a group exposed to filtered exhaust without particulate matter; and a group exposed to clean air. The exposure period was from day 7 until day 20 of pregnancy. In addition, 15 pregnant rats were treated with aromatase inhibitors or testosterone to clarify the process by which diesel exhaust exerts its toxicity. The anogenital distance was significantly longer in male and female fetuses from both exhaust-exposed groups than in those of the control. Differentiation of the testis, ovary, and thymus was delayed and disturbed. Maternal testosterone and progesterone levels, which increased due to pregnancy whether or not the rats were exposed, were significantly higher and lower, respectively, in the pregnant rats exposed to total exhaust and filtered exhaust. The serum adrenocorticotropic hormone (ACTH) level and urinary excretion of 17-hydroxycorticosteroids (OHCS) did not differ among the pregnant groups. These results indicate that elevated testosterone did not result from elevated maternal adrenal function. The feto-placental-ovarian unit and inhibition of aromatase activity and synthesis caused by diesel exhaust inhalation might have played an essential role in the accumulation of testosterone. Since both exhaust-exposed groups showed almost the same reactions toward the inhalation, the gaseous phase must have included the relevant toxicants.
A pedestal designed to facilitate intensive care
Authors: B. T. Le Roux, N. W. H. Ormonde, W. O. Servant
Journal: Thorax (1968)

A pedestal for the provision of essential services at the bedside in an intensive care area is described and illustrated. The aim is to facilitate the relay of information on vital functions from the patient to monitors without transgression of free space about the patient. Modifications in basic design which would increase the value of such a pedestal in special circumstances are indicated.
Renal allograft protection with losartan in Fisher→Lewis rats: Hemodynamics, macrophages, and cytokines
Authors: Farzad Ziai, Hiroaki Nagano, Mamoru Kusaka, Ana J. Coito, Julia L. Troy, Kari C. Nadeau, Helmut G. Rennke, Nicholas L. Tilney, Barry M. Brenner, Harald S. Mackenzie
Journal: Kidney International (2000)
MECHANISM OF EPILEPSY
Authors: Cheolsu Shin, M.D, James O. McNamara, M.D
Journal: Annual Review of Medicine (1994)

▪ Abstract Epilepsy is a collection of diverse disorders that together affect approximately 1% of the general population. Current therapies are largely symptomatic and are aimed at controlling seizures in affected individuals. This review focuses on emerging insights into mechanisms underlying the most common form of epilepsy—complex partial epilepsy—and also addresses progress in molecular genetic approaches. Such developments will hopefully lead to more effective therapies.
A Knock-In Mouse Model of Gastrointestinal Stromal Tumor Harboring <i>Kit</i> K641E
Authors: Brian P. Rubin, Cristina R. Antonescu, James P. Scott-Browne, Melissa L. Comstock, Yansong Gu, Munir R. Tanas, Carol B. Ware, Jessica Woodell
Journal: Cancer Research (2005)

Abstract A mouse model of gastrointestinal stromal tumor (GIST) has been developed by a knock-in gene targeting strategy, which introduced a Kit gene K641E mutation, originally identified in sporadic human GISTs and in the germ line of familial GIST syndrome patients. Homozygous and heterozygous Kit K641E mice develop gastrointestinal pathology with complete penetrance and all Kit K641E homozygotes die by age 30 weeks due to gastrointestinal obstruction by hyperplastic interstitial cells of Cajal (ICC) or GISTs. Heterozygous mice have less extensive ICC hyperplasia and smaller GISTs, suggesting a dose-response relationship between oncogenically activated Kit and ICC proliferation. Immunoprecipitation and Western blotting reveal GISTs to contain abundant phosphorylated/activated Kit. In addition to ICC hyperplasia and GISTs, homozygous Kit K641E mice exhibit loss-of-function Kit phenotypes, including white coat color, decreased numbers of dermal mast cells, and sterility, indicating that despite its oncogenic activity the mutant form cannot accomplish many activities of the wild-type gene. Kit K641E reproduces the pathology associated with the familial GIST syndrome and thus is an excellent model to study Kit pathway activation, ICC biology, GIST pathogenesis, and preclinical validations of GIST therapies and mechanisms of drug resistance.
Clinical and Radiographic Correlates of Primary and Reactivation Tuberculosis
Authors: Elvin Geng, Barry Kreiswirth, Joe Burzynski, Neil W. Schluger
Journal: JAMA (2005)

The traditional teaching that pulmonary tuberculosis characterized by lymphadenopathy, effusions, and lower or mid lung zone infiltrates on chest radiography represents "primary" disease from recently acquired infection, whereas upper lobe infiltrates and cavities represent secondary or reactivation disease acquired in the more distant past, is not based on well-established clinical evidence. Furthermore, it is not known whether the atypical radiograph common in human immunodeficiency virus (HIV)-associated tuberculosis is due to a preponderance of primary progressive disease or altered immunity.To analyze the relationship between recently acquired and remotely acquired pulmonary tuberculosis, clinical and demographic variables, and radiographic features by using molecular fingerprinting and conventional epidemiology.A retrospective, hospital-based series of 456 patients treated at a New York City medical center between 1990 and 1999. Eligible patients had to have had at least 1 positive respiratory culture for Mycobacterium tuberculosis and available radiographic data.Radiographic appearance as measured by the presence or absence of 6 features: upper lobe infiltrate, cavitary lesion, adenopathy, effusions, lower or mid lung zone infiltrate, and miliary pattern. Radiographs were considered typical if they had an upper lobe infiltrate or cavity whether or not other features were present. Atypical radiographs were those that had adenopathy, effusion, or mid lower lung zone infiltrates or had none of the above features.Human immunodeficiency virus infection was most commonly associated with an atypical radiographic appearance on chest radiograph with an odds ratio of 0.20 (95% confidence interval, 0.13-0.31). Although a clustered fingerprint, representing recently acquired disease, was associated with typical radiograph in univariate analysis (odds ratio, 0.68; 95% confidence interval, 0.47-0.99), the association was lost when adjusted for HIV status.Time from acquisition of infection to development of clinical disease does not reliably predict the radiographic appearance of tuberculosis. Human immunodeficiency virus status, a probable surrogate for the integrity of the host immune response, is the only independent predictor of radiographic appearance. The altered radiographic appearance of pulmonary tuberculosis in HIV is due to altered immunity rather than recent acquisition of infection and progression to active disease.
Does the DSM-IV Clinical Significance Criterion for Major Depression Reduce False Positives? Evidence From the National Comorbidity Survey Replication
Authors: Jerome C. Wakefield, Mark F Schmitz, Judith C. Baer
Journal: American Journal of Psychiatry (2010)

To reduce false positive diagnoses, DSM-IV added a clinical significance criterion to many diagnostic criteria sets requiring that symptoms cause significant distress or impairment. The DSM-V Task Force is considering whether clinical significance should remain a diagnostic threshold or become a separate dimension, as it is in ICD. Yet, the criterion's effectiveness in validly reducing the prevalence of specific disorders remains unclear. Critics have argued that for some categories, notably major depression, the criterion is redundant with symptoms, which are inherently distressing or impairing. The authors empirically evaluated the criterion's effect on the prevalence of major depression in the community. This report also considers more broadly the relationship of symptoms to impairment in diagnosis.Subjects were respondents, aged 18 to 54 years, who participated in the National Comorbidity Survey Replication (N=6,707). The effect of the clinical significance criterion's distress and impairment components on major depression was assessed in this sample. Distress questions were administered to all respondents reporting persistent sadness (> or = 2 weeks) or the equivalent. Questions pertaining to role impairment were asked of all respondents satisfying major depression symptom-duration criteria.Of 2,071 individuals reporting persistent sadness or the equivalent, 97.2% (N=2,016) satisfied criteria for distress. Of 1,542 individuals satisfying depression symptom-duration criteria, 96.2% (N=1,487) satisfied criteria for impairment.These findings support the redundancy thesis. Distress is virtually redundant with symptoms of persistent sadness, even in the absence of major depression, and impairment is almost always entailed by major depression-level symptoms. Thus, the clinical significance criterion does not substantially reduce the prevalence of major depression in the community. The DSM-V Task Force should consider eliminating the criterion and explore alternative ways to identify false positives in the diagnosis of depression. The criterion's status for other disorders should be evaluated on a disorder-by-disorder basis because the diagnostic relationship between symptoms and impairment varies across categories.
[50] ANTIVIRAL ACTIVITY OF THE NON-NUCLEOSIDE POLYMERASE INHIBITOR, HCV-796, IN COMBINATION WITH PEGYLATED INTERFERON ALFA-2b IN TREATMENT-NAIVE PATIENTS WITH CHRONIC HCV
Authors: S.A. Villano, D. Raible, D. Harper, J. Speth, P. Chandra, P. Shaw, G. Bichier
Journal: Journal of Hepatology (2007)
Intravenous antibiotic treatment at home can provide higher quality care
Authors: C. P Conlon, J. Kayley, D. G Lalloo, A. R Berendt
Journal: BMJ (1997)

Editor—The tone of Dilip Nathwani and Peter Davey's article on community based intravenous antibiotic treatment in Britain is unnecessarily negative.1 We agree, however, that outpatient intravenous antibiotic treatment should be driven by a concern for quality rather than as a cost saving practice. Such therapy was developed in the United States because clinicians wanted to maintain quality care for patients with infections requiring intravenous treatment in the face of pressure from third party …
Development of a Cardiac Neocavity After Mechanic Double-Valve Replacement
Authors: Achim Barmeyer, Kai Muellerleile, Gunnar K. Lund, Alexander Stork, Nils Gosau, Andreas Koops, Sebastian Gehrmann, Thomas Hofmann, Ditmar H. Koschyk, Claus Nolte-Ernsting, Gerhard Adam, Thomas Meinertz
Journal: Circulation (2005)