tbuckley/cabot-search huggingface dataset:
Radioactivity in Rat Mammary Gland After the Administration of 2-Acetylaminofluorene-9-&lt;sup&gt;14&lt;/sup&gt;C and Its &lt;italic&gt;N&lt;/italic&gt;-Hydroxy Metabolite&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Douglas H. Janss, Charles C. Irving
Journal: JNCI Journal of the National Cancer Institute (1972)

After intraperitoneal injection of either 2-acetylaminofluorene-9-14C (AAF-9-14C) or N-hydroxy-AAF-9-14C into female rats, both compounds were rapidly absorbed. However, the initial tissue levels of radioactivity after injection of AAF-9-14C were much higher than those after N-hydroxy-AAF-9-14C. The specific radioactivity of the mammary parenchymal cells, relative to that of plasma, rose gradually from 3–24 hours following an injection of either compound. But, when specific radioactivity of liver or mammary fat cells was related to that of plasma, the level either remained constant or fell. While rats were Fed a diet containing 0.04% AAF-9-14C, the amount (pmoles) of AAF-9-14C bound per mg of mammary parenchymal cell DNA rose sharply for the first 2 weeks, and thereafter the level remained constant. AAF binding to protein rose gradually for 6 weeks, then increased dramatically, and by 8 weeks reached a level greater than that bound to DNA. The present data coupled with those of previous reports indicated that no simple correlation between uptake and binding of AAF to cellular DNA and protein and the susceptibility of the tissue to the carcinogenic property of this compound exists. However, additional investigations as to the relationship between binding of specific chemicals to mammary parenchymal cell macromolecules and their carcinogenicity may be critical for our understanding of mammary neoplasia.
Kartagener's Syndrome (Situs Inversus, Bronchiectasis and Chronic Sinusitis)
Authors: Melvin Katz, E. Edward Benzier, Louis Nangeroni, Benjamin Sussman
Journal: New England Journal of Medicine (1953)

THE triad of situs inversus, bronchiectasis and chronic sinusitis is known as Kartagener's syndrome. First reported by Kartagener in 1933, the syndrome had been described in approximately 40 cases up to 1951.1 The following case is presented as an additional example of the syndrome:J. R., a 20-year-old Puerto Rican boy, was referred to the Kips Bay Chest Clinic by his physician because of frequent upper respiratory infections and a chronic, moderately productive cough. The cough had been present since childhood, particularly in the morning on arising. No hemoptysis had occurred. (He had had a chronic postnasal "drip" with frequent . . .
Abstract 277: Investigation of the signaling factors involved in Ras/MAPK-promoted metastasis in the <i>PTEN</i>−/−<i>TP53</i>−/− mouse model.
Authors: Heather S. Tillman, Juan Juan Yin, Yen Nien Liu, Musaddiq Awan, Philip Martin, Kathleen Kelly
Journal: Cancer Research (2013)

Abstract The most significant challenges for advanced prostate cancer patients are resistance to androgen-deprivation therapy and the dissemination of metastatic cancer cells. Our study begins to address how enhanced Ras signaling cooperates with combined TP53 and PTEN loss for enhanced metastatic capability. Because neither PTEN nor TP53 deletion alone is not sufficient for metastasis, we asked what other signaling pathways are required. Ras pathway activation is implicated in prostate cancer metastatic progression in comprehensive genetic analyses of human prostate tumors. We introduced a lentiviral vector expressing K-rasG12V into a non-metastatic PTEN−/−/TP53−/- adenocarcinoma cell line (clone 2). Orthotopic prostate injection of clone2/Ras expressing cells resulted in 100% pulmonary metastasis. The metastatic phenotype was paralleled by an inhibition of sarcomatoid carcinoma transformation. We hypothesized that Ras signaling modified TGFβ-mediated EMT signaling, which we have previously demonstrated leads to sarcomatoid carcinoma formation in this model. Multiple pathways downstream of TGFβ initiate signaling including SMAD4 dependent transcription and other non-SMAD mediated pathways like TAK1 induced NF-κB activation. Pathologic analysis of nuclear p65 labeling, a canonical NF-κB marker, showed enhanced labeling in clone2/Ras developed tumors and lung metastases and undetectable levels in clone 2 developed tumors. These in vivo findings suggest enhanced canonical NF-κB signaling may enable Ras transformed prostate cancer cells with metastatic capability. Citation Format: Heather S. Tillman, Juan Juan Yin, Yen Nien Liu, Musaddiq Awan, Philip Martin, Kathleen Kelly. Investigation of the signaling factors involved in Ras/MAPK-promoted metastasis in the PTEN−/−TP53−/− mouse model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 277. doi:10.1158/1538-7445.AM2013-277
THU0491 Genome-Wide Transcriptional Profiling of Isolated Immune Cell Populations from SLE Patients with Different Ancestral Backgrounds
Authors: S. Sharma, Z. JIn, E. Rosenzweig, S. Rao, K. Ko, T.B. Niewold
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a complex multi-system autoimmune disease of uncertain etiology. Patients from different ancestral backgrounds demonstrate differences in clinical manifestations and autoantibody profiles. <h3>Objectives</h3> In this study we examined genome-wide transcriptional patterns in major immune cell subsets across different ancestral backgrounds. <h3>Methods</h3> Peripheral blood was collected and run on 208 Illumina HumanHT-12 V4 expression BeadChip arrays. Subjects included 21 African-American (AA) and 21 European-American (EA) SLE patients, 5 AA and 5 EA controls. CD4<sup>+</sup> T-cells, CD8<sup>+</sup> T-cells, monocytes and B cells were purified by flow sorting. Each cell subset from each subject was run on a separate array. Differentially expressed genes (DEGs) were determined by comparing cases and controls of the same ancestral background. <h3>Results</h3> The overlap in DEG lists between different cell types from the same ancestral background was very modest (&lt;1%). Typically between 5-10% of DEGs were shared when comparing the same cell type between different ancestral backgrounds. Global IFN-stimulated gene (ISG) expression revealed that AA subjects demonstrated more concordance across all studied cell types. Two subgroups of patients were identified based on the ISG expression profiles. One subgroup showed higher ISGs expression in all cell types, and the other subgroup had higher ISG expression only in T and B lymphocytes but not in monocytes. <h3>Conclusions</h3> We find striking differences in gene expression between different immune cell subsets and between ancestral backgrounds in SLE patients. The IFN signature is diverse, with different transcripts represented in different cell populations, and signature-positive cell subsets differed in EA vs. AA patients. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5291
A phase I study of weekly docetaxel (DTX) and biweekly oxaliplatin (Ox) in patients with advanced solid tumours
Authors: J. Millar, S. McDowell, E. Dillon, U. McDermott, A. Morrison, R. Wilson, M. Eatock
Journal: Journal of Clinical Oncology (2005)

2098 Background: DTX and Ox are active against a wide range of tumour types. DTX is usually administered in a 3 weekly schedule, resulting in the dose limiting toxicity of myelosuppression. This may be reduced by weekly administration. The main dose-limiting toxicity (DLT) of Ox is transient acute dysaesthesia and cumulative peripheral neuropathy. In view of pre-clinical evidence of synergy between DTX and Ox, we have conducted this phase I trial. Methods: Patients for whom treatment with DTX was indicated were eligible. DTX was given on days 1, 8, 15, 22, 29 and 36 and Ox administered on days 1, 15 and 29 of an 8 week schedule at starting doses of DTX 20 mg/m2 and Ox 65mg/m2. Results: To date 16 patients, median age 55 years, have been recruited. Primary disease sites: upper GI (12 patients), small bowel (1), squamous cell skin (1), epithelioid sarcoma (1) and unknown (1). Patients were treated as follows: dose level (DL)1 - 3 patients, DL2 - 6 patients, DL3 - 3 patients, DL-3 - 4 patients (1 patient did not receive treatment and was replaced). No DLT were observed in cohort 1.1 Patient in DL2 experienced grade 3 fatigue. 8 patients in DLs 1 and 2 developed progressive fatigue during the 1st and 2nd cycles of treatment. Subsequent cohorts were treated in a 4 weekly cycle with DTX on days 1, 8 and 15 and Ox on days 1 and 15. 2 patients in DL 3 (DTX 25mg/m2, Ox 85mg/m2), experienced DLT with fatigue and diarrhoea. In DL-3 (DTX 20 mg/m2 and Ox 85mg/m2), there were no DLT. In all cycles, haematological toxicity was low with grade III/IV neutropenia occurring in 1 patient. 1 patient experienced grade II cold-induced dysaesthesia and 1 patient grade II sensorimotor neuropathy due to L4/5 disc protrusion, confirmed on MRI. 15 patients were evaluable for response. Responses have been observed in 4/12 patients with gastro-oesophageal cancer. Conclusions: At the recommended dose of DTX 20 mg/m2 and Ox 85mg/m2, this is a tolerable treatment worthy of further study. We plan to recruit a further 12 patients at this dose level to obtain further data on toxicity, activity and pharmacokinetics. No significant financial relationships to disclose.
P19 GeneXpert MTB.Rif assay improves the diagnostic yield of EBUS-TBNA in smear-negative intra-thoracic tuberculous lymphadenopathy
Authors: D. J. Dhasmana, C. J. Bradley, P. George, D. W. Connell, P. Molyneaux, A. Singanayagam, A. Lalvani, A. Jepson, O. M. Kon, G. S. Cooke
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Tuberculosis notifications in the UK continue to rise and the diagnosis of both disease and drug resistance can be challenging. Endobronchial ultrasound (EBUS) and EBUS-guided transbronchial nodal aspirates (TBNA) have been shown recently to be a safe and effective tool in the diagnosis of intra-thoracic TB lymphadenopathy. New molecular techniques, notably the GeneXpert MTB.Rif system (Cepheid) have shown great promise in the diagnosis of pulmonary disease but have not been evaluated in intra-thoracic nodal disease. <h3>Methods</h3> As part of an ongoing study, consecutive patients with intra-thoracic lymphadenopathy were prospectively studied within our tertiary EBUS service between January 2010 and March 2011. In addition to standard cytological and microbiological investigations, a single GeneXpert MTB.Rif assay was performed on EBUS-TBNA samples. Using established methods, a final diagnosis was given of definite/highly probable TB, possible TB or not TB/alternative diagnosis. Performance of the GeneXpert MTB.Rif assay was then evaluated in the context of these final diagnoses. <h3>Results</h3> 74 patients (3 HIV-positive) underwent EBUS-TBNA sampling. Nineteen have been diagnosed with definite/highly probable TB to date. A single GeneXpert assay had a sensitivity of 67% (8/12) from culture-positive TBNA. 11/15 (73%) of patients with a positive culture from any tissue and 13/19 (68%) patients classed as definite/highly probable TB had positive GeneXpert results. One case of confirmed MDR-TB was correctly identified and treatment started promptly. Fifteen patients had positive GeneXpert MTB.Rif results from EBUS-TBNA: 13/15 were given immediate TB treatment. One of the remaining two cases without strong microbiological or cytological findings was subsequently diagnosed with active tuberculosis supported by evidence of PET-positive mediastinal lymph nodes. The other case appears not to have active disease and remains under follow-up. <h3>Conclusions</h3> A single GeneXpert MTB.Rif assay has good sensitivity in the context of culture-positive intra-thoracic tuberculous lymphadenopathy and can provide an immediate diagnosis of likely MDR-TB. Positive PCR results were seen in two patients where conventional techniques were inconclusive and in one provided the main support for the diagnosis. These results suggest the addition of the GeneXpert MTB.Rif assay to the investigation of intra-thoracic nodal disease improves diagnostic yield.
CS-24 * PYRUVATE KINASE M2-MEDIATED SUBCELLULAR LOCALIZATION OF HuR REGULATES GLIOMA GROWTH
Authors: J. Mukherjee, S. Obha, R. Pieper
Journal: Neuro-Oncology (2014)

HuR is an RNA-binding protein that influences the stability and translation of hundreds of different RNAs, and when overexpressed as in gliomas contribute to tumor formation. HuR, however, is typically localized to the nucleus, and the factors that regulate its export to the cytoplasm, and thus function, remain poorly defined. We here report that pyruvate kinase M2, a glycolytic enzyme over-expressed in glioma, also regulates HuR sub-cellular localization, and uses this ability to control RNA metabolism and facilitate cell cycle progression. Specifically shRNA-mediated suppression of PKM2 in multiple GBM cell lines shifted HuR from the nucleus to the cytoplasm, which in turn led to increased cap-independent p27 mRNA translation and cell cycle arrest. In control GBM cells, HuR was tyrosine phosphorylated, and PKM2, a nuclear phosphotyrosine-binding protein, co-immunoprecipitated with HuR but not with exogenous HuR mutated (Y200A) to prevent tyrosine phosphorylation. Consistent with this observation, exogenous WT HuR accumulated in the nucleus whereas Y200A HuR accumulated in the cytoplasm, even in the presence of PKM2, and Y200A HuR expression, unlike that of WT HuR, failed to rescue cells from the high levels of p27 and cell cycle arrest induced by PKM2 knockdown. HuR was also associated with the nuclear export adapters pp32 and APRIL and mechanistically, the binding of PKM2 blocked the interaction of the HuR/pp32/APRIL complex with CRM1 nuclear exporter thereby limiting HuR cytoplasmic transport. Significantly, the associations between low nuclear PKM2, high cytoplasmic HuR, high p27 expression, and growth arrest noted in control and PKM2 knockdown GBM cells were also noted in the same cells grown as xenografts as well as in primary human GBM. These results therefore define PKM2 as a regulator of HuR cellular localization and function, and also directly link metabolic regulation to the control of RNA metabolism, cell cycle progression, and tumor growth.
Suppression of in Vitro Lymphocyte Responses by Chloroquine
Authors: Dahlia Hurvitz, Kurt Hirschhorn
Journal: New England Journal of Medicine (1965)

THE antimalarial drug chloroquine has found clinical use in the suppression of some symptoms in rheumatoid arthritis and disseminated lupus erythematosus, diseases associated with abnormalities of the immune response.1 Chloroquine has more recently been suggested as effective symptomatic therapy in infectious mononucleosis, a disease associated with abnormalities of lymphocytes and abnormal antibodies.2 The current experiments were undertaken to study its effect on specific and nonspecific stimulation of cultured human peripheral blood lymphocytes to derive possible information Concerning its mechanism of action in the diseases mentioned above.Materials and MethodsPeripheral blood lymphocytes were obtained from normal subjects and cultured by . . .
Diuretic 68Ga DOTANOC PET/CT in Imaging of Bladder Paraganglioma
Authors: Varun Singh Dhull, Sellam Karunanithi, Saurabh Arora, Tarun Kumar Jain, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2014)

Urinary bladder paragangliomas are exceedingly rare tumors. A 22-year-old woman with bladder paraganglioma underwent Ga DOTANOC PET/CT for proper localization of the primary tumor and to rule out locoregional and distant metastases. Ga DOTANOC-avid bladder mass was detected with no other abnormal site of radiotracer uptake elsewhere. Although radioactive urine can mask urinary paragangliomas, diuretic method can aid tumor detection by Ga DOTANOC PET/CT.
THU0451 Disease Activity before, During and after Pregnancy in Women with Juvenile Idiopathic Arthritis
Authors: B. Jakobsen, A. S. Helvik, S. N. Stafne, M. Wallenius, T. S. Moksnes, H. S. Koksvik
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Several studies have reported an interaction between pregnancy and inflammatory rheumatic disease. Pregnancy may affect the rheumatic disease, and vice versa. Previous studies have shown that about 50 % of women with juvenile idiopathic arthritis (JIA) can expect a flare in disease activity within 3-6 months postpartum. <h3>Objectives</h3> To study disease activity from pre-pregnancy to six months postpartum in women with JIA. <h3>Methods</h3> A total of 22 women with JIA were included in the study. An inconsistent number of women (N= 6-22), due to missing visits, were assessed prospectively related to pregnancy. To assess disease activity at each visit, the DAS-28-CRP(3) with 28 joint count, c-reactive protein (CRP) was used. In addition medical use was registered by the number of disease modifying anti rheumatic drugs (DMARDs). Registrations were recorded pre-pregnancy, 1<sup>st</sup> trimester (1-12 weeks), 2<sup>nd</sup> trimester (13-27 weeks), 3<sup>rd</sup> trimester (28-40 weeks), six weeks postpartum and six months postpartum. Non-parametric tests using the Wilcoxon test for related samples were performed. DAS-28-CRP(3) scores was tested from pre-pregnancy to each visit, and changes from visit to visit was explored. Minimal clinical important difference (MCID) was set to 0.6 according to EULAR response criteria (1) for moderate change in DAS-28-CRP(3). <h3>Results</h3> Mean age was 27.8 years (range 18-36 years), and mean disease duration was 20.5 (range 8-33). Pre-pregnancy the women used a mean of 0.53 DMARDs (range 0-2), six weeks postpartum a mean of 0.39 DMARDs (range 0-1) and six months postpartum a mean of 0.57 DMARDs (range 0-2). There was a wide range in DAS-28-CRP(3) scores but there were no statistical significant changes in DAS-28-CRP(3) from pre-pregnancy to six weeks and six months post partum (see table 1). <h3>Conclusions</h3> There were no significant changes in DAS-28-CRP(3) during pregnancy compared with pre-pregnancy scores. The women had temporary better scores in disease activity at 3<sup>rd</sup> trimester compared to six weeks postpartum. When comparing DAS-28-CRP(3) from pre-pregnancy to six weeks and six months postpartum, there was no change. Overall, the disease activity scores improved though pregnancy, and a clinically significant flare was not observed postpartum. <h3>References</h3> Franse J, van Riel PLCM. The Disease Activity Score and the EULAR response criteria. Clin Exp Rheumatol 2005; 23(Suppl. 39): S93-S99. <h3>Disclosure of Interest</h3> None Declared
Efficacy of Oral N-Acetylcysteine in the Treatment of Acetaminophen Overdose
Authors: Martin J. Smilkstein, Gary L. Knapp, Kenneth W. Kulig, Barry H. Rumack
Journal: New England Journal of Medicine (1988)

During the investigational use of oral N-acetylcysteine as an antidote for poisoning with acetaminophen, 11,195 cases of suspected acetaminophen overdose were reported. We describe the outcomes of 2540 patients with acetaminophen ingestions treated with a loading dose of 140 mg of oral N-acetylcysteine per kilogram of body weight, followed four hours later by 70 mg per kilogram given every four hours for an additional 17 doses. Patients were categorized for analysis on the basis of initial plasma acetaminophen concentrations and the interval between ingestion and treatment. Hepatotoxicity developed in 6.1 percent of patients at probable risk when N-acetylcysteine was started within 10 hours of acetaminophen ingestion and in 26.4 percent of such patients when therapy was begun 10 to 24 hours after ingestion. Among patients at high risk who were treated 16 to 24 hours after an acetaminophen overdose, hepatotoxicity developed in 41 percent — a rate lower than that among historical controls. When given within eight hours of acetaminophen ingestion, N-acetylcysteine was protective regardless of the initial plasma acetaminophen concentration. There was no difference in outcome whether N-acetylcysteine was started zero to four or four to eight hours after ingestion, but efficacy decreased with further delay. There were 11 deaths among the 2540 patients (0.43 percent); in the nine fatal cases in which aminotransferase was measured before treatment, values were elevated before N-acetylcysteine was started. No deaths were clearly caused by acetaminophen among patients in whom N-acetylcysteine therapy was begun within 16 hours. We conclude that N-acetylcysteine treatment should be started within eight hours of an acetaminophen overdose, but that treatment is still indicated at least as late as 24 hours after ingestion. On the basis of available data, the 72-hour regimen of oral N-acetylcysteine is as effective as the 20-hour intravenous regimen described previously, and it may be superior when treatment is delayed. (N Engl J Med 1988;319:1557–62.)
PWE-034 Patient-reported Experience Of Comfort And Dignity In Flexible Sigmoidoscopy: Data From The Nhs Bowel Scope Screening Pilot
Authors: C Von Wagner, H Bowyer, CJ Rees, W Atkin, J Wardle
Journal: Gut (2014)

<h3>Introduction</h3> The NHS Bowel Cancer Screening Programme started flexible sigmoidoscopy (FS) screening (also known as Bowel Scope Screening, BSS) at six centres across England (Gateshead, Guildford, London, Medway, Norwich, Wolverhampton) in March 2013. The aim of this analysis was to investigate the extent to which high levels of patient satisfaction recorded in previous UK trials can be replicated in the early stages of a routine screening programme. <h3>Methods</h3> We used used data from an ongoing study monitoring patient-reported experience in the pilot phase of the BSS Programme. We report data from the ‘post-AM questionnaire’ which is given to patients at the end of their FS appointment and supposed to be completed on the following day. <h3>Results</h3> As of January 2014, we had received 2,324 questionnaires. Satisfaction with the test was high with 98.8% of patients being either satisfied (21.1%) or very satisfied (77.7%). Nonetheless, 43% of patients reported moderate (34%) or severe pain (9%) which was high compared with the St Marks’ demonstration programme<sup>1</sup> and the UK Flexible Sigmoidoscopy Trial<sup>2</sup> (Figure 1). Women were three times as likely to report severe pain during the test than men (14.3 vs 4.6%), and twice as likely to find the test as more painful than they had expected (39.9 vs 20.1% respectively). Only about 1 in 10 patients reported being moderately (9.8%) or severely (1.4%) embarrassed during the test, with women being slightly more likely than men to fall into these categories (13.4 vs. 8.9%). Women also had a much stronger preference for the test to be carried out by a female practitioner than men (41.2% vs 7.1% respectively). <h3>Conclusion</h3> The vast majority of patients were satisfied with their experience of FS screening. However, levels of pain appear high when compared with previous trials. Emphasis should be placed on ensuring that patients have as comfortable a procedure as possible. Additional consideration should be given to women being able to choose the sex of the practitioner performing the test. <h3>References</h3> 1 Robb K, Lo S, Power E, <i>et al</i>. Patient-reported outcomes following flexible sigmoidoscopy screening for colorectal cancer in a demonstration screening programme in the UK. <i>J Med Screen</i> 2012;19:171–176 2 Taylor T, Williamson S, Wardle J, <i>et al</i>. Acceptability of flexible sigmoidoscopy screening in older adults in the United Kingdom. <i>J Med Screen</i> 2000;7:38–45 <h3>Disclosure of Interest</h3> None Declared.