tbuckley/cabot-search huggingface dataset:
microRNA Signature and Expression of <i>Dicer</i> and <i>Drosha</i> Can Predict Prognosis and Delineate Risk Groups in Neuroblastoma
Authors: Ruey-Jen Lin, You-Chin Lin, Jeremy Chen, Huan-Hsien Kuo, Yuan-Yan Chen, Mitchell B. Diccianni, Wendy B. London, Chih-Hao Chang, Alice L. Yu
Journal: Cancer Research (2010)

Neuroblastoma is a common childhood tumor and accounts for 15% of pediatric cancer deaths. To investigate the microRNA (miRNA) profile and role of Dicer and Drosha in neuroblastoma, we assessed the expression of 162 human miRNAs, Dicer and Drosha in 66 neuroblastoma tumors by using real-time PCR methods. We found global downregulation of miRNA expression in advanced neuroblastoma and identified 27 miRNAs that can clearly distinguish low- from high-risk patients. Furthermore, expression levels of Dicer or Drosha were low in high-risk neuroblastoma tumors, which accounted for global downregulation of miRNAs in advanced disease and correlated with poor outcome. Notably, for patients with non-MYCN-amplified tumors, low expression of Dicer can serve as a significant and independent predictor of poor outcome (hazard ratio, 9.6; P = 0.045; n = 52). Using plausible neural networks to select a combination of 15 biomarkers that consist of 12 miRNAs' signature, expression levels of Dicer and Drosha, and age at diagnosis, we were able to segregate all patients into four distinct patterns that were highly predictive of clinical outcome. In vitro studies also showed that knockdown of either Dicer or Drosha promoted the growth of neuroblastoma cell lines. Our results reveal that a combination of 15 biomarkers can delineate risk groups of neuroblastoma and serve as a powerful predictor of clinical outcome. Moreover, our findings of growth promotion by silencing Dicer/Drosha implied their potential use as therapeutic targets for neuroblastoma.
Abstract LB-304: Smad7-Skp2 complex orchestrates c-Myc stability
Authors: Tae-Aug Kim, Jin-Muk Kang, John Niderhuber, Seong-Jin Kim
Journal: Cancer Research (2014)

Abstract In most of human cancer, the c-Myc proto-oncogene is highly activated. Dysregulation of c-Myc oncoprotein contributes to drive tumorigenesis in numerous tissues and organs. Thus, targeting c-Myc stability can be a critical step for cancer therapy. Here we report Smad7 as a key molecule to regulate c-Myc stability and activity by recruiting F-box protein, Skp2. Ectopic expression of Smad7 down-regulated the protein level of c-Myc without affecting transcription level and significantly repressed its transcriptional activity, leading to inhibition of cell proliferation and tumorigenic activity. Furthermore, Smad7 enhanced ubiquitination of c-Myc through direct interaction with c-Myc and recruitment of Skp2. Ablation of Smad7 resulted in less sensitivity to the growth inhibitory effect of TGF-β by inducing stable c-Myc expression. In conclusion, these findings that Smad7 functions as a transductory role in c-Myc oncoprotein degradation and enhances the cytostatic effect of TGF-β signaling provide new insightful therapeutic approach for cancer treatment. Citation Format: Tae-Aug Kim, Jin-Muk Kang, John Niderhuber, Seong-Jin Kim. Smad7-Skp2 complex orchestrates c-Myc stability. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-304. doi:10.1158/1538-7445.AM2014-LB-304
Medical groups voice doubts over changes to gun background checks
Authors: M. McCarthy
Journal: BMJ (2013)

Some US medical groups are concerned that changes in the rules governing the reporting of patients with mental illness to the national gun background check system may undermine the doctor-patient relationship and unfairly stigmatize patients with mental health problems.

In January, in the wake of the Sandy Hook Elementary School shooting in Newtown, Connecticut, that left 20 school children and six adults dead, President Barack Obama issued 23 executive orders directing federal agencies to take action to reduce gun violence.

One of the orders called on federal agencies to reduce any legal barriers that may be preventing states from reporting the names of people who are prohibited by law from possessing guns, in particular any barriers …
P17.56 * A 3-DIMENSIONAL MATRIX ASSAY TO HELP PREDICT TREATMENT RESPONSE TO TEMOZOLOMIDE IN PATIENTS WITH GLIOBASTOMA: UPDATE OF RESULTS AND SUBGROUP ANALYSIS OF PATIENTS UNDERGOING MGMT TESTING
Authors: J. F. Megyesi, P. Costello, W. McDonald, D. Macdonald, J. Easaw
Journal: Neuro-Oncology (2014)

INTRODUCTION: Usual treatment for glioblastoma is surgical resection, if possible, followed by radiotherapy with adjuvant chemotherapy using temozolomide. However a significant number of patients have a short response to temozolomide and subsequently a poorer prognosis. We investigated the possibility that surgical specimens obtained at the time of surgery might provide valuable information regarding sensitivity to chemotherapies, including temozolomide. In order to do this we used a 3-dimensional matrix assay that mimics brain. We analyzed a subgroup of these patients for O-6-methylguanine-DNA methyltransferase (MGMT) status and correlated this with the response of tumor tissue in the assay to temozolomide. METHODS: Records for patients treated for newly diagnosed or recurrent glioblastoma were analyzed. All patients had undergone surgical resection and tumor specimens at time of surgery were available for culture in a 3-dimensional matrix assay and observed for growth and invasion. Drug effects on mean invasion and growth were expressed as a ratio relative to control conditions. Length of survival was compared between temozolomide treated patients whose screening results had predicted a positive or negative response to temozolomide. The MGMT status of a subgroup of these patients was analyzed and correlated with the response of tumor tissue in the assay to temozolomide. RESULTS: Fifty-eight patients with glioblastoma were assessed. Each patient's tumor displayed a unique invasion and response profile. We looked in particular at the correlation between the outcome of a patient with glioblastoma treated with temozolomide and the response of that patient's tumor tissue to temozolomide in the 3-dimensional assay. Mean survival time for patients whose tumors were not significantly sensitive to temozolomide in the assay was 181.7 +/- 43 days. Mean survival time for patients whose tumors were significantly sensitive to temozolomide in the assay was 290.0 +/- 33 days. Twelve patients underwent MGMT testing. In 10 of the 12 patients there was a correlation between tumor response in the assay and MGMT status. CONCLUSION: The 3-dimensional assay may help predict glioblastoma patients who will show a treatment response to temozolomide. There appears to be a positive correlation between the response profiles in the assay to the MGMT status of the patient's tumor.
Positron Emission Tomography Revealed Diffuse Involvement of the Lower Legs and Occult Extracutaneous Lesions in Subcutaneous Panniculitis-Like T-cell Lymphoma
Authors: Kenjiro Mitsuhashi, Mitsuru Momose, Akihiro Masuda, Yuichiro Tsunemi, Toshiko Motoji
Journal: Clinical Nuclear Medicine (2013)

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a very rare type of cutaneous lymphoma that localizes primarily in the subcutaneous adipose tissue without palpable involvement of the lymph nodes. Most often, it presents as multiple, painless, subcutaneous nodules on the extremities and trunk. In this study, we describe an unusual case of SPTCL that mimicked phlegmonous inflammation; PET/CT revealed massive diffuse involvement of the lower legs, low-grade nodal active disease, and occult involvement of the intra-abdominal visceral fat. A repeat PET/CT study after CHOP chemotherapy revealed complete resolution of abnormal FDG uptake in the initially involved sites.
Pulmonary Haemosiderosis in Mitral Stenosis
Authors: A. C. Lendrum
Journal: BMJ (1947)

game of bridge while talking or thinking about something quite foreign to cards.The above ability or the lack of it has a great bearing on the making of a good or a bad driver.Driving is so easy in a well-found car that it is no longer, in most circumstances, a whole-time job.One must perforce think of more than the driving, and it is here that the trouble arises.If one can only do one thing at a time, then when one's mind wanders, which it inevitably will sooner or later, then the driving suffers, and one becomes a potential danger.Many drivers will most of the time unconsciously react correctly to road stimuli, but this unconscious or subconscious reaction is, not to be trusted, it is too vulnerable to variations of physical health, alcohol, and other factors.When one considers such slogans as " Keep your eye on the ball " and " Don't speak to the man at the wheel," it may sound heretical to suggest that in order to be a tolerably safe driver it is necessary to keep only part of one's conscious mind on the business of driving, and to expect more from all drivers at all times is being unreasonable.But I myself would certainly feel safer being driven by a garrulous, agile-minded driver,than
Medical Aspects of Atomic Energy
Authors: Shields Warren
Journal: New England Journal of Medicine (1948)

THE Atomic Energy Commission has been charged by you and your fellow citizens with the responsibility of ensuring that the best use will be made of this new source of energy consistent with the national security as well as with maintaining the secret of the atomic bomb and making it available as a weapon. In such a program medicine naturally has a significant role. There is first the problem of maintaining health of the workers in the varied processes incident to the activities of the atomic-energy program. These hazards range from those of radioactive substances in amounts undreamed of a . . .
Self-management reduces both short- and long-term hospitalisation in COPD
Authors: M-A. Gadoury
Journal: European Respiratory Journal (2005)

The aim of the present study was to assess the long-term impact on hospitalisation of a self-management programme for chronic obstructive pulmonary disease (COPD) patients. A multicentre, randomised clinical trial was carried out involving 191 COPD patients from seven hospitals. Patients who had one or more hospitalisations in the year preceding study enrolment were assigned to a self-management programme "Living Well with COPD<sup>TM</sup>" or to standard care. Hospitalisations from all causes were the primary outcome and were documented from the provincial hospitalisation database; emergency visits were recorded from the provincial health insurance database. Most patients were elderly, not highly educated, had advanced COPD (reflected by a mean forced expiratory volume in one second of 1 L), and almost half reported a dyspnoea score of 5/5 (modified Medical Research Council). At 2 years, there was a statistically significant and clinically relevant reduction in all-cause hospitalisations of 26.9% and in all-cause emergency visits of 21.1% in the intervention group as compared to the standard-care group. After adjustment for the self-management intervention effect, the predictive factors for reduced hospitalisations included younger age, sex (female), higher education, increased health status and exercise capacity. In conclusion, in this study, patients with chronic obstructive pulmonary disease who received educational intervention with supervision and support based on disease-specific self-management maintained a significant reduction in hospitalisations after a 2-year period.
Ocular Manifestations of AIDS
Authors: S M Whitcup
Journal: JAMA (1996)

<h3>SELECTED CASE</h3> A 17-year-old patient with hemophilia A was diagnosed with transfusion-acquired human immunodeficiency virus (HIV) infection in 1987. Antiretroviral therapy for diminishing CD4 cell counts included zidovudine for 3 years followed by didanosine and lamivudine (known then as 3TC). An initial ophthalmic screening examination in December 1992 revealed visual acuity of 20/20 in each eye, and retinal examination showed several nerve fiber layer infarcts (cotton-wool spots) in the left eye. In November 1993 the patient had no visual complaints, but on routine eye examination, visual acuity was 20/32 in the right eye and 20/25 in the left eye. Retinal examination revealed bilateral cytomegalovirus (CMV) retinitis (Figure), and the patient was started on intravenous ganciclovir at a dose of 5 mg/kg twice daily. Other medications included rifabutin (150 mg daily), captopril (12.5 mg twice a day), digoxin (0.37 mg daily), megestrol acetate (40 mg three times a day), lamivudine (175
Venesection in the Treatment of Gunshot Wounds of the Chest
Authors: F. J. W. Porter
Journal: BMJ (1901)

in their care of the patients, and never seemed to be able to do enough for them.Too much cannot be said in praise of the nurses who worked hard night and day doing their utmost to relieve the sufferings of their patients, to whose welfare they seemed to be devoted.They infused the same spirit into their orderlies, who one and al1 did most excellent work under the most trying circumstances.
Chronic Obstructive Pulmonary Disease Is Associated with an Increase in Urinary Levels of Isoprostane F<sub>2 α</sub>-III, an Index of Oxidant Stress
Authors: DOMENICO PRATICÒ, STEFANIA BASILI, MARIO VIERI, CORRADO CORDOVA, FRANCESCO VIOLI, GARRET A. FITZGERALD
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Oxidative stress has been suggested as a potential mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). It has been difficult to address this hypothesis because of the limitations of conventional indices of lipid peroxidation in vivo. F2-isoprostanes (iPs) are prostaglandin isomers formed by free radical dependent peroxidation of arachidonic acid. Urinary iPF2 α-III is a relatively abundant iPs produced in humans. In the present study, we investigated whether COPD is associated with enhanced oxidative stress by measuring urinary levels of this compound. Urinary excretion of iPF2 α-III was determined in 38 patients with COPD and 30 sex- and age-matched healthy control subjects. Levels of iPF2 α-III were significantly higher in patients with COPD (median, 84 pmol / mmol creatinine; range, 38 to 321) than in healthy controls (median, 35.5 pmol / mmol creatinine; range, 15 to 65) (p < 0.0001). This elevation was independent of age, sex, smoking history, or duration of the disease. An inverse relationship was observed with the level of PaO2 (r = − 0.38, p = 0.019). Aspirin treatment failed to decrease urinary levels of iPF2 α-III (102 ± 8 versus 99.2 ± 7.3 pmol / mmol creatinine), whereas 11-dehydro TxB2 was significantly reduced (695 ± 74 versus 95 ± 10 pmol / mmol creatinine) (p < 0.0001). Elevated levels of iPF2 α-III (median, 125 pmol / mmol creatinine; range, 110 to 170) in five patients with COPD declined (median, 90 pmol / mmol creatinine; range, 70 to 110) (p < 0.001) as an acute exacerbation in their clinical condition resolved. Increased urinary iPF2 α-III is consistent with the hypothesis that oxidative stress occurs in COPD. This provides a basis for dose finding and evaluation of antioxidant therapy in the treatment of this disease.
Cross sectional investigation of the effects of inhaled corticosteroids on bone density and bone metabolism in patients with asthma.
Authors: A F Wisniewski, S A Lewis, D J Green, W Maslanka, H Burrell, A E Tattersfield
Journal: Thorax (1997)

BACKGROUND: Bone mineral density has been reduced in patients with asthma taking inhaled corticosteroids in some cross sectional studies and this could be important if treatment is continued for several decades. The possibility of confounding by age, menopausal status, physical activity and, especially, past oral steroid use has not been excluded in most studies. The present study was designed to assess the magnitude of any reduction in bone mineral density in relation to inhaled steroid use after adjusting for these factors. METHODS: Bone mineral density (BMD), vertebral fractures, and markers of bone metabolism (serum osteocalcin, procollagen peptide I, bone-specific alkaline phosphatase, and urinary deoxypyridinoline cross links) were measured in 81 patients with asthma age 20-40 years; 34 patients (19 men) who had never had inhaled or systemic steroids and 47 (19 men) who had taken inhaled steroids for at least five years with limited exposure to systemic steroids in the past. Data relating to past medication use, physical activity, smoking, and other confounding factors were collected by questionnaire. The relation between inhaled steroid dose and duration and BMD was assessed by linear regression analysis, accounting for potential confounders including weight, exercise, and oral steroid use. RESULTS: The 47 patients taking an inhaled steroid had a mean current dose of 620 micrograms/day (range 100-3000 micrograms), a mean duration of use of 7.8 years, and had had a mean of 0.85 courses of prednisolone in the past. There was no significant difference in mean BMD values between those who were and those who were not on inhaled steroids in men or women. However, on multivariate analysis, cumulative inhaled steroid dose was associated with a reduction in posterior-anterior (P-A) and lateral lumbar spine bone mineral density in women, equivalent to a 0.11 standard deviation reduction in bone density per 1000 micrograms/day inhaled steroid per year after adjustment for potential confounding factors (95% CI for P-A spine 0.01 to 0.22; for lateral spine 0.02 to 0.21). Previous oral steroid use was not an important confounding factor in these patients. Inhaled steroid use was not related to BMD at the wrist or hip in women or at any skeletal site in men. Women taking an inhaled steroid had lower levels of serum osteocalcin than those not taking them, although this was not dose related. Inhaled steroid use was not associated with differences in other markers of bone metabolism in men or women or with the presence of vertebral fractures. CONCLUSIONS: Although an effect of confounding factors cannot be excluded entirely in a cross sectional study, our findings are in keeping with an effect of inhaled steroid therapy in reducing bone density in the spine in women and provide an estimate of the magnitude of this effect.
Identification of Waldo-A and Waldo-B, Two Closely Related Non-LTR Retrotransposons in Drosophila
Authors: Isabelle Busseau, Eugène Berezikov, Alain Bucheton
Journal: Molecular Biology and Evolution (2001)

We have identified two novel, closely related subfamilies of non-long-terminal-repeat (non-LTR) retrotransposons in Drosophila melanogaster, the Waldo-A and Waldo-B subfamilies, that are in the same lineage as site-specific LTR retrotransposons of the R1 clade. Both contain potentially active copies with two large open reading frames, having coding capacities for a nucleoprotein as well as endonuclease and reverse transcriptase activities. Many copies are truncated at the 5′ end, and most are surrounded by target site duplications of variable lengths. Elements of both subfamilies have a nonrandom distribution in the genome, often being inserted within or very close to (CA)n arrays. At the DNA level, the longest elements of Waldo-A and Waldo-B are 69% identical on their entire length, except for the 5′ untranslated regions, which have a mosaic organization, suggesting that one arose from the other following new promoter acquisition. This event occurred before the speciation of the D. melanogaster subgroup of species, since both Waldo-A and Waldo-B coexist in other species of this subgroup.
Inguinal Hernias and Employment
Authors: Joseph L. Crumrine
Journal: JAMA (1982)

<h3>To the Editor.—</h3> In a recent issue ofThe Journal(1981;246:1019), T. Forrest Fisher, MD, answered a question regarding hernias on behalf of the Occupational Medical Practice Committee. The executive board of the Occupational Medical Association of New Jersey has reviewed this answer and believes clarification is needed. Statements are made that "The committee finds no data to show that people with enlarged internal inguinal rings and no hernia subsequently have a higher incidence of inguinal hernia" and "There is nothing in the medical literature to support the contention that a patient with an inguinal hernia is incapable of lifting heavy objects." Does the literature contain any data to the contrary? Is the committee recommending that no lifting restrictions be placed on an individual employee with a definite inguinal hernia and a moderate-sized defect? What references are available to substantiate this position? Part of the answer regarding medical indications for
Thrombocytopenia Found Uncommonly During Heparin Therapy
Authors: Peter J. Powers
Journal: JAMA (1979)

In a prospective study to determine the frequency of thrombocytopenia in patients treated with intravenous heparin sodium of porcine gut origin, only four of 120 patients with suspected venous thromboembolism showed a depression of the platelet count to below 150 x 10(9)/L. In two of these patients, heparin was not considered to be the cause of thrombocytopenia because the platelet count, which fell transiently, rose again while heparin therapy was continued. These results indicate that thrombocytopenia is an uncommon complication of anticoagulant therapy with heparin derived from porcine gut mucosa.
Endotoxin Induces Respiratory Failure and Increases Surfactant Turnover and Respiration Independent of Alveolocapillary Injury in Rats
Authors: Kate G. Davidson, Andrew D. Bersten, Heather A. Barr, Kay D. Dowling, Terence E. Nicholas, Ian R. Doyle
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Although endotoxin-induced acute lung injury is associated with inflammation, alveolocapillary injury, surfactant dysfunction, and altered lung mechanics, the precise sequence of these changes is polemic. We have studied the early pathogenesis of acute lung injury in spontaneously breathing anesthetized rats after intravenous infusion of Salmonella abortus equi endotoxin. The animals became hypoxic, and airway resistance, tissue resistance, lung elastance, and static compliance all deteriorated well before any change in alveolar neutrophils, macrophages, lung fluid (99mTc-labeled diethylenetriamine pentaacetic acid), or 125I-albumin flux, which were only appreciably increased at 8.5 hours. Lung elastance deteriorated before airway resistance, indicating that the compliance change was specific rather than caused by reduced lung volume. The subcellular and alveolar content of surfactant proteins A and B, cholesterol, disaturated phospholipids, and phospholipid classes remained normal in the face of a dramatic increase in the synthesis and turnover of 3H-disaturated phosphatidylcholine. Our findings indicate that the increase in surfactant disaturated phospholipid turnover reflects, at least in part, an approximately five-fold increase in "sigh frequency." We suggest that endotoxin has direct effects on tissue resistance and lung elastance independent of surfactant composition and that the initial respiratory failure results primarily from endotoxin-induced ventilation/perfusion mismatch independent of edema or alveolocapillary injury per se.