tbuckley/cabot-search huggingface dataset:
Nasopharyngeal carcinoma: molecular biomarker discovery and progress.
Authors: William Cho
Journal: Molecular Cancer (2007)

Nasopharyngeal carcinoma (NPC) is a rare malignancy in most part of the world and it is one of the most confusing, commonly misdiagnosed and poorly understood diseases. The cancer is an Epstein-Barr virus-associated malignancy with a remarkable racial and geographical distribution. It is highly prevalent in southern Asia where the disease occurs at a prevalence about a 100-fold higher compared with other populations not at risk. The etiology of NPC is thought to be associated with a complex interaction of genetic, viral, environmental and dietary factors. Thanks to the advancements in genomics, proteomics and bioinformatics in recent decades, more understanding of the disease etiology, carcinogenesis and progression has been gained. Research into these components may unravel the pathways in NPC development and potentially decipher the molecular characteristics of the malignancy. In the era of molecular medicine, specific treatment to the potential target using technologies such as immunotherapy and RNAi becomes formulating from bench to bedside application and thus makes molecular biomarker discovery more meaningful for NPC management. In this article, the latest molecular biomarker discovery and progress in NPC is reviewed with respect to the diagnosis, monitoring, treatment and prognostication of the disease.
Efficacy of roflumilast in former and current smokers with COPD
Authors: Peter Calverley, Udo-Michael Goehring, Fernando Martinez, Neil Barnes
Journal: European Respiratory Journal (2011)

Background/Rationale: A history of smoking is common in COPD pts. Pooled data from four 1-year studies of the selective phosphodiesterase 4 inhibitor roflumilast (ROF) were analysed to investigate the effects of smoking history on response to ROF.

Methods: Two studies enrolled pts with severe COPD associated with chronic bronchitis and a history of exacerbations and two studies enrolled pts with or without bronchitis and exacerbations. Following a 4-week placebo run-in, pts received ROF 500μg or placebo (PBO) for 52 wks. Primary endpoints were change in exacerbation rate and FEV1. We performed an analysis of these results according to smoking status.

Results: Mean age (SD) was 64.13 (9.17) yrs; 3440 (59.5%) pts were former smokers and 2337 (40.5%) pts were current smokers.

View this table:

Table 1





Conclusions: The efficacy of ROF vs PBO in reducing the rate of moderate or severe exacerbations and improving pre- and post-BD FEV1 in pts with established COPD was independent of smoking history.
Transformation of Human Leukocytes With Epstein-Barr Virus After Cellular Exposure to Chemical or Physical Mutagens&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: E E Henderson, R Ribecky
Journal: JNCI Journal of the National Cancer Institute (1980)

Assays that quantitate leukocyte transformation were used to determine the effect of two chemical and two physical mutagens on Epstein-Barr virus (EBV)-induced transformation of human umbilical cord leukocytes (HUCL). After treatment of HUCL with methyl methanesulfonate (MMS). UV light, or X-rays, lymphocyte transformation by EBV displayed a typical "survival" curve usually associated with agent toxicity in dividing cell populations. Viral transformation showed increasing resistance to each of these agents if the lymphocytes were treated after virus infection. No enhancement of viral transformation was detected following MMS, X-ray, or UV treatment. In contrast, after sublethal doses of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were administered, HUCL were more readily transformed by exogenous EBV. Also, in direct contrast to the other mutagens tested, EBV-induced transformation became markedly more sensitive to MNNG when leukocytes were treated after virus infection. Neither chemicals nor radiation alone was capable of initiating HUCL transformation, nor could infectious EBV be routinely recovered from transformed HUCL treated with MNNG or radiation. These results suggest that MNNG enhanced transformation by predisposing leukocytes toward transformation during EBV infection.
Effect of Smoking Cessation on Multiple Sclerosis Prognosis
Authors: Ryan Ramanujam, Anna-Karin Hedström, Ali Manouchehrinia, Lars Alfredsson, Tomas Olsson, Matteo Bottai, Jan Hillert
Journal: JAMA Neurology (2015)

<h3>Importance</h3> Smoking tobacco is a well-established risk factor for multiple sclerosis (MS), a chronic inflammatory disorder of the central nervous system usually characterized by bouts and remissions and typically followed by a secondary progressive (SP) course. However, it is not clear whether smoking after diagnosis is detrimental. <h3>Objective</h3> To determine whether smoking after MS diagnosis is associated with a change in time to SP disease. <h3>Design, Setting, and Participants</h3> Cross-sectional study of patients with prevalent MS who smoked at diagnosis (n = 728) taken from the Genes and Environment in Multiple Sclerosis Study, which consists of patients from the Swedish National MS Registry. The study entrance date was at time of first-year smoking. The study was conducted between November 2008 and December 2011, with patient environmental data collected from November 2009 to March 2011 via questionnaire. Study participants were from all counties in Sweden diagnosed as having MS at the time of the Genes and Environment in Multiple Sclerosis Study and registered in the Swedish National MS Registry. Patients with MS with relapsing-remitting disease course or SP were included. These patients' conditions were diagnosed according to the McDonald criteria and the patients responded to recruitment letters with detailed questionnaires. <h3>Exposure</h3> Smoking, considered yearly after diagnosis and combined into a time-invariant covariate before diagnosis. <h3>Main Outcomes and Measures</h3> Time to SPMS, measured using an accelerated failure time model, with smoking as a time-varying covariate. Other covariates included sex, age at diagnosis, snuff use, and smoking before diagnosis. <h3>Results</h3> The optimized model illustrated that each additional year of smoking after diagnosis accelerated the time to conversion to SPMS by 4.7% (acceleration factor, 1.047; 95% CI, 1.023-1.072;<i>P</i> &lt; .001). Kaplan-Meier plots demonstrated that those who continued to smoke continuously each year after diagnosis converted to SPMS faster than those who quit smoking, reaching SP disease at 48 and 56 years of age, respectively. <h3>Conclusions and Relevance</h3> This study provides evidence that continued smoking is associated with an acceleration in time to SPMS and that those who quit fare better. Therefore, we propose that patients with MS should be advised to stop smoking once a diagnosis has been made, not only to lessen risks for comorbidities, but also to avoid aggravating MS-related disability.
Transformation of Spleen Cells Three Hours After Infection In Vivo With Friend Leukemia Virus 2
Authors: Giovanni B. Rossi, Gustavo Cudkowicz, Charlotte Friend
Journal: JNCI Journal of the National Cancer Institute (1973)

Three hours after DBA/2 mice were infected with Friend leukemia virus (FLV), hemopoietic cells in the spleen were transformed into neoplastic cells as judged by 2 parameters: 1) the acquisition of autonomous growth potential on intravenous transplantation into nonirradiated histocompatible mice; 2) the serial transplantability in subcutaneous as well as hemopoietic sites. Both criteria sharply distinguished transformed cells from normal hemopoietic cells which do not grow in non irradiated mice and in the subcutaneous tissue. Transformation occurred in the initi'ally infected hosts and not after spleen cell transplantation by way of virus carried in the inoculum: InFected cells killed by sonic disruption or freezing and thawing fai led to induce transformation; cells harvested after <3 hours of exposure to FLV were not transformed; the pattern of hybrid resistance of (C57BL/6 × DBA/2)F1 and (BALB/c × DBA/2)F1 mice against the DBA/2 cells harvested 3 or more hours after inFection was similar to that displayed against normal hemopoietic and leukemic DBA/2 cells; and finally, the Fv-1 and Fv-2 genotype of the hybrids, which control susceptibility to infection, was not consistent with the possibility that the transformed cells were of host (F1) rather than donor (DBA/2) origin. The acquisition of autonomous growth potential and increased susceptibility to hybrid resistance (i.e., altered expression of hybrid-histocompatibility genes) are both early events in Friend virus-induced leukemogenesis, and the association might be significant.
Distinct Phenotype Clusters in Childhood Inflammatory Brain Diseases: Implications for Diagnostic Evaluation
Authors: Tania Cellucci, Pascal N. Tyrrell, Marinka Twilt, Shehla Sheikh, Susanne M. Benseler
Journal: Arthritis & Rheumatology (2013)

To identify distinct clusters of children with inflammatory brain diseases based on clinical, laboratory, and imaging features at presentation, to assess which features contribute strongly to the development of clusters, and to compare additional features between the identified clusters.A single-center cohort study was performed with children who had been diagnosed as having an inflammatory brain disease between June 1, 1989 and December 31, 2010. Demographic, clinical, laboratory, neuroimaging, and histologic data at diagnosis were collected. K-means cluster analysis was performed to identify clusters of patients based on their presenting features. Associations between the clusters and patient variables, such as diagnoses, were determined.A total of 147 children (50% female; median age 8.8 years) were identified: 105 with primary central nervous system (CNS) vasculitis, 11 with secondary CNS vasculitis, 8 with neuronal antibody syndromes, 6 with postinfectious syndromes, and 17 with other inflammatory brain diseases. Three distinct clusters were identified. Paresis and speech deficits were the most common presenting features in cluster 1. Children in cluster 2 were likely to present with behavior changes, cognitive dysfunction, and seizures, while those in cluster 3 experienced ataxia, vision abnormalities, and seizures. Lesions seen on T2/fluid-attenuated inversion recovery sequences of magnetic resonance imaging were common in all clusters, but unilateral ischemic lesions were more prominent in cluster 1. The clusters were associated with specific diagnoses and diagnostic test results.Children with inflammatory brain diseases presented with distinct phenotypical patterns that are associated with specific diagnoses. This information may inform the development of a diagnostic classification of childhood inflammatory brain diseases and suggest that specific pathways of diagnostic evaluation are warranted.
Osteoporosis services in secondary care: A UK survey
Authors: R E Rowe, C C Cooper
Journal: Journal of the Royal Society of Medicine (2000)

Summary A 1994 survey indicated that only 13 health authorities in the UK were purchasing access to dual X-ray absorptiometry (DXA), the most accurate measure of osteoporosis risk. By 1998 the number of centres (including private facilities providing DXA) was 161. All these were sent a questionnaire concerning their activities. 124 (77%) responded, and the survey found that DXA machines operate, on average, for only 3.6 days a week. Funding of and access to diagnostic services for osteoporosis varies greatly. There is clear scope for greater efficiency in the use of existing DXA machines and more equitable access to diagnostic services is required for effective management of osteoporosis.
Fluid challenges in intensive care: the FENICE study
Authors: Maurizio Cecconi, Christoph Hofer, Jean-Louis Teboul, Ville Pettila, Erika Wilkman, Zsolt Molnar, Giorgio Della Rocca, Cesar Aldecoa, Antonio Artigas, Sameer Jog, Michael Sander, Claudia Spies, Jean-Yves Lefrant, Daniel De Backer
Journal: Intensive Care Medicine (2015)

Fluid challenges (FCs) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units. There are clear benefits and harms from fluid therapy. Limited data on the indication, type, amount and rate of an FC in critically ill patients exist in the literature. The primary aim was to evaluate how physicians conduct FCs in terms of type, volume, and rate of given fluid; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC. This was an observational study conducted in ICUs around the world. Each participating unit entered a maximum of 20 patients with one FC. 2213 patients were enrolled and analyzed in the study. The median [interquartile range] amount of fluid given during an FC was 500 ml (500–1000). The median time was 24 min (40–60 min), and the median rate of FC was 1000 [500–1333] ml/h. The main indication for FC was hypotension in 1211 (59 %, CI 57–61 %). In 43 % (CI 41–45 %) of the cases no hemodynamic variable was used. Static markers of preload were used in 785 of 2213 cases (36 %, CI 34–37 %). Dynamic indices of preload responsiveness were used in 483 of 2213 cases (22 %, CI 20–24 %). No safety variable for the FC was used in 72 % (CI 70–74 %) of the cases. There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive, with an uncertain or with a negatively judged response. The current practice and evaluation of FC in critically ill patients are highly variable. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed FCs is not always taken into account.
Escape of Small Numbers of Allogeneic Lymphoma Cells From Immune Surveillance 2
Authors: Enzo Bonmassar, Emma Menconi, Abraham Goldin, Gustavo Cudkowicz
Journal: JNCI Journal of the National Cancer Institute (1974)

Cells of 4 radiation-induced lymphomas in C57BL/10, B10.129(5M), and B10.A mice were transplanted into congenic-resistant hosts across the major histocompatibility barrier. Relatively small grafts (10-105 cells) consistently escaped immune surveillance and grew progressively, whereas larger grafts (106-107 cells) were rejected. The mechanism of this dilution escape was investigated with the B10.A lymphoma (H-2a) transplanted into H-2K-lr incompatible B10.A(5R) mice (H-2f). The recipients were subjected to splenectomy, adoptive or active immunization before and after tumor grafting, and various schedules of antitumor and immunosuppressive treatments. The tumor cells were used after either serial syngeneic or allogeneic passages under conditions of dilution escape. The results did not support the hypotheses that active enhancing responses by the host, antigen simplification of tumor cells, and reduced immunosensitivity of lymphoma grafts influenced dilution escape. The hypothesis of creeping tumor growth to a population size overwhelming the host's immune defenses (i.e., the “sneaking through” mechanism) was inadequate to account for all experimental findings. Evidence was obtained that factors depressing antilymphoma allograft reactivity were associated with tumor cells. Hence dilution escape may be the result of a nonspecific inhibition of antilymphoma allograft reactions before the initially small tumor cell population reaches the size to be immunogenic.
Association of angiotensin I-converting enzyme gene polymorphism with susceptibility to antiproteinuric effect of angiotensin I-converting enzyme inhibitors in patients with proteinuria.
Authors: T Moriyama, H Kitamura, S Ochi, M Izumi, K Yokoyama, A Yamauchi, N Ueda, T Kamada, E Imai
Journal: Journal of the American Society of Nephrology (1995)

The antiproteinuric effect of angiotensin I-converting enzyme (ACE) inhibitors in patients with renal diseases of various origins has been well recognized. However, individual responses regarding the degree of decrease in urinary protein excretion appear to vary considerably. The mechanism underlying this variable response to ACE inhibitors has not been clarified yet. A possible role of ACE gene insertion/deletion (I/D) polymorphism in the responsiveness to antiproteinuric effect of ACE inhibitors is examined. Thirty-six patients with proteinuria (23 men and 13 woman; mean age, 47 +/- 13 yr) were studied. These patients were classified into two groups on the basis of the percent decrease in their urinary protein excretion: the effective group, those with a decrease in proteinuria (18 patients, -64 +/- 19%) and the noneffective group (18 patients, +13 +/- 40%). A 287-base pair (bp) I/D polymorphism in the ACE gene was examined by polymerase chain reaction. The allelic frequencies of the ACE gene were I/D = 0.53/0.47 in the effective group and I/D = 0.81/0.19 in the noneffective group. The difference in the allelic frequencies between the two groups was significant (chi 2 = 6.25, P = 0.0114 < 0.05). Furthermore, the difference in the responsiveness of proteinuria to ACE inhibition between genotype II versus genotype ID + DD was statistically significant (chi 2 = 4.05, P = 0.0442 < 0.05). There was no significant difference between the two groups with regard to initial urinary protein level, blood pressure, renal function, and daily sodium intake. The genetic susceptibility to the antihypertensive effect of ACE inhibitors was also studied, but no significant relation was observed. This study suggests the association of ACE gene I/D polymorphism with the antiproteinuric efficacy of ACE inhibitors in patients with proteinuria.
Systemic mastocytosis in adults: 2013 update on diagnosis, risk stratification, and management
Authors: Animesh Pardanani
Journal: American Journal of Hematology (2013)

Disease overview : Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extracutaneous organs. Diagnosis : The major criterion is presence of multifocal clusters of morphologically abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and/or CD2, and presence of KIT D816V. Risk stratification : The 2008 World Health Organization (WHO) classification of SM has been shown to be prognostically relevant. Classification of SM patients into indolent (SM), aggressive SM (ASM), SM associated with a clonal non‐MC lineage disease (SM‐AHNMD) and mast cell leukemia (MCL) subgroups is a useful first step in establishing prognosis. Management : SM treatment is generally palliative. ISM patients have a normal life expectancy and receive symptom‐directed therapy; infrequently, cytoreductive therapy may be indicated for refractory symptoms. ASM patients have disease‐related organ dysfunction; interferon‐α (±corticosteroids) can control dermatological, hematological, gastrointestinal, skeletal, and mediator‐release symptoms, but is hampered by poor tolerability. Similarly, cladribine has broad therapeutic activity, with particular utility when rapid MC debulking is indicated; the main toxicity is myelosuppression. Imatinib has a therapeutic role in the presence of an imatinib‐sensitive KIT mutation or in KIT D816‐unmutated patients. Treatment of SM‐AHNMD is governed primarily by the non‐MC neoplasm; hydroxyurea has modest utility in this setting. Investigational drugs : Dasatinib's in vitro anti‐ KITD816V activity has not translated into significant therapeutic activity in most SM patients. In contrast, recently updated data confirms Midostaurin's significant anti‐MC activity in patients with advanced SM. Am. J. Hematol. 88:612–624, 2013. © 2013 Wiley Periodicals, Inc.
Effects of Butyrate, Retinol, and Retinoic Acid on Human Y-79 Retinoblastoma Cells Growing in Monolayer Cultures
Authors: A Kyritsis, G Joseph, G J Chader
Journal: JNCI Journal of the National Cancer Institute (1984)

The effects of butyrate, retinol, and retinoic acid were tested on growth and differentiation of human Y-79 retinoblastoma cells in monolayer cultures. Treatment with 4 mM butyrate resulted in marked growth inhibition of cells, due mostly to increased death rate. The effect was greater in serum-supported cultures in which the proliferation rate was high and the effect was less in the serum-free, defined medium in which the cells were differentiated and the growth rate was slow, suggesting a cell-cycle-specific action of this substance. Moreover, butyrate induced morphologic changes in the viable cells; these changes consisted of an elongated appearance of the cells and of retraction of long processes formed in the serum-free-supported cultures. Retinol at 20 μM also affected the cell viability both in serum-containing and in serum-free culture medium. Retinoic acid at 50 μM induced reversible growth inhibition of cells growing in serum-containing medium and cell death in the defined medium-supported cultures. Combination of 0.5 mM butyrate with 50 μM retinoic acid resulted in an enhanced inhibition of growth in an apparently synergistic fashion. These results demonstrated that butyrate, retinol, and retinoic acid suppressed Y-79 cell growth in vitro and could be useful in future studies of these compounds in retinoblastoma tumors in vivo.
Drug-induced sleep endoscopy in pediatric obstructive sleep apnoea syndrome
Authors: An Boudewyns, Stijn Verhulst, Mieke Maris, Vera Saldien, Paul Van de Heyning
Journal: European Respiratory Journal (2013)

Introduction: About 25% of otherwise healthy children have persistent obstructive sleep apnoea (OSA) following adenotonsillectomy.  Aim: To investigate whether therapeutic decision making based upon upper airway evaluation by means of drug-induced sleep endoscopy (DISE) may improve treatment outcome.  Methods: Non-obese, non-syndromic and surgically naive OSA children underwent an upper airway endoscopy following administration of sevoflurane and/or propofol. The upper airway was examined under spontaneous breathing and the site (s) of upper airway obstruction or hypotonia were documented. Treatment decisions where based upon polysomnographic data and findings during DISE.  Results: Nineteen children age 5.2 (±3.6) years, BMI 15.8 (± 2.3) kg/m2, obstructive apnea/hypopnea index (OAHI) 21.6/r (± 27.8)/hr were included. Upper airway obstruction at the level of adenoids and tonsils was found in 15, these children were treated with adenotonsillectomy. Adenotomy was performed in 1 child with obstruction limted to the adenoidregion. Two children were treated with CPAP because of tonguebase collapse (n=1) or global hypotonia (n=1). One child with hypotonia and collapse of the epiglottis received orthodontic treatment. Postoperative polysomnographic data are presently available for 8 of those treated with adenotonsillectomy and all had an OAHI   Conclusions: This pilot study shows that drug-induced sleependoscopy is feasible in OSA children and DISE-directed treatment may improve therapeutic (surgical) outcomes.