tbuckley/cabot-search huggingface dataset:
Gene Expression Profiling for Discovery of Novel Markers of Minimal Disease
Authors: Virginie F. Viprey, Susan A. Burchill
Journal: Clinical Cancer Research (2009)

To the Editor: As Cheung et al. (1) report, accurate assessment of minimal disease is essential to inform the fight to cure children with neuroblastoma. Cheung et al. have exploited gene expression profiling to identify and prioritize targets for the detection of this disease using quantitative reverse transcriptase-PCR (RT-PCR). Eight of 34 genes are prioritized for investigation.Using a similar approach, we and others have previously identified three key mRNA targets (2); one of these targets (Phox2B) has also been prioritized by Cheung et al. Interestingly, the sensitivity and specificity of Phox2B as a target for the detection of minimal disease by quantitative RT-PCR in children with neuroblastoma has been corroborated (3, 4). However, differences in the remaining putative targets for optimal detection of minimal disease may lead to skepticism about the value of genome-wide expression data to inform candidate selection. Unfortunately, a direct comparison of data from the two Affymetrix array minimal disease studies in neuroblastoma (1, 2) is limited due to several differences in methods. First, the study of Cheung et al. (1) used the Affymetrix human U95 platform, in contrast to the U133 Plus 2.0 array used in our study (2). Using the U95 platform, Cheung et al. identified MEG3 and MLLT11 as specific sequences, although these probe sets also match to an additional five and two potential targets, respectively. This reinforces the importance of careful verification of probe-set gene annotation (2). Cheung et al. (1) report that they have excluded targets known to be expressed in bone marrow from healthy volunteers, although they do not describe the steps taken to identify such genes. Searching the National Center for Biotechnology Information expressed sequence tag database for the 34 potential markers of minimal disease identified by Cheung et al., we found that six of these genes have previously been described in bone marrow (CCND1, KIF21A, MLLT11, PFN2, UCHL1, and MAOA) and 11 in peripheral blood (CCND1, KIF21A, MLLT11, PFN2, KIF5C, MEG3, GRIA2, DDC, RGS5, KIF1A, and GABRB3) from healthy volunteers. Not surprisingly then, all but DDC were subsequently detected in normal blood using quantitative RT-PCR (1). The selection of eight targets for detection of minimal disease by Cheung et al. (1) is therefore questionable. The precision of minimal disease detection using quantitative RT-PCR will be facilitated by standardized assays for selected candidate genes not expressed in the normal hemopoietic compartments (2, 5).The clinical significance of minimal disease detected by quantitative RT-PCR for individual mRNAs emphasizes the importance of this disease and the studies by Cheung et al. (1), although it is unfortunate that they did not investigate the independent prognostic significance of detecting disease using individual and multiple marker sets (4).No potential conflicts of interest were disclosed.
ACALCULOUS ADENOMYOMATOSIS OF THE GALLBLADDER
Authors: G. Bevan
Journal: Gut (1970)

The course of acalculous adenomyomatosis of the gallbladder in six patients is described. It is suggested that, even in the absence of gallstones, cholecystectomy should be advised when this condition is demonstrated radiographically in symptomatic subjects. The cause of the pain is unknown but it is probably related to excessive neuromuscular activity of the hyperplastic gallbladder wall. One of the patients was found also to have an adenomatous polyp containing areas of adenocarcinoma. Although this polyp was not situated within an area of adenomyomatosis, it is possible that, as in most other patients with carcinoma of the gallbladder, previous disease may have predisposed to malignant change.
Twenty four hour intragastric acidity analysis for the future.
Authors: R Walt
Journal: Gut (1986)

Leading articleTwenty four hour intragastric acidity analysis for the future Studies of 24 hour intragastric acidity have been useful in the investigation of effects of diet,' 2 and drugs on gastric acidity in ulcer patients 3 and normal volunteers.14-178][19] The obvious advantage of the technique is that acidity is measured during relatively long periods of time under conditions which approximate to daily living.These conditions are easily reproduced and thus comparative studies are possible.The technique is labour intensive, however, and has some disadvantages.During the day only acidity is measured, as it is not possible to assess the volume of gastric secretion.Duodenogastric reflux almost certainly occurs, but cannot be estimated.Complete collections of gastric juice are sometimes made at night, to allow assessment of nocturnal secretion.Nocturnal acidity assessed in this way, however, poorly reflects 'real life' acidity because of continual aspiration of gastric contents.When small numbers of replicate studies have been done the results have been reasonable1 2 814 but the exact reproducibility and the magnitude of error implicit in the studies has not been accurately determined.Unfortunately the relationship of acidity to the aetiology, clinical manifestations and management of peptic ulcer disease is unclear.The results from acidity measurements may have little practical bearing on care of patients.If one assumes, as most do, that acid is detrimental to the duodenal mucosa (at least in some individuals), then decreasing the duodenal acid load would seem logical.It is not known whether small volumes of high acidity or large volumes of lower acidity are more damaging.It is not even clear whether the magnitude or timing of inhibition of acidity, or secretion, is of importance in clinical terms.Indeed, inhibition of 24 hour intragastric acidity is not a prerequisite for clinical efficacy with antisecretory agents.Nevertheless, it might be anticipated that drugs with similar effects on acidity would have similar clinical activity.On the other hand, drugs which produce virtual anacidity - for example, omeprazole -seem to accelerate duodenal ulcer healing compared with H2-receptor antagonists.20 21lthough one may question the relevance of the measurement of 24 hour intragastric acidity to clinical management, useful pharmacological comparisons between doses and drugs can be made.It has even been suggested that studies of nocturnal gastric acidity might identify those patients who respond poorly to H2-receptor antagonists. 2When drugs are used in the longer term, knowledge of the 24 hour acidity profile might alert one to potential problems related to hypoacidity such as bacterial colonisation and hypergastrinaemia (which could be predicted with omeprazole23 11 but are unlikely with conventional H2-receptor antago- 1
Knowledge of lung cancer symptoms and risk factors in the UK: development of a measure and results from a population-based survey
Authors: Alice E Simon, Dorota Juszczyk, Nina Smyth, Emily Power, Sara Hiom, Michael D Peake, Jane Wardle
Journal: Thorax (2012)

<h3>Objectives</h3> To develop and validate a Lung Cancer Awareness Measure (Lung CAM) and explore the demographical and social predictors of lung cancer awareness in the general population. <h3>Methods study 1</h3> Symptoms and risk factors for lung cancer were identified from the medical literature and health professional expertise in an iterative process. Test–retest reliability, internal reliability, item analyses, construct validity and sensitivity to changes in awareness of the Lung CAM were assessed in three samples (total N=191). <h3>Results study 1</h3> The Lung CAM demonstrated good internal (Cronbach9s α=0.88) and test–retest reliability (r=0.81, p&lt;0.001). Validity was supported by lung cancer experts scoring higher than equally educated controls (t(106)=8.7, p&lt;0.001), and volunteers randomised to read lung cancer information scoring higher than those reading a control leaflet (t(81)=3.66, p&lt;0.001). <h3>Methods study 2</h3> A population-based sample of 1484 adults completed the Lung CAM in a face-to-face, computer-assisted interview. <h3>Results study 2</h3> Symptom awareness was low (average recall of one symptom) and there was little awareness of risk factors other than smoking. Familiarity with cancer, and being from a higher socioeconomic group, were associated with greater awareness. <h3>Conclusions</h3> Using a valid and reliable tool for assessing awareness showed the UK population to have low awareness of lung cancer symptoms and risk factors. Interventions to increase lung cancer awareness are needed to improve early detection behaviour.
Childhood Abuse and Lifetime Psychopathology in a Community Sample
Authors: Harriet L. MacMillan, Jan E. Fleming, David L. Streiner, Elizabeth Lin, Michael H. Boyle, Ellen Jamieson, Eric K. Duku, Christine A. Walsh, Maria Y.-Y. Wong, William R. Beardslee
Journal: American Journal of Psychiatry (2001)

The authors assessed lifetime psychopathology in a general population sample and compared the rates of five psychiatric disorder categories between those who reported a childhood history of either physical or sexual abuse and those who did not.A modified version of the Composite International Diagnostic Interview and a self-completed questionnaire on child abuse were administered to a probability sample (N=7,016) of Ontario residents 15 to 64 years of age.Those reporting a history of childhood physical abuse had significantly higher lifetime rates of anxiety disorders, alcohol abuse/dependence, and antisocial behavior and were more likely to have one or more disorders than were those without such a history. Women, but not men, with a history of physical abuse had significantly higher lifetime rates of major depression and illicit drug abuse/dependence than did women with no such history. A history of childhood sexual abuse was also associated with higher rates of all disorders considered in women. In men, the prevalence of disorders tended to be higher among those who reported exposure to sexual abuse, but only the associations with alcohol abuse/dependence and the category of one or more disorders reached statistical significance. The relationship between a childhood history of physical abuse and lifetime psychopathology varied significantly by gender for all categories except for anxiety disorders. Although not statistically significant, a similar relationship was seen between childhood history of sexual abuse and lifetime psychopathology.A history of abuse in childhood increases the likelihood of lifetime psychopathology; this association appears stronger for women than men.
Cellular Lipids of the Legionnaires' Disease Bacterium
Authors: W. R. FINNERTY
Journal: Annals of Internal Medicine (1979)

We qualitatively and quantitatively analyzed the simple and complex lipids of 10 Legionnaires' disease bacteria. The phospholipids in decreasing order of concentration were phosphatidylcholine, phosphatidylethanolamine, cardiolipin, phosphatidylmonomethylethanolamine, phosphatidylglycerol, and phosphatidyldimethylethanolamine. The total phospholipids averaged 96 micromoles per gram dry cell weight. Phospholipid fatty acids were solely branched-chain fatty acids and were, in decreasing order of concentration, iso-C16:0, anteiso-C15:0, anteiso-C17:0, iso-C14:0, iso-C16:l, and an unidentified fatty acid. Neutral lipids identified were free fatty acid, ubiquinone, triglyceride, diglyceride, monoglyceride, and wax ester. Neutral lipid fatty acids consisted predominately of branched-chain fatty acids, normal fatty acids, and a minor unidentified fatty acid. Analysis of the cellular lipids of 10 Legionnaires' disease bacteria revealed an unusual and novel microorganism.
Relation Between Pulmonary Vein Firing and Extent of Left Atrial–Pulmonary Vein Connection in Patients With Atrial Fibrillation
Authors: Hiroshi Nakagawa, Hiroshi Aoyama, Karen J. Beckman, Sunny S. Po, Richard Wu, Deborah Lockwood, Peter Spector, James D. Calame, Daniel L. Lustgarten, Lisa Herring, Can Hasdemir, Dalip Singh, Ralph Lazzara, Warren M. Jackman
Journal: Circulation (2004)

The purpose of this study was to measure the extent of left atrial-pulmonary vein (LA-PV) connections and determine the relation to PV firing in patients with atrial fibrillation (AF).Ten close-bipolar (1 mm-spacing) Lasso electrograms were recorded circumferentially around 210 PVs (excluding 2 right middle PVs and 4 left common trunks) in 62 patients with AF. PV firing was provoked by isoproterenol (4 microg/min) and cardioversion of pacing-induced AF. The width of each LA-PV connection was measured in tenths of PV circumference, based on number of continuous close-bipolar Lasso electrode sites required for ablation (10% for each close-bipolar electrode site). One, 2, or 3 to 4 discrete LA-PV connections (discrete connection defined by ablation along 10% to 30% of PV circumference) were present in 18 (9%), 31 (14%), and 32 (15%) of 210 PVs, respectively: 1 broad connection (ablation along continuous 40% to 80% circumference) in 46 (22%) PVs; 1 broad plus other broad or discrete connections in 54 (26%) PVs; and a circumferential connection (ablation along 90% to 100%) in 29 (14%) PVs. Circumferential LA-PV connections were more common in superior than in inferior PVs (20% versus 7%, P<0.01). There was no major difference in distribution of the other types of LA-PV connections between the four PVs. PV firing occurred in 27%, 47%, and 72% of PVs with discrete only, broad and circumferential connections, respectively (P<0.01). Dissociated PV potentials after isolation were more common in arrhythmogenic (firing) PVs (32% versus 8%, P<0.01).The extent of LA-PV connections corresponds with arrhythmognesis. The incidence of PV firing increases with progressively wider LA-PV connections (discrete versus broad versus circumferential).
Jesse Bullowa, specific treatment for pneumonia, and the development of the controlled clinical trial
Authors: Scott H Podolsky
Journal: Journal of the Royal Society of Medicine (2009)

Jesse Bullowa's 1928 report on the use of antipneumococcic serum in lobar pneumonia1 was subtitled ‘Data necessary for a comparison between cases treated with serum and cases not so treated, and the importance of a significant control series of cases’. It stands out as one of the most sophisticated invocations of the controlled clinical trial in the 1920s, and as a self‐conscious attempt to justify and promote the methodology. Indeed, Bullowa's contribution to a symposium on the treatment of pneumonia at the New York Academy of Medicine in December 1927 was entitled simply ‘The control’.2 In focusing explicit attention on methodological issues, Bullowa made clear that he wished to determine ‘whether there was conclusive proof that the serum is of value’.1

Bullowa, nearly 50 years old at the time of his presentation at the New York Academy of Medicine, was a clinical professor at the New York University College of Medicine3 and co‐director, with Milton Rosenbluth, of Harlem Hospital's pneumonia service, then ‘the largest therapy unit of any hospital in the city’.4 During the previous decade, Rufus Cole and his colleagues at the Hospital of the Rockefeller Institute had introduced serotype‐specific antiserum for the treatment of pneumococcal pneumonia (as of 1928, only four such pneumococcal serotypes were known). When the Metropolitan Life Insurance Company lost 24 million dollars in excess death benefits during the influenza epidemic of 1918, it established an Influenza Commission, which would soon focus its attention upon pneumonia and its treatment with antipneumococcal antiserum.5 Intending to fund alternate control studies at multiple institutions,6 the company would ultimately fund published studies arising from Bellevue and Harlem Hospitals in New York, and from Boston City Hospital.7–9 However, none of the pneumonia investigators – who included such eventual luminaries as Russell Cecil (at Bellevue Hospital in New York) and Maxwell Finland (at Boston City Hospital) – would so explicitly advocate the methodology of the controlled clinical trial as would Jesse Bullowa.
Phase I/II Trial and Pharmacokinetic Study of Cixutumumab in Pediatric Patients With Refractory Solid Tumors and Ewing Sarcoma: A Report From the Children's Oncology Group
Authors: Suman Malempati, Brenda Weigel, Ashish M. Ingle, Charlotte H. Ahern, Julie M. Carroll, Charles T. Roberts, Joel M. Reid, Stephen Schmechel, Stephan D. Voss, Steven Y. Cho, Helen X. Chen, Mark D. Krailo, Peter C. Adamson, Susan M. Blaney
Journal: Journal of Clinical Oncology (2011)

A phase I/II study of cixutumumab (IMC-A12) in children with refractory solid tumors was conducted. This study was designed to assess the toxicities, pharmacokinetics, and pharmacodynamics of cixutumumab in children to determine a recommended phase II dose and to assess antitumor activity in Ewing sarcoma (ES).
Itk and Fyn Make Independent Contributions to T Cell Activation
Authors: X. Charlene Liao, Dan R. Littman, Arthur Weiss
Journal: The Journal of Experimental Medicine (1997)

Itk is a member of the Btk/Tec/Itk family of nonreceptor protein tyrosine kinases (PTKs), and has been implicated in T cell antigen receptor (TCR) signal transduction. Lck and Fyn are the Src-family nonreceptor PTKs that are involved in TCR signaling. To address the question of how these members of different families of PTKs functionally contribute to T cell development and to T cell activation, mice deficient for both Itk and either Lck or Fyn were generated. The Itk/Lck doubly deficient mice exhibited a phenotype similar to that of Lck-deficient mice. The phenotype of the Itk/Fyn doubly deficient mice was similar to that of Itk deficient mice. However the Itk/Fyn doubly deficient mice exhibited a more severe defect in TCR-induced proliferation of thymocytes and peripheral T cells than did mice deficient in either kinase alone. These data support the notion that Itk and Fyn both make independent contributions to TCR-induced T cell activation.
Insulin-like growth factor I improves intestinal barrier function in cirrhotic rats
Authors: Vicente Lorenzo-Zuñiga, Carlos M Rodriguez-Ortigosa, Ramon Bartoli, Maria Luz Martinez-Chantar, Laura Martinez-Peralta, Ana Pardo, Isabel Ojanguren, Jorge Quiroga, Ramon Planas, Jesus Prieto
Journal: Gut (2006)

<b>Background and aims:</b> In liver cirrhosis, disruption of the intestinal barrier facilitates bacterial translocation and spontaneous bacterial peritonitis. Insulin-like growth factor I (IGF-I) is an anabolic hormone synthesised by hepatocytes that displays hepatoprotective activities and trophic effects on the intestine. The aim of this study was to investigate the effect of IGF-I on intestinal barrier function in cirrhotic rats. <b>Methods:</b> In rats with carbon tetrachloride induced cirrhosis, we investigated the effect of IGF-I therapy on: (a) portal pressure; (b) intestinal histology and permeability to endotoxin and bacteria; (c) intestinal expression of cyclooxygenase 2 (COX-2) and tumour necrosis factor α (TNF-α), two factors that influence in a positive and negative manner, respectively, the integrity of the intestinal barrier; (d) intestinal permeability to <sup>3</sup>H-mannitol in rats with bile duct ligation (BDL); and (e) transepithelial electrical resistance (TER) of polarised monolayers of rat small intestine epithelial cells. <b>Results:</b> IGF-I therapy reduced liver collagen expression and portal pressure in cirrhotic rats, induced improvement in intestinal histology, and caused a reduction in bacterial translocation and endotoxaemia. These changes were associated with diminished TNF-α expression and elevated COX-2 levels in the intestine. IGF-I reduced intestinal permeability in BDL rats and enhanced barrier function of the monolayers of epithelial intestinal cells where lipopolysaccharide (LPS) caused a decrease in TER that was reversed by IGF-I. This effect of IGF-I was associated with upregulation of COX-2 in LPS treated enterocytes. <b>Conclusions:</b> IGF-I enhances intestinal barrier function and reduces endotoxaemia and bacterial translocation in cirrhotic rats. IGF-I therapy might be useful in the prevention of spontaneous bacterial peritonitis in liver cirrhosis.
Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes
Authors: Harald H H Göring, Joanne E Curran, Matthew P Johnson, Thomas D Dyer, Jac Charlesworth, Shelley A Cole, Jeremy B M Jowett, Lawrence J Abraham, David L Rainwater, Anthony G Comuzzie, Michael C Mahaney, Laura Almasy, Jean W MacCluer, Ahmed H Kissebah, Gregory R Collier, Eric K Moses, John Blangero
Journal: Nature Genetics (2007)
Decoding the Histone Code: Role of H3K36me3 in Mismatch Repair and Implications for Cancer Susceptibility and Therapy
Authors: Guo-Min Li
Journal: Cancer Research (2013)

DNA mismatch repair (MMR) maintains genome stability primarily by correcting replication-associated mismatches. Defects in MMR lead to several human cancers characterized by frequent alterations in simple repetitive DNA sequences, a phenomenon called microsatellite instability (MSI). In most MSI-positive cancers, genetic or epigenetic changes that alter the function or expression of an essential MMR protein have been identified. However, in a subset of MSI-positive cancers, epigenetic or genetic changes have not been found in known MMR genes, such that the molecular basis of the MMR defect in these cells remains unknown. A possible answer to this puzzle emerged recently when it was discovered that H3K36me3, a well-studied posttranslational histone modification or histone mark, plays a role in regulating human MMR in vivo. In this review, potential roles for this histone mark to modulate genome stability and cancer susceptibility in human cells are discussed.
An eruption associated with alphavirus infection
Authors: P. AUTIO, K.M. NIEMI, A.-L. KARINIEMI
Journal: British Journal of Dermatology (1996)

Some alphaviruses, e.g. Sindbis, cause an acute febrile illness associated with papular rashes and arthralgia. The diagnosis is usually serological and, hence, the histopathology of the rashes has been poorly elucidated. We report on two patients with rapidly healing eruptions associated with Sindbis virus infection. The histopathology of the rashes showed large, pronounced lymphohistiocytic infiltrates with atypical lymphoid cells around the hair follicles, changes not usually seen in rapidly-healing dermatoses.