tbuckley/cabot-search huggingface dataset:
Allelic Imbalance Analysis Using a Single-Nucleotide Polymorphism Microarray for the Detection of Bladder Cancer Recurrence
Authors: Marieke J.H. Coenen, Martine Ploeg, Mascha M.V.A.P. Schijvenaars, Erik B. Cornel, Herbert F.M. Karthaus, Hans Scheffer, J. Alfred Witjes, Barbara Franke, Lambertus A.L.M. Kiemeney
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Non–muscle-invasive bladder cancer is a frequently occurring cancer, with an extremely high recurrence risk. Recurrence detection is based on cytology and urethrocystoscopy. A previous study suggested that a single-nucleotide polymorphism (SNP) array may be effective for noninvasive detection of allelic imbalances in urine. We investigated whether this method is suitable to detect allelic imbalance as an indicator of recurrences in non–muscle-invasive bladder cancer follow-up. Experimental Design: DNA from blood and urine from 158 patients (113 with and 45 without recurrence) was hybridized to the Affymetrix GeneChip Mapping 10K 2.0. Allelic imbalance detection was based on SNPs showing changes from heterozygosity in blood to homozygosity in urine and on automatic analysis of copy number changes using Copy Number Analyser for GeneChip. Results: Urine samples with tumor showed allelic imbalance at 0.4% of all informative SNPs. In samples without tumors, 0.04% of these SNPs were affected (P = 0.07). In addition, Copy Number Analyser for GeneChip analysis showed more copy number changes in samples with a tumor (P = 0.001). Losses and gains of chromosomal regions showed clustering, overlapping with known bladder cancer loci. However, 25 (22%) patients with a tumor recurrence did not display any regions with copy number changes, whereas 24 (53%) individuals without a recurrence did. Receiver operating characteristic curve analysis using the number of SNPs displaying copy number changes from the Copy Number Analyser for GeneChip analysis resulted in an area under the curve of only 0.67 (95% confidence interval, 0.58-0.76). Conclusion: Single-nucleotide polymorphism microarray analysis of allelic imbalance in urine cannot replace urethrocystoscopy and cytology for the detection of recurrences in non–muscle-invasive bladder cancer follow-up.
UK blood service is responding to current needs
Authors: E A E Robinson
Journal: BMJ (1999)

EDITOR —Booth's comments on blood donation have to be considered in the context of delivering a national service to donors, hospitals, and patients. The National Blood Service needs to collect 10000 voluntary blood donations every day to meet the needs of all the hospitals in England and north Wales. We are keen to consider partnerships with hospitals where our combined efforts could provide a better as well as a cost effective service to patients and donors. Indeed, we already hold …
Gene from a Psoriasis Susceptibility Locus Primes the Skin for Inflammation
Authors: Ronald Wolf, Francesca Mascia, Alif Dharamsi, O. M. Zack Howard, Christophe Cataisson, Val Bliskovski, Jason Winston, Lionel Feigenbaum, Ulrike Lichti, Thomas Ruzicka, Triantafyllos Chavakis, Stuart H. Yuspa
Journal: Science Translational Medicine (2010)

Psoriasis candidate genes promote susceptibility to skin inflammation and provide a treatment approach for psoriasis-related inflammation.
Are Asthma Medications and Management Related to Deaths from Asthma?
Authors: MICHAEL J. ABRAMSON, MICHAEL J. BAILEY, FIONA J. COUPER, JAN S. DRIVER, OLAF H. DRUMMER, ANDREW B. FORBES, JOHN J. McNEIL, E. HAYDN WALTERS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

There is controversy about the role of β -agonists in asthma mortality, and the impact of asthma management plans remains unclear. We compared blood β -agonist levels in patients dying from asthma with those in controls, and estimated the risks associated with specific classes of medication and patterns of management. We identified 89 asthma deaths and recruited 322 patients presenting to hospitals with acute asthma. A questionnaire was administered to the next of kin in 51 cases, and to 202 controls. Blood drawn from 35 cases and 229 controls was assayed for salbutamol. Smoking, drinking, and family problems were significantly more likely among the cases of asthma death than among the controls. The two groups were reasonably well matched with regard to markers of chronic asthma severity. Cases of asthma death were significantly less likely than controls to use a peak flow meter. Written action plans were associated with a 70% reduction in the risk of death. Use of nebulized bronchodilators or oral steroids was significantly more likely in cases of asthma death. Mean blood salbutamol concentrations were 2.5 times higher in cases of asthma. The use of oral steroids for an attack of asthma reduced the risk of death by 90%. More widespread adoption of written asthma management plans, with less reliance on β -agonists and closer medical supervision, should reduce asthma mortality.
More Accurate Quantification of Pulmonary Blood Flow by Magnetic Resonance Imaging Than by Lung Perfusion Scintigraphy in Patients With Fontan Circulation
Authors: Sohrab Fratz, John Hess, Markus Schwaiger, Stefan Martinoff, Heiko C. Stern
Journal: Circulation (2002)

Background— Quantitative evaluation of pulmonary perfusion using lung perfusion scintigraphy in patients with atriopulmonary anastomosis (APA) or total cavopulmonary connection (TCPC) or partial cavopulmonary connection (PCPC) is difficult because of preferential draining of the venae cavae to one lung. Scintigraphy is the gold standard. Phase-velocity MRI (PV-MRI) is a new technique for determining pulmonary perfusion. The aim of this study was therefore to determine whether PV-MRI is more accurate than scintigraphy for quantitative evaluation of pulmonary perfusion ratios in patients with APA, TCPC, or PCPC. Methods and Results— We studied 15 patients with APA, TCPC, or PCPC (16±7 years old, 4 female). Twelve patients (15±8 years old, 3 female) with a single pulmonary blood source supplied by a subpulmonary ventricle, ensuring complete mixing of the radioactive tracer before entering the pulmonary circulation, served as controls. Pulmonary scintigraphy and PV-MRI were performed in all patients. Bland-Altman analysis showed a clinically unacceptable difference of 7.1% right pulmonary blood flow (27.2% upper and −13.0% lower limit of agreement) between the two methods in the study group. The two methods agreed excellently in the control group (difference, 1.6%; 4.0% upper and −7.2% lower limit of agreement), showing that the bad agreement in the study group was caused by the problems encountered using pulmonary scintigraphy in patients with APA, TCPC, or PCPC. Conclusions— Because of preferential caval flow into either lung, PV-MRI is more accurate for evaluating pulmonary perfusion ratios than lung perfusion scintigraphy in patients with Fontan-like circulation.
Development of specific receptors for N-formylated chemotactic peptides in a human monocyte cell line stimulated with lymphokines
Authors: MC Pike, DG Fischer, HS Koren, R Snyderman
Journal: The Journal of Experimental Medicine (1980)

A human monocyte-like cell line, U937, when grown in continuous culture, does not secrete lysosomal enzymes or migrate towards chemotactic factors. When the cells are stimulated by lymphokines, however, they develop the ability both to migrate directionally and to secrete enzymes in response to several types of chemoattractants. The development, by stimulated cells, of chemotactic and secretory responses to one class of chemoattractants, the N- formylated peptides, is accompanied by the appearance on the cells of specific binding sites for these substances. Using tritiated N-formyl- methionyl-leueyl-phenylalanine (fMet-Leu-[(3)H]Phe) as a ligand, it was determined that unstimulated U937 cells possess no detectable binding sites. However, after stimulation with lymphocyte culture supernates for 24, 48, and 72 h, they developed 4,505 (+/-) 1,138, 22,150(+/-) 4,030, and 37,200 (+/-) 8,000 sites/cell, respectively. The dissociation constants for the interaction of fMet-Leu-[SH]Phe with the binding sites were approximately the same regardless of stimulation time and ranged between 15 and 30 nM. The binding of fMet-Leu-[(3)H]Phe by stimulated U937 cells was rapid and readily reversed by the addition of a large excess of unlabeled peptide. The affinity of a series of N-formylated peptides for binding to U937 cells exactly reflected the potency of the peptides in inducing lysosomal enzyme secretion and chemotaxis. The availability of a continuous human monocytic cell line that can be induced to express receptors for N-formylated peptides will provide a useful tool not only for the characterization of such receptors but also for the delineation of regulatory mechanisms involved in cellular differentiation and the chemotactic response.
MESENCHYME AND MESOTHELIUM
Authors: Warren H. Lewis
Journal: The Journal of Experimental Medicine (1923)

The migratory mesenchymal cells in cultures of the embryonic chick heart show all stages of transformation from the bipolar and multipolar reticular cells to the flat mesothelial forms. One can actually observe this change in form. Such mesothelial cells seem to differ from the mesenchymal cells only in form and not in structure, indicating that mesothelium is to be considered not as a tissue differentiated from the mesenchyme, but merely as a change or transformation in form. These observations, together with those of W. C. Clarke, indicate that, in the healing of wounds of the mesothelium lining the peritoneal, pleural, and serous cavities, new mesothelium may arise from the subjacent mesenchyme by the change in form of its cells, and that the repair after abrasions of the mesothelium is not necessarily brought about by a spreading of the adjacent mesothelium over the wound, such as occurs in repair of skin wounds.
Lung Cancer Screening Trial Financed by Tobacco-Funded Foundation, Sparks Debate
Authors: R. Twombly
Journal: JNCI Journal of the National Cancer Institute (2008)

F or those who are worried about conflicts of interest in medical research, the news that a cigarette company helped fund a major lung cancer screening study, revealed in a front page story in the New York Times and in the Cancer Letter , represented a perfect storm of ethical issues that could further erode public confidence in the value of academic science. The story highlighted how two discrete issues that research institutions grapple with — fi nancial confl ict of interest and use of tobacco company money to fund research — came together in a highly unusual way, complicating the inter pretation of results from internationally known re searchers and a major medical institution. The Times and the Cancer Letter reported that Weill Cornell Medical College researchers Claudia Henschke, M.D., Ph.D., and David Yankelevitz, M.D., its dean, Antonio Gotto, M.D., D.Phil., and the vice chairman of the college board of overseers, Arthur J. Mahon, were offi cers of a charity called the Foundation for Lung Cancer: Early Detection, Prevention, and Treatment. That charity was almost exclusively funded by $3.6 million in funds donated by the Vector Group, the holding company for Liggett Tobacco, which makes several different brands of cigarettes. Henschke and Yankelevitz used the funds as seed money to help launch studies to test whether computed tomography (CT) screening of patients at risk for lung cancer can lead to early detection of the disease. Published studies from the group have shown a connection between CT screening and improved detection, and results from the Cornell-led International Early Lung Cancer Action Program (I-ELCAP), published in the New England Journal of Medicine in 2006, demonstrate that CT screening saves lives, according to Henschke. The fi ndings created controversy among lung cancer researchers, some of whom said that the nonrandomized study did not prove that such screening could reduce mortality. But the connection between Liggett Tobacco and the researchers was not transparent in the journals that published results of I-ELCAP and earlier studies. The foundation was listed as one of 32 funding sources in the NEJM publication, but not the fact that it contained Liggett Tobacco funds and little else.
Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis
Authors: M. Balsells, A. Garcia-Patterson, I. Sola, M. Roque, I. Gich, R. Corcoy
Journal: BMJ (2015)

<b>Objective</b> To summarize short term outcomes in randomized controlled trials comparing glibenclamide or metformin versus insulin or versus each other in women with gestational diabetes requiring drug treatment. <b>Design</b> Systematic review and meta-analysis. <b>Eligibility criteria for selecting studies</b> Randomized controlled trials that fulfilled all the following: (1) published as full text; (2) addressed women with gestational diabetes requiring drug treatment; (3) compared glibenclamide <i>v</i> insulin, metformin <i>v</i> insulin, or metformin <i>v</i> glibenclamide; and (4) provided information on maternal or fetal outcomes. <b>Data sources</b> Medline, CENTRAL, and Embase were searched up to 20 May 2014. <b>Outcomes measures</b> We considered 14 primary outcomes (6 maternal, 8 fetal) and 16 secondary (5 maternal, 11 fetal) outcomes. <b>Results</b> We analyzed 15 articles, including 2509 subjects. Significant differences for primary outcomes in glibenclamide <i>v</i> insulin were obtained in birth weight (mean difference 109 g (95% confidence interval 35.9 to 181)), macrosomia (risk ratio 2.62 (1.35 to 5.08)), and neonatal hypoglycaemia (risk ratio 2.04 (1.30 to 3.20)). In metformin <i>v</i> insulin, significance was reached for maternal weight gain (mean difference −1.14 kg (−2.22 to −0.06)), gestational age at delivery (mean difference −0.16 weeks (−0.30 to −0.02)), and preterm birth (risk ratio 1.50 (1.04 to 2.16)), with a trend for neonatal hypoglycaemia (risk ratio 0.78 (0.60 to 1.01)). In metformin <i>v</i> glibenclamide, significance was reached for maternal weight gain (mean difference −2.06 kg (−3.98 to −0.14)), birth weight (mean difference −209 g (−314 to −104)), macrosomia (risk ratio 0.33 (0.13 to 0.81)), and large for gestational age newborn (risk ratio 0.44 (0.21 to 0.92)). Four secondary outcomes were better for metformin in metformin <i>v</i> insulin, and one was worse for metformin in metformin <i>v</i> glibenclamide. Treatment failure was higher with metformin than with glibenclamide. <b>Conclusions</b> At short term, in women with gestational diabetes requiring drug treatment, glibenclamide is clearly inferior to both insulin and metformin, while metformin (plus insulin when required) performs slightly better than insulin. According to these results, glibenclamide should not be used for the treatment of women with gestational diabetes if insulin or metformin is available. <b>Systematic review registration</b>NCT01998113
Increased exercise ventilation in patients with chronic heart failure: intact ventilatory control despite hemodynamic and pulmonary abnormalities.
Authors: M J Sullivan, M B Higginbotham, F R Cobb
Journal: Circulation (1988)

This study was designed to determine the pathophysiologic basis of increased exercise ventilation in the presence of chronic heart failure. Sixty-four ambulatory patients with chronic heart failure and 38 age-matched normal control subjects performed exercise according to identical staged, symptom-limited bicycle exercise protocols with measurement of hemodynamic, ventilatory, and metabolic responses. Compared with normal subjects, ventilation and the ratio of ventilation to CO2 production (Ve/VCO2), and pulmonary capillary wedge pressure were elevated in patients at rest and during exercise. The ratio of pulmonary dead space to tidal volume (Vd/Vt) also was elevated in the heart failure group at rest and during exercise and was closely related to Ve/VCO2 (all r greater than .72, p less than .001). Rest and exercise arterial PCO2 regulation was normal in patients. Peak exercise Ve/VCO2 did not correlate with pulmonary vascular pressures, but was inversely related to cardiac output (r = -.49, p less than .001). Thus, neurohumoral ventilatory control mechanisms are intact in patients with chronic heart failure and act to maintain normal PaCO2 levels in the face of increased pulmonary dead space. Activation of abnormal reflexes due to hemodynamic derangements during exercise are not important in determining ventilation in the presence of chronic heart failure. The demonstration of a correlation between decreased cardiac output and increased ventilation in the patient group suggests that attenuated pulmonary perfusion may play a role in causing exercise hyperpnea in the presence of chronic heart failure by producing ventilation perfusion abnormalities and thereby increasing physiologic pulmonary dead space.
Identification of Stage‐Specific Genes Associated With Lupus Nephritis and Response to Remission Induction in (NZB × NZW)F1 and NZM2410 Mice
Authors: Ramalingam Bethunaickan, Celine C. Berthier, Weijia Zhang, Ridvan Eksi, Hong‐Dong Li, Yuanfang Guan, Matthias Kretzler, Anne Davidson
Journal: Arthritis & Rheumatology (2014)

Objective To elucidate the molecular mechanisms involved in renal inflammation during the progression, remission, and relapse of nephritis in murine lupus models using transcriptome analysis. Methods Kidneys from (NZB × NZW)F1 (NZB/NZW) and NZM2410 mice were harvested at intervals during the disease course or after remission induction. Genome‐wide expression profiles were obtained from microarray analysis of perfused kidneys. Real‐time polymerase chain reaction (PCR) analysis for selected genes was used to validate the microarray data. Comparisons between groups using SAM, and unbiased analysis of the entire data set using singular value decomposition and self‐organizing maps were performed. Results Few changes in the renal molecular profile were detected in prenephritic kidneys, but a significant shift in gene expression, reflecting inflammatory cell infiltration and complement activation, occurred at proteinuria onset. Subsequent changes in gene expression predominantly affected mitochondrial dysfunction and metabolic stress pathways. Endothelial cell activation, tissue remodeling, and tubular damage were the major pathways associated with loss of renal function. Remission induction reversed most, but not all, of the inflammatory changes, and progression toward relapse was associated with recurrence of inflammation, mitochondrial dysfunction, and metabolic stress signatures. Conclusion Immune cell infiltration and activation is associated with proteinuria onset and is reversed by immunosuppressive therapy, but disease progression is associated with renal hypoxia and metabolic stress. Optimal therapy for lupus nephritis may therefore need to target both immune and nonimmune disease mechanisms. In addition, the overlap of a substantial subset of molecular markers with those expressed in the kidneys of lupus patients suggests potential new biomarkers and therapeutic targets.
The in vitro induction of immunological tolerance in the B lymphocyte by oligovalent thymus-dependent antigens.
Authors: J W Schrader
Journal: The Journal of Experimental Medicine (1975)

B-cell tolerance has been induced by oligovalent thymus-dependent antigens in an entirely in vitro system. Dissociated spleen cells from congenitally athymic (nu/nu) mice were preincubated for 24 h with 0.1 -- 1 mg/ml of either fowl gamma globulin (FGG) of DNP-human gamma globulin (DNP-HGG). After washing, the cells were tested for the ability to mount in vitro, thymus-independent responses against FGG and DNP. A state of specific responsiveness to either FGG or DNP was thus demonstrated. Features of this wholly in vitro system that paralleled previous findings on the in vivo induction of B-cell tolerance in nu/nu mice were the kinetics, 24 h being required for tolerance induction in either case, the abrogation of tolerance induction by the presence of POL both in vivo and in vitro, and finally the observation that in neither case was there a requirement for the antigens to be deaggregated. It was shown that DNP-(Fab) 2 fragments prepared from HGG induced DNP-specific tolerance indicating that the Fc piece was not required for tolerance induction in this in vitro system. DNP-bovine serum albumin was less effective than DNP-HGG or DNP-(Fab)2. Preincubation with subtoxic concentrations of DNP-lysine of DNP-epsilon-capric acid had only a marginal effect on DNP responsiveness. Since nu/nu mice, lacking in detectable T-cell function, were used as spleen cell donors, this work provides further evidence that B-cell tolerance to thymus-dependent antigens can be induced without the participation of T cells. It is suggested that B-cell tolerance to thymus-dependent antigens occurs when the antigen in a sufficient concentration and over a sufficient period of time has direct access to the B cell. This contact with antigen must be in the absence of an additional influence provided either by adjuvants like endotoxin or POL, or by activated macrophages, which may be stimulated by activated T cells; otherwise not tolerance but B-cell activation will occur.
METABOLIC FATE OF FOOD COLORANTS
Authors: Thomas M. Parkinson, Joseph P. Brown
Journal: Annual Review of Nutrition (1981)

Evaluation of the chemical and biological data on synthetic and natural food colorants indicates that synthetic colorants in general have been studied more thoroughly than their natural counterparts. The increasing use of natural colorants in processed foods at levels higher than those found in natural sources has raised concern about deficiencies in knowledge, in some cases, of their exact chemical composition, stability, metabolic fate, and toxic potential. Additional studies, particularly of comparative metabolic fate in experimental animals and in man and of genotoxic potential, are required. Until studies with natural colorants comparable to those carried out with synthetic colorants have been completed and evaluated, greater safety of natural colorants cannot be assumed.