tbuckley/cabot-search huggingface dataset:
Urinary Cell mRNA Profiles and Differential Diagnosis of Acute Kidney Graft Dysfunction
Authors: Marie Matignon, Ruchuang Ding, Darshana M. Dadhania, Franco B. Mueller, Choli Hartono, Catherine Snopkowski, Carol Li, John R. Lee, Daniel Sjoberg, Surya V. Seshan, Vijay K. Sharma, Hua Yang, Bakr Nour, Andrew J. Vickers, Manikkam Suthanthiran, Thangamani Muthukumar
Journal: Journal of the American Society of Nephrology (2014)

Noninvasive tests to differentiate the basis for acute dysfunction of the kidney allograft are preferable to invasive allograft biopsies. We measured absolute levels of 26 prespecified mRNAs in urine samples collected from kidney graft recipients at the time of for-cause biopsy for acute allograft dysfunction and investigated whether differential diagnosis of acute graft dysfunction is feasible using urinary cell mRNA profiles. We profiled 52 urine samples from 52 patients with biopsy specimens indicating acute rejection (26 acute T cell–mediated rejection and 26 acute antibody-mediated rejection) and 32 urine samples from 32 patients with acute tubular injury without acute rejection. A stepwise quadratic discriminant analysis of mRNA measures identified a linear combination of mRNAs for CD3ε, CD105, TLR4, CD14, complement factor B, and vimentin that distinguishes acute rejection from acute tubular injury; 10-fold cross-validation of the six-gene signature yielded an estimate of the area under the curve of 0.92 (95% confidence interval, 0.86 to 0.98). In a decision analysis, the six-gene signature yielded the highest net benefit across a range of reasonable threshold probabilities for biopsy. Next, among patients diagnosed with acute rejection, a similar statistical approach identified a linear combination of mRNAs for CD3ε, CD105, CD14, CD46, and 18S rRNA that distinguishes T cell–mediated rejection from antibody-mediated rejection, with a cross-validated estimate of the area under the curve of 0.81 (95% confidence interval, 0.68 to 0.93). Incorporation of these urinary cell mRNA signatures in clinical decisions may reduce the number of biopsies in patients with acute dysfunction of the kidney allograft.
THE ORGANIZATION OF BEHAVIORAL REPERTOIRE IN MOTOR CORTEX
Authors: Michael Graziano
Journal: Annual Review of Neuroscience (2006)

Motor cortex in the primate brain was once thought to contain a simple map of the body's muscles. Recent evidence suggests, however, that it operates at a radically more complex level, coordinating behaviorally useful actions. Specific subregions of motor cortex may emphasize different ethologically relevant categories of behavior, such as interactions between the hand and the mouth, reaching motions, or defensive maneuvers to protect the body surface from impending impact. Single neurons in motor cortex may contribute to these behaviors by means of their broad tuning to idiosyncratic, multijoint actions. The mapping from cortex to muscles is not fixed, as was once thought, but instead is fluid, changing continuously on the basis of feedback in a manner that could support the control of higher-order movement parameters. These findings suggest that the motor cortex participates directly in organizing and controlling the animal's behavioral repertoire.
Does Dairy Calcium Intake Enhance Weight Loss Among Overweight Diabetic Patients?
Authors: Danit R. Shahar, Relly Abel, Asher Elhayany, Hillel Vardi, Drora Fraser
Journal: Diabetes Care (2007)

To examine the effect of dairy calcium consumption on weight loss and improvement in cardiovascular disease (CVD) and diabetes indicators among overweight diabetic patients.This was an ancillary study of a 6-month randomized clinical trial assessing the effect of three isocaloric diets in type 2 diabetic patients: 1) mixed glycemic index carbohydrate diet, 2) low-glycemic index diet, and 3) modified Mediterranean diet. Low-fat dairy product consumption varied within and across the groups by personal choice. Dietary intake, weight, CVD risk factors, and diabetes indexes were measured at baseline and at 6 months.A total of 259 diabetic patients were recruited with an average BMI >31 kg/m2 and mean age of 55 years. No difference was found at baseline between the intervention groups in CVD risk factors, diabetes indicators, macronutrient intake, and nutrient intake from dairy products. Dairy calcium intake was associated with percentage of weight loss. Among the high tertile of dairy calcium intake, the odds ratio for weight loss of >8% was 2.4, P = 0.04, compared with the first tertile, after controlling for nondairy calcium intake, diet type, and the change in energy intake from baseline. No association was noted between dairy calcium and other health indexes except for triglyceride levels.A diet rich in dairy calcium intake enhances weight reduction in type 2 diabetic patients. Such a diet could be tried in diabetic patients, especially those with difficulty adhering to other weight reduction diets.
Chronic necrotising pulmonary aspergillosis caused by Aspergillus niger in a mildly immunocompromised host
Authors: M Yamaguchi, H Nishiya, K Mano, O Kunii, H Miyashita
Journal: Thorax (1992)

Abstract A middle aged man with diabetes mellitus and chronic alcoholic hepatitis developed chronic necrotising pulmonary aspergillosis or semi-invasive aspergillosis due to Aspergillus niger.
Transcription factors RUNX1 and RUNX3 in the induction and suppressive function of Foxp3+ inducible regulatory T cells
Authors: Sven Klunker, Mark M.W. Chong, Pierre-Yves Mantel, Oscar Palomares, Claudio Bassin, Mario Ziegler, Beate Rückert, Flurina Meiler, Mübeccel Akdis, Dan R. Littman, Cezmi A. Akdis
Journal: The Journal of Experimental Medicine (2009)

Forkhead box P3 (FOXP3)+CD4+CD25+ inducible regulatory T (iT reg) cells play an important role in immune tolerance and homeostasis. In this study, we show that the transforming growth factor-β (TGF-β) induces the expression of the Runt-related transcription factors RUNX1 and RUNX3 in CD4+ T cells. This induction seems to be a prerequisite for the binding of RUNX1 and RUNX3 to three putative RUNX binding sites in the FOXP3 promoter. Inactivation of the gene encoding RUNX cofactor core-binding factor-β (CBFβ) in mice and small interfering RNA (siRNA)-mediated suppression of RUNX1 and RUNX3 in human T cells resulted in reduced expression of Foxp3. The in vivo conversion of naive CD4+ T cells into Foxp3+ iT reg cells was significantly decreased in adoptively transferred CbfbF/F CD4-cre naive T cells into Rag2−/− mice. Both RUNX1 and RUNX3 siRNA silenced human T reg cells and CbfbF/F CD4-cre mouse T reg cells showed diminished suppressive function in vitro. Circulating human CD4+ CD25high CD127− T reg cells significantly expressed higher levels of RUNX3, FOXP3, and TGF-β mRNA compared with CD4+CD25− cells. Furthermore, FOXP3 and RUNX3 were colocalized in human tonsil T reg cells. These data demonstrate Runx transcription factors as a molecular link in TGF-β–induced Foxp3 expression in iT reg cell differentiation and function.
The role of the fiberoptic bronchoscopy in the management of community-acquired pneumonia in adults
Authors: Ginevra Del Giudice, Gaetano Beatrice, Angelo Romano, Emanuela Carpentieri, Assunta Micco, Antonio Russo, Mario Del Donno
Journal: European Respiratory Journal (2013)

Fiberoptic bronchoscopy (FBO) in Community-Acquired Pneumonia (CAP) is indicated in Intensive Care settings, in Immunocompromised patients and in CAP not responsive to antibiotic treatment. The FBO has a dual role to allow a targeted bacterial isolation and a more accurate toilet of tracheobronchial secretions in the airways.

Aim and Methods : 98 pts (81 M, mean age 68 yrs, BMI 25) with diagnosis of CAP, from 2010 to 2011, were evaluated by performing a FBO. All patients were selected according to the values of pH, PaO2/FiO2, PaCO2 mmHg and evaluation of APACHE III score, Kelly-Matthay score and CURB-65 score.

View this table:

Caracheristics of both group in admission





Results: In 47 out of 58 patients, those undergoing FBO, were identified pathogenic species on bronchial mucus aspirated, with a higher prevalence of Pseudomonas aeruginosa and Entero-bacteracee. The improvement of respiratory symptoms and laboratory parameters, at a mean of 4 days from the execution of the FBO, was obtained. Moreover, we observed a reduction in the average time of hospitalization (9 vs 14 gg). Conclusions: In this study, is evident that the routine application of FBO may lead to the identification of a high percentage of pathogens (81% in our patients), significantly reduce the time of hospitalization and limit the costs associated with complications.
Nocturnal Light Environments Influence Color Vision and Signatures of Selection on the OPN1SW Opsin Gene in Nocturnal Lemurs
Authors: Carrie C. Veilleux, Edward E. Louis, Deborah A. Bolnick
Journal: Molecular Biology and Evolution (2013)

Although loss of short-wavelength-sensitive (SWS) cones and dichromatic color vision in mammals has traditionally been linked to a nocturnal lifestyle, recent studies have identified variation in selective pressure for the maintenance of the OPN1SW opsin gene (and thus, potentially dichromacy) among nocturnal mammalian lineages. These studies hypothesize that purifying selection to retain SWS cones may be associated with a selective advantage for nocturnal color vision under certain ecological conditions. In this study, we explore the effect of nocturnal light environment on OPN1SW opsin gene evolution in a diverse sample of nocturnal lemurs (106 individuals, 19 species, and 5 genera). Using both phylogenetic and population genetic approaches, we test whether species from closed canopy rainforests, which are impoverished in short-wavelength light, have experienced relaxed selection compared with species from open canopy forests. We identify clear signatures of differential selection on OPN1SW by habitat type. Our results suggest that open canopy species generally experience strong purifying selection to maintain SWS cones. In contrast, closed canopy species experience weaker purifying selection or a relaxation of selection on OPN1SW. We also found evidence of nonfunctional OPN1SW genes in all Phaner species and in Cheirogaleus medius, implying at least three independent losses of SWS cones in cheirogaleids. Our results suggest that the evolution of color vision in nocturnal lemurs has been influenced by nocturnal light environment.
Treatment of Bronchial Asthma With Cromolyn
Authors: M. Henry Williams
Journal: JAMA (1969)

Cromolyn sodium (Intal [Britain]) is a new drug which is neither a bronchodilator nor a corticosteroid, but which possesses antiallergic properties which might make it useful for treatment of bronchial asthma. A number of reports in the British literature have indicated a favorable effect of this drug, but in many of the studies it was possible for the patient to have distinguished between drug and placebo. The present report summarizes the results of a randomized, doubleblind crossover trial of cromolyn in 17 patients with bronchial asthma in which it was impossible for the patients to know which of the two compounds was drug and which was placebo. For each patient, the physician judged whether or not either of the unknown compounds was of clinical value. This judgment was largely based on the patient's subjective response. The excess of preferences for active compound indicate a 95% probability that the drug was more effective than the placebo. Objective evidence of efficacy (ventilatory function) was not impressive, but it is concluded that this new drug has a beneficial effect on patients with bronchial asthma.
Growth and Molecular Interactions between Tamoxifen and Trastuzumab
Authors: Alejandro Vázquez-Martín, Ramon Colomer, Santiago Ropero, Javier Abel Menéndez
Journal: Clinical Cancer Research (2005)

To the editor: In the February 15, 2004 issue of Clinical Cancer Research, Argiris et al. ([1][1]) have presented some studies of the interaction between tamoxifen and trastuzumab on breast cancer cells. They evaluated cell growth, cell cycle, human epidermal growth factor receptor 2 (HER2)
Farber's disease without central nervous system involvement: bone-marrow transplantation provides a promising new approach
Authors: K Ehlert, J Roth, M Frosch, N Fehse, N Zander, J Vormoor
Journal: Annals of the Rheumatic Diseases (2006)

Farber’s disease is a lysosomal storage disorder caused by acid ceramidase deficiency.1 The main symptoms in patients without central nervous system (CNS) involvement (type 2/3), are caused by leucocyte dysregulation,2 with impaired apoptosis and signal transduction caused by intracellularly accumulated ceramide, leading to the inflammatory component of this disorder, with swelling of joints, granuloma formation, contractures and inflammatory airway involvement.6 Current treatment focuses on pain management, physical treatment, surgical correction of contractures and treatment with anti-inflammatory drugs. In rheumatoid disorders such as juvenile rheumatoid arthritis, immunosuppression or autologous haematopoietic stem cell transplantation (HSCT) can afford a substantial benefit, as treatment is based on suppression of abundant inflammatory responses by …
Effects of Irbesartan on Intracellular Antioxidant Enzyme Expression and Activity in Adolescents and Young Adults With Early Diabetic Angiopathy
Authors: Francesco Chiarelli, Daniele Di Marzio, Francesca Santilli, Angelika Mohn, Annalisa Blasetti, Francesco Cipollone, Andrea Mezzetti, Alberto Verrotti
Journal: Diabetes Care (2005)

Defective intracellular antioxidant enzyme production (IAP) has been demonstrated in adults with diabetic nephropathy. The objective of this study was to evaluate the effects of irbesartan, an angiotensin II receptor antagonist, on IAP in adolescents and young adults with type 1 diabetes and early signs of retinopathy and nephropathy.This prospective, matched case-control study was conducted between November 2001 and December 2002 among 14 type 1 diabetic patients with early signs of angiopathy (ages 14-21 years), 11 type 1 diabetic patients without angiopathy (ages 12-22 years), and 10 healthy volunteers (ages 16-22 years). Skin fibroblasts were obtained by skin biopsies from the anterior part of the forearm and cultured in Dulbecco's modified Eagle's medium. The activity and mRNA expression of CuZn superoxide dismutase (CuZnSOD), Mn superoxide dismutase (MnSOD), catalase (CAT), and glutathione peroxidase (GPX) were measured before and after 6 months of treatment with irbesartan (150 mg/day); on both occasions, antioxidant enzyme activity was evaluated at different glucose concentrations (5 and 22 mmol/l).At a normal glucose concentration (5 mmol/l), the activity and mRNA expression of CuZnSOD (0.50 +/- 0.21 units/mg protein, 4.4 +/- 1.5 mRNA/glyceraldehyde-3-phosphate dehydrogenase), MnSOD (0.26 +/- 0.04 units/mg protein, 0.08 +/- 0.07 mRNA), CAT (0.32 +/- 0.08 units/mg protein, 4.8 +/- 1.3 mRNA), and GPX (0.53 +/- 0.09 units/mg protein, 2.2 +/- 0.9 mRNA) were not different among the three groups (only values of diabetic subjects with angiopathy are shown). At high glucose concentrations, the activity and mRNA expression of CuZnSOD increased similarly in all groups (diabetic subjects with angiopathy: 0.93 +/- 0.26 units/mg protein, 9.4 +/- 2.1 mRNA); that of CAT and GPX increased in only control subjects and diabetic subjects without angiopathy (diabetic subjects with angiopathy: 0.33 +/- 0.09 units/mg protein and 5.0 +/- 1.4 mRNA; 0.54 +/- 0.10 units/mg protein and 2.3 +/- 1.0 mRNA, respectively). MnSOD did not change in any group. Treatment with irbesartan in adolescents with diabetic angiopathy was able to restore CAT and GPX activity and mRNA expression after exposure to high glucose concentrations. Markers of oxidative stress (serum malondialdehyde, fluorescent products of lipid peroxidation, monocyte chemoattractant protein-1, and 8-isoprostanes prostaglandin F(2alpha)) were significantly reduced after treatment with irbesartan.Adolescents and young adults with early signs of diabetic angiopathy have defective intracellular antioxidant enzyme production and activity. Treatment with irbesartan can substantially improve the activity and production of these enzymes in skin fibroblasts.
Ancestry in translational genomic medicine: handle with care
Authors: David Gurwitz, Jeantine E Lunshof
Journal: Genome Medicine (2009)

Disparities in health outcomes of members of different ancestral or ethnic groups can be observed in both developed and developing countries and continue to be a global concern. Genomic medicine can help toward closing this gap by expanding the knowledge on novel alleles related to disease risk and drug response, their frequencies, and their relation with disease and drug-response phenotypes, in as many countries and ethnic groups as possible. Without such knowledge, genomic medicine cannot deliver upon its promise of contributing to health for all. However, the use of ancestry or ethnicity-related genetic information as a selection criterion for assigning varying levels of access to health care is condemnable. Translational genomic medicine will allow for individualized clinical decision making - doing away with the use of race, ethnicity or ancestry as a proxy.
TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis
Authors: Betsy C. Taylor, Colby Zaph, Amy E. Troy, Yurong Du, Katherine J. Guild, Michael R. Comeau, David Artis
Journal: The Journal of Experimental Medicine (2009)

Intestinal epithelial cells (IECs) produce thymic stromal lymphopoietin (TSLP); however, the in vivo influence of TSLP-TSLP receptor (TSLPR) interactions on immunity and inflammation in the intestine remains unclear. We show that TSLP-TSLPR interactions are critical for immunity to the intestinal pathogen Trichuris. Monoclonal antibody-mediated neutralization of TSLP or deletion of the TSLPR in normally resistant mice resulted in defective expression of Th2 cytokines and persistent infection. Susceptibility was accompanied by elevated expression of interleukin (IL) 12/23p40, interferon (IFN) gamma, and IL-17A, and development of severe intestinal inflammation. Critically, neutralization of IFN-gamma in Trichuris-infected TSLPR(-/-) mice restored Th2 cytokine responses and resulted in worm expulsion, providing the first demonstration of TSLPR-independent pathways for Th2 cytokine production. Additionally, TSLPR(-/-) mice displayed elevated production of IL-12/23p40 and IFN-gamma, and developed heightened intestinal inflammation upon exposure to dextran sodium sulfate, demonstrating a previously unrecognized immunoregulatory role for TSLP in a mouse model of inflammatory bowel disease.
Myokinase Activity of Coronary Arteries
Authors: C. JELLEFF CARR, FREDERICK K. BELL, J. NEIL HURST, JOHN C. KRANTZ
Journal: Circulation Research (1954)

In exploring the mechanism of action of vasodilating drugs an attempt has been made to study the enzyme systems of the blood vessels. A transphosphatase of the myokinase type has been found to be present in the coronary arteries of the steer. The activity has been studied under the optimal conditions for this enzyme system. Coronary arterial tissue may be maintained at the temperature of dry ice for a number of days without significant loss of enzyme activity. This will permit an investigation of the effects of drugs upon the activity of these enzymes.
Height as a Sex-Cancer Mediator? Interpret With Caution
Authors: Lois A. Gelfand, Amanda N. Baraldi
Journal: JNCI Journal of the National Cancer Institute (2013)

jnci.oxfordjournals.org © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. meta-analysis of prospective studies of height and total cancer risk. Lancet Oncol. 2011;12(8):785–794. 7. Lango Allen H, Estrada K, Lettre G, et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature. 2010;467(7317):832–838. 8. Gunnell D, Okasha M, Davey Smith G, Oliver SE, Sandhu J, Holly JMP. Height, leg length, and cancer risk: a systematic review. Epidemiol Rev. 2001;23(2):313–342. 9. Clayton PE, Banerjee I, Murray PG, Renehan AG. Growth hormone, the insulin-like growth factor axis, insulin and cancer risk. Nat Rev Endocrinol. 2011;7(1):11–24. Funding This work was supported by Cancer Research UK and the UK Medical Research Council. The sponsors had no role in the writing of the editorial or the decision to submit the editorial for publication.
Myosin types in the human heart. An immunofluorescence study of normal and hypertrophied atrial and ventricular myocardium.
Authors: L Gorza, J J Mercadier, K Schwartz, L E Thornell, S Sartore, S Schiaffino
Journal: Circulation Research (1984)

Two distinct myosin heavy chain isoforms, referred to as alpha and beta, were identified in the human heart with specific antimyosin antibodies. By indirect immunofluorescence, myosin heavy chain alpha was found to be a major component of atrial myosin and a minor component of ventricular myosin, while heavy chain beta was found to be a major component of ventricular myosin and a minor component of atrial myosin. In the normal heart, there was marked individual variability in the proportion of ventricular myocytes reactive for heavy chain alpha. Atrial myocytes staining for heavy chain beta were rare in the left atrium and more numerous in the right atrium, especially in the crista terminalis and in the interatrial septum. Surgical and autoptic specimens from hypertrophied left ventricles of patients with mitral regurgitation showed a myosin immunoreactivity pattern similar to that of normal specimens. Very rare muscle cells reactive for heavy chain alpha were seen in the hypertrophied left ventricles of subjects with hypertension and in the hypertrophied right ventricles of subjects with tetralogy of Fallot. A dramatic transformation of myosin heavy chain composition was observed in hypertrophied left atria of patients with mitral stenosis, with a shift to heavy chain beta in a large proportion of atrial myocytes. The findings indicate that chronic exposure to hemodynamic overload can induce marked changes in the myosin heavy chain composition of human atria, whereas it affects only slightly that of the ventricles.