tbuckley/cabot-search huggingface dataset:
Molecular Markers of Acute Upper Airway Inflammation in Workers Exposed to Fuel-Oil Ash
Authors: MARK A. WOODIN, RUSS HAUSER, YOUCHENG LIU, THOMAS J. SMITH, PAUL D. SIEGEL, DANIEL M. LEWIS, DAVID J. TOLLERUD, DAVID C. CHRISTIANI
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Biomarkers in nasal lavage (NL) fluid may be useful in determining the presence and severity of upper airway inflammation. We studied 18 boilermakers overhauling a large, oil-fired boiler and 11 utility workers who served as controls for 6 wk. NL was performed before (NL1), during (NL2), and after (NL3) the overhaul. We measured nasal fluid levels of interleukins 6 (IL-6) and 8 (IL-8), eosinophilic cationic protein (ECP), and myeloperoxidase (MPO) as markers of response to fuel-oil ash exposure. In boilermakers, MPO was elevated during boiler work versus preboiler work (mean = 33.8 versus 22.7 ng/ml, p < 0.05), and at the 2-wk postexposure lavage (NL3) it had declined to 24.2 ng/ml (p = 0.08). Mean IL-8 levels increased in boilermakers between NL1 and NL2 (mean = 83.8 versus 134.8 pg/ml, p < 0.05), then decreased at NL3 (mean = 134.8 versus 89.0 pg/ml, p < 0.05). Nasal fluid vanadium increased in boilermakers between NL1 and NL2 (median < 1.0 versus 4.7 ppb, respectively, p < 0.05), then decreased at NL3 (median, 4.7 versus < 1.0 ppb, respectively, p < 0.05). Levels of IL-6 and ECP did not change significantly during the study. Utility workers showed no significant change in any marker during the study period. Particulate matter < 10 μ m (PM10) levels were higher for boilermakers than for utility workers before boiler work (geometric mean (GM) = 0.40 versus 0.10 mg/m3, p < 0.05). This difference was more significant during boiler work (GM = 0.47 versus 0.13 mg/m3, p < 0.001). Ozone levels were low during the study. These data suggest that exposure to fuel-oil ash results in acute upper airway inflammation, potentially mediated by increased IL-8 levels and the recruitment and activation of polymorphonuclear leukocytes. These changes were associated with significantly increased PM10 levels and concentrations of upper airway vanadium.
Can Whole-body Magnetic Resonance Imaging with Diffusion-weighted Imaging Replace Tc 99m Bone Scanning and Computed Tomography for Single-step Detection of Metastases in Patients with High-risk Prostate Cancer?
Authors: Frédéric E. Lecouvet, Jawad El Mouedden, Laurence Collette, Emmanuel Coche, Etienne Danse, François Jamar, Jean-Pascal Machiels, Bruno Vande Berg, Patrick Omoumi, Bertrand Tombal
Journal: European Urology (2012)
STRUCTURAL AND FUNCTIONAL TRANSFORMATIONS IN THE TUBULAR EPITHELIUM OF THE DOG'S KIDNEY IN CHRONIC BRIGHT'S DISEASE AND THEIR RELATION TO MECHANISMS OF RENAL COMPENSATION AND FAILURE
Authors: Jean Oliver, Frank Bloom, Muriel MacDowell
Journal: The Journal of Experimental Medicine (1941)

1. The wall of the proximal convolution in chronic canine nephritis is composed of various types of epithelial cells which can be recognized as definite structural types from their cytological characteristics. 2. The function of these cell types, as tested by their reaction to the administration of trypan blue, varies with their structural constitution. 3. As a result of the varied cellular content of its wall the abnormal proximal convolution handles trypan blue by mechanisms which differ both quantitatively and qualitatively from those of the normal convolution. 4. A distinguishing characteristic of the decompensated kidney in chronic canine nephritis is the inability of its epithelium to concentrate trypan blue within its cells and to prevent diffusion of the dye from the lumen into the tubule wall. 5. It follows: (a) (from conclusion 3), that it cannot be assumed that the renal mechanisms concerned with other substances are not unaltered and that comparisons of blood and urine concentrations (clearances) have similar significance in the normal and nephritic kidney; (b) (from conclusion 4), that tubular dysfunction may play a part in the ultimate failure of the compensating kidney in all forms of chronic Bright's disease where the tubule walls are similarly affected.
Epigenetic factors influencing resistance to nuclear reprogramming
Authors: Vincent Pasque, Jerome Jullien, Kei Miyamoto, Richard P. Halley-Stott, J.B. Gurdon
Journal: Trends in Genetics (2011)

Patient-specific somatic cell reprogramming is likely to have a large impact on medicine by providing a source of cells for disease modelling and regenerative medicine. Several strategies can be used to reprogram cells, yet they are generally characterised by a low reprogramming efficiency, reflecting the remarkable stability of the differentiated state. Transcription factors, chromatin modifications, and noncoding RNAs can increase the efficiency of reprogramming. However, the success of nuclear reprogramming is limited by epigenetic mechanisms that stabilise the state of gene expression in somatic cells and thereby resist efficient reprogramming. We review here the factors that influence reprogramming efficiency, especially those that restrict the natural reprogramming mechanisms of eggs and oocytes. We see this as a step towards understanding the mechanisms by which nuclear reprogramming takes place.
Diagnostic and therapeutic potential of miRNA signatures in patients with hepatocellular carcinoma
Authors: Florie Borel, Pavlina Konstantinova, Peter L.M. Jansen
Journal: Journal of Hepatology (2012)

MicroRNAs (miRNAs) are evolutionary conserved small non-coding RNAs that regulate gene expression by mediating post-transcriptional silencing of target genes. Since miRNAs are involved in fine-tuning of physiological responses, they have become of interest for diagnosis and therapy of a number of diseases. Moreover, the role of dysregulated miRNAs in maintaining the malignant phenotype has profound implications for cancer therapy. We will review the best defined cellular miRNAs and changes in their expression profile in hepatocellular carcinoma (HCC). Cellular miRNAs can also be released into the circulation, and these miRNAs are detected in most body fluids. Circulating miRNAs are associated with HCC and are possible biomarkers. Finally, by affecting several clinically relevant targets, artificially increasing or decreasing the expression level of a given miRNA offers fascinating therapeutic perspectives. We will therefore highlight recent developments in miRNA-based gene therapy with a focus on their therapeutic potential for HCC.
Endoluminal gastroplication in children with significant gastro-oesophageal reflux disease
Authors: M Thomson
Journal: Gut (2004)

<b>Aims:</b> To describe paediatric experience, and to assess complications and therapeutic effectiveness of the use of endoluminal gastroplication in children with gastro-oesophageal reflux disease (GORD) refractory to, or dependent on, proton pump inhibitors. <b>Methods:</b> Seventeen (five male) consecutive children/adolescents (median (range) age 12.4 (6.1–15.9) years, median (range) weight 46.0 (16.5–87.5) kg) with GORD either dependent for more than 12 months on proton pump inhibitors or non-responsive to medical treatment underwent endoscopic gastroplication using a flexible endoscopic sewing device (EndoCinch). Three plications were placed in gastric tissue below the lower oesophageal sphincter. Drug dose requirement, pH measurements, daily symptom severity and frequency, and validated reflux (QOLRAD) and general gastrointestinal (GSRS) quality of life scores were compared before and after endoscopic gastroplication. <b>Results:</b> All patients showed post-treatment improvement in symptom severity, frequency, and quality of life scores (p&lt;0.0001). Three patients with recurrent symptomatic GORD had a repeat procedure within six weeks and did well subsequently. At up to 33 months of follow up (median 23), 14/17 patients remained off all antireflux medications, and 14/17 had maintained their symptomatic improvement. All pH parameters improved and had returned to normal values in 14/16 patients post-treatment and in 6/9 after one year of follow-up: in particular the reflux index had decreased from a median of 16.6% (0.9–67%) to 2.5% (0.7–15.7%) (p&lt;0.0001) six weeks and 4.3% (2.2–20.6) (p&lt;0.02) 12 months post-procedure. The only complication observed was gastric bleeding in one patient due to previously undiagnosed coagulopathy, which spontaneously resolved. <b>Conclusions:</b> Endoluminal gastroplication is an effective and safe procedure in children/adolescents with significant GORD refractory to, or dependent on, medical anti-GORD therapy.
Understanding the Slow Depletion of Memory CD4+ T Cells in HIV Infection
Authors: Andrew Yates, Jaroslav Stark, Nigel Klein, Rustom Antia, Robin Callard
Journal: PLoS Medicine (2007)

Background The asymptomatic phase of HIV infection is characterised by a slow decline of peripheral blood CD4+ T cells. Why this decline is slow is not understood. One potential explanation is that the low average rate of homeostatic proliferation or immune activation dictates the pace of a “runaway” decline of memory CD4+ T cells, in which activation drives infection, higher viral loads, more recruitment of cells into an activated state, and further infection events. We explore this hypothesis using mathematical models. Methods and Findings Using simple mathematical models of the dynamics of T cell homeostasis and proliferation, we find that this mechanism fails to explain the time scale of CD4+ memory T cell loss. Instead it predicts the rapid attainment of a stable set point, so other mechanisms must be invoked to explain the slow decline in CD4+ cells. Conclusions A runaway cycle in which elevated CD4+ T cell activation and proliferation drive HIV production and vice versa cannot explain the pace of depletion during chronic HIV infection. We summarize some alternative mechanisms by which the CD4+ memory T cell homeostatic set point might slowly diminish. While none are mutually exclusive, the phenomenon of viral rebound, in which interruption of antiretroviral therapy causes a rapid return to pretreatment viral load and T cell counts, supports the model of virus adaptation as a major force driving depletion.
Efficacy and safety of abediterol (LAS100977) in patients with COPD: Phase II, randomised, crossover study
Authors: Jutta Beier, Helena Pujol, Beatriz Seoane, Eulalia Jimenez, Carol Astbury, Sandrine Ruiz, Gonzalo de Miquel
Journal: European Respiratory Journal (2013)

Background: The bronchodilatory efficacy and safety of single doses of once-daily abediterol, a novel LABA in development for the treatment of asthma and COPD, vs placebo and indacaterol in patients with moderate-to-severe COPD were assessed.

Methods: Adult patients with COPD (mean FEV1 1.72 L; 58.0% predicted [post-BD]) received single doses of abediterol 0.625, 2.5, 5 and 10 µg via Genuair®, indacaterol 150 µg via Breezhaler® and placebo in a 6-period crossover study. The primary endpoint was change from baseline to trough FEV1. Secondary endpoints included change from baseline in normalized FEV1 AUC0-24, and peak FEV1. Safety, tolerability and abediterol pharmacokinetics (subgroup analysis) were assessed.

Results: A total of 63/70 randomized patients completed the study. Lung-function data are summarized (Table). The percentage of patients with ≥1 IMP-related TEAE was ≤3% for each abediterol dose; similar to placebo (2.9%) and indacaterol 150 µg (2.9%). Peak abediterol plasma concentration was reached within 0.5–1.5 h post-dose (n=20). Dose proportionality in Cmax and AUC(0-t) was observed.

View this table:

Table. Change from baseline (LS means difference vs placebo), L





Conclusions: Single inhaled doses of abediterol 0.625–10 µg induced and maintained significant bronchodilation vs placebo and were well tolerated. The bronchodilatory effect of abediterol 2.5, 5 and 10 µg was significantly greater than indacaterol 150 µg.
Thyroarytenoid Muscle Electrical Activity During Spontaneous Apneas in Preterm Lambs
Authors: SYLVAIN RENOLLEAU, PATRICK LETOURNEAU, THÉOPHILE NIYONSENGA, JEAN-PAUL PRAUD, Bruno Gagné
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Laryngeal dynamics plays a major role during perinatal life, a period of respiratory control immaturity. Continuous electromyographic (EMG) activity of a laryngeal adductor muscle (thyroarytenoid [TA] muscle), was recently observed throughout provoked central apneas, either isolated or during induced periodic breathing, in full-term lambs. The aim of the present study was to test if continuous TA EMG activity was also present during spontaneous apneas in nonsedated preterm lambs. We studied 7 premature lambs (term 131 +/- 1 d of postconceptional age). Premature birth was induced after acceleration of fetal lung maturation. Electrodes for diaphragm, inferior pharyngeal constrictor (IPC), and TA electromyograms, electrocardiogram, electroencephalogram, eye movement, and airflow recordings were implanted. Radiotelemetry recordings were repeated from 135 to 149 +/- 8 d of postconceptional age. A total of 2,088 apneas (2,020 central and 68 mixed) >/= 3 s were recorded in the lambs, including 57 epochs of periodic breathing. Continuous TA EMG activity was present throughout 88.4% of all apneas and 98.4% of apneas during periodic breathing, regardless of the sleep stage. These results suggest that active glottic closure is frequent during spontaneous central apneas in this model of prematurity. This unique model will allow us to study controlling mechanisms and consequences of glottic closure during neonatal apneas.
RTVP-1, a Tumor Suppressor Inactivated by Methylation in Prostate Cancer
Authors: Chengzhen Ren, Likun Li, Guang Yang, Terry L. Timme, Alexei Goltsov, Chenghui Ren, Xiaorong Ji, Josephine Addai, Hongbin Luo, Michael M. Ittmann, Timothy C. Thompson
Journal: Cancer Research (2004)

Abstract We previously identified and characterized a novel p53-regulated gene in mouse prostate cancer cells that was homologous to a human gene that had been identified in brain cancers and termed RTVP-1 or GLIPR. In this report, we document that the human RTVP-1 gene is also regulated by p53 and induces apoptosis in human prostate cancer cell lines. We show that the expression of the human RTVP-1 gene is down-regulated in human prostate cancer specimens compared with normal human prostate tissue at the mRNA and protein levels. We further document epigenetic changes consistent with RTVP-1 being a tumor suppressor in human prostate cancer.
Identification of Metastasis-Suppressive microRNAs in Primary Melanoma
Authors: Doug Hanniford, Miguel F. Segura, Judy Zhong, Elliot Philips, Xavier Jirau-Serrano, Farbod Darvishian, Russell S. Berman, Richard L. Shapiro, Anna C. Pavlick, Brian Brown, Iman Osman, Eva Hernando
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Surgical management of primary melanoma is curative for most patients with clinically localized disease at diagnosis; however, a substantial number of patients recur and progress to advanced disease. Understanding molecular alterations that influence differential tumor progression of histopathologically similar lesions may lead to improved prognosis and therapies to slow or prevent metastasis.
Urinary 2-Hydroxyestrone/16 -Hydroxyestrone Ratio and Risk of Breast Cancer in Postmenopausal Women
Authors: G. Ursin, S. London, F. Z. Stanczyk, E. Gentzschein, A. Paganini-Hill, R. K. Ross, M. C. Pike
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: It has been suggested that women who metabolize a larger proportion of their endogenous estrogen via the 16α-hydroxylation pathway may be at elevated risk of breast cancer compared with women who metabolize proportionally more estrogen via the 2-hydroxylation pathway. However, the supporting epidemiologic data are scant. Consequently, we compared the ratio of urinary 2-hydroxyestrone (2-OHE 1 ) to 16α-hydroxyestrone (16α-OHE 1 ) in postmenopausal women with breast cancer and in healthy control subjects. METHODS: Estrogen metabolites were measured in urine samples obtained from white women who had participated in a previous population-based, breast cancer case-control study at our institution. All P values are from two-sided tests. RESULTS: All of the urinary estrogens measured, with the exception of estriol, were higher in the 66 case patients than in the 76 control subjects. The mean value of urinary 2-OHE 1 in case patients was 13.8% ( P = .20) higher than that in control subjects, 16α-OHE 1 was 12.1% ( P = .23) higher, estrone was 20.9% higher ( P = .14), and 17β-estradiol was 12.0% higher ( P = .36). The ratio of 2-OHE 1 to 16α-OHE 1 was 1.1% higher in the patients ( P = .84), contrary to the hypothesis. Compared with women in the lowest third of the values for the ratio of urinary 2-OHE 1 to 16α-OHE 1 , women in the highest third were at a nonstatistically significantly increased risk of breast cancer (odds ratio = 1.13; 95% confidence interval = 0.46-2.78), again contrary to the hypothesis. CONCLUSION: This study does not support the hypothesis that the ratio of the two hydroxylated metabolites (2-OHE 1 /16α-OHE 1 ) is an important risk factor for breast cancer.
Effect of Ergocornine on Transplanted Mammary Tumor Growth and Pituitary Prolactin Level in BALB/c Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D V Singh, J Meites, L Halmi, K H Kortright, M J Brennan
Journal: JNCI Journal of the National Cancer Institute (1972)

The effect of ergocornine (Eg) on transplanted D2-mammarytumor growth was investigated in 28 BALB/c mice, which were divided in 2 groups and given subcutaneous injections for 5 weeks. The control group received saline-ethanol. The experimental group received 20 μg Eg/day for the 1st week, 50 μg/day for the 2d-4th weeks, and 100 μg/day for the 5th week. Throughout treatment, tumors in control mice grew more rapidly than tumors in the Eg-freated animals. Mammary tumor growth was suppressed by Eg but the tumors did not regress significantly below their initial size. When Eg treatment was terminated at the end of 5 weeks, a prompt renewal of mammary tumor growth was observed and the rate of growth paralleled that of tumors in the controls. Pituitary prolactin levels were decreased about 70% by Eg treatment as compared to prolactin levels in the controls. These results indicate that growth of transplanfable D2-mammary tumors in BALB/c agent-free mice is decreased by Eg, and that this is associated with reduced pituitary prolactin levels.
Genetic variation in promoter sequence of B cell-activating factor gene is associated with increased risk of myositis development
Authors: M. Faustova, P. Novota, O. Krystufkova, H. Hulejova, J. Vencovsky
Journal: Annals of the Rheumatic Diseases (2010)

The protein encoded by B cell-activating factor (BAFF) gene is a member of the tumour necrosis factor (ligand) superfamily. This protein is expressed by myeloid line cells (dendritic cells, macrophages, monocytes), partly by T cells and is secreted mostly by dendritic cells. It increases the survival of B cells in vitro and regulates peripheral B cells. It also seems to play a role in T cell activation providing a co-stimulatory signal. The promoter region of BAFF gene contains …
Protein Kinase C and Gi/o Proteins Are Involved in Adenosine- and Ischemic Preconditioning—Mediated Renal Protection
Authors: H. THOMAS LEE, CHARLES W. EMALA
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Renal ischemic reperfusion (IR) injury is a significant clinical problem in anesthesia and surgery. Recently, it was demonstrated that both renal ischemic preconditioning (IPC) and systemic adenosine pretreatment protect against renal IR injury. In cardiac IPC, pertussis toxin-sensitive G-proteins ( i.e. , G i/o ), protein kinase C (PKC), and ATP-sensitive potassium (K + ATP ) channels are implicated in this protective signaling pathway. The aim of this study was to elucidate the signaling pathways that are responsible for renal protection mediated by both IPC and adenosine pretreatment. In addition, because A 1 adenosine receptor antagonist failed to block renal IPC, whether activation of bradykinin, muscarinic, or opioid receptors can mimic renal IPC was tested because these receptors have been implicated in cardiac IPC. Rats were acutely pretreated with chelerythrine or glibenclamide, selective blockers of PKC and K + ATP channels, respectively, before IPC or adenosine pretreatment. Some rats were pretreated with pinacidil (K + ATP channel opener), bradykinin, methacholine, or morphine before renal ischemia. Twenty-four h later, plasma creatinine was measured. Separate groups of rats received pertussis toxin intraperitoneally 48 h before being subjected to the above protective protocols. IPC and adenosine pretreatment protected against renal IR injury. Pretreatment with pertussis toxin and chelerythrine abolished the protective effects of both renal IPC and adenosine. However, glibenclamide pretreatment had no effect on either renal IPC or adenosine-induced renal protection, indicating no apparent role for K + ATP channels. Moreover, pinacidil, bradykinin, methacholine, and morphine failed to protect renal function. Therefore, the conclusion is that cellular signal transduction pathways of renal IPC and adenosine pretreatment in vivo involve G i/o proteins and PKC but not K + ATP channels. Unlike cardiac IPC, bradykinin, muscarinic, and opioid receptors do not mediate renal IPC.
Effect of venovenous bypass on perioperative renal function in liver transplantation: Results of a randomized, controlled trial
Authors: L Grande, A Rimola, E Cugat, L Alvarez, J C Garcia-Valdecasas, P Taurá, J Beltran, J Fuster, A M Lacy, F J González, J Tabet, A Cifuentes, R Rull, C Ramos, J Visa, J Rodés
Journal: Hepatology (1996)

Although venovenous bypass (VVBP) has been suggested to protect the kidneys during liver transplantation and its systematic use has therefore been recommended, this beneficial effect of VVBP has not been clearly demonstrated. In a prospective, randomized, controlled trial, 77 patients receiving liver transplants for chronic liver disease were allocated to be supported with VVBP (group 1, 38 patients) or not (group 2, 39 patients). Both groups were similar in relation to preoperative clinical and laboratory data and operative transfusion requirements. Inulin clearance and urinary β2-microglobulin and N-acetyl-β-D-glucosaminidase (NAG) excretion (to determine glomerular filtration rate and tubular damage, respectively) were measured at different perioperative periods (anesthesia induction, hepatectomy, anhepatic phase, biliary anastomosis, and 24 hours after surgery). A significant decrease in inulin clearance and increase in tubular damage markers were observed in the anhepatic phase, which only partly improved in the subsequent phases. No significant differences were observed between groups 1 and 2 at any perioperative phase, except during the anhepatic phase, in which a more marked renal function impairment occurred in group 2 patients. However, renal function on the 7th postoperative day and the need for hemodialysis/ hemofiltration during the 1st week were similar in both groups. Among 40 variables analyzed, only low mean arterial pressure at anesthesia induction was identified as an independent predictor for early postoperative severe renal failure (inulin clearance < 10 mL/min/1.73 m2 at the 24th postoperative hour), with no significant relationship between this complication and the use of venovenous bypass. Renal function markedly deteriorates during liver transplantation, and renal impairment persists during the early postoperative period. Because VVBP support is not associated with any clear benefit in renal function, its systematic use does not seem to be justified.