tbuckley/cabot-search huggingface dataset:
Nasal obstruction as a risk factor for sleep apnoea syndrome
Authors: F. Lofaso, A. Coste, M.P d′ortho, F Zerah-Lancner, C Delclaux, F Goldenberg, A Harf
Journal: European Respiratory Journal (2000)

Nasal obstruction has frequently been mentioned as a possible risk factor in obstructive sleep apnoea syndrome (OSAS). Over a 2-yr period, 541 unselected consecutive snorers referred for suspected breathing disorders during sleep were included to undergo posterior rhinomanometry. In addition cephalometric landmarks and body mass index (BMI) were obtained. Polysomnography was used to determine the number of abnormal respiratory events that occurred during sleep. OSAS was defined as 15 episodes, or more, of apnoea or hypopnoea per hour of sleep (AHI). Of the 541 consecutive snorers 528 underwent nasal resistance measurement by posterior rhinomanometry (failure rate: 2.4%). Patients with OSAS (259 patients) had higher nasal resistance than patients without OSAS (2.6+/-1.6 hPa x L x s(-1) versus 2.2+/-1.0 hPa x L x s(-1), respectively, p<0.005). A stepwise multiple regression analysis showed that BMI, male sex, nasal resistance, and cephalometric parameters were contributing factors to the AHI. The r2-value of the multiple regression analysis was 0.183. Nasal resistance contributed 2.3% of the variance (p<0.0001), whereas mandibular plane-hyoid distance, BMI, male sex and age contributed 6.2%, 4.6%, 3% and 1.3% of the variance, respectively. To conclude, daytime nasal obstruction is an independent risk factor for OSAS.
Profound invariant natural killer T-cell deficiency in inflammatory arthritis
Authors: S. J. Tudhope, A. von Delwig, J. Falconer, A. Pratt, T. Woolridge, G. Wilson, J. D. Isaacs, W.-F. Ng
Journal: Annals of the Rheumatic Diseases (2010)

Data from rodent models indicate that invariant natural killer T (iNKT) cells are key regulators of many immune responses including autoimmune arthritis, but their role in human diseases is unclear. The aims of this study are to determine whether iNKT cell frequency and function are altered in patients with rheumatoid arthritis (RA), and the clinical significance of such iNKT cell abnormalities.Peripheral blood iNKT cell frequency and proliferative response to an iNKT cell-specific agonist, α-galactosylceramide were measured in 46 RA patients (including 23 untreated, newly diagnosed patients), 22 healthy controls and 27 patients presenting with recent-onset joint pain. The relationship between iNKT cell frequency and clinical characteristics and the effects of immunosuppressive treatment was examined.Compared with healthy controls, RA patients had a decreased frequency of peripheral blood iNKT cells (median 0.001% vs 0.021%, p<0.001) and the proliferative response of this subset to α-galactosylceramide was also diminished in the patient group (median fold-expansion 31 vs 121, p=0.037). These abnormalities preceded the initiation of disease-modifying or immunosuppressive therapy, whose effect was to increase the circulating iNKT cell frequency (p=0.037). Furthermore, iNKT cell frequency correlated inversely with the systemic inflammatory marker, C-reactive protein (p=0.008). Finally, in patients presenting with recent-onset joint symptoms, normal peripheral blood iNKT cell frequency predicted a non-inflammatory cause of joint pain.iNKT cell deficiency is present in patients with RA and other inflammatory arthropathy. Normal iNKT cell frequency predicts non-inflammatory causes of joint pain.
1318 FIBROSIS PROGRESSION IN PATIENTS WITH CHRONIC HEPATITIS C IS NOT INFLUENCED BY IL28B POLYMORPHISMS
Authors: A. Aghemo, F. Marabita, S. De Nicola, M.G. Rumi, C. Cheroni, R. Scavelli, M. Crimi, R. Soffredini, S. Abrignani, R. De Francesco, M. Colombo
Journal: Journal of Hepatology (2011)
Proteomic Characterization of Novel Alternative Splice Variant Proteins in Human Epidermal Growth Factor Receptor 2/neu–Induced Breast Cancers
Authors: Rajasree Menon, Gilbert S. Omenn
Journal: Cancer Research (2010)

Multifaceted alternative splicing in cancer cells greatly diversifies protein structure independently of genome changes, but the characterization of cancer-associated splice variants is quite limited. In this study, we used mass spectrometric data to interrogate a custom-built database created with three-frame translations of mRNA sequences from Ensembl and ECgene to find alternative splice variant proteins. In mass spectrometric files from liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses of normal mouse mammary glands or mammary tumors derived from conditional human epidermal growth factor receptor 2 (Her2)/neu transgenic mice, we identified a total of 608 alternative splice variants, of which peptides from 216 proteins were found only in the tumor sample. Among the 608 splice variants were 68 novel proteins that were not completely matched to any known protein sequence in mice, for which we found known functional motifs. Biological process enrichment analysis of the splice variants identified suggested the involvement of these proteins especially in cell motility and translation initiation. The cancer-associated differentially expressed splice variant proteins offer novel biomarker candidates that may function in breast cancer progression or metastasis.
Combination Therapy of an Orthotopic Renal Cell Carcinoma Model Using Intratumoral Vector-Mediated Costimulation and Systemic Interleukin-2
Authors: Chie Kudo-Saito, Elizabeth K. Wansley, M. Eilene Gruys, Robert Wiltrout, Jeffrey Schlom, James W. Hodge
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Interleukin (IL)-2 therapy is currently used for therapy of renal cell carcinoma (RCC). However, it is only effective in approximately 10% to 15% of patients, showing a need for additional therapies. We have previously described a replication-defective fowlpox vector encoding three costimulatory molecules (B7-1, ICAM-1, and LFA-3), designated rF-TRICOM. Here, we show that intratumoral administration of rF-TRICOM in an orthotopic RCC model effectively enhances tumor immunogenicity and reduces tumor burden in mice and the combination of rF-TRICOM and IL-2 is more effective than either therapy alone. Experimental Design: RCC cells were implanted under the capsule of the kidney, and mice were given rF-TRICOM intratumorally 14 days later. We compared the effect of rF-TRICOM, rF-granulocyte macrophage colony-stimulating factor (GM-CSF), and two doses of IL-2 and combinations of the above on antitumor efficacy and survival. Host CD4+ and CD8+ T-cell responses were also evaluated. Results: The results show that (a) systemic IL-2 therapy was moderately effective in the reduction of tumor burden in an orthotopic RCC model; (b) a single intratumoral injection of rF-TRICOM and rF-GM-CSF significantly reduced tumor burden; (c) the addition of systemic IL-2 to intratumoral rF-TRICOM/rF-GM-CSF administration resulted in further reduction of tumor burden, decrease in the incidence of metastasis, and extended survival in tumor-bearing mice above that seen with either treatment alone; and (d) CD8+ T cells played a critical role in the antitumor effect seen with rF-TRICOM/rF-GM-CSF + IL-2 therapy. Finally, the addition of systemic recombinant IL-15 or intratumoral vector-delivered IL-15 to intratumoral rF-TRICOM/rF-GM-CSF administration resulted in substantially more tumor-free mice than either therapy alone. Conclusions: These studies show that intratumoral administration of rF-TRICOM admixed with rF-GM-CSF is effective at reducing tumor burden in mice and the addition of IL-2 further contributes to this effect. These studies thus form the rationale for combination immunotherapy clinical trials in patients with RCC.
Interaction of Pseudomonas aeruginosa with human respiratory mucosa in vitro
Authors: KW Tsang, A Rutman, E Tanaka, V Lund, A Dewar, PJ Cole, R Wilson
Journal: European Respiratory Journal (1994)

Pseudomonas aeruginosa commonly infects the airways of patients with cystic fibrosis and bronchiectasis. It produces several toxins that slow ciliary beat, stimulate mucus production and damage epithelium. It adheres to epithelial cells, damaged mucosa (in animal models), and mucus. However, little is known of the interaction of P. aeruginosa with intact human respiratory mucosa. We have studied the interactions of a nonmucoid clinical isolate of P. aeruginosa with adenoid tissue in a novel organ culture model with an air-mucosal interphase P. aeruginosa (5.9 +/- 0.9 x 10(6) colony-forming units (cfu)) was pipetted onto the organ culture surface, and incubated for 15 min, 1, 2, 4, 8, 12, 16, and 24 h, at 37 degrees C in 5% CO2 in a humidified atmosphere. Assessment has been made by transmission and scanning electron microscopy. Transmission electron microscopy (TEM) showed that uninfected organ cultures had normal ultrastructure. TEM of infected organ cultures at 8 h showed significant epithelial damage: 43.9 +/- 10% of cells extruding from the epithelial surface, 17.7 +/- 3% of cells with loss of cilia, 32.9 +/- 10.2% of cells with mitochondrial damage, and 11.6 +/- 3% of cells with cytoplasmic blebbing. P. aeruginosa only infrequently adhered to normal epithelium, but adhered to areas of epithelial damage and to basement membrane. Scanning electron microscopy (SEM) of organ cultures up to 2 h found P. aeruginosa only infrequently associated with mucus. SEM at 4 h revealed P. aeruginosa predominantly associated with mucus and extruded damaged epithelial cells, but also occasionally associated with cilia, and very occasionally with unciliated cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Research on Cerebral Electrotherapy (Electrosleep): Some Suggestions
Authors: BERNARD L. FRANKEL
Journal: American Journal of Psychiatry (1974)

The author discusses the methodological shortcomings of previous studies on cerebral electrotherapy (CET) and suggests various methodological and design procedures that need to be incorporated into future studies if the question of the therapeutic effectiveness and applicability of CET is to be conclusively settled. Among the procedures he recommends are double-blind methods of research and improved techniques of evaluation and follow-up.
HPV testing as a screen for cervical cancer
Authors: A. Goodman
Journal: BMJ (2015)

Human papillomavirus (HPV) has been identified as a necessary factor in the development of pre-invasive and invasive cancers of the lower genital tract, of which cervical cancer is the most prevalent. A molecular understanding of malignant transformation and epidemiologic information has led to the development of many strategies for detection and early intervention. Newer tests for oncogenic subtypes of HPV have made it possible to predict the risk of future development of cervical cancer. This review summarizes the current understanding of HPV related disease and examines the role of HPV testing as a screening tool for cervical cancer. It summarizes the data from prospective and randomized controlled trials on HPV screening from Europe and North America and includes smaller studies from low and middle income countries where cervical cancer is the most common cancer in women.
The Effect in Premature Infants of Prenatal Corticosteroids on Endogenous Surfactant Synthesis as Measured with Stable Isotopes
Authors: JAN ERIK H. BUNT, VIRGILIO P. CARNIELLI, J. L. DARCOS WATTIMENA, WIM C. HOP, PIETER J. J. SAUER, LUC J. I. ZIMMERMANN
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Most in vitro studies show that prenatal administration of corticosteroids stimulates the synthesis of surfactant phosphatidylcholine (PC), but studies in animals are controversial. Whether prenatal corticosteroids stimulate surfactant PC synthesis in humans has not been studied. We studied endogenous surfactant PC synthesis in relation to prenatal corticosteroid treatment in 27 preterm infants with respiratory distress syndrome. Infants received a 24-h infusion of the stable isotope [U-13C]glucose, starting ∼ 5 h after birth. We measured 13C-incorporation into palmitic acid in surfactant PC from serial tracheal aspirates and in plasma triglycerides and phospholipids by isotope-ratio mass spectrometry. Premature infants had received either zero (n = 11), one (n = 4), or two doses (n = 12) of prenatal betamethasone (12 mg intramuscularly). The fractional synthesis rate (FSR) of surfactant PC from glucose was 1.7 ± 0.3%/d without corticosteroid treatment, 2.9 ± 1.4%/d with one dose of prenatal corticosteroid, and 5.8 ± 1.3%/d after two doses of prenatal corticosteroid. Using multiple regression analysis, we found that the FSR of surfactant PC increased by 40% (confidence interval: 7 to 82%/d, p < 0.02) per dose of corticosteroid and doubled after two doses of corticosteroid. The 13C-enrichment of plasma triglycerides and phospholipids was not increased by corticosteroid. These data show for the first time that prenatal corticosteroid treatment stimulates surfactant synthesis in the preterm infant.
CELL INTERACTIONS BETWEEN HISTOINCOMPATIBLE T AND B LYMPHOCYTES
Authors: David H. Katz, Martin E. Dorf, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1974)

In our initial studies on the question of histocompatibility requirements in T-B-cell interactions, we found that no cooperation occurred with mixtures of T and B cells from BALB/c (H-2d) and A/J (H-2a) donors, respectively (1). These particular strains are identical for genes in the S and D regions of the H-2 complex but possess major differences at the K-end. Many differences are known to exist in the I region as well. Thus, these early data indicated that gene identities only at the D-end are insufficient to permit optimal cooperative interactions to occur under these conditions.
Cyr61/CCN1 signaling is critical for epithelial-mesenchymal transition and stemness and promotes pancreatic carcinogenesis
Authors: Inamul Haque, Smita Mehta, Monami Majumder, Kakali Dhar, Archana De, Douglas McGregor, Peter J Van Veldhuizen, Sushanta K Banerjee, Snigdha Banerjee
Journal: Molecular Cancer (2011)

Abstract Background Despite recent advances in outlining the mechanisms involved in pancreatic carcinogenesis, precise molecular pathways and cellular lineage specification remains incompletely understood. Results We show here that Cyr61/CCN1 play a critical role in pancreatic carcinogenesis through the induction of EMT and stemness. Cyr61 mRNA and protein were detected in the early precursor lesions and their expression intensified with disease progression. Cyr61/CCN1 expression was also detected in different pancreatic cancer cell lines. The aggressive cell lines, in which the expressions of mesenchymal/stem cell molecular markers are predominant; exhibit more Cyr61/CCN1 expression. Cyr61 expression is exorbitantly higher in cancer stem/tumor initiating Panc-1-side-population (SP) cells. Upon Cyr61/CCN1 silencing, the aggressive behaviors are reduced by obliterating interlinking pathobiological events such as reversing the EMT, blocking the expression of stem-cell-like traits and inhibiting migration. In contrast, addition of Cyr61 protein in culture medium augments EMT and stemness features in relatively less aggressive BxPC3 pancreatic cancer cells. Using a xenograft model we demonstrated that cyr61/CCN1 silencing in Panc-1-SP cells reverses the stemness features and tumor initiating potency of these cells. Moreover, our results imply a miRNA-based mechanism for the regulation of aggressive behaviors of pancreatic cancer cells by Cyr61/CCN1. Conclusions In conclusion, the discovery of the involvement of Cyr61/CCN1 in pancreatic carcinogenesis may represent an important marker for PDAC and suggests Cyr61/CCN1 can be a potential cancer therapeutic target.
Effects of propranolol inhalation on the diurnal increase in FEV1 and on propranolol airways responsiveness in atopic subjects with asthma.
Authors: Y Oosterhoff, G H Koeter, D S Postma
Journal: Thorax (1995)

Propranolol inhalation provocation tests are used to measure indirect airways responsiveness in the investigation of asthma. In this study the effects of repeated propranolol inhalation provocation tests within the same day on normal diurnal variation in the forced expiratory volume in one second (FEV1) and subsequent propranolol airways responsiveness were investigated.Fifteen atopic asthmatic subjects were challenged with doubling concentrations of propranolol at 08.00 and 16.00 hours on the same study day and at 16.00 hours on a control day to exclude changes related to normal diurnal variation.Mean (SD) baseline FEV1 at 16.00 hours on the study day was 3.38 (0.23) 1, significantly lower than the value at 16.00 hours on the control day of 3.70 (0.24) 1 (p = 0.001). No differences were found between the geometric mean provocative concentration of propranolol causing a 20% fall in FEV1 (PC20) measured on the study day (08.00 hours, 9.3 mg/ml; 16.00 hours, 11.3 mg/ml) and on the control day (16.00 hours 9.3 mg/ml).The results suggest that propranolol provocation at 08.00 hours has a long lasting effect on FEV1, thereby counteracting the normal diurnal increase in diameter of the airways. This makes propranolol challenge tests less suitable for studying indirect airways responsiveness in the course of one day. Because the FEV1 does not return to control values, it is not possible to determine whether tachyphylaxis to repeated propranolol challenge with a time interval of up to eight hours occurs.
Depression and All-Cause and Coronary Heart Disease Mortality Among Adults With and Without Diabetes
Authors: Leonard E. Egede, Paul J. Nietert, Deyi Zheng
Journal: Diabetes Care (2005)

OBJECTIVE—The aim of this study was to evaluate the effect of depression on all-cause and coronary heart disease (CHD) mortality among adults with and without diabetes. RESEARCH DESIGN AND METHODS—We studied 10,025 participants in the population-based National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study who were alive and interviewed in 1982 and had complete data for the Center for Epidemiologic Studies Depression Scale. Four groups were created based on diabetes and depression status in 1982: 1) no diabetes, no depression (reference group); 2) no diabetes, depression present; 3) diabetes present, no depression; and i4) diabetes present, depression present. Cox proportional hazards regression models were used to calculate multivariate-adjusted hazard ratios (HRs) of death for each group compared with the reference group. RESULTS—Over 8 years (83,624 person-years of follow-up), 1,925 deaths were documented, including 522 deaths from CHD. Mortality rate per 1,000 person-years of follow-up was highest in the group with both diabetes and depression. Compared with the reference group, HRs for all-cause mortality were no diabetes, depression present, 1.20 (95% CI 1.03–1.40); diabetes present, no depression 1.88 (1.55–2.27); and diabetes present, depression present, 2.50 (2.04–3.08). HRs for CHD mortality were no diabetes, depression present, 1.29 (0.96–1.74); diabetes present, no depression 2.26 (1.60–3.21); and diabetes present, depression present, 2.43 (1.66–3.56). CONCLUSIONS—The coexistence of diabetes and depression is associated with a significantly increased risk of death from all causes, beyond that due to having either diabetes or depression alone.
Wilkinson Support Calculated with Exact Probabilities: An Example Using Floricaula/LEAFY Amino Acid Sequences that Compares Three Hypotheses Involving Gene Gain/Loss in Seed Plants
Authors: Michael W. Frohlich, George F. Estabrook
Journal: Molecular Biology and Evolution (2000)

This paper describes a method for quantifying the extent to which a character supports a hypothesized monophyletic group. The basic idea was first proposed by Wilkinson in 1998; hence, we call it Wilkinson support. A character provides Wilkinson support if it could have changed state on the branch leading to the hypothesized monophyletic group without requiring any extra steps in an evolutionary tree. We describe a method to determine the exact probability that a character would provide Wilkinson support for a random group of the same size as the hypothesized monophyletic group. A character's weight is defined as the negative natural log of this probability. The sum over all characters of these weights in a data set is a measure of total weighted support. We exemplify this method using 30 Floricaula/LEAFY amino acid sequences. One copy of this gene occurs in angiosperms, but two copies occur in the other four seed plant groups. Angiosperms could have been primitively single-copy or could have lost either of the two paralogs. These possibilities correspond to three hypotheses of monophyly. We use total weighted Wilkinson support to evaluate these three hypotheses, and all three are shown to be significantly different from random as individual hypothesized monophyletic groups. Comparing these three hypotheses for total weighted support reveals that one has much more support than do the other two. This hypothesis favors the “mostly-male” theory of flowering-plant origins.
Individual patient data meta-analysis: a promising approach for evidence synthesis in reproductive medicine
Authors: K. A. Broeze, B. C. Opmeer, F. van der Veen, P. M. Bossuyt, S. Bhattacharya, B. W. J. Mol
Journal: Human Reproduction Update (2010)

Systematic reviews and accompanying meta-analyses are the cornerstones of evidence-based medicine. Systematic reviews summarize clinical evidence; meta-analyses provide summary estimates of the treatment effect or the diagnostic test accuracy. Although deemed to provide the highest level of evidence, their clinical value is limited as they can only summarize aggregated data. In these meta-analyses the true variability of the treatment effects cannot be explored to the desired extent, because the meta-analyses cannot distinguish between patients with different clinical profiles. Systematic reviews and meta-analyses based on individual patient data (IPD), described as the 'gold standard' for systematic reviews are a promising approach that might overcome these limitations. IPD meta-analyses allow treatment effects and diagnostic accuracy to be estimated at the level of relevant patient subgroups. This enables researchers to investigate the effectiveness of treatment in patients with different profiles. In this article, we address the opportunities of systematic reviews and meta-analyses using IPD in reproductive medicine. We discuss its potential based on three clinical examples: single versus double embryo transfer in IVF, the diagnosis of tubal pathology and the prognostic value of ovarian reserve tests. We propose to show potential advantages of IPD systematic reviews and meta-analyses in providing stratified clinical evidence, which could improve medical care.