tbuckley/cabot-search huggingface dataset:
Interaction of antibodies against cytomegalovirus with heat-shock protein 60 in pathogenesis of atherosclerosis
Authors: Caterina Bason, Roberto Corrocher, Claudio Lunardi, Patrizia Puccetti, Oliviero Olivieri, Domenico Girelli, Riccardo Navone, Ruggero Beri, Enrico Millo, Alberto Margonato, Nicola Martinelli, Antonio Puccetti
Journal: The Lancet (2003)
Surveillance of &lt;EMPH TYPE="ITAL"&gt;BRCA1&lt;/EMPH&gt; and &lt;EMPH TYPE="ITAL"&gt;BRCA2&lt;/EMPH&gt; Mutation Carriers With Magnetic Resonance Imaging, Ultrasound, Mammography, and Clinical Breast Examination
Authors: Ellen Warner
Journal: JAMA (2004)

ContextCurrent recommendations for women who have a BRCA1 or BRCA2 mutation are to undergo breast surveillance from age 25 years onward with mammography annually and clinical breast examination (CBE) every 6 months; however, many tumors are detected at a relatively advanced stage. Magnetic resonance imaging (MRI) and ultrasound may improve the ability to detect breast cancer at an early stage.ObjectiveTo compare the sensitivity and specificity of 4 methods of breast cancer surveillance (mammography, ultrasound, MRI, and CBE) in women with hereditary susceptibility to breast cancer due to a BRCA1 or BRCA2 mutation.Design, Setting, and ParticipantsA surveillance study of 236 Canadian women aged 25 to 65 years with BRCA1 or BRCA2 mutations who underwent 1 to 3 annual screening examinations, consisting of MRI, mammography, and ultrasound at a single tertiary care teaching hospital between November 3, 1997, and March 31, 2003. On the day of imaging and at 6-month intervals, CBE was performed.Main Outcome MeasuresSensitivity and specificity of each of the 4 surveillance modalities, and sensitivity of all 4 screening modalities vs mammography and CBE.ResultsEach imaging modality was read independently by a radiologist and scored on a 5-point Breast Imaging Reporting and Data System scale. All lesions with a score of 4 or 5 (suspicious or highly suspicious for malignancy) were biopsied. There were 22 cancers detected (16 invasive and 6 ductal carcinoma in situ). Of these, 17 (77%) were detected by MRI vs 8 (36%) by mammography, 7 (33%) by ultrasound, and 2 (9.1%) by CBE. The sensitivity and specificity (based on biopsy rates) were 77% and 95.4% for MRI, 36% and 99.8% for mammography, 33% and 96% for ultrasound, and 9.1% and 99.3% for CBE, respectively. There was 1 interval cancer. All 4 screening modalities combined had a sensitivity of 95% vs 45% for mammography and CBE combined.ConclusionsIn BRCA1 and BRCA2 mutation carriers, MRI is more sensitive for detecting breast cancers than mammography, ultrasound, or CBE alone. Whether surveillance regimens that include MRI will reduce mortality from breast cancer in high-risk women requires further investigation.
Production of interleukin-8, RANTES and MCP-1 in intrinsic and extrinsic asthmatics
Authors: SG Folkard, J Westwick, AB Millar
Journal: European Respiratory Journal (1997)

The aim of this study was to determine the relative production of chemokines interleukin-8 (IL-8), regulated on activation, normal T-cell expressed and secreted (RANTES) and monocyte chemotactic protein-1 (MCP-1) by intrinsic and extrinsic asthmatics. Nine intrinsic asthmatics, 10 extrinsic asthmatics, five nonatopic and five atopic controls underwent bronchoalveolar lavage (BAL). Total BAL cells were cultured in the presence or absence of lipopolysaccharide. Chemokines were measured in BAL cell supernatants and in cell-free bronchoalveolar lavage fluid (BALF) by enzyme-linked immunoabsorbent assay (ELISA). BAL cell cytospins were stained immunohistochemically for chemokines. BAL cells from asthmatics produced more IL-8 than controls (statistically significant for extrinsic asthma). RANTES was elevated in the BAL cell supernatants of four out of nine intrinsic asthmatics as compared to nonatopic controls (not statistically significant). RANTES levels in the BAL cell supernatants of extrinsic asthmatics were all low. MCP-1 production by BAL cells was similar in all groups. Immunostaining of BAL cell cytospins showed the macrophage to be the predominant positive-staining cell type and correlated well with supernatant data. Measurement of chemokines in BALF showed significantly elevated IL-8 in intrinsic asthma compared to nonatopic controls, but no increase in extrinsic asthmatics relative to atopic control RANTES was elevated in three out of nine BALFs from intrinsic asthmatics compared with nonatopic controls (not statistically significant). MCP-1 was not elevated above control levels in BALF of either asthma group. These results suggest an up-regulation in the production of interleukin-8 and regulated on activation, normal T-cell expressed and secreted, but not monocyte chemotactic protein-1 (MCP-1), by macrophages in the bronchoalveolar lavage of asthmatic subjects. In addition, the data suggest that regulated on activation, normal T-cell, expressed and secreted, may be differentially produced by macrophages in atopic and nonatopic asthma.
Selective Killing of Cancer Cells by Suppression of Geminin Activity
Authors: Wenge Zhu, Melvin L. DePamphilis
Journal: Cancer Research (2009)

Abstract Eukaryotic cells normally restrict genome duplication to once per cell division. In metazoa, re-replication of DNA during a single S phase seems to be prevented solely by suppressing CDT1 activity, a protein required for loading the replicative MCM DNA helicase. However, siRNA suppression of geminin (a specific inhibitor of CDT1) arrested proliferation only of cells derived from cancers by inducing DNA re-replication and DNA damage that spontaneously triggered apoptosis. None of these effects were detected either in cells derived from normal human tissues or in cells immortalized by a viral oncogene. To induce these effects in noncancer cells required suppression of both geminin and cyclin A, another cell cycle regulator. Therefore, initiating DNA replication in some cancer cells is limited solely by regulating the level of CDT1 activity with geminin, whereas noncancer cells contain additional safeguards that prevent DNA re-replication. These results show that inhibition of geminin activity could be used to selectively kill cancer cells without harming other cells. [Cancer Res 2009;69(11):4870–7]
Transcriptional Repression of Hepatic <i>Cytochrome P450 3A4</i> Gene in the Presence of Cancer
Authors: Kellie A. Charles, Laurent P. Rivory, Sandie L. Brown, Christopher Liddle, Stephen J. Clarke, Graham R. Robertson
Journal: Clinical Cancer Research (2006)

Many chemotherapeutic drugs have an inherent lack of safety due to interindividual variability of hepatic cytochrome P450 (CYP) 3A4 drug metabolism. This reduction in CYP3A4 in cancer patients is possibly mediated by cytokines associated with tumor-derived inflammation. We sought to examine this link by using an explant sarcoma in a novel transgenic mouse model of human CYP3A4 regulation.Engelbreth-Holm-Swarm sarcoma cells were injected into the hindlimb of transgenic CYP3A4/lacZ mice. Hepatic expression of the human CYP3A4 transgene was analyzed by direct measurement of the reporter gene product, beta-galactosidase enzyme activity. Hepatic expression of murine Cyp3a was analyzed at the mRNA, protein, and function levels. The acute phase response was assessed by examining cytokines [interleukin-6 (IL-6) and tumor necrosis factor] in serum, liver, or tumor as well as hepatic expression of serum amyloid protein P.Engelbreth-Holm-Swarm sarcoma elicited an acute phase response that coincided with down-regulation of the human CYP3A4 transgene in the liver as well as the mouse orthologue Cyp3a11. The reduction of murine hepatic Cyp3a gene expression in tumor-bearing mice resulted in decreased Cyp3a protein expression and consequently a significant reduction in Cyp3a-mediated metabolism of midazolam. Circulating IL-6 was elevated and IL-6 protein was only detected in tumor tissue but not in hepatic tissue.The current study provides a mechanistic link between cancer-associated inflammation and impaired drug metabolism in vivo. Targeted therapy to reduce inflammation may provide improved clinical benefit for chemotherapy drugs metabolized by hepatic CYP3A4 by improving their pharmacokinetic profile.
Changes in prevalence, incidence and spontaneous loss of gastro-oesophageal reflux symptoms: a prospective population-based cohort study, the HUNT study
Authors: Eivind Ness-Jensen, Anna Lindam, Jesper Lagergren, Kristian Hveem
Journal: Gut (2011)

Changes in the occurrence of gastro-oesophageal reflux symptoms (GORS) in the population remain uncertain. This study aimed to determine the prevalence changes, the incidence and the spontaneous loss of GORS.This population-based cohort study was conducted within the Nord-Trøndelag Health Study (the HUNT study), a longitudinal series of population-based health surveys in Nord-Trøndelag County, Norway. The study base encompassed all adult residents in the county, and the participants reported the degree of GORS during the previous 12 months. The number of participants included were 58,869 (64% response rate) in 1995-7 and 44,997 (49%) in 2006-9. Of these, 29,610 persons (61%) were prospectively followed up for an average of 11 years.Between 1995-7 and 2006-9, the prevalence of any, severe and at least weekly GORS increased by 30% (from 31.4% to 40.9%), 24% (from 5.4% to 6.7%) and 47% (from 11.6% to 17.1%), respectively. The average annual incidence of any and severe GORS was 3.07% and 0.23%, respectively. In women, but not men, the incidence of GORS increased with increasing age. The average annual spontaneous loss (not due to antireflux medication) of any and severe GORS was 2.32% and 1.22%, respectively. The spontaneous loss of GORS decreased with increasing age.Between 1995-7 and 2006-9 the prevalence of GORS increased substantially. At least weekly GORS increased by 47%. The average annual incidence of severe GORS was 0.23%, and the corresponding spontaneous loss was 1.22%. The incidence and spontaneous loss of GORS were influenced by sex and age.
Health-related quality of life and functional status in end-stage COPD: a longitudinal study
Authors: J.M. Habraken, W.M. van der Wal, G. ter Riet, E.J.M. Weersink, F. Toben, P.J.E. Bindels
Journal: European Respiratory Journal (2010)

Since there is still a dearth of information about the end stage of chronic obstructive pulmonary disease (COPD), the main aim of this study was to examine the development of health-related quality of life (HRQoL) and functional status over time in COPD patients in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV. 82 Dutch COPD patients completed the St George’s Respiratory Questionnaire (SGRQ) for HRQoL and the Groningen Activities for Daily Living Restriction Scale (GARS) for functional status every 3 months during the year following enrolment. Survival was followed up to 5 yrs after enrolment. Data were analysed by stratifying the study population into severity subgroups according to the lowest, intermediate and highest tertile of SGRQ and GARS at baseline. Outcome measures were change in SGRQ and GARS scores over time and survival time. In the majority of patients, scores on the SGRQ and GARS declined gradually over time. In the subgroup of 32 patients that died within 2 yrs of enrolment, these scores also declined gradually, without steep deteriorations. In patients with end-stage COPD, HRQoL and functional status deteriorated gradually over time, indicating that clinicians did not gain much additional support for differentiating the end stage of COPD by considering HRQoL and functional status using the SGRQ and GARS.
A novel myeloid-like NK cell progenitor in human umbilical cord blood
Authors: Sonia A. Perez, Panagiota A. Sotiropoulou, Dimitra G. Gkika, Louisa G. Mahaira, Dimitrios K. Niarchos, Angelos D. Gritzapis, Yiannis G. Kavalakis, Aris I. Antsaklis, Constantin N. Baxevanis, Michael Papamichail
Journal: Blood (2003)
Analysis of the T-Cell Receptor Repertoires of Tumor-Infiltrating Conventional and Regulatory T Cells Reveals No Evidence for Conversion in Carcinogen-Induced Tumors
Authors: James P. Hindley, Cristina Ferreira, Emma Jones, Sarah N. Lauder, Kristin Ladell, Katherine K. Wynn, Gareth J. Betts, Yogesh Singh, David A. Price, Andrew J. Godkin, Julian Dyson, Awen Gallimore
Journal: Cancer Research (2010)

A significant enrichment of CD4(+)Foxp3(+) T cells (regulatory T cells, Treg) is frequently observed in murine and human carcinomas. As Tregs can limit effective antitumor immune responses, thereby promoting tumor progression, it is important that the mechanisms underpinning intratumoral accumulation of Tregs are identified. Because of evidence gathered mostly in vitro, the conversion of conventional T cells (Tconv) into Tregs has been proposed as one such mechanism. We assessed the contribution of conversion in vivo by analyzing the TCR (T-cell receptor) repertoires of Tconvs and Tregs in carcinogen-induced tumors in mice. Our results indicate that the TCR repertoires of Tregs and Tconvs within tumor-infiltrating lymphocytes (TIL) are largely distinct. Indeed, the cell population with the greatest degree of repertoire similarity with tumor-infiltrating Tregs was the Treg population from the tumor-draining lymph node. These findings demonstrate that conversion of Tconvs does not contribute significantly to the accumulation of tumor-infiltrating Tregs; rather, Tconvs and Tregs arise from different populations with unique TCR repertoires. Enrichment of Tregs within TILs most likely, therefore, reflects differences in the way that Tregs and Tconvs are influenced by the tumor microenvironment. Elucidating the nature of these influences may indicate how the balance between tumor-infiltrating Tregs and Tconvs can be manipulated for therapeutic purposes.
The Population Genomics of Repeated Evolution in the Blind Cavefish Astyanax mexicanus
Authors: Martina Bradic, Henrique Teotónio, Richard L. Borowsky
Journal: Molecular Biology and Evolution (2013)

Distinct populations of Astyanax mexicanus cavefish offer striking examples of repeatable convergence or parallelism in their independent evolutions from surface to cave phenotypes. However, the extent to which the repeatability of evolution occurred at the genetic level remains poorly understood. To address this, we first characterized the genetic diversity of 518 single-nucleotide polymorphisms (SNPs), obtained through RAD tag sequencing and distributed throughout the genome, in seven cave and three groups of surface populations. The cave populations represented two distinct lineages (old and new). Thirty-one SNPs were significantly differentiated between surface and old cave populations, two SNPs were differentiated between surface and new cave populations, and 44 SNPs were significantly differentiated in both old and new cave populations. In addition, we determined whether these SNPs map to the same locations of previously described quantitative trait loci (QTL) between surface and cave populations. A total of 25 differentiated SNPs co-map with several QTL, such as one containing a fibroblast growth factor gene (Fgf8) involved in eye development and lens size. Further, the identity of many SNPs that co-mapped with QTL was the same in independently derived cave populations. These conclusions were further confirmed by haplotype analyses of SNPs within QTL regions. Our findings indicate that the repeatability of evolution at the genetic level is substantial, suggesting that ancestral standing genetic variation significantly contributed to the population genetic variability used in adaptation to the cave environment.
New reference ranges for interpreting forced expiratory manoeuvres in infants and implications for clinical interpretation: a multicentre collaboration
Authors: Sooky Lum, Vassiliki Bountziouka, Angela Wade, Ah-Fong Hoo, Jane Kirkby, Antonio Moreno-Galdo, Ines de Mir, Olaia Sardon-Prado, Paula Corcuera-Elosegui, Joerg Mattes, Luis Miguel Borrego, Gwyneth Davies, Janet Stocks
Journal: Thorax (2015)

The raised volume rapid thoracoabdominal compression (RVRTC) technique is commonly used to obtain full forced expiratory manoeuvres from infants, but reference equations derived from 'in-house' equipment have been shown to be inappropriate for current commercially available devices. <h3>Aim</h3> To explore the impact of equipment differences on RVRTC outcomes, derive robust equipment-specific RVRTC reference ranges and investigate their potential clinical impact on data interpretation. <h3>Method</h3> RVRTC data from healthy subjects using Jaeger BabyBody or the 'Respiratory Analysis Software Program, RASP' systems were collated from four centres internationally. Data were excluded if gestational age &lt;37 weeks or birth weight &lt;2.5 kg. Reference equations for RVRTC outcomes were constructed using the LMS (lambda–mu–sigma) method, and compared with published equations using data from newborn screened infants with cystic fibrosis (CF). <h3>Results</h3> RVRTC data from 429 healthy infants (50.3% boys; 88% white infants) on 639 occasions aged 4–118 weeks were available. When plotted against length, flows were significantly higher with RASP than Jaeger, requiring construction of separate equipment-specific regression equations. When comparing results derived from the new equations with those from widely used published equations based on different equipments, discrepancies in forced expiratory volumes and flows of up to 2.5 z-scores were observed, the magnitude of which increased with age. According to published equations, 25% of infants with CF fell below the 95% limits of normal for FEV<sub>0.5</sub>, compared with only 10% when using the new equations. <h3>Conclusions</h3> Use of equipment-specific prediction equations for RVRTC outcomes will enhance interpretation of infant lung function results; particularly during longitudinal follow-up.
Effect of expansion of extracellular fluid volume on renal phosphate handling
Authors: Wadi N. Suki, Manuel Martinez-Maldonado, Diane Rouse, Arthur Terry
Journal: Journal of Clinical Investigation (1969)

To examine the specific effect of extracellular fluid (ECF) volume expansion on phosphate excretion studies were performed in thyroparathyroidectomized dogs receiving saline solution intravenously. The natriuresis resulting from ECF volume expansion was consistently accompanied by an increase in phosphate excretion. The possible role of increased filtered load of phosphate was eliminated in experiments in which the filtered load of phosphate was reduced by acute reduction in the glomerular filtration rate. Despite considerable reductions in filtered phosphate, ECF volume expansion resulted in a consistent increase in phosphate excretion. Furthermore, the possible contribution of alteration in blood composition was investigated in experiments in which saline was infused during thoracic inferior vena cava constriction. In these experiments saline infusion failed to increase sodium or phosphate excretion. Cessation of saline infusion and release of caval constriction resulted in a prompt natriuresis and increased phosphate excretion. It is concluded from these studies that extracellular fluid volume expansion results in an increased phosphate excretion in the parathyroidectomized dog. This effect is the specific consequence of ECF volume expansion and is not due to increase in the filtered load of phosphate or alterations in blood composition.
Urban air pollution and emergency admissions for asthma in four European cities: the APHEA Project
Authors: J. Sunyer, C. Spix, P. Quenel, A. Ponce-de-Leon, A. Ponka, T. Barumandzadeh, G. Touloumi, L. Bacharova, B. Wojtyniak, J. Vonk, L. Bisanti, J. Schwartz, K. Katsouyanni
Journal: Thorax (1997)

BACKGROUND: A study was undertaken to assess the combined association between urban air pollution and emergency admissions for asthma during the years 1986-92 in Barcelona, Helsinki, Paris and London. METHODS: Daily counts were made of asthma admissions and visits to the emergency room in adults (age range 15-64 years) and children (&lt; 15 years). Covariates were short term fluctuations in temperature and humidity, viral epidemics, day of the week effects, and seasonal and secular trends. Estimates from all the cities were obtained for the entire period and separately by warm or cold seasons using Poisson time-series regression models. Combined associations were estimated using meta-analysis techniques. RESULTS: Daily admissions for asthma in adults increased significantly with increasing ambient levels of nitrogen dioxide (NO2) (relative risk (RR) per 50 micrograms/m3 increase 1.029, 95% CI 1.003 to 1.055) and non-significantly with particles measured as black smoke (RR 1.021, 95% CI 0.985 to 1.059). The association between asthma admissions and ozone (O3) was heterogeneous among cities. In children, daily admissions increased significantly with sulphur dioxide (SO2) (RR 1.075, 95% CI 1.026 to 1.126) and non-significantly with black smoke (RR 1.030, 95% CI 0.979 to 1.084) and NO2, though the latter only in cold seasons (RR 1.080, 95% CI 1.025 to 1.140). No association was observed for O3. The associations between asthma admissions and NO2 in adults and SO2 in children were independent of black smoke. CONCLUSIONS: The evidence of an association between air pollution at current urban levels and emergency room visits for asthma has been extended to Europe. In addition to particles, NO2 and SO2--by themselves or as a constituent of a pollution mixture--may be important in asthma exacerbations in European cities.
Inhalation characteristics with Spiromax® (S) versus Turbuhaler® (T) dry powder inhalers (DPI) in healthy adults (HA) and in patients with asthma (A) or COPD
Authors: Wahida Azouz, Philip Chetcuti, Harold Hosker, Dinesh Saralaya, Henry Chrystyn
Journal: European Respiratory Journal (2013)

Objective: The ability of patients to achieve a satisfactory inhalation manoeuvre through a DPI is affected by age, training and severity of their asthma or COPD. We measured inhalation characteristics when patients and HA inhaled through placebo S and T.  Methods: HA and patients with asthma (Child CA 6–11y, Adolescent AA 12–17y and adults >17y) or COPD were randomised in an open-label crossover design to S or T and received verbal training (using each patient information leaflet). An inhalation profile recorder was attached to each device to measure the inhalation manoeuvre. The profile with the highest peak inspiratory flow (PIF in L/min) was used for analysis.  Results: Asthma patients had a mean FEV 1  %pred of 54–69% and COPD patients of 52%. Inhalation parameters: PIF, maximum pressure change (MPC in kPa), initial acceleration of flow (ACC in kPa/sec) and time to PIF (Tp in sec) are presented in Table 1.  Conclusions: Patients (regardless of age and baseline disease severity) achieved more favourable inhalation parameters to deaggregate the metered dose in a S than those through the T.  Funding: TEVA Pharmaceuticals.