tbuckley/cabot-search huggingface dataset:
Repeatability and bronchodilator reversibility of lung function in young children
Authors: Samatha Sonnappa, Cristina M. Bastardo, Angie Wade, Andrew Bush, Janet Stocks, Paul Aurora
Journal: European Respiratory Journal (2012)

Knowledge of short- and longer-term repeatability of lung function in health and disease is essential to determine bronchodilator reversibility thresholds and to recognise if changes in lung function represent disease progression, therapeutic intervention or normal variability. Multiple-breath washout indices (lung clearance index, conductive ventilation inhomogeneity ( S cond )) and specific airway resistance (s R aw ) were measured in healthy children and stable wheezers. Measurements were performed at baseline and after 20 min without intervention to assess repeatability and determine bronchodilator reversibility thresholds. Bronchodilator reversibility was assessed by repeating baseline measurements 20 min after inhaled salbutamol. 28 healthy controls, mean± sd age 6.1±0.7 years and 62 wheezers 5.4±0.6 years were tested. Baseline variability in multiple-breath washout indices and s R aw was not significantly different between wheezers and healthy controls. Significant bronchodilator reversibility was only observed in wheezers for S cond (16%), but in both wheezers (37%) and healthy controls (20%) for s R aw . Some wheezers and healthy controls demonstrated increases in multiple-breath washout indices post-bronchodilator. Lung clearance index and s R aw demonstrate low baseline variability in healthy and diseased subjects. Neither multiple-breath washout indices nor s R aw are ideal for assessing bronchodilator reversibility in young children with stable wheeze. These findings will help to interpret the effect of therapeutic interventions in children with respiratory diseases.
Protesters force hospital to abandon lecture on euthanasia by shouts of "murderer" and "Nazi"
Authors: A. O'Dowd
Journal: BMJ (2009)

A lecture debating the legalisation of euthanasia had to be abandoned last week when the medical speakers were threatened by angry audience members.

The lecture, due to be held at Cork University Hospital (CUH) in Ireland, was halted as audience members surrounded the speakers and verbally attacked them.

One of the speakers, Len Doyal, a supporter of some forms of legalised euthanasia under strictly regulated conditions, had to be escorted away to safety by security staff. He condemned the experience as a “sad violation of freedom of speech.”

Professor Doyal, emeritus professor of medical ethics at Queen Mary, University of London, and professor of healthcare ethics at the University of East Anglia, said that he was disturbed by the event and the lack of support from the police present.

The lecture, entitled “Why euthanasia should be legalised,” …
Lack of α-synuclein increases amyloid plaque accumulation in a transgenic mouse model of Alzheimer's disease
Authors: Verena Kallhoff, Erica Peethumnongsin, Hui Zheng
Journal: Molecular Neurodegeneration (2007)

Alpha-synuclein is a small soluble, cytosolic protein which associates with vesicular membranes. It is a component of intracellular Lewy bodies present in Parkinson's disease and a subset of Alzheimer's disease (AD). In addition, early studies identified a fragment of alpha-synuclein in the amyloid plaques of AD patients. Hypothesizing that alpha-synuclein might modify the AD pathogenic process, we crossed the Tg2576 strain of APP transgenic mice onto an alpha-synuclein knockout background to determine the effects of alpha-synuclein on Abeta production and plaque deposition. We found that alpha-synuclein deficiency does not affect the Abeta levels, nor does it alter the age of onset of plaque pathology. To our surprise, however, loss of alpha-synuclein leads to a significant increase in plaque load in all areas of the forebrain at 18 months of age. This is associated with an increase in another synaptic protein, synaptophysin. We thus conclude that alpha-synuclein is not involved in seeding of the plaques, but rather suppresses the progression of plaque pathology at advanced stages.
Magnetic Resonance Imaging of the Cardiovascular System
Authors: John R. Beljan
Journal: JAMA (1988)

State-of-the-art magnetic resonance imaging (MRI) generates high-resolution images of the cardiovascular system. Conventional MRI techniques provide images in six to ten minutes per tomographic slice. New strategies have substantially improved the speed of imaging. The technology is relatively expensive, and its cost-effectiveness remains to be defined in relation to other effective, less expensive, and noninvasive technologies, such as echocardiography and nuclear medicine. The ultimate role of MRI will depend on several factors, including the development of specific applications such as (1) noninvasive angiography, especially of the coronary arteries; (2) noninvasive, highresolution assessment of regional myocardial blood flow distribution (eg, using paramagnetic contrast agents); (3) characterization of myocardial diseases using proton-relaxation property changes; and (4) evaluation of in vivo myocardial biochemistry. The three-dimensional imaging capability and the ability to image cardiovascular structures without contrast material give MRI a potential advantage over existing noninvasive diagnostic imaging techniques. This report analyzes current applications of MRI to the cardiovascular system and speculates on their future. (<i>JAMA</i>1988;259:253-259)
Osteodysplasty (Melnick and Needles syndrome). Report of a case.
Authors: F Coste, P Maroteaux, L Chouraki
Journal: Annals of the Rheumatic Diseases (1968)

The multiplicity of inherited skeletal dysplasias make their diagnosis difficult, especially in rare or atypical cases.A problem of this kind was posed about 2 years ago by a 50-year-old womant who presented many osseous deformities, which we were unable to classify until, about 4 months after we first saw her, Melnick and Needles (1966) described several members of two families who presented exactly the same clinical picture as our patient.According to these authors this was a new syndrome, and this opinion we share. Case ReportA married woman aged 50 years consulted us in February, 1966, because of pain in the right hip which had developed progressively for the past year.During infancy difficulty in walking had led to the discovery of osseous deformities, and during childhood she was treated for rickets.She had her first menses at 13 years and married at 24.Her first pregnancy, 3 years later, ended in a premature delivery in the seventh month.Delivery was difficult, requiring anaesthesia and forceps, and the baby died after 2 weeks.Soon afterwards a new pregnancy ended in the seventh month in haemorrhages and foetal death.She was dissuaded from having any further pregnancies and she adopted a child.Her general appearance is striking because of the many morphological abnormalities, although her general health is good, she is of normal intelligence, and her sight and hearing are good.The upper arms are short in contrast with abnormally long forearms and hands, a lengthened trunk, and narrow shoulders.The face is chubby and red (Fig. 1) with pimples and a receding chin (Fig. 2), surmounted by a high forehead.There is some degree of asymmetrical exophthalmos, predominating on the left side.The irregular teeth required much treat- ment and were finally replaced by dentures.Because of the narrow shoulders (biacromial diameter 32 cm.) and the long neck, the head (circumference= 57 cm.) seems too large compared with the width of the body.The height (1.55 m.) is normal and the weight (61 kg.) slightly excessive.The arms (Fig. 3) are short and sagittally bowed with a posterior concavity.The forearms turn away from the trunk.Extension of the elbows is limited and the wrists seem thick, but the hands * Given at a meeting of the Heberden Society in November, 1967.
Association of increased CCL5 and CXCL7 chemokine expression with neutrophil activation in severe stable COPD
Authors: A Di Stefano, G Caramori, I Gnemmi, M Contoli, L Bristot, A Capelli, F L M Ricciardolo, F Magno, S E. D'Anna, A Zanini, M Carbone, F Sabatini, C Usai, P Brun, K F Chung, P J Barnes, A Papi, I M Adcock, B Balbi
Journal: Thorax (2009)

<h3>Background:</h3> Increased numbers of activated neutrophils have been reported in the bronchial mucosa of patients with stable chronic obstructive pulmonary disease (COPD), particularly in severe disease. <h3>Objectives:</h3> To investigate the expression of neutrophilic chemokines and adhesion molecules in bronchial biopsies from patients with stable COPD of different severity (GOLD stages I–IV) compared with age-matched control subjects, smokers with normal lung function and never smokers. <h3>Methods:</h3> The expression of CCL5, CXCL1, 5, 6, 7 and 8, CXCR1, CXCR2, CD11b and CD44 was measured in the bronchial mucosa using immunohistochemistry, confocal immunofluorescence, real-time quantitative polymerase chain reaction (RT-QPCR) and Western blotting (WB). <h3>Results:</h3> The numbers of CCL5+ epithelial cells and CCL5+ and CXCL7+ immunostained cells were increased in the bronchial submucosa of patients with stable severe COPD compared with control never smokers and smokers with normal lung function. This was also confirmed at the level of mRNA expression. The numbers of CCL5+ cells in the submucosa of patients with COPD were 2–15 times higher than any other chemokines. There was no correlation between the number of these cells and the number of neutrophils in the bronchial submucosa. Compared with control smokers, the percentage of neutrophils co-expressing CD11b and CD44 receptors was significantly increased in the submucosa of patients with COPD. <h3>Conclusion:</h3> The increased expression of CCL5 and CXCL7 in the bronchial mucosa of patients with stable COPD, together with an increased expression of extracellular matrix-binding receptors on neutrophils, may be involved in the pathogenesis of COPD.
Effectiveness of antibiotics given before admission in reducing mortality from meningococcal disease: systematic review
Authors: Susan J M Hahné, André Charlett, Bernadette Purcell, Susanne Samuelsson, Ivonne Camaroni, Ingrid Ehrhard, Sigrid Heuberger, Maria Santamaria, James M Stuart
Journal: BMJ (2006)

Objective To review the evidence for effectiveness of treatment with antibiotics before admission in reducing case fatality from meningococcal disease. Design Systematic review. Data sources Cochrane register of trials and systematic reviews, database of abstracts of reviews of effectiveness, health technology assessment, and national research register in England and Wales, Medline, Embase, and CAB Health. Included studies Studies describing vital outcome of at least 10 cases of meningococcal disease classified by whether or not antibiotics were given before admission to hospital. Results 14 observational studies met the review criteria. Oral antibiotic treatment given before admission was associated with reduced mortality among cases (combined risk ratio 0.17, 95% confidence interval 0.07 to 0.44). In seven studies in which all included patients were seen in primary care, the association between parenteral antibiotics before admission and outcome was inconsistent (χ2 for heterogeneity 11.02, P = 0.09). After adjustment for the proportion given parenteral antibiotics before admission, there was no residual heterogeneity. A higher proportion of patients given parenteral antibiotics before admission was associated with reduced mortality after such treatment and vice versa (P = 0.04). Conclusion Confounding by severity is the most likely explanation both for the beneficial effect of oral antibiotics and the harmful effect observed in some studies of parenteral antibiotics. We cannot conclude whether or not antibiotics given before admission have an effect on case fatality. The data are consistent with benefit when a substantial proportion of cases are treated.
High prevalence of subclinical tuberculosis in HIV-1-infected persons without advanced immunodeficiency: implications for TB screening
Authors: T. Oni, R. Burke, R. Tsekela, N. Bangani, R. Seldon, H. P. Gideon, K. Wood, K. A. Wilkinson, T. H. M. Ottenhoff, R. J. Wilkinson
Journal: Thorax (2011)

<h3>Background</h3> The prevalence of asymptomatic tuberculosis (TB) in recently diagnosed HIV-1-infected persons attending pre-antiretroviral therapy (ART) clinics is not well described. In addition, it is unclear if the detection of <i>Mycobacterium tuberculosis</i> in these patients clearly represents an early asymptomatic phase leading to progressive disease or transient excretion of bacilli. <h3>Objective</h3> To describe the prevalence and outcome of subclinical TB disease in HIV-1-infected persons not eligible for ART. <h3>Methods</h3> The study was conducted in 274 asymptomatic ART-naïve HIV-1-infected persons in Khayelitsha Day Hospital, Cape Town, South Africa. All participants were screened for TB using a symptom screen and spoligotyping was performed to determine genotypes. <h3>Results</h3> The prevalence of subclinical TB disease was 8.5% (95% CI 5.1% to 13.0%) (n=18; median days to culture positivity 17 days), with 22% of patients being smear-positive. Spoligotyping showed a diverse variety of genotypes with all paired isolates being of the same spoligotype, effectively excluding cross-contamination. 56% of patients followed up developed symptoms 3 days to 2 months later. All were well and still in care 6–12 months after TB diagnosis; 60% were started on ART. A positive tuberculin skin test (OR 4.96, p=0.064), low CD4 count (OR 0.996, p=0.06) and number of years since HIV diagnosis (OR 1.006, p=0.056) showed trends towards predicting TB disease. <h3>Conclusion</h3> This study found a high prevalence but good outcome (retained in care) of subclinical TB disease in HIV-1-infected persons. The results suggest that, in high HIV/TB endemic settings, a positive HIV-1 test should prompt TB screening by sputum culture irrespective of symptoms, particularly in those with a positive tuberculin skin test, longer history of HIV infection and low CD4 count. Operational difficulties in resource-constrained settings with respect to screening with TB culture highlight the need for rapid and affordable point-of-care tests to identify persons with clinical and subclinical TB disease.
Hyaluronate Fragments Reverse Skin Atrophy by a CD44-Dependent Mechanism
Authors: Gürkan Kaya, Christian Tran, Olivier Sorg, Raymonde Hotz, Denise Grand, Pierre Carraux, Liliane Didierjean, Ivan Stamenkovic, Jean-Hilaire Saurat
Journal: PLoS Medicine (2006)

Skin atrophy is a common manifestation of aging and is frequently accompanied by ulceration and delayed wound healing. With an increasingly aging patient population, management of skin atrophy is becoming a major challenge in the clinic, particularly in light of the fact that there are no effective therapeutic options at present.Atrophic skin displays a decreased hyaluronate (HA) content and expression of the major cell-surface hyaluronate receptor, CD44. In an effort to develop a therapeutic strategy for skin atrophy, we addressed the effect of topical administration of defined-size HA fragments (HAF) on skin trophicity. Treatment of primary keratinocyte cultures with intermediate-size HAF (HAFi; 50,000-400,000 Da) but not with small-size HAF (HAFs; <50,000 Da) or large-size HAF (HAFl; >400,000 Da) induced wild-type (wt) but not CD44-deficient (CD44-/-) keratinocyte proliferation. Topical application of HAFi caused marked epidermal hyperplasia in wt but not in CD44-/- mice, and significant skin thickening in patients with age- or corticosteroid-related skin atrophy. The effect of HAFi on keratinocyte proliferation was abrogated by antibodies against heparin-binding epidermal growth factor (HB-EGF) and its receptor, erbB1, which form a complex with a particular isoform of CD44 (CD44v3), and by tissue inhibitor of metalloproteinase-3 (TIMP-3).Our observations provide a novel CD44-dependent mechanism for HA oligosaccharide-induced keratinocyte proliferation and suggest that topical HAFi application may provide an attractive therapeutic option in human skin atrophy.
Grey scale ultrasound in Crohn's disease.
Authors: S Holt, E Samuel
Journal: Gut (1979)

Grey scale ultrasound examination was performed in 20 patients with Crohn's disease of varying extent and severity. In 15 of the 20 patients studied, thickening of the wall of the terminal ileum and caecum, with adjoining inflammatory changes in the mesentery, produced recognisable patterns on longitudinal and transverse ultrasonographs. Grey scale ultrasound, although not providing the specificity or detail of conventional radiology, can be helpful in the assessment of ileocaecal Crohn's disease, particularly in younger patients where the radiation hazards of repeated x-ray examinations are undesirable.
Modulation of hepatic mRNA levels after administration of lipopolysaccharide and diphtheria and tetanus toxoids and pertussis vaccine adsorbed (dtp vaccine) to mice
Authors: Sherry S. Ansher, Walter Thompson
Journal: Hepatology (1994)

Administration of whole-cell diphtheria and tetanus toxoids and pertussis vaccine adsorbed (DTP vaccine) caused marked depression in the expression of mRNA for isozymes of cytochrome P-450 in the livers of endotoxin-responsive and nonresponsive mice. The levels of expression of mRNA for a polycyclic aromatic hydrocarbon-inducible (CYP1A2) and an ethanol-inducible (CYP2E1) form of P-450 were reduced by 70% to 80% 8 to 12 hr after vaccination or Bordetella pertussis endotoxin administration. These effects are preceded by marked increases (threefold to sixfold) in mRNA expression for interleukin-6, interleukin-1 and tumor necrosis factor in both strains of mice, with maximal increases 1 to 2 hr after injection. This is the first demonstration that levels of cytokine mRNA are altered in the liver in response to DTP vaccine administration. The finding of increased cytokine mRNA in the livers of mice injected with vaccine supports a role for cytokines as mediators of the decreased levels of cytochrome P-450. In addition, inducible nitric oxide synthase mRNA expression is also increased after vaccine administration, with a peak at 4 hr. The temporal relationship of the increased cytokine mRNA expression, increased nitric oxide synthase and decreased expression of P-450 mRNAs suggests a mechanism by which cytokines mediate the induction of nitric oxide synthase, which increases nitric oxide and decreases the activities of some cytochromes P-450.
Adaptation of the diaphragm and the vastus lateralis in mild-to-moderate COPD
Authors: M. Doucet, R. Debigaré, D.R. Joanisse, C. Côté, P. LeBlanc, J. Grégoire, J. Deslauriers, R. Vaillancourt, F. Maltais
Journal: European Respiratory Journal (2004)

The chronology of diaphragm and vastus lateralis adaptation in chronic obstructive pulmonary disease (COPD) has not been studied. The hypothesis of this study was that muscle changes would occur earlier in the diaphragm than in the vastus lateralis in COPD, a finding that would suggest that local factors would be more important than systemic factors in determining the muscle phenotypic expression, at least in mild-to-moderate disease. The adaptation of the vastus lateralis and diaphragm muscles was evaluated in patients with mild-to-moderate COPD and in subjects with normal pulmonary function. In both groups, the oxidative potential and the number of lipofuscin inclusions were higher in the diaphragm than in the vastus lateralis. Compared to control, the diaphragm in COPD had a higher oxidative capacity and a higher proportion of type I fibres, with a reciprocal decrease in type IIA fibres, while there was no difference in diaphragmatic cross sectional areas, capillarisation and lipofuscin inclusions. No significant differences were found in the vastus lateralis from both groups. In conclusion, these data indicate that the diaphragm in controls and in chronic obstructive pulmonary disease has a higher oxidative potential than the vastus lateralis, and that muscle adaptation occurs earlier in the diaphragm than in the vastus lateralis in mild-to-moderate chronic obstructive pulmonary disease.
Promoter Methylation and Silencing of the Retinoic Acid Receptor- Gene in Lung Carcinomas
Authors: A. K. Virmani, A. Rathi, S. Zochbauer-Muller, N. Sacchi, Y. Fukuyama, D. Bryant, A. Maitra, S. Heda, K. M. Fong, F. Thunnissen, J. D. Minna, A. F. Gazdar
Journal: JNCI Journal of the National Cancer Institute (2000)

Retinoic acid plays an important role in lung development and differentiation, acting primarily via nuclear receptors encoded by the retinoic acid receptor-beta (RARbeta) gene. Because receptor isoforms RARbeta2 and RARbeta4 are repressed in human lung cancers, we investigated whether methylation of their promoter, P2, might lead to silencing of the RARbeta gene in human lung tumors and cell lines.Methylation of the P2 promoter from small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cell lines and tumor samples was analyzed by the methylation-specific polymerase chain reaction (PCR). Expression of RARbeta2 and RARbeta4 was analyzed by reverse transcription-PCR. Loss of heterozygosity (LOH) was analyzed by PCR amplification followed by electrophoretic separation of PCR products. Statistical differences were analyzed by Fisher's exact test with continuity correction.The P2 promoter was methylated in 72% (63 of 87) of SCLC and in 41% (52 of 127) of NSCLC tumors and cell lines, and the difference was statistically significant (two-sided P:<.001). By contrast, in 57 of 58 control samples, we observed only the unmethylated form of the gene. Four tumor cell lines with unmethylated promoter regions expressed both RARbeta2 and RARbeta4. Four tumor lines with methylated promoter regions lacked expression of these isoforms, but demethylation by exposure to 5-aza-2'-deoxycytidine restored their expression. LOH at chromosome 3p24 was observed in 100% (13 of 13) of SCLC lines and 67% (12 of 18) of NSCLC cell lines, and the difference was statistically significant (two-sided P: =.028).Methylation of the RARbeta P2 promoter is one mechanism that silences RARbeta2 and RARbeta4 expression in many lung cancers, particularly SCLC. Chemical demethylation is a potential approach to lung cancer therapy.
Eukaryotic Penelope-Like Retroelements Encode Hammerhead Ribozyme Motifs
Authors: Amelia Cervera, Marcos De la Peña
Journal: Molecular Biology and Evolution (2014)

Small self-cleaving RNAs, such as the paradigmatic Hammerhead ribozyme (HHR), have been recently found widespread in DNA genomes across all kingdoms of life. In this work, we found that new HHR variants are preserved in the ancient family of Penelope-like elements (PLEs), a group of eukaryotic retrotransposons regarded as exceptional for encoding telomerase-like retrotranscriptases and spliceosomal introns. Our bioinformatic analysis revealed not only the presence of minimalist HHRs in the two flanking repeats of PLEs but also their massive and widespread occurrence in metazoan genomes. The architecture of these ribozymes indicates that they may work as dimers, although their low self-cleavage activity in vitro suggests the requirement of other factors in vivo. In plants, however, PLEs show canonical HHRs, whereas fungi and protist PLEs encode ribozyme variants with a stable active conformation as monomers. Overall, our data confirm the connection of self-cleaving RNAs with eukaryotic retroelements and unveil these motifs as a significant fraction of the encoded information in eukaryotic genomes.