tbuckley/cabot-search huggingface dataset:
Changes in symptoms, peak expiratory flow, and sputum flora during treatment with antibiotics of exacerbations in patients with chronic obstructive pulmonary disease in general practice.
Authors: A P Sachs, G H Koeter, K H Groenier, D van der Waaij, J Schiphuis, B Meyboom-de Jong
Journal: Thorax (1995)

BACKGROUND--Bacterial infections of the lower airways during an exacerbation in patients with asthma or chronic obstructive pulmonary disease (COPD) may be the cause of an exacerbation or the consequence of a viral infection or an increase in airways limitation. To determine whether bacterial infection is an important component in the pathogenesis of an exacerbation, the effects of antimicrobial treatment must be studied. METHODS--Patients with asthma or COPD seen in general practice were studied in a double blind randomised manner to investigate whether the antimicrobial drugs amoxicillin (500 mg three times daily), cotrimoxazole (960 mg twice daily), or a placebo, each when added to a short course of oral corticosteroids, can accelerate recovery from exacerbations. Patients were instructed to contact their own physician early in the morning when complaints of increased shortness of breath, wheezing, or exacerbations of cough with or without sputum production occurred. Treatment effects were evaluated over the next 14 days by studying symptom scores (wheeze, dyspnoea, cough with and without mucus production, and awakening with dyspnoea), peak expiratory flow values (PEF, expressed as % predicted), and sublingual temperature. Bacteriological study of the sputum was made at the onset of an exacerbation and 7, 21 and 35 days afterwards. RESULTS--Of 195 patients enrolled 71 (36%) contacted their physician for symptoms of an exacerbation. Symptoms improved in all three groups, improvements ranging from 0.54 to 0.75 points per day on a four point scale. PEF% predicted showed improvements in the three groups after the exacerbation, ranging from 0.34% to 0.78% predicted per day, finally returning to baseline values. Sublingual temperature did not change. Six of 71 patients consulted their physician because of a relapse between four and 24 days after the start of treatment. In only two of the 50 sputum samples, collected during an exacerbation, and which contained &gt; or = 10(5) bacteria in culture sensitive to the chosen antibiotic given, did any benefit from antimicrobial treatment occur. During the recovery period sputum purulence improved irrespective of antibiotic treatment. CONCLUSIONS--Antibiotics given with a short course of oral prednisolone during an exacerbation do not accelerate recovery as measured by changes in peak flow and symptom scores in ambulatory patients with mild to moderate asthma or COPD when treated by their general practitioners. Moreover, antibiotics do not reduce the number of relapses after treating an exacerbation.
Validation of a non-radiographic ankle arthrometer
Authors: Tanja Nauck, Heinz Lohrer
Journal: British Journal of Sports Medicine (2011)

Introduction Commonly used stress tests require radiography. The respective reliability and sensitivity is still under debate. We developed a non-radiographic ankle arthrometer to objectively assess mechanical ankle stability. The aim of the present study was to validate the ankle arthrometer in a cadaver and in vivo set up. Methods Cadaver study Nine cadaver specimens were tested under different anterior drawer load and ankle angle positions against standardised radiography. Lateral ankle ligaments were sequentially cut during testing procedure. Stiffness was calculated and the diagnostic validity of the ankle arthrometer was analysed. In vivo study 23 subjects participated in the study. An orthopaedic surgeon first performed a manual anterior talar drawer test to classify the subjects’ ankles as stable or unstable. Subjects then underwent ankle arthrometer testing up to 200 N anterior drawer load twice and the stiffness were calculated. Results Cadaver study Stable and unstable ankles were significantly differentiated by stiffness analyses (p=0.01) with the ankle arthrometer adjusted to 0 degrees of plantarflexion and 50 N anterior drawer load application. Results from the ankle arthrometer radiographs and the standardised stress testing device correlated significantly (r=0.73–0.94; p=0.00–0.03). Stiffness analyses discriminate stable and unstable ankles with a sensitivity of 91.7% and specificity of 62.5%. In vivo study Using the manual anterior drawer test, 16 ankles were classified as stable and 7 as unstable. Stiffness group analysis differentiated stable from unstable ankles significantly (p=0.00 and p=0.01). Test-retest demonstrated an accurate reliability (intraclass correlation coefficient=0.80). Conclusions Validation and reliability of the non-radiographic ankle arthrometer was demonstrated in a cadaver and in vivo set up. The ankle arthrometer stiffness analyses may be relevant to screen athletes at risk for lateral ankle instability, for follow-up studies, and to implement preventive strategies.
Short term effects of aerobic training in the clinical management of moderate to severe asthma in children
Authors: J A. Neder, L. E Nery, A. C Silva, A. L B Cabral, A. L G Fernandes
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Aerobic training has a number of well known beneficial effects in both normal and asthmatic children. However, the impact of training on the clinical management of the underlying bronchial asthma remains controversial, particularly in the most severe patients. <h3>METHODS</h3> Clinical evaluation, spirometric tests, symptom limited maximum exercise testing, and exercise challenge tests were performed in a group of children with stable moderate to severe asthma. Forty two patients (24 boys) aged 8–16 were evaluated twice: before and after supervised aerobic training (group 1, n = 26) and two months apart (untrained group 2, n = 16). <h3>RESULTS</h3> Spirometric and maximal exercise variables in the initial evaluation were significantly reduced in group 1 (p&lt;0.05) but medication and clinical scores and the occurrence of exercise induced bronchospasm (EIB) did not differ between the two groups. Aerobic improvement with training (maximal oxygen uptake and/or anaerobic threshold increment &gt;10% and 100 ml) was inversely related to the baseline level of fitness and was independent of disease severity. Although the clinical score and the occurrence of EIB did not change after training, aerobic improvement was associated with a significant reduction in the medication score and the daily use of both inhaled and oral steroids (p&lt;0.05). <h3>CONCLUSIONS</h3> Aerobic improvement with training in less fit asthmatic children is related to a short term decrease in the daily use of inhaled and oral steroids, independent of the severity of the disease.
Marrow Stem Cells Shift Gene Expression and Engraftment Phenotype with Cell Cycle Transit
Authors: Jean-François Lambert, Meng Liu, Gerald A. Colvin, Mark Dooner, Christina I. McAuliffe, Pamela S. Becker, Bernard G. Forget, Sherman M. Weissman, Peter J. Quesenberry
Journal: The Journal of Experimental Medicine (2003)

We studied the genetic and engraftment phenotype of highly purified murine hematopoietic stem cells (lineage negative, rhodamine-low, Hoechst-low) through cytokine-stimulated cell cycle. Cells were cultured in interleukin (IL)-3, IL-6, IL-11, and steel factor for 0 to 48 h and tested for engraftment capacity in a lethally irradiated murine competitive transplant model. Engraftment showed major fluctuations with nadirs at 36 and 48 h of culture and recovery during the next G1. Gene expression of quiescent (0 h) or cycling (48 h) stem cells was compared with lineage positive cells by 3′ end PCR differential display analysis. Individual PCR bands were quantified using a 0 to 9 scale and results were visually compared using color-coded matrices. We defined a set of 637 transcripts expressed in stem cells and not expressed in lineage positive cells. Gene expression analyzed at 0 and 48 h showed a major shift from “stem cell genes” being highly expressed at 0 h and turned off at 48 h, while “cell division” genes were turned on at 48 h. These observations suggest stem cell gene expression shifts through cell cycle in relation to cell cycle related alterations of stem cell phenotype. The engraftment defect is related to a major phenotypic change of the stem cell.
Endothelial progenitors in pulmonary hypertension: new pathophysiology and therapeutic implications
Authors: G. P. Fadini, A. Avogaro, G. Ferraccioli, C. Agostini
Journal: European Respiratory Journal (2010)

Pulmonary hypertension is a progressive and disabling disease with as yet unclear pathogenesis, limited treatment options and poor prognosis. This is why the discovery of new pathogenic mechanisms and therapeutic strategies are needed. Endothelial progenitor cells (EPCs) are bone marrow-derived cells involved in endothelial homeostasis, as well as physiological and pathological angiogenesis. Experimental and clinical studies have been conducted to understand the possible contribution of EPCs to the pathogenesis of pulmonary hypertension. Conflicting results have been obtained regarding the protective versus harmful effects of EPCs on the pulmonary vasculature. However, preliminary clinical trials using EPC-based therapies in patients with pulmonary hypertension show benefit of this approach, thus revealing EPCs as potential therapeutic targets. This review critically summarises the complex and conflicting data on EPCs and pulmonary hypertension, in both humans and animals, putting them into the context of lung (patho)physiology. The resulting scenario identifies EPCs as a novel and fascinating tool to study pathophysiology and therapy in the setting of pulmonary hypertension.
Epidemiology of primary brain tumors: Current concepts and review of the literature
Authors: Margaret Wrensch, Yuriko Minn, Terri Chew, Melissa Bondy, Mitchel S. Berger
Journal: Neuro-Oncology (2002)

The purpose of this review is to provide a sufficiently detailed perspective on epidemiologic studies of primary brain tumors to encourage multidisciplinary etiologic and prognostic studies among surgeons, neuro-oncologists, epidemiologists, and molecular scientists. Molecular tumor markers that predict survival and treatment response are being identified with hope of even greater gains in this area from emerging array technologies. Regarding risk factors, studies of inherited susceptibility and constitutive polymorphisms in genes pertinent to carcinogenesis (for example, DNA repair and detoxification genes and mutagen sensitivity) have revealed provocative findings. Inverse associations of the history of allergies with glioma risk observed in 3 large studies and reports of inverse associations of glioma with common infections suggest a possible role of immune factors in glioma genesis or progression. Studies continue to suggest that brain tumors might result from workplace, dietary, and other personal and residential exposures, but studies of cell phone use and power frequency electromagnetic fields have found little to support a causal connection with brain tumors; caveats remain. The only proven causes of brain tumors (that is, rare hereditary syndromes, therapeutic radiation, and immune suppression giving rise to brain lymphomas) account for a small proportion of cases. Progress in understanding primary brain tumors might result from studies of well-defined histologic and molecular tumor types incorporating assessment of potentially relevant information on subject susceptibility and environmental and noninherited endogenous factors (viruses, radiation, and carcinogenic or protective chemical exposures through diet, workplace, oxidative metabolism, or other sources). Such studies will require the cooperation of researchers from many disciplines.
Synopsis of Neurology
Authors: J. W. A. Turner
Journal: BMJ (1952)

<h3>Abstract</h3> Inadequate management of household and industrial wastes pose major challenges to human and environmental health. Advances in synthetic biology may help address these challenges by engineering biological systems to perform new functions such as biomanufacturing of high-value compounds from low-value waste streams and bioremediation of industrial pollutants. The current emphasis on microbial systems for biomanufacturing, which often require highly pre-processed inputs and sophisticated infrastructure, is not feasible for many waste streams. Concerns about transgene biocontainment have limited the release of engineered microbes or plants for bioremediation. Engineering animals may provide opportunities for utilizing various waste streams that are not suitable for microbial biomanufacturing while effective transgene biocontainment options should enable <i>in situ</i> bioremediation. Here, we engineer the model insect <i>Drosophila melanogaster</i> to express a functional laccase from the fungus <i>Trametes trogii</i>. Laccase expressing flies reduced concentrations of the endocrine disruptor bisphenol A by more than 50% when present in their growth media. A lyophilized powder made from engineered adult flies retained substantial enzymatic activity, degrading more than 90% of bisphenol A and the textile dye indigo carmine in aqueous solutions. Our results demonstrate that transgenic animals may be used to bioremediate environmental contaminants <i>in vivo</i> and serve as novel production platforms for industrial enzymes. These results support further development of insects, and possibly other animals, as bioproduction platforms and their potential use in bioremediation.
"Orphan" Retrogenes in the Human Genome
Authors: J. Ciomborowska, W. Rosikiewicz, D. Szklarczyk, W. Makalowski, I. Makalowska
Journal: Molecular Biology and Evolution (2012)

Gene duplicates generated via retroposition were long thought to be pseudogenized and consequently decayed. However, a significant number of these genes escaped their evolutionary destiny and evolved into functional genes. Despite multiple studies, the number of functional retrogenes in human and other genomes remains unclear. We performed a comparative analysis of human, chicken, and worm genomes to identify "orphan" retrogenes, that is, retrogenes that have replaced their progenitors. We located 25 such candidates in the human genome. All of these genes were previously known, and the majority has been intensively studied. Despite this, they have never been recognized as retrogenes. Analysis revealed that the phenomenon of replacing parental genes with their retrocopies has been taking place over the entire span of animal evolution. This process was often species specific and contributed to interspecies differences. Surprisingly, these retrogenes, which should evolve in a more relaxed mode, are subject to a very strong purifying selection, which is, on average, two and a half times stronger than other human genes. Also, for retrogenes, they do not show a typical overall tendency for a testis-specific expression. Notably, seven of them are associated with human diseases. Recognizing them as "orphan" retrocopies, which have different regulatory machinery than their parents, is important for any disease studies in model organisms, especially when discoveries made in one species are transferred to humans.
The <i>in vivo</i> effect of triethylphosphine gold (auranofin), sodium aurothiomalate and azathioprine on lymphocyte subsets of patients with rheumatoid arthritis
Authors: B. K. Pedersen, B. ÅBom
Journal: Allergy (1988)

The percentages of CD5+ (pan T), CD8+ (mainly T suppressor) and CD4+ (mainly T helper) cells were studied in 80 patients with rheumatoid arthritis (RA), grouped according to medication into four groups: 1) controls, not receiving remission-inducing therapy, 2) patients on oral gold (triethylphosphine gold, auranofin), 3) patients on parenteral gold (sodium aurothiomalate) and 4) patients on azathioprine. The total number of lymphocytes was not influenced by treatment with auranofin or sodium aurothiomalate, while the number of lymphocytes was depressed in the azathioprine-treated group (P less than 0.01). Neither treatment with azathioprine or parenteral gold, nor treatment with azathioprine influenced the CD4+/CD8+ ratio.
c-Jun Protects Hypoxia-Inducible Factor-1α from Degradation via Its Oxygen-Dependent Degradation Domain in a Nontranscriptional Manner
Authors: Bing Yu, Ze-Hong Miao, Yi Jiang, Mei-Hong Li, Na Yang, Ting Li, Jian Ding
Journal: Cancer Research (2009)

Abstract Although hypoxia-inducible factor-1α (HIF-1α) has long been intensively investigated as a drug target by interfering with its expression or transcriptional function, the regulatory mechanisms of HIF-1α remain to be further clarified. We report here that c-Jun associates with HIF-1α via its oxygen-dependent degradation domain, masks the sites for ubiquitination, and thus protects HIF-1α from proteasome-executing degradation. All of these together resulted in the stabilization and accumulation of HIF-1α, consequently promoting the transcription of its target gene and driving angiogenesis-related events. The stabilization of HIF-1α was dependent on the domains of c-Jun for DNA binding and heterodimerization but independent of the Ser63/73 phosphorylation that is critical for transcriptional function. These findings highlight a previously unrecognized nontranscriptional function of c-Jun on the one hand and a distinct regulatory mechanism of HIF-1α activity on the other, consequently offering profound mechanistic insights into multiple events simultaneously involving both c-Jun and HIF-1α in tumor progression. [Cancer Res 2009;69(19):7704–12]
Impact of Diabetes on Long-Term Survival After Acute Myocardial Infarction
Authors: Kenneth J. Mukamal, Richard W. Nesto, Mylan C. Cohen, James E. Muller, Malcolm Maclure, Jane B. Sherwood, Murray A. Mittleman
Journal: Diabetes Care (2001)

OBJECTIVE—To determine the effect of diabetes on long-term survival after acute myocardial infarction and to compare its effect with that of a previous myocardial infarction. RESEARCH DESIGN AND METHODS—In a prospective cohort study, we followed 1,935 patients hospitalized with a confirmed acute myocardial infarction at 45 U.S. medical centers between 1989 and 1993, as part of the Determinants of Myocardial Infarction Onset Study. Trained interviewers performed chart reviews and face-to-face interviews with all patients. We analyzed survival using Cox proportional hazards regression to control for potentially confounding factors. RESULTS—Of the 1,935 patients, 320 (17%) died during a mean follow-up of 3.7 years. A total of 399 patients (21%) had previously diagnosed diabetes. Diabetes was associated with markedly higher total mortality in unadjusted (hazard ratio [HR] 2.4; 95% CI 1.9–3.0) and adjusted (1.7; 1.3–2.1) analyses. The magnitude of the effect of diabetes was identical to that of a previous myocardial infarction. The effect of diabetes was not significantly modified by age, smoking, household income, use of thrombolytic therapy, type of hypoglycemic treatment, or duration of diabetes, but the risk associated with diabetes was higher among women than men (adjusted HRs 2.7 vs. 1.3, P = 0.01). CONCLUSIONS—Diabetes is associated with markedly increased mortality after acute myocardial infarction, particularly in women. The increase in risk is of the same magnitude as a previous myocardial infarction and provides further support for aggressive treatment of coronary risk factors among diabetic patients.
Identification of targets of leptin action in rat hypothalamus.
Authors: M W Schwartz, R J Seeley, L A Campfield, P Burn, D G Baskin
Journal: Journal of Clinical Investigation (1996)

The hypothesis that leptin (OB protein) acts in the hypothalamus to reduce food intake and body weight is based primarily on evidence from leptin-deficient, ob/ob mice. To investigate whether leptin exerts similar effects in normal animals, we administered leptin intracerebroventricularly (icv) to Long-Evans rats. Leptin administration (3.5 microg icv) at the onset of nocturnal feeding reduced food intake by 50% at 1 h and by 42% at 4 h, as compared with vehicle-treated controls (both P < 0.05). To investigate the basis for this effect, we used in situ hybridization (ISH) to determine whether leptin alters expression of hypothalamic neuropeptides involved in energy homeostasis. Two injections of leptin (3.5 microg icv) during a 40 h fast significantly decreased levels of mRNA for neuropeptide Y (NPY, which stimulates food intake) in the arcuate nucleus (-24%) and increased levels of mRNA for corticotrophin releasing hormone (CRH, an inhibitor of food intake) in the paraventricular nucleus (by 38%) (both P < 0.05 vs. vehicle-treated controls). To investigate the anatomic basis for these effects, we measured leptin receptor gene expression in rat brain by ISH using a probe complementary to mRNA for all leptin receptor splice variants. Leptin receptor mRNA was densely concentrated in the arcuate nucleus, with lower levels present in the ventromedial and dorsomedial hypothalamic nuclei and other brain areas involved in energy balance. These findings suggest that leptin action in rat hypothalamus involves altered expression of key neuropeptide genes, and implicate leptin in the hypothalamic response to fasting.
ON CANCER OF THE DUODENUM AND SMALL INTESTINE: Being the Presidential Address delivered to the Medical Society of London, October 12th, 1914
Authors: J. Bland-Sutton
Journal: BMJ (1914)

THE distribution of cancer in the section of the alimentary canal known as the gastro-intestinal tract is remarkable.Cancer is very comimon in the stomaelc, but in the intes- tine be'tween the pylorus and the ileo-caecal valve it is unconiit'on.Primary cancer is rare in any part of tlle small intestine, but it occurs more frequently in tle duodenum, short as it is, tllan in the jejunum or the ileunm CANCER OF THE DUODENUM.A study of the effects produced by cancer of the duo- denum lisows tllat the time-lhonoured divisioni of this section of the small intestine into first, second and thlird
Two genetic markers closely linked to adult polycystic kidney disease on chromosome 16.
Authors: S T Reeders, M H Breuning, G Corney, S J Jeremiah, P Meera Khan, K E Davies, D A Hopkinson, P L Pearson, D J Weatherall
Journal: BMJ (1986)

The genetic locus for autosomal dominant adult polycystic kidney disease was recently assigned to chromosome 16 by the finding of genetic linkage to the alpha globin gene cluster. Further study showed that the phosphoglycolate phosphatase locus is also closely linked to both the locus for adult polycystic kidney disease and the alpha globin gene cluster. These findings have important implications for the prenatal and presymptomatic diagnosis of adult polycystic kidney disease and for a better understanding of its pathogenesis.