tbuckley/cabot-search huggingface dataset:
Effects of rhDNase on purulent airway secretions in chronic bronchitis
Authors: E. Puchelle, J-M. Zahm, S. de Bentzmann, C. Grosskopf, S. Shak, D. Mougel, J-M. Polu
Journal: European Respiratory Journal (1996)

Recombinant human deoxyribonuclease (rhDNase) has been demonstrated to reduce in vitro the viscosity and to improve the transport capacity of purulent respiratory mucus in cystic fibrosis. During episodes of exacerbation of chronic bronchitis, the patients generally expectorate purulent mucus. Purulence of mucus is associated with an increased deoxyriboneucleic acid (DNA) concentration. We analyzed in vitro the potential effect of rhDNase on chronic bronchitis mucus transport by the ciliary activity (frog palate model) and by simulated cough (cough machine model), as well as the effect on mucus viscosity (controlled stress rheometer) and surface properties (contact angle). Purulent sputa collected from patients with chronic bronchitis (n = 15) during an episode of exacerbation were incubated for 30 min at 37 degrees C with either rhDNase at two different concentrations (final concentration 2 or 4 micrograms.mL-1) or placebo. The median mucociliary transport rate was significantly improved by rhDNase from 0.68 with placebo to 0.79 and 0.83 with 2 and 4 micrograms.mL-1 of rhDNase, respectively. A significant improvement in mucus cough transport was also induced by rhDNase from 25.5 mm with placebo to 27.0 mm with either 2 or 4 micrograms.mL-1 rhDNase. These improvements in mucus transport capacity were associated with alterations in the physical properties of the mucus. The mucus median control viscosity (511.4 Pa.s) and median contact angle (0.85 rd) significantly decreased to 112.5 Pa.s and 0.74 rd, respectively, in the presence of 4 micrograms.mL-1 of rhDNase. These findings demonstrate that recombinant deoxyribonuclease may exert a beneficial effect on mucus clearance in vitro by altering the viscosity and surface properties of the purulent chronic bronchitic sputum samples.
Early warning skin signs in AIDS and persistent generalized lymphadenopathy
Authors: M.F. MUHLEMANN, M.G. ANDERSON, F.J. PARADINAS, P.R. KEY, S.G. DAWSON, B.A. EVANS, I.M. MURRAY-LYON, J.J. CREAM
Journal: British Journal of Dermatology (1986)

Distinctive patterns of skin disease other than Kaposi's sarcoma have been seen in patients with AIDS, in others with persistent generalized lymphadenopathy (PGL) and in a group at high risk of developing AIDS. We found a chronic acneiform folliculitis on the face, back, chest and buttocks, extensive cutaneous fungal infections and a striking neck and beard impetigo. These skin diseases were not present in asymptomatic male homosexual control subjects, 32% of whom were found to have antibodies to human T cell lymphotropic virus type III (HTLV‐III). We regard these dermatoses as early warning signs of AIDS.
The end of overeating
Authors: Rexford S. Ahima
Journal: Journal of Clinical Investigation (2009)

In The end of overeating: taking control of the insatiable American appetite, David A. Kessler presents an engaging perspective of the obesity epidemic. About two-thirds of adults in the United States are overweight. The number of overweight and obese children is also growing at an alarming rate. These trends have adverse consequences on health because obesity increases the risk of chronic diseases, notably diabetes, cardiovascular diseases, obstructive sleep apnea, and cancer. Obesity is also a major cause of disability and may shorten lifespan. As commissioner of the Food and Drug Administration under Presidents George H.W. Bush and Bill Clinton, Kessler led the fight against tobacco companies to place their products under federal regulation. He also pushed through legislation for nutritional labeling of food. The idea for his book came to Kessler while watching a patient on The Oprah Winfrey Show describe how her struggles with food and weight affected her life. During his tenure as dean of the Yale School of Medicine, and later the University of California at San Francisco School of Medicine, Kessler embarked on a mission to unravel the factors underlying the rising incidence of obesity. He analyzed his own eating habits, watched others eating at restaurants and other locations, reviewed publications, and interviewed basic scientists and clinicians as well as food industry executives and workers. Kessler’s theory can be summed up as follows: Modern foods, particularly American foods, are designed not to satisfy, but rather to stimulate the reward pathways in the brain, conditioning us to crave more food.
The Phosphorus Pills of the British Pharmacop ia
Authors: J. A. Thompson
Journal: BMJ (1876)

AN extended experience in the use of hammocks for invalid transit has confirmed their utility, and it is now my desire to place some additional facts on record with reference to a new stretcher .andhammock-van.Strtchers.--Thediagram shows the form of stretcher in use at the Westminster Hospital for carrying patients from the wards to the open air.(Fig. I.) The poles are placed on the shoulders, or borne at
Predicting persistent disease among children who wheeze during early life
Authors: R.J. Kurukulaaratchy, S. Matthews, S.T. Holgate, S.H. Arshad
Journal: European Respiratory Journal (2003)

This study sought to determine factors influencing the persistence of early life wheezing up to the age of 10 yrs and to create a score identifying those with the highest risk of persistent disease. Children were seen at birth, 1, 2, 4 and 10 yrs in a whole population birth cohort study (n=1,456). Information was collected prospectively on wheeze prevalence and subjects were classified into wheezing phenotypes. Early life genetic and environmental risk factors were recorded and skin-prick testing (SPT) was performed at 4 yrs. Independently significant factors for persisting wheeze were identified at logistic regression and used to create a score for persistence. Wheezing persistence from the first 4 yrs to the age of 10 yrs occurred in 37% of early life wheezers. Independent significance for persistence was associated with asthmatic family history, atopic SPT at 4 yrs and recurrent chest infections at 2 yrs, whilst recurrent nasal symptoms at 1 yr conferred reduced risk. A cumulative risk score using these factors identified wheezing persistence in 83% scoring 4 and transience in 80% scoring 0. Thus, a combination of genetic predisposition, early life atopy and recurrent chest infections favours the persistence of early life wheezing. Risk scores using such knowledge could provide prognostic guidance on the outcome of early wheeze.
Mechanisms of Sunitinib Resistance in Gastrointestinal Stromal Tumors Harboring <i>KIT</i>AY502-3ins Mutation: An <i>In vitro</i> Mutagenesis Screen for Drug Resistance
Authors: Tianhua Guo, Mihai Hajdu, Narasimhan P. Agaram, Hiroko Shinoda, Darren Veach, Bayard D. Clarkson, Robert G. Maki, Samuel Singer, Ronald P. DeMatteo, Peter Besmer, Cristina R. Antonescu
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Although tyrosine kinase inhibitors have improved survival in advanced gastrointestinal stromal tumor (GIST), complete response is rare and most patients eventually fail the first-line treatment with imatinib. Sunitinib malate is the only approved second-line therapy for patients with imatinib-resistant or imatinib-intolerant GIST. The clinical benefit of sunitinib is genotype-dependent in regards to both primary and secondary mutations, with GIST patients harboring the KITAY502-3ins exon 9 mutation being the most sensitive. Experimental Design: As sunitinib resistance is now emerging, our goal was to investigate mechanisms of progression and to test the efficacy of novel tyrosine kinase inhibitor on these resistant mutants in vitro. N-ethyl-N-nitrosourea mutagenesis of Ba/F3 cells expressing the KITAY502-3ins mutant was used to investigate novel patterns of resistant mutations evolving in the presence of sunitinib. Results: Tumors from patients who developed sunitinib resistance after at least 1 year of radiographic response were analyzed, showing similar findings of a primary KITAY502-3ins mutation and a secondary mutation in the KIT activation loop. Ba/F3 cells expressing these sunitinib-resistant double mutants showed sensitivity to both dasatinib and nilotinib. Conclusions: Sunitinib resistance in GIST shares similar pathogenetic mechanisms identified in imatinib failure, with acquisition of secondary mutations in the activation domain after an extended initial response to the drug. Moreover, in vitro mutagenesis with or without N-ethyl-N-nitrosourea of Ba/F3 cells expressing KITAY502-3ins showed acquisition of secondary mutations restricted to the second kinase domain of KIT. In contrast, in vitro resistance to imatinib produces a broader spectrum of secondary mutations including mutations in both KIT kinase domains. (Clin Cancer Res 2009;15(22):686270)
* Virulence factors, antimicrobial resistance genes and protein structure of crohn's disease-derived
Authors: T. Elliott, B. Hudspith, N. Rayment, L. Randall, G. Wu, A. Boussioutas, J. Hermon-Taylor, J. Brostoff, L. Petrovska, J. D. Sanderson
Journal: Gut (2011)

<h3>Introduction</h3> Intracellular <i>Escherichia coli</i> isolates are found in up to 60% of gut biopsies from patients with Crohn9s disease (CD). Although adherent invasive <i>E coli</i> (AIEC) are described, other intracellular <i>E coli</i> are frequently isolated but specific pathogenic determinants for these have not been identified by conventional techniques. DNA microarray and Matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) mass spectrometry enable rapid and accurate DNA and proteomic analysis of bacteria. <h3>Aims</h3> To investigate for virulence and antimicrobial resistance (AMR) genes in, and analyse the structure of CD-related intracellular <i>E coli</i> isolates. <h3>Methods</h3> 17 <i>E coli</i> strains were isolated using gentamicin protection assay from gut biopsies of 17 CD patients (ileal n=7, colonic n=10). DNA was extracted for analysis by DNA microarray (Prodigy) of 392 virulence and AMR genes. DNA PCR was performed for an additional 18 virulence genes. For Bruker Biotyper MALDI-TOF sample preparation, several colonies of each bacterial strain were spotted onto target plate and prepared as described previously. 10 replicates of the mass/charge spectra for each strain were compared to spectra from a bacterial database. <h3>Results</h3> Virulence factors were identified by DNA microarray in a number of <i>E coli</i> strains including senB (encodes enterotoxin), Iha (encodes an adhesin) Sat (toxin of uropathogenic <i>E coli</i>), iron regulation genes and microcin synthesis genes. DNA PCR revealed additional virulence factors including ibeA (associated with <i>E coli</i> invasion in neonatal meningitis) in 2 strains. A minority of strains were positive for AMR genes relating to β-lactams, sulphonamides, tetracycline and streptomycin. MALDI-TOF analysis confirmed the bacteria as <i>E coli</i> and clustered the Crohn9s disease <i>E coli</i> strains together and separate from other <i>E coli</i> strains on the Bruker database. There was no clustering within CD strains in relation to disease or biopsy site or immunomodulation. <h3>Conclusion</h3> Although CD appears to be at least in part a host immune disorder, pathogenic factors of various organisms may still play a role in pathogenesis. A number of genes encoding for virulence factors have been identified in a proportion of CD-related <i>E coli</i> strains which warrant further investigation (eg, whole gene sequencing and functional assays). Most strains had no antimicrobial resistance genes. Further MALDI-TOF comparison of CD-related bacterial structure with commensal and IBD-related bacteria may be revealing.
Better Preservation of Peritoneal Morphologic Features and Defense in Rats after Long-Term Exposure to a Bicarbonate/Lactate-Buffered Solution
Authors: Liesbeth H. P. Hekking, Mohammad Zareie, Bas A. J. Driesprong, Dirk Faict, Angelique G. A. Welten, Inge de Greeuw, Inge L. Schadee-Eestermans, Carin E. G. Havenith, Jacob van den Born, Piet M. Ter Wee, Robert H. J. Beelen
Journal: Journal of the American Society of Nephrology (2001)

ABSTRACT. The long-term effects of a standard lactate-buffered dialysis fluid and a new, two-chamber, bicarbonate/lactate-buffered dialysis fluid (with fewer glucose degradation products and a neutral pH) were compared in an in vivo peritoneal exposure model. Rats were given daily injections, via an access port, of 10 ml of standard solution or bicarbonate/lactate-buffered solution for 9 to 10 wk. The omentum, peritoneum, and mesothelial cell layer were screened for morphologic changes. In addition, the bacterial clearing capacity of the peritoneal cells was studied. Significantly more milky spots and blood vessels were observed in the omenta of animals treated with standard solution (P < 0.03 for both parameters). Electron-microscopic analysis demonstrated dramatic changes in the appearance of the vascular endothelial cells of the milky spots and a severely damaged or even absent mesothelium on the peritoneal membrane of the standard solution-treated animals. In contrast, the mesothelium was still present in the bicarbonate/lactate-buffered solution group, although the cells lost microvilli. Both peritoneal dialysis fluids significantly increased the density of mesothelial cells (per square millimeter) on the surface of the liver and the thickness of the submesothelial extracellular matrix of the peritoneum (both P < 0.04 for both fluids versus control). A significantly better ex vivo bacterial clearing capacity was observed with peritoneal cells from the bicarbonate/lactate-buffered solution group, compared with the standard solution group (P < 0.05 in both experiments). These results demonstrate that instillation of bicarbonate/lactate-buffered solution into rats for 9 to 10 wk preserves both morphologic and immune parameters much more effectively, compared with standard solution. These findings may be of considerable clinical importance.
Comparison of health-related quality of life in rheumatoid arthritis, psoriatic arthritis and psoriasis and effects of etanercept treatment
Authors: Vibeke Strand, Veronika Sharp, Andrew S Koenig, Grace Park, Yifei Shi, Brian Wang, Debra J Zack, David Fiorentino
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> To compare health-related quality of life (HRQoL) before and after treatment with etanercept in patients with moderate to severe rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis using spydergram representations. <h3>Methods</h3> Data from randomised, controlled trials of etanercept in patients with RA, PsA and psoriasis were analysed. HRQoL was assessed by the medical outcomes survey short form 36 (SF-36) physical (PCS) and mental (MCS) component summary and domain scores. Baseline comparisons with age and gender-matched norms and treatment-associated changes in domain scores were quantified using spydergrams and the health utility SF-6D measure. <h3>Results</h3> Mean baseline PCS scores were lower than age and gender-matched norms in patients with RA and PsA, but near normative values in patients with psoriasis; MCS scores at baseline were near normal in PsA and psoriasis but low in RA. Treatment with etanercept resulted in improvements in PCS and MCS scores as well as individual SF-36 domains across all indications. Mean baseline SF-6D scores were higher in psoriasis than in RA or PsA; clinically meaningful improvements in SF-6D were observed in all three patient populations following treatment with etanercept. <h3>Conclusions</h3> Patients with RA, PsA and psoriasis demonstrated unique HRQoL profiles at baseline. Treatment with etanercept was associated with improvements in PCS and MCS scores as well as individual domain scores in patients with RA, PsA and psoriasis.
Colorectal Cancer Subtyping Consortium (CRCSC) Identifies Consensus of Molecular Subtypes
Authors: R. Dienstmann, J. Guinney, M. Delorenzi, A. De Reynies, P. Roepman, A. Sadanandam, L. Vermeulen, A. Schlicker, E. Missiaglia, C. Soneson, L. Marisa, K. Homicsko, X. Wang, I. Simon, P. Laurent-Puig, L. Wessels, J.P. Medema, S. Kopetz, S. Friend, S. Tejpar
Journal: Annals of Oncology (2014)
WIDE AWAKE Mediates the Circadian Timing of Sleep Onset
Authors: Sha Liu, Angelique Lamaze, Qili Liu, Masashi Tabuchi, Yong Yang, Melissa Fowler, Rajnish Bharadwaj, Julia Zhang, Joseph Bedont, Seth Blackshaw, Thomas E. Lloyd, Craig Montell, Amita Sehgal, Kyunghee Koh, Mark N. Wu
Journal: Neuron (2014)
Diagnosis of pneumococcal pneumonia by polymerase chain reaction (PCR) in whole blood: a prospective clinical study
Authors: M L L Lorente
Journal: Thorax (2000)

<h3>BACKGROUND</h3> <i>Streptococcus pneumoniae</i> is the leading cause of community acquired pneumonia; however, only a small proportion of cases can be detected by conventional methods. The ability of the polymerase chain reaction (PCR) test performed on whole blood samples to identify patients with pneumococcal pneumonia was investigated. <h3>METHODS</h3> One hundred and fourteen consecutive adult patients with community acquired pneumonia were evaluated by a wide battery of diagnostic tests in order to determine the aetiology. Blood samples from these patients and 50 controls were also tested by the nested PCR test to detect selected pneumolysin gene fragments of <i>S pneumoniae</i>. <h3>RESULTS</h3> The patients were divided into four groups: (1) 40 patients with pneumococcal pneumonia in 22 of whom (55%) the PCR was positive (eight of 11 with bacteraemia and 14 of 29 without); (2) 30 with pneumonia due to other pathogens in all of whom the PCR was negative; (3) 44 with pneumonia of unknown aetiology in 14 of whom (32%) PCR was positive, and (4) 50 controls in whom the PCR test was positive in two (4%). Thus, the sensitivity of the test was 55% and the specificity 100% (81% if positive PCR tests among undiagnosed patients are considered as false positive results). <h3>CONCLUSION</h3> PCR applied to whole blood samples appears to be a sensitive and very specific diagnostic test for identifying patients with pneumococcal pneumonia with a potential application in clinical practice.
Targeted cancer therapy with a novel low-dose rate α-emitting radioimmunoconjugate
Authors: Jostein Dahle, Jørgen Borrebæk, Thora J. Jonasdottir, Anne Kristine Hjelmerud, Katrine B. Melhus, Øyvind S. Bruland, Oliver W. Press, Roy H. Larsen
Journal: Blood (2007)
-Radiation Sensitivity and Risk of Glioma
Authors: M. L. Bondy, L.-E. Wang, R. El-Zein, M. de Andrade, M. S. Selvan, J. M. Bruner, V. A. Levin, W. K. Alfred Yung, P. Adatto, Q. Wei
Journal: JNCI Journal of the National Cancer Institute (2001)

About 9% of human cancers are brain tumors, of which 90% are gliomas. gamma-Radiation has been identified as a risk factor for brain tumors. In a previous pilot study, we found that lymphocytes from patients with glioma were more sensitive to gamma-radiation than were lymphocytes from matched control subjects. In this larger case-control study, we compared the gamma-radiation sensitivity of lymphocytes from glioma patients with those from control subjects and investigated the association between mutagen sensitivity and the risk for developing glioma.We used a mutagen sensitivity assay (an indirect measure of DNA repair activity) to assess chromosomal damage. We gamma-irradiated (1.5 Gy) short-term lymphocyte cultures from 219 case patients with glioma and from 238 healthy control subjects frequency matched by age and sex. After irradiation, cells were cultured for 4 hours, and then Colcemid was added for 1 hour to arrest cells in mitosis. Fifty metaphases were randomly selected for each sample and scored for chromatid breaks. All statistical tests were two-sided.We observed a statistically significantly higher frequency of chromatid breaks per cell from case patients with glioma (mean = 0.55; 95% confidence interval [CI] = 0.50 to 0.59) than from control subjects (mean = 0.44; 95% CI = 0.41 to 0.48) (P<.001). Using 0.40 (the median number of chromatid breaks per cell in control subjects) as the cut point for defining mutagen sensitivity and adjusting for age, sex, and smoking status, we found that mutagen sensitivity was statistically significantly associated with an increased risk for glioma (odds ratio = 2.09; 95% CI = 1.43 to 3.06). When the data were divided into tertiles, the relative risk for glioma increased from the lowest tertile to the highest tertile (trend test, P<.001).gamma-Radiation-induced mutagen sensitivity of lymphocytes may be associated with an increased risk for glioma, a result that supports our earlier preliminary findings.
Vitamin B12 excretion by the rat small intestine
Authors: C. A. Loehry, B. Creamer
Journal: Gut (1969)

Two phases of intestinal excretion are demonstrated after a parenteral dose of <sup>58</sup>Co vitamin B<sub>12</sub>. The first phase was maximal immediately after injection, and was related to plasma radioactivity. The second phase was delayed 36 to 48 hours and was related to labelled cells reaching the tips of the villi. The loss of vitamin B<sub>12</sub> through increased exudation and rapid cell exfoliation together with failure of reabsorption may play a part in the deficiency state seen in the coeliac syndrome.
INTERGROUP PHAGE REACTIONS AND TRANSDUCTION BETWEEN GROUP C AND GROUP A STREPTOCOCCI
Authors: Lewis W. Wannamaker, Susan Almquist, Stephen Skjold
Journal: The Journal of Experimental Medicine (1973)

In a study of intergroup reactions, four virulent Group A streptococcal phages were found to form plaques in high titer on lawns prepared from a number of Group C streptococcal strains. Whether the phages were propagated on the homologous (Group A) strain or a heterologous (Group C) strain did not appear to influence consistently the plaque-forming efficiency on lawns prepared from a homologous (Group A) or a heterologous (Group C) strain or to alter significantly the percent of Group C strains which showed plaque formation. Considerable variability was found in the ability of temperate phages to lyse strains of a heterologous group. A single Group C indicator strain was lysed by a high percentage of freshly induced temperate Group A phages. A single temperate Group C phage lysed a significant proportion of Group A strains when freshly induced or when propagated on a Group A strain. Intragroup transduction of streptomycin resistance was demonstrated between Group C strains. Intergroup transduction of streptomycin resistance and also bacitracin resistance was achieved between Group C and Group A streptococci. These observations provide evidence that Group A streptococci can serve as recipients in intergroup transmission of genetic information. Ultraviolet irradiation of the transducing lysate and lowering the propagation temperature of the transducing lysate increased the frequency of transduction in both the intragroup and intergroup transduction systems.