tbuckley/cabot-search huggingface dataset:
Intravenous antibiotics reduce the presence of<i>Aspergillus</i>in adult cystic fibrosis sputum
Authors: Caroline G Baxter, Riina Rautemaa, Andrew M Jones, A Kevin Webb, Matthew Bull, Eshwar Mahenthiralingam, David W Denning
Journal: Thorax (2013)

<h3>Background</h3> <i>Pseudomonas aeruginosa</i> and <i>Aspergillus fumigatus</i> frequently co-colonise the airways of patients with cystic fibrosis (CF). This study aimed to assess the impact of short-term administration of intravenous antipseudomonal antibiotics during CF exacerbations on the presence of <i>Aspergillus</i>. <h3>Methods</h3> Pre- and post-antibiotic sputum samples from 26 adult patients with CF and chronic <i>Pseudomonas</i> colonisation were analysed for the presence of <i>Aspergillus</i> by fungal culture, real-time PCR and galactomannan antigen (GM). Lung function (forced expiratory volume in 1 s and forced vital capacity % predicted) and blood levels of total IgE, specific <i>A fumigatus</i> IgE and specific <i>A fumigatus</i> IgG were measured at the start and end of antibiotics. Respiratory viral real-time PCR and bacterial community profiling using ribosomal intergenic spacer analysis (RISA) were performed to estimate concurrent changes in the lung microbiome. <h3>Results</h3> <i>Aspergillus</i> PCR and GM were more sensitive than culture in detecting <i>Aspergillus</i> species (culture 8%, GM 31%, PCR 77%). There was a significant decline in the presence of <i>Aspergillus</i>, measured both by PCR and GM index, following antibacterial therapy (PCR: median increase in crossing threshold 1.7 (IQR 0.5–3.8), p&lt;0.001; GM: median fall in GM index 0.7 (IQR 0.4–1.6), p=0.016). All patients improved clinically with a significant increase in lung function (p&lt;0.0001). RISA community analysis showed large changes in bacterial community similarity in 67% of patients following antibiotics. Viral RT-PCR demonstrated the presence of a concurrent respiratory virus in 27% of patients. <h3>Conclusions</h3> Intravenous antibiotics targeting <i>Pseudomonas</i> during CF pulmonary exacerbations have a negative impact on the presence of <i>Aspergillus</i> in sputum samples.
Whipple's disease
Authors: Xavier Puéchal
Journal: Annals of the Rheumatic Diseases (2013)

Whipple's disease is a chronic, systemic infection caused by Tropheryma whipplei . Gene amplification, isolation and DNA sequencing of T whipplei have extended our knowledge of this pathogen, which is now recognised as a ubiquitous commensal bacterium. The spectrum of signs associated with T whipplei has now been extended beyond the classic form, which affects middle-aged men, and begins with recurrent arthritis followed several years later by digestive problems associated with other diverse clinical signs. Children may present an acute primary infection, but only a small number of people with a genetic predisposition subsequently develop authentic Whipple's disease. This bacterium may also cause localised chronic infections with no intestinal symptoms: endocarditis, central nervous system involvement, arthritis, uveitis and spondylodiscitis. An impaired T H 1 immune response is seen. T whipplei replication in vitro is dependent on interleukin 16 and is accompanied by the apoptosis of host cells, facilitating dissemination of the bacterium. In patients with arthritis, PCR with samples of joint fluid, saliva and stools has become the preferred examination for diagnosis. Immunohistochemical staining is also widely used for diagnosis. Treatment is based on recent microbiological data, but an immune reconstitution syndrome and recurrence remain possible. The future development of serological tests for diagnosis and the generalisation of antigen detection by immunohistochemistry should make it possible to obtain a diagnosis earlier and thus to decrease the morbidity, and perhaps also the mortality, associated with this curable disease which may, nonetheless, be fatal if diagnosed late or in an extensive systemic form.
Increased PD-L1 expression in KRAS mutated premalignant human bronchial epithelial cells is enhanced by LKB1 loss and mediated by ERK activation
Authors: Mi-Heon Lee, Jane Yanagawa, Rui Li, Tonya C Walser, Kostyantyn Krysan, Gerald Wang, Jonathan W Goldman, Edward B Garon Garon, Gang Zeng, Sherven Sharma, John D Minna, David Carbone, Steven M Dubinett, Jay M Lee
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts PD-1/PD-L1 immune checkpoint pathway mediates tumor evasion from the immune system, and may be associated with poor prognosis in lung cancer. Activating KRAS mutations and LKB1 loss are common mutations in non-small cell lung carcinoma (NSCLC). Patients with mutated KRAS
Semen enhances HIV infectivity and impairs the antiviral efficacy of microbicides
Authors: Onofrio Zirafi, Kyeong-Ae Kim, Nadia R. Roan, Silvia F. Kluge, Janis A. Müller, Shibo Jiang, Benjamin Mayer, Warner C. Greene, Frank Kirchhoff, Jan Münch
Journal: Science Translational Medicine (2014)

Endogenous amyloids in semen impair the antiretroviral efficacy of drugs targeting HIV directly, but do not impair maraviroc, which targets the cellular CCR5 receptor.
Pathobiology of liver fibrosis: a translational success story
Authors: Youngmin A Lee, Michael C Wallace, Scott L Friedman
Journal: Gut (2015)

Reversibility of hepatic fibrosis and cirrhosis following antiviral therapy for hepatitis B or C has advanced the prospect of developing antifibrotic therapies for patients with chronic liver diseases, especially non-alcoholic steatohepatitis. Mechanisms of fibrosis have focused on hepatic stellate cells, which become fibrogenic myofibroblasts during injury through 'activation', and are at the nexus of efforts to define novel drug targets. Recent studies have clarified pathways of stellate cell gene regulation and epigenetics, emerging pathways of fibrosis regression through the recruitment and amplification of fibrolytic macrophages, nuanced responses of discrete inflammatory cell subsets and the identification of the 'ductular reaction' as a marker of severe injury and repair. Based on our expanded knowledge of fibrosis pathogenesis, attention is now directed towards strategies for antifibrotic therapies and regulatory challenges for conducting clinical trials with these agents. New therapies are attempting to: 1) Control or cure the primary disease or reduce tissue injury; 2) Target receptor-ligand interactions and intracellular signaling; 3) Inhibit fibrogenesis; and 4) Promote resolution of fibrosis. Progress is urgently needed in validating non-invasive markers of fibrosis progression and regression that can supplant biopsy and shorten the duration of clinical trials. Both scientific and clinical challenges remain, however the past three decades of steady progress in understanding liver fibrosis have contributed to an emerging translational success story, with realistic hopes for antifibrotic therapies to treat patients with chronic liver disease in the near future.
<sup>99m</sup> Tc-HL91
Authors: Robert D. Okada, Gerald Johnson, Kiem N. Nguyen, Barbara Edwards, Colin M. Archer, James D. Kelly
Journal: Circulation (1997)

Background 99m Tc-HL91 is a potential imaging agent that has demonstrated increased uptake in hypoxic tumor cells. The purpose of this study was to determine if 99m Tc-HL91 demonstrates increased uptake and retention in ischemic and hypoxic myocardium. Methods and Results 99m Tc-HL91 (11.1 MBq) was infused over 10 minutes, followed by a 60-minute clearance phase. Activity was monitored by using an NaI detector. Three groups were studied using Krebs-Henseleit buffer (KH): controls (12 mL/min, n=6), low-flow ischemic (1 mL/min, n=7), and hypoxic (12 mL/min, n=8). Two groups were perfused with KH, red blood cells, and albumin: controls (6 mL/min, n=6) and low-flow ischemic (0.5 mL/min, n=6). For the KH hearts, the 99m Tc-HL91 peak uptake progressively increased from control (6.3±0.5 μCi, mean±SEM) to hypoxic (9.1±1.0 μCi) to low flow (44.0±2.6 μCi; P &lt;.01). The peak uptake low-flow/control ratio was 7:1. Final retention increased progressively from control (0.8±0.1 μCi) to hypoxic (2.9±0.5 μCi) to low flow (10.9±1.3 μCi; P &lt;.01). The final low-flow/control activity ratio was 13.6:1. Similar results were observed in the red blood cell–perfused control and low-flow groups. Conclusions This study introduces a new myocardial “hot spot” imaging agent, 99m Tc-HL91. This agent demonstrates increased myocardial uptake and retention in hypoxic and low-flow ischemic models. Further in vivo imaging studies are warranted to determine the clinical potential of this agent.
Trusts are wasting millions by failing to bulk buy equipment, warn MPs
Authors: A. O'Dowd
Journal: BMJ (2011)

NHS trusts are losing millions of pounds because they are failing to buy expensive high tech equipment for hospitals in bulk, claim MPs.

They found that the way that equipment such as magnetic resonance imaging (MRI) and computed tomography (CT) scanners and linear accelerator (linac) machines are bought and used is not providing value for money for the taxpayer.

The report, published on 25 October by the parliamentary public accounts select committee, finds that in the past three years NHS trusts in England spent around £50m (€57m; $80m) a year on buying MRI and CT scanners and linear accelerators and that the current value of these machines in the NHS is around £1bn.

MPs on the committee said that since 2007 the Department of Health has devolved responsibility for procuring and …
Leptomeningeal metastasis: a Response Assessment in Neuro-Oncology critical review of endpoints and response criteria of published randomized clinical trials
Authors: Marc Chamberlain, Riccardo Soffietti, Jeffrey Raizer, Roberta Rudà, Dieta Brandsma, Willem Boogerd, Sophie Taillibert, Morris D Groves, Emilie Le Rhun, Larry Junck, Martin van den Bent, Patrick Y Wen, Kurt A Jaeckle
Journal: Neuro-Oncology (2014)

To date, response criteria and optimal methods for assessment of outcome have not been standardized in patients with leptomeningeal metastasis (LM). A Response Assessment in Neuro-Oncology working group of experts in LM critically reviewed published literature regarding randomized clinical trials (RCTs) and trial design in patients with LM. A literature review determined that 6 RCTs regarding the treatment of LM have been published, all of which assessed the response to intra-CSF based chemotherapy. Amongst these RCTs, only a single trial attempted to determine whether intra-CSF chemotherapy was of benefit compared with systemic therapy. Otherwise, this pragmatic question has not been formally addressed in patients with solid cancers and LM. The methodology of the 6 RCTs varied widely with respect to pretreatment evaluation, type of treatment, and response to treatment. Additionally there was little uniformity in reporting of treatment-related toxicity. One RCT suggests no advantage of combined versus single-agent intra-CSF chemotherapy in patients with LM. No specific intra-CSF regimen has shown superior efficacy in the treatment of LM, with the exception of liposomal cytarabine in patients with lymphomatous meningitis. Problematic with all RCTs is the lack of standardization with respect to response criteria. There was considerable variation in definitions of response by clinical examination, neuroimaging, and CSF analysis. Based upon a review of published RCTs in LM, there exists a significant unmet need for guidelines for evaluating patients with LM in clinical practice as well as for response assessment in clinical trials.
Specialized keratin expression pattern in human ridged skin as an adaptation to high physical stress
Authors: None Swensson, None Langbein, None Mcmillan, None Stevens, None Leigh, None Mclean, None Lane, None Eady
Journal: British Journal of Dermatology (1998)

We have analysed the expression of keratins in the epidermis of normal human palm and sole skin (ridged skin) using immunohistochemistry and in situ hybridization. The epidermis of human ridged skin expresses a more complex pattern of keratins than thin skin, which is probably due to the greater stress that ridged skin has to withstand. In addition to keratin K9, we document specific expression patterns of keratins K6, K16 and K17 which are suggestive of regional adaptations of this epidermis to a high cell turnover rate. In particular, the sequestered location of nests of K17-positive cells at the bottom of the deep primary epidermal ridges supports the notion of functional heterogeneity of basal cells and suggests that the K17-positive sites may include stem cells. Expression of K6 and K16 in some basal and most suprabasal keratinocytes is compatible with a constitutively high proliferative activity of normal ridged epidermis, but may also reflect different physical properties of the suprabasal cells, in contrast with regions expressing K9. The distinct labelling patterns observed in primary and secondary epidermal ridges as well as epidermal layers above dermal papillae suggest the existence of local microenvironmental niches leading to differences in keratinocyte differentiation.
Endoscopic submucosal dissection of gastric lesions by using a master and slave transluminal endoscopic robot: an animal survival study
Authors: Z. Wang, S. Phee, D. Lomanto, R. Goel, P. Rebala, Z. Sun, S. Trasti, N. Reddy, J. Wong, K. Ho
Journal: Endoscopy (2012)

<b>Background and study aims:</b> The feasibility of performing endoscopic submucosal dissection (ESD) using the Master and Slave Transluminal Endoscopic Robot (MASTER), a robotics-enhanced surgical system, has been shown in our previous study. This study aimed to further explore, in an animal survival study, the 2-week outcome of using MASTER to perform ESD. <b>Patients and methods:</b> In this prospective study, ESD was performed on five female pigs (weighing 32.4 – 36.8 kg) under general anesthesia using the MASTER. The animals were observed for 2 weeks before being humanely killed for necropsy examination. The main outcome measures were completeness of resection, procedure-related complications, and survival at 2 weeks. <b>Results:</b> The procedure was successfully completed in all five pigs. It took a mean of 21.8 minutes (range 6 – 39 minutes) to complete the ESD of each gastric lesion. All lesions were excised en bloc; the average dimension of the lesions was 77 mm (range 25 – 104 mm). One pig sustained a small intraoperative perforation which was identified and successfully clipped. After completion of the ESD procedures, all pigs survived well for 2 weeks. Necropsy was performed, with intraoperative gastroscopy identifying all the ESD sites as healed. Histopathologic examination showed all ESD sites had healed with partial epithelialization. Microbiological tests of the peritoneal fluid showed only microbes typically found in pigs. <b>Conclusion:</b> Performing ESD with MASTER was feasible and safe in this 2-week animal survival study.
SEPARATION OF THE TOXINS OF BACILLUS DYSENTERIÆ SHIGA
Authors: James E. McCartney, Peter K. Olitsky
Journal: The Journal of Experimental Medicine (1923)

By the suppression, through anaerobiosis, of the exotoxin-producing activity of Bacillus dysenteriæ Shiga a pure endotoxin is produced directly from the culture. The duality of the poison of Shiga bacillus is further substantiated by studies on the diffusion of exotoxin, or neurotoxin, and endotoxin, or enterotoxin, by means of collodion sacs, implanted intraabdominally in rabbits or placed in vitro.
Fully Discharging Phases
Authors: Yoshio Yamanouchi, James E. Brewer, Kenneth F. Olson, Kent A. Mowrey, Todor N. Mazgalev, Bruce L. Wilkoff, Patrick J. Tchou
Journal: Circulation (1999)

Background —Phase-2 voltage and maximum pulse width are dependent on phase-1 pulse characteristics in a single-capacitor biphasic waveform. The use of 2 separate output capacitors avoids these limitations and may allow waveforms with lower defibrillation thresholds. A previous report also suggested that the optimal tilt may be &gt;70%. This study was designed to determine an optimal biphasic waveform by use of a combination of 2 separate and fully (95% tilt) discharging capacitors. Methods and Results —We performed 2 external defibrillation studies in a pig ventricular fibrillation model. In group 1, 9 waveforms from a combination of 3 phase-1 capacitor values (30, 60, and 120 μF) and 3 phase-2 capacitor values (0=monophasic, 1/3, and 1.0 times the phase-1 capacitor) were tested. Biphasic waveforms with phase-2 capacitors of 1/3 times that of phase 1 provided the highest defibrillation efficacy (stored energy and voltage) compared with corresponding monophasic and biphasic waveforms with the same capacitors in both phases except for waveforms with a 30-μF phase-1 capacitor. In group 2, 10 biphasic waveforms from a combination of 2 phase-1 capacitor values (30 and 60 μF) and 5 phase-2 capacitor values (10, 20, 30, 40, and 50 μF) were tested. In this range, phase-2 capacitor size was more critical for the 30-μF phase-1 than for the 60-μF phase-1 capacitor. The optimal combinations of fully discharging capacitors for defibrillation were 60/20 and 60/30 μF. Conclusions —Phase-2 capacitor size plays an important role in reducing defibrillation energy in biphasic waveforms when 2 separate and fully discharging capacitors are used.
Autoantibodies to opsonins of apoptotic cells in systemic lupus erythematosus
Authors: P C Limburg
Journal: Annals of the Rheumatic Diseases (2005)

Does anti-serum amyloid P component have any clinical relevance?

The major immunological features of systemic lupus erythematosus (SLE) comprise the almost uniform presence of autoantibodies to nuclear antigens and the presence of immune complexes in the blood vessels and tissues, leading to inflammatory reactions. Especially since the studies by Casciola-Rosen and others, the central significance of the process of apoptosis in the aetiology and pathophysiology of SLE is becoming increasingly clear.1

Apoptosis or programmed cell death is the major physiological mechanism by which multicellular organisms can reorganise their cellular composition without letting cells die by necrosis, which would lead to the induction of inflammation. Clearance of apoptotic cells depends on structural changes of the apoptotic cell itself, opsonisation of apoptotic cells by several serum proteins, and binding and subsequent phagocytosis of opsonised apoptotic cells by neighbouring phagocytic cells. These processes have been studied in detail, although many questions still remain about the development and expression of disease in SLE.

Apoptosis is usually induced by exogenous stress—for instance, ultraviolet sunlight or deprival of essential growth factors, and leads to the activation of a cascade of proteases (caspases) and other enzymes. This ultimately results in proteolytic cleavage as well as modification of many cellular constituents. Most prominent of these is the chromatin, which contains densely packed DNA in combination with histones and other nuclear proteins, which is cleaved into nucleosomes, the major target of autoantibodies in SLE.

At the level of the cell membrane, structural changes result in the extracellular exposure of normally intracellular phospholipids, as well as release (blebbing) of membrane vesicles. Importantly, these vesicles may contain modified or unmodified intracellular and intranuclear proteins that are the target of the autoimmune response in SLE.1 This process leads to the binding of opsonising serum proteins and the subsequent binding to …
Gall bladder emptying in severe idiopathic constipation
Authors: C Penning, H A J Gielkens, J B V M Delemarre, C B H W Lamers, A A M Masclee
Journal: Gut (1999)

It has been suggested that slow transit constipation (STC) may be part of a panenteric motor disorder.To evaluate motility of an upper gastrointestinal organ, the gall bladder, in 16 patients with STC and 20 healthy controls.Gall bladder emptying (ultrasonography) was studied in response to neural, cephalic-vagal stimulation with modified sham feeding (MSF) for 90 minutes and in response to hormonal stimulation with cholecystokinin (CCK, 0.5 IDU/kg/h) for 60 minutes.Fasting gall bladder volume in patients with STC (17 (2) cm(3)) was significantly (p<0. 01) reduced compared with that in controls (24 (2) cm(3)). Gall bladder emptying in response to MSF was significantly reduced in patients with STC expressed both as percentage emptying (11 (5)% versus 22 (3)%; p<0.05) and as absolute emptying (2.1 (0.7) cm(3) versus 4.9 (0.7) cm(3); p<0.02). However, percentage gall bladder emptying in response to CCK was not different between patients and controls (73 (4)% versus 67 (4)%) although the absolute reduction in gall bladder volume was significantly (p<0.05) smaller in patients (10.7 (1.1) cm(3) versus 15.3 (1.4) cm(3)).Patients with slow transit constipation have smaller fasting gall bladder volumes, impaired gall bladder responses to vagal cholinergic stimulation, but normal gall bladder responses to hormonal stimulation with CCK. These results point to abnormalities in gastrointestinal motility proximal from the colon in slow transit constipation and more specifically, impaired neural responsiveness.
CO AS A CELLULAR SIGNALING MOLECULE
Authors: Hong Pyo Kim, Stefan W. Ryter, Augustine M.K. Choi
Journal: The Annual Review of Pharmacology and Toxicology (2005)

▪ Abstract Many biological functions of heme oxygenase (HO), such as cytoprotection against oxidative stress, vasodilation, neurotransmission in the central or peripheral nervous systems, and anti-inflammatory, anti-apoptotic, or anti-proliferative potential, have been attributed to its enzymatic byproduct carbon monoxide (CO), although roles for biliverdin/bilirubin and iron have also been proposed. In addition to these well-characterized effects, recent findings reveal that HO-derived CO may act as an oxygen sensor and circadian modulator of heme biosynthesis. In lymphocytes, CO may participate in regulatory T cell function. A number of the known signaling effects of CO depend on stimulation of soluble guanylate cyclase and/or activation of mitogen-activated protein kinases (MAPK). Furthermore, modulation of caveolin-1 status may serve as an essential component of certain aspects of CO action, such as growth control. In this review, we summarize recent findings of the beneficial or detrimental effects of endogenous CO with an emphasis on the signaling pathways and downstream targets that trigger the action of this gas.