tbuckley/cabot-search huggingface dataset:
Circulating leptin levels in juvenile idiopathic arthritis: a marker of nutritional status?
Authors: F Perfetto
Journal: Annals of the Rheumatic Diseases (2004)

Weight loss is common in juvenile idiopathic arthritis (JIA) and has been positively correlated with an increase in the production of proinflammatory cytokines.To assess if plasma leptin is a mediator of cytokine dependent decreased food intake during inflammatory diseases and if it is increased in JIA.Leptin levels were determined in 31 patients with polyarticular disease and in 37 with oligoarticular disease; 32 healthy children served as controls.Patients had significantly reduced body mass index (BMI) compared with controls (17.3 (3) v 19.1 (3) kg/m(2); p<0.005). Leptin was significantly lower in patients than controls (8.1 (4.8) v 10.7 (7.3) ng/ml; p = 0.036), but leptin/BMI values were similar. Absolute (8.2 (4.8) v 8 (4.9); p>0.05) and normalised (0.45 (0.24) v 0.47 (0.24); p>0.05) leptin levels were not significantly different between patients with active and inactive disease and between patients with oligoarticular and polyarticular arthritis (7.8 (4.4) v 8.6 (5.3); p>0.05 and 0.45 (0.23) v 0.48 (0.26); p>0.05, respectively).Leptin production per unit of fat mass is similar in patients and controls. The hypothesis that high levels of proinflammatory cytokines that characterise JIA might induce an increase of adipocytes leptin production is not supported by the results. Leptin may be a marker of nutritional status of JIA.
Breathing pattern and central ventilatory drive in mild and moderate generalised myasthenia gravis.
Authors: F Garcia Rio, C Prados, E Diez Tejedor, S Diaz Lobato, R Alvarez-Sala, J Villamor, J M Pino
Journal: Thorax (1994)

BACKGROUND--Myasthenia gravis is a specific autoimmune disease characterised by weakness and fatigue. Respiratory muscle weakness has been studied using the determination of maximal respiratory pressures, but the response of respiratory centres is not well characterised. This study was undertaken to determine the breathing pattern and the central ventilatory drive in patients with mild and moderate generalised myasthenia gravis. METHODS--Twenty four patients with myasthenia gravis were studied, divided into two groups. Group 1 included 13 subjects (eight women and five men aged 23-64) with mild generalised myasthenia gravis, and group 2 was composed of 15 patients (11 women and four men aged 23-69) with moderate generalised myasthenia gravis. A control group comprised 15 healthy persons with a similar age and sex distribution. Spirometric measurements and maximal respiratory pressures were performed under basal conditions in all subjects, and the rate and depth of breathing and the inspiratory occlusion pressure in the mouth in the first 0.1 second (P0.1) were measured. RESULTS--No difference was detected for parameters of breathing pattern between patients in group 1 and control subjects, although P0.1 was higher in those in group 1. Subjects in group 2 had a lower tidal ventilation, shorter inspiratory time, and a higher frequency with a higher P0.1 than control subjects. CONCLUSIONS--Mild myasthenia gravis causes increased neuromuscular drive with a normal breathing pattern. Moderate myasthenia gravis is characterised by a more rapid shallow breathing pattern.
Risk of Colorectal Cancer After Detection and Removal of Adenomas at Colonoscopy: Population-Based Case-Control Study
Authors: Hermann Brenner, Jenny Chang-Claude, Alexander Rickert, Christoph M. Seiler, Michael Hoffmeister
Journal: Journal of Clinical Oncology (2012)

Empirical evidence for recommendations of surveillance intervals after detection and removal of adenomas at colonoscopy is still sparse and mostly based on observations of adenoma recurrence. We aimed to assess risk of colorectal cancer (CRC) according to time since polypectomy and factors that might be relevant for risk stratification.In a population-based case-control study conducted in Germany, detailed history and results of previous large-bowel endoscopies were obtained by interview and from medical records. Risk of CRC among participants with detection of at least one adenoma at a preceding colonoscopy compared with participants without previous large-bowel endoscopy was assessed according to time since polypectomy among 2,582 cases with CRC and 1,798 matched controls.Adjusted odds ratios (95% CIs) of CRC for participants with polypectomy less than 3, 3 to 5, and 6 to 10 years ago (using participants without previous endoscopy as reference group) were 0.2 (0.2 to 0.3), 0.4 (0.3 to 0.6), and 0.9 (0.5 to 1.5), respectively. Strong, significant risk reduction within 5 years was consistently seen for women and men, younger and older participants, patients with and without high-risk polyps (three or more polyps, at least one polyp ≥ 1 cm, at least one polyp with villous components), and those with and without polypectomy in the right colon. With adjusted odds ratios of 0.1 (0.1 to 0.2), 0.3 (0.2 to 0.5) and 0.4 (0.2 to 0.8) for patients with polypectomy less than 3, 3 to 5, and 6 to 10 years ago, risk reduction was particularly strong for left-sided CRC.Extension of surveillance intervals to 5 years should be considered, even after detection and removal of high-risk polyps.
Imaging and Coding in the Olfactory System
Authors: John S Kauer, Joel White
Journal: Annual Review of Neuroscience (2001)

Functional imaging methods permit analysis of neuronal systems in which activity is broadly distributed in time and space. In the olfactory system the dimensions that describe odorant stimuli in "odorant space" are still poorly defined. One way of trying to characterize the attributes of this space is to examine the ways in which its dimensions are encoded by the neurons and circuits making up the system and to compare these responses with physical-chemical attributes of the stimuli and with the output behavior of the animal. For documenting distributed events as they occur, imaging methods are among the few tools available. We are still in the early stages of this analysis; however, a number of recent studies have contributed new information to our understanding of the odorant coding problem. This paper describes imaging results in the context of other data that have contributed to our understanding of how odors are encoded by the peripheral olfactory pathway.
Paradoxical inhibition of fibrinogen binding and potentiation of α-granule release by specific types of inhibitors of glycoprotein IIb–IIIa
Authors: D Schneider
Journal: Cardiovascular Research (2000)

Objective: To determine whether glycoprotein (GP) IIb–IIIa inhibitors can paradoxically augment activation of platelets, activation of GP IIb–IIIa, α-granule degranulation, and lysosome release were induced after exposure of platelets to GP IIb–IIIa inhibitors. Methods: ADP-induced platelet activation was assessed after exposure of platelets to Abciximab, or to a non-peptide ligand, the free acid of Orbofiban (Orbofibana). Activation of GP IIb–IIIa was detected based on binding of fluorochrome labeled fibrinogen or a labeled monoclonal antibody, PAC-1. α-Granule degranulation was detected based on surface expression of P-selectin and lysosome release was detected based on surface expression of CD63. Results: Despite significant inter-individual variability in inhibition of fibrinogen binding in response to each of the GP IIb–IIIa inhibitors used, a concentration dependent decrease in fibrinogen binding was seen with each agent in samples from each subject. Binding of PAC-1 was inhibited in a parallel manner. Abciximab increased ADP-induced P-selectin expression. Orbofibana did not alter ADP-induced P-selectin expression. Neither agent altered ADP-induced CD63 expression. When platelets were exposed to Abciximab and Orbofibana, both Abciximab and Orbofibana were found in the α-granules (by confocal microscopy), consistent with potentiation of agonist-induced release of α-granular products associated with uptake of proteins. Conclusions: Specific types of GP IIb–IIIa inhibitors can paradoxically augment agonist-induced release of α-granules despite inhibiting agonist-induced fibrinogen binding.
Yet another role for the “good” matrix protein: Laminin in regenerating liver
Authors: Jacquelyn J. Maher
Journal: Hepatology (1992)

After partial hepatectomy, the liver is capable of complete regeneration, restoring normal hepatic size, architecture, and function. To study the role of the extracellular matrix in regeneration, the temporal and spatial sequence of deposition of several of its components, including collagen types I, III, and IV, laminin, and fibronectin, in rat liver, after an 80% hepatectomy, was characterized by light microscopy immunohistochemistry. A minimum of five animals were studied for each date. In agreement with previous reports, subsequent to 80% hepatectomy, there was a brisk mitosis of hepatocytes. The mitotic activity was maximal at 48 hours, primarily in the periportal and centrilobular zones, and resulted in the formation of hepatocyte clusters and widening of the hepatic plates. Of the extracellular matrix components studied, laminin was the one demonstrating the most dramatic changes. By 24 hours, laminin appeared in the hepatic sinusoids reaching a maximum staining intensity at 48 hours. Intracellular laminin was prominent in numerous nonparenchymal cells, with many having the morphology, location, and desmin content characteristic of Ito cells. Laminin staining decreased in the sinusoids at 4 days; however, some intracellular staining of Ito cells was present even at 8 days after hepatectomy. At the completion of regeneration, there was no evidence of any substantial change in the ratio: extracellular matrix/cell mass. The results indicate that: (a) hepatocytes can divide without prior removal of the subsinusoidal extracellular matrix; (b) during regeneration, hepatocyte division precedes sinusoidal formation; (c) during hepatic regeneration, and in spite of the presence of laminin in Ito cells, no basement membranes are formed; (d) the prominent expression of laminin and its proposed functions in morphogenesis suggest a critical role for this matrix component in the formation and reorganization of the regenerating liver.
Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML)
Authors: B Hanfstein, M C Müller, R Hehlmann, P Erben, M Lauseker, A Fabarius, S Schnittger, C Haferlach, G Göhring, U Proetel, H-J Kolb, S W Krause, W-K Hofmann, J Schubert, H Einsele, J Dengler, M Hänel, C Falge, L Kanz, A Neubauer, M Kneba, F Stegelmann, M Pfreundschuh, C F Waller, S Branford, T P Hughes, K Spiekermann, G M Baerlocher, M Pfirrmann, J Hasford, S Saußele, A Hochhaus
Journal: Leukemia (2012)
Bromocriptine treatment of female infertility: report of 13 pregnancies.
Authors: M O Thorner, G M Besser, A Jones, J Dacie, A E Jones
Journal: BMJ (1975)

Thirteen pregnancies occurred in 12 women who were treated with bromocriptine for infertility. Pretreatment prolactin levels were recorded in 11 patients and were normal in three. Five patients had suspected pituitary tumours, and they received irradiation to prevent swelling of the pituitary and the consequent visual field defects caused by the pressure of the swollen gland on the optic nerve. Ten of the 13 pregnancies have come to term, and all the babies were normal. When a patient with a pituitary tumour developed a visual field defect in the 38th week of pregnancy labour was induced and the defect disappeared after delivery. No multiple pregnancies occurred and there were no major complications.
Evidence for a Role of Dendritic Filopodia in Synaptogenesis and Spine Formation
Authors: Noam E. Ziv, Stephen J Smith
Journal: Neuron (1996)

Axo-dendritic synaptogenesis was examined in live hippocampal cell cultures using the fluorescent dyes DiO to label dendrites and FM 4–64 to label functional presynaptic boutons. As the first functional synaptic boutons appeared in these cultures, numerous filopodia (up to 10 μm long) were observed to extend transiently (mean lifetime 9.5 min) from dendritic shafts. With progressively increasing numbers of boutons, there were coincident decreases in numbers of transient filopodia and increases in numbers of stable dendritic spines. Dendritic filopodia were observed to initiate physical contacts with nearby axons. This sometimes resulted in filopodial stabilization and formation of functional presynaptic boutons. These findings suggest that dendritic filopodia may actively initiate synaptogenic contacts with nearby (5–10 μm) axons and thereafter evolve into dendritic spines.
CRN2 enhances the invasiveness of glioblastoma cells
Authors: Anja Ziemann, Simon Hess, Ridhirama Bhuwania, Stefan Linder, Peter Kloppenburg, Angelika A. Noegel, Christoph S. Clemen
Journal: Neuro-Oncology (2013)

Movement of tumor cells involves dynamic remodeling of the actin cytoskeleton, which is regulated by actin binding proteins, such as CRN2 (synonyms: coronin 1C, coronin 3). In vitro, CRN2 participates in secretion, matrix degradation, protrusion formation, and cell migration. Furthermore, expression of CRN2 correlates with the malignant phenotype of human diffuse gliomas. CRN2's effects on actin polymerization and F-actin bundling are abolished by protein kinase 2 (CK2) dependent phosphorylation at serine 463.We generated human U373 glioblastoma cell lines with knock-down of CRN2 or over-expression of CRN2 variants and studied their behavior in vitro and ex vivo in organotypic brain slice cultures.CRN2 over-expression and expression of the S463A phospho-resistant CRN2 variant increase proliferation, matrix degradation, and invasion but decrease adhesion and formation of invadopodia-like extensions in vitro. Knock-down of CRN2 and expression of S463D phospho-mimetic CRN2 generally have opposite effects. Analysis of invadopodia-like cell extensions shows a diffuse relocalization of F-actin in CRN2 knockdown cells, whereas expression of S463A and S463D mutant CRN2 causes enrichments of F-actin structures at the center and rime zone, respectively. Fluorescence recovery after photobleaching studies of CRN2 and F-actin in lamellipodia show that both CRN2 variants decrease the turnover of actin filaments. Glioblastoma cells over-expressing wild-type or S463A CRN2, which were transplanted onto brain slices, characteristically developed into tumors with an invasive phenotype.Overall, our data indicate that CRN2 participates in cancer progression via modulation of the actin cytoskeleton.
Novel pulmonary biomarkers in the diagnosis of VAP
Authors: P. Johnston, D. F McAuley, C. M O'Kane
Journal: Thorax (2010)

Ventilator-associated pneumonia (VAP) is reported to occur in up to 20–27% of mechanically ventilated patients, and impacts healthcare in terms of patient morbidity, mortality and expenditure.1–3 The concept of VAP seems straightforward—that is, alveolar inflammation due to an infectious agent that was not present at the time of initiation of mechanical ventilation. However, the diagnosis remains difficult. Importantly, this difficulty in diagnosis of VAP leads to potential over-/underprescription of antibiotics and misguided treatment.

The American Thoracic Society guidelines of 20053 suggest that the use of readily available clinical data is adequate to inform the diagnosis of VAP. However, while such an approach has the advantage of being straightforward to apply, when compared with postmortem histological specimens the resultant sensitivity and specificity were 69% and 75%, respectively,4 indicating the need for better diagnostic systems. More complex scoring systems combining clinical and microbiological data, for example the clinical pulmonary infection score5 and national nosocomial infection surveillance system,6 have been proposed for the diagnosis of VAP, but have also been criticised for non-specificity.7 The addition of quantitative culture results from endotracheal secretions, or more complex samples including protected specimens, brushings or bronchoalveolar lavage fluid (BAL),3 to the clinical scoring systems for diagnosing VAP goes some way to reducing the potential overdiagnosis of VAP.8 Quantitative microbiological cultures are limited by their reduced sensitivity in patients who have been treated with antimicrobials in the preceding 3 days.9 10 Finally, laboratories do not routinely test for atypical pathogens. Recent work has highlighted a significant prevalence of anaerobic bacteria,11 viruses12 and fungi13 14 in intubated patients, although their role in VAP remains unclear.

Ideally, therefore, in diagnosing VAP we could distinguish colonisation from infection causing pulmonary inflammation, and remain confident of a negative diagnosis in …
Effectiveness of Multicomponent Nonpharmacological Delirium Interventions
Authors: Tammy T. Hshieh, Jirong Yue, Esther Oh, Margaret Puelle, Sarah Dowal, Thomas Travison, Sharon K. Inouye
Journal: JAMA Internal Medicine (2015)

<h3>Importance</h3> Delirium, an acute disorder with high morbidity and mortality, is often preventable through multicomponent nonpharmacological strategies. The efficacy of these strategies for preventing subsequent adverse outcomes has been limited to small studies to date. <h3>Objective</h3> To evaluate available evidence on multicomponent nonpharmacological delirium interventions in reducing incident delirium and preventing poor outcomes associated with delirium. <h3>Data Sources</h3> PubMed, Google Scholar, ScienceDirect, and the Cochrane Database of Systematic Reviews from January 1, 1999, to December 31, 2013. <h3>Study Selection</h3> Studies examining the following outcomes were included: delirium incidence, falls, length of stay, rate of discharge to a long-term care institution (institutionalization), and change in functional or cognitive status. <h3>Data Extraction and Synthesis</h3> Two experienced physician reviewers independently and blindly abstracted data on outcome measures using a standardized approach. The reviewers conducted quality ratings based on the Cochrane risk-of-bias criteria for each study. <h3>Main Outcomes and Measures</h3> We identified 14 interventional studies. The results for outcomes of delirium incidence, falls, length of stay, and institutionalization were pooled for the meta-analysis, but heterogeneity limited our meta-analysis of the results for change in functional or cognitive status. Overall, 11 studies demonstrated significant reductions in delirium incidence (odds ratio [OR], 0.47; 95% CI, 0.38-0.58). Four randomized or matched trials reduced delirium incidence by 44% (OR, 0.56; 95% CI, 0.42-0.76). The rate of falls decreased significantly among intervention patients in 4 studies (OR, 0.38; 95% CI, 0.25-0.60); in 2 randomized or matched trials, the rate of falls was reduced by 64% (OR, 0.36; 95% CI, 0.22-0.61). Length of stay and institutionalization also trended toward decreases in the intervention groups, with a mean difference of −0.16 (95% CI, −0.97 to 0.64) day shorter and the odds of institutionalization 5% lower (OR, 0.95; 95% CI, 0.71-1.26). Among higher-quality randomized or matched trials, length of stay trended −0.33 (95% CI, −1.38 to 0.72) day shorter, and the odds of institutionalization trended 6% lower (OR, 0.94; 95% CI, 0.69-1.30). <h3>Conclusions and Relevance</h3> Multicomponent nonpharmacological delirium prevention interventions are effective in reducing delirium incidence and preventing falls, with a trend toward decreasing length of stay and avoiding institutionalization. Given the current focus on prevention of hospital-based complications and improved cost-effectiveness of care, this meta-analysis supports the use of these interventions to advance acute care for older persons.
HLA Class I Binding Motifs Derived from Random Peptide Libraries Differ at the COOH Terminus from Those of Eluted Peptides
Authors: Miles P. Davenport, Katherine J. Smith, Dan Barouch, Scott W. Reid, Wanda M. Bodnar, Anthony C. Willis, Donald F. Hunt, Adrian V.S. Hill
Journal: The Journal of Experimental Medicine (1997)

Recombinant HLA-A2, HLA-B8, or HLA-B53 heavy chain produced in Escherichia coli was combined with recombinant β2-microglobulin (β2m) and a pool of randomly synthesised nonamer peptides. This mixture was allowed to refold to form stable major histocompatability complex (MHC) class I complexes, which were then purified by gel filtration chromatography. The peptides bound to the MHC class I molecules were subsequently eluted and sequenced as a pool. Peptide binding motifs for these three MHC class I molecules were derived and compared with previously described motifs derived from analysis of naturally processed peptides eluted from the surface of cells. This comparison indicated that the peptides bound by the recombinant MHC class I molecules showed a similar motif to naturally processed and presented peptides, with the exception of the peptide COOH terminus. Whereas the motifs derived from naturally processed peptides eluted from HLA-A2 and HLA-B8 indicated a strong preference for hydrophobic amino acids at the COOH terminus, this preference was not observed in our studies. We propose that this difference reflects the effects of processing or transport on the peptide repertoire available for binding to MHC class I molecules in vivo.
Mucoadhesive microparticles with a nanostructured surface for enhanced bioavailability of glaucoma drug
Authors: Chun Gwon Park, Young Kook Kim, Mi Jeung Kim, Min Park, Myung Hun Kim, Seung Ho Lee, Sung Yoon Choi, Won Seok Lee, You Jung Chung, Young Eun Jung, Ki Ho Park, Young Bin Choy
Journal: Journal of Controlled Release (2015)
Muscle activity during the golf swing
Authors: A McHardy, H Pollard
Journal: British Journal of Sports Medicine (2005)

In the right hands, the golf swing is a motion that inspires looks of awe from the public. It is a complex movement of the whole body to generate power to a golf ball to propel the ball great distances with accuracy. This movement relies on the coordinated sequence of muscle activation to produce a fluid and reproducible movement. This paper reviews the literature on golf swing related muscle activity. The phases of this activity are discussed with a view to assisting the practitioner in understanding the swing. Such understanding may help in the management of the injured golfer.