tbuckley/cabot-search huggingface dataset:
First-line analysis of the effects of treatment on progression of structural changes in knee osteoarthritis over 24 months: data from the osteoarthritis initiative progression cohort
Authors: Johanne Martel-Pelletier, Camille Roubille, François Abram, Marc C Hochberg, Marc Dorais, Philippe Delorme, Jean-Pierre Raynauld, Jean-Pierre Pelletier
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To determine, using data from participants enrolled in the progression cohort of the OAI, the effects of conventional osteoarthritis (OA) pharmacological treatment and those of the combination of glucosamine and chondroitin sulfate (Glu/CS) on knee structural changes. <h3>Methods</h3> Six hundred patients with knee OA were stratified based on whether or not they received for 24 consecutive months the OA conventional pharmacological treatment and/or Glu/CS. The main outcomes were knee structural changes, including the loss of joint space width (JSW) and of cartilage volume measured by quantitative MRI. <h3>Results</h3> Participants reported taking (+) (n=300) or not taking (–) (n=300) OA treatment (analgesic/NSAIDs). The +analgesic/NSAIDs participants had higher Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (p&lt;0.001) and smaller JSW (p=0.01), reflecting more severe disease at baseline. In the –analgesic/NSAIDs group, participants taking Glu/CS had significantly reduced loss of cartilage volume at 24 months in the medial central plateau (p=0.007). Further subdivision revealed that this effect of Glu/CS occurred in participants with a higher severity of the disease (JSW≤median). In the +analgesic/NSAIDs group, those taking Glu/CS had significantly reduced loss of cartilage volume in the global plateau at 12 months (p=0.05), and in the central plateau at 24 months (p=0.05). These effects occurred in participants with less disease severity (JSW&gt;median). By contrast, no significant reduction in JSW was found between all groups. <h3>Conclusions</h3> In +analgesic/NSAIDs groups and –analgesic/NSAIDs groups, participants who took Glu/CS had reduced loss of cartilage volume over 24 months in subregions when assessed with qMRI, arguing for a disease-modifying effect of Glu/CS which could not be identified by X-rays.
Does low-field dedicated extremity MRI (E-MRI) reliably detect bone erosions in rheumatoid arthritis? A comparison of two different E-MRI units and conventional radiography with high-resolution CT scanning
Authors: A Duer-Jensen, B Ejbjerg, E Albrecht-Beste, A Vestergaard, U M. Dohn, M L. Hetland, M Ostergaard
Journal: Annals of the Rheumatic Diseases (2008)

To compare the ability of two different E-MRI units and conventional radiography (CR) to identify bone erosions in rheumatoid arthritis (RA) metacarpophalangeal (MCP) and wrist joints with CT scanning as the standard reference method.20 patients with RA and 5 controls underwent CR, CT and two E-MRI examinations (Esaote Biomedica Artoscan and MagneVu MV1000) of one hand during a 2-week period. In all modalities, each bone of the wrist and MCP joints was blindly evaluated for erosions. MagneVu images were also assessed for the proportion of each bone being visualised.550 bones were examined. CT, Artoscan, MagneVu and CR detected 188, 116, 55 and 45 bones with erosions, respectively. The majority were located in the carpal bones. The sensitivity of the Artoscan for detecting erosions was higher than that of the MagneVu and CR (MCP joints: 0.68, 0.54 and 0.57, respectively; wrists: 0.50, 0.23 and 0.29). Corresponding specificities for detecting erosions were 0.94, 0.93 and 0.99, respectively, in the MCP joints and 0.92, 0.98 and 0.98 in the wrist. The MagneVu allowed visualisation of 1.5 cm of the ventral-dorsal diameter of the bone. In the wrist, 31.6% of bones were visualised entirely and 37.9% of bones were 67-99% visualised. In MCP joints, 84.2% of bones were visualised entirely and 15.8% of bones were 67-99% visualised.With CT as the reference method for detecting erosions in RA hands, the Artoscan showed higher sensitivity than the MagneVu and CR. All imaging modalities had high specificities. The better performance of the Artoscan should be considered when selecting an imaging method in RA.
Priming of neutrophils for enhanced release of oxygen metabolites by bacterial lipopolysaccharide. Evidence for increased activity of the superoxide-producing enzyme.
Authors: L A Guthrie, L C McPhail, P M Henson, R B Johnston
Journal: The Journal of Experimental Medicine (1984)

We investigated the capacity of bacterial endotoxin (lipopolysaccharide, LPS) to modify the oxidative metabolic response to membrane stimulation of human neutrophils. Neutrophils were pretreated for 60 min with LPS, 10 ng/ml, then stimulated by exposure to fixed immune complexes, the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP), or phorbol myristate acetate. Release of superoxide anion (O-2) was up to 7-times greater in cells preincubated with LPS, depending upon the stimulus used. Consumption of oxygen and release of hydrogen peroxide (H2O2) were similarly increased, using FMLP as stimulus. The enhancement was accompanied by a reduction in lag time and an increase in the rate of the response, but the duration of the oxidative events was not changed. The molecular basis for the augmented oxidative response of LPS-pretreated cells was investigated. Preincubation with LPS at 0 degrees C prevented priming, but preincubation in the presence of cycloheximide or chelation of extracellular calcium ion did not. Neutrophils preincubated with LPS had slightly decreased numbers of binding sites and equivalent binding affinity for radiolabeled FMLP. Possible changes in the enzyme responsible for the oxidative burst were analyzed by studying NADPH-dependent generation of O-2 by particulate fractions from cells preincubated with LPS or buffer, then stimulated before cell disruption. The fraction prepared from LPS-pretreated neutrophils exhibited greater release of O-2 over a wide range of concentrations of NADPH. The calculated apparent Km for NADPH was equivalent in the two fractions, but the Vmax was increased 2.5-fold in the subcellular fraction from LPS-pretreated cells. These results suggest that LPS could increase neutrophil-mediated host defense or the tissue damage associated with endotoxemia by enhancing the generation of oxygen metabolites by neutrophils. These results also support the concept that the neutrophil is not an end-stage cell in regard to function or metabolic activity.
What's hot that the other lot got
Authors: Benjamin Prudon
Journal: Thorax (2014)

Continuous positive airway pressure (CPAP) use for middle-aged patients with symptomatic moderate-severe obstructive sleep apnoea (OSA) has a clear evidence base showing patient benefit and cost effectiveness. Despite many clinicians using CPAP in older patients, specific evidence for this practice is limited. McMillan et al ( Lancet Respir Med 2014. pii: S2213-2600(14)70172-9) have reported the results of the PREDICT trial (CPAP in older people with OSA syndrome). This UK trial involved 14 recruiting sites, where consecutive patients aged 65 years or above with an Oxygen Desaturation Index of >7.5/h and an Epworth Sleepiness Scale >8 were randomised to receive either CPAP therapy (autoset device) with best supportive care, or best supportive care alone, for 12 months. Two hundred and seventy-eight patients were recruited with 140 patients allocated to CPAP. The mean age across both treatment groups was 71 (SD 4.6) years, Oxygen Desaturation Index (ODI) 28.7 (19.1) and Epworth Sleepiness Scale (ESS) 11.6 (3.7). At 3 months, the ESS was …
Massage as a Therapeutic Agent
Authors: W. Murrell
Journal: BMJ (1886)

The temperature of the bedroom was 28°Fahr.at a2 .x. ; a minimum thermometer showed 23°since the previous d.nuary 31st.I found him, at the time of visit, sitting out in the sn.The next day previously to the "visit," he wilfully left Maloja for Italy, descending 3,800 feet in five hours.It was reported that he gained strength slowly, but made a good reenvery.This man, who was a plasterer, contracted his pneumonia from the effects of rapid and extreme variations of temperature, and irritant coke-fumes.Although he was a native of Italy, tainted with malaria, and not a robust subject, he made a good recovery in the dry air of the Engadine during the coldest part of winter.Externally, in a Stevensoil's screen, thermometers indicated the fol- lowing temperatuires, during the man's illness: mean temperature, Flahr., 18.6°(9 A.M.), 25.8' (noon), 27.7°(3 P.Ms.); maximntum, 38' Fahr.; minimum, 4°Fahr.Thc "mean weight of moisture sus- pended in the air," calculated at noon by Apjohn's formula, was 11 grains per 10 cubic feet of atmosphere; (at Ke', the mean for the whole month of January equalled 25 grains per 10 cuibic feet).The mean "drying power of the air," or weight of vapour wbhich 10 cubic feet were still capable of absorbing, was 5.3 grains.
Interferon and Granulopoiesis Signatures in Systemic Lupus Erythematosus Blood
Authors: Lynda Bennett, A. Karolina Palucka, Edsel Arce, Victoria Cantrell, Josef Borvak, Jacques Banchereau, Virginia Pascual
Journal: The Journal of Experimental Medicine (2003)

Systemic lupus erythematosus (SLE) is a prototype systemic autoimmune disease characterized by flares of high morbidity. Using oligonucleotide microarrays, we now show that active SLE can be distinguished by a remarkably homogeneous gene expression pattern with overexpression of granulopoiesis-related and interferon (IFN)-induced genes. Using the most stringent statistical analysis (Bonferroni correction), 15 genes were found highly up-regulated in SLE patients, 14 of which are targets of IFN and one, defensin DEFA-3, a major product of immature granulocytes. A more liberal correction (Benjamini and Hochberg correction) yielded 18 additional genes, 12 of which are IFN-regulated and 4 granulocyte-specific. Indeed immature neutrophils were identified in a large fraction of SLE patients white blood cells. High dose glucocorticoids, a standard treatment of disease flares, shuts down the interferon signature, further supporting the role of this cytokine in SLE. The expression of 10 genes correlated with disease activity according to the SLEDAI. The most striking correlation (P < 0.001, r = 0.55) was found with the formyl peptide receptor-like 1 protein that mediates chemotactic activities of defensins. Therefore, while the IFN signature confirms the central role of this cytokine in SLE, microarray analysis of blood cells reveals that immature granulocytes may be involved in SLE pathogenesis.
Impaired intracellular transport and cell surface expression of nonpolymorphic HLA-E: evidence for inefficient peptide binding.
Authors: M Ulbrecht, J Kellermann, J P Johnson, E H Weiss
Journal: The Journal of Experimental Medicine (1992)

The assembly of the classical, polymorphic major histocompatibility complex class I molecules in the endoplasmic reticulum requires the presence of peptide ligands and beta 2-microglobulin (beta 2m). Formation of this trimolecular complex is a prerequisite for efficient transport to the cell surface, where presented peptides are scanned by T lymphocytes. The function of the other class I molecules is in dispute. The human, nonclassical class I gene, HLA-E, was found to be ubiquitously transcribed, whereas cell surface expression was difficult to detect upon transfection. Pulse chase experiments revealed that the HLA-E heavy chain in transfectants, obtained with the murine myeloma cell line P3X63-Ag8.653 (X63), displays a significant reduction in oligosaccharide maturation and intracellular transport compared with HLA-B27 in corresponding transfectants. The accordingly low HLA-E cell surface expression could be significantly enhanced by either reducing the culture temperature or by supplementing the medium with human beta 2m, suggesting inefficient binding of endogenous peptides to HLA-E. To analyze whether HLA-E binds peptides and to identify the corresponding ligands, fractions of acid-extracted material from HLA-E/X63 transfectants were separated by reverse phase HPLC and were tested for their ability to enhance HLA-E cell surface expression. Two fractions specifically increased the HLA class I expression on the HLA-E transfectant clone.
Sentinel Lymph Node Histopathology in Breast Cancer: Minimal Disease Versus Artifact
Authors: Beverley A. Carter, David L. Page
Journal: Journal of Clinical Oncology (2006)

The presence or absence of tumor deposits in axillary lymph nodes in patients with breast carcinoma remains central to staging and prognosis as well as guidance of treatment decisions. Sentinel lymph node biopsy can be reliably performed by experienced teams to avoid axillary dissection and its resultant morbidities in recognized subsets of breast cancer patients. 1 With general acceptanceofsentinellymphnodeexaminationhascometheincreasing
Oxidative Damage Targets Complexes Containing DNA Methyltransferases, SIRT1, and Polycomb Members to Promoter CpG Islands
Authors: Heather M. O'Hagan, Wei Wang, Subhojit Sen, Christina DeStefano Shields, Stella S. Lee, Yang W. Zhang, Eriko G. Clements, Yi Cai, Leander Van Neste, Hariharan Easwaran, Robert A. Casero, Cynthia L. Sears, Stephen B. Baylin
Journal: Cancer Cell (2011)
Interleukin 2 transcription factors as molecular targets of cAMP inhibition: delayed inhibition kinetics and combinatorial transcription roles.
Authors: D Chen, E V Rothenberg
Journal: The Journal of Experimental Medicine (1994)

Elevation of cAMP can cause gene-specific inhibition of interleukin 2 (IL-2) expression. To investigate the mechanism of this effect, we have combined electrophoretic mobility shift assays and in vivo genomic footprinting to assess both the availability of putative IL-2 transcription factors in forskolin-treated cells and the functional capacity of these factors to engage their sites in vivo. All observed effects of forskolin depended upon protein kinase A, for they were blocked by introduction of a dominant negative mutant subunit of protein kinase A. In the EL4.E1 cell line, we report specific inhibitory effects of cAMP elevation both on NF-kappa B/Rel family factors binding at -200 bp, and on a novel, biochemically distinct "TGGGC" factor binding at -225 bp with respect to the IL-2 transcriptional start site. Neither NF-AT nor AP-1 binding activities are detectably inhibited in gel mobility shift assays. Elevation of cAMP inhibits NF-kappa B activity with delayed kinetics in association with a delayed inhibition of IL-2 RNA accumulation. Activation of cells in the presence of forskolin prevents the maintenance of stable protein-DNA interactions in vivo, not only at the NF-kappa B and TGGGC sites of the IL-2 enhancer, but also at the NF-AT, AP-1, and other sites. This result, and similar results in cyclosporin A-treated cells, imply that individual IL-2 transcription factors cannot stably bind their target sequences in vivo without coengagement of all other distinct factors at neighboring sites. It is proposed that nonhierarchical, cooperative enhancement of binding is a structural basis of combinatorial transcription factor action at the IL-2 locus.
Idiopathic ventricular arrhythmia arising from the mitral annulus
Authors: Hiroshi Tada, Sachiko Ito, Shigeto Naito, Kenji Kurosaki, Shoichi Kubota, Aiko Sugiyasu, Taketsugu Tsuchiya, Kohei Miyaji, Minoru Yamada, Yasunori Kutsumi, Shigeru Oshima, Akihiko Nogami, Koichi Taniguchi
Journal: Journal of the American College of Cardiology (2005)
Enhanced Responses of Blood Pressure, Renal Function, and Aldosterone to Angiotensin I in the DD Genotype Are Blunted by Low Sodium Intake
Authors: Frank G. H. van der Kleij, Paul E. de Jong, Rob H. Henning, Dick de Zeeuw, Gerjan Navis
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Angiotensin-converting enzyme (ACE) activity is increased in the DD genotype, but the functional significance for renal function is unknown. Blunted responses of BP and proteinuria to ACE inhibition among DD renal patients during periods of high sodium intake were reported. It was therefore hypothesized that sodium status affects the phenotype in the ACE I/D polymorphism. The effects of angiotensin I (AngI) and AngII among 27 healthy subjects, with both low (50 mmol sodium/d) and liberal (200 mmol sodium/d) sodium intakes, were studied. Baseline mean arterial pressure (MAP) values, renal hemodynamic parameters, and renin-angiotensin system parameters were similar for all genotypes with either sodium intake level. With liberal sodium intake, the increases in MAP, renal vascular resistance, and aldosterone levels during AngI infusion (8 ng/kg per min) were significantly higher for the DD genotype, compared with the ID and II genotypes (all parameters presented as percent changes ± 95% confidence intervals), with mean MAP increases of 22 ± 2% (DD genotype), 13 ± 5% (ID genotype), and 12 ± 6% (II genotype) (P < 0.05), mean increases in renal vascular resistance of 100.1 ± 19.7% (DD genotype), 73.0 ± 16.3% (ID genotype), and 63.2 ± 16.9% (II genotype) (P < 0.05), and increases in aldosterone levels of 650 ± 189% (DD genotype), 343 ± 71% (ID genotype), and 254 ± 99% (II genotype) (P < 0.05). Also, the decrease in GFR was more pronounced for the DD genotype, with mean decreases of 17.9 ± 4.7% (DD genotype), 8.8 ± 3.4% (ID genotype), and 6.4 ± 5.9% (II genotype) (P < 0.05). The effective renal plasma flow, plasma AngII concentration, and plasma renin activity values were similar for the genotypes. In contrast, with low sodium intake, the responses to AngI were similar for all genotypes. The responses to AngII were also similar for all genotypes, with either sodium intake level. In conclusion, the responses of MAP, renal hemodynamic parameters, and aldosterone concentrations to AngI are enhanced for the DD genotype with liberal but not low sodium intake. These results support the presence of gene-environment interactions between ACE genotypes and dietary sodium intake.
Sleep clinical record: an aid to rapid and accurate diagnosis of paediatric sleep disordered breathing
Authors: Maria Pia Villa, Maria Chiara Paolino, Rosa Castaldo, Nicola Vanacore, Alessandra Rizzoli, Silvia Miano, Marco Del Pozzo, Marilisa Montesano
Journal: European Respiratory Journal (2012)

Overnight polysomnography (PSG) is an expensive procedure which can only be used in a minority of cases, although it remains the gold standard for the diagnosis of sleep disordered breathing (SDB). The objective of this study was to develop a simple, PSG-validated tool to screen SDB, thus reducing the use of PSG. For every participant we performed PSG and a sleep clinical record was completed. The sleep clinical record consists of three items: physical examination, subjective symptoms and clinical history. The clinical history analyses behavioural and cognitive problems. All three items were used to create a sleep clinical score (SCS). We studied 279 children, mean± sd age 6.1±3.1 years, 63.8% male; 27.2% with primary snoring and 72.8% with obstructive sleep apnoea (OSA) syndrome. The SCS was higher in the OSA syndrome group compared to the primary snoring group (8.1±9.6 versus 0.4±0.3, p&lt;0.005), correlated with apnoea/hypopnoea index (p=0.001) and had a sensitivity of 96.05%. Positive and negative likelihood ratios were 2.91 and 0.06, respectively. SCS may effectively be used to screen patients as candidates for PSG study for suspected OSA syndrome, and to enable those with a mild form of SDB to receive early treatment.
Alveolar epithelial type II cells from embryonic stem cells: knights in shining armour?
Authors: H. Fehrenbach
Journal: European Respiratory Journal (2012)

Today, the pulmonary epithelium is generally accepted to possess unique properties that go far beyond the role as a mere physical barrier protecting an organism’s interior against the detrimental effects exerted by airborne environmental challenges, such as gases, particles, allergens or microorganisms. The specific tasks respiratory epithelial cells have to fulfil differ along the bronchiotracheal tract down to the alveoli [1, 2]. Accordingly, there is a continuous change in the cellular composition of the epithelium along the airway tract reflecting remarkable structural and functional differentiation. Besides long-known roles of the epithelium, such as mucociliary clearance, lung fluid balance and surfactant homeostasis, which assure the removal of particles and cells, the avoidance of oedema and the proper adjustment of surface tension, respectively, are additional important functions that have been identified in recent years related to the regulation of innate and adaptive immune responses [3–6].

In order to guarantee that these functions, which are critical for the proper function of the lungs, can be maintained continuously, mechanisms of epithelial repair and regeneration involving a plethora of mediators and pathways have evolved [7]. Region-specific epithelial “task forces”, i.e. local progenitor cells including alveolar epithelial type II cells (AECII), or perhaps only a specific subset of these [8], are “defined” to accomplish epithelial repair and regeneration in the different regions along the respiratory tract [9–11]. Until a recent study …
Number of living organ donations in UK rose by 8% in past year
Authors: A. O'Dowd
Journal: BMJ (2010)

The number of people becoming a living organ donor in the United Kingdom has risen by 8% in the past year, alongside a sharp rise in bone marrow donations, says the annual review of the body that regulates the use of human tissue, published on 15 June.

The Human Tissue Authority’s report says that the number of living organ donations was 1140 in 2009-10, up by 8% from the 2008-9 figure of 1058.

Living donation is regulated by the authority through a system of independent assessment. It received 1143 reports for consideration in …
Molecular and biological characterization of a herpes simplex virus type 1 (HSV-1) neuroinvasiveness gene.
Authors: K M Izumi, J G Stevens
Journal: The Journal of Experimental Medicine (1990)

Pathogenetic studies of herpes simplex virus type 1 (HSV-1) strains ANG and its mouse brain-passaged descendant ANG path revealed no difference in neurovirulence but a significant difference in neuroinvasiveness. Thus, both viruses induced a fatal encephalitis in mice after direct injection into the brain, but only ANG path induced lethal neurologic disease after inoculation on rear footpads. The difference in neuroinvasiveness is not related to the capacity to replicate in mouse neural tissues or mouse cells in general, but is specifically related to virus entry into the peripheral nervous system in the footpad. Marker rescue experiments in which ANG path genes were used to confer neuroinvasiveness on ANG indicated that the gene that codes for glycoprotein D (gD) is responsible for the phenotypic difference. Analyses of the gD genes by dideoxy-sequencing techniques identified a base difference in the coding sequences and predicted that the ANG gD gene codes for alanine (GCC codon) at amino acid position 84 in the open reading frame and the ANG path gD gene codes for glycine (GGC codon) at this site. Using these data, an oligonucleotide probe predicted to be specific for the ANG path gD gene was prepared, and in Southern blot analyses, this probe revealed that neuroinvasiveness-rescued agents had incorporated the base change seen in the ANG path gD gene. We conclude that HSV-1 glycoprotein D functions to effect neuroinvasiveness and we discuss potential mechanisms that may be involved.