tbuckley/cabot-search huggingface dataset:
Synthesis and release of human cartilage matrix proteoglycans are differently regulated by nitric oxide and prostaglandin-E2
Authors: S C Mastbergen, J W J Bijlsma, F P J G Lafeber
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> Recent studies showed beneficial effects of COX-2 inhibition on proteoglycan turnover of both IL-1β/tumour necrosis factor α (TNFα) damaged cartilage and of osteoarthritic cartilage. Although proteoglycan release and content were normalised, proteoglycan synthesis was only partially influenced. Prostaglandin-E<sub>2</sub> is the main product formed by COX-2. We therefore evaluate the role of prostaglandin-E<sub>2 </sub>in relation to nitric oxide in disturbing cartilage proteoglycan turnover. <h3>Methods:</h3> Human healthy cartilage, alone or in the presence of IL-1β+TNFα, was cultured for 7 days with or without prostaglandin-E<sub>2</sub> or the selective COX-2 inhibitor (celecoxib 10 μM). Changes in cartilage matrix proteoglycan turnover, levels of prostaglandin-E<sub>2</sub> and nitric oxide were determined. <h3>Results:</h3> Proteoglycan synthesis and release of the cartilage were not affected by prostaglandin-E<sub>2</sub> alone. Addition of IL-1β+TNFα to healthy cartilage resulted in inhibition of proteoglycan synthesis and increase in proteoglycan release. When prostaglandin-E<sub>2</sub> was added, in addition to IL-1β+TNFα, proteoglycan release increased further, but proteoglycan synthesis was not influenced further. Addition of a selective COX-2 inhibitor to the IL-1β+TNFα treated cartilage inhibited the enhanced prostaglandin-E<sub>2</sub> production and almost completely normalised proteoglycan release, whereas synthesis remained unaffected. Also, the enhanced NO-levels remained elevated. Prostaglandin-E<sub>2</sub> levels correlated significantly with proteoglycan release, whereas NO levels correlated significantly with proteoglycan synthesis. <h3>Conclusion:</h3> The present results suggest involvement of prostaglandin-E<sub>2</sub> in enhanced cartilage proteoglycan release but not synthesis, although healthy cartilage has to be sensitised by IL-1β+tumour necrosis factor α (TNFα). IL-1β+TNFα induced NO seems to be involved in inhibition of proteoglycan synthesis, independent of prostaglandin-E<sub>2</sub>, and thus seems insensitive to regulation by (selective) COX-2 inhibitors.
HLA-DRB1 alleles associated with polymyalgia rheumatica in northern Italy: correlation with disease severity
Authors: C. Salvarani, L. Boiardi, V. Mantovani, A. Ranzi, F. Cantini, I. Olivieri, M. Bragliani, E. Collina, P. Macchioni
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> To examine the association of HLA-DRB1 alleles with polymyalgia rheumatica (PMR) in a Mediterranean country and to explore the role of HLA-DRB1 genes in determining disease severity. <h3>METHODS</h3> A five year prospective follow up study of 92 consecutive PMR patients diagnosed by the secondary referral centre of rheumatology of Reggio Emilia, Italy was conducted. HLA-DRB1 alleles were determined in the 92 patients, in 29 DR4 positive rheumatoid arthritis (RA) patients, and in 148 controls from the same geographical area by polymerase chain reaction amplification and oligonucleotide hybridisation. <h3>RESULTS</h3> No significant differences were observed in the frequencies of HLA-DRB1 types and in the expression of HLA-DRB 70–74 shared motif between PMR and controls. The frequency of the patients with double dose of epitope was low and not significantly different in PMR and in controls. No significant differences in the distribution of HLA-DR4 subtypes were observed between DR4+ PMR, DR+ RA, and DR4+ controls. Results of the univariate analysis indicated that an erythrocyte sedimentation rate (ESR) at diagnosis &gt; 72 mm 1st h, the presence of HLA-DR1, DR10, rheumatoid epitope, and the type of rheumatoid epitope were significant risk factors associated with relapse/recurrence. Cox proportional hazards modelling identified two variables that independently increased the risk of relapse/recurrence: ESR at diagnosis &gt; 72 mm 1st h (RR=1.5) and type 2 (encoded by a non-DR4 allele) rheumatoid epitope (RR=2.7). <h3>CONCLUSION</h3> These data from a Mediterranean country showed no association of rheumatoid epitope with PMR in northern Italian patients. A high ESR at diagnosis and the presence of rheumatoid epitope encoded by a non-DR4 allele are independent valuable markers of disease severity.
Clinical testing of implanted pacemakers
Authors: E. Sowton, K. Gray
Journal: Thorax (1971)

The function of implanted pacemakers was assessed at a special pacemaker clinic at intervals of three to six months. Measurements of the basic discharge rate of the pacemaker were made and the waveform was recovered from skin electrodes and displayed on an oscilloscope screen. The impulse was photographed from the screen and subsequent waveform analysis was carried out. Reproducible results were obtained for measurements of peak amplitude and impulse duration provided unipolar electrodes were in use and the patients were studied in the same position. The range of variation of the measurements during the lifetime of different models of normally functioning pacemakers is given. Test measurements taken before failing pacemakers were removed have been correlated with the subsequently established cause of failure and the waveform analysis test has been shown to be clinically reliable. The value of the test depended largely upon the type of pacemaker but it correlated well with rate changes in pacemakers designed to slow as battery exhaustion developed. The clinical value of waveform analysis tests is in the diagnosis of exit block, electrode failure, and premature battery exhaustion and in determining the optimum time for pacemaker replacements. The indications for replacement of pacemakers at the National Heart Hospital are given. Initial experience with an automatic analyser with three types of pacemaker shows that rapid measurements of the waveform parameters can be achieved with accuracy.
Blocking IL-6 trans-Signaling Prevents High-Fat Diet-Induced Adipose Tissue Macrophage Recruitment but Does Not Improve Insulin Resistance
Authors: Michael J. Kraakman, Helene L. Kammoun, Tamara L. Allen, Virginie Deswaerte, Darren C. Henstridge, Emma Estevez, Vance B. Matthews, Bronwyn Neill, David A. White, Andrew J. Murphy, Lone Peijs, Christine Yang, Steve Risis, Clinton R. Bruce, Xiao-Jun Du, Alex Bobik, Robert S. Lee-Young, Bronwyn A. Kingwell, Ajithkumar Vasanthakumar, Wei Shi, Axel Kallies, Graeme I. Lancaster, Stefan Rose-John, Mark A. Febbraio
Journal: Cell Metabolism (2015)

Highlights•IL-6 trans-signaling recruits macrophages to adipose tissue in HFD-induced obesity•Blocking IL-6 trans-signaling with sgp130Fc prevents HFD-induced ATM accumulation•Prevention of ATM accumulation in obesity does not rescue insulin resistance•Blocking IL-6 trans-signaling does not exacerbate HFD-induced insulin resistanceSummaryInterleukin-6 (IL-6) plays a paradoxical role in inflammation and metabolism. The pro-inflammatory effects of IL-6 are mediated via IL-6 "trans-signaling," a process where the soluble form of the IL-6 receptor (sIL-6R) binds IL-6 and activates signaling in inflammatory cells that express the gp130 but not the IL-6 receptor. Here we show that trans-signaling recruits macrophages into adipose tissue (ATM). Moreover, blocking trans-signaling with soluble gp130Fc protein prevents high-fat diet (HFD)-induced ATM accumulation, but does not improve insulin action. Importantly, however, blockade of IL-6 trans-signaling, unlike complete ablation of IL-6 signaling, does not exacerbate obesity-induced weight gain, liver steatosis, or insulin resistance. Our data identify the sIL-6R as a critical chemotactic signal for ATM recruitment and suggest that selectively blocking IL-6 trans-signaling may be a more favorable treatment option for inflammatory diseases, compared with current treatments that completely block the action of IL-6 and negatively impact upon metabolic homeostasis.Graphical abstract
Further experience of Corynebacterium parvum in malignant pleural effusion.
Authors: D T McLeod, P M Calverley, J W Millar, N W Horne
Journal: Thorax (1985)

The outcome of drug induced pleurodesis has been evaluated in a non-randomised retrospective study of 67 patients with recurrent malignant pleural effusions treated during 1976-83. Fourteen died within 30 days of treatment. Of the remaining 53 patients, 26 studied during 1976-80 were treated with intrapleural mustine hydrochloride, while 27 studied during 1978-83 were treated with intrapleural Corynebacterium parvum. There was no significant difference between the groups in age, sex, or tumour type, most tumours being secondary to bronchial neoplasms. Corynebacterium parvum successfully prevented reaccumulation of the effusion in 24 (92%) patients, while mustine was effective in only 17 (65%) (p less than 0.05). Data on survival were obtained on 47 cases where a single agent was used to induce pleurodesis. In 25 patients treated with C parvum the mean survival was 251 (range 31-1143) days, compared with 119 (range 31-380) days for the 22 patients in whom mustine was used. Survival of the C parvum group was significantly greater (p less than 0.01). The difference was principally due to the greater number of long term survivors in the C parvum group, nine of this group living for more than 180 days (mean 574, range 180-1143 days) compared with only four such survivors in the mustine group (mean 263, range 193-380 days). This study confirms our initial impression that C parvum is highly effective in controlling recurrent malignant pleural effusions. The finding of unexpected long term survivors with C parvum treatment suggests that this treatment may have an additional effect on the progression of disease, a finding that merits further investigation.
FDA given new powers over data reporting to national clinical trials registry
Authors: B. Roehr
Journal: BMJ (2012)

The US Food and Drug Administration (FDA) has been given the authority to monitor and enforce the reporting of required data to the national clinical trials registry (ClinicalTrials.gov). 

Authority for the registry previously rested with the Secretary of Health but was transferred to the FDA on 26 September.1 The move is seen as a streamlining or rationalization of administrative responsibilities and will probably result in enhanced accountability.

The National Institute for Health’s (NIH) National Library of Medicine operates the ClinicalTrials.gov database. A 2007 change in the law required that “basic results” for certain clinical trials, including those submitted to the FDA for …
Yeast Infections — Human Genetics on the Rise
Authors: Steven M. Holland, Donald C. Vinh
Journal: New England Journal of Medicine (2009)

We lead inextricably mycotic lives: yeasts leaven our bread, ferment our wine and beer, and inhabit our skins, mouths, and gastrointestinal tracts; however, not all is harmony. Hippocrates reported aphthous ulcers consistent with thrush in patients with severe debilitation, but it was not until the 1840s that in the newly emerging field of clinical experimental medicine that thrush — as well as other mycotic conditions, including ringworm — was recognized as being caused by transmissible fungi. In 1923 Christine Marie Berkhout named what we now call Candida albicans, for the white robe, toga candida, worn by Roman senators and senatorial . . .
Experts on Alimentary Tract Cancer
Authors: R. B. Welbourn
Journal: BMJ (1970)

The lack of sequence in the chapters of the book, presumably dictated by their availability and topicality, makes this first vol- ume a series of monographs rather than a comprehensive book, but does not detract from the excellent overall review-well laid out, easily read, adequately illustrated, comprehensive and authoritative-of the in- dividual subjects.This book can be highly recommended, both for libraries and for the practising surgeon and his
The Endothelin System: Evolution of Vertebrate-Specific Ligand-Receptor Interactions by Three Rounds of Genome Duplication
Authors: I. Braasch, J.-N. Volff, M. Schartl
Journal: Molecular Biology and Evolution (2009)

Morphological innovations like the acquisition of the neural crest as well as gene family expansions by genome duplication are considered as major leaps in the evolution of the vertebrate lineage. Using comparative genomic analyses, we have reconstructed the evolutionary history of the endothelin system, a signaling pathway consisting of endothelin ligands and their G protein-coupled receptors. The endothelin system plays a key role in cardiovascular regulation as well as in the development of diverse neural crest derivatives like pigment cells and craniofacial bone structures, which are hot spots of diversity in vertebrates. However, little is known about the origin and evolution of the endothelin system in the vertebrate lineage. We show that the endothelin core system, that is, endothelin ligands (Edn) and their receptors (Ednr), is a vertebrate-specific innovation. The components of the endothelin core system in modern vertebrate genomes date back to single genes that have been duplicated during whole-genome duplication events. After two rounds of genome duplication during early vertebrate evolution, the endothelin system of an ancestral gnathostome consisted of four ligand and four receptor genes. The previously unknown fourth endothelin ligand Edn4 has been kept in teleost fish but lost in tetrapods. Bony vertebrates generally possess three receptor genes, EdnrA, EdnrB1, and EdnrB2. EdnrB2 has been lost secondarily in the mammalian lineage from a chromosome that gave rise to the sex chromosomes in therians (marsupials and placentals). The endothelin system of fishes was further expanded by a fish-specific genome duplication and duplicated edn2, edn3, ednrA, and ednrB1 genes have been retained in teleost fishes. Functional divergence analyses suppose that following each round of genome duplication, coevolution of ligands and their binding regions in the receptors has occurred, adjusting the endothelin signaling system to the increase of possible ligand-receptor interactions. Furthermore, duplications of genes involved in the endothelin system are associated with functional specialization for the development of particular neural crest derivatives. Our results support an important role for newly emerging ligands and receptors as components of signaling pathways and their expansion through genome duplications in the evolution of the vertebrate neural crest.
Vagotomy without Diarrhoea
Authors: D. Johnston, C. S. Humphrey, B. E. Walker, C. N. Pulvertaft, J. C. Goligher
Journal: BMJ (1972)

The incidence of diarrhoea after three types of vagotomy was assessed "blind" at a gastric follow-up clinic one year after operation. Diarrhoea was recorded in 24% of patients after truncal vagotomy and pyloroplasty, in 18% after selective vagotomy and pyloroplasty, but in only 2% of patients after highly selective vagotomy without a drainage procedure. The incidence of diarrhoea was significantly less (P < 0.01) after highly selective vagotomy than after either of the other procedures.Hypertonic glucose solution given by mouth to 15 representative patients from each group and to 15 patients before operation provoked the onset of diarrhoea in 67% of the patients who had undergone truncal vagotomy and pyloroplasty, in 60% of those who had undergone selective vagotomy and pyloroplasty, in 13% of those who had undergone highly selective vagotomy without a drainage procedure, and in none of the preoperative patients. Again the difference between the "highly selective" group and the other two groups of vagotomized patients was statistically significant.It is suggested that postvagotomy diarrhoea is attributable both to unregulated gastric emptying after truncal or selective vagotomy with a drainage procedure and to the extragastric denervation produced by truncal vagotomy. "Postvagotomy" diarrhoea can be virtually eliminated by using highly selective vagotomy without a drainage procedure.
Telomeric damage in early stage of chronic lymphocytic leukemia correlates with shelterin dysregulation
Authors: Adeline Augereau, Claire T'kint de Roodenbeke, Thomas Simonet, Serge Bauwens, Béatrice Horard, Mary Callanan, Dominique Leroux, Laurent Jallades, Gilles Salles, Eric Gilson, Delphine Poncet
Journal: Blood (2011)
Assessing Bias in Studies of Prognostic Factors
Authors: Jill A. Hayden, Danielle A. van der Windt, Jennifer L. Cartwright, Pierre Côté, Claire Bombardier
Journal: Annals of Internal Medicine (2013)

Previous work has identified 6 important areas to consider when evaluating validity and bias in studies of prognostic factors: participation, attrition, prognostic factor measurement, confounding measurement and account, outcome measurement, and analysis and reporting. This article describes the Quality In Prognosis Studies tool, which includes questions related to these areas that can inform judgments of risk of bias in prognostic research. A working group comprising epidemiologists, statisticians, and clinicians developed the tool as they considered prognosis studies of low back pain. Forty-three groups reviewing studies addressing prognosis in other topic areas used the tool and provided feedback. Most reviewers (74%) reported that reaching consensus on judgments was easy. Median completion time per study was 20 minutes; interrater agreement (κ statistic) reported by 9 review teams varied from 0.56 to 0.82 (median, 0.75). Some reviewers reported challenges making judgments across prompting items, which were addressed by providing comprehensive guidance and examples. The refined Quality In Prognosis Studies tool may be useful to assess the risk of bias in studies of prognostic factors.
Fatty Liver of Pregnancy
Authors: David G. Conaster
Journal: JAMA (1975)

To the Editor.—  Cano et al provide in their recent article (231:159, 1975) an excellent description of the course of acute fatty liver of pregnancy. Their experience supports the previous report by Dr. Holzbach ( Obstet Gynecol 43:740, 1974) of the association of acute fatty liver of pregnancy with disseminated intravascular coagulation (DIC).  We must disagree with the implication in the closing paragraph that prompt recognition and treatment of the DIC might improve the prognosis. It is clearly stated in one of the authors' references ( Acta Med Scand , suppl 444, 1966), and by Holzbach, that the only chance for both mother and child is therapeutic cesarean section as early as possible after the onset of acute fatty liver symptoms. If this is done, the DIC will probably resolve spontaneously. Treatment with heparin may improve the prognosis if used in conjunction with expeditious delivery, but as the only treatment, especially in the
FAAP20: a novel ubiquitin-binding FA nuclear core-complex protein required for functional integrity of the FA-BRCA DNA repair pathway
Authors: Abdullah Mahmood Ali, Arun Pradhan, Thiyam Ramsingh Singh, Changhu Du, Jie Li, Kebola Wahengbam, Elke Grassman, Arleen D. Auerbach, Qishen Pang, Amom Ruhikanta Meetei
Journal: Blood (2012)
What's really doing the work here? Knowledge representation or the Higher-Order Thought theory of consciousness?
Authors: Gerard O'Brien, Jonathan Opie
Journal: Behavioral and Brain Sciences (1999)

Dienes &amp; Perner offer us a theory of explicit and implicit knowledge that promises to systematise a large and diverse body of research in cognitive psychology. Their advertised strategy is to unpack this distinction in terms of explicit and implicit representation. But when one digs deeper one finds the “Higher-Order Thought” theory of consciousness doing much of the work. This reduces both the plausibility and usefulness of their account. We think their strategy is broadly correct, but that consensus on the explicit/implicit knowledge distinction is still a fair way off.
Dr Foster patient safety ratings are flawed, confusing, and outdated, trusts say
Authors: Z. Kmietowicz
Journal: BMJ (2009)

<h3>Objective</h3> The course of disease in juvenile idiopathic arthritis (JIA) is unpredictable with episodes of activity and remission. In order to identify predictive factors, 93 SNPs, JIA subtype, age at onset and ANA status were studied in relation to disease course. <h3>Methods</h3> Genetic and clinical parameters were analysed in a cohort of 272 Caucasian patients with persistent oligoarthritis (n=129), extended oligoarthritis (n=57) and rheumatoid factor negative polyarthritis (n=86). Categories of disease course (remitting (n=65), intermediate (n=96) and unremitting (n=111)) were designed based on the cumulative time spent in active disease in the first 2 years. <h3>Results</h3> Univariate analysis revealed association of the course of disease with JIA subtype (p=5.7*10<sup>–5</sup>) and three SNPs; <i>VTCN1</i> rs10 923 223 (p=4.4*10<sup>−5</sup>), <i>VTCN1</i> rs12 046 117 (p=0.017) and <i>CDK6</i> rs42 041 (p=0.038). In a subsequent multivariate ordinal logistic regression analysis, <i>VTCN1</i> rs10 923 223 (OR 0.41, 95%-CI 0.26 to 0.63) and JIA subtype (OR 3.8, 95%-CI 2.0 to 7.2; OR 2.5, 95%-CI 1.4 to 4.2, for extended oligoarthritis and RF-negative polyarthritis vs persistent oligoarthritis, respectively) were the strongest independent factors for course of disease. <h3>Conclusions</h3> This study provides evidence that <i>VTCN1</i>, encoding B7-H4, is associated with course of disease in selected subtypes of JIA. <i>VTCN1</i> might be useful in predicting the course of disease.
1α,25-dihydroxyvitamin D3 modulates Ia antigen expression induced by interferon-γ and prostaglandin E2 production in Pam 212 cells
Authors: M. TANI, A. KOMURA, T. HORIKAWA
Journal: British Journal of Dermatology (1992)

Recent investigations suggest that 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] has an effect on the regulation of immune responses and that keratinocyte (KC) expression of major histocompatibility complex class II antigens may be involved in immune responses. We investigated the modulation by 1 alpha,25(OH)2D3 of Ia antigen expression induced by interferon-gamma (IFN-gamma) and prostaglandin E2 (PGE2) production in Pam 212 cells. 1 alpha,25(OH)2D3 at 10(-6), 10(-8) or 10(-10) M significantly decreased the levels of IFN-gamma-induced Ia antigen expression in Pam 212 cells. Pam 212 cells produced PGE2 and 1 alpha,25-(OH)2D3 enhanced Pam 212 cell PGE2 production. However, indomethacin (1, 5 and 10 micrograms/ml) did not abrogate the inhibitory effect of 1 alpha,25(OH)2D3 on IFN-gamma induction of Ia antigen expression in Pam 212 cells, indicating that the products of the cyclo-oxygenase pathway do not mediate 1 alpha,25(OH)2D3 inhibition of IFN-gamma induction of Pam 212 cell Ia antigen expression. Our studies suggest that in Pam 212 cells the levels of Ia antigen expression induced by IFN-gamma and PGE2 production are negatively and positively regulated by 1 alpha,25(OH)2D3, respectively, and that 1 alpha,25(OH)2D3 may play a role in the regulation of immune responses.
Management is more than pills
Authors: M. Thacker, G L. Moseley, H. Flor
Journal: BMJ (2009)

We have one important caveat in relation to Freynhagen and Bennett’s review—that evidence based non-pharmacological treatment for neuropathic pain was absent.1

Several randomised controlled trials show that graded motor imagery reduces pain and disability in chronic complex regional pain syndrome 1 (CRPS1) and phantom limb pain after amputation or brachial plexus …
TCTAP C-206 Percutaneous Trans-Catheter Coil Embolization for Large Pseudoaneurysm After the Peroneal Artery Puncture for Retrograde Approach to Below-the-Knee Occlusion
Authors: Youhei Yanagita, Tatsuya Nakama, Yoshisato Shibata
Journal: Journal of the American College of Cardiology (2015)
TCTAP A-099 Unique Endoprosthesis Designed to Treat Aorto-Iliac Aneurysms: A Single Centre Early Experience
Authors: Dainis Krievins, Janis Savlovskis, Kaspars Kisis, Marcis Gedins, Natalija Ezite, Artis Knapsis, Kristaps Zarins
Journal: Journal of the American College of Cardiology (2015)