tbuckley/cabot-search huggingface dataset:
Reliability of high-resolution ultrasonography in the assessment of Achilles tendon enthesopathy in seronegative spondyloarthropathies
Authors: E Filippucci, S Z. Aydin, O Karadag, F Salaffi, M Gutierrez, H Direskeneli, W Grassi
Journal: Annals of the Rheumatic Diseases (2009)

The present study was mainly aimed at investigating the interobserver and intraobserver reproducibility of ultrasound (US) results in the assessment of Achilles tendon enthesopathy in patients with seronegative spondyloarthropathies (SpA).A total of 28 patients with a diagnosis of SpA according to the European Spondyloarthropathy Study Group criteria were included. The patient female/male ratio was 1.8 (18/10), mean age was 42 (range 25-75) years and mean disease duration was 9 (range 1-35) years. Mean (SD) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) scores were 32.4 (14.5) and 26.3 (9.2), respectively. Bilateral Achilles tendon US examinations were carried out independently by three investigators using a MyLab70 XVG (Esaote Biomedica, Genoa, Italy), equipped with a broadband 6-18 MHz linear probe. Each Achilles tendon was scanned for assessing the presence/absence of US findings indicative of enthesopathy according to the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) preliminary definition. The same findings were also scored on a 3-grade semiquantitative scoring system on which investigators reached a consensus prior to the study. Total additive scores per Achilles tendon were calculated.Moderate to excellent interobserver and intraobserver agreements were found for most of the US findings indicative of enthesopathy. Similar results were obtained using semiquantitative assessments, with weighted kappa values estimating the interobserver and intraobserver agreements for soft tissue inflammation of 0.696 and 0.816, respectively and for tissue damage 0.711 and 0.901, respectively.US assessment of Achilles tendon enthesopathy in patients with SpA, using the OMERACT preliminary definition, was found to be reliable. Bone irregularity and entheseal hypoechogenicity were the most difficult abnormalities to reach agreement on.
A Cluster of Mutations in the UMOD Gene Causes Familial Juvenile Hyperuricemic Nephropathy with Abnormal Expression of Uromodulin
Authors: Karin Dahan, Olivier Devuyst, Michèle Smaers, Didier Vertommen, Guy Loute, Jean-Michel Poux, Béatrice Viron, Christian Jacquot, Marie-France Gagnadoux, Dominique Chauveau, Mathias Büchler, Pierre Cochat, Jean-Pierre Cosyns, Béatrice Mougenot, Mark H. Rider, Corinne Antignac, Christine Verellen-Dumoulin, Yves Pirson
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Familial juvenile hyperuricemic nephropathy (FJHN [MIM 162000]) is an autosomal-dominant disorder characterized by abnormal tubular handling of urate and late development of chronic interstitial nephritis leading to progressive renal failure. A locus for FJHN was previously identified on chromosome 16p12 close to the MCKD2 locus, which is responsible for a variety of autosomal-dominant medullary cystic kidney disease (MCKD2). UMOD , the gene encoding the Tamm-Horsfall/uromodulin protein, maps within the FJHN/MCKD2 critical region. Mutations in UMOD were recently reported in nine families with FJHN/MCKD2 disease. A mutation in UMOD has been identified in 11 FJHN families (10 missense and one in-frame deletion)—10 of which are novel—clustering in the highly conserved exon 4. The consequences of UMOD mutations on uromodulin expression were investigated in urine samples and renal biopsies from nine patients in four families. There was a markedly increased expression of uromodulin in a cluster of tubule profiles, suggesting an accumulation of the protein in tubular cells. Consistent with this observation, urinary excretion of wild-type uromodulin was significantly decreased. The latter findings were not observed in patients with FJHN without UMOD mutations. In conclusion, this study points to a mutation clustering in exon 4 of UMOD as a major genetic defect in FJHN. Mutations in UMOD may critically affect the function of uromodulin, resulting in abnormal accumulation within tubular cells and reduced urinary excretion. E-mail: Dahan@gmed.ucl.ac.be
Association of OPRM1 and COMT Single-Nucleotide Polymorphisms With Hospital Length of Stay and Treatment of Neonatal Abstinence Syndrome
Authors: Elisha M Wachman, Marie J Hayes, Mark S Brown, Jonathan Paul, Karen Harvey-Wilkes, Norma Terrin, Gordon S Huggins, Jacob V Aranda, Jonathan M Davis
Journal: JAMA (2013)

<h3>Importance</h3>Neonatal abstinence syndrome (NAS) caused by in utero opioid exposure is a growing problem; genetic factors influencing the incidence and severity have not been previously examined. Single-nucleotide polymorphisms (SNPs) in the μ-opioid receptor (OPRM1), multidrug resistance (ABCB1), and catechol-o-methyltransferase (COMT) genes are associated with risk for opioid addiction in adults.<h3>Objective</h3>To determine whether SNPs in the OPRM1, ABCB1, and COMT genes are associated with length of hospital stay and the need for treatment of NAS.<h3>Design, Setting, and Participants</h3>Prospective multicenter cohort study conducted at 5 tertiary care centers and community hospitals in Massachusetts and Maine between July 2011 and July 2012. DNA samples were genotyped for SNPs, and then NAS outcomes were correlated with genotype. Eighty-six of 140 eligible mother-infant dyads were enrolled. Infants were eligible if they were 36 weeks' gestational age or older and exposed to methadone or buprenorphine in utero .<h3>Main Outcomes and Measures</h3>Primary outcome measure was length of hospital stay, with between-group differences expressed as β and calculated with linear regression models. Secondary outcome measures included need for any medical treatment for NAS and treatment with 2 or more medications.<h3>Results</h3>Infants with the OPRM1 118A&gt;G AG/GG genotype had shortened length of stay (β = −8.5 days; 95% CI, −14.9 to −2.1 days; P = .009) and were less likely to receive any treatment than AA infants (48% vs 72%; adjusted odds ratio, 0.76; 95% CI, 0.63-0.96; P = .006). The COMT 158A&gt;G AG/GG genotype was associated with shortened length of stay (β = −10.8 days; 95% CI, −18.2 to −3.4 days; P = .005) and less treatment with 2 or more medications (18% vs 56%; adjusted odds ratio, 0.68; 95% CI, 0.55-0.86; P = .001) than the AA genotype. Associations with the ABCB1 SNPs were not significant.<h3>Conclusions and Relevance</h3>Among infants with NAS, variants in the OPRM1 and COMT genes were associated with a shorter length of hospital stay and less need for treatment. These preliminary findings may provide insight into the mechanisms underlying NAS.
Prevalence of cryptogenic transaminitis in the Leeds coeliac cohort
Authors: A. Sainsbury, T. Fitzgerald, H. Davies, P. D. Howdle, S. M. Everett, J. S. Jennings
Journal: Gut (2011)

<h3>Introduction</h3> Coeliac disease may be associated with a number of liver diseases. These include primary biliary cirrhosis, primary sclerosing cholangitis1 and elevated transaminases.2 We aimed to identify patients with coeliac disease and abnormal liver function tests. <h3>Methods</h3> A database of patients with coeliac disease was established in Leeds in 2001. We retrospectively analysed this database. We searched our coeliac database to identify those with liver function test data. <h3>Results</h3> A total of 537 individuals were recorded on the database. Overall 29% male, 71% female, mean age at diagnosis 43 years (range 0–88 years). Initial duodenal biopsy by Marsh grade: 0 18.9%, I 9.7%, II 31.2%, III 22.5% and IV 17.7%. There was a family history of coeliac disease (1st degree relative) in 12.7%. Selective IgA deficiency occurred in 1.7%. Data on ALT were available in 219 individuals. ALT was elevated in 11.9% (range 40–147 IU/l). 85% of these individuals were female. No association was found with alcohol consumption (mean 2.7 IU/week), weight (mean 67.8 kg), or compliance with a gluten-free diet. One individual had autoimmune thyroid disease, two weakly positive ANA and one was HIV positive. Data on ALP were available in 251 individuals. ALP was elevated in 5.2% (range 304–916 IU/l). Two individuals were ANA positive. No patient underwent liver biopsy. <h3>Conclusion</h3> 11.9% of the population had elevated trasaminases. None of these had impaired liver function or established liver disease. The data is open to bias by the lack of liver histology and incomplete drug histories. Nevertheless, it supports the proposition that coeliac disease can be a potential cause of a cryptogenic transaminitis.
Notch Signaling Contributes to the Expression of Cardiac Markers in Human Circulating Progenitor Cells
Authors: Masamichi Koyanagi, Philipp Bushoven, Masayoshi Iwasaki, Carmen Urbich, Andreas M. Zeiher, Stefanie Dimmeler
Journal: Circulation Research (2007)

It has been demonstrated that adult human circulating endothelial progenitor cells (EPCs) can differentiate to a cardiomyogenic phenotype. Notch signaling promotes epithelial-to-mesenchymal transformation and plays a role in heart and vessel development. Here, we investigated the role of Notch activation for cardiac differentiation of EPCs in a coculture system with neonatal cardiomyocyte. After coculture, Notch activation was transiently detected in EPCs, as determined by immunohistochemical detection of NICD (the intracellular cleavage fragment of Notch-1) and expression of human Notch target genes. Inhibition of gamma-secretase blocked Notch cleavage and NICD translocation. Furthermore, the expression of the cardiac marker protein alpha-sarcomeric actinin and troponin T was significantly suppressed by gamma-secretase inhibition or addition of soluble recombinant Jagged-1, indicating that Notch activation facilitates cardiac marker gene expression. Because noncanonical Wnts have previously been shown to promote cardiac differentiation, we additionally determined the influence of Notch activation on the expression of Wnt5a and Wnt11. Wnt5a and Wnt11 expression in the human cells was induced by the coculture and was blocked by gamma-secretase inhibition. Likewise, stimulation of Notch signaling by immobilized Jagged-1 promoted Wnt5a expression in EPCs. These data suggest that Notch is activated upon coculture of EPCs with neonatal rat cardiac myocytes. Gamma-secretase-dependent Notch activation is required for cardiac gene expression in human cells and induces the expression of noncanonical Wnt proteins, which may act in a paracrine manner to further amplify cardiac differentiation.
Gastrointestinal surgery in old age: issues of equality and quality
Authors: D GWYN SEYMOUR
Journal: Gut (1997)

Many recent developments in gastrointestinal surgery are of particular relevance to older people. They include new methods for the treatment or palliation of carcinoma, an increasing use of laparoscopic techniques (although the benefits of many of the approaches have yet to be proved in randomised controlled trials), and new treatments for non-malignant anal problems such as incontinence and prolapse.1-4 Meanwhile, the role of elective surgery in the field of peptic ulceration continues to decrease because of more effective medical treatments.1 

The majority of research studies in the older surgical patient have confined their attention to the surgical ward, typically correlating the immediate preoperative risk factors with the immediate postoperative outcome.5 6 Although valuable insights can be gained from such studies, they are not considered further in the present review. Rather, it is argued here that we need to take a wider view of the referral and treatment process if our older patients are to benefit from the rapid developments that are occurring in gastrointestinal surgery. The first part of this review therefore considers the process by which older people with a gastrointestinal problem find their way (or fail to find their way) to appropriate surgical treatment. It is here that issues of equality of access and treatment are most likely to arise. The second part of the review argues that we need to improve the way that medical, surgical and anaesthetic services are organised so as to improve overall quality of care. For reasons of space, the biliary tract and pancreas have been excluded from the discussion.

### SHOULD AGE BY ITSELF BE A BAR TO SURGERY?

Simple statistical analyses show an association between increasing age and increasing postoperative mortality.5 6 It is all too easy to conclude that this relation comes about because of loss of physiological reserve associated with the aging process, but it …
GENETIC ANALYSIS OF B CELL ANTIGEN RECEPTOR SIGNALING
Authors: Tomohiro Kurosaki
Journal: Annual Review of Immunology (1999)

In B lymphocytes, a signaling complex that contributes to cell fate decisions is the B cell antigen receptor (BCR). Data from knockout experiments in cell lines and mice have revealed distinct functions for the intracellular protein tyrosine kinases (Lyn, Syk, Btk) in BCR signaling and B cell development. Combinations of intracellular signaling pathways downstream of these PTKs determine the quality and quantity of BCR signaling. For example, concerted actions of the PLC-gamma 2 and PI3-K pathways are required for proper calcium responses. Similarly, the regulation of ERK and JNK responses involves both PLC-gamma 2 and GTPases pathways. Since the immune response in vivo is regulated by alteration of these signaling outcomes, achieving a precise understanding of intracellular molecular events leading to B lymphocyte proliferation, deletion, anergy, receptor editing, and survival still remains a challenge for the future.
The Potential Negative Effect of High‐Dose Glucosamine on the Chondrocyte: Comment on the Article by Caramés et al
Authors: Li‐Bo Jiang, Jian Zhang, Jian Dong
Journal: Arthritis & Rheumatology (2013)

We read with great interest the recent article by Caramés et al, who demonstrated that glucosamine can activate autophagy in human chondrocytes and in mouse knee joints by inhibiting the Akt/FoxO/mammalian target of rapamycin pathway (1). Importantly, the authors proved that intraperitoneal and oral administration of glucosamine induced similar levels of autophagy in the cartilage, thus providing a convenient method for inducing autophagy in vivo in the future. Similarly, another study also demonstrated the inductive effect of glucosamine on autophagy in HeLa and COS-7 cells (2). Glucosamine has been shown to play antiinflammatory, anticatabolic, and antiapoptotic roles in the chondrocyte (3, 4), and in the future autophagy might be identified as a mechanism mediating these effects. However, as mentioned in reports suggesting double roles of autophagy in disease (5), the negative effect of "autophagic cell death" on chondrocytes may need to be elucidated. After treating normal chondrocytes from SD rats with 100 mM glucosamine for 24 hours, we observed that the cytoplasm of cells in monolayer culture was filled with numerous vacuoles (Figure 1). When the incubation time was extended, an increasing number of chondrocytes died, which indicated that glucosamine at high concentrations may lead to autophagic cell death. Although we could not determine whether the cells died due to autophagy, the results suggested that high-dose glucosamine may have a negative effect on cell viability. Photomicrographs obtained by phase-contrast microscopy, showing the morphology of chondrocytes treated with 100 mM glucosamine for 24 hours, at A, lower magnification (100×) and B, higher magnification (400×). In accordance with our observations, De Mattei et al showed that glucosamine at doses of 6.5 mg/ml (∼30 mM) and 25 mg/ml (∼116 mM) decreased cell viability in bovine cartilage explants by 28% and >90%, respectively (6). Moreover, ultrastructural analysis showed that the cells in which death was induced by glucosamine exhibited obvious vacuoles in the cytoplasm (6). In addition, Walsh and colleagues reported that after 4 days and 7 days of exposure to glucosamine at a dose of 4.5 mg/ml (∼20 mM), the DNA content of annulus fibrosus cells was reduced by 75% and 89%, respectively (7). Therefore, it may be imperative to place the emphasis on the concentration when treating chondrocytes with glucosamine. In summary, although an increasing number of studies have suggested that there may be a role for autophagy in the treatment of arthritis, further studies, especially in the human system, are still needed to rule out any negative effects. Supported by the Natural Science Foundation of China (grant 81372002) and the "Technology Innovation Action Plan" Key Project of the Shanghai Science and Technology Commission (grant 12411951300).
Adoptive transfer of T-helper cell type 1 clones attenuates an asthmatic phenotype in mice
Authors: K. Irifune, A. Yokoyama, K. Sakai, A. Watanabe, H. Katayama, H. Ohnishi, H. Hamada, M. Nakajima, N. Kohno, J. Higaki
Journal: European Respiratory Journal (2005)

T-helper cell type 1 (Th1) cells have been postulated to have a significant role in protective immunity against allergic diseases. However, recent studies using polarised Th1 cells showed conflicting effects on both airway responsiveness and eosinophilic inflammation in a mouse asthma model. The current study explored the effects of adoptive transfer of established Th1 clones on a murine model of atopic asthma. Mice (BALB/c) were sensitised with ovalbumin (OVA) and challenged with aerosolised OVA (5%, 20 min) for 5 days. Just before starting the first challenge, Th1 clones (5×10 6 ·body −1 ) or PBS alone were injected via the tail vein. After assessment of airway responsiveness to methacholine, bronchoalveolar lavage fluid (BALF) was obtained. Histological examination, including morphometric analysis, measurement of cytokines in the BALF and Northern blotting of lung chemokines, was also performed. Adoptive transfer of Th1 clones showed a significantly increased total number of cells, whereas significantly decreased eosinophils were found in the BALF, when compared with mice with injection of vehicle alone or splenic mononuclear cells. Administration of Th1 clones significantly decreased the infiltration of eosinophils but increased mononuclear cells in the peribronchial area. Goblet cell hyperplasia and peribronchial fibrosis were also suppressed by Th1 clones. The transfer of Th1 cells significantly decreased airway responsiveness. Th1 injection significantly increased interferon gamma in the BALF, but significantly decreased interleukin (IL)-5 and IL-13. Eotaxin mRNA was predominantly expressed in the lungs of asthma model mice, whereas RANTES (regulated on activation, normal T-cell expressed and secreted) predominates in such mice with Th1 transfer. In conclusion, results suggest that the adoptive transfer of T-helper cell type 1 clones can suppress both lung eosinophilia and airway responsiveness, but increase noneosinophilic inflammation in a mouse model of asthma.
Hematopoietic Prostaglandin D Synthase Suppresses Intestinal Adenomas in<i>Apc</i>Min/+ Mice
Authors: Jae Man Park, Yoshihide Kanaoka, Naomi Eguchi, Kosuke Aritake, Sava Grujic, Alicia M. Materi, Virgilio S. Buslon, Brigette L. Tippin, Alan M. Kwong, Eduardo Salido, Samuel W. French, Yoshihiro Urade, Henry J. Lin
Journal: Cancer Research (2007)

Abstract Aspirin and other nonsteroidal anti-inflammatory drugs prevent some cases of colon cancer by inhibiting prostaglandin (PG) synthesis. PGE2 promotes colon neoplasia, as shown by knockout mouse studies on enzymes and receptors in the PG cascade. A few experiments 20 to 30 years ago suggested that PGD2 may suppress tumors, but a role for biosynthetic enzymes for PGD2 in tumor development has not been studied. We report here that disruption of the gene for hematopoietic PGD synthase in ApcMin/+ mice led to ∼50% more intestinal adenomas compared with controls. Tumor size was not affected. By immunohistochemistry, we detected hematopoietic PGD synthase mainly in macrophages and monocytes of the gut mucosa. The mean number of tumors did not increase with knockout of the gene for the lipocalin type of the enzyme, which is not produced in the intestine. On the other hand, ApcMin/+ mice with transgenic human hematopoietic PGD synthase tended to have 80% fewer intestinal adenomas. The transgene produced high mRNA levels (375-fold over endogenous). There was a suggestion of higher urinary excretion of 11β-PGF2α and a lower excretion of a PGE2 metabolite in transgenic mice, but differences (30–40%) were not statistically significant. The results support an interpretation that hematopoietic PGD synthase controls an inhibitory effect on intestinal tumors. Further studies will be needed to prove possible mechanisms, such as routing of PG production away from protumorigenic PGE2 or inhibition of the nuclear factor-κB cascade by PGD2 metabolites. [Cancer Res 2007;67(3):881–9]
Albuminuria in chronic heart failure: prevalence and prognostic importance
Authors: Colette E Jackson, Scott D Solomon, Hertzel C Gerstein, Sofia Zetterstrand, Bertil Olofsson, Eric L Michelson, Christopher B Granger, Karl Swedberg, Marc A Pfeffer, Salim Yusuf, John JV McMurray
Journal: The Lancet (2009)
Prepared for sudden cardiac arrest? A cross-sectional study of automated external defibrillators in amateur sport
Authors: Owen Cronin, Joseph Jordan, Fionnuala Quigley, Michael G Molloy
Journal: British Journal of Sports Medicine (2013)

Sudden cardiac arrest (SCA) is a rare but tragic part of professional and amateur sport. Following multiple high profile deaths in professional sport over the past two decades, there has been a significant trend towards the widespread availability of automated external defibrillators (AEDs) at amateur sports grounds.To examine the availability of AEDs in amateur sports clubs in Cork, Ireland, and to investigate club practices with respect to the purchase, accessibility, maintenance and use of AEDs.A cross-sectional survey of 218 amateur Gaelic Athletic Association (GAA), soccer and rugby clubs was conducted between July and September 2012. Club committee representatives answered a 22-point questionnaire.126 GAA clubs and 28 soccer and 17 rugby (n=171) clubs were enrolled in this study. A total of 81.3% of amateur clubs own an AED. We estimate an AED-use rate of one AED use for every 54.5 years an AED is available. Almost 50% of club representatives thought the location of their club AED could be improved while 12.9% of clubs admitted to not maintaining their club AED on a regular basis.A large proportion of amateur clubs in Cork City and County own an AED. Many clubs engage in regular maintenance and storage of AEDs. However, this study identifies several areas for improvement in facilitating a secure chain of survival for players in the event of an SCA.