tbuckley/cabot-search huggingface dataset:
Stage-specific binding of Leishmania donovani to the sand fly vector midgut is regulated by conformational changes in the abundant surface lipophosphoglycan.
Authors: D L Sacks, P F Pimenta, M J McConville, P Schneider, S J Turco
Journal: The Journal of Experimental Medicine (1995)

The life cycle of Leishmania parasites within the sand fly vector includes the development of extracellular promastigotes from a noninfective, procyclic stage into an infective, metacyclic stage that is uniquely adapted for transmission by the fly and survival in the vertebrate host. These adaptations were explored in the context of the structure and function of the abundant surface lipophosphoglycan (LPG) on Leishmania donovani promastigotes. During metacyclogenesis, the salient structural feature of L. donovani LPG is conserved, involving expression of a phosphoglycan chain made up of unsubstituted disaccharide-phosphate repeats. Two important developmental modifications were also observed. First, the size of the molecule is substantially increased because of a twofold increase in the number of phosphorylated disaccharide repeat units expressed. Second, there is a concomitant decrease in the presentation of terminally exposed sugars. This later property was indicated by the reduced accessibility of terminal galactose residues to galactose oxidase and the loss of binding by the lectins, peanut agglutinin, and concanavalin A, to metacyclic LPG in vivo and in vitro. The loss of lectin binding was not due to downregulation of the capping oligosaccharides as the same beta-linked galactose or alpha-linked mannose-terminating oligosaccharides were present in both procyclic and metacyclic promastigotes. The capping sugars on procyclic LPG were found to mediate procyclic attachment to the sand fly midgut, whereas these same sugars on metacyclic LPG failed to mediate metacyclic binding. And whereas intact metacyclic LPG did not inhibit procyclic attachment, depolymerized LPG inhibited as well as procyclic LPG, demonstrating that the ligands are normally buried. The masking of the terminal sugars is attributed to folding and clustering of the extended phosphoglycan chains, which form densely distributed particulate structures visible on fracture-flip preparations of the metacyclic surface. The exposure and subsequent masking of the terminal capping sugars explains the stage specificity of promastigote attachment to and release from the vector midgut, which are key events in the development of transmissible infections in the fly.
Swollen Elbow Following Trauma
Authors: Robert D. Hunter
Journal: JAMA (1974)

<h3>History</h3> A WOMAN was seen in the emergency room following a fall. She complained of pain in the elbow. Examination demonstrated swelling of the elbow with a decreased range of motion. Roentgenograms were obtained (Fig 1 and 2). <h3>Diagnosis</h3> Fracture of the elbow with positive fat pad sign. <h3>Comment</h3> The lateral roentgenogram of the elbow (Fig 1) shows two soft-tissue curvilinear radiolucencies, one projecting anterior to and the other posterior to the distal area of the humerus just above the elbow joint. Neither the anteroposterior nor the lateral view shows a fracture. The lucent shadows represent the fat pads overlying the distal area of the humerus, displaced by fluid in the elbow joint. Fat pads are often seen on the lateral roentgenogram of the flexed elbow in a patient who has had recent trauma, and are generally associated with a fracture. In most cases, the fracture is apparent radiographically, and
T cell epitopes of prothrombin in patients with antiphospholipid syndrome
Authors: K Yoshida
Journal: Annals of the Rheumatic Diseases (2003)

Antiphospholipid syndrome (APS) is characterised by arterial and/or venous thrombosis and recurrent fetal loss in association with the presence of antiphospholipid antibodies (aPL). In addition to β2-glycoprotein I, prothrombin (PT) is an important autoantigen recognised by aPL. PT is a coagulation proenzyme abundantly present in blood (70–100 μg/ml), and binds to negatively charged phospholipids such as phosphatidylserine. PT comprises two major domains, fragment-1 (F-1) and prethrombin-1 (Pre-1). We previously reported that antiprothrombin antibody (aPT) is a mixture of antibodies against both F-1 and Pre-1, and that there are significant clinical differences between anti-F-1 and anti-Pre-1.1,2

aPL, including aPT, are not mere serological markers of the disease, but are important players in the pathogenesis of APS. Therefore, antigen-specific immunosuppressive treatments, if developed, will help to prevent …
The Effect of Selective Cyclooxygenase-2 Inhibition in Barrett's Esophagus Epithelium: An In Vitro Study
Authors: Navtej S. Buttar, Kenneth K. Wang, Marlys A. Anderson, Ross A. Dierkhising, Rodney J. Pacifico, Krishnawatie K. Krishnadath, Lori S. Lutzke
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Individuals with Barrett's esophagus, in which the normal squamous esophageal epithelium is replaced with a columnar mucosa, are at increased risk for esophageal adenocarcinoma. Mucosal injury may be involved in the progression to neoplasia via the synthesis of prostaglandins and other mediators of inflammation. Cyclooxygenase (COX)-2 is the rate-limiting enzyme involved in prostaglandin synthesis. We examined the effect of inhibiting COX-2 activity in Barrett's esophageal cells. Methods: Primary esophageal epithelial and fibroblast cell cultures were established from endoscopic biopsy specimens from 20 consecutive patients with Barrett's esophagus. COX-2 expression and activity were determined on pooled cell cultures by reverse transcription–polymerase chain reaction and prostaglandin E2 (PGE2) enzyme immunoassay, respectively. Proliferation was measured by Ki-67 staining. PGE2 levels were determined in supernatants from epithelial cells treated with the selective COX-2 inhibitor NS-398, proinflammatory cytokines (interleukin 1β and tumor necrosis factor-α), and conditioned medium from fibroblast cultures (both unstimulated and stimulated with proinflammatory cytokines). Results: Esophageal epithelial cells and fibroblasts expressed COX-2 messenger RNA. Compared with control-treated cells, NS-398 decreased proliferation of Barrett's esophageal epithelial cells by 55% (95% confidence interval = 47.1% to 63.8%; P<.001) and decreased COX-2 activity. The addition of exogenous PGE2 reversed the antiproliferative effect of NS-398 on Barrett's esophageal epithelial cells. Proinflammatory cytokines did not affect COX-2 activity in esophageal epithelial cells but stimulated COX-2 activity in fibroblasts. However, conditioned medium from unstimulated and stimulated fibroblasts increased COX-2 activity in esophageal epithelial cells. Conclusion: COX-2 is functionally active in Barrett's esophagus because treatment with the COX-2 inhibitor hinders proliferation of Barrett's esophageal epithelial cells in culture, but proliferation is restored by treatment with prostaglandin. These results raise the possibility that inhibition of COX-2 may have chemopreventive potential for Barrett's esophagus.
Validation of a Counseling Strategy to Promote the Adoption and the Maintenance of Physical Activity by Type 2 Diabetic Subjects
Authors: Chiara Di Loreto, Carmine Fanelli, Paola Lucidi, Giuseppe Murdolo, Arianna De Cicco, Natascia Parlanti, Fausto Santeusanio, Paolo Brunetti, Pierpaolo De Feo
Journal: Diabetes Care (2003)

OBJECTIVE—There is enough evidence that physical activity is an effective therapeutic tool in the management of type 2 diabetes. The present study was designed to validate a counseling strategy that could be used by physicians in their daily outpatient practice to promote the adoption and maintenance of physical activity by type 2 diabetic subjects. RESEARCH DESIGN AND METHODS—The long-term (2-year) efficacy of the behavioral approach (n = 182) was compared with usual care treatment (n = 158) in two matched, randomized groups of patients with type 2 diabetes who had been referred to our Outpatient Diabetes Center. The outcome of the intervention was consistent patient achievement of an energy expenditure of &amp;gt;10 metabolic equivalents (METs)-h/week through voluntary physical activity. RESULTS—After 2 years, 69% of the patients in the intervention group (27.1 ± 2.0 METs × h/week) and 18% of the control group (4.1 ± 0.8 METs × h/week) achieved the target (P &amp;lt; 0.001) with significant (P &amp;lt; 0.001) improvements in BMI (intervention group 28.9 ± 0.2 versus control group 30.4 ± 0.3 kg/m2) and HbA1c (intervention group 7.0 ± 0.1 versus control group 7.6 ± 0.1%). CONCLUSIONS—This randomized, controlled study shows that physicians can motivate most patients with type 2 diabetes to exercise long-term and emphasizes the value of individual behavioral approaches in daily practice.
Impaired plasmacytoid dendritic cell maturation and differential chemotaxis in chronic hepatitis C virus: associations with antiviral treatment outcomes
Authors: J A Mengshol, L Golden-Mason, N Castelblanco, K A Im, S M Dillon, C C Wilson, H R Rosen
Journal: Gut (2009)

<h3>Background:</h3> Dendritic cell (DC) defects may contribute to chronicity in hepatitis C virus (HCV) infection and determine response to PEG–interferon and ribavirin therapy via poor T cell stimulation. Studies to date have produced inconsistent results regarding DC maturation and function: no large study has examined DCs before and after therapy. <h3>Aims:</h3> We examined if DC defects in maturation and chemotaxis are present by comparing therapeutic responders to non-responders. <h3>Methods:</h3> We analysed peripheral DCs of 64 HCV genotype 1-infected patients from the Virahep-C study 2 weeks before and 24 weeks after therapy. We used flow cytometry to enumerate plasmacytoid DC (pDC) and myeloid DCs (mDC) and quantify expression of chemokine receptors and maturation markers. Chemotaxis was measured with an in vitro assay. <h3>Results:</h3> Pre-treatment frequencies of pDCs and mDCs were significantly lower in HCV patients than controls and successful therapy normalised pDCs. Levels of CXCR3 and CXCR4 on pDCs were higher at baseline compared to normal controls and decreased with therapy. Pre-therapy levels of co-stimulatory marker CD40 and the maturation marker CD83 were higher in pDCs of patients chronically infected with HCV compared to normal patients, and levels of both markers dropped significantly with therapy in the SVR+ group only. Other maturation markers (CD86 and CCR7) were not elevated suggesting a partially activated phenotype. Baseline chemotaxis of pDCs to CXCL12 and CXCL10 predicted failure of antiviral response and correlated with the histological activity index inflammation score. <h3>Conclusions:</h3> Plasmacytoid DC defects exist in chronic HCV and successful antiviral therapy normalises many phenotypic and functional abnormalities.
Novel mutation of connexin 31 causing erythrokeratoderma variabilis
Authors: L. Feldmeyer, L. Plantard, B. Mevorah, M. Huber, D. Hohl
Journal: British Journal of Dermatology (2005)

Journal Article Novel mutation of connexin 31 causing erythrokeratoderma variabilis Get access L. Feldmeyer, L. Feldmeyer Institute of Cell Biology, ETH Zürich, SwitzerlandDermatogenetic Unit and Laboratory for Cutaneous Biology, Department of Dermatology, University Hospital, Lausanne, Switzerland Search for other works by this author on: Oxford Academic Google Scholar L. Plantard, L. Plantard Dermatogenetic Unit and Laboratory for Cutaneous Biology, Department of Dermatology, University Hospital, Lausanne, Switzerland Search for other works by this author on: Oxford Academic Google Scholar B. Mevorah, B. Mevorah Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel Search for other works by this author on: Oxford Academic Google Scholar M. Huber, M. Huber Dermatogenetic Unit and Laboratory for Cutaneous Biology, Department of Dermatology, University Hospital, Lausanne, Switzerland Search for other works by this author on: Oxford Academic Google Scholar D. Hohl D. Hohl Institute of Cell Biology, ETH Zürich, SwitzerlandDermatogenetic Unit and Laboratory for Cutaneous Biology, Department of Dermatology, University Hospital, Lausanne, Switzerland Daniel Hohl. E‐mail: daniel.hohl@chuv.hospvd.ch Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 5, 1 May 2005, Pages 1072–1074, https://doi.org/10.1111/j.1365-2133.2005.06561.x Published: 01 May 2005
Serum YKL-40 is a marker of prognosis and disease status in high-grade gliomas
Authors: F. M. Iwamoto, A. F. Hottinger, S. Karimi, E. Riedel, J. Dantis, M. Jahdi, K. S. Panageas, A. B. Lassman, L. E. Abrey, M. Fleisher, L. M. DeAngelis, E. C. Holland, A. Hormigo
Journal: Neuro-Oncology (2011)

The objective of this study was to evaluate whether longitudinal levels of serum YKL-40 correlate with disease status or survival in adults with gliomas. Patients with histologically confirmed gliomas were eligible for this longitudinal study. Serum samples were collected prospectively and concurrently with MRI scans at multiple time points during the course of the disease. YKL-40 levels determined by ELISA were correlated with radiographic disease status and survival. We performed a multivariate survival analysis including well-known prognostic factors such as age, performance status, and extent of surgical resection. Three hundred and forty-three patients with gliomas (41 low-grade, 105 anaplastic, and 197 glioblastoma) were accrued. Two-year survival from registration was 29% for glioblastomas, 62% for anaplastic gliomas, and 83% for low-grade gliomas. A total of 1740 serum samples were collected, and 95.6% of samples had matching MRI scans. Serum YKL-40 level was significantly lower in patients with no radiographic disease compared with patients with radiographic disease in both the anaplastic glioma (P= .0008) and the glioblastoma (P= .0006) cohorts. Serum levels of YKL-40 in patients with low-grade gliomas were not associated with radiographic disease status. Increases in YKL-40 were independently associated with worse survival in anaplastic gliomas (hazard ratio [HR] = 1.4, P= .01) and glioblastomas (HR = 1.4, P< .0001). Longitudinal increases in serum YKL-40 are associated with increased risk of death in patients with glioblastomas and anaplastic gliomas. YKL-40 is also a putative indicator of disease status in these patients.
Calcineurin mediates human tumor necrosis factor alpha gene induction in stimulated T and B cells.
Authors: A E Goldfeld, E Tsai, R Kincaid, P J Belshaw, S L Schrieber, J L Strominger, A Rao
Journal: The Journal of Experimental Medicine (1994)

The tumor necrosis factor alpha (TNF-alpha) gene is rapidly transcribed in activated T cells via a calcium-dependent pathway that does not require de novo protein synthesis, but is completely blocked by the immunosuppressive drugs cyclosporin A (CsA) and FK506. Here we show that calcineurin phosphatase activity is both necessary and sufficient for TNF-alpha gene transcription in T cells, and identify the factor that binds to the kappa 3 element of the TNF-alpha gene promoter as the target for calcineurin action. The ability of analogues of CsA and FK506 to block calcineurin phosphatase activity correlates completely with their ability to inhibit induction of TNF-alpha mRNA, induction of a TNF-alpha promoter reporter plasmid in transiently transfected T cells, and induction of the kappa 3 binding factor in an electrophoretic mobility shift assay. Moreover, a cDNA encoding the constitutively active form of calcineurin is sufficient to activate the TNF-alpha promoter and the kappa 3 element. TNF-alpha gene transcription is also highly inducible, CsA-sensitive, and protein synthesis-independent in B cells stimulated through their surface immunoglobulin receptors. Using the panel of CsA and FK506 analogues, we show that calcineurin participates in the induction of TNF-alpha transcription in activated B cells. These results extend our previous demonstration that the kappa 3 binding factor is related to NFATp, the preexisting subunit of nuclear factor of activated T cells, and suggest that calcineurin-mediated modification of the kappa 3 binding factor in T cells is of key importance in the induction of TNF-alpha transcription.
Acupuncture for the Treatment of Cocaine Addiction
Authors: Arthur Margolin, Herbert D. Kleber, S. Kelly Avants, Janet Konefal, Frank Gawin, Elena Stark, James Sorensen, Eleanor Midkiff, Elizabeth Wells, T. Ron Jackson, Milton Bullock, Patricia D. Culliton, Sharon Boles, Roger Vaughan
Journal: JAMA (2002)

Auricular acupuncture is widely used to treat cocaine addiction in the United States and Europe. However, evidence from controlled studies regarding this treatment's effectiveness has been inconsistent.To investigate the effectiveness of auricular acupuncture as a treatment for cocaine addiction.Randomized, controlled, single-blind clinical trial conducted from November 1996 to April 1999.Six community-based clinics in the United States: 3 hospital-affiliated clinics and 3 methadone maintenance programs.Six hundred twenty cocaine-dependent adult patients (mean age, 38.8 years; 69.2% men); 412 used cocaine only and 208 used both opiates and cocaine and were receiving methadone maintenance.Patients were randomly assigned to receive auricular acupuncture (n = 222), a needle-insertion control condition (n = 203), or a relaxation control condition (n = 195). Treatments were offered 5 times weekly for 8 weeks. Concurrent drug counseling was also offered to patients in all conditions.Cocaine use during treatment and at the 3- and 6-month postrandomization follow-up based on urine toxicology screens; retention in treatment.Intent-to-treat analysis of urine samples showed a significant overall reduction in cocaine use (odds ratio, 1.40; 95% confidence interval, 1.11-1.74; P =.002) but no differences by treatment condition (P =.90 for acupuncture vs both control conditions). There were also no differences between the conditions in treatment retention (44%-46% for the full 8 weeks). Counseling sessions in all 3 conditions were poorly attended.Within the clinical context of this study, acupuncture was not more effective than a needle insertion or relaxation control in reducing cocaine use. Our study does not support the use of acupuncture as a stand-alone treatment for cocaine addiction or in contexts in which patients receive only minimal concurrent psychosocial treatment. Research will be needed to examine acupuncture's contribution to addiction treatment when provided in an ancillary role.
Independent Effects of Systemic and Peritoneal Inflammation on Peritoneal Dialysis Survival
Authors: Mark Lambie, James Chess, Kieron L. Donovan, Yong Lim Kim, Jun Young Do, Hi Bahl Lee, Hyunjin Noh, Paul F. Williams, Andrew J. Williams, Sara Davison, Marc Dorval, Angela Summers, John D. Williams, John Bankart, Simon J. Davies, Nicholas Topley
Journal: Journal of the American Society of Nephrology (2013)

Systemic inflammation, as evidenced by elevated inflammatory cytokines, is a feature of advanced renal failure and predicts worse survival. Dialysate IL-6 concentrations associate with variability in peritoneal small solute transport rate (PSTR), which has also been linked to patient survival. Here, we determined the link between systemic and intraperitoneal inflammation with regards to peritoneal membrane function and patient survival as part of the Global Fluid Study, a multinational, multicenter, prospective, combined incident and prevalent cohort study (n=959 patients) with up to 8 years of follow-up. Data collected included patient demographic characteristics, comorbidity, modality, dialysis prescription, and peritoneal membrane function. Dialysate and plasma cytokines were measured by electrochemiluminescence. A total of 426 survival endpoints occurred in 559 incident and 358 prevalent patients from 10 centers in Korea, Canada, and the United Kingdom. On patient entry to the study, systemic and intraperitoneal cytokine networks were dissociated, with evidence of local cytokine production within the peritoneum. After adjustment for multiple covariates, systemic inflammation was associated with age and comorbidity and independently predicted patient survival in both incident and prevalent cohorts. In contrast, intraperitoneal inflammation was the most important determinant of PSTR but did not affect survival. In prevalent patients, the relationship between local inflammation and membrane function persisted but did not account for an increased mortality associated with faster PSTR. These data suggest that systemic and local intraperitoneal inflammation reflect distinct processes and consequences in patients treated with peritoneal dialysis, so their prevention may require different therapeutic approaches; the significance of intraperitoneal inflammation requires further elucidation.
Patient satisfaction with nursing consultations in a rheumatology outpatient clinic: a 21-month randomised controlled trial in patients with inflammatory arthritides
Authors: Hege Svean Koksvik, Kåre Birger Hagen, Erik Rødevand, Petter Mowinckel, Tore K Kvien, Heidi A Zangi
Journal: Annals of the Rheumatic Diseases (2013)

To study the effect of individual nursing consultations in patients treated with disease-modifying antirheumatic drugs (DMARDs) in a rheumatology outpatient setting.Patients with inflammatory arthritides (IA) who had started with a DMARD regimen 3 months before were randomised to two different follow-up consultation systems: either follow-up by a clinical nurse specialist (CNS) or by a medical doctor (MD) in rheumatology 3, 9 and 21 months after randomisation. The primary outcome was patient satisfaction measured by Leeds Satisfaction Questionnaire (LSQ). Secondary outcomes included coping, disease activity, pain, fatigue, patient's global assessment of disease activity and health related quality of life. Effects at 9 and 21 months were estimated by Least Square means calculated from the final mixed model.Of 68 patients randomised, 65 patients completed assessments at 21 months. Statistically significant improvements in favour of the CNS group were found in all LSQ subscales (all p values<0.001) and in overall satisfaction at 9 months (adjusted mean between-group difference 0.74, 95% CI -0.96 to -0.52) and at 21 months (-0.69, 96% CI -0.87 to -0.50). Disease activity Score 28 joint count (DAS-28) was improved from baseline to 9 months in both groups and improvement was maintained at 21 months, but without any group difference. No statistically significant between-group differences were found in any of the other secondary outcomes.Patients with IA are likely to benefit from nurse consultations in terms of increased satisfaction with care compared with MD consultations and without loss of efficacy in terms of clinical outcomes. The study is registered as a clinical trial at the ClinicalTrials.gov (NCT00403676).