tbuckley/cabot-search huggingface dataset:
Demonstration and identification of monoclonal proteins in the urine of patients with Sjogren's syndrome.
Authors: H.M Moutsopoulos, R Costello, A.A Drosos, A.K Mavridis, N.M Papadopoulos
Journal: Annals of the Rheumatic Diseases (1985)

Fresh sera and concentrated urine from 17 patients with primary Sjögren's syndrome (SS) were fractionated by high-resolution agarose electrophoresis to investigate the presence of monoclonal immunoglobulins or their components. Homogeneous protein bands were found in the gamma-globulin region in 47% of serum samples and 76% of urine specimens of all patients tested. These monoclonal proteins were detected more often in patients with extraglandular SS (77% in serum, 100% in the urine) than in patients with glandular SS (14% in serum, 43% in the urine). Immunofixation electrophoresis showed that the majority of these monoclonal proteins were free kappa or lambda light chains. Fractionation of unconcentrated parotid salivas from five SS patients failed to reveal the presence of monoclonal light chains or immunoglobulins. The present findings further substantiate our previous observation that a monoclonal process coexists with the polyclonal activation in SS patients.
Randomised placebo controlled multicentre trial to assess short term clarithromycin for patients with stable coronary heart disease: CLARICOR trial
Authors: Christian M Jespersen, Bodil Als-Nielsen, Morten Damgaard, Jørgen Fischer Hansen, Stig Hansen, Olav H Helø, Per Hildebrandt, Jørgen Hilden, Gorm B Jensen, Jens Kastrup, Hans Jørn Kolmos, Erik Kjøller, Inga Lind, Henrik Nielsen, Lars Petersen, Christian Gluud
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To determine if the macrolide clarithromycin affects mortality and cardiovascular morbidity in patients with stable coronary heart disease. <b>Design</b> Centrally randomised multicentre trial. All parties at all stages were blinded. Analyses were by intention to treat. <b>Setting</b> Five Copenhagen University cardiology departments and a coordinating centre. <b>Participants</b> 13 702 patients aged 18 to 85 years who had a discharge diagnosis of myocardial infarction or angina pectoris in 1993–9 and alive in August 1999 were invited by letter; 4373 were randomised. <b>Interventions</b> Two weeks9 treatment with clarithromycin 500 mg/day or matching placebo. <b>Main outcome measures</b> Primary outcome: composite of all cause mortality, myocardial infarction, or unstable angina pectoris during three years9 follow-up. Secondary outcome: composite of cardiovascular mortality, myocardial infarction, or unstable angina pectoris. The outcomes were obtained from Danish registers and were blindly assessed by the event committee. <b>Results</b> 2172 participants were randomised to clarithromycin and 2201 to placebo. We found no significant effects of clarithromycin on the primary outcome (hazard ratio 1.15, 95% confidence interval 0.99 to 1.34) or secondary outcome (1.17, 0.98 to 1.40). Mortality was significantly higher in the clarithromycin arm (1.27, 1.03 to 1.54; P = 0.03) as a result of significantly higher cardiovascular mortality (1.45, 1.09 to 1.92; P = 0.01). <b>Conclusions</b> Short term clarithromycin in patients with stable coronary heart disease may cause significantly higher cardiovascular mortality. The long term safety of clarithromycin in patients with stable ischaemic heart disease should be examined. <b>Trial registration</b>ClinicalTrials.govNCT00121550.
Molecular Pathways: Human Leukocyte Antigen G (HLA-G)
Authors: Giuseppe Curigliano, Carmen Criscitiello, Lucia Gelao, Aron Goldhirsch
Journal: Clinical Cancer Research (2013)

Human leukocyte antigen G (HLA-G) is a nonclassical MHC class I molecule that exerts important tolerogenic functions. Its main physiologic expression occurs in the placenta, where it participates in the maternal tolerance toward the fetus. HLA-G expression was found in embryonic tissues, in adult immune privileged organs, and in cells of the hematopoietic lineage. It is expressed in various types of primary solid (melanoma, head and neck, lung, urogenital, gastrointestinal, and breast cancers) and hematologic malignancies (acute leukemia, lymphomas) and metastases. HLA-G ectopic expression is observed in cancer, suggesting that its expression is one strategy used by tumor cells to escape immune surveillance. In this review, we will focus on HLA-G expression in cancers and its association with the prognosis. We will highlight the underlying molecular mechanisms of impaired HLA-G expression, the immune tolerant function of HLA-G in tumors, and the potential diagnostic use of membrane-bound and soluble HLA-G as a biomarker to identify tumors and to monitor disease stage. As HLA-G is a potent immunoinhibitory molecule, its blockade remains an attractive therapeutic strategy against cancer. Elimination of HLA-G-expressing cancer cells would be important in the efficacy of anticancer therapies.
THE METHOD OF SPREAD OF GAS GANGRENE INTO LIVING MUSCLE
Authors: J. W. McNee, J. S. Dunn
Journal: BMJ (1917)

Ttis contribution to the pathology of gas gangrene deals primarily with the method of spread of the acute disease into living muscle.In our experience gas gangrene is essentially a muscle disease, and we have never seen it conmmence wlhere injury of muscle could be excluded.The somewhat rare cases of "metastatic" gas gangrene, sucl as those described by MIullally and McNee,l Kenneth Taylor,' etc., come into the same category, the primary focus in every instance being in damaged muscular tissue.No example of gas gangrene beginning in, and remaining localized to, the subeutaneous tissut lhas been met witlh, and a condlition spreading below the skin whiclh is met witlh in base lhospitals would appear to merit some special investigation-before a relationship to the general type of gas gangrene can be estab-FI lished...
Is No Evidence of Disease Activity a Realistic Goal for Patients With Multiple Sclerosis?
Authors: Jaime Imitola, Michael K. Racke
Journal: JAMA Neurology (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
The Wnt Target Jagged-1 Mediates the Activation of Notch Signaling by Progastrin in Human Colorectal Cancer Cells
Authors: Julie Pannequin, Caroline Bonnans, Nathalie Delaunay, Joanne Ryan, Jean-François Bourgaux, Dominique Joubert, Frédéric Hollande
Journal: Cancer Research (2009)

Abstract The Wnt and Notch signaling pathways are both abnormally activated in colorectal cancer (CRC). We recently showed that progastrin depletion inhibited Wnt signaling and increased goblet cell differentiation of CRC cells. Here, we show that progastrin down-regulation restores the expression by CRC cells of the early secretory lineage marker Math-1/Hath-1 due to an inhibition of Notch signaling. This effect is mediated by a decreased transcription of the Notch ligand Jagged-1, downstream of β-catenin/Tcf-4. Accordingly, recombinant progastrin sequentially activated the transcription of Wnt and Notch target genes in progastrin-depleted cells. In addition, restoration of Jagged-1 levels in these cells is sufficient to activate Tcf-4 activity, demonstrating the occurrence of a feedback regulation from Notch toward Wnt signaling. These results suggest that progastrin could be instrumental in maintaining the concomitant activation of Wnt and Notch pathways in CRC cells, further highlighting the interest of progastrin targeting for the clinical management of CRC. [Cancer Res 2009;69(15):6065–73]
THE IMMUNOGENICITY OF DINITROPHENYL AMINO ACIDS
Authors: J. R. Frey, A. L. de Weck, H. Geleick, W. Lergier
Journal: The Journal of Experimental Medicine (1969)

Numerous dinitrophenyl amino acid preparations injected intradermally induced contact hypersensitivity to dinitrochlorobenzene, delayed type skin reactions to DNP-amino acids, and anti-DNP antibodies in guinea pigs. Some DNP-amino adds induced precipitating anti-DNP antibodies in rabbits as well. Some of the DNP-ammo acids studied were regularly immunogenic, possible immunogenic impurities having been excluded by extensive purification procedures. Others were either constantly nonimmunogenic or irregularly immunogenic, e.g., their immunogenicity varying from one preparation lot to another. By means of extensive chemical analyses and the establishment of dose-response curves, we were able to demonstrate in most cases that the immunogenicity was not due to contamination with unreacted dinitrofluorobenzene or other DNP derivatives, to photodecomposition or other degradation products, or to DNP-protein contaminants. Nevertheless, the irregular immunogenicity of several DNP-amino acid preparations can only be explained by a highly immunogenic impurity (or impurities) which we were unable to detect analytically. The regular immunogenicity of some other DNP-amino acids (e.g. di-DNP-L-histidine) appears to be based on a "transconjugation" phenomenon, the DNP group being able to split off from its amino acid carrier and to conjugate secondarily with proteins in vivo and in vitro. Accordingly, the interpretation of some recent data concerning the immunogenicity of low molecular weight hapten-amino acids may have to be reevaluated.
Pregnancy, Delivery, and Neonatal Complications in a Population Cohort of Women With Schizophrenia and Major Affective Disorders
Authors: Assen V. Jablensky, Vera Morgan, Stephen R. Zubrick, Carol Bower, Li-Anne Yellachich
Journal: American Journal of Psychiatry (2004)

This study ascertained the incidence of complications during pregnancy, labor, and delivery and the neonatal characteristics of infants born to women with schizophrenia, bipolar disorder, or major depression in a population-based cohort.
PWE-091 Monitoring faecal occult blood test positivity in the NHS bowel cancer screening programme
Authors: C Burtonwood, P Butler, M Young, S Halloran
Journal: Gut (2012)

<h3>Introduction</h3> The guaiac-based faecal occult blood test (gFOBt) used by the NHS Bowel Cancer Screening Programme relies on subjective visual assessment of colour change to determine positivity. The Southern Hub, one of five Programme Hubs in England, serves a total population of about 14.4 million people and handles about one million gFOBt kits every year. <h3>Methods</h3> Test kit readers are tested for colour blindness and visual acuity before structured training and a period of supervision. Consistent test positivity within predefined limits is a quality measure of test kit readers and their performance is subject to weekly scrutiny. The percentage of positive test spots (six per test kit) is recorded weekly for every reader who completes &gt;100 kits. The acceptable spot positivity range has been fixed at between 1.0% and 4.0%, based on an approximation of ±2 SDs from the mean percentage positivity for all Hub staff over a rolling 6-month time period. <h3>Results</h3> Screening Hubs have noticed characteristic positivity patterns among readers and this reflects the subjective nature of the measurement system. The data challenge Hubs to investigate idiosyncratic test kit reading habits of staff, to modify behaviour as indicated and monitor anticipated improvements in reading performance. The screening algorithm adopted in England results in approximately 85% of screen-positive participants completing two or three test kits. While this minimises the impact of individual readers, it adds complexity to the analysis of reader positivity. Repeat kits have a higher positivity and can bias reader weekly mean positivity rates. For all readers with high weekly positivity the proportion of second and third kits read forms part of the weekly assessment. <h3>Conclusion</h3> The Southern Hub has monitored reader positivity since August 2010 and the results are encouraging, with a reduction in reader imprecision and outliers. Initially, there was some resistance to monitoring positivity rates and the fear of being an outlier has the potential to lead staff to inappropriately modify their kit reading behaviour. New staff attend training sessions to learn about the concept of reader positivity and the interventions that may be put in place if their positivity falls outside the acceptable range. The process has now been widely accepted and the number of occasions that positivity falls outside this range per month is used as a key performance indicator. <h3>Competing interests</h3> None declared.
Development of Laparoscopic Surgery and Training Facilities in Europe: Results of a Survey of the European Society of Uro-Technology (ESUT)
Authors: M.P. Laguna, L.C. Schreuders, J.J. Rassweiler, C.C. Abbou, R. van Velthoven, G. Janetschek, G. Breda, J.J.M.C.H. de la Rosette
Journal: European Urology (2004)
IL-5 and IL-13 are predictors of asthma remission; results from a birth cohort
Authors: Daniel Neville, Vereesh Patil, Laurie Lau, Ramesh Kurukulaaratchy, Hasan Arshad
Journal: European Respiratory Journal (2013)

Background:  Cross-sectional studies have identified the local cytokine response in asthma leans towards a Th-2 bias. However little is understood about differences in the peripheral inflammatory response between persistent childhood asthmatics and those that go into adolescent remission. This study investigated; 1) Changes in cytokine profiles in a whole population birth cohort, 2) The differences in cytokine levels between persistent asthmatics and remission asthmatics, 3) Whether there is a peripheral predictor of asthmatic remission.  Methods:  A whole population birth cohort was established on the Isle of Wight in 1989. At 10 and 18 years of age participants had blood samples taken and answered ISAAC questionnaires to assess their symptoms. At age 18, participants were defined as either ‘persistent asthmatics’ (asthma diagnosed at both 10 and 18 years), or ‘remission asthmatics’ (asthma only diagnosed at 10 years). IL-5 and IL-13 levels were measured in the serum samples taken at both 10 and 18 years.  Results:  Cytokine levels were measured in 282 participants from samples taken at age 10. Of these 282, 11 were defined as persistent asthmatics and 7 as remission asthmatics. At 10 years of age it was found that IL-5 (p=0.02) and IL-13 (p=0.05) levels were significantly higher in persistent asthmatics compared to remission asthmatics.  Conclusion:  This study has brought much needed understanding to spontaneous asthma remission. At 10 years of age cytokines IL-5 and IL-13 are significantly higher in the serum of those children that will have persistent asthma compared to those that will go into remission. These cytokine levels can predict which asthmatic children will ‘grow out’ of their asthma.
Thrombectomy within 8 Hours after Symptom Onset in Ischemic Stroke
Authors: Tudor G Jovin, Angel Chamorro, Erik Cobo, María A de Miquel, Carlos A Molina, Alex Rovira, Luis San Román, Joaquín Serena, Sonia Abilleira, Marc Ribó, Mònica Millán, Xabier Urra, Pere Cardona, Elena López-Cancio, Alejandro Tomasello, Carlos Castaño, Jordi Blasco, Lucía Aja, Laura Dorado, Helena Quesada, Marta Rubiera, María Hernandez-Pérez, Mayank Goyal, Andrew M Demchuk, Rüdiger von Kummer, Miquel Gallofré, Antoni Dávalos
Journal: New England Journal of Medicine (2015)

We aimed to assess the safety and efficacy of thrombectomy for the treatment of stroke in a trial embedded within a population-based stroke reperfusion registry.During a 2-year period at four centers in Catalonia, Spain, we randomly assigned 206 patients who could be treated within 8 hours after the onset of symptoms of acute ischemic stroke to receive either medical therapy (including intravenous alteplase when eligible) and endovascular therapy with the Solitaire stent retriever (thrombectomy group) or medical therapy alone (control group). All patients had confirmed proximal anterior circulation occlusion and the absence of a large infarct on neuroimaging. In all study patients, the use of alteplase either did not achieve revascularization or was contraindicated. The primary outcome was the severity of global disability at 90 days, as measured on the modified Rankin scale (ranging from 0 [no symptoms] to 6 [death]). Although the maximum planned sample size was 690, enrollment was halted early because of loss of equipoise after positive results for thrombectomy were reported from other similar trials.Thrombectomy reduced the severity of disability over the range of the modified Rankin scale (adjusted odds ratio for improvement of 1 point, 1.7; 95% confidence interval [CI], 1.05 to 2.8) and led to higher rates of functional independence (a score of 0 to 2) at 90 days (43.7% vs. 28.2%; adjusted odds ratio, 2.1; 95% CI, 1.1 to 4.0). At 90 days, the rates of symptomatic intracranial hemorrhage were 1.9% in both the thrombectomy group and the control group (P=1.00), and rates of death were 18.4% and 15.5%, respectively (P=0.60). Registry data indicated that only eight patients who met the eligibility criteria were treated outside the trial at participating hospitals.Among patients with anterior circulation stroke who could be treated within 8 hours after symptom onset, stent retriever thrombectomy reduced the severity of post-stroke disability and increased the rate of functional independence. (Funded by Fundació Ictus Malaltia Vascular through an unrestricted grant from Covidien and others; REVASCAT ClinicalTrials.gov number, NCT01692379.).
Generation of stable monoclonal antibody–producing B cell receptor–positive human memory B cells by genetic programming
Authors: Mark J Kwakkenbos, Sean A Diehl, Etsuko Yasuda, Arjen Q Bakker, Caroline M M van Geelen, Michaël V Lukens, Grada M van Bleek, Myra N Widjojoatmodjo, Willy M J M Bogers, Henrik Mei, Andreas Radbruch, Ferenc A Scheeren, Hergen Spits, Tim Beaumont
Journal: Nature Medicine (2009)
Latent Autoimmune Diabetes in Adults in a South Asian Population of the U.K.
Authors: Abigail C. Britten, Karen Jones, Carina Törn, Magnus Hillman, Birgitte Ekholm, Sudhesh Kumar, Anthony H. Barnett, Marilyn Ann Kelly
Journal: Diabetes Care (2007)

Type 2 diabetes is four- to sixfold more common in the South Asian population of the U.K. than in the indigenous white Caucasian population. A subset of all patients initially diagnosed with type 2 diabetes shows evidence of slowly evolving islet autoimmunity, termed latent autoimmune diabetes in adults (LADA). LADA is characterized by the presence of circulating autoantibodies specific for islet proteins and by insulin independence for at least 6 months postdiagnosis (1).

A recent pilot study in Birmingham, U.K., suggested that 27% of South Asians initially presenting with type 2 diabetes were positive for autoantibodies to GAD65 and/or insulinoma-associated protein (IA)-2 (2). This is significantly higher than the islet autoimmunity frequency of 10% observed in white Caucasians diagnosed with type 2 diabetes (3,4). The study in South Asians was carried out in a very small cohort, however, and the findings require confirmation in a much larger study group. The aim of this study was to determine the prevalence of LADA in a larger U.K.-resident South Asian population and to characterize the phenotypic features and genetic basis of the disease in this ethnic group.

A total of 500 South Asian subjects with type 2 diabetes (mean [range] age 55 years [31-89] and disease duration 7 years [0-29]) (Table 1) were consecutively recruited in Birmingham, U.K., and Coventry, U.K., as part of the U.K. Asian Diabetes Study. A total of 206 normoglycemic …
Molecularly and clinically related drugs and diseases are enriched in phenotypically similar drug-disease pairs
Authors: Ingo Vogt, Jeanette Prinz, Mónica Campillos
Journal: Genome Medicine (2014)

The incomplete understanding of disease causes and drug mechanisms of action often leads to ineffective drug therapies or side effects. Therefore, new approaches are needed to improve treatment decisions and to elucidate molecular mechanisms underlying pathologies and unwanted drug effects.
Risks of adverse pregnancy and birth outcomes in women treated or not treated with mood stabilisers for bipolar disorder: population based cohort study
Authors: R. Boden, M. Lundgren, L. Brandt, J. Reutfors, M. Andersen, H. Kieler
Journal: BMJ (2012)

<b>Objective</b> To investigate the risks of adverse pregnancy and birth outcomes for treated and untreated bipolar disorder during pregnancy. <b>Design</b> Population based cohort study using data from national health registers. <b>Setting</b> Sweden. <b>Participants</b> 332 137 women with a last menstrual period anytime after 1 July 2005 and giving birth anytime before the end of 31 December 2009. Women with a record of at least two bipolar diagnoses were identified and grouped as treated (n=320)—those who had filled a prescription for mood stabilisers (lithium, antipsychotics, or anticonvulsants) during pregnancy—or untreated (n=554). Both groups were compared with all other women giving birth (n=331 263). <b>Main outcome measures</b> Preterm birth, mode of labour initiation, gestational diabetes, infants born small or large for gestational age, neonatal morbidity, and congenital malformations. <b>Results</b> Of the untreated women, 30.9% (n=171) were induced or had a planned caesarean delivery compared with 20.7% (n=68 533) without bipolar disorder (odds ratio 1.57, 95% confidence interval 1.30 to 1.90). The corresponding values for the treated women were 37.5% (n=120) (2.12, 1.68 to 2.67). The risks of preterm birth in both treated and untreated women were increased by 50%. Of the untreated women, 3.9% (n=542) had a microcephalic infant compared with 2.3% (324 844) of the women without bipolar disorder (1.68, 1.07 to 2.62). The corresponding values for the treated women were 3.3% (n=311) (1.26, 0.67 to 2.37). Similar trends were observed for risks of infants being small for gestational age infants for weight and length. Among infants of untreated women, 4.3% (n=24) had neonatal hypoglycaemia compared with 2.5% (n=8302) among infants of women without bipolar disorder (1.51, 1.04 to 2.43), and 3.4% (n=11) of the treated women (1.18, 0.64 to 2.16). The analyses of variation in outcomes did not support any significant differences between treated and untreated women. <b>Conclusions</b> Bipolar disorder in women during pregnancy, whether treated or not, was associated with increased risks of adverse pregnancy outcomes.