tbuckley/cabot-search huggingface dataset:
Anti-cyclic citrullinated peptide antibodies are a collection of anti-citrullinated protein antibodies and contain overlapping and non-overlapping reactivities
Authors: A. Ioan-Facsinay, H. el-Bannoudi, H. U. Scherer, D. van der Woude, H. A. Menard, M. Lora, L. A. Trouw, T. W. J. Huizinga, R. E. M. Toes
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objective</h3> Anti-citrullinated protein antibodies (ACPA) and anti-cyclic citrullinated peptide (anti-CCP) antibodies are a hallmark of rheumatoid arthritis and are believed to play a role in disease pathogenesis. These antibodies are typically detected in ELISA with citrullinated peptides (eg, CCP2) or proteins as antigens. The absolute concentration of anti-CCP antibodies in serum is unknown. Although antibodies to several citrullinated proteins can mainly be detected within anti-CCP-positive sera, it is currently unknown whether anti-CCP antibodies are in fact ACPA. Likewise, it is unknown to what extent antibody responses to different citrullinated antigens are crossreactive. <h3>Methods</h3> An affinity purification method was established in which citrullinated antigen-specific antibodies were eluted from ELISA plates and then used for detection of other citrullinated antigens in ELISA or western blot. For additional crossreactivity studies, ELISA-based inhibition assays were performed with citrullinated or control peptides as inhibitors. <h3>Results</h3> The concentration of anti-CCP IgG antibodies was estimated to be at least 30 μg/ml in patients with high anti-CCP levels (&gt;1600 μg/ml). Affinity-purified anti-CCP antibodies were able to recognise citrullinated fibrinogen (cit-fib) and citrullinated myelin basic protein (cit-MBP) on western blot. Furthermore, antibodies specific for cit-fib and cit-MBP were crossreactive. However, additional crossreactivity studies indicated that non-overlapping antibody responses to citrullinated peptides can also exist in patients. <h3>Conclusions</h3> This report shows for the first time that anti-CCP antibodies recognise multiple citrullinated proteins and are thus a collection of ACPA. More importantly, the data indicate that different ACPA responses are crossreactive, but that crossreactivity is not complete, as distinct non-crossreactive responses can also be detected in patients with RA.
Association of the TNFa13 microsatellite with systemic sclerosis in Japanese patients
Authors: F. Takeuchi
Journal: Annals of the Rheumatic Diseases (2000)

To elucidate the contribution of microsatellite polymorphisms of TNFa and TNFb alleles to the pathogenesis of systemic sclerosis (SSc) by comparing the allele distribution among populations with different HLA susceptibility genes in SSc.TNFa and TNFb microsatellite polymorphisms were determined by PCR in 54 Japanese and 50 German SSc patients and in normal controls. HLA-DR genotyping was carried out by PCR-SSCP.The frequency of TNFa13 was significantly increased in Japanese SSc (p=0. 011, OR=8.53, 95% confidence intervals (95%CI)=2.46, 32.51, and p<1. 0 x 10E-5, OR=10.35, 95%CI=4.88, 22.09) and SSc with antitopoisomerase I antibody (a-Scl-70) (p=0.021, OR=33.25, 95%CI=3. 39, 800.76, and p<1.0 x 10E-5, OR=24.42, 95%CI=8.40, 72.83), compared with the German patient group and German controls, respectively. This increase was not only attributable to a higher prevalence of TNFa13 in Japanese compared with Germans (p=0.005, OR=3.55, 95%CI=1.60, 7.85) but was also caused by an increase in SSc, especially in the a-Scl-70 positive patients (p=0.028, OR=6.88, 95%CI=1.16, 22.60) compared with Japanese controls. TNFa13 was positively in linkage disequilibrium with HLA-DRB1*1502 (LD=0.053, t=2.69). Association analysis indicated that both TNFa13 and DRB1*1502 might have comparable probabilities of being susceptibility factors for SSc with a-Scl-70 in Japanese. Prevalences of TNFa6 and 13 were significantly increased and prevalences of TNFa2, and 7 were significantly decreased in Japanese controls as compared with German controls.TNFa13 is a genetic marker for SSc with a-Scl-70 in Japanese patients. Various differences in the prevalences of TNFa alleles between Japanese and German controls were established.
Genetic Analysis As a Practical Tool to Diagnose Hereditary Angioedema with Normal C1 Inhibitor: A Case Report
Authors: Luisa Karla P. Arruda, Luana Delcaro, Priscila B. Botelho Palhas, Marina M. Dias, Valdair F. Muglia, Erick C. Castelli, Konrad Bork, Adriana S. Moreno
Journal: Journal of Allergy and Clinical Immunology (2015)
Felty's syndrome. Clinical and serological analysis of 34 cases.
Authors: C W Sienknecht, M B Urowitz, W Pruzanski, H B Stein
Journal: Annals of the Rheumatic Diseases (1977)

Review of 34 cases of Felty9s syndrome showed this to be a form of 9super9 rheumatoid disease because of the severity of joint disease, the prominence of extra-articular features and the remarkable incidence of infection. The response to splenectomy in these 34 patients was shown by a return towards normal of peripheral blood abnormalities and a decrease in bone marrow granulopoiesis. Although some patients remained free of infection after splenectomy, others have continued to have infections despite the return of white blood cell counts to normal levels. Although splenectomy and subsequent increase in white blood cell levels may be beneficial, our experience suggests that other factors are important in the susceptibility to infection of Felty9s syndrome patients. Moreover, we think that splenectomy may have been instrumental in the fatal infection of one of our patients.
Optimal Use of a Panel of Methylation Markers with GSTP1 Hypermethylation in the Diagnosis of Prostate Adenocarcinoma
Authors: Yutaka Tokumaru, Susan V. Harden, Dong-Il Sun, Keishi Yamashita, Jonathan I. Epstein, David Sidransky
Journal: Clinical Cancer Research (2004)

Abstract Purpose: In this study, we tested the ability of a panel of hypermethylation markers to improve the sensitivity of histologic prostate cancer detection in sextant needle biopsies. Experimental Design: We obtained fresh-frozen sextant biopsies from 72 excised prostates and directly compared blinded histologic review and quantitative real-time methylation-specific PCR for hypermethylation of four genes, Tazarotene-induced gene 1 (TIG1), adenomatous polyposis coli (APC), retinoic acid receptor β2 (RARβ2), and glutathione S-transferase π (GSTP1) to detect the presence of prostate cancer. Results were compared with the final surgical pathological review of the resected prostates as the gold standard. Results: Histologic review alone detected carcinoma with a sensitivity of 64% (39 of 61 cases) and 100% specificity. Quantitative real-time methylation-specific PCR for TIG1, APC, RARβ2, and GSTP1 detected carcinoma with a sensitivity of 70%, 79%, 89%, and 75%, respectively, with 100% specificity for all of the genes. Using this panel of methylation markers in combination with histology resulted in the detection of 59 of 61 (97%) cases of prostate with 100% specificity, a 33% improvement over histology alone. Conclusion: The use of a panel of methylation markers as an adjunct to histologic review may substantially augment prostate cancer diagnosis from needle biopsies.
Raised plasma levels of asymmetric dimethylarginine are associated with cardiovascular events, disease activity, and organ damage in patients with systemic lupus erythematosus
Authors: I E M Bultink
Journal: Annals of the Rheumatic Diseases (2005)

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide inhibitor and a new independent risk factor for endothelial dysfunction and cardiovascular disease.To investigate the relationship between plasma ADMA levels and cardiovascular events (CVEs) and disease characteristics in patients with systemic lupus erythematosus (SLE).Demographic and clinical data were collected and plasma ADMA levels were measured in 107 patients with SLE. A modified organ damage index was calculated as defined by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), excluding CVE as an item.Cardiovascular disease, defined as > or =1 previous arterial CVE, was recorded in 16/107 (15%) patients with SLE and increased across tertiles of ADMA levels (p = 0.023 for trend). Mean plasma ADMA levels were significantly higher in patients with SLE with a history of CVEs than in patients without a CVE history (p = 0.018). In multiple regression analysis a high SLEDAI score, high modified SDI, high titre of anti-dsDNA antibodies, and low serum HDL were significantly associated with high plasma ADMA levels.In patients with SLE, plasma ADMA levels are significantly associated with CVEs, measures of disease activity, and organ damage, independently of an unfavourable lipid profile.
Frequency formats are a small part of the base rate story
Authors: Dale Griffin, Derek J. Koehler, Lyle Brenner
Journal: Behavioral and Brain Sciences (2007)

Abstract Manipulations that draw attention to extensional or set-based considerations are neither sufficient nor necessary for enhanced use of base rates in intuitive judgments. Frequency formats are only one part of the puzzle of base-rate use and neglect. The conditions under which these and other manipulations promote base-rate use may be more parsimoniously organized under the broader notion of case-based judgment.
Which 5-ASA?
Authors: S P L Travis
Journal: Gut (2002)

hen Asacol commands 65% of the UK market, can so many British gastroenterologists be wrong?Possibly.The market leader in France is Pentasa (72%) and is Salofalk in Germany (57%).In Canada it is Asacol (46%).Nevertheless, a Cochrane review of 11 trials involving 1598 patients showed that sulphasalazine was more effective than other 5-aminosalicylic acid (5-ASA) drugs for maintaining remission in ulcerative colitis (odds ratio (OR) 1.29, confidence interval (CI) 1.06-1.57). 1 Diagnosis, disease location, activity, side effect profile, efficacy, and cost all affect the choice of 5-ASA.5-ASA acts on and is metabolised by intestinal epithelial cells.Consequently, ulcerative colitis (a mucosal disease) is more susceptible to treatment by 5-ASA than transmural Crohn's disease.Mega doses of mesalazine (>4 g/day) may be an initial alternative to steroids for mild-moderately active ulcerative colitis and reduce the risk of relapse after small intestinal (but not colonic) resection for Crohn's disease. 2 If such high doses are to be used it makes sense to use a 5-ASA with little systemic absorption.Plasma 5-ASA concentrations are approximately 2 µmol/l for sulphasalazine, Pentasa, olsalazine, or balsalazide, compared with >6 µmol/l for Asacol and >13 µmol/l for Salofalk. 3s far as disease location is concerned, the key to treatment is a high concentration of 5-ASA at the site of inflammation.Suppositories are often appropriate for proctitis because >90% liquid 5-ASA enemas bypass the rectum. 4For active proctitis, a 1 g Pentasa suppository is more rapidly effective than two 500 mg Claversal (similar to Asacol) suppositories 5 and also maintains remission. 6or distal or left sided disease, suppositories can be combined with enemas.Asacol foam is better tolerated than liquid 5-ASA, while expensive Salofalk enemas provide double the necessary dose.The optimum dose for topical treatment is 1 g. 7he main role for 5-ASA remains maintenance of remission in ulcerative colitis.Individual 5-ASA derivatives all show comparable efficacy to sulphasalazine but the therapeutic advantage of the parent compound 1 should be noted.Azo bonded compounds may be better for distal disease, which predominates in ulcerative colitis, and olsalazine was better than Asacol 8 in one of the very few direct comparisons between 5-ASA derivatives.The advantage of balsalazide over Asacol 9 however, welcomed as an azo bonded compound with few side effects, has been disappointing.In any case, the theoretical advantage of azo bonded compounds for distal disease can be overcome simply by increasing the dose of mesalazine.The principal advantage of 5-ASA derivatives over sulphasalazine is that they are better tolerated.In the Cochrane review of maintenance therapy 1 however, sulphasalazine and 5-ASA had similar adverse event profiles (OR 1.16 (CI 0.62-2.16),and 1.31 (CI 0.86-1.99),respectively).The numbers needed to harm also favoured sulphasalazine, being 171 and 78, respectively.Even so, . . . . . . . . . .
METABOLISM, TOXICITY AND MANNER OF ACTION OF GOLD COMPOUNDS USED IN THE TREATMENT OF ARTHRITIS. I. HUMAN PLASMA AND SYNOVIAL FLUID CONCENTRATION AND URINARY EXCRETION OF GOLD DURING AND FOLLOWING TREATMENT WITH GOLD SODIUM THIOMALATE, GOLD SODIUM THIOSULFATE, AND COLLOIDAL GOLD SULFIDE
Authors: R. H. Freyberg, Walter D. Block, S. Levey
Journal: Journal of Clinical Investigation (1941)
The Evolving Role of Radiation Therapy in the Management of Colorectal Cancer
Authors: B. Sischy, L. L. Gunderson
Journal: CA A Cancer Journal for Clinicians (1986)

In recent years, considerable progress has been made in the use of diagnostic tech niques for the clinical evaluation of patients with colorectal cancer.For example, com puted tomography scanning, magnetic resonance imaging, and isotope studies, such as the use of antimony colloid for the dem onstration of the patency of regional nodes, are all being used to assess various prog-' nostic indicators, such as the degree of penetration of the tumor into or through the bowel wall and the involvement of adjacent organs and nodes.In addition, carcinoem bryonic antigen assays show promise for the detection of subclinical recurrent or metastatic colorectal cancer. Historical PerspectiveSurgery has been the mainstay of therapy for colorectal cancer since 1908, when Miles' performed the first abdominoperi neal (A-P) resection; his report stressed the metastatic potential of the disease.Since then, various modifications and extensions of the procedure have been tried.
Diagnostic accuracy of power Doppler ultrasound in patients with chronic tennis elbow
Authors: C du Toit, M Stieler, R Saunders, L Bisset, B Vicenzino
Journal: British Journal of Sports Medicine (2008)

To determine the diagnostic accuracy of power Doppler and grey scale ultrasonography, assess the relationship between severity measures and neovascularity, and describe the intra-tendon distribution of neovascularity in chronic tennis elbow.Between group cross sectional study.Sports medicine clinic and radiology centre.32 affected elbows (median and range of duration: 10; 3-120 months) and 18 unaffected contralateral elbows in 25 patients (mean age 50 years) with lateral elbow pain, and 38 unaffected elbows in 19 asymptomatic participants (mean age 45 years) underwent a clinical examination (reference standard test) and grey scale and power Doppler ultrasonographic examination.Ultrasound examination with power Doppler identified neovascularity and grey scale ultrasound changes (lateral epicondyle bony spurring or irregularity, maximum anterior-posterior thickness, and echo characteristics) of the common extensor tendon.Power Doppler had a strong positive likelihood ratio of 45.39, whereas a combined null finding in power Doppler and grey scale ultrasonography resulted in a robust negative likelihood ratio of 0.05. Grey scale changes were generally not as diagnostically accurate. Common extensor tendon neovascularity was equally distributed between the superficial and deep part of the tendon, and clinical severity measures did not correlate with neovascularity scores.Neovascularity identified with power Doppler ultrasonography when compared to grey scale changes (alone or in combination with Doppler) was diagnostically superior in identifying chronic tennis elbow. The lack of both neovascularity and grey scale changes on ultrasound examination also substantially increase the probability that the condition is not present and should prompt the clinician to consider other causes for lateral elbow pain.
The sigma-1 receptor: a molecular chaperone for the heart and the soul?
Authors: H. Ehmke
Journal: Cardiovascular Research (2011)

This editorial refers to ‘Decreased brain sigma-1 receptor contributes to the relationship between heart failure and depression’ by K. Ito et al. , pp. 33–40, this issue. 

Heart failure patients suffer much more often from clinically relevant depression than the general population. The prevalence of depression among heart failure patients steeply increases with the severity of heart failure, reaching a rate of >40% in patients with New York Heart Association functional class IV, and the risk of death and secondary events is more than two-fold higher in heart failure patients with depression than in non-depressed patients.1 However, while these epidemiological data clearly suggest a significant role of depression in the clinical course of heart failure, the biological mechanisms contributing to this association are still incompletely understood. Ito et al. 2 provide experimental evidence that sigma-1 receptors expressed in the central nervous system may play a crucial role in the link between heart failure and depression.

The sigma-1 receptor is widely expressed in many tissues, including the brain, lung, liver, adrenal glands, and the heart. It was originally postulated as an opioid receptor to explain the drug-induced psychotic effects of N -allylnormetazocine (SKF-10047) in dogs,3 but subsequent studies disproved this concept by demonstrating that the …
Association Study of Prostate Cancer Susceptibility Variants with Risks of Invasive Ovarian, Breast, and Colorectal Cancer
Authors: Honglin Song, Thibaud Koessler, Shahana Ahmed, Susan J. Ramus, Susanne Krüger Kjaer, Richard A. DiCioccio, Eva Wozniak, Estrid Hogdall, Alice S. Whittemore, Valerie McGuire, Bruce A.J. Ponder, Clare Turnbull, Sarah Hines, Nazneen Rahman, Rosalind A. Eeles, Douglas F. Easton, Simon A. Gayther, Alison M. Dunning, Paul D.P. Pharoah
Journal: Cancer Research (2008)

Abstract Several prostate cancer susceptibility loci have recently been identified by genome-wide association studies. These loci are candidates for susceptibility to other epithelial cancers. The aim of this study was to test these tag single nucleotide polymorphisms (SNP) for association with invasive ovarian, colorectal, and breast cancer. Twelve prostate cancer–associated tag SNPs were genotyped in ovarian (2,087 cases/3,491 controls), colorectal (2,148 cases/2,265 controls) and breast (first set, 4,339 cases/4,552 controls; second set, 3,800 cases/3,995 controls) case-control studies. The primary test of association was a comparison of genotype frequencies between cases and controls, and a test for trend stratified by study where appropriate. Genotype-specific odds ratios (OR) were estimated by logistic regression. SNP rs2660753 (chromosome 3p12) showed evidence of association with ovarian cancer [per minor allele OR, 1.19; 95% confidence interval (95% CI), 1.04–1.37; Ptrend = 0.012]. This association was stronger for the serous histologic subtype (OR, 1.29; 95% CI, 1.09–1.53; P = 0.003). SNP rs7931342 (chromosome 11q13) showed some evidence of association with breast cancer (per minor allele OR, 0.95; 95% CI, 0.91–0.99; Ptrend = 0.028). This association was somewhat stronger for estrogen receptor–positive tumors (OR, 0.92; 95% CI, 0.87–0.98; P = 0.011). None of these tag SNPs were associated with risk of colorectal cancer. In conclusion, loci associated with risk of prostate cancer may also be associated with ovarian and breast cancer susceptibility. However, the effects are modest and warrant replication in larger studies. [Cancer Res 2008;68(21):8837–42]
Multiple listerial liver abscesses.
Authors: D Jenkins, J E Richards, Y Rees, A C Wicks
Journal: Gut (1987)

Hepatic involvement in listeriosis is uncommon in adults. Cases previously reported include three presenting as acute hepatitis and three of listerial liver abscesses found at necropsy. We report a case of multiple listerial liver abscesses. We believe this to be the first time this diagnosis has been made in a living patient.
Breathing easy with carbon monoxide
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

Ancient Greek philosophers extolled moderation in all things. On page 283, Minamoto and colleagues show that carbon monoxide (CO) inhalation is no exception. In a mouse model of trachea transplantation, inhaled CO—in moderation—prevented the development of lethal obstructive airway disease.






Figure 

Inhaled carbon monoxide reduces T cell (brown) invasion of the airways following allogeneic tracheal transplantation.




CO gas is both a toxic air pollutant and a normal byproduct of cellular heme metabolism. Although CO is well-known for its role as an asphyxiant, recent studies have revealed its virtues, which include anti-inflammatory and anti-apoptotic effects on a variety of cell types. CO has also been shown to inhibit the rejection of xenogeneic heart transplants in rats.

Minamoto et al. now add to that list of virtues by showing that treating mice with low-dose inhaled CO reduced the T cell infiltration and airway obstruction that develops after allogeneic tracheal transplantation. The benefits of endogenous CO were evident based on comparisons with mice that received grafts lacking the CO-synthesizing enzyme hemoxygenase-1 (Hmox-1), which developed more severe disease than mice that received wild-type grafts.This group previously showed that the development of post-transplant airway obstruction requires the expression of inducible nitric oxide synthase (iNOS). They now find that CO counterbalances the production of nitric oxide by inhibiting the activation of the transcription factor NF-κB, which drives the expression of iNOS.

This came as a surprise to the authors, as most other known effects of CO depend on activation of the MAP kinase or cyclic GMP signaling pathways. Further experiments are required to determine how CO inhibits NF-κB activation. But in the meantime, these data suggest that increasing endogenous CO levels might be therapeutic in transplant patients who develop a lethal, and currently untreatable, complication of lung transplantation called obliterative bronchiolitis.