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Sample records for suspected primary antibody

  1. Cutaneous manifestations associated with antiphospholipid antibodies in patients with suspected primary antiphospholipid syndrome: a case-control study.

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    Naldi, L; Locati, F; Marchesi, L; Cortelazzo, S; Finazzi, G; Galli, M; Brevi, A; Cainelli, T; Barbui, T

    1993-01-01

    OBJECTIVE: To study the association of a variety of dermatological manifestations related to vascular abnormalities with antiphospholipid antibodies in patients with suspected primary antiphospholipid syndrome. METHOD: Case-control study. Consecutive patients referred to the coagulation and haemostasis service of a general hospital for the first determination of antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) and newly diagnosed disorders (for example, thrombocytopenia, thrombotic disorders, and unexplained repeated abortions) were selected. Patients were examined by two dermatologists according to predefined criteria, and information about general characteristics and relevant dermatological and medical histories were collected using an ad hoc questionnaire. The study was limited to patients without evidence of systemic lupus erythematosus. A total of 35 patients was examined; 13 subjects were positive for lupus anticoagulant or anticardiolipin antibodies, or both (cases), and 22 were negative (controls). RESULTS: Moderate to severe livedo reticularis and acrocyanosis were significantly associated with antiphospholipid antibodies, with relative risks of 13.1 (95% confidence interval 1.1 to 149.0) and 8.6 (95% confidence interval 1.1 to 65.1). Capillaritis was also associated with the antibodies. Histories of Raynaud's phenomenon and superficial thrombophlebitis were more common in cases than controls. CONCLUSIONS: This study provides quantitative evidence of the association of antiphospholipid antibodies with several cutaneous diseases in which vascular abnormalities seem to play a major part. The study suggests that these manifestations might appear early in the development of the antiphospholipid syndrome. PMID:8484676

  2. The Clinical Utility of Measuring IgG Subclass Immunoglobulins During Immunological Investigation for Suspected Primary Antibody Deficiencies.

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    Parker, Antony R; Skold, Markus; Ramsden, David B; Ocejo-Vinyals, J Gonzalo; López-Hoyos, Marcos; Harding, Stephen

    2017-11-08

    Measurement of IgG subclass concentrations is a standard laboratory test run as part of a panel to investigate the suspicion of antibody deficiency. The assessment is clinically important when total IgG is within the normal age-specific reference range. The measurement is useful for diagnosis of IgG subclass deficiency, to aid the diagnosis of specific antibody deficiency, as a supporting test for the diagnosis of common variable immunodeficiency, as well as for risk stratification of patients with low IgA. The measurement of IgG subclasses may also help determine a revaccination strategy for patients and support patient management. In certain circumstances, the measurement of IgG subclasses may be used to monitor a patient's humoral immune system. In this review, we discuss the utility of measuring IgG subclass concentrations. © The Author 2017. Published by Oxford University Press on behalf of American Society for Clinical Pathology.

  3. Educational paper: Primary antibody deficiencies

    NARCIS (Netherlands)

    G.J.A. Driessen (Gertjan); M. van der Burg (Mirjam)

    2011-01-01

    textabstractPrimary antibody deficiencies (PADs) are the most common primary immunodeficiencies and are characterized by a defect in the production of normal amounts of antigen-specific antibodies. PADs represent a heterogeneous spectrum of conditions, ranging from often asymptomatic selective IgA

  4. [Viral load test conducive to excluding negative subjects from suspects in HIV antibody detections].

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    Hei, Fa-Xin; Zhang, Qi-Yun; Sun, Wei-Dong; Zhang, Qin; Ye, Jing-Rong; Liu, Hai-Lin; Lu, Hong-Yan

    2008-01-01

    To study whether plasma viral load testing is helpful to exclude ones free from Human immunodeficiency virus (HIV) infections from suspects in HIV antibody detections. 19 Specimens, which showed disconcordant results of the two HIV EIA testing (S/CO test, were selected. Viral load of the specimens were detected. A six-month follow up survey in detecting HIV antibody was conducted in these subjects. None of these 19 cases was observed to be positive HIV viral loads and there was no any progress in WB bands development during the follow-up period. The possibility of HIV infection could be excluded. When the specimens react with very low intensity in both EIA and WB, negative viral load result is conducive to exclude negative subjects from suspects in HIV antibody detections.

  5. Imaging spectrum of primary antiphospholipid antibody syndrome

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    Yoon, Kwon Ha; Won, Jong Jin [Wonkwang University Hospital, Iksan (Korea, Republic of); Ha, Hyun Kwon; Kim, Jung Hoon; Kim, Jeong Gon; Ki, Won Woo; Kim, Pyo Nyun; Lee, Moon Gyu; Auh, Yong Ho [Asan Medical Center, Seoul (Korea, Republic of)

    1998-04-01

    Antiphospholipid antibody syndrome is recognized as one of the most important causes of hypercoagulability. It can be clinically diagnosed if patients have experienced unexplained recurrent venous or arterial thrombosis, recurrent fetal loss, or thrombocytopenia in the presence of circulating autoantibodies to phospholipids, such as anticardiolipin antibody or lupus anticoagulant. Approximately half of all patients with this syndrome do not have associated systemic disease, and their condition is described as primary antiphospholipid antibody syndrome (PAPS). In the remainder, the syndrome is accompanied by systemic lupus erythematosus or other connective tissue diseases, and is known as secondary antiphospholipid syndrome (1). The purpose of this paper is to illustrate the systemic manifestation of PAPS, focusing on the radiological findings of CT, MR and angiography in clinically proven patients. (author). 8 refs., 10 figs.

  6. Antimitochondrial antibody-negative primary biliary cirrhosis.

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    Mendes, Flavia; Lindor, Keith D

    2008-06-01

    There is a subset of patients who have biochemical and histologic features consistent with primary biliary cirrhosis (PBC) who lack antimitochondrial antibodies (AMA). This entity is usually referred to as AMA-negative PBC or alternatively autoimmune cholangitis. Patients who have AMA-negative PBC are believed to have a similar clinical course, response to treatment, and prognosis as their AMA-positive counterparts. As more sensitive and specific serologic tests are developed to detect serum AMA, it is possible we may find that these patients initially believed to be AMA-negative are indeed AMA-positive, suggesting a single disease process.

  7. Immunobiology of Primary Antibody Deficiencies: Towards a new classification

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    G.J.A. Driessen (Gertjan)

    2013-01-01

    textabstractPrimary antibody deficiencies (PADs) are the most common primary immunodeficiencies. The hallmark of PADs is a defect in the production of normal amounts of antigen specific antibodies. These antibodies or immunoglobulins are indispensible for the adaptive immune response against a wide

  8. Pattern Electroretinography in Glaucoma Suspects and Early Primary Open Angle Glaucoma

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    Ebrahim Jafarzadehpour

    2013-01-01

    Full Text Available Purpose: To explore retinal ganglion cell (RGC dysfunction in glaucoma suspects and patients with early primary open angle glaucoma (POAG using pattern electroretinography (PERG. Methods: Twenty glaucoma suspects (glaucomatous optic disc appearance, 15 early POAG (based on abnormal discs and abnormal visual fields and 16 normal controls were enrolled. Transient PERG was recorded in response to 0.8΀ and 16΀ black and white checkerboard stimuli. Amplitude and peak time (latency of the P50 and N95 components of the PERG response, and the ratio of N95 amplitude in response to 0.8΀ and 16΀ checks were measured. Results: N95 peak time (latency was significantly increased in both early manifest POAG and glaucoma suspects as compared to normal controls (P<0.001. In early POAG, N95 amplitude in response to small (0.8΀ checks and the small/large check ratio were reduced in comparison to normal eyes (P<0.05. However, in glaucoma suspects no significant N95 amplitude reduction was observed. No significant difference was observed among the study groups in terms of P50 amplitude or peak time. Conclusion: The N95 PERG response demonstrated uncoupled peak time and amplitude alterations in glaucoma. N95 peak time was significantly increased both in glaucoma suspects and early POAG; N95 amplitude reduction was present only in early POAG. PERG may detect RGC dysfunction (increased latency before cell death (decreased amplitude occurs.

  9. Occurrence of antibodies to Anaplasma phagocytophilum in patients with suspected tick-borne encephalitis

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    Zuzana Kalinová

    2015-09-01

    None of the examined patients with suspected TBE had the disease confirmed. Hoever, as shown by the results, the relative risk of occurrence of anaplasmosis is higher in people examined for some another vector-borne disease (in this case TBE. Therefore, the performance of screening examinations in patients suspected of having any tick-borne disease is very important.

  10. Dog erythrocyte antigens (DEA) 1, 4, 7 and suspected naturally occurring anti-DEA 7 antibodies in Italian Corso dogs.

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    Spada, E; Proverbio, D; Priolo, V; Ippolito, D; Baggiani, L; Perego, R; Pennisi, M G

    2017-04-01

    We sought to determine the prevalence of dog erythrocyte antigen (DEA) 1, 4 and 7 and naturally occurring anti-DEA7 antibodies in Italian Corso dogs. In addition, we correlated DEAs with different epidemiologic variables, compared the prevalence of DEAs against other canine populations and assessed the risk of sensitisation and transfusion reactions (TRs) following unmatched transfusion. Blood samples from 100 Corso dogs were evaluated for DEA 1, 4, 7 and naturally occurring anti-DEA 7 antibodies. Seventy-one percent of samples were DEA 1-negative, 100% tested DEA 4-positive, and 95% tested DEA 7-negative. Suspected anti-DEA7 antibodies were found in 32% dogs. The DEA 1 and 7-negative phenotypes were significantly more common than in most canine populations. When a previously tested Italian canine population was considered as blood donors for Corso dogs, the risk of DEA 1 sensitisation using DEA 1 untyped blood was 29%, and of acute haemolytic TRs after a second untyped DEA 1-incompatible transfusion was 8%. The potential for delayed TRs between DEA 7-negative Corso dogs with suspected naturally occurring anti-DEA 7 antibodies receiving untyped DEA 7-positive blood was 11%. Conversely, when Corso dogs were blood donors for the same population, the risk of DEA 1 sensitisation was 17% and the risk of an acute haemolytic TR after a second DEA 1-incompatible blood transfusion was 3%. Corso dogs can be suitable blood donors. Additional studies are needed to clarify whether the high prevalence of naturally occurring anti-DEA 7 antibodies in this breed could increase their risk of delayed TRs when they are blood recipients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. A management programme for suspected heart failure in primary care in cooperation with specialists in cardiology.

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    Mejhert, Märit; Kahan, Thomas

    2015-03-01

    The diagnosis of new onset congestive heart failure (CHF) is often difficult as symptoms and signs are non-specific. Proper diagnostic investigations and treatments are underused in primary care. To describe a management programme for patients with suspected CHF in primary care in cooperation with specialists in cardiology. Prospective study of 102 consecutive primary care patients with suspected new onset CHF referred to an easily accessible hospital-based cardiology outpatient clinic management programme. Following clinical examination, ECG, echocardiography, blood chemistry including NT-proBNP, and assessment of NYHA class and quality of life (EQ5D), patients with a confirmed diagnosis of CHF were prescribed medication with advice on titration and target doses. Trained CHF nurses gave Information on CHF and provided follow up. Half (47%) of the referred patients had the diagnosis of CHF confirmed. Low NT-proBNP values (CHF group was 86% ACE-inhibitors/angiotensin receptor blockers, 61% ß-blocking agents, and 81% diuretics (P CHF in primary care, with referral to a hospital-based specialist team, can be applied successfully.

  12. Prevalence of Anti-Thyroid Antibodies in Patients with Primary ...

    African Journals Online (AJOL)

    Objective: To determine prevalence of thyroid antimicrosomal and antithyroglobulin antibodies among patients with primary thyroid disorders. Design: Descriptive cross-sectional study. Setting: Kenyatta National Hospital, July 2003 to August 2004. Results: Antimicrosomal antibodies (anti-TPOAbs) were detected in 51.4% ...

  13. Resident-performed laser peripheral iridotomy in primary angle closure, primary angle closure suspects, and primary angle closure glaucoma

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    Kam JP

    2017-10-01

    Full Text Available Jason P Kam, Emily M Zepeda, Leona Ding, Joanne C Wen Department of Ophthalmology, University of Washington, Seattle, WA, USA Purpose: To investigate the power use and complication frequency of resident-performed laser peripheral iridotomy (LPI.Methods: A retrospective analysis of 196 eyes from 103 patients who underwent neodymium: yttrium-aluminum-garnet laser iridotomy performed by resident physicians from January 1, 2010 through April 30, 2015 at a university-based county hospital was done. All patients were treated for primary angle closure, primary angle closure suspects, and primary angle closure glaucoma. Data were collected on pre- and post-laser intraocular pressure (IOP, ethnicity, laser parameters and complications. Mean power use and frequency of complications were evaluated. Complications included elevated post-laser IOP at 30–45 minutes (≥8 mmHg, hyphema, aborted procedures, and lasering non-iris structures. The number of repeated LPI procedures, was also recorded.Results: Mean total power used for all residents was 78.2±68.7 mJ per eye. Power use by first-year trainees was significantly higher than second- and third-year trainees (103.5±75.5 mJ versus 73.7±73.8 mJ and 67.2±56.4 mJ, respectively, p=0.011. Complications included hyphema or microhyphema in 17.9% (35/196, IOP spikes in 5.1% (10/196, aborted procedures in 1.1% (3/196 and lasering non-iris structures in 0.5% (1/196. LPI was repeated in 22.4% of cases (44/196 with higher incidence of repeat LPI among non-Caucasian compared to the Caucasian subjects (p=0.02. Complication rates did not differ with increased training (p=0.16.Conclusion: Total power used for LPI decreased with increased resident training, while the complication rate did not differ significantly among resident classes. Complication rates were comparable to rates reported in the literature for attending-performed LPIs. Keywords: laser, iridotomy, resident, complications, power, energy

  14. Determination of neuronal antibodies in suspected and definite Creutzfeldt-Jakob disease

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    O. Grau-Rivera (Oriol); R. Sánchez-Valle (Raquel); A. Saiz (Albert Abe); J.L. Molinuevo (José Luis); R. Bernabé (Reyes); E. Munteis (Elvira); F. Pujadas (Francesc); A. Salvador (Antoni); J. Saura (Júlia); A. Ugarte (Antonio); M.J. Titulaer (Maarten); J. Dalmau (Josep); F. Graus (Francesc)

    2014-01-01

    textabstractIMPORTANCE: Creutzfeldt-Jakob disease (CJD) and autoimmune encephalitis with antibodies against neuronal surface antigens (NSA-abs) may present with similar clinical features. Establishing the correct diagnosis has practical implications in the management of care for these patients.

  15. Seroprevalence of IgG anti-Toxocara species antibodies in a population of patients with suspected allergy

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    Qualizza R

    2011-11-01

    Full Text Available Rosanna Qualizza1, Cristoforo Incorvaia2, Romualdo Grande3, Eleni Makri2, Luigi Allegra31Allergy Service, 2Allergy/Pulmonary Rehabilitation, Istituti Clinici di Perfezionamento, 3IRCCS Fondazione Cà Granda, Milan, ItalyBackground: Toxocara canis is an intestinal nematode affecting dogs and cats, which causes human infection when embryonated eggs excreted in dog feces are ingested. Humans are paratenic hosts. Although the larvae do not develop into adult worms in the human body, they may migrate to various tissues and organs where they can survive for several years, giving rise to several clinical symptoms, which can present in allergy-like form.Methods: Over 5 years, we examined 9985 patients referred for suspected allergies, based on symptoms such as dermatitis, urticaria, rhinitis, asthma, and conjunctivitis; 753 patients who had allergy tests negative or unrelated to clinical history were tested for seropositivity to T. canis by enzyme-linked immunosorbent assay (ELISA or Western blotting (WB.Results: In 240 patients (31.8%, ELISA or WB or both tests were positive for T. canis immunoglobulin G (IgG antibodies: in particular, 64 of them (26.7% were positive to ELISA, 110 (45.8% to WB, and 66 (27.5% to both tests. Asthma was the most common clinical presentation. Two thirds of patients underwent subsequent anthelmintic therapy and showed a complete remission of symptoms and, in 43% of patients retested by ELISA and WB, became negative to Toxocara.Conclusion: These findings strongly suggest that T. canis plays a significant role in inducing chronic symptoms presenting as suspected allergies.Keywords: suspected allergy, Toxocara canis, enzyme-linked immunosorbent assay, Western blotting, anthelmintic therapy

  16. Virus antibody dynamics in primary and secondary dengue infections.

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    Gujarati, Tanvi P; Ambika, G

    2014-12-01

    Dengue viral infections show unique infection patterns arising from its four serotypes, (DENV-1,2,3,4). Its effects range from simple fever in primary infections to potentially fatal secondary infections. We analytically and numerically analyse virus dynamics and humoral response in a host during primary and secondary dengue infection for long periods using micro-epidemic models. The models presented here incorporate time delays, antibody dependent enhancement, a dynamic switch and a correlation factor between different DENV serotypes. We find that the viral load goes down to undetectable levels within 7-14 days as is observed for dengue infection, in both cases. For primary infection, the stability analysis of steady states shows interesting dependence on the time delay involved in the production of antibodies from plasma cells. We demonstrate the existence of a critical value for the immune response parameter, beyond which the infection gets completely cured. For secondary infections with a different serotype, the homologous antibody production is enhanced due to the influence of heterologous antibodies. The antibody production is also controlled by the correlation factor, which is a measure of similarities between the different DENV serotypes involved. Our results agree with clinically observed humoral responses for primary and secondary infections.

  17. Antimitochondrial antibodies and other antibodies in primary biliary cirrhosis: diagnostic and prognostic value.

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    Muratori, Luigi; Granito, Alessandro; Muratori, Paolo; Pappas, Georgios; Bianchi, Francesco B

    2008-05-01

    Antimitochondrial antibodies (AMA) are the serologic cornerstone in the diagnosis of primary biliary cirrhosis (PBC), even if they are not detectable in a proportion of patients, notwithstanding the most sensitive and sophisticated technologies used. To fill in the serologic gap in AMA-negative PBC, there is sound evidence to consider antinuclear antibody (ANA) patterns, such as anti-multiple nuclear dots and anti-membranous/rim-like, as PBC-specific surrogate hallmarks of the disease, and their detection can be considered virtually diagnostic. Furthermore, particular ANA specificities, such as anti-gp210, anti-p62, anticentromere antibodies, and anti-dsDNA, may provide additional diagnostic and prognostic information.

  18. Anterior segment morphology after laser iridotomy in primary angle closure suspects.

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    Mansoori, Tarannum; Balakrishna, Nagalla

    2017-11-12

    To evaluate and compare the changes in anterior segment parameters in primary angle closure suspects before and after laser peripheral iridotomy and intrasession repeatability of measurements before laser iridotomy as assessed by Scheimpflug-Placido disc topographer. Before laser iridotomy, 56 eyes of 56 primary angle closure suspect patients underwent anterior segment analysis with the Sirius Scheimpflug-Placido disc topographer system using glaucoma analysis mode, which was repeated a week after iridotomy. Anterior segment parameters such as central anterior chamber depth, central corneal thickness, anterior chamber volume and iridocorneal angle were analysed before and after laser iridotomy and compared with paired t-test. Three consecutive scans were obtained to assess the intrasession repeatability of measurements before iridotomy by a single examiner and intraclass correlation co-efficient was calculated. Multivariate regression analysis was performed to evaluate the predictors associated with iridocorneal angle narrowing. Intraclass correlation co-efficient values ranged from 0.982 for anterior chamber volume to 0.998 for the iridocorneal angle. After laser iridotomy, mean central anterior chamber depth increased from 2.14 ± 0.29 mm to 2.21 ± 0.28 mm (p = 0.04), mean anterior chamber volume increased from 96.2 ± 16.98 mm 3 to 98.14 ± 15.87 mm 3 (p angle widened from 33.38 ± 3.96° to 34.82 ± 4.27° (p = 0.01), compared with pre-iridotomy status. There was no change in central corneal thickness, intraocular pressure or pupil diameter. Multivariate regression analysis model showed that at one week after iridotomy, iridocorneal angle opening was positively correlated with age (β = 0.773, p = 0.005) and anterior chamber volume (β = 1.308, p angle closure suspect patients. The Scheimpflug-Placido disc topographer provides reproducible measurements of the iridocorneal angle and other parameters

  19. SEVA TB ELISA - Multi antigen and antibody assays for serodiagnosis of suspected cases of pulmonary and extra pulmonary tuberculosis in tertiary care hospital -A retrospective study

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    Pranita J Waghmare

    2012-10-01

    Full Text Available Objective: To assess the usefulness of in-house developed multiantigen and antibody assays, in diagnosis of both pulmonary and extra-pulmonary tuberculosis. Method: Clinically suspected cases of 31 pulmonary and 171 extra-pulmonary tuberculosis (TB were screened by ELISA using cocktail (ES-31 + EST-6 antigen and their specific antibodies (anti ES-31 + anti EST-6 IgG for detection of antibody and and antigen (circulating antigen and immune complexed antigen respectively and correlated with antituberculosis therapy in retrospective study. Results: Out of 31 cases of pulmonary TB screened, 15 patients showed ELISA positivity out of which five cases were given antituberculosis therapy. Out of 171 cases of EPTB screened, 76 cases showed ELISA positivity out of which 18 were given antituberculosis therapy. Further 4 EPTB cases which showed AFB negativity were given ATT. The data was further analyzed based on PTB & EPTB, adults and children, OPD and IPD patients to understand false positivity in clinically suspected PTB and EPTB cases. There was significant correlation (108/202 cases with ELISA negativity and no ATT advised in clinically suspected PTB and EPTB patients. Conclusions: In house developed multi antigen and antibody assays have been observed to be quite useful as adjunct test in serodiagnosis of suspected cases of tuberculosis in particular extrapulmonary tuberculosis.

  20. A STUDY ON SEROPREVALENCE OF DENGUE IGM ANTIBODY IN SUSPECTED CASE OF DENGUE FEVER IN AND AROUND JAMNAGAR, GUJARAT (INDIA

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    Saurabh Chhotalal Gamit

    2017-12-01

    Full Text Available BACKGROUND Dengue virus belongs to family Flaviviridae, it spread by the bite of infected Aedes mosquitoes. It breeds in fresh water. It causes a wide spectrum of illness from mild illness to severe fatal Dengue Haemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS. The aim of the study is to find out seroprevalence of dengue IgM in and around Jamnagar by presence of virus specific dengue IgM antibody from serum samples taken from suspected dengue patients. MATERIALS AND METHODS This is retrospective study conducted at tertiary care hospital, Jamnagar. Patient with history of dengue fever more than 5 days were included in the study. Serum samples were screened for dengue IgM by ELISA method. Study was conducted in our institute from July 2016 to June 2017. Total 1202 serum samples of suspected patient of dengue IgM by ELISA method. RESULTS Out of 1202 samples, total 254 (21.13% were positive for dengue IgM Ab among this- 177 (69.69% male and 77 (30.31% female and 78 (30.71% were 0-20 of age, 131 (51.57% were 20-40 of age and 45 (17.72% were 40 of age. 175 (82.28% positive cases between October to December in post-monsoon season. CONCLUSION Study shows that prevalence of dengue fever is more in post-monsoon season, more common in middle age group and in male than female, so early diagnosis is very important to reduce mortality rate

  1. [Autoimmune cholangitis or primary biliary cirrhosis without antimitochondrial antibodies?].

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    Saló, J; Caballería, L; Bruguera, M; Parés, A; Rodés, J

    1997-01-01

    The term cholangitis or autoimmune cholangiopathy is applied to patients with a disease similar to primary biliary cirrhosis because of its clinical and histologic characteristics but in whom there is a repeated absence of antimitochondrial antibodies and, by the contrary, the presence of antinuclear antibodies. The initial description of these cases was carried out in 1987. Good response was observed to treatment with glucocorticoids in these first cases and others described later. A series of 13 female patients with features of autoimmune cholangitis diagnosed from 1987 to 1993 in the Hospital Clinic i Provincial from Barcelona, Spain, is retrospectively reviewed. These patients were compared with 13 patients with primary biliary cirrhosis diagnosed on the basis of clinical and histologic criteria and the presence of antimitochondrial antibodies. No relevant clinical or histological differences were observed between the two groups of patients. Six patients with autoimmune cholangitis underwent treatment with glucocorticoids with unequal response, and in 5 cases ursodeoxycholic acid was administered with a slight analytical improvement being observed. According to these results and the current data of these patients, autoimmune cholangitis should be considered as a variety of primary biliary cirrhosis, the main characteristic of which would be the absence of antimitochondrial antibodies more than that of being a specific, independent disease.

  2. High seroprevalence of Borrelia miyamotoi antibodies in forestry workers and individuals suspected of human granulocytic anaplasmosis in the Netherlands

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    S. Jahfari

    2014-09-01

    Full Text Available Substantial exposure to Borrelia miyamotoi occurs through bites from Ixodes ricinus ticks in the Netherlands, which also transmit Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum. Direct evidence for B. miyamotoi infection in European populations is scarce. A flu-like illness with high fever, resembling human granulocytic anaplasmosis, has been attributed to B. miyamotoi infections in relatively small groups. Borrelia miyamotoi infections associated with chronic meningoencephalitis have also been described in case reports. Assuming that an IgG antibody response against B. miyamotoi antigens reflects (endured infection, the seroprevalence in different risk groups was examined. Sera from nine out of ten confirmed B. miyamotoi infections from Russia were found to be positive with the recombinant antigen used, and no significant cross-reactivity was observed in secondary syphilis patients. The seroprevalence in blood donors was set at 2.0% (95% CI 0.4–5.7%. Elevated seroprevalences in individuals with serologically confirmed, 7.4% (2.0–17.9%, or unconfirmed, 8.6% (1.8–23%, Lyme neuroborreliosis were not significantly different from those in blood donors. The prevalence of anti-B. miyamotoi antibodies among forestry workers was 10% (5.3–16.8% and in patients with serologically unconfirmed but suspected human granulocytic anaplasmosis was 14.6% (9.0–21.8%; these were significantly higher compared with the seroprevalence in blood donors. Our findings indicate that infections with B. miyamotoi occur in tick-exposed individuals in the Netherlands. In addition, B. miyamotoi infections should be considered in patients reporting tick bites and febrile illness with unresolved aetiology in the Netherlands, and other countries where I. ricinus ticks are endemic.

  3. Diagnostic prediction models for suspected pulmonary embolism: systematic review and independent external validation in primary care

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    Geersing, Geert-Jan; Lucassen, Wim A M; Erkens, Petra M G; Stoffers, Henri E J H; van Weert, Henk C P M; Büller, Harry R; Hoes, Arno W; Moons, Karel G M

    2015-01-01

    Objective To validate all diagnostic prediction models for ruling out pulmonary embolism that are easily applicable in primary care. Design Systematic review followed by independent external validation study to assess transportability of retrieved models to primary care medicine. Setting 300 general practices in the Netherlands. Participants Individual patient dataset of 598 patients with suspected acute pulmonary embolism in primary care. Main outcome measures Discriminative ability of all models retrieved by systematic literature search, assessed by calculation and comparison of C statistics. After stratification into groups with high and low probability of pulmonary embolism according to pre-specified model cut-offs combined with qualitative D-dimer test, sensitivity, specificity, efficiency (overall proportion of patients with low probability of pulmonary embolism), and failure rate (proportion of pulmonary embolism cases in group of patients with low probability) were calculated for all models. Results Ten published prediction models for the diagnosis of pulmonary embolism were found. Five of these models could be validated in the primary care dataset: the original Wells, modified Wells, simplified Wells, revised Geneva, and simplified revised Geneva models. Discriminative ability was comparable for all models (range of C statistic 0.75-0.80). Sensitivity ranged from 88% (simplified revised Geneva) to 96% (simplified Wells) and specificity from 48% (revised Geneva) to 53% (simplified revised Geneva). Efficiency of all models was between 43% and 48%. Differences were observed between failure rates, especially between the simplified Wells and the simplified revised Geneva models (failure rates 1.2% (95% confidence interval 0.2% to 3.3%) and 3.1% (1.4% to 5.9%), respectively; absolute difference −1.98% (−3.33% to −0.74%)). Irrespective of the diagnostic prediction model used, three patients were incorrectly classified as having low probability of pulmonary

  4. Residual Angle Closure One Year After Laser Peripheral Iridotomy in Primary Angle Closure Suspects.

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    Baskaran, Mani; Yang, Elizabeth; Trikha, Sameer; Kumar, Rajesh S; Wong, Hon Tym; He, Mingguang; Chew, Paul T K; Foster, Paul J; Friedman, David; Aung, Tin

    2017-11-01

    To determine the incidence and baseline clinical and anterior segment optical coherence tomography (AS-OCT) predictors associated with residual angle closure as assessed by gonioscopy 1 year after laser peripheral iridotomy (LPI) in primary angle closure suspects (PACS). Subanalysis of randomized controlled trial data. AS-OCT images from 181 PACS subjects ≥50 years of age were analyzed using customized software before and 1 year after LPI. Other parameters assessed were intraocular pressure (IOP) and axial length (Axl). Residual angle closure was defined as the inability to see the posterior trabecular meshwork for at least 2 quadrants on gonioscopy after LPI. Multivariate regression analysis determined the baseline predictors of residual angle closure 1 year after LPI. The mean age of participants was 62.4 (standard deviation 9.9) years. The majority were female (137, 75.7%) and Chinese (174, 96.1%). At 1 year post LPI, 148 (81.8%) subjects had gonioscopic residual angle closure. Univariate analysis showed that baseline Axl, anterior chamber area, anterior chamber volume, angle opening distance at 750 μm from the scleral spur, and angle recess area were smaller while baseline lens vault and iris curvature were larger in residual angle closure subjects (all P angle closure. One year after LPI, >80% of PACS had gonioscopic residual angle closure. Greater baseline iris volume and higher IOP at baseline are independent risk factors for residual gonioscopic angle closure. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Changes in ocular biometry and anterior chamber parameters after pharmacologic mydriasis and peripheral iridotomy in primary angle closure suspects

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    Mohammad Reza Razeghinejad

    2016-07-01

    Conclusions: This study showed no change in the ocular biometric and anterior chamber parameters including iridocorneal angle after PI and/or pharmacologic mydriasis except for increments in anterior chamber volume. This factor has the potential to be used as a numerical proxy for iris position in evaluating and monitoring patients with primary angle closure suspects after PI.

  6. Antimitochondrial antibodies in primary biliary cirrhosis: the role of xenobiotics.

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    Long, S Alice; Van de Water, Judy; Gershwin, M Eric

    2002-02-01

    Primary biliary cirrhosis is an enigmatic autoimmune disease of women characterized by antimitochondrial antibodies and destruction of intrahepatic bile ducts. The etiology of PBC is unknown, but we present data herein that the disease may be induced by xenobiotic (i.e. chemicals) exposure. In particular, we postulate that halogenated compounds will bind to the autoantigen, break tolerance, and lead to an intense mucosal response.

  7. Can ultrasound be used as the primary imaging in children with suspected Crohn disease?

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    Tsai, Timothy L; Marine, Megan B; Wanner, Matthew R; Cooper, Matthew L; Steiner, Steven J; Ouyang, Fangqian; Gregory Jennings, S; Karmazyn, Boaz

    2017-07-01

    There is growing literature on the use of ultrasound (US) for evaluation of Crohn disease in adults, but few studies have been conducted on children. Several studies demonstrated high accuracy of US in the diagnosis of Crohn disease. Using US as the primary screening imaging modality for Crohn disease can reduce health care costs, the need for sedation and ionizing radiation exposure. The aim of our study is to determine if US can be used for screening evaluation of pediatric Crohn disease. A prospective cohort study of pediatric patients undergoing MR enterography (MRE) for suspected or known history of Crohn disease was performed, with gray-scale and Doppler US of the terminal ileum done immediately before or after MRE. US images were interpreted by two radiologists (Reader 1 and Reader 2) not involved in image acquisition, in blinded and randomized fashion. US findings of Crohn disease including bowel wall thickening, wall stratification, increased vascularity on Doppler, lymphadenopathy, fat infiltration and extraintestinal complications were evaluated. MRE findings of terminal ileitis were considered the reference standard. Demographic data, body mass index (BMI), symptoms, and laboratory, endoscopic and histopathological data were obtained from electronic medical records. Forty-one patients (mean age: 13.7 years: 4.6-18.9 years) were evaluated. Mean BMI was 21.2 (range: 13-40.2); 10 patients (24.3%) were either overweight or obese. Final diagnoses were Crohn disease (n=24), ulcerative colitis (n=4) and normal/non-inflammatory bowel disease-related diagnoses (n=13). US demonstrated sensitivity of 67% and 78% and specificity of 78% and 83%, by Reader 1 and Reader 2, respectively. MRE sensitivity and specificity were 75% and 100%, respectively, compared to final clinicopathological diagnosis. Interobserver agreement between Reader 1 and Reader 2 was good (0.6Crohn disease in children, US has limited sensitivity for detecting terminal ileitis.

  8. Determining early referral criteria for patients with suspected inflammatory arthritis presenting to primary care physicians: a cross-sectional study

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    Almoallim H

    2017-04-01

    , swelling of metacarpophalangeal joint 2 or 5, swelling of proximal inter-phalangeal joint 2 or 3, wrist swelling, wrist tenderness, a positive test for rheumatoid factor, and a positive test for anti-citrullinated protein antibodies. Conclusion: Nine variables should be the basis of early referral criteria. It should aid PCPs in making appropriate early referrals of patients with suspected inflammatory arthritis, accelerating diagnosis and initiation of treatment. Keywords: inflammatory arthritis, rheumatoid, diagnosis, primary care, early referral criteria

  9. Antinuclear antibodies as ancillary markers in primary biliary cirrhosis.

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    Granito, Alessandro; Muratori, Paolo; Quarneti, Chiara; Pappas, Georgios; Cicola, Ronny; Muratori, Luigi

    2012-01-01

    Antimitochondrial antibodies are the serological hallmark of primary biliary cirrhosis (PBC). Besides antimitochondrial antibodies, the autoantibody profile of PBC includes antinuclear antibodies (ANA) which are detectable by indirect immunofluorescence in up to 50% of PBC patients. Two immunofluorescence patterns are considered 'PBC-specific': the multiple nuclear dots and rim-like/membranous patterns. The target antigens of the multiple nuclear dots pattern have been identified as Sp100 and promyelocytic leukemia protein, whereas the rim-like/membranous pattern is given by autoantibodies recognizing multiple proteins such as gp210, nucleoporin p62 and the lamin B receptor. Other ANA, especially those already known in the rheumatological setting, such as anticentromere, anti-SSA/Ro and anti-dsDNA antibodies, can be frequently found in PBC, often coexisting in the same patient. In this article, we will report on recent progress in the antigenic characterization of ANA in PBC, their detection with both traditional assays and Western blot/ELISA with molecularly defined nuclear antigens, and we will discuss their clinical significance.

  10. Pathogenetic Role of Thyrotropin Receptor Antibody in the Development of Hyperthyroidism Following Primary Hypothyroidism *

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    Shong, Young Kee; Cho, Bo Youn; Hong, Sung Kwan; Lee, Hong Kyu; Koh, Chang-Soon; Min, Hun Ki

    1989-01-01

    The authors measured thyrotropin binding inhibitory immunoglobulin (TBII), thyroid stimulating antibody (TSAb), and thyroid stimulation blocking antibody (TSBAb) sequentially in patients who developed hyperthyroidism following primary hypothyroidism, and compared changes in these various funcional parameters of thyrotropin receptor antibody (TRAb) with clinical manifestations, in order to investigate the role of TRAb in the development of hyperthyroidism following primary hypothyroidism. In a...

  11. Ultrasonography of major salivary glands compared with parotid and labial gland biopsy and classification criteria in patients with clinically suspected primary Sjögren's syndrome.

    Science.gov (United States)

    Mossel, Esther; Delli, Konstantina; van Nimwegen, Jolien F; Stel, Alja J; Kroese, Frans G M; Spijkervet, Fred K L; Vissink, Arjan; Arends, Suzanne; Bootsma, Hendrika

    2017-11-01

    To assess the validity of ultrasound of major salivary glands (sUS) compared with parotid and labial gland biopsies, sialometry, anti-SSA/Ro antibody status and classification criteria in patients clinically suspected with primary Sjögren's syndrome (pSS). 103 consecutive outpatients with clinically suspected pSS underwent sUS. Parenchymal echogenicity, homogeneity, hypoechogenic areas, hyperechogenic reflections and clearness of salivary gland border were scored according to the Hocevar scoring system. Total ultrasound score was calculated as the sum of these domains (range 0-48). Absolute agreement between sUS and parotid (83%) and labial (79%) gland biopsy outcome was good. Negative sUS predicts negative parotid gland biopsy, and positive sUS predicts positive labial gland biopsy. Compared with the American European Consensus Group (AECG) classification, sUS showed an absolute agreement of 82%, sensitivity of 71% and specificity of 92%. Compared with the American College of Rheumatology (ACR) classification, absolute agreement was 86%, sensitivity was 77% and specificity was 92%. Compared with the ACR-European League Against Rheumatism (EULAR) classification, absolute agreement was 80%, sensitivity was 67% and specificity was 94%. Positive sUS predicts classification, but negative sUS does not exclude classification. The combination of positive sUS with presence of anti-SSA/Ro antibodies or negative sUS with absence of anti-SSA/Ro antibodies showed a high predictive value for classification as pSS or non-pSS. In our prospective inception cohort study derived from daily clinical practice, absolute agreement between sUS and salivary gland biopsies was slightly higher for parotid compared with labial gland biopsies. The combination of positive sUS and presence of anti-SSA/Ro antibodies highly predicts classification according to the AECG, ACR and ACR-EULAR classification criteria. © Article author(s) (or their employer(s) unless otherwise stated in the text of

  12. Dutch Suspects of Terrorist Activity: A Study of Their Biographical Backgrounds Based on Primary Sources.

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    Maarten van Leyenhorst

    2017-09-01

    Full Text Available With the impending defeat of ISIS in Syria and Iraq, supporters of terrorist groups, among them home-grown supporters and returning foreign fighters, have become a huge security threat to their country of return. Some have committed attacks in western countries, even while under the surveillance of authorities. Counter-terrorism is confronted with enormous challenges. One of the most prominent issues is the absence of evidence based knowledge on early warning signs. Experts on radicalization and terrorism have emphasized that neither typologies of terrorists nor accurate descriptions of generalizable risks can be made. This leads to opportunities for those who are willing to prepare and commit acts of terrorism to do so, without the agencies in charge of monitoring such individuals being able to accurately identify relevant threats. An additional deficiency in counter-terrorism research, is its dependency on historic and secondary source material. One of various actors in the Netherlands tasked to evaluate and mitigate relevant risks of terrorist suspects and offenders, is the Dutch Probation Service (DPS. In response to today’s prevailing terrorist threat, a specialized section of the DPS is set up to identify and supervise potential problem behaviour of those who are suspected or convicted of terrorism. The authors have been involved in this Unit Terrorism, Extremism and Radicalization (TER for years. As professionals of TER, the authors have had unique access to both judicial data, such as police files and prosecutor’s data, as to experts in the Dutch field of counter-terrorism. The authors have analysed the pre-sentencing advices of twenty-six clients of the DPS. These files are comprised of several socio-economic, historical, psychopathological and behavioural indicators. The goals are to learn from the analysis of the biographical backgrounds of the suspects and to stimulate the debate on management and supervision of terrorist

  13. Primary Biliary Cirrhosis-Specific Antimitochondrial Antibodies in Neonatal Haemochromatosis

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    Daniel S. Smyk

    2013-01-01

    Full Text Available Background and Aim. Neonatal hemochromatosis (NH is characterised by severe liver injury and extrahepatic siderosis sparing the reticuloendothelial system. Its aetiology is obscure, although it has been proposed as an alloimmune disease, resulting from immunological reaction to self-antigens (alloantigens which the body recognizes as foreign. We studied an infant with NH and his mother whose sera contained antimitochondrial antibody (AMA, the hallmark of primary biliary cirrhosis (PBC. Material and Methods. To investigate the origin of AMA in the infant, we studied isotype distributions in serum from the mother and infant. Serum samples were obtained at diagnosis of NH, after liver transplantation (LT; age 1 month, and over the ensuing 17 months. Results. At NH diagnosis, infant and maternal serum contained AMA of the IgG isotype, predominantly of the G3 and G1 subclasses. AMA strongly reacted against the pyruvate dehydrogenase complex E2 subunit (PDC-E2, the major PBC-specific AMA autoantigen. Anti-PDC-E2 responses in both infant and mother declined over time, being present 2 months after LT (mother and child and absent 10 months later (mother and 17 months later (child. Conclusion. The association of maternally transferred IgG1 and IgG3 subclass AMA with the appearance of liver damage in an infant with NH may suggest a causal link between antibody and liver damage.

  14. Primary biliary cirrhosis-specific antimitochondrial antibodies in neonatal haemochromatosis.

    Science.gov (United States)

    Smyk, Daniel S; Mytilinaiou, Maria G; Grammatikopoulos, Tassos; Knisely, A S; Mieli-Vergani, Giorgina; Bogdanos, Dimitrios P; Vergani, Diego

    2013-01-01

    Neonatal hemochromatosis (NH) is characterised by severe liver injury and extrahepatic siderosis sparing the reticuloendothelial system. Its aetiology is obscure, although it has been proposed as an alloimmune disease, resulting from immunological reaction to self-antigens (alloantigens) which the body recognizes as foreign. We studied an infant with NH and his mother whose sera contained antimitochondrial antibody (AMA), the hallmark of primary biliary cirrhosis (PBC). To investigate the origin of AMA in the infant, we studied isotype distributions in serum from the mother and infant. Serum samples were obtained at diagnosis of NH, after liver transplantation (LT; age 1 month), and over the ensuing 17 months. At NH diagnosis, infant and maternal serum contained AMA of the IgG isotype, predominantly of the G3 and G1 subclasses. AMA strongly reacted against the pyruvate dehydrogenase complex E2 subunit (PDC-E2), the major PBC-specific AMA autoantigen. Anti-PDC-E2 responses in both infant and mother declined over time, being present 2 months after LT (mother and child) and absent 10 months later (mother) and 17 months later (child). The association of maternally transferred IgG1 and IgG3 subclass AMA with the appearance of liver damage in an infant with NH may suggest a causal link between antibody and liver damage.

  15. Acute adrenal insufficiency due to primary antiphospholipid antibody syndrome

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    Kishore Kumar Behera

    2013-01-01

    Full Text Available Introduction: We report a case of acute adrenal insufficiency (AAI in a patient with antiphospholipid syndrome (APS. Case Report: A 44-year-old female patient presented to us with acute abdominal pain associated with recurrent vomiting and giddiness. On examination, her blood pressure was 80/50 mm Hg. Systemic examination was normal. Further evaluation revealed hypocortisolemia with elevated plasma adrenocorticotropin hormone indicative of primary adrenal insufficiency. Her abdominal computed tomography scan showed features of evolving bilateral adrenal infarction. Etiological work-up revealed prolonged activated thromboplastin time, which didn′t correct with normal plasma, her anti-cardiolipin antibody and lupus anticoagulant were also positive. She was diagnosed to have APS with adrenal insufficiency and she was started on intravenous steroids and heparin infusion. Conclusion: AAI due to the APS can present with acute abdominal pain followed by hypotension. A high index of suspicion is needed to make the correct diagnosis and to initiate appropriate treatment.

  16. Predicting acute viral hepatitis serum markers (A and E) in patients with suspected acute viral hepatitis attending primary health care centers in Baghdad: a one year cross-sectional study.

    Science.gov (United States)

    Al-Naaimi, Ahmed Samir; Turky, Atallah Mekhlef; Khaleel, Hanan Abdulghafoor; Jalil, Rasha Waleed; Mekhlef, Olah A; Kareem, Susan Abdul; Hasan, Nadia Yousif; Dhadain, Azhar Abdulla

    2012-08-21

    Viral hepatitis is an important preventable infectious disease with various rates of occurrence in different areas of the world. The main objective of the present study was to evaluate the role of some risk factors in predicting a positive acute viral hepatitis marker among patients with suspected acute viral hepatitis in a primary health care setting in Baghdad. Besides, finding out the occurrence of jaundice, contribution of viruses A and E to the cases that have occurred in Baghdad province was also searched for. Over a period of 1 year a descriptive cross sectional study was carried out at the primary health care centers in Baghdad. A questionnaire form was used to collect data about demographic factors and the results of the investigations. Total serum bilirubin and bilirubin in urine were done at the primary health care center laboratory. The rest of the sera samples were sent to Hepatitis referral Lab at Central Public Health Laboratory (CPHL) to be tested for anti HAV IgM and anti HEV IgM using ELISA technique. A total of 7,576,372 consultations to primary health care centers were recorded in Baghdad. Among those a total of 2,692 cases (35.5 per 100,000 consultations) were labeled as acute viral hepatitis cases. A positive hepatitis viral marker (A, B, C and E) was found in 1,332 cases (17.6 per 100,000 consultations). More than two fifths (44.8%) of cases were positive for anti-HAV antibodies and another 1.6% had positive anti-HEV antibodies. During 1 year period, the rate of occurrence of suspected acute viral hepatitis cases was 35.5 per 100000 of consultations to the primary health care centers in Baghdad. Of the total suspected cases, only 17.6 per 100000 of the consultations were positive for one of the viral hepatitis markers. Those who tested positive for one of the viral hepatitis markers represent 49.5% of the suspected cases. Proportion of anti HAV IgM positive tests among suspected cases was 44.8%. Factors that were able to predict positive Anti

  17. The Knowledge of Lung Tuberculosis Suspects for Sputum Examination Attitude In The Kamoning Primary Health Care

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    Puteri Febriana Arivany

    2017-04-01

    Full Text Available Tuberculosis is an infectious disease caused by the Mycobacterium tuberculosis. Tuberculosis (TB is an infectious disease mostly attacks the lungs TB disease is transmitted by smear positive TB patients through the air when an infected person coughs or sneezes in the form of droplets. Sputum examination is an effort to enforce TB diagnose and to determine the potential of this transmission. The aims was conducted to determine the relationship between the respondents’ knowledge andthe sputum examination in the health center Kamoning Sampang. This research used analytic observational study with survey method using cross sectional. The research performed in 60 patients and sampling method used is imple random sampling. The independent variabel consist of education, occupation, income respondents, education and attitude of the respondent in conducting sputum examination. The strength of correlation was measured by Contingency Coefficient and Odd Ratio (OR were analyzed using chi-square test. Contingency Coefficient of respondents knowledge knowledge suspected pulmonary tuberculosis in sputum examination is 0,253 and OR = 3,600. The conclusion is there was a weak correlation between the respondents knowledge and sputum examination. Symptoms and treatment of pulmonary TB can be identified if the health workers in collaboration with religious leaders and community leaders to provide the Information according to age and education of the respondents. Keywords: knowledge, attitude, TB suspect, sputum examination

  18. Antimitochondrial antibody-negative primary biliary cirrhosis: a subset of primary biliary cirrhosis.

    Science.gov (United States)

    Liu, Bin; Shi, Xu Hua; Zhang, Feng Chun; Zhang, Wen; Gao, Li Xia

    2008-02-01

    Antimitochondrial antibodies (AMA) are the hallmark in primary biliary cirrhosis (PBC); nevertheless, it has long been recognized that 5-10% patients with typical features compatible with PBC do not have detectable AMA, and they were referred to as 'AMA-negative PBC'. This study aimed to evaluate whether AMA-negative/positive PBC represents different clinical entities. We compared the clinical, laboratory, percentage of regulatory T cells (Tregs) in peripheral blood, liver biopsy features and response to treatment of the two groups of patients. The first group was comprised of 12 patients with 'AMA-negative PBC'. The second was made up of another 12 PBC patients with positive AMA. Antimitochondrial antibodies-negative/positive patients were remarkably similar in terms of clinical manifestations, liver biochemistries and histological findings. The frequency of anti-nuclear antibodies, anti-smooth-muscle antibody, anti-gp210 and anti-sp100 antibody showed no significant difference between the two groups. A significantly lower mean percentage of CD4+CD25(high) T cells was observed in peripheral blood mononuclear cells of AMA-negative/positive PBC patients compared with that of the 12 control subjects (5.8+/-1.8 and 5.4+/-1.4% vs. 7.6+/-1.7% respectively; P=0.014 and 0.004). However, no difference could be found between AMA-negative and AMA-positive PBC patients (P=0.599). After 1 year treatment with ursodeoxycholic acid, the two groups showed similar response. Antimitochondrial antibody-negative/positive PBC patients are similar in clinical, laboratory, percentage of Treg in peripheral blood, liver biopsy features and response to treatment. This suggests that AMA-negative PBC may be a variant of AMA-positive PBC rather than a separate clinical entity.

  19. Immunoblotting as a confirmatory test for antimitochondrial antibodies in primary biliary cirrhosis.

    Science.gov (United States)

    Provenzano, G; Diquattro, O; Craxì, A; Almasio, P; Pinzello, G; Marino, L; Fiorentino, G; Rinaldi, F; Pagliaro, L

    1993-01-01

    Primary biliary cirrhosis is characterised by the presence of antimitochondrial antibodies which are directed against components of mitochondrial dehydrogenase complexes. The specificity of antimitochondrial antibodies for primary biliary cirrhosis as detected by immunoblotting was investigated. Commercially available preparations of pyruvate and oxo-glutarate dehydrogenases and beef-heart mitochondria were used as source of antigens. Sera from 47 primary biliary cirrhosis patients (46 of whom were antimitochondrial antibody positive by immunofluorescence), 16 non-primary biliary cirrhosis patients (antimitochondrial antibody positive by immunofluorescence), 23 liver-kidney microsomal antibody positive chronic active hepatitis patients, and 32 patients with connective tissue diseases were examined. Of the 47 subjects with primary biliary cirrhosis, 43 (91%) and 13 (28%) tested positive by immunoblotting for pyruvate and oxo-glutarate dehydrogenase, respectively. Only three primary biliary cirrhosis patients were negative for both antigens, including the only one shown to be antimitochondrial antibody negative by immunofluorescence. The other two patients were positive by immunoblotting with beef-heart mitochondria. In contrast, only three of 16 (19%) non-primary biliary cirrhosis patients who were antimitochondrial antibody positive by immunofluorescence tested positive by immunoblotting (for both pyruvate dehydrogenase and beef-heart mitochondria). None of the 23 liver-kidney microsomal antibody positive and the 32 patients with rheumatic diseases were positive by immunoblotting with any antigen. Our data show that immunoblotting with commercially available oxo-acid dehydrogenases is a reproducible method for the detection of antimitochondrial antibodies highly specific for primary biliary cirrhosis. Images p546-a PMID:8491404

  20. Paediatric gastroenterology evaluation of overweight and obese children referred from primary care for suspected non-alcoholic fatty liver disease

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    Schwimmer, J B; Newton, K P; Awai, H I; Choi, L J; Garcia, M A; Ellis, L L; Vanderwall, K; Fontanesi, J

    2013-01-01

    Background Screening overweight and obese children for non-alcoholic fatty liver disease (NAFLD) is recommended by paediatric and endocrinology societies. However, gastroenterology societies have called for more data before making a formal recommendation. Aim To determine whether the detection of suspected NAFLD in overweight and obese children through screening in primary care and referral to paediatric gastroenterology resulted in a correct diagnosis of NAFLD. Methods Information generated in the clinical evaluation of 347 children identified with suspected NAFLD through screening in primary care and referral to paediatric gastroenterology was captured prospectively. Diagnostic outcomes were reported. The diagnostic performance of two times the upper limit of normal (ULN) for alanine aminotransferase (ALT) was assessed. Results Non-alcoholic fatty liver disease was diagnosed in 55% of children identified by screening and referral. Liver disease other than NAFLD was present in 18% of those referred. Autoimmune hepatitis was the most common alternative diagnosis. Children with NAFLD had significantly (P gastroenterology has the potential to identify clinically relevant liver pathology. Consensus is needed on how to value the risk and rewards of screening and referral, to identify children with liver disease in the most appropriate manner. PMID:24117728

  1. Pyoderma Vegetans: A Case Report in a Child Suspected to Primary Immunodeficiency and Review of the Literature

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    Mahboubeh Mansouri

    2015-07-01

    Full Text Available Pyoderma vegetans (PV is a rare inflammatory disorder characterized by vegetating pustules and plaques affecting the skin and mucosal membranes. It is believed that this entity is mostly associated with inflammatory bowel disease (IBD, chronic malnutrition, human immunodeficiency virus (HIV, malignancies, and other immunocompromised states. Pyoderma vegetans occurs more commonly in young and middle-aged adults. There is no sex predilection for this entity. The lesions could heal spontaneously, but usually recur and become chronic. Our patient was an 11-year-old girl suspected to have primary combined immunodeficiency complicated by chronic recurrent vegetating pustular lesions on the face and postauricular area since one year of age. The histological features of the lesions were consistent with pyoderma vegetans. This is the first case of PV beginning from early infancy in the setting of primary immunodeficiency and in an unusual location.

  2. Prevalence of antimicrobial resistant Escherichia coli from patients with suspected urinary tract infection in primary care, Denmark.

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    Córdoba, Gloria; Holm, Anne; Hansen, Frank; Hammerum, Anette M; Bjerrum, Lars

    2017-10-10

    Escherichia coli is the most common pathogen causing Urinary Tract Infections (UTI). Data from the current National Surveillance program in Denmark (DANMAP) may not accurately represent the prevalence of resistant E. coli in primary care, because only urine samples from complicated cases may be forwarded to the microbiological departments at hospitals for diagnostic examination. The aim of this study was to assess the prevalence of resistant E. coli to the most commonly used antimicrobial agents in primary care in a consecutive sample of patients from general practice. Observational study carried out from December 2014 to December 2015. Thirty-nine general practices from The Capital Region of Denmark included adult patients with urinary tract symptoms and suspected UTI. All urine samples were sent to the central laboratory Statens Serum Institut (SSI). Significant bacteriuria was interpreted according to the European Urinalysis Standards. Susceptibility testing was performed and interpreted according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) standards. From the 39 general practices 505 patients were recruited. Completed data were obtained from 485 (96%) patients. According to the European Urinalysis Standards, 261 (54%) patients had positive bacteriuria. The most common uropathogen in patients with uncomplicated (uUTI) and complicated (cUTI) urinary tract infection was E. coli 105 (69%) and 76 (70%), respectively. Eighty-two (45%) of 181 E. coli isolates were resistant to at least one of the tested antibiotics and 50 out of 82 isolates were resistant to two or more antimicrobial agents. The highest resistance-rate was found against ampicillin 34% (95% CI 24;42) in uUTI and 36% (24;46) in cUTI. There were no differences in the distribution of resistance between uncomplicated and complicated cases. The prevalence of resistance was similar to the one reported in DANMAP 2014. In E. coli from uUTI there is high resistance rates to

  3. Secondary Antibody Deficiency in Glucocorticoid Therapy Clearly Differs from Primary Antibody Deficiency.

    Science.gov (United States)

    Wirsum, Clemens; Glaser, Cornelia; Gutenberger, Sylvia; Keller, Baerbel; Unger, Susanne; Voll, Reinhard E; Vach, Werner; Ness, Thomas; Warnatz, Klaus

    2016-05-01

    The aim of this study was to identify characteristics of hypogammaglobulinemia secondary to glucocorticoid therapy and their value in the differential diagnosis to primary forms of antibody deficiency. We investigated prevalence and character of hypogammaglobulinemia in a cohort of 36 patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) on glucocorticoid therapy in comparison to a gender- and age-matched cohort of hospital controls. We therefore determined serum immunoglobulin levels as well as B- and T cell-subsets in the peripheral blood of all participants. In addition, prior serum immunoglobulin levels and clinical data of the GCA and PMR patients were extracted from the electronic patient data-base. 21/36 GCA/PMR patients on glucocorticoid treatment developed antibody deficiency. In 19 patients this included IgG and in 13 patients IgG was the only affected isotype. The reduction of IgG was persistent in nearly 50 % of these patients during the observed period. GCA/PMR patients had reduced circulating naive and transitional B cells (p = 0.0043 and p = 0.0002 respectively) while IgM, IgG and IgA memory B cells were preserved. Amongst T-cell subsets, we found a reduction of CD4 memory T cells (p IgG deficiency, preserved IgA production and class-switched memory B cells, by these markers this form of secondary hypogammaglobulinemia can be clearly distinguished from common variable immunodeficiency (CVID).

  4. Primary vs. Secondary Antibody Deficiency: Clinical Features and Infection Outcomes of Immunoglobulin Replacement

    Science.gov (United States)

    Duraisingham, Sai S.; Buckland, Matthew; Dempster, John; Lorenzo, Lorena; Grigoriadou, Sofia; Longhurst, Hilary J.

    2014-01-01

    Secondary antibody deficiency can occur as a result of haematological malignancies or certain medications, but not much is known about the clinical and immunological features of this group of patients as a whole. Here we describe a cohort of 167 patients with primary or secondary antibody deficiencies on immunoglobulin (Ig)-replacement treatment. The demographics, causes of immunodeficiency, diagnostic delay, clinical and laboratory features, and infection frequency were analysed retrospectively. Chemotherapy for B cell lymphoma and the use of Rituximab, corticosteroids or immunosuppressive medications were the most common causes of secondary antibody deficiency in this cohort. There was no difference in diagnostic delay or bronchiectasis between primary and secondary antibody deficiency patients, and both groups experienced disorders associated with immune dysregulation. Secondary antibody deficiency patients had similar baseline levels of serum IgG, but higher IgM and IgA, and a higher frequency of switched memory B cells than primary antibody deficiency patients. Serious and non-serious infections before and after Ig-replacement were also compared in both groups. Although secondary antibody deficiency patients had more serious infections before initiation of Ig-replacement, treatment resulted in a significant reduction of serious and non-serious infections in both primary and secondary antibody deficiency patients. Patients with secondary antibody deficiency experience similar delays in diagnosis as primary antibody deficiency patients and can also benefit from immunoglobulin-replacement treatment. PMID:24971644

  5. Primary antiphospholipid antibody syndrome with adrenal hemorrhage in a child : a case report

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    Kim, Dong Hun; Lee, Soo Hyun; Kim, Hyun Joo; Yoo, Han Wook; Yoon, Chong Hyun [Ulsan Univ. College of Medicine, Seoul (Korea, Republic of)

    1999-11-01

    Primary antiphospholipid antibody syndrome is a disease that is clinically diagnosed if a patient suffers recurrent thromboses, stroke, recurrent fetal loss, livedo reticularis, and thrombocytopenia, without evidence of systemic lupus erythematosus or other connective diseases. Adrenal hemorrhage in a patient with primary antiphospholipid antibody syndrome is a rarely recognized, but potentially catastrophic disorder. We recently encountered bilateral adrenal hemorrhaging in a child with antiphospholipid antibody syndrome and casem as well as reviewing the literature.

  6. High concentration of antimitochondrial antibodies predicts progressive primary biliary cirrhosis.

    Science.gov (United States)

    Flisiak, Robert; Pelszynska, Maria; Prokopowicz, Danuta; Rogalska, Magdalena; Grygoruk, Urszula

    2005-09-28

    To evaluate the serum concentration of antimitochondrial antibodies (AMAs) as a prognostic indicator of progressive primary biliary cirrhosis (pPBC). Serum concentrations of AMA subtypes (anti-M2, anti-M4, and anti-M9), biochemical indices of liver function and Mayo risk factor (MRF) were determined in 30 women with diagnosed primary biliary cirrhosis (PBC) selected among 348 females with elevated alkaline phosphatase but without signs of hepatic decompensation. They were followed up for 5 years for possible development of hepatic decompensation. Anti-M2 concentration was significantly correlated with bilirubin and albumin levels as well as MRF, whereas anti-M4 was significantly correlated with albumin level, prothrombin time and MRF. During the 5-year follow-up, progressive PBC (pPBC) was diagnosed in 3 among 23 patients available for evaluation. These 3 patients were positive for both anti-M2 and anti-M4. Anti-M2 serum concentration exceeded 1 300 RU/mL in patients with pPBC and only in 1 among 20 non-progressive PBC persons (5%). Anti-M4 serum concentration exceeded 400 RU/mL in 2 of the progressive patients and none in the non-progressive group. In contrast, anti-M9 serum concentration was below 100 RU/mL in all patients with pPBC, and higher than 100 RU/mL in 11 women (55%) among the non-progressive group. Females with elevated alkaline phosphatase and high anti-M2 and anti-M4 concentrations are at a high risk for developing pPBC. Quantitative AMA detection should be considered as a method for early diagnosis of pPBC.

  7. Antimitochondrial antibody negative primary biliary cirrhosis: a distinct syndrome of autoimmune cholangitis.

    Science.gov (United States)

    Michieletti, P; Wanless, I R; Katz, A; Scheuer, P J; Yeaman, S J; Bassendine, M F; Palmer, J M; Heathcote, E J

    1994-01-01

    This study reports on a group of 20 patients with an initial diagnosis of primary biliary cirrhosis (PBC) whose serum tested negative for antimitochondrial antibodies by immunofluorescence. All had a clinical history compatible with primary biliary cirrhosis, and results of biochemical, histological, and radiological investigations were consistent with this diagnosis despite the absence of antimitochondrial antibodies by immunofluorescence. For comparison, these patients were matched for sex and serum bilirubin with 20 antimitochondrial antibody positive (> 1:160) and histologically confirmed primary biliary cirrhosis patients who served as controls. Serum samples from both groups were retested blindly for antimitochondrial antibodies using immunoblotting and for antibodies to the major M2 mitochondrial autoantigens by enzyme linked immunosorbent assay (ELISA). Three antimitochondrial antibody immunofluorescence negative patients had antimitochondrial antibodies by immunoblotting and ELISA; the remaining 17 patients were confirmed negative by all methods. The antimitochondrial antibody immunofluorescence positive controls were verified by immunoblotting or ELISA, or both. All 17 patients negative for antimitochondrial antibodies had antinuclear antibodies, often in high titres, compared with 3/17 of the antimitochondrial antibody positive controls (p = 0.0001). Additionally, the antimitochondrial antibody negative group also had significantly higher smooth muscle antibody titres (p = 0.03) and lower serum IgM (p = 0.01) and aspartate aminotransferase (p = 0.03) activities than the antimitochondrial antibody positive controls. Analysis of clinical findings, histological tests, serum bilirubin, alkaline phosphatase, alanine aminotransferase, and IgG, disclosed no significant differences between the two groups. This paper describes a group of patients with the clinical and histological features of PBC but who do not fulfil the usual criteria necessary to make this

  8. Approach to the diagnosis and management of suspected exercise-induced bronchoconstriction by primary care physicians

    OpenAIRE

    Hull, James H; Hull, Peter J; Parsons, Jonathan P; Dickinson, John W; Ansley, Les

    2009-01-01

    Abstract Background Exercise-related respiratory symptoms in the diagnosis of exercise-induced bronchoconstriction (EIB) have poor predictive value. The aim of this study was to evaluate how athletes presenting with these symptoms are diagnosed and managed in primary care. Methods An electronic survey was distributed to a random selection of family practitioners in England. The survey was designed to assess the frequency with which family practitioners encounter adults with exercise-related r...

  9. Prevalence of antimicrobial resistant Escherichia coli from patients with suspected urinary tract infection in primary care, Denmark

    DEFF Research Database (Denmark)

    Cordoba, Gloria; Holm, Anne; Hansen, Frank

    2017-01-01

    Background: Escherichia coli is the most common pathogen causing Urinary Tract Infections (UTI). Data from the current National Surveillance program in Denmark (DANMAP) may not accurately represent the prevalence of resistant E. coli in primary care, because only urine samples from complicated...... 485 (96%) patients. According to the European Urinalysis Standards, 261 (54%) patients had positive bacteriuria. The most common uropathogen in patients with uncomplicated (uUTI) and complicated (cUTI) urinary tract infection was E. coli 105 (69%) and 76 (70%), respectively. Eighty-two (45%) of 181 E......: Observational study carried out from December 2014 to December 2015. Thirty-nine general practices from The Capital Region of Denmark included adult patients with urinary tract symptoms and suspected UTI. All urine samples were sent to the central laboratory Statens Serum Institut (SSI). Significant bacteriuria...

  10. Antibiotic prescriptions for suspected respiratory tract infection in primary care in South America

    DEFF Research Database (Denmark)

    Cordoba, Gloria; Caballero, Lidia; Sandholdt, Håkon

    2017-01-01

    OBJECTIVES: To describe and compare antibiotic prescribing patterns for primary care patients with respiratory tract infections (RTIs) in four South American countries. METHODS: This was a prospective observational study. General practitioners (GPs) from Argentina, Bolivia, Paraguay and Uruguay......%) of these received an antibiotic prescription. There was a wide variation across countries in the use and selection of antibiotics. For example, 94% of patients with acute bronchitis were prescribed antibiotics in Bolivia, while in Uruguay only 21% received antibiotics. Amoxicillin was the most commonly prescribed...

  11. The diagnosis of antimitochondrial antibody-negative primary biliary cholangitis.

    Science.gov (United States)

    Ozaslan, Ersan; Efe, Cumali; Gokbulut Ozaslan, Nihal

    2016-11-01

    Autoimmune liver diseases are heterogenous disorders that share largely non-specific clinical, serological and pathological features. The correct diagnosis requires discriminative features which are highly specific, for example high-titer antimitochondrial antibodies (AMA) and florid duct lesion in primary biliary cholangitis (PBC). However, the imperfect sensitivities of these characteristic features and abuse of scoring systems led to many artificial diagnoses such as overlap syndromes and outliers for example "autoimmune cholangitis" which is now called as "AMA-negative PBC". Patients lacking detectable AMA (up to 20% in indirect immunofluorescence - IF), but otherwise presenting signs and symptoms of PBC should be regarded as affected by "AMA-negative PBC" because they seem to follow a natural history similar to that of their AMA positive counterparts. The complementary use of IF, ELISA and immunoblotting have disclosed that the majority of patients initially considered AMA-negative are in fact AMA positive. Moreover, the use of PBC-specific ANA's like Gp210 and sp100 have diminished the AMA-negative cases (if truly exists!) to less than 5%. The histological spectrum of PBC includes typical florid duct lesions and/or compatible features such as non-specific hepatitic and biliary findings. In the absence of florid duct lesion and AMA positivity, histology alone cannot differentiate PBC from other biliary disorders. However, the analysis of compatible histological features with the clinical, serological and imaging findings usually points to a specific diagnosis. In this review, we present serological, clinical and pathological pitfalls regarding AMA-negative PBC including illustrative cases and a diagnostic algorithm. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. Immunoblotting as a confirmatory test for antimitochondrial antibodies in primary biliary cirrhosis.

    OpenAIRE

    Provenzano, G; Diquattro, O; Craxì, A; Almasio, P; Pinzello, G; Marino, L; Fiorentino, G; Rinaldi, F; Pagliaro, L

    1993-01-01

    Primary biliary cirrhosis is characterised by the presence of antimitochondrial antibodies which are directed against components of mitochondrial dehydrogenase complexes. The specificity of antimitochondrial antibodies for primary biliary cirrhosis as detected by immunoblotting was investigated. Commercially available preparations of pyruvate and oxo-glutarate dehydrogenases and beef-heart mitochondria were used as source of antigens. Sera from 47 primary biliary cirrhosis patients (46 of who...

  13. Incidence of Ascaris suum-specific antibodies in Austrian patients with suspected larva migrans visceralis (VLM) syndrome.

    Science.gov (United States)

    Schneider, Renate; Auer, Herbert

    2016-03-01

    The pig roundworm, Ascaris suum, is commonly found in domestic pigs all over the world. The transmission to humans takes place by ingestion of infective A. suum eggs present in soil because pig manure is widely used as fertilizer. The possible role of A. suum in the human visceral larva migrans (VLM) syndrome has been discussed controversially during past decades, even though various case reports, particularly from Japan document pulmonal, hepatic and even cerebral symptoms caused by migrating A. suum larvae after ingestion of infected row meat (liver) or contaminated vegetables. We examined 4481 sera by A. suum immunoblot (As-IB) and 5301 sera by Toxocara-ELISA from patients with symptoms associated with the VLM syndrome during three consecutive years (2012-2014). The incidence of A. suum-specific antibodies was 13.2 %, the incidence of T. canis specific antibodies 12.9 % and from a part of the As-IB positive sera (n = 417) additional Toxocara serology was performed to demonstrate the specificity of our tests. Only 56 out of the 417 (13.4 %) sera showed antibodies to both helminth species demonstrating that double infections exist. Interestingly the age distribution of the patients showed that 2.8 % of the Ascaris-positive patients were younger than 21 years, while in the Toxocara-positive group 13.4 % were suum worms causing intestinal ascariosis is extremely rare in Central European countries, the zoonotic potential of A. suum is considerably underestimated. We suggest that the performance of reliable immunoserological tests, in all industrialized countries where pigs are raised and their manure is used as fertilizer, could help to assess the actual potential of A. suum as causative agent of the VLM syndrome in humans.

  14. Identifying patients with suspected pancreatic cancer in primary care: derivation and validation of an algorithm.

    Science.gov (United States)

    Hippisley-Cox, Julia; Coupland, Carol

    2012-01-01

    Pancreatic cancer has the worst survival for any cancer and is often diagnosed late when the cancer is advanced. Chances of survival are more likely if patients can be diagnosed earlier. To derive and validate an algorithm to estimate absolute risk of having pancreatic cancer in patients with and without symptoms in primary care. Cohort study using data from 375 UK QResearch® general practices for development and 189 for validation. Included patients were aged 30-84 years, free at baseline from a diagnosis of pancreatic cancer and had not had dysphagia, abdominal pain, abdominal distension, appetite loss, or weight loss recorded in the preceding 12 months. The primary outcome was incident diagnosis of pancreatic cancer recorded in the following 2 years. Risk factors examined included: age, body mass index, smoking status, alcohol, deprivation, diabetes, pancreatitis, previous diagnosis of cancer apart from pancreatic cancer, dysphagia, abdominal pain, abdominal distension, appetite loss, weight loss, diarrhoea, constipation, tiredness, itching, and anaemia. Cox proportional hazards models were used to develop separate risk equations in males and females. Measures of calibration and discrimination assessed performance in the validation cohort. There were a total of 1415 incident cases of pancreatic cancer from 4.1 million person-years in the derivation cohort. Independent predictors in both males and females were age, smoking, type 2 diabetes, chronic pancreatitis, abdominal pain, appetite loss, and weight loss. Abdominal distension was a predictor for females only; dysphagia and constipation were predictors for males only. On validation, the algorithms explained 59% of the variation in females and 62% in males. The receiver operating characteristic statistics were 0.84 (females) and 0.87 (males). The D statistic was 2.44 (females) and 2.61 (males). The 10% of patients with the highest predicted risks contained 62% of all pancreatic cancers diagnosed over the

  15. Approach to the diagnosis and management of suspected exercise-induced bronchoconstriction by primary care physicians

    Directory of Open Access Journals (Sweden)

    Hull James H

    2009-06-01

    Full Text Available Abstract Background Exercise-related respiratory symptoms in the diagnosis of exercise-induced bronchoconstriction (EIB have poor predictive value. The aim of this study was to evaluate how athletes presenting with these symptoms are diagnosed and managed in primary care. Methods An electronic survey was distributed to a random selection of family practitioners in England. The survey was designed to assess the frequency with which family practitioners encounter adults with exercise-related respiratory symptoms and how they would approach diagnostic work-up and management. The survey also evaluated awareness of and access to diagnostic tests in this setting and general knowledge of prescribing asthma treatments to competitive athletes. Results 257 family practitioners completed the online survey. One-third of respondents indicated they encountered individuals with this problem at a frequency of more than one case per month. Over two-thirds of family practitioners chose investigation as an initial management strategy, while one-quarter would initiate treatment based on clinical information alone. PEFR pre- and post-exercise was the most commonly selected test for investigation (44%, followed by resting spirometry pre- and post-bronchodilator (35%. Short-acting β2-agonists were the most frequently selected choice of treatment indicated by respondents (90%. Conclusion Family practitioners encounter individuals with exercise-related respiratory symptoms commonly and although objective testing is often employed in diagnostic work-up, the tests most frequently utilised are not the most accurate for diagnosis of EIB. This diagnostic approach may be dictated by the reported lack of access to more precise testing methods, or may reflect a lack of dissemination or awareness of current evidence. Overall the findings have implications both for the management and hence welfare of athletes presenting with this problem to family practitioners and also for the

  16. Intravenous and oral levetiracetam in patients with a suspected primary brain tumor and symptomatic seizures undergoing neurosurgery: the HELLO trial.

    Science.gov (United States)

    Bähr, Oliver; Hermisson, Mirjam; Rona, Sabine; Rieger, Johannes; Nussbaum, Susanne; Körtvelyessy, Peter; Franz, Kea; Tatagiba, Marcos; Seifert, Volker; Weller, Michael; Steinbach, Joachim P

    2012-02-01

    Levetiracetam (LEV) is a newer anticonvulsant with a favorable safety profile. There seem to be no relevant drug interactions, and an intravenous formulation is available. Therefore, LEV might be a suitable drug for the perioperative anticonvulsive therapy of patients with suspected brain tumors undergoing neurosurgery. In this prospective study (NCT00571155) patients with suspected primary brain tumors and tumor-related seizures were perioperatively treated with oral and intravenous LEV up to 4 weeks before and until 4 weeks after a planned neurosurgical procedure. Thirty patients with brain tumor-related seizures and intended neurosurgery were included. Three patients did not undergo the scheduled surgery after enrollment, and two patients were lost to follow-up. Therefore, 25 patients were fully evaluable. After initiation of therapy with LEV, 100% of the patients were seizure-free in the pre-surgery phase (3 days up to 4 weeks before surgery), 88% in the 48 h post-surgery phase and 84% in the early follow-up phase (48 h to 4 weeks post surgery). Treatment failure even after dose escalation to 3,000 mg/day occurred in three patients. No serious adverse events related to the treatment with LEV occurred. Our data show the feasibility and safety of oral and intravenous LEV in the perioperative treatment of tumor-related seizures. Although this was a single arm study, the efficacy of LEV appears promising. Considering the side effects and interactions of other anticonvulsants, LEV seems to be a favorable option in the perioperative treatment of brain tumor-related seizures.

  17. In-depth analysis of the antibody response of individuals exposed to primary dengue virus infection.

    Directory of Open Access Journals (Sweden)

    Ruklanthi de Alwis

    2011-06-01

    Full Text Available Humans who experience a primary dengue virus (DENV infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and, potentially, exacerbate disease. The actual binding sites of human antibody on the DENV particle are not well defined. We characterized the specificity and neutralization potency of polyclonal serum antibodies and memory B-cell derived monoclonal antibodies (hMAbs from 2 individuals exposed to primary DENV infections. Most DENV-specific hMAbs were serotype cross-reactive and weakly neutralizing. Moreover, many hMAbs bound to the viral pre-membrane protein and other sites on the virus that were not preserved when the viral envelope protein was produced as a soluble, recombinant antigen (rE protein. Nonetheless, by modifying the screening procedure to detect rare antibodies that bound to rE, we were able to isolate and map human antibodies that strongly neutralized the homologous serotype of DENV. Our MAbs results indicate that, in these two individuals exposed to primary DENV infections, a small fraction of the total antibody response was responsible for virus neutralization.

  18. In-Depth Analysis of the Antibody Response of Individuals Exposed to Primary Dengue Virus Infection

    Science.gov (United States)

    de Alwis, Ruklanthi; Beltramello, Martina; Messer, William B.; Sukupolvi-Petty, Soila; Wahala, Wahala M. P. B.; Kraus, Annette; Olivarez, Nicholas P.; Pham, Quang; Brian, James; Tsai, Wen-Yang; Wang, Wei-Kung; Halstead, Scott; Kliks, Srisakul; Diamond, Michael S.; Baric, Ralph; Lanzavecchia, Antonio; Sallusto, Federica; de Silva, Aravinda M.

    2011-01-01

    Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and, potentially, exacerbate disease. The actual binding sites of human antibody on the DENV particle are not well defined. We characterized the specificity and neutralization potency of polyclonal serum antibodies and memory B-cell derived monoclonal antibodies (hMAbs) from 2 individuals exposed to primary DENV infections. Most DENV-specific hMAbs were serotype cross-reactive and weakly neutralizing. Moreover, many hMAbs bound to the viral pre-membrane protein and other sites on the virus that were not preserved when the viral envelope protein was produced as a soluble, recombinant antigen (rE protein). Nonetheless, by modifying the screening procedure to detect rare antibodies that bound to rE, we were able to isolate and map human antibodies that strongly neutralized the homologous serotype of DENV. Our MAbs results indicate that, in these two individuals exposed to primary DENV infections, a small fraction of the total antibody response was responsible for virus neutralization. PMID:21713020

  19. Kinetics of Epstein-Barr Virus (EBV) Neutralizing and Virus-Specific Antibodies after Primary Infection with EBV.

    Science.gov (United States)

    Bu, Wei; Hayes, Gregory M; Liu, Hui; Gemmell, Lorraine; Schmeling, David O; Radecki, Pierce; Aguilar, Fiona; Burbelo, Peter D; Woo, Jennifer; Balfour, Henry H; Cohen, Jeffrey I

    2016-04-01

    Prospective studies of antibodies to multiple Epstein-Barr virus (EBV) proteins and EBV neutralizing antibodies in the same individuals before, during, and after primary EBV infection have not been reported. We studied antibody responses to EBV in college students who acquired primary EBV infection during prospective surveillance and correlated the kinetics of antibody response with the severity of disease. Neutralizing antibodies and enzyme-linked immunosorbent assay (ELISA) antibodies to gp350, the major target of neutralizing antibody, reached peak levels at medians of 179 and 333 days after the onset of symptoms of infectious mononucleosis, respectively. No clear correlation was found between the severity of the symptoms of infectious mononucleosis and the peak levels of antibody to individual viral proteins or to neutralizing antibody. In summary, we found that titers of neutralizing antibody and antibodies to multiple EBV proteins increase over many months after primary infection with EBV. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  20. Diagnostic value of anti-gp210 antibodies in primary biliary cirrhosis: a case-based review.

    Science.gov (United States)

    Valour, Florent; Durupt, Stéphane; Khenifer, Safia; Durieu, Isabelle

    2013-06-26

    Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterised by chronic cholestasis usually associated with antimitochondrial antibodies. Moreover, several types of antinuclear antibodies have been associated with primary biliary cirrhosis. We describe an 83-year-old man, in whom the exploration of a chronic cholestasis led to the diagnosis of primary biliary cirrhosis despite negative antimitochondrial antibodies, regarding the presence of anti-gp210 antibodies. Found in 25% of patients, these antinuclear antibodies must be sought before a strong suspicion of primary biliary cirrhosis with antimitochondrial antibodies negative, as they are highly specific of the disease. They are generally associated with a more aggressive form of PBC.

  1. Antimitochondrial antibody negative primary biliary cirrhosis: a distinct syndrome of autoimmune cholangitis.

    OpenAIRE

    Michieletti, P; Wanless, I R; Katz, A; Scheuer, P J; Yeaman, S J; Bassendine, M F; Palmer, J M; Heathcote, E J

    1994-01-01

    This study reports on a group of 20 patients with an initial diagnosis of primary biliary cirrhosis (PBC) whose serum tested negative for antimitochondrial antibodies by immunofluorescence. All had a clinical history compatible with primary biliary cirrhosis, and results of biochemical, histological, and radiological investigations were consistent with this diagnosis despite the absence of antimitochondrial antibodies by immunofluorescence. For comparison, these patients were matched for sex ...

  2. B-cell Development and Primary Antibody Deficiencies

    NARCIS (Netherlands)

    M.C. van Zelm (Menno)

    2007-01-01

    textabstractB lymphocytes are generated throughout life from hematopoietic stem cells in bone marrow, and contribute to the immune system by the production of antigen-specific antibodies (immunoglobulins; Ig). Two distinct phase of B-cell development can be distinguished: 1) antigen-independent

  3. Diagnostic value of anti-gp210 antibodies in primary biliary cirrhosis: a case-based review

    OpenAIRE

    Valour, Florent; Durupt, Stéphane; Khenifer, Safia; Durieu, Isabelle

    2013-01-01

    Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterised by chronic cholestasis usually associated with antimitochondrial antibodies. Moreover, several types of antinuclear antibodies have been associated with primary biliary cirrhosis. We describe an 83-year-old man, in whom the exploration of a chronic cholestasis led to the diagnosis of primary biliary cirrhosis despite negative antimitochondrial antibodies, regarding the presence of anti-gp210 antibodies. Found in 25% ...

  4. Changes in choroidal thickness after prophylactic iridectomy in primary angle closure suspect eyes using enhanced depth imaging optical coherence tomography

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2015-01-01

    Full Text Available Purpose: The aim of the present study was to evaluate the effect of surgical peripheral iridectomy (SPI on choroidal thickness in primary angle-closure suspect (PACS eyes. Materials and Methods: This was a prospective observational case series of 30 subjects with PACS. Ocular biometry was performed before SPI (baseline and then 1 week later. Choroid was imaged by enhanced depth imaging optical coherence tomography (EDI-OCT. The choroidal thickness of the subfoveal area at 1 and 3 mm diameter around the fovea was determined. Central anterior chamber depth (ACD, lens thickness (LT, vitreous chamber depth (VCD, and axial length (AL were measured by A-scan ultrasound. Parameters were compared before SPI (baseline and 1 week later. Results: Thirty eyes of 30 patients with mean age of 61.53 ± 7.98 years were studied. There was no significant difference in the choroidal thickness at all macular locations before and after SPI (all P > 0.05. Mean subfoveal choroidal thickness was 279.61 μm ± 65.50 μm before and 274.54 μm ± 63.36 μm after SPI (P = 0.308. There was also no significant change in central ACD, LT, VCD, and LT after SPI (all P > 0.05. Conclusions: SPI does not appear to alter choroidal thickness in PACS eyes, as assessed using EDI-OCT. Long-term follow-up of PACS eyes treated with SPI may provide further insight into the effects of this treatment modality on the choroid.

  5. Hypogammaglobulinemia in BLT humanized mice--an animal model of primary antibody deficiency.

    Directory of Open Access Journals (Sweden)

    Francisco Martinez-Torres

    Full Text Available Primary antibody deficiencies present clinically as reduced or absent plasma antibodies without another identified disorder that could explain the low immunoglobulin levels. Bone marrow-liver-thymus (BLT humanized mice also exhibit primary antibody deficiency or hypogammaglobulinemia. Comprehensive characterization of B cell development and differentiation in BLT mice revealed other key parallels with primary immunodeficiency patients. We found that B cell ontogeny was normal in the bone marrow of BLT mice but observed an absence of switched memory B cells in the periphery. PC-KLH immunizations led to the presence of switched memory B cells in immunized BLT mice although plasma cells producing PC- or KLH- specific IgG were not detected in tissues. Overall, we have identified the following parallels between the humoral immune systems of primary antibody deficiency patients and those in BLT mice that make this in vivo model a robust and translational experimental platform for gaining a greater understanding of this heterogeneous array of humoral immunodeficiency disorders in humans: (i hypogammaglobulinemia; (ii normal B cell ontogeny in bone marrow; and (iii poor antigen-specific IgG response to immunization. Furthermore, the development of strategies to overcome these humoral immune aberrations in BLT mice may in turn provide insights into the pathogenesis of some primary antibody deficiency patients which could lead to novel clinical interventions for improved humoral immune function.

  6. Antibody

    Science.gov (United States)

    An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples ... microorganisms (bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produced when the immune system mistakenly ...

  7. Prevalence of IgA Antibodies to Endomysium and Tissue Transglutaminase in Primary Biliary Cirrhosis

    Directory of Open Access Journals (Sweden)

    Helen R Gillett

    2000-01-01

    Full Text Available The association between celiac disease and primary biliary cirrhosis has been described in several case reports and small screening studies, with varying prevalence rates. Stored sera from 378 patients with primary biliary cirrhosis were tested for immunoglobulin (Ig A endomysium and tissue transglutaminase antibodies. Ten patients were positive for both antibodies (2.6%; five of these patients had had small bowel biopsies confirming celiac disease. A further 44 patients (11.6% had raised titres of IgA tissue transglutaminase antibody but were negative for IgA endomysium antibody. The increased prevalence of celiac-related antibodies in patients with primary biliary cirrhosis suggests that the two conditions are associated, although the reason for the association remains unclear. Patients with primary biliary cirrhosis should be considered to be at high risk for celiac disease. Although liver biochemistry does not improve when these patients are fed a gluten-free diet, the complications of untreated celiac disease warrant the identification and treatment of the condition in this population.

  8. Kidney disease in primary anti-phospholipid antibody syndrome.

    Science.gov (United States)

    Gracia-Tello, Borja; Isenberg, David

    2017-07-01

    APS is an autoimmune disease defined by the presence of arterial or venous thrombotic events and/or pregnancy morbidity in patients who test positive for aPL. APS can be isolated (primary APS) or associated with other autoimmune diseases. The kidney is a major target organ in APS, and renal thrombosis can occur at any level within the vasculature of the kidney (renal arteries, intrarenal vasculature and renal veins). Histological findings vary widely, including ischaemic glomeruli and thrombotic lesions without glomerular or arterial immune deposits on immunofluorescence. Renal involvement in patients with definite APS is treated with long-term anticoagulants as warfarin, but new treatments are being tried. The aim of this article is to review the links between primary APS and kidney disease. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Comparison of the 68Ga-DOTATATA PET/CT, FDG PET/CT, and MIBG SPECT/CT in the Evaluation of Suspected Primary Pheochromocytomas and Paragangliomas.

    Science.gov (United States)

    Jing, Hongli; Li, Fang; Wang, Ling; Wang, Zhenghua; Li, Wei; Huo, Li; Zhang, Jingjing

    2017-07-01

    Anatomical imaging modalities including CT and MRI are the mainstay of evaluation of primary pheochromocytoma or paraganglioma. However, nuclear medicine imaging is frequently necessary to determine the nature of the lesions. The purpose of this investigation is to assess which commonly used nuclear medicine modality might have a better diagnostic value in this clinical setting. Eight patients who had been suspected of having either primary pheochromocytoma or primary paraganglioma and 1 patient with known pheochromocytoma were included in the analysis. Among the 8 patients without known diagnosis, 7 had been suggested by anatomical imaging modalities, whereas one of them presented with initial negative anatomical imaging interpretation. All of 9 patients underwent Ga-DOTATATA PET/CT, FDG PET/CT, and MIBG SPECT/CT for further evaluation. The imaging findings were compared with postsurgical pathology and follow-up. Both Ga-DOTATATA PET/CT and MIBG SPECT/CT accurately identified 9 primary tumors, whereas FDG PET/CT showed increased activity in 8 of 9 primary tumors. Both Ga-DOTATATA and FDG PET/CT are able to detect associated extra-adrenal lesions not shown on MIBG study in patients with multiple endocrine neoplasia syndrome. Ga-DOTATATA PET/CT could be the nuclear medicine imaging choice to evaluate suspected primary pheochromocytoma or paraganglioma, especially in the situation of multiple endocrine neoplasia syndrome.

  10. Factors of Innate and Adaptive Local Immunity in Children with Primary Deficiencies of Antibody Formation

    Directory of Open Access Journals (Sweden)

    L.I. Chernyshova

    2013-10-01

    Full Text Available In 40 children with various types of primary immunodeficiencies (PID of antibody formation we examined factors of local immunity in saliva. It is found that in the saliva of children with PID of antibody formation in comparison with immunocompetent children the concentration of factors of adaptive immunity is significantly reduced. Lack of adaptive immunity in the PID of antibody formation to some extent is compensated by increased concentrations of innate immune factors on the mucous membranes — the free Sc, as well as lactoferrin in selective immunodeficiency of IgA. At PID of antibody formation we observed increased TNF-α level in the saliva, which may indicate the persistence of local inflammation on the membranes of the respiratory tract.

  11. ANTIMITOCHONDRIAL ANTIBODY PROFILES IN PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS BEFORE ORTHOTOPIC LIVER-TRANSPLANTATION AND TITERS OF ANTIMITOCHONDRIAL ANTIBODY-SUBTYPES AFTER TRANSPLANTATION

    NARCIS (Netherlands)

    HUIZENGA, [No Value; GIPS, CH; BERG, PA

    Four antimitochondrial antibody profiles (A-D) have been defined in primary biliary cirrhosis according to the presence of antibodies to M2, M4, M8, and M9 in ELISA and the complement fixation test: A: anti-M9 positive in ELISA and western blot, B: anti-M9 and/or anti-M2 positive in ELISA, C:

  12. Mycoplasma antigens as a possible trigger for the induction of antimitochondrial antibodies in primary biliary cirrhosis.

    Science.gov (United States)

    Berg, Christoph P; Kannan, Thirumalai R; Klein, Reinhild; Gregor, Michael; Baseman, Joel B; Wesselborg, Sebastian; Lauber, Kirsten; Stein, Gerburg M

    2009-07-01

    In primary biliary cirrhosis (PBC), autoreactivity mainly targets members of the pyruvate dehydrogenase complex (PDC). Because PDC subunits are expressed on the surface of mycoplasma and molecular mimicry may be one aetiological factor, we analysed the presence of mammalian and mycoplasma PDC-specific antibodies in PBC patients. Antibodies to porcine PDC and Mycoplasma pneumoniae (mp) antigens mpPDH-C (to be designated mpPDC-E2 chain), mpPDH-B (to be designated mpPDC-E1beta chain), mpCARDS TX and mpP1 were investigated in sera from 43 PBC patients, 19 patients with autoimmune hepatitis and 11 healthy controls by an enzyme-linked immunosorbent assay and Western blotting. To study the rate of acute mycoplasma infection, an adhesin P1-specific polymerase chain reaction (PCR) was performed. Immune reactivity to the mpPDC-E2 antigen was significantly enhanced in PBC patients (83.7%) as compared with controls (overall frequency of 36.7%), while antibodies to the porcine PDC-E2 chain were found only in PBC patients (88%) excluding a simple cross-reactivity of PDC-related antibodies. This observation was confirmed by inhibition studies demonstrating that porcine PDC did not inhibit mycoplasma PDC-specific antibodies and vice versa. The occurrence of antibodies to mpPDC seems to precede the occurrence of antibodies to porcine PDC. Infection with mycoplasma was equally distributed in the groups as evidenced by an antibody frequency comparable to CARDS TX and P1 and PCR reactivity. Because PBC patients show a significantly enhanced frequency of mpPDC-E2-related antibodies, besides other factors, molecular mimicry between surface molecules of mycoplasma and epitopes of the autoantigen may play a central role in the aetiopathology of PBC.

  13. Serial Analysis of Antimitochondrial Antibody in Patients with Primary Biliary Cirrhosis

    Directory of Open Access Journals (Sweden)

    Gordon D. Benson

    2004-01-01

    Full Text Available Antimitochondrial antibodies (AMAs are the classic serologic marker in primary biliary cirrhosis (PBC. However, there have been only limited attempts to study changes in titer or isotype analysis of such AMAs in patients followed for long periods of time

  14. A Case of Antimitochondrial Antibody Negative Primary Biliary Cirrhosis from Bangladesh and Review of Literature.

    Science.gov (United States)

    Begum, Roksana; Mahtab, Mamun-Al; Al Mamun, Ayub; Kumar Saha, Biplob; Shahadat Hossain, Sharker Mohammad; Chandra Das, Dulal; Fazle Akbar, Sheikh Mohammad; Kamal, Mohammad; Rahman, Salimur

    2015-01-01

    Primary biliary cirrhosis (PBC) is very closely associated with the presence of antimitochondrial antibodies (AMA). Nevertheless, 5 to 10% of patients with typical features of primary biliary cirrhosis do not have detectable AMA. They are referred to as AMA negative PBC. We report a case of PBC who was AMA-negative. The patient was a middle-aged woman seeking help of dermatologist for her complaint of itching. The diagnosis was confirmed by histopathology, whereas other possible causes of cirrhosis were excluded. Begum R, Mahtab MA, Mamun AA, Saha BK, Hossain SMS, Saha DC, Akbar SMF, Kamal M, Rahman S. A Case of Antimitochondrial Antibody Negative Primary Biliary Cirrhosis from Bangladesh and Review of Literature. Euroasian J Hepato-Gastroenterol 2015;5(2):122-126.

  15. Prevalence of coeliac disease in primary biliary cirrhosis and of antimitochondrial antibodies in adult coeliac disease patients in Italy.

    Science.gov (United States)

    Floreani, A; Betterle, C; Baragiotta, A; Martini, S; Venturi, C; Basso, D; Pittoni, M; Chiarelli, S; Sategna Guidetti, C

    2002-04-01

    Although an association between primary biliary cirrhosis and coeliac disease has recently been reported in Northern Europe, there are still conflicting data concerning this issue. To evaluate both the prevalence of coeliac disease in a series of primary biliary cirrhosis patients and that of antimitochondrial antibodies in a series of adult biopsy proven coeliac disease patients from Northern Italy. A total of 87 primary biliary cirrhosis patients (79 female, 8 male) were screened for both IgA-transglutaminase antibodies and antiendomysium antibodies and, in those with either IgA-transglutaminase antibodies or antiendomysium antibodies positivity, upper endoscopy with distal duodenum biopsy was offered. In those who refused upper endoscopy, the intestinal permeability test with lactulose/mannitol excretion was performed. Antiendomysium antibodies positivity was detected in 3 subjects (3.4%), all of whom had serum IgA-transglutaminase antibodies above the normal range, and fulfilled the diagnosis of coeliac disease. Of 21 other patients with serum IgA-transglutaminase antibodies above the normal range, 17 underwent upper endoscopy which revealed normal duodenum architecture. The remaining 4 patients underwent the lactulose/mannitol excretion test which was within the normal range. Sera from 108 adult coeliac disease patients were tested for antimitochondrial antibodies and positivity was found in 4 patients (3.7%): all had normal liver biochemistry tests, whereas 2 of them also presented thyroid disease. Antibodies directed to the 74-kDa polypeptide of antimitochondrial antibodies were found in 3 out of 4 antimitochondrial antibodies+ve patients. These results suggest an association between primary biliary cirrhosis and coeliac disease similar to that observed in the Northern European series. In conclusion, screening for coeliac disease with antiendomysium antibodies in primary biliary cirrhosis is justified, and screening for antimitochondrial antibodies is

  16. Antinuclear antibodies giving the 'multiple nuclear dots' or the 'rim-like/membranous' patterns: diagnostic accuracy for primary biliary cirrhosis.

    Science.gov (United States)

    Granito, A; Muratori, P; Muratori, L; Pappas, G; Cassani, F; Worthington, J; Guidi, M; Ferri, S; DE Molo, C; Lenzi, M; Chapman, R W; Bianchi, F B

    2006-12-01

    Serum antinuclear antibodies giving the 'multiple nuclear dots' or the 'rim-like/membranous' patterns are frequently detected by indirect immunofluorescence on HEp-2 cells in patients with primary biliary cirrhosis. To assess the accuracy of multiple nuclear dot and rim-like/membranous antinuclear antibodies for the diagnosis of primary biliary cirrhosis. Sera from 4371 consecutive patients referred to our laboratory were analysed under code for antinuclear antibodies testing by indirect immunofluorescence on HEp-2 cells. Review of the clinical records of the 4371 patients allowed identification of 101 patients with antimitochondrial antibody-positive primary biliary cirrhosis and 22 with antimitochondrial antibody-negative variant. Multiple nuclear dot and/or rim-like/membranous patterns were found in 59 (1.3%) of the 4371 patients: 31 antimitochondrial antibody-positive primary biliary cirrhosis, 17 antimitochondrial antibody-negative primary biliary cirrhosis and 11 non-primary biliary cirrhosis. The specificity for primary biliary cirrhosis of both the antinuclear antibodies pattern was 99%. Positive predictive value and likelihood ratio for a positive test were 86% (95% CI: 72.7-94) and 221 (95% CI: 91.7-544) for multiple nuclear dot, 79% (95% CI: 62.2-90.1) and 132 (95% CI: 56.8-312.7) for rim-like/membranous, respectively. Multiple nuclear dot and rim-like/membranous antinuclear antibodies are rare findings. Their positivity strongly suggests the diagnosis of primary biliary cirrhosis, irrespective of antimitochondrial antibody status. The high specificity for primary biliary cirrhosis makes them a useful diagnostic tool especially in antimitochondrial antibody-negative patients.

  17. Phenotyping and auto-antibody production by liver-infiltrating B cells in primary sclerosing cholangitis and primary biliary cholangitis.

    Science.gov (United States)

    Chung, Brian K; Guevel, Bardia T; Reynolds, Gary M; Gupta Udatha, D B R K; Henriksen, Eva Kristine Klemsdal; Stamataki, Zania; Hirschfield, Gideon M; Karlsen, Tom Hemming; Liaskou, Evaggelia

    2017-02-01

    Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are immune-mediated biliary diseases that demonstrate prominent and restricted genetic association with human leukocyte antigen (HLA) alleles. In PBC, anti-mitochondrial antibodies (AMA) are specific and used as diagnostic biomarkers. PSC-relevant auto-antibodies remain controversial despite a distinct HLA association that mirrors archetypical auto-antigen driven disorders. Herein, we compared antibody-secreting B cells (ASCs) in PSC and PBC liver explants to determine if liver-infiltrating ASCs represent an opportune and novel source of disease-relevant auto-antibodies. Using enzymatic digestion and mechanical disruption, liver mononuclear cells (LIMCs) were isolated from fresh PSC and PBC explants and plasmablast (CD19+CD27+CD38hiCD138-) and plasma cell (CD19+CD27+CD38hiCD138+) ASCs were enumerated by flow cytometry. We observed 45-fold fewer plasma cells in PSC explants (n = 9) compared to PBC samples (n = 5, p < 0.01) and 10-fold fewer IgA-, IgG- and IgM-positive ASCs (p < 0.05). Liver-infiltrating ASCs from PSC and PBC explants were functional and produced similar concentrations of IgA, IgG and IgM following 2 weeks of culture. Antibody production by PBC ASCs (n = 3) was disease-specific as AMA to pyruvate dehydrogenase complex E2 subunit (PDC-E2) was detected by immunostaining, immunoblotting and ELISA. Antibody profiling of PSC supernatants (n = 9) using full-length recombinant human protein arrays (Cambridge Protein Arrays) revealed reactivities to nucleolar protein 3 (5/9) and hematopoietic cell-specific Lyn substrate 1 (3/9). Array analysis of PBC supernatants (n = 3) detected reactivities to PDC-E2 and hexokinase 1 (3/3). In conclusion, we detected unique frequencies of liver-infiltrating ASCs in PSC and PBC and in so doing, highlight a feasible approach for understanding disease-relevant antibodies in PSC. Copyright © 2016. Published by Elsevier Ltd.

  18. Spooky Suspects

    Science.gov (United States)

    Pacifici, Lara

    2011-01-01

    This activity presents an option for covering biology content while engaging students in an investigation that highlights the spirit of Halloween. Students are engaged in the story line and have fun trying to solve the mystery kidnapping by using science skills to examine the evidence and eliminate some ghoulish suspects. (Contains 1 figure.)

  19. Coping, quality of life, and hope in adults with primary antibody deficiencies

    Directory of Open Access Journals (Sweden)

    Stray-Pedersen Asbjørg

    2005-05-01

    Full Text Available Abstract Background Living with a chronic disease, such as primary antibody deficiency, will often have consequences for quality of life. Previous quality-of-life studies in primary antibody deficiency patients have been limited to different treatment methods. We wanted to study how adults with primary antibody deficiencies manage their conditions and to identify factors that are conducive to coping, good quality of life and hope. Methods Questionnaires were sent to all patients ≥20 years of age with primary antibody deficiencies who were served by Rikshospitalet University Hospital. The questionnaires consisted of several standardized scales: Ferrans and Powers Quality of Life Index (QLI, Short Form-36 (SF-36, Jalowiec Coping Scale (JCS, Nowotny Hope Scale (NHS, and one scale we devised with questions about resources and pressures in the past. Of a total of 91, 55 patients (aged 23–76 years answered the questionnaires. The questionnaire study were supplemented with selected interviews of ten extreme cases, five with low and five with high quality of life scores. Results Among the 55 patients, low quality of life scores were related to unemployment, infections in more than four organs, more than two additional diseases, or more than two specific occurrences of stress in the last 2–3 months. Persons with selective IgA deficiency had significantly higher QLI scores than those with other antibody deficiencies. An optimistic coping style was most frequent used, and hope values were moderately high. Based on the interviews, the patients could be divided into three groups: 1 low QLI scores, low hope values, and reduced coping, 2 low QLI scores, moderate hope values, and good coping, and 3 high QLI scores, moderate to strong hope values, and good coping. Coping was related to the patients' sense of closeness and competence. Conclusion Low quality of life scores in adults with primary antibody deficiencies were linked to unemployment and disease

  20. Validation of two age dependent D-dimer cut-off values for exclusion of deep vein thrombosis in suspected elderly patients in primary care: retrospective, cross sectional, diagnostic analysis

    OpenAIRE

    Schouten, Henrike J; Koek, H L; Oudega, Ruud; Geersing, Geert-Jan; Janssen, Kristel J M; Johannes J M van Delden; Moons, Karel G.M.

    2012-01-01

    Objective To determine whether the use of age adapted D-dimer cut-off values can be translated to primary care patients who are suspected of deep vein thrombosis. Design Retrospective, cross sectional diagnostic study. Setting 110 primary care doctors affiliated with three hospitals in the Netherlands. Participants 1374 consecutive patients (936 (68.1%) aged >50 years) with clinically suspected deep vein thrombosis. Main outcome measures Proportion of patients with D-dimer values below two pr...

  1. Detection of Anti-Paracoccidioides brasiliensis antibodies in suspected tuberculosis patients = Detecção de anticorpos anti-Paracoccidioides brasiliensis em pacientes suspeitos de tuberculose

    Directory of Open Access Journals (Sweden)

    Maria Luiza Dias Fraga Peron

    2010-07-01

    Full Text Available Paracoccidioidomycosis (PCM is an important systemic mycosis in LatinAmerica that occurs as active disease in 1-2% of Paracoccidioides brasiliensis infected people. Like PCM, tuberculosis (TB affects mainly the lungs and the clinical and radiological aspects do notalways allow differentiation between them. The aim of this study was to carry out serological investigation for detecting anti-P. brasiliensis antibodies, by three serological methods, in patientswith symptoms suggestive of pulmonary TB. From August 2005 to September 2006, 76 patients with pulmonary symptoms suspected for TB were attended at the Regional Specialties Center Laboratory in the city of Paranavaí, Paraná, Brazil and submitted to microbiological TB research, ELISA, immunodiffusion and immunoblotting for PCM. Of all the individuals, 21 (27.63% were reactive to P. brasiliensis by ELISA and 11 (14.47% showed a laboratory diagnosis of pulmonary TB. Of all the individuals serologically reactive to P. brasiliensis, by ELISA, none had positive results by immunodiffusion and one reacted with antigen 43 kDa when Immunobloting was carried out. Our results lead us to reflect a necessity to obtain a more specific serologic test for diagnosis of PCM disease in patients with respiratory symptoms considering the high number of individuals reactive to P. brasiliensis especially in endemic areas.Paracoccidioidomicose (PCM é importante micose sistêmica na América Latina, que ocorre como doença ativa em 1-2% dos indivíduos infectados com Paracoccidioides brasiliensis. Assim como a PCM, a tuberculose (TB afeta principalmente os pulmões, porém os aspectos clínicos e radiológicos nem sempre permitem a diferenciação entreessas doenças. O objetivo deste estudo foi realizar um inquérito sorológico para a detecção de anticorpos anti-P. brasiliensis, utilizando três métodos sorológicos, em pacientes com sintomassugestivos de tuberculose pulmonar. De agosto de 2005 a setembro de

  2. Antibody response to a major human Pneumocystis carinii surface antigen in patients without evidence of immunosuppression and in patients with suspected atypical pneumonia

    DEFF Research Database (Denmark)

    Lundgren, Bettina; Lebech, M; Lind, K

    1993-01-01

    under evaluation due to atypical pneumonia, 76 patients showed no change in the titre of antibodies to Legionella spp. or Mycoplasma pneumoniae in two consecutive serum samples. Three of these 76 patients (4%) demonstrated an increase in the level of IgG antibodies to gp95 in the paired samples. One...

  3. Serum lipids and anti-oxidized LDL antibodies in primary antiphospholipid syndrome.

    Science.gov (United States)

    Bećarević, M; Andrejević, S; Miljić, P; Bonaci-Nikolić, B; Majkić-Singh, N

    2007-01-01

    The link between specific antibodies and atherogenesis in primary antiphospholipid syndrome (PAPS) is less strong than for thrombosis, although clearly the two processes are related and thrombosis is the main complication of atherosclerosis, a process known as atherothrombosis. The aim of this study was to investigate the influence of serum lipid levels and anti-oxidized LDL (oxLDL) antibodies on the clinical features of 42 patients with PAPS (mean age 40.45+/-13.37; 32 women and 10 men), and to compare them with 47 control subjects (mean age 39.68+/-13.93; 33 women and 14 men). Total cholesterol, HDL and triglyceride concentrations were determined by enzymatic methods. LDL was calculated according to the Friedwald formula. Anticardiolipin, anti-oxidized LDL and anti-Beta2glycoprotein I antibodies were detected by ELISA. A significant association was found between arterial events and triglyceride, LDL and cholesterol concentrations, but multivariate analysis showed that cholesterol concentrations were the most important predictor of arterial events (p=0.012). Cerebrovascular insults were the most significantly associated with cholesterol concentrations (p=0.011). Myocardial infarctions were more frequently present in patients more than 40 years of age (p=0.032). No significant association of the investigated parameters with venous thromboses was found. Recurrent abortions were not associated with the presence or concentrations of the investigated parameters. Although patients had increased concentrations of anti-oxLDL antibodies, no significant association was found between the titres of anti-oxLDL antibodies and clinical features of APS. In patients with PAPS, lipid concentrations are a better predictor for arterial events than anti-oxLDL antibodies.

  4. Detection of primary colorectal cancer with indium 111 monoclonal antibody B72. 3

    Energy Technology Data Exchange (ETDEWEB)

    Doerr, R.J.; Abdel-Nabi, H.; Baker, J.M.; Steinberg, S. (Veterans Affairs Medical Center, Buffalo, NY (USA))

    1990-12-01

    B72.3 is a murine monoclonal antibody of the immunoglobulin subclass IgG1 directed against TAG-72, a cell surface antigen present on colorectal carcinoma cells. We investigated the utility of scanning with indium 111-labeled B72.3 in 16 patients with a high clinical suspicion of or biopsy-proven primary colorectal cancer. Each patient received 1 or 2 mg of B72.3 monoclonal antibody labeled with 152 MBq of indium 111. Patients underwent scanning 2 to 3 days and 7 days after infusion by planar and emission computed tomography. Nineteen lesions were confirmed in 12 patients. Three patients with benign polyps had true-negative monoclonal antibody scans. Indium 111-labeled imaging of B72.3 detected nine of 19 lesions. Unsuspected tumor sites were identified by monoclonal antibody scan in three patients. By detection of additional abdominal disease and extra-abdominal spread, indium 111-labeled scanning of B72.3 directly affected treatment in 18% of patients.

  5. EBV-positive primary central nervous system lymphomas in monozygote twins with common variable immunodeficiency and suspected multiple sclerosis.

    Science.gov (United States)

    Jensen, M K; Koch-Henriksen, N; Johansen, P; Varming, K; Christiansen, C B; Knudsen, F

    1997-12-01

    Common variable immunodeficiency represents the most frequently occurring primary immunodeficiency disorder and is usually detected sporadically in patients with no family history of immunodeficiency. We present the case stories of two monozygote twins, who following a period of decreasing serum immunoglobulins developed primary central nervous system lymphomas. One twin had clinical and paraclinical features mimicking multiple sclerosis. Immunohistochemical investigations on biopsy tissue showed expression of the bcl-2 and p53 gene products, and Epstein-Barr virus (EBV) encoded small RNA's (EBER) indicating latent infection were detected in lymphoma cells using in situ hybridisation techniques. The pathogenetic role of EBV in oncogenesis is discussed.

  6. Patients Suspected of Irritable Bowel Syndrome-Cross-Sectional Study Exploring the Sensitivity of Rome III Criteria in Primary Care

    DEFF Research Database (Denmark)

    Engsbro, Anne Line; Begtrup, Luise Mølenberg; Kjeldsen, Jens

    2013-01-01

    The Rome III criteria for irritable bowel syndrome (IBS) are recommended by guidelines to help identify the syndrome. The majority of IBS patients are managed in primary care, where a pragmatic approach to diagnosis is usually adopted, using clinical judgment and knowledge about the patient. Many...

  7. Antibody levels to tetanus, diphtheria, measles and varicella in patients with primary immunodeficiency undergoing intravenous immunoglobulin therapy: a prospective study.

    Science.gov (United States)

    Nobre, Fernanda Aimée; Gonzalez, Isabela Garrido da Silva; Simão, Raquel Maria; de Moraes Pinto, Maria Isabel; Costa-Carvalho, Beatriz Tavares

    2014-06-21

    Patients with antibody deficiencies depend on the presence of a variety of antibody specificities in intravenous immunoglobulin (IVIG) to ensure continued protection against pathogens. Few studies have examined levels of antibodies to specific pathogens in IVIG preparations and little is known about the specific antibody levels in patients under regular IVIG treatment. The current study determined the range of antibodies to tetanus, diphtheria, measles and varicella in IVIG products and the levels of these antibodies in patients undergoing IVIG treatment. We selected 21 patients with primary antibody deficiencies who were receiving regular therapy with IVIG. Over a period of one year, we collected four blood samples from each patient (every 3 months), immediately before immunoglobulin infusion. We also collected samples from the IVIG preparation the patients received the month prior to blood collection. Antibody levels to tetanus, diphtheria, measles and varicella virus were measured in plasma and IVIG samples. Total IgG levels were determined in plasma samples. Antibody levels to tetanus, diphtheria, varicella virus and measles showed considerable variation in different IVIG lots, but they were similar when compared between commercial preparations. All patients presented with protective levels of antibodies specific for tetanus, measles and varicella. Some patients had suboptimal diphtheria antibody levels. There was a significant correlation between serum and IVIG antibodies to all pathogens, except tetanus. There was a significant correlation between diphtheria and varicella antibodies with total IgG levels, but there was no significant correlation with antibodies to tetanus or measles. The study confirmed the variation in specific antibody levels between batches of the same brand of IVIG. Apart from the most common infections to which these patients are susceptible, health care providers must be aware of other vaccine preventable diseases, which still exist

  8. Synchronous Low-grade Appendiceal Mucinous Neoplasm and Primary Peritoneal Low-grade Serous Carcinoma: A First Description of These 2 Neoplasms Presenting Together as Suspected Peritoneal Carcinomatosis.

    Science.gov (United States)

    Sekulic, Miroslav; Pichler Sekulic, Simona; Movahedi-Lankarani, Saeid

    2017-09-01

    Low-grade appendiceal mucinous neoplasm is a neoplasm typically of appendiceal origin, which is characterized by diffuse peritoneal involvement by pools of mucin with mucinous epithelium lacking high-grade cytologic atypia, and clinically presents as suspected peritoneal carcinomatosis. A similar clinical presentation can sometimes be seen with disseminated low-grade serous carcinomas of the peritoneum, fallopian tubes, or ovaries; however, this neoplasm is histologically characterized by tubal-type epithelium and invasive or confluent growth. In this case report, we describe a patient presenting with a clinical examination and radiologic features suggestive of peritoneal carcinomatosis and a prominent pelvic mass; however, after pathologic review, the patient was proven to have peritoneal involvement by both low-grade appendiceal mucinous neoplasm of appendiceal origin and a low-grade peritoneal primary serous carcinoma. In short, we present the first description of low-grade appendiceal mucinous neoplasm and serous carcinoma of the peritoneum presenting synchronously, providing morphologic characterization and immunohistochemical studies supporting the diagnosis, and illustrating a rare instance in which 2 neoplastic processes are underlying clinically suspected peritoneal carcinomatosis.

  9. A sensitive bead assay for antimitochondrial antibodies: Chipping away at AMA-negative primary biliary cirrhosis.

    Science.gov (United States)

    Oertelt, Sabine; Rieger, Roman; Selmi, Carlo; Invernizzi, Pietro; Ansari, Aftab A; Coppel, Ross L; Podda, Mauro; Leung, Patrick S C; Gershwin, M Eric

    2007-03-01

    The antimitochondrial response in primary biliary cirrhosis (PBC) is the most highly directed and specific self-reacting antibody in human immunopathology. Originally, antimitochondrial antibodies (AMAs) were detected by indirect immunofluorescence (IIF) and found in approximately 90% of well-documented patients with PBC. The introduction of recombinant autoantigens and the use of immunoblotting have increased the sensitivity and specificity of AMAs, and they are now considered positive in approximately 95% of patients with PBC. Clearly, accurate autoantibody detection represents one of the fundamental requirements for reliable diagnostics in autoimmunity. To address the 5% of AMA-negative patients with PBC, we have generated and validated a bead assay for the detection of AMA. We enrolled 120 patients with PBC, including a non-random group of 30 rigorously proven AMA-negative patients, 50 healthy subjects, and 74 controls with autoimmune diseases (18 with primary sclerosing cholangitis, 16 with autoimmune hepatitis, and 40 with systemic lupus erythematosus). Individual bead assays were done with the three mitochondrial autoantigens, PDC-E2, BCOADC-E2, and OGDC-E2. As expected, 90 of 90 previously known AMA-positive patients remained positive with this assay but, interestingly, 20% of the rigorously defined AMA-negative patient group had antibodies to one or more of the mitochondrial autoantigens. Furthermore, 100% of these newly detected AMA-positive patients were anti-nuclear antibody (ANA) positive. The development of this assay reflects the potential for automated detection with rapid and reliable assaying and further highlights the diminished number of truly AMA-negative PBC patients.

  10. HIV-1 Cross-Reactive Primary Virus Neutralizing Antibody Response Elicited by Immunization in Nonhuman Primates.

    Science.gov (United States)

    Wang, Yimeng; O'Dell, Sijy; Turner, Hannah L; Chiang, Chi-I; Lei, Lin; Guenaga, Javier; Wilson, Richard; Martinez-Murillo, Paola; Doria-Rose, Nicole; Ward, Andrew B; Mascola, John R; Wyatt, Richard T; Karlsson Hedestam, Gunilla B; Li, Yuxing

    2017-11-01

    Elicitation of broadly neutralizing antibody (bNAb) responses is a major goal for the development of an HIV-1 vaccine. Current HIV-1 envelope glycoprotein (Env) vaccine candidates elicit predominantly tier 1 and/or autologous tier 2 virus neutralizing antibody (NAb) responses, as well as weak and/or sporadic cross-reactive tier 2 virus NAb responses with unknown specificity. To delineate the specificity of vaccine-elicited cross-reactive tier 2 virus NAb responses, we performed single memory B cell sorting from the peripheral blood of a rhesus macaque immunized with YU2gp140-F trimers in adjuvant, using JR-FL SOSIP.664, a native Env trimer mimetic, as a sorting probe to isolate monoclonal Abs (MAbs). We found striking genetic and functional convergence of the SOSIP-sorted Ig repertoire, with predominant VH4 or VH5 gene family usage and Env V3 specificity. Of these vaccine-elicited V3-specific MAbs, nearly 20% (6/33) displayed cross-reactive tier 2 virus neutralization, which recapitulated the serum neutralization capacity. Substantial similarities in binding specificity, neutralization breadth and potency, and sequence/structural homology were observed between selected macaque cross-reactive V3 NAbs elicited by vaccination and prototypic V3 NAbs derived from natural infections in humans, highlighting the convergence of this subset of primate V3-specific B cell repertories. Our study demonstrated that cross-reactive primary virus neutralizing B cell lineages could be elicited by vaccination as detected using a standardized panel of tier 2 viruses. Whether these lineages could be expanded to acquire increased breadth and potency of neutralization merits further investigation.IMPORTANCE Elicitation of antibody responses capable of neutralizing diverse HIV-1 primary virus isolates (designated broadly neutralizing antibodies [bNAbs]) remains a high priority for the vaccine field. bNAb responses were so far observed only in response to natural infection within a subset

  11. Antibody response to a major human Pneumocystis carinii surface antigen in patients without evidence of immunosuppression and in patients with suspected atypical pneumonia

    DEFF Research Database (Denmark)

    Lundgren, Bettina; Lebech, M; Lind, K

    1993-01-01

    IgG and IgM antibodies to a purified human Pneumocystis carinii surface antigen (gp95) were measured in 694 serum specimens from two different population groups using an EIA technique. In a population of 441 patients with no evidence of immunosuppression, the percentage of persons positive for Ig......G antibodies to gp95 was significantly lower in the age group 1 to 9 years (30%, 23/77) compared to persons 10 to 19 years old (56%, 49/88). In the age group 1 to 14 years there was a significant correlation between the percentage of persons with IgG antibodies to gp95 and age. In 106 consecutive patients...... under evaluation due to atypical pneumonia, 76 patients showed no change in the titre of antibodies to Legionella spp. or Mycoplasma pneumoniae in two consecutive serum samples. Three of these 76 patients (4%) demonstrated an increase in the level of IgG antibodies to gp95 in the paired samples. One...

  12. Development of subtype-specific and heterosubtypic antibodies to the influenza A virus hemagglutinin after primary infection in children.

    OpenAIRE

    Burlington, D B; Wright, P F; van Wyke, K L; Phelan, M A; Mayner, R E; Murphy, B R

    1985-01-01

    Children undergoing primary infection with an H1N1 or H3N2 influenza A virus developed subtype-specific hemagglutination inhibition antibodies and enzyme-linked immunosorbent assay antibodies to purified hemagglutinin (HA) of the infecting virus subtype. They also developed lower titered ELISA antibodies to the noninfecting H1 or H3 HA and to H8 (an avian strain) HA. Thus, after primary infection with an influenza A virus, children develop enzyme-linked immunosorbent assay, but not hemaggluti...

  13. Changes in titers of antimitochondrial and antinuclear antibodies during the course of primary biliary cirrhosis.

    Science.gov (United States)

    Masuda, J; Omagari, K; Matsuo, I; Kinoshita, H; Sakimura, K; Hazama, H; Ohba, K; Isomoto, H; Murase, K; Murata, I; Kohno, S

    2001-02-01

    A case of primary biliary cirrhosis (PBC) in whom a complete biochemical (serum bilirubin, transaminases and alkaline phosphatase) remission was noted after combination treatment with ursodeoxycholic acid (UDCA) and corticosteroid is reported. The antimitochondrial antibody (AMA) detected by indirect immunofluorescence was initially positive, and the antinuclear antibody (ANA) was negative, but these two antibodies subsequently fluctuated independently (AMA-positive/ANA-negative, AMA-negative/ANA-negative, AMA-negative/ANA-positive, AMA-positive/ANA-positive, and again AMA-negative/ANA-positive) in spite of a lack of histopathological improvement in the liver after treatment. The clinical presentation in our case suggests that in some cases the diagnosis of PBC or so-called autoimmune cholangitis (AIC) might depend on the 'phase' of the same disease. Our results also suggest that detailed immunoreactive profiles against 2-oxo-acid dehydrogenase complex (2-OADC) enzymes by using immunoblotting, together with a serial histological examination, should provide more precise information for a diagnosis of PBC.

  14. Anti-M3 muscarinic acetylcholine receptor antibodies in patients with primary biliary cirrhosis.

    Science.gov (United States)

    Tsuboi, Hiroto; Ohira, Hiromasa; Asashima, Hiromitsu; Tsuzuki, Sayaka; Iizuka, Mana; Matsuo, Naomi; Kondo, Yuya; Matsumoto, Isao; Sumida, Takayuki

    2014-12-01

    M3 muscarinic acetylcholine receptor (M3R) is expressed in biliary tracts as well as in exocrine glands. It is reported that some patients with primary biliary cirrhosis (PBC) carry autoantibodies against M3R. The aim of this study is to clarify the presence, potential use as diagnostic marker and clinical roles of anti-M3R antibodies in PBC. We synthesized peptides encoding the extracellular domains of human-M3R, including the N-terminal region, the first, second and third extracellular loops. Antibodies against these regions were examined by peptide-based enzyme-linked immunoassay in sera of 90 patients with PBC and 40 with chronic hepatitis C (CHC), 21 with non-alcoholic steatohepatitis (NASH), 10 with primary sclerosing cholangitis (PSC), 14 with obstructive jaundice, 10 with drug-induced liver injury and 42 healthy controls. Antibodies to the N-terminal, first, second and third loop were detected in 90.0% (81/90), 73.3% (66/90), 76.7% (69/90) and 66.7% (60/90) of PBC, in 67.5% (27/40), 10.0% (4/40), 67.5% (27/40) and 27.5% (11/40) of CHC, in 85.7% (18/21), 9.5% (2/21), 4.8% (1/21) and 57.1% (12/21) of NASH, in 60.0% (6/10), 20.0% (2/10), 60.0% (6/10) and 60.0% (6/10) of PSC, in 100.0% (14/14), 0% (0/14), 64.3% (9/14) and 78.6% (11/14) of obstructive jaundice, in 100.0% (10/10), 0% (0/10), 30.0% (3/10) and 10.0% (1/10) of drug-induced liver injury, and in 4.8% (2/42), 7.1% (3/42), 2.4% (1/42) and 2.4% (1/42) of the controls, respectively. A high frequency of PBC carried anti-M3R antibodies. Anti-M3R antibodies against the first loop of M3R are a potentially useful diagnostic marker for PBC. © 2014 The Japan Society of Hepatology.

  15. Antineutrophil antibodies define clinical and genetic subgroups in primary sclerosing cholangitis.

    Science.gov (United States)

    Hov, Johannes R; Boberg, Kirsten M; Taraldsrud, Eli; Vesterhus, Mette; Boyadzhieva, Maria; Solberg, Inger Camilla; Schrumpf, Erik; Vatn, Morten H; Lie, Benedicte A; Molberg, Øyvind; Karlsen, Tom H

    2017-03-01

    The strongest genetic risk factors in primary sclerosing cholangitis (PSC) are encoded in the HLA complex. Antineutrophil cytoplasmic antibodies (ANCA) have been reported in up to 94% of PSC patients, but their clinical significance and immunogenetic basis are ill defined. We aimed to characterize clinical and genetic associations of ANCA in PSC. Antineutrophil cytoplasmic antibodies were analysed with indirect immunofluorescence in 241 Norwegian PSC patients. HLA-B and HLA-DRB1 genotyping was performed in the patients and in 368 healthy controls. Data on perinuclear ANCA (pANCA) and HLA-DRB1 were available from 274 ulcerative colitis (UC) patients without known liver disease. Antineutrophil cytoplasmic antibodies were found in 193 (80%) of the PSC patients, with pANCA in 169 (70%). ANCA-positive patients were younger than ANCA negative at diagnosis of PSC and had a lower frequency of biliary cancer (9% vs 19%, P=.047). There were no differences between PSC patients with and without inflammatory bowel disease. Genetically, the strong PSC risk factors HLA-B*08 (frequency in healthy 13%) and DRB1*03 (14%) were more prevalent in ANCA-positive than -negative patients (43% vs 25%, P=.0012 and 43% vs 25%, P=.0015 respectively). The results were similar when restricting the analysis to pANCA-positive patients. In UC patients without liver disease, HLA-DRB1*03 was more prevalent in pANCA-positive compared with -negative patients (P=.03). Antineutrophil cytoplasmic antibodies identified PSC patients with particular clinical and genetic characteristics, suggesting that ANCA may mark a clinically relevant pathogenetic subgroup in the PSC-UC disease spectrum. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Anti-MOG antibody-positive ADEM following infectious mononucleosis due to a primary EBV infection: a case report.

    Science.gov (United States)

    Nakamura, Yoshitsugu; Nakajima, Hideto; Tani, Hiroki; Hosokawa, Takafumi; Ishida, Shimon; Kimura, Fumiharu; Kaneko, Kimihiko; Takahashi, Toshiyuki; Nakashima, Ichiro

    2017-04-19

    Anti-Myelin oligodendrocyte glycoprotein (MOG) antibodies are detected in various demyelinating diseases, such as pediatric acute disseminated encephalomyelitis (ADEM), recurrent optic neuritis, and aquaporin-4 antibody-seronegative neuromyelitis optica spectrum disorder. We present a patient who developed anti-MOG antibody-positive ADEM following infectious mononucleosis (IM) due to Epstein-Barr virus (EBV) infection. A 36-year-old healthy man developed paresthesia of bilateral lower extremities and urinary retention 8 days after the onset of IM due to primary EBV infection. The MRI revealed the lesions in the cervical spinal cord, the conus medullaris, and the internal capsule. An examination of the cerebrospinal fluid revealed pleocytosis. Cell-based immunoassays revealed positivity for anti-MOG antibody with a titer of 1:1024 and negativity for anti-aquaporin-4 antibody. His symptoms quickly improved after steroid pulse therapy followed by oral betamethasone. Anti-MOG antibody titer at the 6-month follow-up was negative. This case suggests that primary EBV infection would trigger anti-MOG antibody-positive ADEM. Adult ADEM patients can be positive for anti-MOG antibody, the titers of which correlate well with the neurological symptoms.

  17. Efficacy of anti-CD47 antibody-mediated phagocytosis with macrophages against primary effusion lymphoma.

    Science.gov (United States)

    Goto, Hiroki; Kojima, Yuki; Matsuda, Kouki; Kariya, Ryusho; Taura, Manabu; Kuwahara, Kazuhiko; Nagai, Hirokazu; Katano, Harutaka; Okada, Seiji

    2014-07-01

    Recently, the critical role of CD47 on the surface of resistant cancer cells has been proposed in their evasion of immunosurveillance. Primary effusion lymphoma (PEL) is a subtype of aggressive non-Hodgkin lymphoma that shows serous lymphomatous effusion in body cavities, especially in advanced acquired immunodeficiency syndrome (AIDS). PEL is resistant to conventional chemotherapy and has a poor prognosis. In this study, we evaluated the effect of anti-CD47 antibody (Ab) on PEL in vitro and in vivo. Surface CD47 of PEL cell lines was examined by flow cytometry. Efficacy of knocking down CD47 or anti-CD47 Ab-mediated phagocytosis against PEL was evaluated using mouse peritoneal macrophages and human macrophages in vitro. Primary PEL cells were injected intraperitoneally into NOD/Rag-2/Jak3 double-deficient (NRJ) mice to establish a direct xenograft mouse model. Surface CD47 of PEL cell lines was highly expressed. Knocking down CD47 and anti-CD47 Ab promoted phagocytic activities of macrophages in a CD47 expression-dependent manner in vitro. Treatment with anti-CD47 Ab inhibited ascite formation and organ invasion completely in vivo compared with control IgG-treated mice. CD47 plays the pivotal role in the immune evasion of PEL cells in body cavities. Therapeutic antibody targeting of CD47 could be an effective therapy for PEL. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Symptoms and risk factors to identify women with suspected cancer in primary care: derivation and validation of an algorithm.

    Science.gov (United States)

    Hippisley-Cox, Julia; Coupland, Carol

    2013-01-01

    Early diagnosis of cancer could improve survival so better tools are needed. To derive an algorithm to estimate absolute risks of different types of cancer in women incorporating multiple symptoms and risk factors. Design and setting: Cohort study using data from 452 UK QResearch® general practices for development and 224 for validation. Included patients were females aged 25-89 years. The primary outcome was incident diagnosis of cancer over the next 2 years (lung, colorectal, gastro-oesophageal, pancreatic, ovarian, renal tract, breast, blood, uterine, cervix, other). Factors examined were: 'red flag' symptoms including weight loss, abdominal pain, indigestion, dysphagia, abnormal bleeding, lumps; general symptoms including tiredness, constipation; and risk factors including age, family history, smoking, alcohol intake, deprivation, body mass index (BMI), and medical conditions. Multinomial logistic regression was used to develop a risk equation to predict cancer type. Performance was tested on a separate validation cohort. There were 23 216 cancers from 1 240 864 females in the derivation cohort. The final model included risk factors (age, BMI, chronic pancreatitis, chronic obstructive pulmonary disease, diabetes, family history, alcohol, smoking, deprivation); 23 symptoms, anaemia and venous thrombo-embolism. The model was well calibrated with good discrimination. The receiver operating curve statistics were lung (0.91), colorectal (0.89), gastro-oesophageal (0.90), pancreas (0.87), ovary (0.84), renal (0.90), breast (0.88), blood (0.79), uterus (0.91), cervix (0.73), other cancer (0.82). The 10% of females with the highest risks contained 54% of all cancers diagnosed over 2 years. The algorithm has good discrimination and could be used to identify those at highest risk of cancer to facilitate more timely referral and investigation.

  19. Symptoms and risk factors to identify men with suspected cancer in primary care: derivation and validation of an algorithm.

    Science.gov (United States)

    Hippisley-Cox, Julia; Coupland, Carol

    2013-01-01

    Early diagnosis of cancer could improve survival so better tools are needed. To derive an algorithm to estimate absolute risks of different types of cancer in men incorporating multiple symptoms and risk factors. Cohort study using data from 452 UK QResearch® general practices for development and 224 for validation. Included patients were males aged 25-89 years. The primary outcome was incident diagnosis of cancer over the next 2 years (lung, colorectal, gastro-oesophageal, pancreatic, renal, blood, prostate, testicular, other cancer). Factors examined were: 'red flag' symptoms such as weight loss, abdominal distension, abdominal pain, indigestion, dysphagia, abnormal bleeding, lumps; general symptoms such as tiredness, constipation; and risk factors including age, family history, smoking, alcohol intake, deprivation score and medical conditions. Multinomial logistic regression was used to develop a risk equation to predict cancer type. Performance was tested on a separate validation cohort. There were 22 521 cancers from 1 263 071 males in the derivation cohort. The final model included risk factors (age, BMI, chronic pancreatitis, COPD, diabetes, family history, alcohol, smoking, deprivation); 22 symptoms, anaemia and venous thrombo-embolism. The model was well calibrated with good discrimination. The receiver operator curve statistics values were: lung (0.92), colorectal (0.92), gastro-oesophageal (0.93), pancreas (0.89), renal (0.94), prostate (0.90) blood (0.83, testis (0.82); other cancers (0.86). The 10% of males with the highest risks contained 59% of all cancers diagnosed over 2 years. The algorithm has good discrimination and could be used to identify those at highest risk of cancer to facilitate more timely referral and investigation.

  20. Autoantibodies to beta2-glycoprotein I in systemic lupus erythematosus and primary antiphospholipid antibody syndrome: clinical correlations in comparison with other antiphospholipid antibody tests.

    Science.gov (United States)

    Day, H M; Thiagarajan, P; Ahn, C; Reveille, J D; Tinker, K F; Arnett, F C

    1998-04-01

    To examine relationships between anti-beta2-glycoprotein (beta2-GPI) antibodies and other antiphospholipid antibody (aPL) tests (aPL ELISA and the lupus anticoagulant or LAC) and the associations of each of these aPL tests with individual clinical manifestations of the antiphospholipid antibody syndrome (APS). IgG and IgM anti-beta2-GPI antibodies were determined by ELISA in 281 patients with SLE, primary APS, or other connective tissue diseases. Frequencies, sensitivities, specificities, and predictive values and correlations of anti-beta2-GPI were compared to the aPL ELISA (IgG and IgM) and LAC for individual (and combined) features of APS. Among 139 patients with positive aPL ELISA and/or LAC tests, 57 (41%) had anti-beta2-GPI antibodies (IgG and/or IgM) compared to 11% of patients with SLE negative for these tests (p = 0.00001). In 130 patients with APS, anti-beta2-GPI occurred in 42% and tended to be more specific but less sensitive than the aPL ELISA or LAC. When all 3 aPL tests were combined, the best sensitivities and negative predictive values were achieved; however, specificity and positive predictive values remained low. Anti-beta2-GPI antibodies occurred more frequently in primary APS (58%) vs secondary antiphospholipid syndromes (33%) (p = 0.008, OR = 2.9). Among 79 patients with SLE negative by both aPL ELISA and LAC, 9 (11 %) were positive for anti-beta2-GPI, 7 of whom had clinical features consistent with APS (representing 5% of all with APS). Stepwise multiple logistic regression analysis revealed beta2-GPI to be most strongly associated with neurological syndromes other than stroke, deep venous thrombosis, and recurrent fetal loss, while LAC was most strongly correlated with stroke and thrombocytopenia. IgM aPL antibodies also were independently associated with neurological syndromes and recurrent fetal loss. Testing for beta2-GPI antibodies may be clinically useful in the diagnosis of APS but cannot supplant other aPL ELISA or LAC. Multivariate

  1. Brief Report : Menopause and Primary Ovarian Insufficiency in Women Treated for Antineutrophil Cytoplasmic Antibody-Associated Vasculitides

    NARCIS (Netherlands)

    Tuin, Janneke; Sanders, Jan-Stephan F; van Beek, André P; Hoek, Annemieke; Stegeman, Coen A

    OBJECTIVE: One of the side effects of cyclophosphamide is earlier menopause and primary ovarian insufficiency. This study was undertaken to investigate the onset of menopause and the incidence of primary ovarian insufficiency in women with antineutrophil cytoplasmic antibody-associated vasculitis

  2. Amoxicillin for acute lower-respiratory-tract infection in primary care when pneumonia is not suspected: a 12-country, randomised, placebo-controlled trial.

    Science.gov (United States)

    Little, Paul; Stuart, Beth; Moore, Michael; Coenen, Samuel; Butler, Christopher C; Godycki-Cwirko, Maciek; Mierzecki, Artur; Chlabicz, Slawomir; Torres, Antoni; Almirall, Jordi; Davies, Mel; Schaberg, Tom; Mölstad, Sigvard; Blasi, Francesco; De Sutter, An; Kersnik, Janko; Hupkova, Helena; Touboul, Pia; Hood, Kerenza; Mullee, Mark; O'Reilly, Gilly; Brugman, Curt; Goossens, Herman; Verheij, Theo

    2013-02-01

    Lower-respiratory-tract infection is one of the most common acute illnesses managed in primary care. Few placebo-controlled studies of antibiotics have been done, and overall effectiveness (particularly in subgroups such as older people) is debated. We aimed to compare the benefits and harms of amoxicillin for acute lower-respiratory-tract infection with those of placebo both overall and in patients aged 60 years or older. Patients older than 18 years with acute lower-respiratory-tract infections (cough of ≤28 days' duration) in whom pneumonia was not suspected were randomly assigned (1:1) to either amoxicillin (1 g three times daily for 7 days) or placebo by computer-generated random numbers. Our primary outcome was duration of symptoms rated "moderately bad" or worse. Secondary outcomes were symptom severity in days 2-4 and new or worsening symptoms. Investigators and patients were masked to treatment allocation. This trial is registered with EudraCT (2007-001586-15), UKCRN Portfolio (ID 4175), ISRCTN (52261229), and FWO (G.0274.08N). 1038 patients were assigned to the amoxicillin group and 1023 to the placebo group. Neither duration of symptoms rated "moderately bad" or worse (hazard ratio 1.06, 95% CI 0.96-1.18; p=0.229) nor mean symptom severity (1.69 with placebo vs 1.62 with amoxicillin; difference -0.07 [95% CI -0.15 to 0.007]; p=0.074) differed significantly between groups. New or worsening symptoms were significantly less common in the amoxicillin group than in the placebo group (162 [15.9%] of 1021 patients vs 194 [19.3%] of 1006; p=0.043; number needed to treat 30). Cases of nausea, rash, or diarrhoea were significantly more common in the amoxicillin group than in the placebo group (number needed to harm 21, 95% CI 11-174; p=0.025), and one case of anaphylaxis was noted with amoxicillin. Two patients in the placebo group and one in the amoxicillin group needed to be admitted to hospital; no study-related deaths were noted. We noted no evidence of

  3. Is prophylactic laser peripheral iridotomy for primary angle closure suspects a risk factor for cataract progression? The Chennai Eye Disease Incidence Study.

    Science.gov (United States)

    Vijaya, Lingam; Asokan, Rashima; Panday, Manish; George, Ronnie

    2017-05-01

    To report the risk of cataract progression among primary angle closure suspects (PACS) 6 years after they underwent laser peripheral iridotomy (LPI). In the Chennai Eye Disease Incidence Study, 6 years after their baseline evaluation, 4421 subjects were examined again. As part of a detailed evaluation cataract was graded using the Lens Opacities Classification System II; progression was defined as change of cataract by two or more grades or history of cataract surgery in the 6-year period. Only bilaterally phakic subjects with less than N2 or C2 or P2 cataract at baseline with no history of any form of glaucoma, primary angle closure and pseudoexfoliation were included. There were 3205 eligible subjects. Of these, 190 had undergone LPI for PACS. In comparison to the study population, they were significantly older (pcataract surgery. The cataract progression rate was significantly greater (OR 1.7, 95% CI 1.3 to 2.4, pcataract were age (pcataract progression; LPI was a risk factor only for cortical cataract (OR 1.6, 95% CI 1.1 to 2.3, p=0.007). There was significant cataract progression in 6 years following LPI for PACS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Age-dependent values of N-terminal pro-B-type natriuretic peptide are superior to a single cut-point for ruling out suspected systolic dysfunction in primary care

    DEFF Research Database (Denmark)

    Hildebrandt, Per; Collinson, Paul O; Doughty, Robert N

    2010-01-01

    The study evaluated the use of age-related decision limits for N-terminal pro-B-type natriuretic peptide (NT-proBNP), for ruling out suspected systolic dysfunction in symptomatic patients in primary care, compared with the present standards.......The study evaluated the use of age-related decision limits for N-terminal pro-B-type natriuretic peptide (NT-proBNP), for ruling out suspected systolic dysfunction in symptomatic patients in primary care, compared with the present standards....

  5. Review article: is there an optimal therapeutic regimen for antimitochondrial antibody-negative primary biliary cirrhosis (autoimmune cholangitis)?

    Science.gov (United States)

    Gisbert, J P; Jones, E A; Pajares, J M; Moreno-Otero, R

    2003-01-01

    Testing for antimitochondrial antibodies is the most useful laboratory procedure in the diagnosis of primary biliary cirrhosis; nevertheless, 5-10% of patients with typical features of primary biliary cirrhosis do not have detectable antimitochondrial antibodies, their condition being referred to as antimitochondrial antibody-negative primary biliary cirrhosis or "autoimmune cholangitis". Uncertainty exists whether antimitochondrial antibody-positive and -negative primary biliary cirrhosis represent distinct entities. We reviewed studies that compared: (i) the clinical, laboratory and histological characteristics of antimitochondrial antibody-positive and -negative primary biliary cirrhosis; (ii) the response to treatment of both conditions; and (iii) the response of autoimmune cholangitis to ursodeoxycholic acid and immunosuppressive therapy. Antimitochondrial antibody-positive and -negative primary biliary cirrhosis were characterized by similar clinical, laboratory and histological abnormalities, clinical course and survival. Antimitochondrial antibody status did not seem to affect the response to ursodeoxycholic acid. At present, the efficacy of therapies for autoimmune cholangitis has not been established in controlled trials. Of 52 patients with autoimmune cholangitis treated with ursodeoxycholic acid in 13 uncontrolled studies, 83% had serum biochemical improvement. Also, a favourable effect of immunosuppressive drugs occurred in 57% of 54 patients with autoimmune cholangitis in 17 uncontrolled studies. Each of these trials included very few patients and most evaluated the effects of treatment on surrogate markers of disease only. No marker that consistently distinguished patients who would respond favourably to ursodeoxycholic acid or immunosuppression was apparent. Consequently, treatment is, at present, empirical. However, ursodeoxycholic acid may be given when histology reveals bile duct lesions, whereas immunosuppressive therapy should probably be

  6. Requirement for continuous antigenic stimulation in the development and differentiation of antibody-forming cells. The effect of passive antibody on the primary and secondary response.

    Science.gov (United States)

    Hanna, M G; Nettesheim, P; Francis, M W

    1969-05-01

    The essential role of continuous antigenic stimulation in the development and differentiation of antibody-forming cells as defined in the X-Y-Z immune cell maturation scheme was examined in these studies. Mice were primed with sheep erythrocytes (SRBC) in an attempt to induce maximum immune progenitor cell conversion (X --> Y). Subsequently antigen was depleted at 1 or 4 days after priming with isologous specific antibody in order to interrupt further immune cell differentiation (Y --> Z). It was reasoned that this condition would result in depression of the functional antibody-producing cell compartment as measured in the intact mice and subsequently in enhancement of the sensitized (Y cell) compartment as measured in the spleen cell transfer system. These data were also correlated with systematic studies of the hyperplasia of the spleen germinal centers. The effect of passive antibody on the primary response to SRBC was a marked decrease indirect and indirect hemolysin-producing cells (DPFC and IPFC). However, there was a lack of correlation in the degree of antibody-mediated 19S and 7S immune cell suppression during the primary response, the DPFC being much less depressed than the IPFC. As measured in the transfer system there was an enhanced 19S sensitized cell compartment and a depressed 7S sensitized cell compartment in 1 day passively immunized mice. This was true whether or not transfers were performed 1, 2, or 4 wk after priming. Similarly, there was an enhanced 19S-sensitized cell compartment with little or no effect on the 7S-sensitized. cell compartment in 4 day passively immunized mice. These data suggest that progeny of the antigen-stimulated progenitor cells (X cell), as a consequence of lack of further antigenic stimulation, were forced into maturation arrest. These studies further demonstrate that isologous passive antibody suppresses germinal center growth regardless of whether the antibody is infused 1, 2, or 4 days after priming. In terms of

  7. Anticardiolipine antibodies in skin and muscle eluates of patients with primary and secondary antiphospholipid syndrome

    Directory of Open Access Journals (Sweden)

    Z S Alekberova

    2004-01-01

    Full Text Available Objective. To detect anticardiolipin antibodies (АСА, anti-p2-GPl antibodies, C3 and C4 complement components in immune complexes including those containing АСА in skin and muscle eluates of pts with systemic lupus erythematosus (SLE and antiphospholipid syndrome (APS. Material and methods . In 7 pts (6 female and I male, 2 with primary APS, 3 with SLE+APS and 2 with SLE skin and muscle biopsies were taken. 6 from 7 pts had thrombotic complications. Eluates were obtained from frozen skin and skeletal muscle biopsies (size was 1,5x0,5 and 0,5x0,5 respectively. Because of small size of biopsies it was not possible to use traditional methods of tissue pounding such as sharp homogenization of tissues in homogenizers with pulverizing and subsequent process of freezing-unfreezing which lead to large protein loss and make impossible serological tissue analysis. Application of acid eluates method by T.E.W. Feltkamp and J,H. Boode of own modification allowed to minimize tissue protein loss and perform serological tissue analysis. Results. Serum of all 7 pts contained antiphospholipid antibodies - IgG-ACA in 3, combination of IgG- und IgM-ACA in 5. In 5 from 7 eluates lgG АСА exceeded 0,109 OO units were revealed. They contained СЗ, C4 and different protein products mostly immunoglobulines. Anti-(I2GP1 antiboddie;. were absent. Conclusion. For the first time presence of АСА in tissues of APS pts was showed which may be of particular interest in studying morphogenesis of local tissue disturbances with participation of immune complexes containing АСА.

  8. Clinical evaluation of serum antimitochondrial antibody-negative primary biliary cirrhosis.

    Science.gov (United States)

    Zhang, Fu-Kui; Jia, Ji-Dong; Wang, Bao-En

    2004-05-01

    Primary biliary cirrhosis (PBC) is characterized by frequent presence of antimitochondrial antibodies (AMAs). The sensitivity and specificity of AMA for PBC are both greater than 90%-95%, so the presence of AMA in serum is the major hallmark in PBC. However, it has long been recognized that in 5%-10% of patients the clinical, biochemical and histological features are diagnostic for PBC, but their sera are consistently tested negative for AMA/AMA-M2. This study aimed to evaluate whether the presence of AMA alters the clinical, serological and histological features of the disease. Clinical data of 70 patients clinically and/or histologically diagnosed with PBC were reviewed. AMA-negative and AMA-positive patients were compared in terms of clinical, biochemical, immunological and histological features. At presentation, 11 patients were serum AMA/AMA-M2 negative. At the initial visit, AMA-negative and AMA-positive patients were similar in terms of age, sex, clinical manifestations, liver biochemistries and histological findings. The mean level of serum immunoglobulin M (IgM) was significantly lower in AMA-negative PBC patients than in AMA-positive PBC patients (2851+/-1418 mg/L vs 6361+/-4928 mg/L, P=0.033). Serum antinuclear antibodies (ANA) and/or smooth muscle antibodies (SMA) were more frequently positive in the AMA-negative PBC patients than in the AMA-positive patients (81.8% vs 40.7%, P=0.031). AMA-negative PBC patients are characterized by relatively lower levels of serum IgM and a higher prevalence of serum ANA/SMA and are not associated with substantial differences in the clinical biochemical and histological spectrum of the disease.

  9. Chronic spinal cord injury impairs primary antibody responses, but spares existing humoral immunity in mice

    Science.gov (United States)

    Oropallo, Michael A.; Held, Katherine S.; Goenka, Radhika; Ahmad, Sifat A.; O’Neill, Patrick J.; Steward, Oswald; Lane, Thomas E.; Cancro, Michael P.

    2012-01-01

    Spinal cord injury (SCI) results in immune depression. To better understand how injury inhibits humoral immunity, the effects of chronic thoracic SCI on B cell development and immune responses to thymus-independent (TI) type-2 and thymus-dependent (TD) antigens were determined. Mice received complete crush injury or control laminectomy at either thoracic level 3 (T3), which disrupts descending autonomic control of the spleen, or at T9, which conserves most splenic sympathetic activity. Although mature B cell numbers were only mildly reduced, bone marrow B cell production was transiently but profoundly depressed immediately after injury. Despite the return of normal B cell production four weeks after SCI, mice receiving T3-injury showed a significant reduction in their ability to mount primary TI-2 or TD immune responses. The latter were marked by decreases in germinal center B cells as well as class switched high-affinity antibody secreting cells. Importantly, injury did not affect affinity maturation per se, pre-existing B cell memory, or secondary humoral immune responses. Together, these findings show that chronic high thoracic SCI impairs the ability to mount optimal antibody responses to new antigenic challenges, but spares previously established humoral immunity. PMID:22523388

  10. New ELISA for detecting primary biliary cirrhosis-specific antimitochondrial antibodies.

    Science.gov (United States)

    Dähnrich, Cornelia; Pares, Albert; Caballeria, Llorenç; Rosemann, Anke; Schlumberger, Wolfgang; Probst, Christian; Mytilinaiou, Maria; Bogdanos, Dimitrios; Vergani, Diego; Stöcker, Winfried; Komorowski, Lars

    2009-05-01

    Antimitochondrial antibodies specific for primary biliary cirrhosis (PBC) target the E2 subunits of 2-oxo acid dehydrogenase complexes, in particular the pyruvate dehydrogenase complex (PDC)-E2. Their antigen-specific detection relies on conventional ELISA using purified PDC. More recent assays have employed a hybrid containing the 3 E2-subunits (MIT3). Some PBC sera react with one or the other preparation, suggesting the presence of nonoverlapping epitopes. We have developed an ELISA (anti-M2-3E) using a mixture of purified PDC and MIT3 as antigenic targets. We compared this assay to anti-MIT3 alone, conventional anti-PDC, and indirect immunofluorescence using 173 PBC and 247 disease controls. The anti-M2-3E ELISA showed a 93.6% diagnostic sensitivity compared with 91.3%, 83.8%, and 87.3% for MIT3, purified PDC, or indirect immunofluorescence, respectively, when all specificities are set to 98.8%. By immunoblotting, anti-M2-3E-positive sera unreactive to purified PDC recognized recombinant E2-subunits of the other 2 complexes, whereas those with no reactivity to MIT3 immunofixed PDC subunits E1alpha or E1beta. The diagnostic accuracy of the anti-M2-3E ELISA for detection of antibodies to 2-oxo acid dehydrogenase complexes exceeds that of conventional ELISA and IFL; its novelty derives from the combination of the MIT3 hybrid and purified PDC.

  11. Serial analysis of antimitochondrial antibody in patients with primary biliary cirrhosis.

    Science.gov (United States)

    Benson, Gordon D; Kikuchi, Kentaro; Miyakawa, Hiroshi; Tanaka, Atsushi; Watnik, Mitchell R; Gershwin, M Eric

    2004-06-01

    Antimitochondrial antibodies (AMAs) are the classic serologic marker in primary biliary cirrhosis (PBC). However, there have been only limited attempts to study changes in titer or isotype analysis of such AMAs in patients followed for long periods of time. We took advantage of stored sera from well-characterized patients with PBC followed for a period of 7-28 years (mean duration of 13.5 years). Immunoblot and enzyme-linked immunosorbant assays were performed against PDC-E2, BCOADC-E2 and OGDC-E2 as well as isotype analysis of antigen-specific IgG, IgA and IgM antibodies against each of these mitochondrial autoantigens. Sera were analyzed for total IgG, IgA and IgM by radial immunodiffusion. The sera titer of AMAs was significantly higher in younger patients with PBC. Indeed, age of onset of clinical PBC was a significant predictor for the highest values of sera AMAs. In contrast, the AMA titer did not significantly change over time in this prolonged longitudinal study. The total sera levels of the individual immunoglobulins did not show a time-dependent change, when based on age of onset of the disease. Higher titers of AMAs were noted in the younger patients. Furthermore, despite this long follow-up, there was no evidence for a significant change in AMA levels; also, levels were not influenced by drug therapy used during the period of observation.

  12. Primary biliary cirrhosis in antimitochondrial antibody-negative patients: Chang Gung Memorial Hospital experience.

    Science.gov (United States)

    Tsou, Yung-Kuan; Yeh, Chau-Ting

    2003-05-01

    It is known that some patients with clinical, histological, and laboratory features of primary biliary cirrhosis (PBC) lack serum antimitochondrial antibodies (AMAs). In Asian countries, clinical information regarding AMA-negative PBC is still limited. In this report, we reviewed our patients with AMA-negative PBC in order to further understand this disease. Clinical features of 36 patients with PBC diagnosed by the histopathologic characteristics of the liver at Chung Gung Memorial Hospital-Lin Kou Medical Center from 1985 to 2000 were reviewed. Of them, 15 were negative and 21 were positive for serum AMAs at presentation. Clinical, biochemical, immunological, and histological parameters were compared between these 2 groups. There were only a few differences between the AMA-negative and -positive groups. Significantly more asymptomatic patients (p=0.0017) and a higher positive rate of serum antinuclear antibodies (ANA) (p=0.0323) were observed in the AMA-negative group. Otherwise, there were no significant differences with regard to clinical, biochemical, immunological, or histological parameters. Interestingly, 4 of the 15 patients with AMA-negative PBC became AMA positive during 10, 23, 47, and 56 (mean, 34) months of follow-up. The results show that patients with AMA-negative PBC tend to be asymptomatic and ANA positive. Some patients may develop positive AMA during follow-up. Our data imply that AMA-negative PBC might be a variant of AMA-positive PBC, rather than a separate disease.

  13. [Antibodies to various phospholipids in SLE patients with primary antiphospholipid syndrome].

    Science.gov (United States)

    Reshetniak, T M; Boĭtsekhovskaia, B; Alekberova, Z S; Kalashnikova, L A; Mach, E S; Zabek, Ia

    1999-01-01

    Antiphospholipid antibodies (aPL) represent a heterogeneous population reacting with negatively charged, less frequently neutral phospholipids and/or phospholipid-binding serum proteins. The study was made of antibodies to a wide spectrum of phospholipids: to negatively charged phospholipids such as phosphatide acid (aPA), cardiolipin (aCL), phosphatidylcholine (aPS), phosphatidylinositol (aPI), phosphatidylglycerol (aPG) and to neutrally charged phospholipid--phosphatidylcholine (aPC)--in 54 patients with systemic lupus erythematosus (SLE) and 29 patients with primary antiphospholipid syndrome (PAPS). The test for lupus anticoagulant (LAC) was also made. aPL in SLE patients free of antiphospholipid syndrome were detected in 61, 36 and 9% (aPC, aPS and aPA, aCL, respectively). aPI and aPG did not exceed normal values. 81% of SLE patients with antiphospholipid syndrome were LAC positive and 88% aPL positive. 60, 53, 44, 40, 13 and 17 were positive to aPC, aPA, aPS, aCL, aPG and aPI, respectively. Among patients with PAPS, the highest positivity was by LAC, occurrence of the other aPL was the same as in SLE patients with antiphospholipid syndrome. aCL, aPA, aPC, aPS, aPG and aPI were found in 55, 52, 41, 38, 31 and 21% of cases, respectively. In clinical manifestations of antiphospholipid syndrome and negative tests for LAC and aCL it is advisable to make tests for aPS and aPC. aPC occur in SLE patients more frequently than the other aPL: in 63% of SLE patients free of antiphospholipid syndrome and in 60% of SLE patients with this syndrome. Antibodies to other phospholipids, but not to cardiolipin, were present in SLE + APS in half of the cases but in SLE + PAPS in one third of the patients. Occurrence of aCL in the serum of SLE + PAPS patients is associated with the presence of antibodies to any other phospholipid irrespective of the charge. The severity of vascular changes did not correlate with the number of aPL variant found in the serum.

  14. Age-dependent values of N-terminal pro-B-type natriuretic peptide are superior to a single cut-point for ruling out suspected systolic dysfunction in primary care

    DEFF Research Database (Denmark)

    Hildebrandt, Per; Collinson, Paul O; Doughty, Robert N

    2010-01-01

    The study evaluated the use of age-related decision limits for N-terminal pro-B-type natriuretic peptide (NT-proBNP), for ruling out suspected systolic dysfunction in symptomatic patients in primary care, compared with the present standards....

  15. Increased prevalence of antimitochondrial antibodies in first-degree relatives of patients with primary biliary cirrhosis.

    Science.gov (United States)

    Lazaridis, Konstantinos N; Juran, Brian D; Boe, Gwen M; Slusser, Joshua P; de Andrade, Mariza; Homburger, Henry A; Ghosh, Karthik; Dickson, E Rolland; Lindor, Keith D; Petersen, Gloria M

    2007-09-01

    Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disorder that can progress to cirrhosis, shortening life expectancy. PBC patients are often asymptomatic, present with biochemical cholestasis, and test positive (>or=90%) for antimitochondrial antibodies (AMAs) in serum. Although AMA positivity without biochemical cholestasis may indicate increased risk of future PBC development, the contribution of these antibodies to pathogenesis remains enigmatic. Environmental risks and genetic determinants are likely implicated in PBC etiology. Given the familial aggregation of PBC, we hypothesized that AMAs also aggregate among relatives of PBC probands. We investigated the prevalence of AMAs in first-degree relatives (FDRs) of PBC probands to examine whether AMAs aggregate in such pedigrees. Using a PBC family registry, we prospectively screened for AMAs in the serum of 306 FDRs in 145 pedigrees, 350 PBC probands, and 196 controls who were age-matched, sex-matched, race-matched, and residence-matched to probands. The prevalence of AMA in FDRs and controls was 13.1% and 1%, respectively. Greater prevalence of AMA was found in female FDRs of PBC probands [sisters (20.7%), mothers (15.1%), and daughters (9.8%)] than in male FDRs [brothers (7.8%), fathers (3.7%), and sons (0%)]. AMAs aggregate among FDRs of PBC probands. Our data have clinical implications for FDRs of PBC probands because AMA positivity may suggest susceptibility to PBC. Thus, the identification and follow-up of these relatives may lead to earlier disease diagnosis and treatment. Furthermore, if AMA development is heritable, this trait will provide a basis to dissect the genetic predisposition to PBC.

  16. SIAE Rare Variants in Juvenile Idiopathic Arthritis and Primary Antibody Deficiencies

    Directory of Open Access Journals (Sweden)

    Eirini Sevdali

    2017-01-01

    Full Text Available Sialic acid acetylesterase (SIAE deficiency was suggested to lower the levels of ligands for sialic acid-binding immunoglobulin-like receptors, decreasing the threshold for B-cell activation. In humans, studies of rare heterozygous loss-of-function mutations in SIAE gene in common autoimmune diseases, including juvenile idiopathic arthritis (JIA, yielded inconsistent results. Considering the distinct pathogenesis of the two main subtypes of JIA, autoinflammatory systemic (sJIA and autoimmune oligo/polyarticular (aJIA, and a predisposition to autoimmunity displayed by patients and families with primary antibody deficiencies (PADs, the aim of our study was to analyze whether SIAE rare variants are associated with both the phenotype of JIA and the autoimmunity risk in families with PADs. A cohort of 69 patients with JIA, 117 healthy children, 54 patients, and family members with PADs were enrolled in the study. Three novel SIAE variants (p.Q343P, p.Y495X, and c.1320+33T>C were found only in patients with aJIA but interestingly also in their healthy relatives without autoimmunity, while none of PAD patients or their relatives carried SIAE defects. Our results show that SIAE rare variants are not causative of autoimmunity as single defects.

  17. Characterization of overlap syndrome between primary biliary cirrhosis and autoimmune hepatitis according to antimitochondrial antibodies status.

    Science.gov (United States)

    Alric, Laurent; Thebault, Sophie; Selves, Janik; Peron, Jean-Marie; Mejdoubi, Sanae; Fortenfant, Françoise; Vinel, Jean-Pierre

    2007-01-01

    Codification of variant forms between Primary Biliary Cirrhosis (PBC) and Autoimmune Hepatitis (AIH) has not been definitively standardized. The aim of this study was to compare among 102 consecutive patients, 2 subsets of overlap syndrome (OS, N=21) with and without antimitochondrial antibody (AMA) to two groups of patients with typical PBC (N=43) or AIH (N=38). OS was defined by the presence in the same patient of at least 2 of 3 accepted criteria of PBC and AIH. Twelve patients with OS were AMA negative and 9 were AMA positive. A lower level of alanine transaminase (139+/-48 vs 269+/-154 IU/L, Pantibodies. OS without AMA differed from those with AMA in that they had more severe bile duct damage including destructive cholangitis (P<0.05), ductopenia (P<0.05), ductular hyperplasia (P<0.05) and a higher METAVIR fibrosis score (2.5+/-0.3 vs 1.3+/-0.3, P<0.05). The response to therapy was not different between PBC, AIH and OS. According to the presence of AMA, 2 homogeneous subgroups of patients with overlap syndrome between PBC and AIH may be identified. AMA status affects clinical presentation and liver disease severity of OS.

  18. Antimitochondrial antibody profiles: are they valid prognostic indicators in primary biliary cirrhosis?

    Science.gov (United States)

    Joshi, Supriya; Cauch-Dudek, Karen; Heathcote, E Jenny; Lindor, Keith; Jorgensen, Roberta; Klein, Reinhild

    2002-04-01

    Retrospective studies have reported that subtypes of antimitochondrial antibodies (AMAs) discriminate between a benign and a progressive course in patients with primary biliary cirrhosis (PBC). Four AMA profiles (A-D) were defined: profiles A and B associated with a benign course and C and D with a progressive course. We aimed to confirm whether AMA profiles predict prognosis in a large sample of North American patients with PBC. Stored pretreatment sera from patients with PBC from two centers were tested for AMA profiles using standard techniques. Proportions of patients in each profile group reaching the endpoints of liver transplantation or death from liver disease were compared. Kaplan-Meier curves were constructed comparing AMA profiles. All 472 patients studied had AMA positive, biopsy-confirmed PBC. Mean age at diagnosis was 53 yr, 90% were female, mean follow-up was 7.6 yr (range = 0.5-23), and 51% received ursodeoxycholic acid for >6 months. Profile A was not detected; 16.7% had profile B; 51.1%, profile C; and 32.2%, profile D. Duration of follow-up was comparable among the different profile groups. The proportions of patients reaching endpoints of death from liver disease or transplantation did not differ among the AMA profiles. No difference in the Kaplan-Meier curves between the different profile groups was observed (p > 0.05). AMA profiles do not predict prognosis in patients with PBC.

  19. Oral and dental health status in patients with primary antibody deficiencies.

    Science.gov (United States)

    Meighani, Ghasem; Aghamohammadi, Asghar; Javanbakht, Honarmand; Abolhassani, Hassan; Nikayin, Sina; Jafari, Seyed Mehryar; Ghandehari Motlagh, Mehdi; Shamshiri, Ahmad Reza; Rezaei, Nima

    2011-12-01

    Primary antibody deficiencies (PAD) are a group of immune system disorders, associated with decreased levels of secretory and protective immunoglobulins. Because of the important role of immunoglobulins in the protection of oral cavity, patients with PADs are more susceptible to dental caries or oral manifestations. This study was performed to investigate the oral and dental manifestations of PADs patients. In this study, 33 patients with PADs (21 common variable immunodeficiency, 8 X-linked agammaglobulinemia and 4 hyper IgM syndrome) and 66 controls were examined; the number of decayed, missed and filled teeth (DMFT) were investigated. Aphthous was the most frequent manifestation in PADs patients (38.7%), which was significantly 16.7% higher than the controls (p=0.03). The patients with PADs showed significantly higher presentation of other oral and dental manifestations, including herpes sores, candidiasis tonsillitis, gingivitis, calculus, enamel hypoplasia and other ulcerations. The mean DMFT scores were 6.15±3.6 and 1.93±0.4 in PADs patients and controls, respectively (p<0.001). Although the patients with common variable immunodeficiency had higher means of DMFT in comparison with other groups of PADs, this difference was not statistically significant. This study showed significantly higher frequency of oral and dental manifestations in the patients with PADs compared to controls. Therefore, regular examination of oral cavity could be suggested in this group of immunodeficient patients.

  20. Virus genotypes and responses of serum-specific antibodies in children with primary mumps and mumps reinfection.

    Science.gov (United States)

    Sakata, Rika; Nagita, Akira; Kidokoro, Minoru; Kato, Atsushi; Ogino, Keiki

    2015-11-01

    Research on children with mumps reinfection after natural infection is limited; there are currently no studies on virus-specific antibody responses in paired sera or genotyping of isolated viruses. This study included 281 children (147 boys and 134 girls, age: 1.2-15.9 y) with primary mumps (240), mumps reinfection after natural infection (9), mumps after previous vaccination (26), and vaccine-associated mumps (6). We measured mumps-specific serum antibodies and analyzed isolated virus genes. During acute illness, series-specific IgM and IgG titers exceeded cutoff values in 240 and 232 children with primary mumps, respectively. During convalescence, IgM antibodies were positive in seven and negative in two of nine children with mumps reinfection occurring after natural infection; among 26 previously vaccinated children, 13 were positive and 13 negative. Mumps viruses were isolated from viral cultures from 42 of the 51 children. Except for 6 vaccine-associated cases, all remaining 36 cases of isolated mumps virus were identified as genotype G. These results suggest that measurement of IgM antibody on any day of acute illness may be indicative of primary mumps but may be inconsistent for diagnosing mumps reinfection after natural infection or previous vaccination.

  1. Stimulation of the primary anti-HIV antibody response by IFN-{alpha} in patients with acute HIV-1 infection

    OpenAIRE

    Adalid-Peralta, Laura; Godot, Véronique; Colin, Céline; Krzysiek, Roman; Tran, Thi; Poignard, Pascal; Venet, Alain; Hosmalin, Anne; Lebon, Pierre; Rouzioux, Christine; Chêne, Geneviève; Emilie, Dominique; The Interprim Anrs 112 Study Group,

    2008-01-01

    International audience; Type I IFNs are needed for the production of antiviral antibodies in mice; whether they also stimulate primary antibody responses in vivo during human viral infections is unknown. This was assessed in patients acutely infected with HIV-1 and treated with IFN-alpha2b. Patients with acute HIV-1 infection were randomized to receive antiretroviral therapy alone (Group A, n=60) or combined for 14 weeks with pegylated-IFN-alpha2b (Group B, n=30). Emergence of anti-HIV antibo...

  2. Anti-mitochondrial antibodies in patients with Graves' disease may not signify primary biliary cirrhosis.

    OpenAIRE

    Perros, P.; Palmer, J. M.; Yeaman, S. J.; Kendall-Taylor, P.

    1994-01-01

    Two patients with Graves' disease were incidentally found to have anti-mitochondrial antibodies by immunofluorescence in the absence of symptoms, clinical signs or biochemical evidence of liver dysfunction. Anti-mitochondrial antibody titres became undetectable in both patients on follow-up. Screening of the patients' sera by immunoblotting against the purified antigens of the M2 complex was negative. We conclude that in these cases, anti-mitochondrial antibodies detected by immunofluorescenc...

  3. Antimitochondrial antibody heterogeneity and the xenobiotic etiology of primary biliary cirrhosis.

    Science.gov (United States)

    Chen, Richy C Y; Naiyanetr, Phornnop; Shu, Shang-An; Wang, Jinjun; Yang, Guo-Xiang; Kenny, Thomas P; Guggenheim, Kathryn C; Butler, Jeffrey D; Bowlus, Christopher; Tao, Mi-Hua; Kurth, Mark J; Ansari, Aftab A; Kaplan, Marshall; Coppel, Ross L; Lleo, Ana; Gershwin, M Eric; Leung, Patrick S C

    2013-04-01

    Antimitochondrial antibodies (AMAs) directed against the lipoyl domain of the E2 subunit of pyruvate dehydrogenase (PDC-E2) are detected in 95% of patients with primary biliary cirrhosis (PBC) and are present before the onset of clinical disease. The recent demonstration that AMAs recognize xenobiotic modified PDC-E2 with higher titers than native PDC-E2 raises the possibility that the earliest events involved in loss of tolerance are related to xenobiotic modification. We hypothesized that reactivity to such xenobiotics would be predominantly immunoglobulin M (IgM) and using sera from a large cohort of PBC patients and controls (n = 516), we examined in detail sera reactivity against either 6,8-bis(acetylthio) octanoic acid (SAc)-conjugated bovine serum albumin (BSA), recombinant PDC-E2 (rPDC-E2) or BSA alone. Further, we also defined the relative specificity to the SAc moiety using inhibition enzyme-linked immunosorbent assay (ELISA); SAc conjugate and rPDC-E2-specific affinity-purified antibodies were also examined for antigen specificity, isotype, and crossreactivity. Reactivity to SAc conjugates is predominantly IgM; such reactivity reflects a footprint of previous xenobiotic exposure. Indeed, this observation is supported by both direct binding, crossreactivity, and inhibition studies. In both early and late-stage PBC, the predominant Ig isotype to SAc is IgM, with titers higher with advanced stage disease. We also note that there was a higher level of IgM reactivity to SAc than to rPDC-E2 in early-stage versus late-stage PBC. Interestingly, this finding is particularly significant in light of the structural similarity between SAc and the reduced form of lipoic acid, a step which is similar to the normal physiological oxidation of lipoic acid. Specific modifications of the disulfide bond within the lipoic-acid-conjugated PDC-E2 moiety, i.e., by an electrophilic agent renders PDC-E2 immunogenic in a genetically susceptible host. Copyright © 2012 American

  4. The fingerprint of antimitochondrial antibodies and the etiology of primary biliary cholangitis.

    Science.gov (United States)

    Shuai, Zongwen; Wang, Jinjun; Badamagunta, Madhu; Choi, Jinjung; Yang, Guoxiang; Zhang, Weici; Kenny, Thomas P; Guggenheim, Kathryn; Kurth, Mark J; Ansari, Aftab A; Voss, John; Coppel, Ross L; Invernizzi, Pietro; Leung, Patrick S C; Gershwin, M Eric

    2017-05-01

    The identification of environmental factors that lead to loss of tolerance has been coined the holy grail of autoimmunity. Our work has focused on the reactivity of antimitochondrial autoantibodies (AMA) to chemical xenobiotics and has hypothesized that a modified peptide within PDC-E2, the major mitochondrial autoantigen, will have been immunologically recognized at the time of loss of tolerance. Herein, we successfully applied intein technology to construct a PDC-E2 protein fragment containing amino acid residues 177-314 of PDC-E2 by joining a recombinant peptide spanning residues 177-252 (PDC-228) with a 62-residue synthetic peptide from 253 to 314 (PP), which encompasses PDC-E2 inner lipoyl domain (ILD). We named this intein-constructed fragment PPL. Importantly, PPL, as well as lipoic acid conjugated PPL (LA-PPL) and xenobiotic 2-octynoic acid conjugated PPL (2OA-PPL), are recognized by AMA. Of great importance, AMA has specificity for the 2OA-modified PDC-E2 ILD peptide backbone distinct from antibodies that react with native lipoylated PDC-E2 peptide. Interestingly, this unique AMA subfraction is of the immunoglobulin M isotype and more dominant in early-stage primary biliary cholangitis (PBC), suggesting that exposure to 2OA-PPL-like compounds occurs early in the generation of AMA. To understand the structural basis of this differential recognition, we analyzed PPL, LA-PPL, and 2OA-PPL using electron paramagnetic resonance spectroscopy, with confirmations by enzyme-linked immunosorbent assay, immunoblotting, and affinity antibody analysis. We demonstrate that the conformation of PDC-E2 ILD is altered when conjugated with 2OA, compared to conjugation with lipoic acid. A molecular understanding of the conformation of xenobiotic-modified PDC-E2 is critical for understanding xenobiotic modification and loss of tolerance in PBC with widespread implications for a role of environmental chemicals in the induction of autoimmunity. (Hepatology 2017;65:1670-1682).

  5. Autoreactive monoclonal antibodies from patients with primary biliary cholangitis recognize environmental xenobiotics.

    Science.gov (United States)

    Tanaka, Toshihiro; Zhang, Weici; Sun, Ying; Shuai, Zongwen; Chida, Asiya Seema; Kenny, Thomas P; Yang, Guo-Xiang; Sanz, Ignacio; Ansari, Aftab; Bowlus, Christopher L; Ippolito, Gregory C; Coppel, Ross L; Okazaki, Kazuichi; He, Xiao-Song; Leung, Patrick S C; Gershwin, M Eric

    2017-09-01

    A major problem in autoimmunity has been identification of the earliest events that lead to breach of tolerance. Although there have been major advances in dissecting effector pathways and the multilineage immune responses to mitochondrial self-antigens in primary biliary cholangitis, the critical links between environmental factors and tolerance remain elusive. We hypothesized that environmental xenobiotic modification of the E2 subunit of the pyruvate dehydrogenase (PDC-E2) inner lipoyl domain can lead to loss of tolerance to genetically susceptible hosts. Previously we demonstrated that serum anti-PDC-E2 autoantibodies cross-react with the chemical xenobiotics 2-octynoic acid and 6,8-bis (acetylthio) octanoic acid and further that there is a high frequency of PDC-E2-specific peripheral plasmablasts. Herein we generated 104 recombinant monoclonal antibodies (mAbs) based on paired heavy-chain and light-chain variable regions of individual plasmablasts derived from primary biliary cholangitis patients. We identified 32 mAbs reactive with native PDC-E2, including 20 specific for PDC-E2 and 12 cross-reactive with both PDC-E2 and 2-octynoic acid and 6,8-bis (acetylthio) octanoic acid. A lower frequency of replacement somatic hypermutations, indicating a lower level of affinity maturation, was observed in the complementarity-determining regions of the cross-reactive mAbs in comparison to mAbs exclusively recognizing PDC-E2 or those for irrelevant antigens. In particular, when the highly mutated heavy-chain gene of a cross-reactive mAb was reverted to the germline sequence, the PDC-E2 reactivity was reduced dramatically, whereas the xenobiotic reactivity was retained. Importantly, cross-reactive mAbs also recognized lipoic acid, a mitochondrial fatty acid that is covalently bound to PDC-E2. Our data reflect that chemically modified lipoic acid or lipoic acid itself, through molecular mimicry, is the initial target that leads to the development of primary biliary

  6. Automated enzymatic mitochondrial antibody assay for the diagnosis of primary biliary cirrhosis: applications of a routine diagnostic tool for the detection of antimitochondrial antibodies.

    Science.gov (United States)

    Hazama, Hiroaki; Omagari, Katsuhisa; Masuda, Jun-Ichi; Ohba, Kazuo; Kinoshita, Hideki; Matsuo, Isao; Isomoto, Hajime; Mizuta, Yohei; Murase, Kunihiko; Murata, Ikuo; Kohno, Shigeru

    2002-03-01

    An automated enzymatic mitochondrial antibody assay (EMA) kit for the diagnosis of primary biliary cirrhosis (PBC) has become commercially available recently. The aim of this study was to assess the clinical utility of the enzyme inhibition assay using this EMA kit for the diagnosis of PBC. We tested the immunoreactivity of sera from 54 histologically confirmed Japanese PBC patients to the 2-oxo-acid dehydrogenase complex (2-OADC) enzymes by enzyme inhibition assay using commercially available TRACE (EMA) assay kit, and compared the results with those of indirect immunofluorescence, commercial enzyme-linked immunosorbent assay (ELISA) using MESACUP Mitochondria M2 kit, and immunoblotting on bovine heart mitochondria. Of the 54 sera, 43 (80%) were positive for antimitochondrial antibodies (AMA) by immunofluorescence, 39 (72%) for enzymatic inhibitory antibody to pyruvate dehydrogenase complex (PDC) by EMA, 33 (61%) for immunoglobulin G (IgG) class anti-PDC antibody by ELISA, and 53 (98%) for IgG, IgM, or IgA class antibodies against at least one of the 2-OADC enzymes by immunoblotting. Of these, 43 (80%) were positive for IgG, IgM, or IgA class antibodies against the E2 subunit of PDC (PDC-E2) by immunoblotting. Thirty-six of the 54 sera (67%) showed identical results in all of the four assays, and 40 (74%) were all negative or positive by EMA, ELISA, and immunoblotting in PDC-relevant reactivity. There was a significant correlation between the number of detected immunoglobulin classes of anti-PDC-E2 by immunoblotting and anti-PDC by EMA (P < 0.0001), and a significant inverse correlation between IgG class anti-PDC by ELISA and units of PDC activity by EMA (r = -0.87, P < 0.0001). Although EMA had lower sensitivity compared with immunofluorescence and immunoblotting, this assay should be included among the routine diagnostic tools for the detection of AMA specific to PBC in clinical laboratories because of its high specificity, objective read-out, and rapid

  7. Clinical management and patient persistence with antibiotic course in suspected group A streptococcal pharyngitis for primary prevention of rheumatic fever: the perspective from a New Zealand emergency department.

    Science.gov (United States)

    Mathan, Jeremy J; Ekart, Jozsef; Houlding, Anthony; Payinda, Gary; Mills, Clair

    2017-06-16

    Rates of acute rheumatic fever in the Northland region are historically among the highest in New Zealand, impacting disproportionately on Māori children and youth. The primary aim of this study was to determine patient persistence to antibiotic treatment for group A streptococcus (GAS) pharyngitis in patients presenting with sore throat to the Whangarei Hospital Emergency Department. Secondarily, this study sought to determine prescriber adherence to the national antibiotic guideline for sore throat management. A retrospective audit of patients presenting to ED with presumed GAS pharyngitis between 1 May 2016 and 31 August 2016 was carried out. Data on patient demographics, clinical examination findings, investigations and antibiotic prescription were extracted from electronic medical records. Patients were contacted and after obtaining consent, were asked about their antibiotic treatment using a standardised telephone interview script. The patient population audited reflects those at high risk for acute rheumatic fever. All patients were discharged on the recommended medication, but only 82.7% (62/75) received the correct length (10 days) of oral antibiotics. Of the total of 75 patients audited, 61 (81%) had a swab taken and 41% (25/61) of these were confirmed positive for GAS. Patients were either advised to commence medication without waiting for a swab result (96%, 72/75) or delay treatment and commence only if no improvement in symptoms (4%, 3/75). Of those advised to commence medication immediately, 94% (67/72) obtained their medication from a community pharmacy. Three patients were advised to stop treatment after confirmation of a negative result. Of those patients assessable for medication persistence (n=65), 73.8% (48/65) of patients were compliant in completing the full course of antibiotic therapy. This is the first study to assess patient persistence to an antibiotic course for GAS after presentation at an emergency department in Northland and possibly

  8. Peri-nuclear antibodies correlate with survival in Greek primary biliary cirrhosis patients

    Science.gov (United States)

    Sfakianaki, Ourania; Koulentaki, Meri; Tzardi, Maria; Tsangaridou, Elena; Theodoropoulos, Panayotis A; Castanas, Elias; Kouroumalis, Elias A

    2010-01-01

    AIM: To investigate possible associations of anti-nuclear envelope antibody (ANEA) with disease severity and survival in Greek primary biliary cirrhosis (PBC) patients. METHODS: Serum samples were collected at diagnosis from 147 PBC patients (85% female), who were followed-up for a median 89.5 mo (range 1-240). ANEA were detected with indirect immunofluorescence on 1% formaldehyde fixed Hep2 cells, and anti-gp210 antibodies were detected using an enzyme linked immunosorbent assay. Findings were correlated with clinical data, histology, and survival. RESULTS: ANEA were detected in 69/147 (46.9%) patients and 31/147 (21%) were also anti-gp210 positive. The ANEA positive patients were at a more advanced histological stage (I-II/III-IV 56.5%/43.5% vs 74.4%/25.6%, P = 0.005) compared to the ANEA negative ones. They had a higher antimitochondrial antibodies (AMA) titer (≤ 1:160/> 1:160 50.7%/49.3% vs 71.8%/28.2%, P = 0.001) and a lower survival time (91.7 ± 50.7 mo vs 101.8 ± 55 mo, P = 0.043). Moreover, they had more advanced fibrosis, portal inflammation, interface hepatitis, and proliferation of bile ductules (P = 0.008, P = 0.008, P = 0.019, and P = 0.027, respectively). They also died more frequently of hepatic failure and/or hepatocellular carcinoma (P = 0.016). ANEA positive, anti-gp210 positive patients had a difference in stage (I-II/III-IV 54.8%/45.2% vs 74.4%/25.6%, P = 0.006), AMA titer (≤ 1:160/> 1:160 51.6%/48.4% vs 71.8%/28.2%, P = 0.009), survival (91.1 ± 52.9 mo vs 101.8 ± 55 mo, P = 0.009), and Mayo risk score (5.5 ± 1.9 vs 5.04 ± 1.3, P = 0.04) compared to the ANEA negative patients. ANEA positive, anti-gp210 negative patients had a difference in AMA titer (≤ 1:160/> 1:160 50%/50% vs 71.8%/28.2%, P = 0.002), stage (I-II/III-IV 57.9%/42.1% vs 74.4%/25.6%, P = 0.033), fibrosis (P = 0.009), portal inflammation (P = 0.018), interface hepatitis (P = 0.032), and proliferation of bile ductules (P = 0.031). Anti-gp210 positive patients had a worse

  9. [Significance of subtype pattern of antimitochondrial antibodies in primary biliary cirrhosis for prognostic parameters and response to ursodeoxycholic acid].

    Science.gov (United States)

    Wirth, H P; Zala, G; Meyenberger, C; Ammann, R

    1995-04-15

    Antimitochondrial antibodies are of considerable importance for the diagnosis of primary biliary cirrhosis. Several subtypes of antimitochondrial antibodies have been identified and the pattern has been associated with prognosis of the disease in the long term course. 22 patients with primary biliary cirrhosis (19 female, 3 male; age 29-66, mean 49 years) were examined for the occurrence of the subtypes of antimitochondrial antibodies anti M2, anti M4 and anti M9. Diagnosis of primary biliary cirrhosis was based on elevated cholestatic enzymes, antimitochondrial antibodies, histology and exclusion of other chronic liver disease in all patients and elevated serum IgM concentration in 18/22 patients. Most patients were included in a study protocol of the Swiss Association for the Study of the Liver and treated with 10 mg/kg/day oral ursodeoxycholic acid. According to the subtype pattern of antimitochondrial antibodies, patients were divided into 4 groups A to D (A: anti M2-, anti M4-, anti M9+; B: anti M2+, anti M4-, anti M9+; C: anti M2+, anti M4-, anti M9- and D: anti M2+, anti M4+, anti M9-). The groups were compared with respect to the prognostically relevant parameters age, bilirubin, albumin, prothrombin time and peripheral edema, as well as the occurrence of granulomas in liver biopsy, galactose elimination capacity and response to treatment with ursodeoxycholic acid during one year. Treatment response was expressed as decrease of the serum concentration of IgM, GPT, alkaline phosphatase, gamma glutamyl transpeptidase and bilirubin. No significant differences between the four groups were found with respect to the prognostically relevant parameters, histology and galactose elimination capacity at study entry.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort.

    Directory of Open Access Journals (Sweden)

    Elise Landais

    2016-01-01

    Full Text Available Broadly neutralizing antibodies (bnAbs are thought to be a critical component of a protective HIV vaccine. However, designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date. Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natural HIV infection is thus critical to the design of a protective vaccine. The IAVI Protocol C program investigates a large longitudinal cohort of primary HIV-1 infection in Eastern and South Africa. Development of neutralization was evaluated in 439 donors using a 6 cross-clade pseudo-virus panel predictive of neutralization breadth on larger panels. About 15% of individuals developed bnAb responses, essentially between year 2 and year 4 of infection. Statistical analyses revealed no influence of gender, age or geographical origin on the development of neutralization breadth. However, cross-clade neutralization strongly correlated with high viral load as well as with low CD4 T cell counts, subtype-C infection and HLA-A*03(- genotype. A correlation with high overall plasma IgG levels and anti-Env IgG binding titers was also found. The latter appeared not associated with higher affinity, suggesting a greater diversity of the anti-Env responses in broad neutralizers. Broadly neutralizing activity targeting glycan-dependent epitopes, largely the N332-glycan epitope region, was detected in nearly half of the broad neutralizers while CD4bs and gp41-MPER bnAb responses were only detected in very few individuals. Together the findings suggest that both viral and host factors are critical for the development of bnAbs and that the HIV Env N332-glycan supersite may be a favorable target for vaccine design.

  11. No prognostic significance of antimitochondrial antibody profile testing in primary biliary cirrhosis.

    Science.gov (United States)

    Vleggaar, Frank P; van Buuren, Henk R

    2004-01-01

    The rate of disease progression varies considerably between individuals with primary biliary cirrhosis (PBC). On the basis of serological subtyping 4 antimitochondrial antibody (AMA) profiles (A, B, C and D) can be defined. The finding of previous studies that profile C/D is associated with a progressive course, in contrast to profile A/B, is a question of debate. The aim of the study was to investigate whether AMA profiles predicted the course for a cohort of Dutch PBC patients. Patients with an established diagnosis of AMA-positive PBC, AMA-negative PBC patients, non-PBC decompensated cirrhotics and healthy volunteers. Serum samples from 38 AMA-positive progressive patients, 31 AMA-positive patients without evidence of progression for at least 6 years, 5 AMA-negative PBC patients, 5 non-PBC decompensated cirrhotics and 5 healthy volunteers were assessed. AMA profiles were determined without knowledge of the clinical data. In the progressive AMA-positive group, 13% had profile A/B and 84% had profile C/D. In the non-progressive group, 13% had profile A/B, 77% profile C/D; 10% had no profile. During follow-up, a change from profile A/B to profile C/D or vice versa was not observed. This study found that not only PBC patients with AMA profile C/D but also patients with profile A/B may run a progressive course and therefore does not support the suggestion that AMA profiles can be used as independent prognostic indicator. The divergent results of this and previous studies may be explained by the selection of different patient populations.

  12. Large-scale characterization study of patients with antimitochondrial antibodies but nonestablished primary biliary cholangitis.

    Science.gov (United States)

    Dahlqvist, Géraldine; Gaouar, Farid; Carrat, Fabrice; Meurisse, Sofia; Chazouillères, Olivier; Poupon, Raoul; Johanet, Catherine; Corpechot, Christophe

    2017-01-01

    The prevalence, clinical characteristics, and outcomes of patients with antimitochondrial antibodies (AMAs), but no clinical evidence of primary biliary cholangitis (PBC), are largely unknown. A prospective study of AMA incidence was conducted through a nation-wide network of 63 French immunology laboratories. Clinical data from 720 of 1,318 AMA-positive patients identified in 1 year were collected. Patients were categorized as either newly diagnosed with PBC (n = 275), previously diagnosed with PBC (n = 216), or with nonestablished diagnosis of PBC (n = 229). The latter group was specifically evaluated. Follow-up data were collected for up to 7 years after detection of AMAs. Prevalence of AMA-positive patients without evidence of PBC was 16.1 per 100,000. These patients had the following characteristics: 78% female; median age 58 years; median AMA titer 1:160; extrahepatic autoimmune disorders 46%; normal serum alkaline phosphatases (ALP) 74%; ALP above 1.5 times the upper limit of normal 13%; and cirrhosis 6%. Compared to those newly diagnosed with PBC, the patients were slightly younger, had lower AMA titers, and lower sex-ratio imbalance. Among the patients with normal ALP and no evidence of cirrhosis, the 5-year incidence rate of PBC was 16%. Whereas no patients died from PBC, the 5-year survival rate was 75%, as compared to 90% in a control, standardized population matched for age and sex (P < 0.05). Nearly half of the newly detected AMAs in clinical practice does not lead to a diagnosis of PBC. PBC is unrecognized in 13% of those cases. Only 1 in 6 patients with AMAs and normal ALP will develop PBC after 5 years. The mortality of AMA-positive patients without PBC is increased irrespective of the risk of PBC development. (Hepatology 2017;65:152-163). © 2016 by the American Association for the Study of Liver Diseases.

  13. Long-term outcomes in antimitochondrial antibody negative primary biliary cirrhosis.

    Science.gov (United States)

    Juliusson, Gunnar; Imam, Mohamad; Björnsson, Einar S; Talwalkar, Jayant A; Lindor, Keith D

    2016-01-01

    Antimitochondrial antibodies (AMA) are a sensitive and specific marker for primary biliary cirrhosis (PBC). AMAs are present in 95% of patients with PBC. However, 5% do not have AMAs and data on these patients is scarce. We aim to evaluate the long-term outcomes of patients with AMA negative PBC. A retrospective chart review of 71 AMA negative PBC patients. Disease presentation, laboratory results, and clinical endpoints were recorded. AMA negative patients were matched on year of diagnosis to a control group of 71 AMA positive patients. Ninety-six percent of the AMA negative patients were of female gender with a median age at diagnosis of 55 years and a length of follow-up of 7.5 years vs. 86% females, a median age of 56 and a follow-up of 8.3 years in the control group. Mean total bilirubin and alkaline phosphatase levels were 0.7 mg/dL vs. 0.6 and 570 U/L vs 341, in AMA negative vs. AMA positive patients at presentation, respectively (p = NS). AMA negative patients did not differ in terms of age, serum IgM levels, ANA status, or length of follow-up. Notably, AMA negative patients had a significantly reduced survival free of liver-related complications including transplantation and death compared to AMA positive patients (p = 0.0182). In this large experience, AMA negative PBC patients had a significantly worse prognosis compared to AMA positive PBC patients. The reason for the difference in prognosis is unclear, as it may be true difference or reflect delays in case detection among AMA negative patients.

  14. The prevalence of ANA antibodies, anticentromere antibodies, and anti-cyclic citrullinated peptide antibodies in patients with primary Sjögren's syndrome compared to patients with dryness symptoms without primary Sjögren's syndrome confirmation.

    Science.gov (United States)

    Maślińska, Maria; Mańczak, Małgorzata; Wojciechowska, Bożena; Kwiatkowska, Brygida

    2017-01-01

    Our study analyses the prevalence of ANA, anti-SS-A, anti-SS-B, and ACA and ACPA antibodies in patients with pSS and with dryness symptoms without pSS confirmation, and the association of ACPA and ACA antibodies with specific clinical symptoms. 113 patients were divided into two groups: I - with diagnosed pSS (N = 75); and II - with dryness without pSS evidence (N = 38). Diagnostics: indirect immunofluorescence (IF; Hep-2 cell line) of antinuclear antibodies (ANA), anti-SS-A anti-SS-B antibodies determined with semi-quantitative method, autoantibody profile (14 antigens, ANA Profil 3 EUROLINE); basic laboratory, ophthalmic examination tests, minor salivary gland biopsy with focus score (FS), joint and lung evaluation, and ESSDAI questionnaire (pSS activity). 88% of group I had ANA antibodies (1 : 320 titre), 5.3% at 1 : 160. Anti-SS-A antibodies were present in 88% of group I, including all ANA 1 : 160. Anti-SS-A antibodies positively correlated with greater and moderate activity of ESSDAI 5 (p = 0.046) and FS. The presence of SS-B antibodies significantly affected disease activity. ACPA present: group I - 13% (associated with higher arthritis incidence; p = 0.003); group II - 8%. ACA antibodies present in 4% of group I, but not in group II. No ACA association with interstitial lung changes (small ACA + group excludes full conclusions). ANA antibodies should also be considered in a titre of less than 1 : 320, but the presence of anti-SS-A antibodies is still the most important immunological marker for pSS. Anti-SS-A antibodies correlate with higher disease activity (ESSDAI ≥ 5) and higher FS. The presence of the anti-SS-B antibody was significantly affected by higher activity of the disease. The incidence of arthritis was higher in patients with ACPA+ pSS compared to ACPA- (p = 0.003). There was no relationship between ACPA and arthritis in patients with dry-type syndrome without diagnosis of pSS.

  15. Thrombotic Primary Antiphospholipid Syndrome: the profile of antibody positivity in patients from North India.

    Science.gov (United States)

    Ahluwalia, Jasmina; Sreedharanunni, Sreejesh; Kumar, Narender; Masih, Joseph; Bose, Sunil Kumar; Varma, Neelam; Varma, Subhash; Singh, Surjit

    2016-09-01

    We evaluated the frequency of antiphospholipid antibody syndrome (APS) in patients presenting with thrombosis of various vascular beds from North India and report the antibody profiles encountered. A retrospective analysis was performed on the laboratory results of aCL (anticardiolipin), aβ2 Gp1 (anti-βeta-2 glycoprotein 1) antibody and LAC (lupus anticoagulant) of 1222 consecutive patients referred to the coagulation laboratory work-up for a hypercoagulable/thrombophilic state over a period of 4 years between 2009 and 2013. LAC was screened with dRVVT (diluted Russel Viper Venom Test) and KCT (Kaolin clotting time), and aCL and aβ2 Gp1 antibodies with commercial enzyme-linked immunosorbent assy kits. The current APS criteria was satisfied in 3.85% of all patients and 4.2% of pediatric patients with thrombosis. The venous circulation was more frequently affected (59.6%). Cerebral arterial and intra-abdominal vein involvement was common. Transient antibody positivity was seen in 44 (3.6%) cases. aβ2 Gp1, aCL and LAC were positive in 95%, 54.5% and 23% of patients with APS, respectively, during the initial visit and 93.6%, 23% and 17%, respectively, during the follow-up visit. Persistent triple positivity was seen in only three cases. At initial testing, positivity for both aCL and aβ2 Gp1 was the most frequent pattern (38% of cases). aβ2 Gp1 antibody was the commonest antibody that was persistently positive in patients with thrombosis. Triple positivity for all antibodies had the highest specificity and positive predictive value to diagnose APS in the first visit, whereas aβ2 Gp1 antibody had the highest sensitivity and negative predictive value. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  16. Investigating B Cell Development, Natural and Primary Antibody Responses in Ly-6A/Sca-1 Deficient Mice.

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    Morgan A Jones

    Full Text Available Ly-6A/Stem cell antigen-1 (Ly-6A/Sca-1 is a glycosylphosphatidylinositol-anchored protein expressed on many cell types including hematopoietic stem cells (HSCs and early lymphoid-specific progenitors. Ly-6A/Sca-1 is expressed on CD4+ T cells and plays a role in regulating cellular responses to foreign antigens. The role of Ly-6A/Sca-1 in primary antibody responses has not been defined. To investigate whether Ly-6A/Sca-1 functions in humoral immunity, we first injected Ly-6A/Sca-1-deficient and wild-type control mice with chicken ovalbumin (c-Ova protein mixed with an adjuvant. We then assessed the ability of the mice to generate a primary antibody response against cOva. We further examined the development of B cells and circulating antibody isotypes in non-immunized Ly-6A/Sca-1deficient mice to determine if Ly6A/Sca-1 functions in development irrespective of antigen-specific immune activation. Ly-6A/Sca-1/Sca-1-deficient mice did not show any significant changes in the number of B lymphocytes in the bone marrow and peripheral lymphoid tissues. Interestingly, Ly-6A/Sca-1/Sca-1-/- mice have significantly elevated serum levels of IgA with λ light chains compared to wild type controls. B cell clusters with high reactivity to anti-IgA λ monoclonal antibody were detected in the lamina propria of the gut, though this was not observed in the bone marrow and peripheral lymphoid tissues. Despite these differences, the Ly-6A/Sca-1deficient mice generated a similar primary antibody response when compared to the wild-type mice. In summary, we conclude that the primary antibody response to cOva antigen is similar in Ly-6A/Sca-1deficient and sufficient mice. In addition, we report significantly higher expression of the immunoglobulin λ light chain by B cells in lamina propria of Ly-6A/Sca-1deficient mice when compared to the wild-type control.

  17. Tubulointerstitial nephritis and Fanconi syndrome in a patient with primary Sjögren's syndrome accompanied by antimitochondrial antibodies: A case report and review of the literature.

    Science.gov (United States)

    Saeki, Takako; Nakajima, Akihiro; Ito, Tomoyuki; Takata, Takuma; Imai, Naofumi; Yoshita, Kazuhiro; Kabasawa, Hideyuki; Yamazaki, Hajime; Narita, Ichiei

    2016-05-04

    We describe a 53-year-old woman with primary Sjögren's syndrome and tubulointerstitial nephritis showing distal renal tubular acidosis and Fanconi syndrome. The patient showed high serum IgM levels and positivity for antimitochondrial antibodies, although her liver function was in normal range. According to our literature review, 75% of patients with tubulointerstitial nephritis who were positive for antimitochondrial antibodies showed Fanconi syndrome, suggesting that these antibodies may directly be associated with the pathophysiology of Fanconi syndrome.

  18. Activity, severity and impact of respiratory disease in primary antibody deficiency syndromes.

    Science.gov (United States)

    Hurst, John R; Workman, Sarita; Garcha, Davinder S; Seneviratne, Suranjith L; Haddock, Jamanda A; Grimbacher, Bodo

    2014-01-01

    Some patients with primary antibody deficiency (PAD) syndromes develop bronchiectasis. In immunocompetent patients with bronchiectasis, key clinico-pathophysiological relationships exist between exacerbation frequency, lung function, health-status, infection and inflammation. It is not known whether such relationships are present in PAD. It is also not known how local and systemic inflammation in PAD compares with that in immunocompetent (non-PAD) bronchiectasis patients. We assessed symptoms, exacerbation frequency, health-status, lung function, CT, airway and systemic inflammation and infection in 33 PAD patients and 20 immunocompetent controls with bronchiectasis. Despite less severe airflow obstruction, PAD patients had similar health-status impairment and greater airway (sputum log10 IL-6 2.71 vs. 1.81 pg/ml, p = 0.001) and greater systemic inflammation than immunocompetent bronchiectasis controls (serum log10 CRP 0.77 vs. 0.36 mg/l, p = 0.001). In PAD, cross-sectional markers of disease severity (CT and lung function) did not relate to inflammatory markers of disease activity, however there was a relationship between FEV1 decline rate and systemic inflammation (IL-6; r = 0.42, p = 0.036) and the magnitude of the systemic inflammatory response was related to that in the airway. Correlation between generic SF36 and respiratory SGRQ questionnaires (r = -0.79, p respiratory involvement. Health-status was associated with dyspnoea (rho = 0.77, p respiratory infection frequency (rho = 0.48, p = 0.016), lung function (FEV1: r = -0.60, p = 0.001) and rate of lung function decline (r = 0.41, p = 0.047). The major findings of this analysis are that in patients with PAD, cross-sectional markers of disease severity such as lung function and CT extent of disease do not reflect disease activity as assessed by airway and systemic inflammation. In addition, there is a relationship between the rate of progression of lung disease and the severity of the systemic

  19. Periodontitis prevalence and serum antibody reactivity to periodontal bacteria in primary Sjögren's syndrome: a pilot study.

    Science.gov (United States)

    Lugonja, Bozo; Yeo, Lorraine; Milward, Michael R; Smith, Diana; Dietrich, Thomas; Chapple, Iain L C; Rauz, Saaeha; Williams, Geraint P; Barone, Francesca; de Pablo, Paola; Buckley, Chris; Hamburger, John; Richards, Andrea; Poveda-Gallego, Ana; Scheel-Toellner, Dagmar; Bowman, Simon J

    2016-01-01

    The aims of this study were as follows: (i) To assess the prevalence of periodontitis among patients with primary Sjögren's syndrome (pSS) and comparator groups of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). (ii) To perform a pilot study to compare serum antibody responses to 10 oral/periodontal bacteria in these patient groups and a historical comparator group of patients with periodontitis. Standard clinical periodontal assessments were performed on 39 pSS, 36 RA and 23 OA patients and "In-house" antibody ELISAs for serum antibodies against 10 oral/periodontal bacteria were performed in these groups. Forty-six percent of the pSS group, 64% of the RA group and 48% of the OA group had moderate/severe periodontitis. These frequencies did not reach statistical significance between groups. Raised antibody levels to Prevotella denticola were found in the pSS, RA and periodontitis groups compared to the OA group. Significant between group differences were seen for Aggregatibacter actinomycetemcomitans, Prevotella intermedia and Campylobacter showae. None of these differences were specifically associated with pSS. This study showed no increase in periodontitis in pSS patients. Although the P. denticola data are of interest, identifying bacterial triggering factors for pSS will likely require alternative strategies including modern techniques such as microbiome analysis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. INFLUENCE OF AGING ON ANTIBODY-FORMATION INVIVO AFTER IMMUNIZATION WITH THE PRIMARY T-CELL DEPENDENT ANTIGEN HELIX-POMATIA HEMOCYANIN

    NARCIS (Netherlands)

    DEGREEF, GE; KALLENBERG, CGM; VANSTAALDUINEN, GJ; REMARQUE, EJ; TJANDRA, YI; HIJMANS, W

    1992-01-01

    The in vivo antibody response to the primary T-cell dependent antigen Helix pomatia Haemocyanin (HPH) was studied, in order to detect the possible presence of a humoral immune deficiency in ageing. The IgG subclass distribution of the specific antibodies was also determined. In order to define a

  1. Discinesia ciliar primária: quando o pediatra deve suspeitar e como diagnosticar? Primary ciliary dyskinesia: when the pediatrician must suspect and how to do the diagnosis?

    Directory of Open Access Journals (Sweden)

    Mary Anne K. Olm

    2007-12-01

    Full Text Available OBJETIVO: Revisar a discinesia ciliar primária (DCP quanto aos seus aspectos ultra-estruturais, discriminar os defeitos ciliares primários dos secundários, descrever o quadro clínico, os testes laboratoriais de triagem e de diagnóstico disponíveis, bem como seu manejo clínico. FONTE DE DADOS: Pesquisa nas bases de dados Medline, Lilacs e SciELO, no período de 1980 a 2007. SÍNTESE DOS DADOS: A DCP é uma doença autossômica recessiva que compromete a estrutura e/ou a função ciliar e, conseqüentemente, o transporte mucociliar. As manifestações clínicas envolvem o trato respiratório superior e inferior, com infecções recorrentes do ouvido médio, seios paranasais e pulmonares, que podem evoluir para bronquiectasias. Outras manifestações incluem situs inversus totalis e infertilidade masculina. O diagnóstico deve ser suspeitado pelos pediatras em várias situações: recém-nascidos de termo com desconforto respiratório sem causa aparente; neonatos portadores de dextrocardia; lactentes com tosse persistente e/ou infecções otorrinolaringológicas de repetição, excluindo-se as imunodeficiências e a fibrose cística; crianças com asma atípica e as com bronquiectasias sem causa definida. Os testes de triagem diagnóstica são os da sacarina e do óxido nítrico nasal. As avaliações do defeito ultra-estrutural e funcional exigem análise por microscopia eletrônica e da freqüência e formato da onda de batimento ciliar. CONCLUSÕES: A DCP, apesar da baixa prevalência, é pouco diagnosticada pelas dificuldades de estabelecer o diagnóstico definitivo do defeito ciliar devido à complexidade da investigação laboratorial e pela falta de reconhecimento da doença pelos médicos. A suspeita clínica e o diagnóstico precoce são fundamentais para reduzir a morbidade e prevenir o desenvolvimento de complicações.OBJECTIVE: To review primary ciliary dyskinesia (PCD and its ultrastructural aspects, to differentiate primary

  2. Antithyroglobulin antibody

    Science.gov (United States)

    Thyroglobulin antibody; Thyroiditis - thyroglobulin antibody; Hypothyroidism - thyroglobulin antibody; Thyroiditis - thyroglobulin antibody; Graves disease - thyroglobulin antibody; Underactive thyroid - thyroglobulin antibody

  3. Antiphosphatidylserine/prothrombin antibodies as biomarkers to identify severe primary antiphospholipid syndrome.

    Science.gov (United States)

    Hoxha, Ariela; Mattia, Elena; Tonello, Marta; Grava, Chiara; Pengo, Vittorio; Ruffatti, Amelia

    2017-05-01

    Anti-phosphatidylserine/prothrombin (aPS/PT) antibodies have begun to be considered potentional biomarkers for antiphospholipid syndrome (APS). This cohort study investigate the role of aPS/PT antibodies as a risk factor for severe APS by evaluating the association between those antibodies and clinical/laboratory profiles of APS. Plasma/serum samples from 197 APS patients, 100 healthy subjects and 106 patients with autoimmune diseases were collected. IgG/IgM aPS/PT antibodies were assayed using commercial ELISA kit. Prevalences of IgG and IgM aPS/PT (p<0.0001 and p=0.0009, respectively) and their titres (p<0.0001 and p=0.0002, respectively) were significantly higher in thrombosis/pregnancy group with respect to pregnancy morbidity alone. Prevalences of IgG and IgM aPS/PT (p<0.0001 and p=0.0004, respectively) and their mean levels (p=0.0001 for both) were significantly higher in the prematurity linked to life-threatening obstetric complications group with respect to miscarriage group. There was a significant relationship between IgG and IgM aPS/PT (p=0.001 and p=0.0002) and their mean levels were higher (p=0.0004 and p=0.0002, respectively) in the thrombotic microangiopathy group, considered a milestone manifestation of catastrophic APS. The relationship between IgG and IgM aPS/PT was significant and mean levels were higher in triple positive antiphospholipid antibody patients than in double and single positivity ones (p<0.0001 for all). APS/PT antibodies were associated to severe thrombosis, severe pregnancy complications inducing prematurity, and vascular microangiopathy, all generally associated to high risk APS forms requiring strong therapy.

  4. Multiplex flow cytometry barcoding and antibody arrays identify surface antigen profiles of primary and metastatic colon cancer cell lines.

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    Kumar Sukhdeo

    Full Text Available Colon cancer is a deadly disease affecting millions of people worldwide. Current treatment challenges include management of disease burden as well as improvements in detection and targeting of tumor cells. To identify disease state-specific surface antigen signatures, we combined fluorescent cell barcoding with high-throughput flow cytometric profiling of primary and metastatic colon cancer lines (SW480, SW620, and HCT116. Our multiplexed technique offers improvements over conventional methods by permitting the simultaneous and rapid screening of cancer cells with reduced effort and cost. The method uses a protein-level analysis with commercially available antibodies on live cells with intact epitopes to detect potential tumor-specific targets that can be further investigated for their clinical utility. Multiplexed antibody arrays can easily be applied to other tumor types or pathologies for discovery-based approaches to target identification.

  5. Primary tumor site and anti-EGFR monoclonal antibody benefit in metastatic colorectal cancer: a meta-analysis.

    Science.gov (United States)

    Li, Dandan; Fu, Qiang; Li, Man; Li, Jun; Yin, Can; Zhao, Jin; Li, Feng

    2017-05-01

    This meta-analysis aimed to document the impact of primary tumor site on anti-EGFR monoclonal antibody (mAb) benefit in metastatic colorectal cancer. Tumors with metastatic left-sided colorectal cancer (LCC) were compared with tumors with metastatic right-sided colon cancer (RCC) with respect to anti-EGFR mAb objective response rate (ORR), overall survival (OS) and progression-free survival (PFS) benefit. Comparing LCC with RCC, LCC was found to have significantly superior anti-EGFR mAb ORR (p analysis demonstrated that LCC had markedly superior anti-EGFR mAb treatment benefit compared with RCC.

  6. [Persistence of hepatitis A virus antibodies after primary immunization and response to revaccination in children and adolescents with perinatal HIV exposure].

    Science.gov (United States)

    Gouvêa, Aída de Fátima Thomé Barbosa; Pinto, Maria Isabel de Moraes; Miyamoto, Maristela; Machado, Daisy Maria; Pessoa, Silvana Duarte; Carmo, Fabiana Bononi do; Beltrão, Suênia Cordeiro de Vasconcelos; Succi, Regina Célia de Menezes

    2015-01-01

    To assess possible factors associated with the loss of antibodies to hepatitis A 7 years after the primary immunization in children of HIV-infected mothers and the response to revaccination in patients seronegative for hepatitis A. Quantification of HAV antibodies by electrochemiluminescence was performed in 39 adolescents followed up at the Pediatric Aids Clinic of Federal University of São Paulo (Unifesp): 29 HIV-infected (HIVgroup) (median age: 12.8 years) and 10 HIV-exposed but non-infected (ENI group) (median age: 13.4 years). All of them received two doses of HAV vaccine (Havrix(®)) in 2002. The median age at primary immunization (PI) was 5.4 years for HIV group and 6.5 years for ENI group. All children, from both groups, had antibodies to HAV >20 mIU/mL after PI. Seven years later, the ENI group showed a median concentration of antibodies = 253.5 mIU/mL, while the HIV group = 113.0 mIU/mL (Mann-Whitney test, p=0.085). All ENI group and 23/29 (79.3%) from HIV group mantained HAV antibodies 7 years after PI. The levels of hepatitis A antibodies in the primary vaccination were the only factor independently associated with maintaining these antibodies for 7 years. The group that lost HAV seropositivity was revaccinated and 83.3% (5/6) responded with antibodies >20 mUI/mL. The antibodies levels acquired in the primary vaccination in the HIV group were the main factor associated with antibodies loss after HAV immunization. Copyright © 2015 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  7. Persistence of hepatitis A virus antibodies after primary immunization and response to revaccination in children and adolescents with perinatal HIV exposure

    Directory of Open Access Journals (Sweden)

    Aída de Fátima Thomé Barbosa Gouvêa

    2015-06-01

    Full Text Available OBJECTIVE: To assess possible factors associated with the loss of antibodies to hepatitis A 7 years after the primary immunization in children of HIV-infected mothers and the response to revaccination in patients seronegative for hepatitis A. METHODS: Quantification of HAV antibodies by electrochemiluminescence was performed in 39 adolescents followed up at the Pediatric Aids Clinic of Federal University of São Paulo (Unifesp: 29 HIV-infected (HIV group (median age: 12.8 years and 10 HIV-exposed but non-infected (ENI group (median age: 13.4 years. All of them received two doses of HAV vaccine (Havrix(r in 2002. RESULTS: The median age at primary immunization (PI was 5.4 years for HIV group and 6.5 years for ENI group. All children, from both groups, had antibodies to HAV >20 mIU/mL after PI. Seven years later, the ENI group showed a median concentration of antibodies = 253.5 mIU/mL, while the HIV group = 113.0 mIU/mL (Mann-Whitney test, p=0.085. All ENI group and 23/29 (79.3% from HIV group mantained HAV antibodies 7 years after PI. The levels of hepatitis A antibodies in the primary vaccination were the only factor independently associated with maintaining these antibodies for 7 years. The group that lost HAV seropositivity was revaccinated and 83.3% (5/6 responded with antibodies >20 mUI/mL. CONCLUSIONS: The antibodies levels acquired in the primary vaccination in the HIV group were the main factor associated with antibodies loss after HAV immunization.

  8. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease.

    Science.gov (United States)

    Schmidt, Amand F; Pearce, Lucy S; Wilkins, John T; Overington, John P; Hingorani, Aroon D; Casas, Juan P

    2017-04-28

    Despite the availability of effective drug therapies that reduce low-density lipoprotein (LDL)-cholesterol (LDL-C), cardiovascular disease (CVD) remains an important cause of mortality and morbidity. Therefore, additional LDL-C reduction may be warranted, especially for patients who are unresponsive to, or unable to take, existing LDL-C-reducing therapies. By inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, monoclonal antibodies (PCSK9 inhibitors) may further reduce LDL-C, potentially reducing CVD risk as well. Primary To quantify short-term (24 weeks), medium-term (one year), and long-term (five years) effects of PCSK9 inhibitors on lipid parameters and on the incidence of CVD. Secondary To quantify the safety of PCSK9 inhibitors, with specific focus on the incidence of type 2 diabetes, cognitive function, and cancer. Additionally, to determine if specific patient subgroups were more or less likely to benefit from the use of PCSK9 inhibitors. We identified studies by systematically searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and Web of Science. We also searched Clinicaltrials.gov and the International Clinical Trials Registry Platform and screened the reference lists of included studies. We identified the studies included in this review through electronic literature searches conducted up to May 2016, and added three large trials published in March 2017. All parallel-group and factorial randomised controlled trials (RCTs) with a follow-up time of at least 24 weeks were eligible. Two review authors independently reviewed and extracted data. When data were available, we calculated pooled effect estimates. We included 20 studies with data on 67,237 participants (median age 61 years; range 52 to 64 years). Twelve trials randomised participants to alirocumab, three trials to bococizumab, one to RG7652, and four to evolocumab. Owing to the small number of trials using agents other than alirocumab

  9. Antibody response to polyomavirus primary infection: high seroprevalence of Merkel cell polyomavirus and lymphoid tissue involvement.

    Science.gov (United States)

    Cason, Carolina; Monasta, Lorenzo; Zanotta, Nunzia; Campisciano, Giuseppina; Maestri, Iva; Tommasino, Massimo; Pawlita, Michael; Villani, Sonia; Comar, Manola; Delbue, Serena

    2018-01-12

    Human polyomaviruses (HPyVs) asymptomatically infect the human population establishing latency in the host, and their seroprevalence can reach 90% in healthy adults. Few studies have focused on the pediatric population, and there are no reports regarding the seroprevalence of all the newly isolated HPyVs among Italian children. Therefore, we investigated the frequency of serum antibodies against 12 PyVs in 182 immunocompetent children from Northeast Italy, by means of a multiplex antibody detection system. Additionally, secondary lymphoid tissues were collected to analyze the presence of HPyV DNA sequences using a specific real-time PCRs or PCRs. Almost 100% of subjects were seropositive for at least one PyV. Seropositivity ranged from 3% for antibodies against simian virus 40 (SV40) in children from 0 to 3 years, to 91% for antibodies against WU polyomavirus (WUPyV) and HPyV10 in children from 8 to 17 years. The mean number of PyV for which children were seropositive increased with the increasing of age: 4 standard deviations (SD) 1.8 in the 0-3-year group, 5 (SD 1.9) in the 4-7-year group, and 6 (SD 2.2) in the 8-17-year group. JC polyomavirus (JCPyV) DNA was detected in 1% of the adenoids, WUPyV in 12% of the tonsils, and 28% of the adenoids, and Merkel cell polyomavirus (MCPyV) was present in 6 and 2% of the tonsils and adenoids, respectively. Our study gives new insights on the serological evidence of exposure to PyVs during childhood, and on their possible respiratory route of transmission.

  10. Antibody and inflammatory responses in laying hens with experimental primary infections of Ascaridia galli.

    Science.gov (United States)

    Marcos-Atxutegi, C; Gandolfi, B; Arangüena, T; Sepúlveda, R; Arévalo, M; Simón, F

    2009-04-06

    Ascaridia galli, an intestinal nematode that affects hens and other domestic and wild birds, causes economic losses in avian exploitations. The present work shows that A. galli stimulates a strong antibody response as well as an intense inflammatory reaction, in the intestinal mucous of experimentally infected Lohmann Brown laying hens. IgG antibodies against soluble extracts of A. galli embrionated eggs and adult worms, were detected in both blood and yolks eggs from infected hens during a period of 105 days after the infection. This indicates that hens transfer to their offspring a part of the IgG antibodies produced when they become infected. The antigens responsible for the stimulation of specific IgG were molecules of 30-34, 44-54 and 58-90 kDa, while in the yolk eggs of infected hens a reactivity directed against antigens of molecular weight (M(w)) lower than 50 kDa was detected. Histology revealed traumatic lesions with leukocyte infiltration, and inflammation of the intestinal wall of the infected hens after 105 days of initial infection. The possible influence of the immune and inflammatory response on the population dynamics of the parasite is discussed.

  11. Circulating antibodies to α-enolase and phospholipase A2 receptor and composition of glomerular deposits in Japanese patients with primary or secondary membranous nephropathy.

    Science.gov (United States)

    Kimura, Yukihiro; Miura, Naoto; Debiec, Hanna; Morita, Hiroyuki; Yamada, Harutaka; Banno, Shogo; Ronco, Pierre; Imai, Hirokazu

    2017-02-01

    Phospholipase A2 receptor (PLA2R) is recognized as a target antigen in primary membranous nephropathy (MN); Anti-α-enolase antibody in primary and secondary MN has been proposed, however, little is known about the potential contribution of α-enolase to the pathogenesis of MN. We evaluated circulating antibodies to α-enolase by a dot blotting system and PLA2R by indirect immunofluorescence, and glomerular deposition of these proteins in 25 patients with primary MN, 20 patients with secondary MN, 44 patients with collagen disease or severe infection, 60 patients with nephritis (each ten patients of IgA nephropathy, focal segmental gloemrulosclerosis, minimal change nephrotic syndrome, membranoproliferative glomeurlonephritis, diabetic glomerulosclerosis, and tubulointerstitial nephritis) as disease control, and 20 healthy subjects. In primary MN, 18 of 25 sera (72 %) showed anti-α-enolase antibody (IgG1 and IgG4, 11 pts; IgG4 alone, six pts; IgG1 alone, one pt). In secondary MN, 15 of 20 sera (75 %) contained anti-α-enolase antibody (IgG1 and IgG3, 13 pts; IgG3 alone, two pts). No circulating anti-α-enolase antibody was found in 44 collagen diseases or septic patients, 60 nephritis without MN, and 20 healthy subjects. Twelve of 25 sera (48 %) from patients with primary MN were positive for anti-PLA2R antibody, whereas all patients with secondary MN were negative. Eight of the 12 PLA2R-positive patients (67 %) with primary MN also had anti α-enolase antibody. Although PLA2R antigen was present in a subepithelial pattern in 10 of 19 (52 %) patients with primary MN, α-enolase was never detected in glomerular deposits in 19 and ten patients with primary and secondary MN, respectively. Circulating anti-α-enolase antibodies are highly present in both primary and secondary MN (about 70 %, respectively), while anti-PLA2R antibodies are specific for primary MN (48 %) with a prevalence apparently lower in the Japanese population than in Chinese and Caucasian

  12. Risk factors for inadequate antibody response to primary rabies vaccination in dogs under one year of age

    Science.gov (United States)

    Wallace, Ryan M.; Pees, Anna; Blanton, Jesse B.

    2017-01-01

    Ensuring the adequacy of response to rabies vaccination in dogs is important, particularly in the context of pet travel. Few studies have examined the factors associated with dogs’ failure to achieve an adequate antibody titer after vaccination (0.5 IU/ml). This study evaluated rabies antibody titers in dogs after primary vaccination. Dogs under one year of age whose serum was submitted to a reference laboratory for routine diagnostics, and which had no prior documented history of vaccination were enrolled (n = 8,011). Geometric mean titers (GMT) were calculated and univariate analysis was performed to assess factors associated with failure to achieve 0.5 IU/mL. Dogs vaccinated at >16 weeks of age had a significantly higher GMT compared to dogs vaccinated at a younger age (1.64 IU/ml, 1.57–1.72, ANOVA p vaccinated vaccinated 12–16 weeks (1.22 IU/ml and 1.21 IU/ml). The majority of dogs failed to reach an adequate titer within the first 3 days of primary vaccination; failure rates were also high if the interval from vaccination to titer check was greater than 90 days. Over 90% of dogs that failed primary vaccination were able to achieve adequate titers after booster vaccination. The ideal timing for blood draw is 8–30 days after primary vaccination. In the event of a failure, most dogs will achieve an adequate serologic response upon a repeat titer (in the absence of booster vaccination). Booster vaccination after failure provided the highest probability of an acceptable titer. PMID:28759602

  13. Risk factors for inadequate antibody response to primary rabies vaccination in dogs under one year of age.

    Science.gov (United States)

    Wallace, Ryan M; Pees, Anna; Blanton, Jesse B; Moore, Susan M

    2017-07-01

    Ensuring the adequacy of response to rabies vaccination in dogs is important, particularly in the context of pet travel. Few studies have examined the factors associated with dogs' failure to achieve an adequate antibody titer after vaccination (0.5 IU/ml). This study evaluated rabies antibody titers in dogs after primary vaccination. Dogs under one year of age whose serum was submitted to a reference laboratory for routine diagnostics, and which had no prior documented history of vaccination were enrolled (n = 8,011). Geometric mean titers (GMT) were calculated and univariate analysis was performed to assess factors associated with failure to achieve 0.5 IU/mL. Dogs vaccinated at >16 weeks of age had a significantly higher GMT compared to dogs vaccinated at a younger age (1.64 IU/ml, 1.57-1.72, ANOVA p < 0.01). There was no statistical difference in GMT between dogs vaccinated <12 weeks and dogs vaccinated 12-16 weeks (1.22 IU/ml and 1.21 IU/ml). The majority of dogs failed to reach an adequate titer within the first 3 days of primary vaccination; failure rates were also high if the interval from vaccination to titer check was greater than 90 days. Over 90% of dogs that failed primary vaccination were able to achieve adequate titers after booster vaccination. The ideal timing for blood draw is 8-30 days after primary vaccination. In the event of a failure, most dogs will achieve an adequate serologic response upon a repeat titer (in the absence of booster vaccination). Booster vaccination after failure provided the highest probability of an acceptable titer.

  14. Triiodothyronine improves the primary antibody response to sheep red blood cells in severely undernourished weanling mice

    Energy Technology Data Exchange (ETDEWEB)

    Filteau, S.M.; Perry, K.J.; Woodward, B.

    1987-09-01

    Three experiments were conducted in which weanling mice were fed a nutritionally complete diet either ad libitum or in restricted quantities such that they lost about 30% of their initial weight over a 14-day period. In Experiments 1 and 2, half the animals from each group received dietary triiodothyronine (T/sub 3/) supplements. In Experiment 3, food-intake-restricted mice were fed graded levels of potassium iodide. Malnutrition reduced the number of nucleated cells per spleen, the number of splenic IgG plaque-forming cells (PFC) per 10/sup 6/ cells, and the serum antibody titers against sheep red blood cells as determined by radioimmunoassay. T/sub 3/ supplements increased antibody titers, the number of nucleated cells per spleen, and both IgM and IgG PFC per 10/sup 6/ spleen cells in malnourished mice, but had no effect on well-nourished mice. The beneficial effect of T/sub 3/ was not a result of improved protein, energy, or iodine status in the malnourished mice.

  15. Antibodies Elicited by Multiple Envelope Glycoprotein Immunogens in Primates Neutralize Primary Human Immunodeficiency Viruses (HIV-1) Sensitized by CD4-Mimetic Compounds.

    Science.gov (United States)

    Madani, Navid; Princiotto, Amy M; Easterhoff, David; Bradley, Todd; Luo, Kan; Williams, Wilton B; Liao, Hua-Xin; Moody, M Anthony; Phad, Ganesh E; Vázquez Bernat, Néstor; Melillo, Bruno; Santra, Sampa; Smith, Amos B; Karlsson Hedestam, Gunilla B; Haynes, Barton; Sodroski, Joseph

    2016-05-15

    The human immunodeficiency virus (HIV-1) envelope glycoproteins (Env) mediate virus entry through a series of complex conformational changes triggered by binding to the receptors CD4 and CCR5/CXCR4. Broadly neutralizing antibodies that recognize conserved Env epitopes are thought to be an important component of a protective immune response. However, to date, HIV-1 Env immunogens that elicit broadly neutralizing antibodies have not been identified, creating hurdles for vaccine development. Small-molecule CD4-mimetic compounds engage the CD4-binding pocket on the gp120 exterior Env and induce Env conformations that are highly sensitive to neutralization by antibodies, including antibodies directed against the conserved Env region that interacts with CCR5/CXCR4. Here, we show that CD4-mimetic compounds sensitize primary HIV-1 to neutralization by antibodies that can be elicited in monkeys and humans within 6 months by several Env vaccine candidates, including gp120 monomers. Monoclonal antibodies directed against the gp120 V2 and V3 variable regions were isolated from the immunized monkeys and humans; these monoclonal antibodies neutralized a primary HIV-1 only when the virus was sensitized by a CD4-mimetic compound. Thus, in addition to their direct antiviral effect, CD4-mimetic compounds dramatically enhance the HIV-1-neutralizing activity of antibodies that can be elicited with currently available immunogens. Used as components of microbicides, the CD4-mimetic compounds might increase the protective efficacy of HIV-1 vaccines. Preventing HIV-1 transmission is a high priority for global health. Eliciting antibodies that can neutralize transmitted strains of HIV-1 is difficult, creating problems for the development of an effective vaccine. We found that small-molecule CD4-mimetic compounds sensitize HIV-1 to antibodies that can be elicited in vaccinated humans and monkeys. These results suggest an approach to prevent HIV-1 sexual transmission in which a virus

  16. The role of anti-CGRP antibodies in the pathophysiology of primary headaches.

    Science.gov (United States)

    Barbanti, Piero; Aurilia, Cinzia; Fofi, Luisa; Egeo, Gabriella; Ferroni, Patrizia

    2017-05-01

    Calcitonin gene-related peptide (CGRP), a potent vasodilator and pain-signaling neuropeptide, is a validated therapeutic target for migraine and cluster headache. Four anti-CGRP monoclonal antibodies (mAbs) have been developed, representing the first specific, mechanism-based, migraine prophylactic treatment. CGRP mAbs demonstrated good efficacy coupled to excellent tolerability and safety in 5 phase II clinical trials. Notably, CGRP mAbs induced complete migraine remission in a patients' subset. To date, more than 20 phase III trials using CGRP mAbs for of episodic and chronic migraine and cluster headache prevention are ongoing. Future investigations will shed light on migraine endophenotypes predictive of good CGRP mAbs responsiveness and provide answers on their long-term cardiovascular safety.

  17. Learning the Relationship between the Primary Structure of HIV Envelope Glycoproteins and Neutralization Activity of Particular Antibodies by Using Artificial Neural Networks

    Science.gov (United States)

    Buiu, Cătălin; Putz, Mihai V.; Avram, Speranta

    2016-01-01

    The dependency between the primary structure of HIV envelope glycoproteins (ENV) and the neutralization data for given antibodies is very complicated and depends on a large number of factors, such as the binding affinity of a given antibody for a given ENV protein, and the intrinsic infection kinetics of the viral strain. This paper presents a first approach to learning these dependencies using an artificial feedforward neural network which is trained to learn from experimental data. The results presented here demonstrate that the trained neural network is able to generalize on new viral strains and to predict reliable values of neutralizing activities of given antibodies against HIV-1. PMID:27727189

  18. Caspase induction by IgA antimitochondrial antibody: IgA-mediated biliary injury in primary biliary cirrhosis.

    Science.gov (United States)

    Matsumura, Shuji; Van De Water, Judy; Leung, Patrick; Odin, Joseph A; Yamamoto, Kazuhide; Gores, Gregory J; Mostov, Keith; Ansari, Aftab A; Coppel, Ross L; Shiratori, Yasushi; Gershwin, M Eric

    2004-05-01

    Anti-mitochondrial antibodies (AMAs) have long been recognized as a serological hallmark of primary biliary cirrhosis (PBC). Although high titers of immunoglobulin (Ig)A AMAs are found in bile, saliva, and urine of patients, a pathogenic role for this antibody has remained elusive. Functional studies of this IgA in general have been impeded by low quantities of antibody and the inability to recover antigen-specific IgA in dimeric form. Using a newly defined synthetic group A. Streptococcus derived peptide, we purified large quantities of dimeric and monomeric IgA from patient sera. The purified IgA was incubated with Madine-Darby canine kidney (MDCK) cells transfected with the human polymeric Ig receptor (pIgR) and the cells studied by flow cytometric analysis for binding of carboxyfluorescein conjugated VAD-fmk peptide to activated caspase enzymes. A total of 87% of PBC patients that were anti-PDC-E2 positive had serum IgA that increased caspase activation in MDCK-pIgR+ cells compared to serum-derived IgA from controls with a maximum reaction 48 hours after addition of IgA. The titer of anti-PDC-E2 IgA among the PBC patients strongly correlated with caspase activation (cc = 0.88). Pre-absorption of the IgA using recombinant 2-oxo-acid dehydrogenase complex significantly diminished this activation. IgG from the same PBC patients did not induce caspase activation. These data suggest that during transcytosis through pIgR-positive cells, exposure to PDC-E2-specific dimeric IgA results in the initiation of caspase activation. In conclusion, we propose that due to an even greater concentration of dimeric IgA in biliary and mucosal secretions, constant transcytosis would render the exposed cells more susceptible to apoptosis resulting in subsequent bile duct damage.

  19. Catalytic domain of PDC-E2 contains epitopes recognized by antimitochondrial antibodies in primary biliary cirrhosis.

    Science.gov (United States)

    Braun, Sandra; Berg, Christoph; Buck, Sandra; Gregor, Michael; Klein, Reinhild

    2010-02-28

    To search for further immunodominant peptides of the pyruvate dehydrogenase complex E2-component (PDC-E2) recognized by antimitochondrial antibodies (AMA) in primary biliary cirrhosis (PBC). Sera from 95 patients with PBC were tested by enzyme-linked immunosorbent assay against 33 synthetic overlapping peptides (25 amino acids; aa) covering the entire length of the E2-subunit of PDC-E2. Furthermore, the inner lipoyl peptide 167-184 was used in an unlipoylated and a lipoylated form as well as coupled to ovalbumin. Sera from 11 AMA negative/ANA positive PBC patients, 63 patients with other liver disorders and 22 healthy blood donors served as controls. Of the 95 PBC-sera, 74% reacted with the peptide 475-499 and 58% with the peptide 407-431 located within the catalytic domain of PDC-E2. Patients with other disorders or healthy controls were positive in only up to 18%. Antibodies to the unlipoylated and lipoylated peptide 167-184 within the inner lipoyl domain were found in only 5% and 11% of the PBC sera, respectively; using ovalbumin-coupled peptides, the incidence increased up to 57% (unlipoylated form). Peptides within the catalytic site of PDC-E2 rather than the previously reported lipoyl binding peptide 167-184 may represent major immunodominant epitopes recognized by AMA in PBC.

  20. Antibody responses to NY-ESO-1 in primary breast cancer identify a subtype target for immunotherapy.

    Directory of Open Access Journals (Sweden)

    Ahmed Hamaï

    Full Text Available The highly immunogenic human tumor antigen NY-ESO-1 (ESO is a target of choice for anti-cancer immune therapy. In this study, we assessed spontaneous antibody (Ab responses to ESO in a large cohort of patients with primary breast cancer (BC and addressed the correlation between the presence of anti-ESO Ab, the expression of ESO in the tumors and their characteristics. We found detectable Ab responses to ESO in 1% of the patients. Tumors from patients with circulating Ab to ESO exhibited common characteristics, being mainly hormone receptor (HR⁻ invasive ductal carcinomas of high grade, including both HER2⁻ and HER2⁺ tumors. In line with these results, we detected ESO expression in 20% of primary HR⁻ BC, including both ESO Ab⁺ and Ab⁻ patients, but not in HR⁺ BC. Interestingly, whereas expression levels in ESO⁺ BC were not significantly different between ESO Ab⁺ and Ab⁻ patients, the former had, in average, significantly higher numbers of tumor-infiltrated lymph nodes, indicating that lymph node invasion may be required for the development of spontaneous anti-tumor immune responses. Thus, the presence of ESO Ab identifies a tumor subtype of HR⁻ (HER2⁻ or HER2⁺ primary BC with frequent ESO expression and, together with the assessment of antigen expression in the tumor, may be instrumental for the selection of patients for whom ESO-based immunotherapy may complement standard therapy.

  1. Antibody responses to NY-ESO-1 in primary breast cancer identify a subtype target for immunotherapy.

    Science.gov (United States)

    Hamaï, Ahmed; Duperrier-Amouriaux, Karine; Pignon, Pascale; Raimbaud, Isabelle; Memeo, Lorenzo; Colarossi, Cristina; Canzonieri, Vincenzo; Perin, Tiziana; Classe, Jean-Marc; Campone, Mario; Jézéquel, Pascal; Campion, Loïc; Ayyoub, Maha; Valmori, Danila

    2011-01-01

    The highly immunogenic human tumor antigen NY-ESO-1 (ESO) is a target of choice for anti-cancer immune therapy. In this study, we assessed spontaneous antibody (Ab) responses to ESO in a large cohort of patients with primary breast cancer (BC) and addressed the correlation between the presence of anti-ESO Ab, the expression of ESO in the tumors and their characteristics. We found detectable Ab responses to ESO in 1% of the patients. Tumors from patients with circulating Ab to ESO exhibited common characteristics, being mainly hormone receptor (HR)⁻ invasive ductal carcinomas of high grade, including both HER2⁻ and HER2⁺ tumors. In line with these results, we detected ESO expression in 20% of primary HR⁻ BC, including both ESO Ab⁺ and Ab⁻ patients, but not in HR⁺ BC. Interestingly, whereas expression levels in ESO⁺ BC were not significantly different between ESO Ab⁺ and Ab⁻ patients, the former had, in average, significantly higher numbers of tumor-infiltrated lymph nodes, indicating that lymph node invasion may be required for the development of spontaneous anti-tumor immune responses. Thus, the presence of ESO Ab identifies a tumor subtype of HR⁻ (HER2⁻ or HER2⁺) primary BC with frequent ESO expression and, together with the assessment of antigen expression in the tumor, may be instrumental for the selection of patients for whom ESO-based immunotherapy may complement standard therapy.

  2. Quantitative analyses reveal distinct sensitivities of the capture of HIV-1 primary viruses and pseudoviruses to broadly neutralizing antibodies.

    Science.gov (United States)

    Kim, Jiae; Jobe, Ousman; Peachman, Kristina K; Michael, Nelson L; Robb, Merlin L; Rao, Mangala; Rao, Venigalla B

    2017-08-01

    Development of vaccines capable of eliciting broadly neutralizing antibodies (bNAbs) is a key goal to controlling the global AIDS epidemic. To be effective, bNAbs must block the capture of HIV-1 to prevent viral acquisition and establishment of reservoirs. However, the role of bNAbs, particularly during initial exposure of primary viruses to host cells, has not been fully examined. Using a sensitive, quantitative, and high-throughput qRT-PCR assay, we found that primary viruses were captured by host cells and converted into a trypsin-resistant form in less than five minutes. We discovered, unexpectedly, that bNAbs did not block primary virus capture, although they inhibited the capture of pseudoviruses/IMCs and production of progeny viruses at 48h. Further, viruses escaped bNAb inhibition unless the bNAbs were present in the initial minutes of exposure of virus to host cells. These findings will have important implications for HIV-1 vaccine design and determination of vaccine efficacy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Does the Maternal Serum IgG Level during Pregnancy in Primary Antibody Deficiency Influence the IgG Level in the Newborn?

    Science.gov (United States)

    Nagendran, Vasantha; Emmanuel, Noel; Bansal, Amolak S

    2015-01-01

    Purpose. To find out if the serum IgG level in the newborn baby was affected by low maternal serum IgG during pregnancy in two newly diagnosed primary antibody deficient patients. Method. Infant cord blood IgG level was compared with maternal IgG level in 2 mothers with newly diagnosed primary antibody deficiency, who declined replacement IgG treatment during pregnancy. Results. Both mothers delivered healthy babies with normal IgG levels at birth. Conclusions. The normal IgG levels and sound health in these 2 babies in spite of low maternal IgG throughout pregnancy raise interesting discussion points about maternofoetal immunoglobulin transport mechanisms in primary antibody deficiency.

  4. Does the Maternal Serum IgG Level during Pregnancy in Primary Antibody Deficiency Influence the IgG Level in the Newborn?

    Directory of Open Access Journals (Sweden)

    Vasantha Nagendran

    2015-01-01

    Full Text Available Purpose. To find out if the serum IgG level in the newborn baby was affected by low maternal serum IgG during pregnancy in two newly diagnosed primary antibody deficient patients. Method. Infant cord blood IgG level was compared with maternal IgG level in 2 mothers with newly diagnosed primary antibody deficiency, who declined replacement IgG treatment during pregnancy. Results. Both mothers delivered healthy babies with normal IgG levels at birth. Conclusions. The normal IgG levels and sound health in these 2 babies in spite of low maternal IgG throughout pregnancy raise interesting discussion points about maternofoetal immunoglobulin transport mechanisms in primary antibody deficiency.

  5. Diagnostic value of specific IgM antibodies in primary HIV infection

    NARCIS (Netherlands)

    Lange, J. M.; Parry, J. V.; de Wolf, F.; Mortimer, P. P.; Goudsmit, J.

    1988-01-01

    Sequential serum samples from 55 homosexual men with primary HIV infection were tested for IgM anti-HIV. An early IgM response was found in 27 out of 55 (49%). In five cases IgM anti-HIV was detected 1-3 1/4 months prior to IgG anti-HIV seroconversion, as detected by a commercially available ELISA,

  6. Does the Maternal Serum IgG Level during Pregnancy in Primary Antibody Deficiency Influence the IgG Level in the Newborn?

    OpenAIRE

    Vasantha Nagendran; Noel Emmanuel; Bansal, Amolak S.

    2015-01-01

    Purpose. To find out if the serum IgG level in the newborn baby was affected by low maternal serum IgG during pregnancy in two newly diagnosed primary antibody deficient patients. Method. Infant cord blood IgG level was compared with maternal IgG level in 2 mothers with newly diagnosed primary antibody deficiency, who declined replacement IgG treatment during pregnancy. Results. Both mothers delivered healthy babies with normal IgG levels at birth. Conclusions. The normal IgG levels and sound...

  7. The Primary Sequence of Acetylcholinesterase and Selective Antibodies for the Detection of Organophosphate Toxicity

    Science.gov (United States)

    1991-06-07

    investigator(s) adhered to the CDC-NIH Guide for Biosafety in Microbiological and Biomedical Laboratories. PI S n ture Date TABLE OF CONTENTS The Primary...d Witt, tihe vicioton ?t tIk%4b WW lod 121-do V~As-u4 l O.i’. aih*i~~~1%YC. *Mo*ttztal I,,m ft Mclf huItncomawc (5 i S . I? %. t"’ ta’lill... measured within the sedimented cells by the Ellman 1.0 method (43). 0 0.5" 0.0 Simultaneous with the construction of the mammalian expression system, we

  8. Detection of Antibody-Dependent Complement-Mediated Inactivation of both Autologous and Heterologous Virus in Primary Human Immunodeficiency Virus Type 1 Infection†

    Science.gov (United States)

    Aasa-Chapman, Marlén M. I.; Holuigue, Sophie; Aubin, Keith; Wong, MaiLee; Jones, Nicola A.; Cornforth, David; Pellegrino, Pierre; Newton, Philippa; Williams, Ian; Borrow, Persephone; McKnight, Áine

    2005-01-01

    Specific CD8 T-cell responses to human immunodeficiency virus type 1 (HIV-1) are induced in primary infection and make an important contribution to the control of early viral replication. The importance of neutralizing antibodies in containing primary viremia is questioned because they usually arise much later. Nevertheless antienvelope antibodies develop simultaneously with, or even before, peak viremia. We determined whether such antibodies might control viremia by complement-mediated inactivation (CMI). In each of seven patients studied, antibodies capable of CMI appeared at or shortly after the peak in viremia, concomitantly with detection of virus-specific T-cell responses. The CMI was effective on both autologous and heterologous HIV-1 isolates. Activation of the classical pathway and direct viral lysis were at least partly responsible. Since immunoglobulin G (IgG)-antibodies triggered the CMI, specific memory B cells could also be induced by vaccination. Thus, consideration should be given to vaccination strategies that induce IgG antibodies capable of CMI. PMID:15709001

  9. Intralesional anti-CD20 antibody for low-grade primary cutaneous B-cell lymphoma: Adverse reactions correlate with favorable clinical outcome.

    Science.gov (United States)

    Eberle, Franziska C; Holstein, Julia; Scheu, Alexander; Fend, Falko; Yazdi, Amir S

    2017-03-01

    Intralesional injection of anti-CD20 antibody (rituximab) has been described as effective therapeutic option for patients with indolent primary cutaneous B-cell lymphoma (PCBL). To date, no parameters that reproducibly predict favorable clinical outcome of this treatment have been identified. The study aims to evaluate the clinical response and adverse effects as well as patients' self-perception of intralesional injection of anti-CD20 antibody for treatment of indolent PCBL compared to other treatment modalities. Eleven patients with PCBL, namely primary cutaneous follicle center lymphoma (n = 9) and primary cutaneous marginal zone lymphoma (n = 2), treated with intralesional anti-CD20 antibody were retrospectively evaluated for response rate and adverse events as well as their self-perception of anti-CD20 antibody therapy and other therapies of PCBL. Patients treated with intralesional anti-CD20 antibody for PCBL showed complete response or partial response in 45 % or 27 % of patients, respectively. Particularly, patients with marked flu-like symptoms after intralesional injection of rituximab responded very well to rituximab. The majority of patients considered rituximab as best therapy compared to other therapies such as excision or radiotherapy. Intralesional rituximab is an effective therapy with high patient satisfaction. Strong therapy induced side effects of fever, chills and headache after administration of rituximab might be used as indicator for favorable response. © 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  10. Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs.

    Science.gov (United States)

    Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A; Thörn, Karolina; Cairns, Tina M; Wegmann, Frank; Sattentau, Quentin J; Eisenberg, Roselyn J; Cohen, Gary H; Harandi, Ali M

    2016-01-01

    Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes.

  11. The presentation and evaluation of a case of systemic Lupus erythematosus and anthiphospholipid antibody syndrome with primary clinical manifestation of chorea

    Directory of Open Access Journals (Sweden)

    Asgary S

    1998-06-01

    Full Text Available Manifestation of chorea in patients with systemic lupus erythematosus (SLE and antiphospholipid antibody syndrome (APA synd. is not common. Moreover, primary presentation of the disease with chorea is rare and only few such cases are reported in literature in recent years. We report here the case of a 28 year old woman who was first seen at the age of 10 with clinical manifestations of chorea. Later she developed deep vein thrombosis, thrombocytpenia, stroke, cardiac valve involvement and recurrent abortions. Laboratory investigations confirmed the diagnosis of SLE and the presence of antiphospholipid antibodies. We present this patient as a case of SLE and antiphospholipid antibody syndrome with chorea being her primary clinical presentation

  12. A quantitative trait locus for a primary antibody response to keyhole limpet hemocyanin on chicken chromosome 14-Confirmation and candidate gene approach

    NARCIS (Netherlands)

    Siwek, M.; Slawinska, A.; Nieuwland, M.G.B.; Witkowski, A.; Zieba, G.; Minozzi, G.; Knol, E.F.; Bednarczyk, M.

    2010-01-01

    A QTL involved in the primary antibody response toward keyhole limpet hemocyanin (KLH) was detected on chicken chromosome 14 in the experimental population, which was created by crossing commercial White Leghorn and a Polish native chicken breed (green-legged partridgelike). The current QTL location

  13. Early intraocular pressure change after peripheral iridotomy with ultralow fluence pattern scanning laser and Nd:YAG laser in primary angle-closure suspect: Kowloon East Pattern Scanning Laser Study Report No. 3.

    Science.gov (United States)

    Chan, Jeffrey Chi Wang; Choy, Bonnie Nga Kwan; Chan, Orlando Chia Chieh; Li, Kenneth Kai Wang

    2018-02-01

    Our purpose was to assess the early intraocular pressure (IOP) changes of ultralow fluence laser iridotomy using pattern scanning laser followed by neodymium:yttrium-aluminum-gamet (Nd:YAG) laser. This is a prospective interventional study. Thirty-three eyes of 33 adult Chinese primary angle-closure suspect subjects were recruited for prophylactic laser peripheral iridotomy. Sequential laser peripheral iridotomy was performed using pattern scanning laser followed by Nd:YAG laser. Visual acuity (VA) and IOP were measured before treatment, at 1 h, 1 day, 1 week, 1 month, 3 months and 6 months after laser. Laser energy used and complications were documented. Corneal endothelial cell count was examined at baseline and 6 months. Patency of the iridotomy was assessed at each follow-up visit. All subjects achieved patent iridotomy in a single session. The mean energy used was 0.335+/-0.088 J for the pattern scanning laser, and 4.767+/-5.780 mJ for the Nd:YAG laser. The total mean energy was 0.339+/-0.089 J. None of the eyes developed a clinically significant IOP spike (≥ 8 mmHg) at 1 h and 1 day after laser use. Only four eyes developed higher IOP at 1 h and all were ≤3 mmHg compared to baseline. The mean IOP was 13.8+/-2.5 mmHg at 1 h and 11.5+/-2.2 mmHg at 1 day, both were significantly lower than baseline (15.8+/-2.1 mmHg) (P angle-closure suspects. Further studies to investigate its role in the treatment of other angle-closure conditions are warranted.

  14. Source and Purity of Dengue-Viral Preparations Impact Requirement for Enhancing Antibody to Induce Elevated IL-1β Secretion: A Primary Human Monocyte Model.

    Science.gov (United States)

    Callaway, Justin B; Smith, Scott A; Widman, Douglas G; McKinnon, Karen P; Scholle, Frank; Sempowski, Gregory D; Dittmer, Dirk P; Crowe, James E; de Silva, Aravinda M; Ting, Jenny P-Y

    2015-01-01

    Dengue virus is a major global health threat and can lead to life-threatening hemorrhagic complications due to immune activation and cytokine production. Cross-reactive antibodies to an earlier dengue virus infection are a recognized risk factor for severe disease. These antibodies bind heterologous dengue serotypes and enhance infection into Fc-receptor-bearing cells, a process known as antibody-dependent enhancement of infection. One crucial cytokine seen elevated in severe dengue patients is IL-1β, a potent inflammatory cytokine matured by the inflammasome. We used a highly-physiologic system by studying antibody-dependent enhancement of IL-1β in primary human monocytes with anti-dengue human monoclonal antibodies isolated from patients. Antibody-enhancement increased viral replication in primary human monocytes inoculated with supernatant harvested from Vero cells infected with dengue virus serotype 2 (DENV-2) 16681. Surprisingly, IL-1β secretion induced by infectious supernatant harvested from two independent Vero cell lines was not enhanced by antibody. Secretion of multiple other inflammatory cytokines was also independent of antibody signaling. However, IL-1β secretion did require NLRP3 and caspase-1 activity. Immunodepletion of dengue virions from the infectious supernatant confirmed that virus was not the main IL-1β-inducing agent, suggesting that a supernatant component(s) not associated with the virion induced IL-1β production. We excluded RNA, DNA, contaminating LPS, viral NS1 protein, complement, and cytokines. In contrast, purified Vero-derived DENV-2 16681 exhibited antibody-enhancement of both infection and IL-1β induction. Furthermore, C6/36 mosquito cells did not produce such an inflammatory component, as crude supernatant harvested from insect cells infected with DENV-2 16681 induced antibody-dependent IL-1β secretion. This study indicates that Vero cells infected with DENV-2 16681 may produce inflammatory components during dengue virus

  15. Source and Purity of Dengue-Viral Preparations Impact Requirement for Enhancing Antibody to Induce Elevated IL-1β Secretion: A Primary Human Monocyte Model.

    Directory of Open Access Journals (Sweden)

    Justin B Callaway

    Full Text Available Dengue virus is a major global health threat and can lead to life-threatening hemorrhagic complications due to immune activation and cytokine production. Cross-reactive antibodies to an earlier dengue virus infection are a recognized risk factor for severe disease. These antibodies bind heterologous dengue serotypes and enhance infection into Fc-receptor-bearing cells, a process known as antibody-dependent enhancement of infection. One crucial cytokine seen elevated in severe dengue patients is IL-1β, a potent inflammatory cytokine matured by the inflammasome. We used a highly-physiologic system by studying antibody-dependent enhancement of IL-1β in primary human monocytes with anti-dengue human monoclonal antibodies isolated from patients. Antibody-enhancement increased viral replication in primary human monocytes inoculated with supernatant harvested from Vero cells infected with dengue virus serotype 2 (DENV-2 16681. Surprisingly, IL-1β secretion induced by infectious supernatant harvested from two independent Vero cell lines was not enhanced by antibody. Secretion of multiple other inflammatory cytokines was also independent of antibody signaling. However, IL-1β secretion did require NLRP3 and caspase-1 activity. Immunodepletion of dengue virions from the infectious supernatant confirmed that virus was not the main IL-1β-inducing agent, suggesting that a supernatant component(s not associated with the virion induced IL-1β production. We excluded RNA, DNA, contaminating LPS, viral NS1 protein, complement, and cytokines. In contrast, purified Vero-derived DENV-2 16681 exhibited antibody-enhancement of both infection and IL-1β induction. Furthermore, C6/36 mosquito cells did not produce such an inflammatory component, as crude supernatant harvested from insect cells infected with DENV-2 16681 induced antibody-dependent IL-1β secretion. This study indicates that Vero cells infected with DENV-2 16681 may produce inflammatory components

  16. Validation of two age dependent D-dimer cut-off values for exclusion of deep vein thrombosis in suspected elderly patients in primary care: retrospective, cross sectional, diagnostic analysis

    Science.gov (United States)

    Koek, H L (Dineke); Oudega, Ruud; Geersing, Geert-Jan; Janssen, Kristel J M; van Delden, Johannes J M; Moons, Karel G M

    2012-01-01

    Objective To determine whether the use of age adapted D-dimer cut-off values can be translated to primary care patients who are suspected of deep vein thrombosis. Design Retrospective, cross sectional diagnostic study. Setting 110 primary care doctors affiliated with three hospitals in the Netherlands. Participants 1374 consecutive patients (936 (68.1%) aged >50 years) with clinically suspected deep vein thrombosis. Main outcome measures Proportion of patients with D-dimer values below two proposed age adapted cut-off levels (age in years×10 μg/L in patients aged >50 years, or 750 μg/L in patients aged ≥60 years), in whom deep vein thrombosis could be excluded; and the number of false negative results. Results Using the Wells score, 647 patients had an unlikely clinical probability of deep vein thrombosis. In these patients (at all ages), deep vein thrombosis could be excluded in 309 (47.8%) using the age dependent cut-off value compared with 272 (42.0%) using the conventional cut-off value of 500 μg/L (increase 5.7%, 95% confidence interval 4.1% to 7.8%). This exclusion rate resulted in 0.5% and 0.3% false negative cases, respectively (increase 0.2%, 0.004% to 8.6%).The increase in exclusion rate by using the age dependent cut-off value was highest in the oldest patients. In patients older than 80 years, deep vein thrombosis could be safely excluded in 22 (35.5%) patients using the age dependent cut-off value compared with 13 (21.0%) using the conventional cut-off value (increase 14.5%, 6.8% to 25.8%). Compared with the age dependent cut-off value, the cut-off value of 750 μg/L had a similar exclusion rate (307 (47.4%) patients) and false negative rate (0.3%). Conclusions Combined with a low clinical probability of deep vein thrombosis, use of the age dependent D-dimer cut-off value for patients older than 50 years or the cut-off value of 750 μg/L for patients aged 60 years and older resulted in a considerable increase in the proportion of patients in

  17. Antimitochondrial antibodies in acute liver failure: implications for primary biliary cirrhosis.

    Science.gov (United States)

    Leung, Patrick S C; Rossaro, Lorenzo; Davis, Paul A; Park, Ogyi; Tanaka, Atsushi; Kikuchi, Kentaro; Miyakawa, Hiroshi; Norman, Gary L; Lee, William; Gershwin, M Eric

    2007-11-01

    In our previous work, including analysis of more than 10,000 sera from control patients and patients with a variety of liver diseases, we have demonstrated that with the use of recombinant autoantigens, antimitochondrial autoantibodies (AMAs) are only found in primary biliary cirrhosis (PBC) and that a positive AMA is virtually pathognomonic of either PBC or future development of PBC. Although the mechanisms leading to the generation of AMA are enigmatic, we have postulated that xenobiotic-induced and/or oxidative modification of mitochondrial autoantigens is a critical step leading to loss of tolerance. This thesis suggests that a severe liver oxidant injury would lead to AMA production. We analyzed 217 serum samples from 69 patients with acute liver failure (ALF) collected up to 24 months post-ALF, compared with controls, for titer and reactivity with the E2 subunits of pyruvate dehydrogenase, branched chain 2-oxo-acid dehydrogenase, and 2-oxo-glutarate dehydrogenase. AMAs were detected in 28/69 (40.6%) ALF patients with reactivity found against all of the major mitochondrial autoantigens. In addition, and as further controls, sera were analyzed for autoantibodies to gp210, Sp100, centromere, chromatin, soluble liver antigen, tissue transglutaminase, and deaminated gliadin peptides; the most frequently detected nonmitochondrial autoantibody was against tissue transglutaminase (57.1% of ALF patients). The strikingly high frequency of AMAs in ALF supports the thesis that oxidative stress-induced liver damage may lead to AMA induction. The rapid disappearance of AMAs in these patients provides further support for the contention that PBC pathogenesis requires additional factors, including genetic susceptibility.

  18. Antibody-free magnetic cell sorting of genetically modified primary human CD4+ T cells by one-step streptavidin affinity purification.

    Directory of Open Access Journals (Sweden)

    Nicholas J Matheson

    Full Text Available Existing methods for phenotypic selection of genetically modified mammalian cells suffer disadvantages of time, cost and scalability and, where antibodies are used to bind exogenous cell surface markers for magnetic selection, typically yield cells coated with antibody-antigen complexes and beads. To overcome these limitations we have developed a method termed Antibody-Free Magnetic Cell Sorting in which the 38 amino acid Streptavidin Binding Peptide (SBP is displayed at the cell surface by the truncated Low Affinity Nerve Growth Receptor (LNGFRF and used as an affinity tag for one-step selection with streptavidin-conjugated magnetic beads. Cells are released through competition with the naturally occurring vitamin biotin, free of either beads or antibody-antigen complexes and ready for culture or use in downstream applications. Antibody-Free Magnetic Cell Sorting is a rapid, cost-effective, scalable method of magnetic selection applicable to either viral transduction or transient transfection of cell lines or primary cells. We have optimised the system for enrichment of primary human CD4+ T cells expressing shRNAs and exogenous genes of interest to purities of >99%, and used it to isolate cells following Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9 genome editing.

  19. Antibody-free magnetic cell sorting of genetically modified primary human CD4+ T cells by one-step streptavidin affinity purification.

    Science.gov (United States)

    Matheson, Nicholas J; Peden, Andrew A; Lehner, Paul J

    2014-01-01

    Existing methods for phenotypic selection of genetically modified mammalian cells suffer disadvantages of time, cost and scalability and, where antibodies are used to bind exogenous cell surface markers for magnetic selection, typically yield cells coated with antibody-antigen complexes and beads. To overcome these limitations we have developed a method termed Antibody-Free Magnetic Cell Sorting in which the 38 amino acid Streptavidin Binding Peptide (SBP) is displayed at the cell surface by the truncated Low Affinity Nerve Growth Receptor (LNGFRF) and used as an affinity tag for one-step selection with streptavidin-conjugated magnetic beads. Cells are released through competition with the naturally occurring vitamin biotin, free of either beads or antibody-antigen complexes and ready for culture or use in downstream applications. Antibody-Free Magnetic Cell Sorting is a rapid, cost-effective, scalable method of magnetic selection applicable to either viral transduction or transient transfection of cell lines or primary cells. We have optimised the system for enrichment of primary human CD4+ T cells expressing shRNAs and exogenous genes of interest to purities of >99%, and used it to isolate cells following Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 genome editing.

  20. A single center 14 years study of infectious complications leading to hospitalization of patients with primary antibody deficiencies

    Directory of Open Access Journals (Sweden)

    Setareh Mamishi

    Full Text Available Primary antibody deficiencies (PADs are a heterogeneous group of disorders, characterized by hypogammaglobulinemia and increased susceptibility to bacterial infections, leading to hospitalizations. This study was performed to determine the main infectious causes of hospital admissions in selective Iranian patients with PADs. Forty patients with PADs, who were admitted to the Infectious Ward of Children's Medical Center Hospital during a 14-year period, were reviewed in this study. There were 115 documented episodes of hospital admission during a 14-year period. The average length of hospital stay was 33.30 ± 25.72 days. Pneumonia was the most prominent infection leading to hospitalization among these patients (n = 48, followed by gastroenteritis (n = 23. Other less frequent causes of hospitalization were fever and neutropenia, septic arthritis, encephalitis, orbital cellulitis, sepsis, urinary tract infection, meningitis, oral ulcer, and lung abscess. The most common causative organisms of diarrhea were: Giardia lamblia, followed by Candida albicans, and Salmonella sp. Many patients with PADs suffer from repeated infections leading to hospitalization, in spite of immunoglobulin replacement therapy. Respiratory tract infections were the prominent cause of hospitalization among studied patients, followed by gastrointestinal infections.

  1. Antimitochondrial antibodies and reactivity to N. aromaticivorans proteins in Icelandic patients with primary biliary cirrhosis and their relatives.

    Science.gov (United States)

    Olafsson, Sigurdur; Gudjonsson, Hallgrimur; Selmi, Carlo; Amano, Katsushi; Invernizzi, Pietro; Podda, Mauro; Gershwin, M Eric

    2004-11-01

    Primary biliary cirrhosis (PBC) is a chronic, progressive cholestatic disease of unknown etiology characterized by serum antimitochondrial antibodies (AMA) directed against a functionally related family of mitochondrial enzymes. We recently suggested that N. aromaticivorans might be the trigger of autoimmunity in PBC. No data are available on the specificity and crossreactivity of AMA in a genetically homogenous group of patients, such as the Icelandic population. To address these issues and to confirm previous findings in a unique population, we obtained sera from 14 PBC patients and 85 first-degree relatives, all of Icelandic descent. We analyzed such sera for AMA specificity using recombinant mitochondrial antigens and for reactivity against N. aromaticivorans proteins. Thirteen of the 14 Icelandic patients with PBC (93%) were found AMA positive. We found that 5/13 AMA positive sera (38%) reacted against PDC-E2 only; 5/13 (or 38%) reacted against BCOADC-E2; and 2/13 (15%) reacted against all three antigens. There was no reactivity against OGDC-E2. Reactivities of patients' sera against N. aromaticivorans were consistent with the AMA status. One serum among the 85 first-degree relatives (1.2%) was found to be AMA-positive, as well as reactive against N. aromaticivorans. Interestingly, despite the homogenous genetic background, the group of Icelandic patients with PBC was heterogeneous in their AMA reactive patterns and also reacted with N. aromaticivorans proteins.

  2. Pediatric glaucoma suspects

    Directory of Open Access Journals (Sweden)

    Kooner K

    2014-06-01

    Full Text Available Karanjit Kooner,1 Matthew Harrison,1 Zohra Prasla,1 Mohannad Albdour,1 Beverley Adams-Huet21Department of Ophthalmology, 2Department of Clinical Sciences, Division of Biostatistics, University of Texas Southwestern Medical Center, Dallas, TX, USAPurpose: To report demographic and ocular features of pediatric glaucoma suspects in an ethnically diverse population of North Central Texas.Design: Retrospective cross-sectional chart review.Participants: Subjects included 75 (136 eyes pediatric glaucoma suspects. Patients with one or more of the following risk factors were included: cup-to disc (C/D ratio of ≥0.6; intraocular pressure (IOP ≥21 mmHg; family history of glaucoma; congenital glaucoma in the opposite eye; history of blunt trauma to either eye; and presence of either Sturge–Weber or Axenfeld–Rieger syndrome, or oculodermal melanocytosis.Methods: Data were extracted from electronic patient medical records. Patient records with incomplete data were excluded. The main outcome measures were race, sex, age, IOP, C/D, family history of glaucoma; and glaucoma treatment.Results: Subjects included 28 (37.3% Hispanics, 20 (26.6% African Americans, 20 (26.6% Caucasians, and seven (9.3% Asians. Forty (53.3% of the patients were male. Suspicious optic disc was seen in 57 (76%; elevated IOP in 25 (33.3%; presence of family history in 13 (17.3%, and Sturge–Weber syndrome in nine (12% patients. The average C/D ratio was 0.58±0.2. The C/D ratios of African American (0.65±0.2, Hispanic (0.63±0.2, and Asian (0.62±0.15 patients were significantly greater than those of Caucasians (0.43±0.18; P=0.0004, 0.0003, and 0.0139, respectively. Caucasian patients were the youngest (7.9±4.8 years. Eleven cases (14.7% required medication.Conclusion: Thirty-three point seven percent of patients seen in the glaucoma clinic were glaucoma suspects. The most common risk factors for suspected glaucoma were suspicious optic discs, elevated IOP, and family history

  3. Risk factors for thrombosis and primary thrombosis prevention in patients with systemic lupus erythematosus with or without antiphospholipid antibodies.

    Science.gov (United States)

    Tektonidou, Maria G; Laskari, Katerina; Panagiotakos, Demosthenes B; Moutsopoulos, Haralampos M

    2009-01-15

    Antiphospholipid antibodies (aPL), namely anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC), have been associated with an increased risk of thrombosis in systemic lupus erythematosus (SLE). We examined additional thrombosis risk factors (aPL profile, SLE-related, and traditional risk factors) and the primary thrombosis prevention in SLE patients with and without aPL. All SLE patients with positive aPL but without previous thrombotic manifestations who were regularly followed up at our department (n = 144) and 144 age- and sex-matched SLE patients with negative aPL were included in this study. The median followup times were 104 and 112 months, respectively. The demographic, clinical, laboratory, and treatment characteristics and the traditional thrombosis risk factors were recorded. The thrombosis rate was 29 per 144 aPL-positive patients (20.1%) and 11 per 144 aPL-negative patients (7.6%; P = 0.003). In multiadjusted analysis, significant predictors of thrombosis were male sex (hazard ratio [HR] 6.25, P LAC (HR 3.48, P = 0.04), and constantly positive aCL (HR 5.87, P = 0.01) for aPL-positive patients, while male sex (HR 7.14, P = 0.03) and hypertension were predictors for aPL-negative patients (HR 6.49, P = 0.03). Additionally, the duration of low-dose aspirin treatment played a protective role against thrombosis in aPL-positive patients (HR per month 0.98, P = 0.05), as did the duration of hydroxychloroquine in both aPL-positive (HR per month 0.99, P = 0.05) and aPL-negative patients (HR per month 0.98, P = 0.04). Independent predictors of thrombosis for aPL-positive patients were male sex, LAC, and constantly positive aCL, and for aPL-negative patients were male sex and hypertension. The duration of low-dose aspirin use played a protective role against thrombosis in aPL-positive patients as did the duration of hydroxychloroquine in both groups.

  4. Overcoming a "probable" diagnosis in antimitochondrial antibody negative primary biliary cirrhosis: study of 100 sera and review of the literature.

    Science.gov (United States)

    Bizzaro, Nicola; Covini, Giovanni; Rosina, Floriano; Muratori, Paolo; Tonutti, Elio; Villalta, Danilo; Pesente, Fiorenza; Alessio, Maria Grazia; Tampoia, Marilina; Antico, Antonio; Platzgummer, Stefan; Porcelli, Brunetta; Terzuoli, Lucia; Liguori, Marco; Bassetti, Danila; Brusca, Ignazio; Almasio, Piero L; Tarantino, Giuseppe; Bonaguri, Chiara; Agostinis, Paolo; Bredi, Elena; Tozzoli, Renato; Invernizzi, Pietro; Selmi, Carlo

    2012-06-01

    Serum anti-mitochondrial antibodies (AMA) are the serological hallmark of primary biliary cirrhosis (PBC), yet up to 15% of PBC sera are AMA negative at routine indirect immunofluorescence (IIF) while being referred to as "probable" cases. The diagnostic role of PBC-specific antinuclear antibodies (ANA) remains to be determined. We will report herein data on the accuracy of new laboratory tools for AMA and PBC-specific ANA in a large series of PBC sera that were AMA-negative at IIF. We will also provide a discussion of the history and current status of AMA detection methods. We included IIF AMA-negative PBC sera (n=100) and sera from patients with other chronic liver diseases (n=104) that had been independently tested for IIF AMA and ANA; sera were blindly tested with an ELISA PBC screening test including two ANA (gp210, sp100) and a triple (pMIT3) AMA recombinant antigens. Among IIF AMA-negative sera, 43/100 (43%) manifested reactivity using the PBC screening test. The same test was positive for 6/104 (5.8%) control sera. IIF AMA-negative/PBC screen-positive sera reacted against pMIT3 (11/43), gp210 (8/43), Sp100 (17/43), both pMIT3 and gp210 (1/43), or both pMIT3 and Sp100 (6/43). Concordance rates between the ANA pattern on HEp-2 cells and specific Sp100 and gp210 ELISA results in AMA-negative subjects were 92% for nuclear dots and Sp100 and 99% for nuclear rim and gp210. Our data confirm the hypothesis that a substantial part of IIF AMA-negative (formerly coined "probable") PBC cases manifest disease-specific autoantibodies when tested using newly available tools and thus overcome the previously suggested diagnostic classification. As suggested by the recent literature, we are convinced that the proportion of AMA-negative PBC cases will be significantly minimized by the use of new laboratory methods and recombinant antigens.

  5. Measurement of HNE-protein adducts in human plasma and serum by ELISA—Comparison of two primary antibodies

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    Daniela Weber

    2013-01-01

    After modification and validation of the protocol for both antibodies, samples of two groups were analyzed: apparently healthy obese (n=62 and non-obese controls (n=15. Although the detected absolute values of HNE–protein adducts were different, depending on the antibody used, both ELISA methods showed significantly higher values of HNE–protein adducts in the obese group.

  6. Preparation of TiO{sub 2} nanosheet-carbon nanotube composite as immobilization platform for both primary and secondary antibodies in electrochemical immunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiaoqiang, E-mail: 13781157777@163.com; Liu, Pepipei; Huo, Xiaohe; Liu, Xiuhua; Liu, Jin

    2016-11-23

    TiO{sub 2} nanosheets (TNSs) were synthesized and deposited on multi-wall carbon nanotubes (MWCNTs) to form a nano-composite through a hydrothermal method, followed by the characterization with various spectroscopic and microscopic techniques. The TNS-MWCNT composite was then applied as not only an electrode scaffold to immobilize primary antibody, but also as a carrier to load secondary antibody and horseradish peroxidase (HRP). In both cases, bis(sulfosuccinimidyl) suberate sodium salt acted as an amino cross-linker to covalently bind the biomolecules on TNS-MWCNT composite through their surface primary amino groups. After the sandwich-type immunoreaction, HPR was quantitatively captured on the electrode surface via the binding between secondary antibody and antigen, and electrochemical response of the immunosensor was then amplified by a H{sub 2}O{sub 2} mediated HRP catalytic reaction. Using α-Fetoprotein as a model analyte, a linear range between 0.005 and 320 ng mL{sup −1} with a detection limit of 2.0 pg mL{sup −1} was achieved by differential pulse voltammetry. The improved immunosensor performance could be attributed to the biocompatibility and high specific surface area of TNS, and excellent electrical conductivity of MWCNTs, which accelerated the electron transfer at the electrode surface. - Highlights: • TiO{sub 2} nanosheet-carbon nanotube composite was synthesized by hydrothermal method. • The composite exhibits improved properties compared to the individuals. • The composite is designed as electrode scaffold for immobilizing primary antibody. • Secondary antibody and horseradish peroxidase are immobilized on the composite as a label. • The tracing label exhibits great amplification effect for immunosensing.

  7. Analysis of specific IgG titers against tick-borne encephalitis in patients with primary antibody deficiency under immunoglobulin substitution therapy: impact of plasma donor origin.

    Science.gov (United States)

    Goldacker, Sigune; Witte, Torsten; Huzly, Daniela; Schlesier, Michael; Peter, Hans-Hartmut; Warnatz, Klaus

    2014-01-01

    Immunoglobulin (Ig) replacement therapy is effective in reducing infections in patients with primary antibody deficiency (PAD). Diversity of specific antibodies is achieved by pooling plasma from over 1000 donors usually of a given geographic region. However, there is no agreement with regard to an optimal vaccination schedule for plasma donors. Especially for tick-borne encephalitis (TBE), regional vaccination rates differ widely among populations due to the epidemiology of the disease. We analyzed specific antibody titers against TBE in comparison to total IgG levels in 162 serum samples collected from 110 PAD patients substituted with polyvalent intravenous IgG or subcutaneous IgG. Some patients received different IgG products over time leading to a total number of 122 different patient-IgG product combinations. Positive TBE-specific IgG levels were detected in 35 cases when measured by standard ELISA and could be confirmed by demonstration of neutralizing antibodies in 31 cases. The detection of specific antibody levels correlated with the geographic origin of the IgG preparations. No titers were detectable in patients substituted with IgG products from North-American donors, whereas variable degrees of anti-TBE titers were observed in patients receiving products from different European countries. We suggest considering the patients' personal risk for TBE when selecting an appropriate Ig preparation. These data support regional plasma donation in order to address the diverse local infection profile.

  8. Human leukocyte antigen Class II associations in serum antimitochondrial antibodies (AMA)-positive and AMA-negative primary biliary cirrhosis.

    Science.gov (United States)

    Stone, Julianne; Wade, Judy A; Cauch-Dudek, Karen; Ng, Chang; Lindor, Keith D; Heathcote, E Jenny

    2002-01-01

    An association of Class II HLA-DR8 antigen is reported in patients with serum antimitochondrial antibodies (AMA)-positive primary biliary cirrhosis (PBC); no information exists as to an association with AMA-negative PBC. We compared the frequency of HLA Class II genes in AMA-positive and AMA-negative PBC patients and healthy controls. Genomic DNA was extracted from the blood of 154 AMA-positive and 26 AMA-negative Caucasian PBC patients and from 216 healthy Caucasian controls and tested for the alleles at two HLA Class II loci, DRbeta1 and DQbeta1. Higher allele frequencies of HLA-DRbeta1*08 and DQbeta1*04 were found in the AMA-positive PBC patients versus controls (14.9% vs. 6.5%, odds ratio (OR)=3.3, global P=0.03 and 14.4% vs. 6.5%, OR=2.6, global P=0.002). All patients positive for DRbeta1*0801 were positive for the DQbeta1*0402 allele, delta score=22 for AMA-positive patients, 11 for controls. In AMA-negative PBC, the frequency of DRbeta1*08 and DQbeta1*04 was 0%, significantly different from the AMA-positive patients (P=0.05, P=0.05). AMA response may identify a group of PBC patients with a distinctive expression of the disease with the response associated with a gene(s) in the class II region of the major histocompatibility complex on the short arm of chromosome 6.

  9. Ae2a,b-deficient mice develop antimitochondrial antibodies and other features resembling primary biliary cirrhosis.

    Science.gov (United States)

    Salas, January T; Banales, Jesús M; Sarvide, Sarai; Recalde, Sergio; Ferrer, Alex; Uriarte, Iker; Oude Elferink, Ronald P J; Prieto, Jesús; Medina, Juan F

    2008-05-01

    Cl(-)/HCO(3)(-) anion exchanger 2 (AE2) is involved in intracellular pH (pH(i)) regulation and transepithelial acid-base transport, including secretin-stimulated biliary bicarbonate excretion. AE2 gene expression was found to be reduced in liver biopsy specimens and blood mononuclear cells from patients with primary biliary cirrhosis (PBC), a disease characterized by chronic nonsuppurative cholangitis associated with antimitochondrial antibodies (AMA) and other autoimmune phenomena. In mice with widespread Ae2 gene disruption, we previously reported altered spermiogenesis and reduced gastric acid secretion. We now describe the hepatobiliary and immunologic changes observed in these Ae2(a.b)-deficient mice. In this murine model, splenocyte pH(i) and T-cell populations were studied by flow cytometry. CD3-stimulated cytokine secretion was estimated using cytokine arrays. AMA were evaluated by immunoblotting and proteomics. Hepatobiliary changes were assessed by immunohistopathology, flow cytometry, and serum biochemistry. Cholangiocyte gene expression was analyzed by real-time polymerase chain reaction. Ae2(a,b)(-/-) mice exhibit splenomegaly, elevated pH(i) in splenocytes, increased production of interleukin-12p70 and interferon gamma, expanded CD8(+) T-cell population, and under represented CD4(+)FoxP3(+)/regulatory T cells. Most Ae2(a,b)(-/-) mice tested positively for AMA, showing increased serum levels of immunoglobulin M and G, and liver-specific alkaline phosphatase. About one third of Ae2(a,b)(-/-) mice had extensive portal inflammation with CD8(+) and CD4(+) T lymphocytes surrounding damaged bile ducts. Cholangiocytes isolated from Ae2(a,b)(-/-) mice showed gene expression changes compatible with oxidative stress and increased antigen presentation. Ae2 deficiency alters pH(i) homeostasis in immunocytes and gene expression profile in cholangiocytes, leading to immunologic and hepatobiliary changes that resemble PBC.

  10. Shift from intravenous or 16% subcutaneous replacement therapy to 20% subcutaneous immunoglobulin in patients with primary antibody deficiencies.

    Science.gov (United States)

    Canessa, Clementina; Iacopelli, Jessica; Pecoraro, Antonio; Spadaro, Giuseppe; Matucci, Andrea; Milito, Cinzia; Vultaggio, Alessandra; Agostini, Carlo; Cinetto, Francesco; Danieli, Maria Giovanna; Gambini, Simona; Marasco, Carolina; Trizzino, Antonino; Vacca, Angelo; De Mattia, Domenico; Martire, Baldassarre; Plebani, Alessandro; Di Gioacchino, Mario; Gatta, Alessia; Finocchi, Andrea; Licciardi, Francesco; Martino, Silvana; De Carli, Marco; Moschese, Viviana; Azzari, Chiara

    2017-03-01

    In patients with primary antibody deficiencies, subcutaneous administration of IgG (SCIG) replacement is effective, safe, well-tolerated, and can be self-administered at home. A new SCIG replacement at 20% concentration (Hizentra®) has been developed and has replaced Vivaglobin® (SCIG 16%). An observational prospective multi-centric open-label study, with retrospective comparison was conducted in 15 Italian centers, in order to investigate whether and to what extent switching to Hizentra® would affect frequency of infusions, number of infusion sites, patients' satisfaction, and tolerability in patients previously treated with Vivaglobin® or intravenous immunoglobulins (IVIG). Any variations of dosage, frequency and duration of the infusions, and of number of infusion sites induced by Hizentra® with respect to the former treatment were recorded. Practical advantages and disadvantages of Hizentra®, with respect to the medicinal product formerly used, and the variations in patients' therapy-related satisfaction were monitored by means of the TSQM (Treatment Satisfaction Questionnaire for Medication); number, frequency, and duration of infectious events and adverse effects were recorded. Eighty-two patients switched to Hizentra®: 19 (23.2%) from IVIG and 63 (76.8%) from Vivaglobin®. The mean interval between infusions was not affected by the shift (7.0 ± 2.0 days with previous treatment versus 7.1 ± 1.2 during Hizentra®). A decrease in the number of infusion sites with Hizentra® was recorded in 12 out of 56 patients for whom these data were available. At 6 months, 89.7% of patients were satisfied with Hizentra®; no difference in terms of effectiveness, side effects, convenience, and global satisfaction was observed. No difference in the incidence of adverse events was reported.

  11. A human antibody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1.

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    Johannes S Gach

    Full Text Available Primary isolates of HIV-1 resist neutralization by most antibodies to the CD4 binding site (CD4bs on gp120 due to occlusion of this site on the trimeric spike. We describe 1F7, a human CD4bs monoclonal antibody that was found to be exceptionally potent against the HIV-1 primary isolate JR-FL. However, 1F7 failed to neutralize a patient-matched primary isolate, JR-CSF even though the two isolates differ by <10% in gp120 at the protein level. In an HIV-1 cross clade panel (n = 157, 1F7 exhibited moderate breadth, but occasionally achieved considerable potency. In binding experiments using monomeric gp120s of select resistant isolates and domain-swap chimeras between JR-FL and JR-CSF, recognition by 1F7 was limited by sequence polymorphisms involving at least the C2 region of Env. Putative N-linked glycosylation site (PNGS mutations, notably at position 197, allowed 1F7 to neutralize JR-CSF potently without improving binding to the cognate, monomeric gp120. In contrast, flow cytometry experiments using the same PNGS mutants revealed that 1F7 binding is enhanced on cognate trimeric Env. BN-PAGE mobility shift experiments revealed that 1F7 is sensitive to the diagnostic mutation D368R in the CD4 binding loop of gp120. Our data on 1F7 reinforce how exquisitely targeted CD4bs antibodies must be to achieve cross neutralization of two closely related primary isolates. High-resolution analyses of trimeric Env that show the orientation of glycans and polymorphic elements of the CD4bs that affect binding to antibodies like 1F7 are desirable to understand how to promote immunogenicity of more conserved elements of the CD4bs.

  12. Effect of concurrent intratracheal lipopolysaccharide and human serum albumin challenge on primary and secondary antibody responses in poultry

    NARCIS (Netherlands)

    Parmentier, H.K.; Klompen, A.L.; Vries Reilingh, de G.; Lammers, A.

    2008-01-01

    Activation of the innate immune system by pathogen-associated molecular patterns (PAMPs) may direct specific immune responses and as a consequence probably significantly affect vaccination. Previously, we described modulation of specific antibody responses to systemically administered model antigens

  13. Younger patients with primary Sjögren's syndrome are more likely to have salivary IgG anti-muscarinic acetylcholine receptor type 3 antibodies.

    Science.gov (United States)

    Jayakanthan, K; Ramya, J; Mandal, Santosh Kumar; Sandhya, P; Gowri, M; Danda, Debashish

    2016-03-01

    Acetylcholine type 3 receptor (M3R) is recognized as an autoantigen in primary Sjögren's syndrome (pSS). Assay of anti-M3R antibody levels in serum is fraught with low sensitivity for diagnosis of pSS. Salivary assay is more likely to improve the diagnostic accuracy. Patients with pSS classified either by the American European Consensus Group (AECG) or American college of Rheumatology (ACR) criteria, attending rheumatology clinic between October 2014 and July 2015 were included. Hospital staff and lupus patients constituted healthy and disease controls, respectively. Evaluation of pSS included clinical evaluation, laboratory tests, ESSDAI and ESSPRI scoring. Unstimulated saliva was collected by the spitting method. Salivary IgG antibody against M3R (anti-M3R) was quantified by indirect ELISA. In this study, 43 patients with pSS, 34 with lupus and 42 healthy controls were recruited. The frequency of anti-M3R antibody levels was 55.81, 17.64 and 7 % for pSS, lupus and healthy controls, respectively. Area under the Receiver Operator Characteristic was 0.7791 (95 % CI,, 0.67-0.87). Sensitivity and specificity of the assay for diagnosis of pSS were 44.19 and 88.16 %, respectively. Salivary anti-M3R IgG antibody positivity was associated with lower age, shorter disease duration and higher globulin levels in our cohort. Salivary anti-M3R IgG antibody assay has high specificity in pSS; younger patients and those with hyperglobulinemia more frequently tested positive for this antibody.

  14. Antimitochondrial antibodies of immunoglobulin G3 subclass are associated with a more severe disease course in primary biliary cirrhosis.

    Science.gov (United States)

    Rigopoulou, Eirini I; Davies, Edward T; Bogdanos, Dimitrios-Petrou; Liaskos, Christos; Mytilinaiou, Maria; Koukoulis, George K; Dalekos, George N; Vergani, Diego

    2007-11-01

    Primary biliary cirrhosis (PBC) is characterised by the presence of immunoglobulin (Ig) G antimitochondrial antibodies (AMA), which are routinely detected by indirect immunofluorescence (IFL) using composite rodent tissue substrate. The IgG subclass distribution and clinical significance of IFL-detected AMA in patients with PBC have not been previously studied in detail. We have examined IgG subclass-specific AMA detected by IFL on rodent liver, kidney and stomach tissue substrate using affinity-purified IgG subclass monospecific antisera as revealing reagents in 95 AMA-positive PBC patients from Greece. AMA of any of the IgG1, IgG2 or IgG3 subclasses were present in 89/95 (93.7%) patients. Among those 89, 55 (61.8%) had IgG1, 2, 3 AMA positivity; eight (9%) had IgG1, 2; seven (7.9%) had IgG2, 3; eight (9%) had IgG1, 3; nine (10.1%) had IgG1 subclass and two (2.2%) single IgG3 AMA reactivity. IgG4 AMA was absent. IgG3 titres were higher than IgG2 and IgG1 (P<0.001) and IgG1 higher than IgG2 (P<0.001). IgG3 AMA-positive patients had a histologically more advanced disease (P<0.01) and were more frequently cirrhotic compared with those who were negative (P<0.01). There was a positive correlation between AMA IgG3 titre and Mayo risk score (r=0.55, P=0.009, Spearman's correlation). Our findings suggest that AMA are not restricted to a specific IgG subclass. AMA of the IgG3 subclass are associated with a more severe disease course, possibly reflecting the peculiar ability of this isotype to engage mediators of damage.

  15. Anticorpos antinucleossomo e síndrome antifosfolipídica: estudo observacional Antinucleosome antibodies and primary antiphospholipid syndrome: an observational study

    Directory of Open Access Journals (Sweden)

    Alexandre Wagner Silva de Souza

    2012-06-01

    Full Text Available OBJETIVO: Avaliar a associação entre a presença de anticorpos antinucleossomo (anti-NCS e a síndrome antifosfolipídica primária (SAFP e o posterior desenvolvimento de lúpus eritematoso sistêmico (LES. MATERIAIS E MÉTODOS: Trinta e seis mulheres com o diagnóstico de SAFP foram avaliadas prospectivamente para manifestações de doenças reumáticas autoimunes e para a presença de anticorpos antifosfolípides, anticorpos antinucleares e anti-NCS/cromatina. RESULTADOS: Após um período médio de seguimento de 45,7 meses, anticorpos anti-NCS/cromatina foram detectados em apenas uma paciente (2,8%, que desenvolveu manifestações de LES tais como poliartrite, linfopenia, neurite óptica, lesões compatíveis com esclerose múltipla em substância branca cerebral e perfil de autoanticorpos altamente sugestivo de LES. CONCLUSÃO: A frequência de anticorpos anti-NCS/cromatina é baixa em pacientes com SAFP, e sua presença pode associar-se ao desenvolvimento de manifestações de LES.OBJECTIVE: To study the association of anti-nucleosome (anti-NCS antibodies in primary antiphospholipid syndrome (APS and the development of systemic lupus erythematosus (SLE during follow-up. MATERIALS AND METHODS: Thirty-six women with primary APS were evaluated prospectively for clinical features of systemic autoimmune diseases and for the presence of antiphospholipid antibodies, antinuclear antibodies and anti-NCS/chromatin antibodies. RESULTS: After a mean follow-up period of 45.7 months, anti-NCS/chromatin antibodies were detected in only one patient (2.8%, who developed features of SLE including polyarthritis, lymphopenia, optic neuritis, multiple sclerosis-like lesions, and an autoantibody profile suggestive of SLE. CONCLUSION: The frequency of anti-NCS/chromatin antibodies in primary APS patients is very low, and they may be associated with the development of SLE manifestations.

  16. Analysis of the clinical relevance of antimitochondrial antibodies to the β- and γ-subunits of the F1F0-ATPase in patients with primary biliary cirrhosis

    Directory of Open Access Journals (Sweden)

    Nann Dominik

    2012-10-01

    Full Text Available Abstract Background In a recent study we showed that in patients with primary biliary cirrhosis (PBC being positive or negative for anti-M2 antibodies reacting with the 2-oxoacid-dehydrogenase complex (ODC also antibodies to the beta- and gamma-subunits of F1F0-ATPase (anti-β, anti-γ occur. This is a mitochondrial enzyme but parts are also expressed on plasma membranes of endothelial cells. Here we wanted to analyse in more detail their clinical relevance. Methods Fifty-nine untreated and histologically defined PBC patients who had been followed for at least five years were included into the study (51 anti-M2 positive, 8 anti-M2 negative. Twenty-three of them were treated in the follow up with ursodeoxycholic acid (UDCA, eight received during a trial methotrexate (MTX. In 13 patients orthotopic liver transplantation (OLT had to be performed. Serum samples before and during therapy were available. Patients were analysed with respect to laboratory parameters, disease activity and histological stages. Patients’ sera were tested by ELISA for IgG- and IgM-antibodies against the beta- and gamma-subunits which had been recombinant expressed in E.coli and highly purified by electro-elution from SDS-gels after electrophoresis. Results Fifty-nine percent of the anti-M2 positive and 50% of the anti-M2 negative PBC patients had anti-β- and/or anti-γ-antibodies. There were no differences between anti-β- and/or anti-γ-antibody positive or negative patients with respect to biochemical parameters, immunoglobulins, histological stages or disease activity. Antibody reactivity significantly decreased during UDCA and MTX-treatment and also after OLT. Conclusions Antibodies to the β- and γ-subunits of F1F0-ATPase occur in anti-M2 positive and –negative PBC but do not have any relevance with respect to clinical activity or prognosis. However, in contrast to the anti-M2 antibodies they decrease during UDCA and immunosuppressive therapy.

  17. Analysis of the clinical relevance of antimitochondrial antibodies to the β- and γ-subunits of the F1F0-ATPase in patients with primary biliary cirrhosis.

    Science.gov (United States)

    Nann, Dominik; Berg, Christoph P; Preuss, Beate E; Klein, Reinhild

    2012-10-24

    In a recent study we showed that in patients with primary biliary cirrhosis (PBC) being positive or negative for anti-M2 antibodies reacting with the 2-oxoacid-dehydrogenase complex (ODC) also antibodies to the beta- and gamma-subunits of F1F0-ATPase (anti-β, anti-γ) occur. This is a mitochondrial enzyme but parts are also expressed on plasma membranes of endothelial cells. Here we wanted to analyse in more detail their clinical relevance. Fifty-nine untreated and histologically defined PBC patients who had been followed for at least five years were included into the study (51 anti-M2 positive, 8 anti-M2 negative). Twenty-three of them were treated in the follow up with ursodeoxycholic acid (UDCA), eight received during a trial methotrexate (MTX). In 13 patients orthotopic liver transplantation (OLT) had to be performed. Serum samples before and during therapy were available. Patients were analysed with respect to laboratory parameters, disease activity and histological stages.Patients' sera were tested by ELISA for IgG- and IgM-antibodies against the beta- and gamma-subunits which had been recombinant expressed in E.coli and highly purified by electro-elution from SDS-gels after electrophoresis. Fifty-nine percent of the anti-M2 positive and 50% of the anti-M2 negative PBC patients had anti-β- and/or anti-γ-antibodies. There were no differences between anti-β- and/or anti-γ-antibody positive or negative patients with respect to biochemical parameters, immunoglobulins, histological stages or disease activity. Antibody reactivity significantly decreased during UDCA and MTX-treatment and also after OLT. Antibodies to the β- and γ-subunits of F1F0-ATPase occur in anti-M2 positive and -negative PBC but do not have any relevance with respect to clinical activity or prognosis. However, in contrast to the anti-M2 antibodies they decrease during UDCA and immunosuppressive therapy.

  18. Anti-Toxoplasma antibody prevalence, primary infection rate, and risk factors in a study of toxoplasmosis in 4,466 pregnant women in Japan.

    Science.gov (United States)

    Sakikawa, Makiko; Noda, Shunichi; Hanaoka, Masachi; Nakayama, Hirotoshi; Hojo, Satoshi; Kakinoki, Shigeko; Nakata, Maki; Yasuda, Takashi; Ikenoue, Tsuyomu; Kojima, Toshiyuki

    2012-03-01

    Toxoplasmosis is a zoonosis caused by infection with Toxoplasma gondii and is prevalent worldwide under various climatic conditions. It is usually asymptomatic, but infection in pregnant women can pose serious health problems for the fetus. However, epidemiological information regarding toxoplasmosis in Japanese pregnant women is limited. This study aimed to determine the prevalence of anti-Toxoplasma antibodies, the primary infection rate, and the risk factors for toxoplasmosis in Japanese pregnant women. We measured anti-Toxoplasma antibody titers in 4,466 pregnant women over a period of 7.5 years and simultaneously conducted interviews to identify the risk factors for toxoplasmosis. The overall prevalence of anti-Toxoplasma antibodies was 10.3%, and it was significantly higher in women aged above 35 years. The rate of primary Toxoplasma infection during pregnancy was estimated to be 0.25%. A possibility of infection in the later stages of pregnancy was identified for those women who were not infected in the early stages. A history of raw meat intake was identified to be a risk factor related to toxoplasmosis. Therefore, to lower the risk of toxoplasmosis, pregnant women should refrain from eating raw and undercooked meat and maintain personal hygiene.

  19. Technology and the Glaucoma Suspect

    National Research Council Canada - National Science Library

    Blumberg, Dana M; De Moraes, Carlos Gustavo; Liebmann, Jeffrey M; Garg, Reena; Chen, Cynthia; Theventhiran, Alex; Hood, Donald C

    2016-01-01

    ...), stereoscopic disc photographs, and automated perimetry as assessed by a group of glaucoma specialists in differentiating individuals with early glaucoma from suspects. Forty-six eyes (46 patients...

  20. [Three cases of suspected re-infection of mumps virus].

    Science.gov (United States)

    Hatanaka, Akio; Kamada, Tomoko; Honda, Keiji; Tazaki, Akihisa; Kishine, Naomi; Kawashima, Yoshiyuki

    2012-08-01

    A 32-year-old woman, 5-year-old girl, and 33-year-old man visited our otorhinolaryngology outpatient clinic with tumentia of the unilateral parotid gland. A high titer of serum IgG antibodies against the mumps virus was detected. Around the same time, other members of their families had the same parotid tumentia, and they were diagnosed as having their first mumps infection. Therefore, the diagnosis of the three cases was strongly suspected to be re-infection with mumps. In Japan, it was classically believed that the mumps virus infection occurs only once in patients and reinfection doesn't occur. However, some pediatricians in Japan have reported that re-infection with mumps is strongly suspected when high titers of serum IgG antibodies against the mumps virus are found at the initial visit. It is now believed many more examples of mumps re-infection cases have existed than we previously believed. When high titers of serum IgG antibodies against the mumps virus are detected at an initial visit in patients who have had mumps previously, re-infection should be strongly suspected. And to make it certain, we suggest that the mumps IgG antibodies should be checked twice to confirm the diagnosis. If elevation of the IgG antibodies persist, the diagnosis will be much more certain.

  1. ICAM-1-based rabies virus vaccine shows increased infection and activation of primary murine B cells in vitro and enhanced antibody titers in-vivo.

    Directory of Open Access Journals (Sweden)

    James E Norton

    Full Text Available We have previously shown that live-attenuated rabies virus (RABV-based vaccines infect and directly activate murine and human primary B cells in-vitro, which we propose can be exploited to help develop a single-dose RABV-based vaccine. Here we report on a novel approach to utilize the binding of Intracellular Adhesion Molecule-1 (ICAM-1 to its binding partner, Lymphocyte Function-associated Antigen-1 (LFA-1, on B cells to enhance B cell activation and RABV-specific antibody responses. We used a reverse genetics approach to clone, recover, and characterize a live-attenuated recombinant RABV-based vaccine expressing the murine Icam1 gene (rRABV-mICAM-1. We show that the murine ICAM-1 gene product is incorporated into virus particles, potentially exposing ICAM-1 to extracellular binding partners. While rRABV-mICAM-1 showed 10-100-fold decrease in viral titers on baby hamster kidney cells compared to the parental virus (rRABV, rRABV-mICAM-1 infected and activated primary murine B cells in-vitro more efficiently than rRABV, as indicated by significant upregulation of CD69, CD40, and MHCII on the surface of infected B cells. ICAM-1 expression on the virus surface was responsible for enhanced B cell infection since pre-treating rRABV-mICAM-1 with a neutralizing anti-ICAM-1 antibody reduced B cell infection to levels observed with rRABV alone. Furthermore, 100-fold less rRABV-mICAM-1 was needed to induce antibody titers in immunized mice equivalent to antibody titers observed in rRABV-immunized mice. Of note, only 10(3 focus forming units (ffu/mouse of rRABV-mICAM-1 was needed to induce significant anti-RABV antibody titers as early as five days post-immunization. As both speed and potency of antibody responses are important in controlling human RABV infection in a post-exposure setting, these data show that expression of Icam1 from the RABV genome, which is then incorporated into the virus particle, is a promising strategy for the development of a

  2. ICAM-1-based rabies virus vaccine shows increased infection and activation of primary murine B cells in vitro and enhanced antibody titers in-vivo.

    Science.gov (United States)

    Norton, James E; Lytle, Andrew G; Shen, Shixue; Tzvetkov, Evgeni P; Dorfmeier, Corin L; McGettigan, James P

    2014-01-01

    We have previously shown that live-attenuated rabies virus (RABV)-based vaccines infect and directly activate murine and human primary B cells in-vitro, which we propose can be exploited to help develop a single-dose RABV-based vaccine. Here we report on a novel approach to utilize the binding of Intracellular Adhesion Molecule-1 (ICAM-1) to its binding partner, Lymphocyte Function-associated Antigen-1 (LFA-1), on B cells to enhance B cell activation and RABV-specific antibody responses. We used a reverse genetics approach to clone, recover, and characterize a live-attenuated recombinant RABV-based vaccine expressing the murine Icam1 gene (rRABV-mICAM-1). We show that the murine ICAM-1 gene product is incorporated into virus particles, potentially exposing ICAM-1 to extracellular binding partners. While rRABV-mICAM-1 showed 10-100-fold decrease in viral titers on baby hamster kidney cells compared to the parental virus (rRABV), rRABV-mICAM-1 infected and activated primary murine B cells in-vitro more efficiently than rRABV, as indicated by significant upregulation of CD69, CD40, and MHCII on the surface of infected B cells. ICAM-1 expression on the virus surface was responsible for enhanced B cell infection since pre-treating rRABV-mICAM-1 with a neutralizing anti-ICAM-1 antibody reduced B cell infection to levels observed with rRABV alone. Furthermore, 100-fold less rRABV-mICAM-1 was needed to induce antibody titers in immunized mice equivalent to antibody titers observed in rRABV-immunized mice. Of note, only 10(3) focus forming units (ffu)/mouse of rRABV-mICAM-1 was needed to induce significant anti-RABV antibody titers as early as five days post-immunization. As both speed and potency of antibody responses are important in controlling human RABV infection in a post-exposure setting, these data show that expression of Icam1 from the RABV genome, which is then incorporated into the virus particle, is a promising strategy for the development of a single-dose RABV

  3. Measurement of HNE-protein adducts in human plasma and serum by ELISA-Comparison of two primary antibodies.

    Science.gov (United States)

    Weber, Daniela; Milkovic, Lidija; Bennett, Stuart J; Griffiths, Helen R; Zarkovic, Neven; Grune, Tilman

    2013-01-01

    There is increasing evidence that non-enzymatic post-translational protein modifications might play key roles in various diseases. These protein modifications can be caused by free radicals generated during oxidative stress or by their products generated during lipid peroxidation. 4-Hydroxynonenal (HNE), a major biomarker of oxidative stress and lipid peroxidation, has been recognized as important molecule in pathology as well as in physiology of living organisms. Therefore, its detection and quantification can be considered as valuable tool for evaluating various pathophysiological conditions. The HNE-protein adduct ELISA is a method to detect HNE bound to proteins, which is considered as the most likely form of HNE occurrence in living systems. Since the earlier described ELISA has been validated for cell lysates and the antibody used for detection of HNE-protein adducts is non-commercial, the aim of this work was to adapt the ELISA to a commercial antibody and to apply it in the analysis of human plasma samples. AFTER MODIFICATION AND VALIDATION OF THE PROTOCOL FOR BOTH ANTIBODIES, SAMPLES OF TWO GROUPS WERE ANALYZED: apparently healthy obese (n=62) and non-obese controls (n=15). Although the detected absolute values of HNE-protein adducts were different, depending on the antibody used, both ELISA methods showed significantly higher values of HNE-protein adducts in the obese group.

  4. Patients with autoimmune hepatitis who have antimitochondrial antibodies need long-term follow-up to detect late development of primary biliary cirrhosis.

    Science.gov (United States)

    Dinani, Amreen M; Fischer, Sandra E; Mosko, Jeff; Guindi, Maha; Hirschfield, Gideon M

    2012-06-01

    Patients with autoimmune hepatitis (AIH) who have antibodies against mitochondrial proteins (AMA positive) are believed to have an autoimmune syndrome that should be managed as AIH. Of patients with AMA-positive AIH, we report on 3 individuals to demonstrate how autoimmune liver disease can progress over time. Specific features of primary biliary cirrhosis (PBC) overlapped in time in these patients. Our observations indicate the importance of careful follow up of patients with AMA-positive AIH; health care professionals that treat such patients should therefore be aware of longitudinal clinical changes that might indicate development of PBC in this setting. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  5. Immunohistochemical detection of VHS virus in paraffin-embedded specimens of rainbow trout (Oncorhynchus mykiss); The influence of primary antibody, fixative, and antigen unmasking on method sensitivity

    DEFF Research Database (Denmark)

    Evensen, O.; Olesen, Niels Jørgen

    1997-01-01

    The influence of the primary antibody, the fixative, and the antigen unmasking technique on the method sensitivity of immunohistochemistry as a method for the identification of viral hemorrhagic septicemia (VHS) virus in paraffin-embedded specimens of naturally infected rainbow trout (Oncorhynchus...... performed on parallel specimens, and the virus titer (TCID50/ml) was determined. Purified nucleocapsid protein (N-protein) of the virus was incorporated in an artificial antigen substrate (polymerized bovine serum albumin), fixed as described above, and embedded in paraffin wax. Microwave unmasking...

  6. Multiple primary syphilis on the lip, nipple-areola and penis: An immunohistochemical examination of Treponema pallidum localization using an anti-T. pallidum antibody.

    Science.gov (United States)

    Fukuda, Hidetsugu; Takahashi, Misaki; Kato, Keiichi; Oharaseki, Toshiaki; Mukai, Hideki

    2015-05-01

    Primary syphilis caused by Treponema pallidum usually develops after sexual contact as an initial solitary sclerosis or hard chancre in the genital region. We describe a case of primary syphilis at three sites in genital and extragenital regions of a man who had sex with men. A 29-year-old man visited our hospital for skin lesions on his lower lip, nipple-areola and penis. A positive syphilis serological test for rapid plasma reagin had a titer of 1:16; the patient also tested positive for specific antibodies against T. pallidum, with a cut-off index of 39.0. Histopathological examination of a nipple-areola biopsy specimen revealed a thickened epidermis and dense infiltration of inflammatory cells extending from the upper dermal layers to the deep dermis. The inflammatory cells were composed of abundant lymphocytes, plasma cells, histiocytes and neutrophils. Immunohistochemical staining for T. pallidum using an anti-T. pallidum antibody showed numerous spirochetes in the lower portion of the epidermis, scattered inside inflammatory cell infiltrate and perivascular sites throughout the dermis. Based on these findings, the patient was diagnosed with primary syphilis. Treatment with oral amoxicillin hydrate was started. Five days after starting treatment, a diffuse maculopapular rash (syphilitic roseola) occurred on his trunk and extremities. Perivascular cuffing due to T. pallidum was present throughout the dermis in the biopsy specimen of a localized lesion of primary syphilis. Moreover, syphilitic roseola, which indicates generalized dissemination of T. pallidum, developed during the course of treatment for primary syphilis. Therefore, we considered perivascular cuffing to be indicative of the dissemination phase. © 2015 Japanese Dermatological Association.

  7. RI-002, an intravenous immunoglobulin containing high titer neutralizing antibody to RSV and other respiratory viruses for use in primary immunodeficiency disease and other immune compromised populations.

    Science.gov (United States)

    Wasserman, Richard L; Greener, Benjamin N; Mond, James

    2017-10-16

    Novel immune globulin (IG) products (RI-002, RI-001) have been designed to provide protection against respiratory syncytial virus (RSV) mediated respiratory illness while at the same time meeting the manufacturing requirements established by FDA for antibody supplementation in immunocompromised subjects. Areas covered: This review covers the manufacture and development of both RI-001 and RI-002, including the selection of plasma donors for IG preparation with high-titers of anti-RSV antibody, in vitro, and preclinical data in the cotton rat model S. hispidus, and clinical trials including Phase II and compassionate use studies of RI-001 and a multi-center, pivotal Phase III study of RI-002 in PIDD patients. Expert commentary: The data demonstrate that RI-002 is efficacious in the prevention and treatment of RSV in preclinical normal and immune suppressed animal models and is safe and efficacious in the treatment of patients with various forms of primary immunodeficiency disease (PIDD). This product offers potential advantages over other available IG's for prophylaxis in immunocompromised patients requiring polyclonal immunoglobulin supplementation because of its unique antibody composition. In addition to its enhanced neutralizing anti-RSV activity and its polyclonal IG composition, there is preclinical data to support the use of RI-002 for humoral protection against other respiratory pathogens.

  8. Is there a link between Hashimoto's thyroiditis and primary hyperparathyroidism? A study of serum parathormone and anti-TPO antibodies in 2267 patients.

    Science.gov (United States)

    Ignjatovic, Vesna D; Matovic, Milovan D; Vukomanovic, Vladimir R; Jankovic, Slobodan M; Džodić, Radan R

    2013-01-01

    According to various authors, thyroid disorders like Hashimoto's thyroiditis (HT), diffuse goiter or multinodular goiter, Graves' disease, medullary or papillary carcinoma could be found in a number of patients with primary hyperparathyroidism (PHPT). This association is more common in elderly women. Neck irradiation, lithium treatment and elevated TSH levels have been suggested as some of the possible causes of this co-existance. The aim of this study was to investigate and determine the prevalence of patients having both HT and PHPT, and the possible relation between these two diseases. We conducted a prospective study during three and a half years. This study included 45,231 patients, which were referred by their general practitioner or endocrinologist, under suspicion of having thyroid and/or parathyroid disease. In these patients we measured serum levels of the following parameters: anti-thyroid peroxidase antibodies (antiTPO-Ab), anti-thyroglobulin antibodies (Tg-Ab), anti-TSH-receptor antibodies (TSHR-Ab), thyroid-stimulating hormone (TSH), parathyroid hormone (PTH) and calcium (Ca). In 2,267 of these 45,231 patients (5.01%) we noticed elevated antiTPO-Ab (3542±3407IU/mL), with statistical significant difference from normal values (normal range 0-70IU/mL), Pgenetical predisposition of both entities.

  9. Human leucocyte antigen (HLA) expression of primary trophoblast cells and placental cell lines, determined using single antigen beads to characterize allotype specificities of anti-HLA antibodies.

    Science.gov (United States)

    Apps, Richard; Murphy, Shawn P; Fernando, Raymond; Gardner, Lucy; Ahad, Tashmeeta; Moffett, Ashley

    2009-05-01

    Human trophoblast cells express an unusual repertoire of human leucocyte antigen (HLA) molecules which has been difficult to define. Close homology between and extreme polymorphism at the classical HLA class-I (HLA-I) loci has made it difficult to generate locus-specific monoclonal antibodies (mAbs). The problem of defining an antibody's reactivity against the thousands of existing HLA-I allotypes has often made it impossible to determine the HLA bound by a mAb in biological samples from a normal outbred population. Here we have used commercially available beads coated with individual HLA-I to characterize experimentally the reactivity of nine mAb against 96 common HLA-I allotypes. In conjunction with donor HLA-I genotyping, we could then define the specific HLA molecules bound by these antibodies in normal individuals. We used this approach to analyse the HLA expression of primary trophoblast cells from normal pregnancies; the choriocarcinoma cells JEG-3 and JAR; and the placental cell lines HTR-8/SVneo, Swan-71 and TEV-1. We confirm that primary villous trophoblast cells are HLA null whereas extravillous trophoblast cells express HLA-C, HLA-G and HLA-E, but not HLA-A, HLA-B or HLA-DR molecules in normal pregnancy. Tumour-derived JEG-3 and JAR cells reflect extravillous and villous trophoblast HLA phenotypes, respectively, but the HLA repertoire of the in vitro derived placental cell lines is not representative of either in vivo trophoblast phenotype. This study raises questions regarding the validity of using the placental cell lines that are currently available as model systems for immunological interactions between fetal trophoblast and maternal leucocytes bearing receptors for HLA molecules.

  10. The diagnostic accuracy of biomarkers for diagnosis of primary biliary cholangitis (PBC) in anti-mitochondrial antibody (AMA)-negative PBC patients: a review of literature.

    Science.gov (United States)

    de Liso, Federica; Matinato, Caterina; Ronchi, Mariangela; Maiavacca, Rita

    2017-11-27

    Primary biliary cholangitis (PBC), also known as primary biliary cirrhosis, is an autoimmune disease of the liver characterized by anti-mitochondrial antibodies (AMA) in 90%-95% of patients. The aim of this study was to evaluate the diagnostic value of several serum biomarkers in patients with PBC but negative for AMA. Some antinuclear antibodies (ANA) pattern, detected by indirect immunofluorescence (IIF), such as multiple nuclear dot (MND) and rim-like patterns are well-known to be specific for PBC. The corresponding nuclear antigens are the components of the nuclear pore complex (Gp210 for rim-like pattern) and Sp100, PML proteins (for MND pattern) detectable by immunoblotting and ELISA methods. More recently, new biomarkers have been evaluated in order to improve the diagnostic sensitivity, such as kelch-like 12 (KLHL12) and hexokinase-1. Considering these different serum biomarkers, studies evaluating their diagnostic role in AMA-negative PBC patients compared to AMA-positive ones and controls were included in this review. Pooled sensitivity and specificity were 37% and 85%, respectively. The overall PPV and NPV mean values were 45% and 83%. Even if all biomarkers are very specific for PBC, the overall sensitivity was poor and therefore is necessary to identify a marker with a greater sensitivity for PBC in AMA-negative patients.

  11. Suspected poisoning of domestic animals by pesticides.

    Science.gov (United States)

    Caloni, Francesca; Cortinovis, Cristina; Rivolta, Marina; Davanzo, Franca

    2016-01-01

    A retrospective study was carried out by reviewing all suspected cases of domestic animal poisoning attributed to pesticides, reported to the Milan Poison Control Centre (MPCC) between January 2011 and December 2013. During this period, pesticides were found to be responsible for 37.3% of all suspected poisoning enquiries received (815). The most commonly species involved was the dog (71.1% of calls) followed by the cat (15.8%), while a limited number of cases involved horses, goats and sheep. Most cases of exposure (47.1%) resulted in mild to moderate clinical signs. The outcome was reported in 59.9% of these cases, with death occurring in 10.4% of them. Insecticides (40.8%) proved to be the most common group of pesticides involved and exposure to pyrethrins-pyrethroids accounted for the majority of calls. According to the MPCC data, there has been a decrease in the number of suspected poisonings cases attributed to pesticides that have been banned by the EU, including aldicarb, carbofuran, endosulfan and paraquat. In contrast, there has been an increase of suspected poisoning cases attributed to the neonicotinoids, imidacloprid and acetamiprid, probably due to their widespread use in recent years. Cases of suspected poisoning that involved exposure to rodenticides accounted for 27.6% of calls received by the MPCC and anticoagulant rodenticides were the primary cause of calls, with many cases involving brodifacoum and bromadiolone. Herbicides were involved in 14.2% of calls related to pesticides and glyphosate was the main culprit in cases involving dogs, cats, horses, goats and sheep. As far as exposure to molluscicides (11.5%) and fungicides (5.9%), most of the cases involved dogs and the suspected poisoning agents were metaldehyde and copper compounds respectively. The data collected are useful in determining trends in poisoning episodes and identifying newly emerging toxicants, thus demonstrating the prevalence of pesticides as causative agents in animal

  12. Glaucoma suspect & Humphrey Field Analyzer a correlation

    Directory of Open Access Journals (Sweden)

    P Dahal

    2012-09-01

    Full Text Available Glaucoma originally meant "clouded", in Greek.The term glaucoma refers to a group of diseases that have in common characteristic optic neuropathy with associated visual field loss for which elevated intraocular pressure is one of the primary risk factor. The purpose of the study is to correlate the clinically diagnosed cases of glaucoma suspect with the Humphrey Field Analyzer (HFA. Fifty cases of glaucoma suspect who attended the glaucoma clinic of Nepal Eye Hospital Tripureswor, Kathmandu, Nepal and who meets at least two criteria, among the four types of glaucoma suspects were advised for the HFA for the study. In this study out of 50 patient, 36 (72% patients had normal visual field. 14 (28% patients had thinning of the neural retinal rim (NRR in both eyes. The significant relation with thinning of neural retina rim and glaucomatous hemifield test was found in the study. Journal of College of Medical Sciences-Nepal,2012,Vol-8,No-1, 23-28 DOI: http://dx.doi.org/10.3126/jcmsn.v8i1.6822

  13. The Architect Syphilis assay for antibodies to Treponema pallidum: an automated screening assay with high sensitivity in primary syphilis.

    Science.gov (United States)

    Young, H; Pryde, J; Duncan, L; Dave, J

    2009-02-01

    To determine the sensitivity and specificity of the Architect Syphilis Chemiluminescence Assay (CLIA): a new highly automated screening test for syphilis. To establish the sensitivity of the Architect Syphilis assay we tested 129 stored sera from serologically characterised cases of untreated syphilis. The sera were selected to contain a disproportionately high number of primary infections. There were 79 primary infections, 29 secondary infections, 9 early latent infections and 12 latent syphilis of unknown duration. To establish the specificity of the assay we tested 1107 sera that had been submitted for routine syphilis serology. The Architect CLIA and the Treponema pallidum particle agglutination test (TPPA) were in total agreement for all untreated infection with sensitivity of 98.4%. This was significantly higher than the sensitivity of the Murex immune capture enzyme (ICE) immunoassay (86%, pArchitect and ICE assays was entirely due to primary stage syphilis (97.5% vs 77.2%, pArchitect CLIA was very high (99.1%, 1049/1059) it was significantly lower (p = 0.016) than that of the Murex ICE assay (99.9%). The Architect CLIA is significantly more sensitive than the Murex ICE screening assay in detecting primary syphilis but it is significantly less specific. Given the relatively high levels of early syphilis, we consider a small increase in the number of confirmatory tests required to exclude false-positive results is worthwhile to increase the detection of primary syphilis by 20%.

  14. Autoimmune hepatitis type 2 associated with an unexpected and transient presence of primary biliary cirrhosis-specific antimitochondrial antibodies: a case study and review of the literature

    Directory of Open Access Journals (Sweden)

    Invernizzi Pietro

    2012-07-01

    Full Text Available Abstract Background Unlike other autoimmune liver diseases, primary biliary cirrhosis (PBC has never been reported in early childhood, while type 2 autoimmune hepatitis (AIH is eminently a paediatric disease. Case presentation We describe a case of type 2 AIH with serological positivity for PBC-specific anti-mitochondrial antibodies (AMA in a 3-year old girl. We found this observation intriguing as AMA and indeed an overlap with PBC are virtually absent in Type 2 AIH, a pediatric form of AIH which is distinct precisely because it is characterized by pathognomonic anti-liver kidney microsomal type 1 (LKM-1 showing a remarkable antigen-specificity directed against cytochrome P4502D6. We also review the literature in relation to AMA positivity in paediatric age and adolescence. In our case, the presence of AIH-2-specific anti-LKM-1 and PBC-specific AMA was confirmed by indirect immunofluorescence (IIF, and immunoblotting and ELISA based on recombinant mitochondrial antigens. The clinical, laboratory and histological features of the child are given in detail. Interestingly the mother was AMA positive without other features of PBC. The child was successfully treated with immunosuppression and five years after the original diagnosis is on a low dose of prednisolone and azathioprine, with no signs of relapse. Anti-LKM-1 antibodies are still present in low titres. AMA were detectable for the first 4 years after the diagnosis and disappeared later. Conclusion This is the first case report in the literature of AIH type 2 with an unexpected PBC-specific AMA positivity in a young child. Response to immunosuppressive treatment was satisfactory and similar to that described in AIH. A review of published reports on AMA positivity in paediatric age shows that the antibody may arise in the context of immunodeficiency and is variably associated with liver damage.

  15. Autoimmune hepatitis type 2 associated with an unexpected and transient presence of primary biliary cirrhosis-specific antimitochondrial antibodies: a case study and review of the literature.

    Science.gov (United States)

    Invernizzi, Pietro; Alessio, Maria Grazia; Smyk, Daniel S; Lleo, Ana; Sonzogni, Aurelio; Fabris, Luca; Candusso, Manila; Bogdanos, Dimitrios P; Iorio, Raffaele; Torre, Giuliano

    2012-07-20

    Unlike other autoimmune liver diseases, primary biliary cirrhosis (PBC) has never been reported in early childhood, while type 2 autoimmune hepatitis (AIH) is eminently a paediatric disease. We describe a case of type 2 AIH with serological positivity for PBC-specific anti-mitochondrial antibodies (AMA) in a 3-year old girl. We found this observation intriguing as AMA and indeed an overlap with PBC are virtually absent in Type 2 AIH, a pediatric form of AIH which is distinct precisely because it is characterized by pathognomonic anti-liver kidney microsomal type 1 (LKM-1) showing a remarkable antigen-specificity directed against cytochrome P4502D6. We also review the literature in relation to AMA positivity in paediatric age and adolescence. In our case, the presence of AIH-2-specific anti-LKM-1 and PBC-specific AMA was confirmed by indirect immunofluorescence (IIF), and immunoblotting and ELISA based on recombinant mitochondrial antigens. The clinical, laboratory and histological features of the child are given in detail. Interestingly the mother was AMA positive without other features of PBC. The child was successfully treated with immunosuppression and five years after the original diagnosis is on a low dose of prednisolone and azathioprine, with no signs of relapse. Anti-LKM-1 antibodies are still present in low titres. AMA were detectable for the first 4 years after the diagnosis and disappeared later. This is the first case report in the literature of AIH type 2 with an unexpected PBC-specific AMA positivity in a young child. Response to immunosuppressive treatment was satisfactory and similar to that described in AIH. A review of published reports on AMA positivity in paediatric age shows that the antibody may arise in the context of immunodeficiency and is variably associated with liver damage.

  16. Antigenic Fingerprinting following Primary RSV Infection in Young Children Identifies Novel Antigenic Sites and Reveals Unlinked Evolution of Human Antibody Repertoires to Fusion and Attachment Glycoproteins.

    Directory of Open Access Journals (Sweden)

    Sandra Fuentes

    2016-04-01

    Full Text Available Respiratory Syncytial Virus (RSV is the major cause of pneumonia among infants. Here we elucidated the antibody repertoire following primary RSV infection and traced its evolution through adolescence and adulthood. Whole genome-fragment phage display libraries (GFPDL expressing linear and conformational epitopes in the RSV fusion protein (F and attachment protein (G were used for unbiased epitope profiling of infant sera prior to and following RSV infection. F-GFPDL analyses demonstrated modest changes in the anti-F epitope repertoires post-RSV infection, while G-GFPDL analyses revealed 100-fold increase in number of bound phages. The G-reactive epitopes spanned the N- and C-terminus of the G ectodomain, along with increased reactivity to the central conserved domain (CCD. Panels of F and G antigenic sites were synthesized to evaluate sera from young children (<2 yr, adolescents (14-18 yr and adults (30-45 yr in SPR real-time kinetics assays. A steady increase in RSV-F epitope repertoires from young children to adults was observed using peptides and F proteins. Importantly, several novel epitopes were identified in pre-fusion F and an immunodominant epitope in the F-p27. In all age groups, antibody binding to pre-fusion F was 2-3 folds higher than to post-fusion form. For RSV-G, antibody responses were high following early RSV infection in children, but declined significantly in adults, using either G proteins or peptides. This study identified unlinked evolution of anti-F and anti G responses and supportive evidence for immune pressure driven evolution of RSV-G. These findings could help development of effective countermeasures including vaccines.

  17. Detection of novel non-M2-related antimitochondrial antibodies in patients with anti-M2 negative primary biliary cirrhosis.

    Science.gov (United States)

    Feuchtinger, M; Christ, S; Preuss, B; Dengjel, J; Duman, S; Stevanovic, S; Klein, R

    2009-07-01

    In 95% of patients with primary biliary cirrhosis (PBC) antimitochondrial antibodies (AMAs) can be detected reacting with at least one of the five components of the M2 antigen identified as the 2-oxoacid dehydrogenase complex (OADC). However, among our PBC sera 15-20% are anti-M2 negative by ELISA and western blotting but in the immunofluorescence test (IFT) they show the typical AMA staining. The aim of the present study was to characterise the target antigen(s) of these non-M2-related AMAs. We analysed sera from 27 patients with clinically and histologically proven PBC being AMA positive by the IFT but anti-M2 negative by ELISA and western blotting. They were tested by western blotting against various 100,000 g supernatants obtained after sonication of mitochondria from rat liver, bovine heart and pig kidney. These were further separated by isopycnic sucrose density centrifugation using different sucrose density fractions. Fourteen of the 27 AMA positive/anti-M2 negative sera (52%) reacted in the western blotting with a 60 kDa protein and eight (29%) with an 80 kDa protein, both present in the 100 000 g supernatant from bovine heart mitochondria accumulating at sucrose densities of 1.14-1.16. An identity of these determinants with any of the M2-related antigens could be excluded. In the 60 kDa band components of the mitochondrial enzymes F(1)F(0)-ATPase, ubiquinone cytochrome c reductase and acyl CoA dehydrogenase were detected by MALDI-TOF analysis; the 80 kDa protein could not be further characterised. AMA positive/anti-M2 negative PBC sera contain antibodies to further mitochondrial antigens at 60 and 80 kDa which do not correspond to any of the M2 determinants. Those antibodies can be detected to a lesser extent in sera from patients with classical anti-M2 positive PBC but not in patients with other hepatic and non-hepatic disorders and may, therefore, represent additional marker antibodies for the serological diagnosis of PBC.

  18. Antimitochondrial antibody

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003529.htm Antimitochondrial antibody To use the sharing features on this page, please enable JavaScript. Antimitochondrial antibodies (AMA) are substances ( antibodies ) that form against mitochondria. ...

  19. Precipitating antibodies in mycoplasma infection.

    Science.gov (United States)

    Menonna, J; Chmel, H; Menegus, M; Dowling, P; Cook, S

    1977-01-01

    The effectiveness of counterimmunoelectrophoresis (CIEP) for detecting human precipitating antibodies to mcyoplasma antigen was compared with the conventional complement fixation (CF) method in a double-blind experiment. Fifty-one sera from patients suspected of having acute mycoplasma infection were tested by both techniques. Dense precipitin lines to mycoplasma antigen developed in 28 sera with CIEP. Twenty-six of 28 had elevated CF titers to this antigen. No precipitin bands were observed in sera with low antibody titers to mycoplasma. These findings indicate that the CIEP test is a specific method for reliably detecting elevated serum CF antibody levels in patients with acute or recent mycoplasma infection. PMID:328527

  20. Human leucocyte antigen alleles and haplotypes and their associations with antinuclear antibodies features in Chinese patients with primary biliary cirrhosis.

    Science.gov (United States)

    Zhao, Dan-Tong; Liao, Hui-Yu; Zhang, Xin; Liu, Yan-Min; Zhao, Yan; Zhang, Hai-Ping; Sun, Li-Mei; Ma, Yin-Xue; Yan, Hui-Ping

    2014-02-01

    Primary biliary cirrhosis (PBC) is an autoimmune liver disease. Genetic factors are critical in determining susceptibility to PBC. Among human leuocyte antigen (HLA) genes, an association between the DRB1*08 allele and PBC has been reported in many populations, but not in Chinese patients. We investigated HLA-A, B, DRB1, and DQB1 alleles and haplotypes in 145 PBC patients and 500 healthy subjects. Patients were also stratified according to autoantibody features, and associations between these and HLA alleles were analyzed. Significant associations existed between HLA-DRB1*08:03 (22.1% vs. 9.0%, Pc genetic background in eastern Asia, and we confirmed the role of HLA genes in determining PBC susceptibility and autoantibody features in the Chinese population. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Primary alveolar echinococcosis: course of larval development and antibody responses in intermediate host rodents with different genetic backgrounds after oral infection with eggs of Echinococcus multilocularis.

    Science.gov (United States)

    Matsumoto, Jun; Kouguchi, Hirokazu; Oku, Yuzaburo; Yagi, Kinpei

    2010-09-01

    We investigated parasite establishment, subsequent larval development and antibody responses in gerbils, cotton rats and 4 inbred mouse strains until 16 weeks post inoculation (p.i.) with 200 eggs of Echinococcus multilocularis. The rate of parasite establishment in the liver determined at 4 weeks p.i. was highest in DBA/2, followed by AKR/N, C57BL/10 and C57BL/6 mice, whereas gerbils harboured few parasite foci. The accurate number of liver lesions in cotton rats could not be determined due to rapid growth and advanced multivesiculation of the parasite observed at 2 weeks p.i. The course of larval development was most advanced in DBA/2 mice with mature protoscolex formation at 16 weeks p.i., followed by AKR/N harbouring metacestodes with sparsely distributed immature protoscoleces. On the other hand, C57BL/6 and C57BL/10 mice had infertile metacestodes without any protoscolex formation. The parasite growth in mice was totally slower than those in gerbils and cotton rats. Specific IgG and IgM responses against 3 types of native crude antigens of larval E. multilocularis were evaluated using somatic extracts of and vesicle fluid of metacestode, and somatic extracts from purified protoscoleces. The 4 mouse strains demonstrated basically similar kinetics with apparent IgG and IgM increases at 9 weeks p.i. and thereafter, except C57BL/10, exhibited higher levels of IgM against crude antigens at some time point of infection. On the other hand, a follow-up determination of specific IgG and IgM levels against recombinant antigens from larval E. multilocularis revealed that each mouse strain showed different antibody-level kinetics. The findings in the present study demonstrate that the course of host-parasite interactions in primary alveolar echinococcosis, caused by larval E. multilocularis, clearly varies among intermediate host rodents with different genetic backgrounds.

  2. Clinical significance of positive immunoblotting but negative immunofluorescence for antimitochondrial antibodies in patients with liver diseases other than primary biliary cirrhosis.

    Science.gov (United States)

    Masuda, Jun-Ichi; Omagar, Katsuhisa; Miyakawa, Hiroshi; Hazama, Hiroaki; Ohba, Kazuo; Kinoshita, Hideki; Matsuo, Isao; Isomoto, Hajime; Murata, Ikuo; Kohno, Shigeru

    2002-03-01

    The serum reaction to anti-2-oxo-acid dehydrogenase complex (2-OADC) enzymes, the antigens recognized by antimitochondrial antibodies (AMA), can be detected by immunoblotting in patients with liver diseases other than primary biliary cirrhosis (PBC), who are negative for AMA by conventional indirect immunofluorescence. Whether the presence of anti-2-OADC is related to PBC or represents preclinical PBC in such patients is obscure at present. We examined the immunoreactivity of AMA by immunofluorescense, immunoblotting, and enzyme inhibition assay in serum samples from 59 patients with liver diseases other than PBC and 71 healthy subjects. We also examined the clinical course of the patients in whom a positive result was obtained to elucidate whether such reaction was a "true" or "false" phenomenon. None of the 130 sera was positive for AMA by indirect immunofluorescence or for anti-pyruvate dehydrogenase complex (PDC) by enzyme inhibition assay. However, seven of 71 (10%) sera from healthy subjects contained weak IgG class antibody to PDC-E2 (four sera) or E2 subunit of branched-chain oxo-acid dehydrogenase complex (BCOADC-E2) (three sera). Of the 59 sera from patients with liver diseases other than PBC, four (7%) reacted against 2-OADC by immunoblotting. Of these, three sera were from patients with chronic hepatitis C virus (HCV) infection, and contained IgG class autoantibody to BCOADC-E2. The serum reactivity to BCOADC-E2 detected by immunoblotting in these three patients diminished after absorption with recombinant BCOADC-E2 fusion protein. During the 3-5 year follow-up period, AMA by immunofluorescence and anti-PDC activity by enzyme inhibition assay were always negative in these three patients. The other one serum was from patient with alcoholic cirrhosis, and contained IgM class autoantibody to E3 binding protein (E3-BP). This patient did not develop PBC during the following 2 years. Our results showed that anti-2-OADC antibodies could be detected in some

  3. TRAF1 Gene Polymorphism Correlates with the Titre of Gp210 Antibody in Patients with Primary Biliary Cirrhosis

    Directory of Open Access Journals (Sweden)

    Agnieszka Kempinska-Podhorodecka

    2012-01-01

    Full Text Available Background. Polymorphisms of TRAF1 (Tumor necrosis factor receptor-associated factor 1 are associated with rheumatoid arthritis (RA. Whether TRAF1 polymorphisms confer increased risk for primary biliary cirrhosis (PBC, an autoimmune liver disease which can co-exist with RA, is unknown. Aim of the Study. To assess the frequency of the RA-conferring susceptibility TRAF1 polymorphisms rs3761847 and rs2900180 in a cohort of PBC patients. The association of TRAF1 polymorphisms with clinical features and autoantibody markers was also analyzed. Methods. We studied 179 PBC patients and 300 controls. Samples were genotyped for TRAF1 gene polymorphisms by real-time PCR. Autoantibodies were tested by ELISA. Results. The frequency of rs3761847 and rs2900180 polymorphisms did not differ between patients and controls. Laboratory or clinical features were not associated with specific polymorphisms. Gp210 autoantibody titres were conspicuously higher among GG homozygotes of rs3761847 as compared with AA homozygotes (P=0.02. In contrast, antichromatin titers were higher in AA compared to GG rs3761847 homozygotes (P=0.04. Rheumatoid factor IgG titres were significantly higher in rs2900180 TT homozygotes than CC homozygotes (P=0.02. Conclusions. TRAF1 polymorphisms occur with the similar frequency in PBC patients and in the general population, but their presence is probably involved in the regulation of specific PBC-related autoantibodies.

  4. A suspected case of Addison’s disease in cattle

    OpenAIRE

    Lambacher, Bianca; Wittek, Thomas

    2015-01-01

    A 4.75-year old Simmental cow was presented with symptoms of colic and ileus. The clinical signs and blood analysis resulted in the diagnosis of suspected primary hypoadrenocorticism (Addison’s disease). Although Addison’s disease has been frequently described in other domestic mammals, to our knowledge, this disease has not previously been reported in cattle.

  5. Serum Reactivity Against Bacterial Pyruvate Dehydrogenase: Increasing the Specificity of Anti-Mitochondrial Antibodies for the Diagnosis of Primary Biliary Cirrhosis

    Directory of Open Access Journals (Sweden)

    Hiroshi Miyakawa

    2006-01-01

    Full Text Available Antimitochondrial antibodies (AMA are the serum hallmark of primary biliary cirrhosis (PBC. However, AMA-positivity can be found in non-PBC sera when lower dilutions are used, thus raising issues about the specificity and sensitivity of the test. AMA reacts primarily with the lipoylated domains of pyruvate dehydrogenase-E2 (PDC-E2 which is highly conserved across species, including bacteria. We studied 77 serum samples, including 24 from patients with anti-PDC-E2-positive PBC and 53 controls (16 with autoimmune hepatitis (AIH, 10 with primary sclerosing cholangitis (PSC, and 27 healthy individuals for their reactivities at serial dilutions (1:10, 1:20 and 1:40 against Escherichia coli DH5 alpha lysate overexpressing human PDC-E2 using immunoblotting (IB. A murine anti-human PDC-E2 monoclonal antibody (mAB was used as control. We further studied positive sera using adsorption with a synthetic E. coli peptide sharing similarity with human PDC-E2. Finally, we verified whether a unique buffer for E. coli preparation could reduce non-specific serum reactivity. Results demonstrated that 100% of anti-PDC-E2-positive PBC and up to 38% of control sera at 1:10 dilution recognized E. coli PDC-E2 at IB while dilution tests indicated that the overall potency of PBC reactivity was 100-fold higher compared to controls. In fact, a subgroup (20-38% of non-PBC sera were positive at low titers but lost the reactivity when absorbed with the synthetic E. coli peptide. Finally, our unique buffer reduced the reactivity of non-PBC sera as measured by ELISA. In conclusion, we demonstrated that weak cross-reactivity with E. coli PDC-E2 occurs in non-PBC sera at lower dilutions and that such reactivity is not due to AMA-positivity. The use of a specific buffer might avoid the risk of false positive AMA determinations when E. coli-expressed recombinant antigens are used.

  6. Seroprevalence and placental transmission of maternal antibodies specific for Neisseria meningitidis Serogroups A, C, Y and W135 and influence of maternal antibodies on the immune response to a primary course of MenACWY-CRM vaccine in the United Kingdom.

    Science.gov (United States)

    Blanchard-Rohner, Geraldine; Snape, Matthew D; Kelly, Dominic F; O'Connor, Daniel; John, Tessa; Kibwana, Elizabeth; Parks, Hannah; Ford, Karen; Dull, Peter M; Pollard, Andrew J

    2013-07-01

    Maternal antibodies give neonates some protection against bacterial infection. We measured antibodies against Neisseria meningitidis serogroups A, C, Y and W135 in mothers and their 2-month-old infants at study enrollment. We also assessed the impact of maternal antibody present at 2 months of age on the immune response to a primary course of quadrivalent meningococcal conjugate vaccine (MenACWY-CRM197) given at 2 and 4 months of age. This was a single-center, open-label, randomized study undertaken in Oxford, United Kingdom. Two hundred sixteen healthy infants were enrolled in the study and vaccinated with MenACWY-CRM197 at 2 and 4 months of age. Blood was obtained from all mothers, in a subset of infants at 2 months and all infants at 5 months. Antibody and memory B-cell responses at 5 months were correlated with maternal antibodies. Mothers had low IgG antibodies against serogroups C, W135 and Y polysaccharides, but high serogroup A antibody, whereas 61-78% had protective human complement serum bactericidal activity (hSBA) (≥1:4) for serogroups C, W135 and Y but only 31% for serogroup A. Only 9%, 32%, 45% and 19% of 2-month-old infants had hSBA ≥1:4 for serogroups A, C, W135 and Y, respectively. Maternal antibody had little association on responses to MenACWY-CRM197, except a moderate negative association between MenC-specific bactericidal antibody at 2 and 5 months (r = -0.5, P = 0.006, n = 28) and between carrier-specific IgG antibody at 2 months and MenC-specific hSBA/IgG antibody at 5 months (r = -0.4, P = 0.02 and 0.04, n = 32 and 23). Nonetheless, 90% of infants achieved protective MenC-hSBA titers after vaccination at 2 and 4 months of age. The levels of serogroup-specific meningococcal antibodies were low in mothers and 2-month-old infants. Immunizing mothers before or during pregnancy with meningococcal conjugate vaccines might increase antibody levels in early infancy and provide protection against infection due to N. meningitidis.

  7. The clinical significance of IgA antimitochondrial antibodies in sera and saliva in primary biliary cirrhosis.

    Science.gov (United States)

    Tanaka, Atsushi; Nezu, Saeko; Uegaki, Satoko; Mikami, Masaki; Okuyama, Shuhei; Kawamura, Naohiro; Aiso, Mitsuhiko; Gershwin, M Eric; Takahashi, Shin-Ichi; Selmi, Carlo; Takikawa, Hajime

    2007-06-01

    It still remains unclear how antimitochondrial autoantibodies (AMA) are involved with immunopathogenesis of primary biliary cirrhosis (PBC). We have suggested the potential role of IgA-AMA in damage to epithelial cells in PBC. In the current study, we investigated whether IgA-AMA were detectable in sera and saliva of PBC patients, to examine the association between detectable IgA-type autoantibodies in sera or saliva and progression of liver diseases. Fifty-three patients with PBC were enrolled, and IgA-AMA in sera and saliva were sought by immunoblotting using pork heart mitochondria as antigens. The progression of PBC was determined as Scheuer's classification consisting of four histological stages. We found IgA-AMA, IgA-anti-PDC-E2, and IgA-anti-E3BP in 43/53 (81%), 37/53 (70%), and 35/53 (66%) sera of patients with PBC, but none of controls. The progression of PBC was statistically associated with presence of IgA-anti-PDC-E2 (P = 0.0124), but neither with IgA-AMA (P = 0.1296) nor anti-IgA-E3BP (P = 0.5973). In saliva, detectable IgA-AMA, IgA-anti-PDC-E2, and IgA-anti-E3BP were noted in 12/26 (46%), 6/26 (23%), and 11/26 (42%), respectively. Detection of IgA-anti-PDC-E2 was strongly associated with progression of PBC (P = 0.0002), whereas detection of IgA-AMA and IgA-anti-E3BP were not associated (P = 0.2145 and P = 0.5118). The current findings suggest that the presence of IgA-anti-PDC-E2 in sera or saliva might be associated with progression of PBC, although a prospective study with PBC patients with detectable IgA-anti-PDC-E2 at early stages will be required to conclude the contribution of IgA-anti-PDC-E2 to the progression of PBC.

  8. Is extra-glandular organ damage in primary Sjögren's syndrome related to the presence of systemic auto-antibodies and/or hypergammaglobulinemia? A long-term cohort study with 110 patients from the Netherlands.

    Science.gov (United States)

    Ter Borg, Evert-Jan; Kelder, Johannes Cornelis

    2017-07-01

    To test the hypothesis that systemic auto-antibodies or hypergammaglobulinemia are related to the prevalence of extra-glandular tissue organ damage (EGOD) in primary Sjögren's syndrome (SS). A real practice-based investigation of a relatively large (n = 110) Dutch cohort of primary SS patients systematically followed up in a large non-academic hospital. After a follow up of mean 8.2 years a significant correlation was found between disease duration and the prevalence of EGOD. We did not observe a relationship between the total number or type of systemic auto-antibodies or hypergammaglobulinemia and the total number of EGOD. However, there was a correlation between the prevalence of polyneuropathy (PNP) and antinuclear antibodies (ANA) as well as anti-Ro/SS-A positivity and there was an inverse relationship between the presence of anti-Ro/SS-A antibodies and primary biliary cirrhosis (PBC). All PBC cases were anti-Ro/SS-A and anti-La/SS-B negative but ANA positive. There was a trend for a higher occurrence of pleuro-pulmonary disease in the ANA negative cases. Although we did not find a relationship between the total number or type of systemic auto-antibodies and the total number of EGOD, there were correlations between specific systemic auto-antibodies and specific types of EGOD. The presence of ANA and anti-Ro/SS-A was associated with the occurrence of PNP, as well as was the absence of anti-Ro/SS-A with PBC. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  9. A nested case-control study on association between hepatitis C virus antibodies and primary liver cancer in a cohort of 9,775 men in Taiwan.

    Science.gov (United States)

    Chang, C C; Yu, M W; Lu, C F; Yang, C S; Chen, C J

    1994-07-01

    Most studies on the association between antibodies against hepatitis C virus (anti-HCV) and primary liver cancer (PLC) were limited to case-series, or cross-sectional case-control studies leaving a controversy on causal temporality. A nested case-control study on 38 newly-developed PLC patients and 152 matched controls selected from a cohort of 9,775 men in Taiwan recruited from September, 1984, to February, 1986, was carried out to examine the relation between HCV infection and PLC. Case-control pairs were matched on age (+/- 1 year), residence, and the date at recruitment. Serum samples collected from study subjects at the initial recruitment were examined for anti-HCV by enzyme immunoassay and hepatitis B surface antigen (HBsAg) by reverse passive hemagglutination assay combined with radioimmunoassay. History of cigarette smoking, alcohol consumption, vegetable consumption, vegetarian habit, and chronic liver diseases were also obtained through standardized interviews according to a structured questionnaire at the recruitment. After adjusting for HBsAg status and other risk factors, the anti-HCV was significantly associated with the development of PLC showing a multivariate-adjusted relative risk of 88.24. The results suggest that HCV infection may play an important role in the etiology of human PLC in Taiwan.

  10. Production of thyrotropin receptor antibodies in acute phase of infectious mononucleosis due to Epstein-Barr virus primary infection: a case report of a child.

    Science.gov (United States)

    Nagata, Keiko; Okuno, Keisuke; Ochi, Marika; Kumata, Keisuke; Sano, Hitoshi; Yoneda, Naohiro; Ueyama, Jun-Ichi; Matsushita, Michiko; Kuwamoto, Satoshi; Kato, Masako; Murakami, Ichiro; Kanzaki, Susumu; Hayashi, Kazuhiko

    2015-01-01

    Various autoantibodies have been reported to be detected during the progression of infectious mononucleosis. We observed a case of infectious mononucleosis due to Epstein-Barr virus primary infection for 2 months, and noticed the transiently increased titer of thyrotropin receptor autoantibodies detected at the acute phase on the 3rd day after admission. At that time, real-time quantitative PCR also revealed the mRNA expressions of an immediate early lytic gene, BZLF1, and a latent gene, EBNA2. The expression of BZLF1 mRNA means that Epstein-Barr virus infects lytically, and EBNA2 protein has an important role in antibody production as well as the establishment of Epstein-Barr virus latency. These results suggest that Epstein-Barr virus lytic infection is relevant to thyrotropin receptor autoantibody production. Thyrotropin receptor autoantibodies stimulate thyroid follicular cells to produce excessive thyroid hormones and cause Graves' disease. Recently, we reported the thyrotropin receptor autoantibody production from thyrotropin receptor autoantibody-predisposed Epstein-Barr virus-infected B cells by the induction of Epstein-Barr virus lytic infection in vitro. This case showed in vivo findings consistent with our previous reports, and is important to consider the pathophysiology of Graves' disease and one of the mechanisms of autoimmunity.

  11. Atlantoaxial subluxation and nasopharyngeal necrosis complicating suspected granulomatosis with polyangiitis.

    Science.gov (United States)

    Mohapatra, Anand; Holekamp, Terrence F; Diaz, Jason A; Zebala, Lukas; Brasington, Richard

    2015-04-01

    Granulomatosis polyangiitis (GPA, formerly Wegener granulomatosis) is a vasculitis that typically involves the upper respiratory tract, lungs, and kidneys. The 2 established methods to confirm a suspicion of GPA are the antineutrophil cytoplasmic antibody (ANCA) test and biopsy. However, ANCA-negative cases have been known to occur, and it can be difficult to find biopsy evidence of granulomatous disease.We report a case of suspected granulomatosis with polyangiitis limited to the nasopharynx. With a negative ANCA and no histological evidence, our diagnosis was founded on the exclusion of other diagnoses and the response to cyclophosphamide therapy. This case is unique because the patient's lesion resulted in atlantoaxial instability, which required a posterior spinal fusion at C1-C2. This is the first reported case of suspected GPA producing damage to the cervical spine and threatening the spinal cord.

  12. Is there an added value of faecal calprotectin and haemoglobin in the diagnostic work-up for primary care patients suspected of significant colorectal disease? A cross-sectional diagnostic study

    NARCIS (Netherlands)

    Elias, Sjoerd G.; Kok, Liselotte; de Wit, NJ; Witteman, Ben J. M.; Goedhard, Jelle G.; Romberg-Camps, Marielle J. L.; Muris, Jean W. M.; Moons, Karel G. M.

    2016-01-01

    Background The majority of primary care patients referred for bowel endoscopy do not have significant colorectal disease (SCD), and are – in hindsight – unnecessarily exposed to a small but realistic risk of severe endoscopy-associated complications. We developed a diagnostic strategy to better

  13. B cells and antibody response in calves primary-infected or re-infected with Cooperia oncophora: influence of priming dose and host responder types.

    Science.gov (United States)

    Kanobana, K; Koets, A; Kooyman, F N J; Bakker, N; Ploeger, H W; Vervelde, L

    2003-11-01

    We investigated whether the generation of protective memory humoral immunity in Cooperia oncophora infected calves occurs in a dose-dependent way and whether it depends on the animal responder types. To this end, serum and mucus antibody responses were measured in animals primary-infected with 30000 or 100000 L3, treated with anthelmintics and subsequently challenged with 100000 L3. A detailed phenotypic and functional analysis of B cells was done in animals infected once or twice with 100,000 L3. Based on the similarity in parasitological variables of animals primed with 30000 or 100000 L3, we concluded that with these doses priming conferred protection in a dose-independent way. Upon challenge significant increases in Cooperia-specific serum and mucus IgG1 and IgA and total serum IgE titres were induced in primed animals in a dose-independent way. In contrast, intermediate and low responders differed in the onset of the production of Cooperia-specific serum IgG1. Furthermore, not only the onset but also the level of total serum IgE significantly differed between intermediate and low responders. Phenotypic and functional analysis of B lymphocytes revealed that (i). priming induced the generation of memory B cells which upon challenge readily differentiated into antibody secreting cells; (ii). sensitised B cells were more efficiently recruited to the intestinal effector sites; (iii). based on the expression of CD62L and CD86 two distinct B cell subpopulation could be differentiated. CD62L(+)CD86(-) B cells that were likely lymphocytes not yet activated and with an enhanced recirculation capacity, and CD62L(-)CD86(+) B cells that were activated B cells with a reduced recirculation ability; and finally (iv). the increased expression of CD86 and subsequent correlations with parameters of the T helper 2 immune response induced by C. oncophora, suggested that CD86- interactions are involved in the generation of protective immunity against Cooperia.

  14. Phage display derived human monoclonal antibodies isolated by binding to the surface of live primary breast cancer cells recognize GRP78

    DEFF Research Database (Denmark)

    Jakobsen, Charlotte G; Rasmussen, Nicolaj; Laenkholm, Anne-Vibeke

    2007-01-01

    of novel targets and human antibodies against them. We have isolated single-chain human mAbs from a large naïve antibody phage display library by panning on a single-cell suspension of freshly isolated live cancer cells from a human breast cancer specimen, and these antibodies were shown to specifically......Clinical trials using monoclonal antibodies (mAb) against cell-surface markers have yielded encouraging therapeutic results in several cancer types. Generally, however, anticancer antibodies are only efficient against a subpopulation of cancers, and there is a strong need for identification...... bound strongly to several cancers, including 45% breast carcinomas, 35% lung cancers, and 86% melanomas, but showed no or weak binding to normal tissues. A yeast two-hybrid screen of a large human testis cDNA library identified the glucose-regulated protein of 78 kDa (GRP78) as the antigen recognized...

  15. Monoclonal Antibodies.

    Science.gov (United States)

    Killington, R. A.; Powell, K. L.

    1984-01-01

    Monoclonal antibodies have provided an exciting addition to the "armory" of the molecular biologist and immunologist. This article discusses briefly the concept of, techniques available for, production of, and possible uses of monoclonal antibodies. (Author)

  16. Thyroid Antibodies

    Science.gov (United States)

    ... Fungal Infections Gout Graves Disease Guillain-Barré Syndrome Hashimoto Thyroiditis Heart Attack and Acute Coronary Syndrome Heart ... hypothyroidism or hyperthyroidism , such as Graves disease or Hashimoto thyroiditis . Thyroid antibody tests include: Thyroid peroxidase antibody ( ...

  17. Seroprevalance of brucellosis among suspected cases in Malaysia.

    Science.gov (United States)

    Jama'ayah, M Z; Heu, J Y; Norazah, A

    2011-06-01

    Brucellosis is a zoonotic disease which can be transmitted by direct or indirect contact with infected animal or their products. It is an important public health problem but little is known on brucellosis in the Malaysian population. The aim of this study was to determine the presence of Brucella antibodies using commercial Brucella IgG and IgM ELISA kits (Vircell, SL, Barcelona Spain). A total of 184 sera from suspected patients were received from 16 hospitals in Malaysia over the years 2004 to 2009. Only 10 serum samples (5.4%) were positive for Brucella antibodies in which 5 showed the presence of both IgM and IgG. Most of the positive patients were occupationally involved with animals. This study suggests the seroprevalance of brucellosis among individuals who have contact with infected animals in Malaysia is low.

  18. Manufacture of Immunoglobulin Products for Patients with Primary Antibody Deficiencies – The Effect of Processing Conditions on Product Safety and Efficacy

    Science.gov (United States)

    Farrugia, Albert; Quinti, Isabella

    2014-01-01

    Early preparations of immunoglobulin (Ig) manufactured from human plasma by ethanol (Cohn) fractionation were limited in their usefulness for substitution therapy in patients with primary antibody deficiencies (PAD), as Ig aggregates formed during manufacture resulted in severe systemic reactions in patients when given intravenously. Developments in manufacturing technology obviated this problem through the capacity to produce concentrated solutions of intact monomeric Ig, revolutionizing PAD treatment and improving patient life expectancy and quality of life. As the need for Ig has grown, manufacturers have refined further manufacturing technologies to improve yield from plasma and produce therapies, which are easier and less expensive to deliver. This has led to the substitution, partly or wholly, of ethanol precipitation by other techniques such as chromatography, and has also stimulated the production of highly concentrated solutions capable of rapid infusion. Ig products have been associated, since their inception, with certain adverse events, including infectious disease transmission, hemolysis, and thromboembolism. The introduction of standardized manufacturing processes and dedicated pathogen elimination steps has removed the risk of infectious disease, and the focus of attention has shifted to other problems, which appear to have increased over the past 5 years. These include hemolysis and thromboembolism, both the cause for substantial concern and the subject of recent regulatory scrutiny and actions. We review the development of manufacturing technology and the emerging evidence that changes for the optimization of yield and convenience has contributed to the recent incidents in certain adverse events. Industry measures under development will be discussed in terms of their potential to improve safety and optimize care for patients with PAD. PMID:25566269

  19. Characterizing Antibodies.

    Science.gov (United States)

    Weis-Garcia, Frances; Carnahan, Robert H

    2017-11-01

    Perhaps because they are such commonly used tools, many researchers view antibodies one-dimensionally: Antibody Y binds antigen X. Although few techniques require a comprehensive understanding of any particular antibody's characteristics, well-executed experiments do require a basic appreciation of what is known and, equally as important, what is not known about the antibody being used. Ignorance of the relevant antibody characteristics critical for a particular assay can easily lead to loss of precious resources (time, money, and limiting amounts of sample) and, in worst-case scenarios, erroneous conclusions. Here, we describe various antibody characteristics to provide a more well-rounded perspective of these critical reagents. With this information, it will be easier to make informed decisions on how best to choose and use the available antibodies, as well as knowing when it is essential and how to determine a particular as yet-undefined characteristic. © 2017 Cold Spring Harbor Laboratory Press.

  20. Second antibody clearance of radiolabeled antibody in cancer radioimmunodetection.

    OpenAIRE

    Sharkey, R.M.; Primus, F J; Goldenberg, D M

    1984-01-01

    The imaging of tumors using radiolabeled antibodies previously has required the implementation of computer-assisted subtraction techniques to reduce background radioactivity. A decrease in radioactivity in the blood of hamsters bearing human colonic tumor xenografts has been achieved by administering a second antibody directed against a radiolabeled primary antibody to carcinoembryonic antigen (CEA). This method was found to reduce the level of blood radioactivity by a factor of 4 within 2 hr...

  1. Ten-day observation of live rabies suspected dogs.

    Science.gov (United States)

    Tepsumethanon, V; Wilde, H; Sitprija, V

    2008-01-01

    This study aimed at analyzing a ten-day observation period of rabies suspected dogs and cats according to six criteria. Dogs and cats suspected of being rabid were brought for observation when they had either bitten a person or another animal or when abnormal behaviour or unusual illness was observed. Between 1985 and 2005, retrospective and prospective data from 1,222 dogs and 303 cats was collected during the ten-day observation period. If an animal had died, brain examination using fluorescent antibody testing was routinely performed. If an animal had survived for > or =10 days, it was released to its owner or transferred to the municipal dog shelter. A total of 644 dogs and 58 cats found rabid died within 10 days of observation. In addition, for 208 dogs confirmed rabid with laboratory tests between 1997 and 2005, six criteria were analysed from the day of submission. This experience with the implemented 10-day observation period confirms the WHO recommendation on identifying suspected rabid dogs or cats under veterinary supervision following a human exposure.

  2. Suspected levamisole intoxication in calves.

    Science.gov (United States)

    Müller, K R; Dwyer, C

    2016-07-01

    A group of 32 Friesian and four Hereford calves, 3-4 months old with body weights between 100-120 kg, were purchased from a weaner sale. On arrival at the property the Hereford calves were treated with a combination anthelmintic containing 2 g/L abamectin and 80 g/L levamisole hydrochloride. Shortly afterwards they developed tremors and frothing from the mouth, and two died overnight. The Friesian calves were treated with the same anthelmintic on the following day, when some showed hypersalivation and frothing from the mouth. Examination of the three most severely affected Friesian calves revealed severe nicotinic-type symptoms including hypersalivation, frothing from the mouth, muscle tremors, recumbency, rapid respiration, hyperaesthesia, and central nervous system depression. Other calves showed mild to moderate signs of intoxication including restlessness, tail switching, salivation, tremors, frequent defaecation, mild colic and jaw chomping. Two calves died shortly afterwards. An adverse drug event investigation revealed that the formulation and quality of the anthelmintic was within the correct specification, and that the drench gun was functioning correctly. Suspected levamisole intoxication due to a combination of possible overdosing, dehydration, and stress caused by transportation and prolonged yarding. Susceptibility to levamisole toxicity in New Zealand calves can be increased if factors like dehydration or stress are present. Levamisole has a narrow margin of safety, and overdosing in calves can easily occur if the dose rate is not based on their actual weight or health status.

  3. Low incidence of positive smooth muscle antibody and high incidence of isolated IgM elevation in Chinese patients with autoimmune hepatitis and primary biliary cirrhosis overlap syndrome: a retrospective study.

    Science.gov (United States)

    Zhao, Pan; Han, Yukun

    2012-01-03

    : Up to now, few data are available regarding the clinical characteristics of autoimmune hepatitis and primary biliary cirrhosis overlap syndrome. The study was to investigate and analyze the prevalent and clinical features of Chinese patients with this disease. Clinical data on patients diagnosed as autoimmune hepatitis and primary biliary cirrhosis overlap syndrome in our hospital from January 2001 to December 2006 were collected and analyzed. Overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis accounted for 10.33% of patients with autoimmune liver diseases during the past six years. For these patients with overlap syndrome, xanthochromia, lethargy and anorexia were the predominant complaints; a low incidence (14/146) of smooth muscle antibody positivity and a high incidence (37/89) of isolated IgM elevation were the main serological characteristics. Overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis was not rare in Chinese patients with clinical manifests of autoimmune liver diseases. Overlap of the diseases should not be disregarded when isolated IgM elevation was exhibited, and smooth muscle antibody might have little diagnostic significance in the overlap syndrome. If it was difficult to make a definite diagnosis, liver biopsy was necessary.

  4. Magnetic resonance imaging of suspected atrial tumors.

    Science.gov (United States)

    Menegus, M A; Greenberg, M A; Spindola-Franco, H; Fayemi, A

    1992-05-01

    Two-dimensional echocardiography has become the standard technique for evaluation of cardiac and paracardiac mass lesions. We have used magnetic resonance imaging (MRI) as an independent assessment of cardiac-associated masses in patients with echocardiograms demonstrating sessile atrial tumors. MRI was performed in seven patients, ages 33 to 84, whose echocardiographic diagnoses included left atrial mass (five), right atrial mass (one), and interatrial mass (one). In four of the patients with a diagnosis of left atrial mass, MRI showed extracardiac compression of the atrium, simulating a tumor (hiatal hernia, tortuous descending aorta, bronchogenic cyst). MRI was entirely normal in one patient with an apparent left atrial mass. MRI elucidated extension of an extracavitary mass into the interatrial septum in two patients. One of these patients with an echocardiographic right atrial mass had extension of a lipoma into the interatrial septum without atrial tumor. MRI confirmed the echocardiographic diagnosis of an interatrial mass in the other patient. We conclude that MRI, because of its ability to define anatomic relationships and tissue characteristics, is a powerful noninvasive tool for evaluating suspected cardiac mass lesions. Although echocardiography remains the primary screening test for the detection of cardiac masses, MRI is a more specific modality for precise diagnosis. Correct MRI interpretation may obviate the need for invasive studies or surgery.

  5. Análise da camada de fibras nervosas da retina com GDx™: validade diagnóstica em glaucoma primário de ângulo aberto e suspeitos de glaucoma Retinal nerve fiber layer analysis with GDxTM: diagnostic value in primary open angle glaucoma and glaucoma suspects

    Directory of Open Access Journals (Sweden)

    João Antonio Prata Junior

    2001-08-01

    Full Text Available Objetivo: Analisar a validade diagnóstica do GDx™ Scanning Laser System em portadores de glaucoma primário de ângulo aberto, bem como, avaliar o seus resultados em pacientes suspeitos de glaucoma. Métodos: Foram submetidos ao exame com o GDx™ Scanning Laser System, 77 glaucomatosos (142 olhos portadores de defeito característico do campo visual, 40 indivíduos normais (80 olhos e 36 suspeitos de glaucoma com pressão intra-ocular (Po acima de 20 e abaixo de 25 mmHg com campo visual normal. Analisou-se a sensibilidade, especificidade, razão de probabilidade e as probabilidades pré e pós-teste. Resultados: Considerando como exame anormal a presença de pelo menos um índice alterado, entre glaucomatosos e normais, observou-se uma especificidade de 82,5% e sensibilidade de 90,1%. A razão de probabilidade encontrada foi de 5,1 e as probabilidades pré e pós-teste de 63,9% e 90% respectivamente. Entre suspeitos e normais, observou-se uma especificidade de 82,5% e sensibilidade de 33,3%. A razão de probabilidade encontrada foi de 1,9 e as probabilidades pré e pós-teste de 8,5% e 15% respectivamente. Conclusão: O GDx™ Scanning Laser System apresenta validade diagnóstica significativa em diferenciar olhos glaucomatosos de normais. Em suspeitos de glaucoma o exame mostrou pouca capacidade na diferenciação dos normais.Purpose: to analyze the diagnostic power of the GDx™ Scanning Laser System in primary open angle glaucoma (POAG and glaucoma suspects. Methods: 77 POAG patients (142 eyes with characteristic visual field loss, 40 normal subjects and 36 glaucoma suspects (72 eyes with intraocular pressure (IOP above 20 and below 25 mmHg with normal visual fields were submitted to GDx™ Scanning Laser System examinations. Sensitivity, specificity, likelihood ratio and pre- and post-test probabilities were calculated. Results: Considering abnormal the presence of at least one parameter out of normal limits, 82.5% specificity and 90

  6. A hospital based pilot study on Epstein-Barr virus in suspected infectious mononucleosis pediatric patients in India.

    Science.gov (United States)

    Janani, Madhuravasal Krishnan; Malathi, Jambulingam; Appaswamy, Andal; Singha, Nishi Rani; Madhavan, Hajib Nariharirao

    2015-10-29

    Infectious mononucleosis (IM) caused by the Epstein-Barr virus (EBV) is commonly diagnosed by detection of antibodies in the patient's sera. Differentiation of acute from chronic and differential diagnosis of EBV-induced IM from IM-like syndrome caused by human cytomegalovirus (CMV) is important. The objective of this study was to standardize and use polymerase chain reaction (PCR) for diagnosis of EBV and evaluate it against enzyme-linked immunosorbent assay (ELISA). ELISA for detection of IgM and IgG antibodies to viral capsid antigen (VCA) and PCR targeting the VCA and EBNA1 gene of EBV and mtrII gene of CMV were performed on180 peripheral blood samples collected from 180 patients with suspected IM. The analytical sensitivity of PCR was evaluated against that of ELISA. Using the standard serological profile as the reference, the EBV-VCA gene was detected in 41 (95%) of 45 samples collected from patients with early primary infections, in 41 (54%) of 75 with recent primary infections, and in7 (17%) of 39 with past infections. The result of VCA PCR was statistically significant in virus detection during early or primary stage of infection. Nineteen (49%) EBV-seropositive samples were positive for CMV by PCR. All control samples tested negative for both VCA and EBNA1by PCR. VCA PCR is sensitive for the detection of EBV DNA in the early or primary stage of infection and can be considered a reliable method to rule out the cross-reactivity and differential diagnosis of EBV-induced IM from IM-like syndrome.

  7. Impact of V2 mutations on escape from a potent neutralizing anti-V3 monoclonal antibody during in vitro selection of a primary human immunodeficiency virus type 1 isolate.

    Science.gov (United States)

    Shibata, Junji; Yoshimura, Kazuhisa; Honda, Akiko; Koito, Atsushi; Murakami, Toshio; Matsushita, Shuzo

    2007-04-01

    KD-247, a humanized monoclonal antibody to an epitope of gp120-V3 tip, has potent cross-neutralizing activity against subtype B primary human immunodeficiency virus type 1 (HIV-1) isolates. To assess how KD-247 escape mutants can be generated, we induced escape variants by exposing bulked primary R5 virus, MOKW, to increasing concentrations of KD-247 in vitro. In the presence of relatively low concentrations of KD-247, viruses with two amino acid mutations (R166K/D167N) in V2 expanded, and under high KD-247 pressure, a V3 tip substitution (P313L) emerged in addition to the V2 mutations. However, a virus with a V2 175P mutation dominated during passaging in the absence of KD-247. Using domain swapping analysis, we demonstrated that the V2 mutations and the P313L mutation in V3 contribute to partial and complete resistance phenotypes against KD-247, respectively. To identify the V2 mutation responsible for the resistance to KD-247, we constructed pseudoviruses with single or double amino acid mutations in V2 and measured their sensitivity to neutralization. Interestingly, the neutralization phenotypes were switched, so that amino acid residue 175 (Pro or Leu) located in the center of V2 was exchanged, indicating that the amino acid at position 175 has a crucial role, dramatically changing the Env oligomeric state on the membrane surface and affecting the neutralization phenotype against not only anti-V3 antibody but also recombinant soluble CD4. These data suggested that HIV-1 can escape from anti-V3 antibody attack by changing the conformation of the functional envelope oligomer by acquiring mutations in the V2 region in environments with relatively low antibody concentrations.

  8. Daratumumab-mediated lysis of primary multiple myeloma cells is enhanced in combination with the human anti-KIR antibody IPH2102 and lenalidomide

    DEFF Research Database (Denmark)

    Nijhof, I. S.; Lammerts van Bueren, J. J.; van Kessel, B.

    2015-01-01

    Despite recent treatment improvements, multiple myeloma remains an incurable disease. Since antibody-dependent cell-mediated cytotoxicity is an important effector mechanism of daratumumab, we explored the possibility of improving daratumumab-mediated cell-mediated cytotoxicity by blocking natural...

  9. Immunoglobulin G antibodies against deamidated-gliadin-peptides outperform anti-endomysium and tissue transglutaminase antibodies in children

    NARCIS (Netherlands)

    Mubarak, A.; Gmelig-Meyling, F. H. J.; Wolters, V. M.; ten Kate, F. J. W.; Houwen, R. H. J.

    2011-01-01

    To investigate the usefulness of deamidated-gliadin-peptides-antibodies in the diagnosis of celiac disease, serology was tested in 212 children suspected with celiac disease who had undergone a small-intestinal-biopsy. For deamidated-gliadin-peptides-antibodies, two kits were tested. Positive and

  10. Interlaboratory study of the primary antibody response to sheep red blood cells in outbred rodents following exposure to cyclophosphamide or dexamethasone.

    Science.gov (United States)

    Loveless, Scott E; Ladics, Gregory S; Smith, Charlene; Holsapple, Michael P; Woolhiser, Michael R; White, Kimber L; Musgrove, D L; Smialowicz, Ralph J; Williams, W

    2007-07-01

    EPA guidelines provide a choice in evaluating humoral immune system function in rats and mice immunized with sheep red blood cells (sRBC): an antibody-forming cell (AFC) assay or a sRBC-specific serum IgM enzyme-linked immunosorbent assay (ELISA). Four different laboratories used both methods to detect suppression of the antibody response by cyclophosphamide (CP) or dexamethasone (DEX). Attempts were made to minimize interlaboratory variability through the use of common reagents and vendors; each laboratory used the same source for rodents, immunosuppressive agents, and one sheep for sRBCs, and determined optimal sRBC concentration for immunization and peak day of antibody response in female CD rats and CD1 mice. The CP dose at which statistical significance was first observed in each species was quite similar within each lab using either assay. For DEX, the AFC assay detected significant and greater suppression at lower concentrations compared to the ELISA in both rats and mice. All labs detected DEX suppression using an AFC assay, whereas only one lab detected significant suppression in both species using an ELISA. For both compounds the magnitude of suppression was greater using the AFC assay, and resulted in ID(50) values which were lower in the AFC assay when compared to the ELISA. In addition, cross-species comparisons of ID(50) values suggested rats were more sensitive than mice. These initial experiments with two chemicals indicated that the AFC assay is consistently better at identifying suppression of a T-dependent antibody response across laboratories following xenobiotic exposures in outbred rats and mice. Additional compounds will need to be evaluated before concluding that one method is superior or more sensitive to the other in detecting suppression of the antibody response.

  11. IMC-EB10, an anti-FLT3 monoclonal antibody, prolongs survival and reduces nonobese diabetic/severe combined immunodeficient engraftment of some acute lymphoblastic leukemia cell lines and primary leukemic samples.

    Science.gov (United States)

    Piloto, Obdulio; Nguyen, Bao; Huso, David; Kim, Kyu-Tae; Li, Yiwen; Witte, Larry; Hicklin, Daniel J; Brown, Patrick; Small, Donald

    2006-05-01

    The class III receptor tyrosine kinase FLT3 is expressed on the blasts of >90% of patients with B-lineage acute lymphoblastic leukemias (ALL). In addition, it is expressed at extremely high levels in ALL patients with mixed lineage leukemia rearrangements or hyperdiploidy and is sometimes mutated in these same patients. In this report, we investigate the effects of treating ALL cell lines and primary samples with human anti-FLT3 monoclonal antibodies (mAb) capable of preventing binding of FLT3 ligand. In vitro studies, examining the ability of two anti-FLT3 mAbs (IMC-EB10 and IMC-NC7) to affect FLT3 activation and downstream signaling in ALL cell lines and primary blasts, yielded variable results. FLT3 phosphorylation was consistently inhibited by IMC-NC7 treatment, but in some cell lines, IMC-EB10 actually stimulated FLT3 activation, possibly as a result of antibody-mediated receptor dimerization. Through antibody-dependent, cell-mediated cytotoxicity, such an antibody could still prove efficacious against leukemia cells in vivo. In fact, IMC-EB10 treatment significantly prolonged survival and/or reduced engraftment of several ALL cell lines and primary ALL samples in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. This occurred even when IMC-EB10 treatment resulted in FLT3 activation in vitro. Moreover, fluorescence-activated cell sorting and PCR analysis of IMC-EB10-treated NOD/SCID mice surviving 150 days post-leukemic cell injection revealed that FLT3 immunotherapy reduced leukemic engraftment below the level of detection in these assays (IMC-EB10 treatment did not select for resistant cells, because cells surviving IMC-EB10 treatment remain sensitive to IMC-EB10 cytotoxicity upon retransplantation. In vivo studies involving either partial depletion or activation of natural killer (NK) cells show that most of the cytotoxic effect of IMC-EB10 is mediated through NK cells. Therefore, such an antibody, either naked or conjugated to radioactive

  12. MRI for clinically suspected pediatric appendicitis: an implemented program

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Michael M.; Gustas, Cristy N.; Choudhary, Arabinda K.; Methratta, Sosamma T.; Hulse, Michael A.; Eggli, Kathleen D.; Boal, Danielle K.B. [Penn State Milton S. Hershey Medical Center, Department of Radiology, Mail Code H066, 500 University Drive, P.O. Box 850, Hershey, PA (United States); Geeting, Glenn [Penn State Milton S. Hershey Medical Center, Department of Emergency Medicine, Hershey, PA (United States)

    2012-09-15

    Emergent MRI is now a viable alternative to CT for evaluating appendicitis while avoiding the detrimental effects of ionizing radiation. However, primary employment of MRI in the setting of clinically suspected pediatric appendicitis has remained significantly underutilized. To describe our institution's development and the results of a fully implemented clinical program using MRI as the primary imaging evaluation for children with suspected appendicitis. A four-sequence MRI protocol consisting of coronal and axial single-shot turbo spin-echo (SS-TSE) T2, coronal spectral adiabatic inversion recovery (SPAIR), and axial SS-TSE T2 with fat saturation was performed on 208 children, ages 3 to 17 years, with clinically suspected appendicitis. No intravenous or oral contrast material was administered. No sedation was administered. Data collection includes two separate areas: time parameter analysis and MRI diagnostic results. Diagnostic accuracy of MRI for pediatric appendicitis indicated a sensitivity of 97.6% (CI: 87.1-99.9%), specificity 97.0% (CI: 93.2-99.0%), positive predictive value 88.9% (CI: 76.0-96.3%), and negative predictive value 99.4% (CI: 96.6-99.9%). Time parameter analysis indicated clinical feasibility, with time requested to first sequence obtained mean of 78.7 +/- 52.5 min, median 65 min; first-to-last sequence time stamp mean 14.2 +/- 8.8 min, median 12 min; last sequence to report mean 57.4 +/- 35.2 min, median 46 min. Mean age was 11.2 +/- 3.6 years old. Girls represented 57% of patients. MRI is an effective and efficient method of imaging children with clinically suspected appendicitis. Using an expedited four-sequence protocol, sensitivity and specificity are comparable to CT while avoiding the detrimental effects of ionizing radiation. (orig.)

  13. Monoclonal Antibodies.

    Science.gov (United States)

    Geskin, Larisa J

    2015-10-01

    Use of monoclonal antibodies (mAbs) has revolutionized cancer therapy. Approaches targeting specific cellular targets on the malignant cells and in tumor microenvironment have been proved to be successful in hematologic malignancies, including cutaneous lymphomas. mAb-based therapy for cutaneous T-cell lymphoma has demonstrated high response rates and a favorable toxicity profile in clinical trials. Several antibodies and antibody-based conjugates are approved for use in clinical practice, and many more are in ongoing and planned clinical trials. In addition, these safe and effective drugs can be used as pillars for sequential therapies in a rational stepwise manner. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Randomized clinical trial of preoperative dexamethasone on postoperative nausea and vomiting after laparoscopy for suspected appendicitis

    DEFF Research Database (Denmark)

    Kleif, J.; Kirkegaard, A.; Vilandt, J.

    2017-01-01

    Background: Few studies have investigated the effects of preoperative dexamethasone in acute surgical patients. This study examined the effects of 8 mg dexamethasone administered intravenously 30 min before surgery for suspected acute appendicitis. Methods: A multicentre, parallel-group, double......-blind, placebo-controlled study was conducted at two university hospitals in Denmark. Adults undergoing laparoscopic surgery for suspected appendicitis were eligible for inclusion. Participants, healthcare staff and investigators were blinded until all data analysis had been done. The primary outcome...

  15. Activity of 8F4, a T-cell receptor-like anti-PR1/HLA-A2 antibody, against primary human AML in vivo.

    Science.gov (United States)

    Sergeeva, A; He, H; Ruisaard, K; St John, L; Alatrash, G; Clise-Dwyer, K; Li, D; Patenia, R; Hong, R; Sukhumalchandra, P; You, M J; Gagea, M; Ma, Q; Molldrem, J J

    2016-07-01

    The PR1 peptide, derived from the leukemia-associated antigens proteinase 3 and neutrophil elastase, is overexpressed on HLA-A2 in acute myeloid leukemia (AML). We developed a high-affinity T-cell receptor-like murine monoclonal antibody, 8F4, that binds to the PR1/HLA-A2 complex, mediates lysis of AML and inhibits leukemia colony formation. Here, we explored whether 8F4 was active in vivo against chemotherapy-resistant AML, including secondary AML. In a screening model, coincubation of AML with 8F4 ex vivo prevented engraftment of all tested AML subtypes in immunodeficient NSG (NOD scid IL-2 receptor γ-chain knockout) mice. In a treatment model of established human AML, administration of 8F4 significantly reduced or eliminated AML xenografts and extended survival compared with isotype antibody-treated mice. Moreover, in secondary transfer experiments, mice inoculated with bone marrow from 8F4-treated mice showed no evidence of AML engraftment, supporting the possible activity of 8F4 against the subset of AML with self-renewing potential. Our data provide evidence that 8F4 antibody is highly active in AML, including chemotherapy-resistant disease, supporting its potential use as a therapeutic agent in patients with AML.

  16. A case of suspect “cyanosis”

    OpenAIRE

    Elisabetta Antonucci; Matteo Conte; Michele Di Pumpo; Giuseppe Antonucci

    2013-01-01

    CLINICAL CASE A 70-year old woman was admitted to our hospital because of fever, asthenia and a suspected stroke. Her medical history showed a congenital cardiopathy (Patent Foramen Ovale, PFO). Skin and oral mucosa pigmentation, orthostatic hypotension, hypoglycemia and hyponatriemia arose the suspect of Addison’s disease. The diagnosis was confirmed by the evaluation of basal levels of plasma ACTH and serum cortisol, and serum cortisol levels after ACTH stimulation. Abdominal CT scan showed...

  17. Thyroid Antibodies

    Science.gov (United States)

    ... Factor Antibody Iron Iron Tests JAK2 Mutation Kidney Stone Analysis Kidney Stone Risk Panel KRAS Mutation Lactate Lactate Dehydrogenase (LD) ... gain Fatigue Dry skin Hair loss Intolerance to cold Constipation A high level of thyroid hormone ( hyperthyroidism ) ...

  18. The phenomenology of specialization of criminal suspects.

    Directory of Open Access Journals (Sweden)

    Michele Tumminello

    Full Text Available A criminal career can be either general, with the criminal committing different types of crimes, or specialized, with the criminal committing a specific type of crime. A central problem in the study of crime specialization is to determine, from the perspective of the criminal, which crimes should be considered similar and which crimes should be considered distinct. We study a large set of Swedish suspects to empirically investigate generalist and specialist behavior in crime. We show that there is a large group of suspects who can be described as generalists. At the same time, we observe a non-trivial pattern of specialization across age and gender of suspects. Women are less prone to commit crimes of certain types, and, for instance, are more prone to specialize in crimes related to fraud. We also find evidence of temporal specialization of suspects. Older persons are more specialized than younger ones, and some crime types are preferentially committed by suspects of different ages.

  19. Solitomab, an epithelial cell adhesion molecule/CD3 bispecific antibody (BiTE), is highly active against primary chemotherapy-resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo.

    Science.gov (United States)

    English, Diana P; Bellone, Stefania; Schwab, Carlton L; Roque, Dana M; Lopez, Salvatore; Bortolomai, Ileana; Cocco, Emiliano; Bonazzoli, Elena; Chatterjee, Sudeshna; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

    2015-02-01

    Solitomab is a novel, bispecific, single-chain antibody that targets epithelial cell adhesion molecule (EpCAM) on tumor cells and also contains a cluster of differentiation 3 (CD3) (T-cell coreceptor) binding region. The authors evaluated the in vitro activity of solitomab against primary chemotherapy-resistant epithelial ovarian carcinoma cell lines as well as malignant cells in ascites. EpCAM expression was evaluated by flow cytometry in 5 primary ovarian cancer cell lines and in 42 fresh ovarian tumor cell cultures in ascites from patients with mainly advanced or recurrent, chemotherapy-resistant disease. The potential activity of solitomab against EpCAM-positive tumor cells was evaluated by flow cytometry, proliferation, and 4-hour chromium-release, cell-mediated cytotoxicity assays. EpCAM expression was detected by flow cytometry in approximately 80% of the fresh ovarian tumors and primary ovarian tumor cell lines tested. EpCAM-positive, chemotherapy-resistant cell lines were identified as resistant to natural killer cell-mediated or T-cell-mediated killing after exposure to peripheral blood lymphocytes in 4-hour chromium-release assays (mean±standard error of the mean, 3.6%±0.7% of cells killed after incubation of EpCAM-positive cell lines with control bispecific antibody). In contrast, after incubation with solitomab, EpCAM-positive, chemotherapy-resistant cells became highly sensitive to T-cell cytotoxicity (mean±standard error of the mean, 28.2%±2.05% of cells killed; Ptreatment of chemotherapy-resistant ovarian cancers that overexpress EpCAM. © 2014 American Cancer Society.

  20. A case of suspect “cyanosis”

    Directory of Open Access Journals (Sweden)

    Elisabetta Antonucci

    2013-05-01

    Full Text Available CLINICAL CASE A 70-year old woman was admitted to our hospital because of fever, asthenia and a suspected stroke. Her medical history showed a congenital cardiopathy (Patent Foramen Ovale, PFO. Skin and oral mucosa pigmentation, orthostatic hypotension, hypoglycemia and hyponatriemia arose the suspect of Addison’s disease. The diagnosis was confirmed by the evaluation of basal levels of plasma ACTH and serum cortisol, and serum cortisol levels after ACTH stimulation. Abdominal CT scan showed atrophy and calcification of adrenal glands. CONCLUSIONS In most cases, Addison’s disease is provoked by autoimmune destruction of the adrenal cortex; however, in our reported patient, tuberculosis could be a possible cause.

  1. Chimeric antibodies.

    Science.gov (United States)

    Kurosawa, Kohei; Lin, Waka; Ohta, Kunihiro

    2014-01-01

    Here we describe a detailed protocol for the one-step preparation of antigen-specific human chimeric immunoglobulin G (IgG) monoclonal antibodies (mAbs) using an in vitro antibody design method referred to as the ADLib (Autonomously Diversifying Library) system. This method employs a chicken B cell line DT40-based library in which the variable regions of the Ig gene loci have been highly diversified by treatment with the histone deacetylase inhibitors. DT40 cells express both membrane-bound and secreted forms of chicken IgM. This property allows a rapid screening and selection of antibody-producing B cells from the library by using magnetic beads conjugated with any antigen of interest. To apply the ADLib system to the direct generation of human chimeric antibody, we have inserted a DNA segment coding for the constant region of human IgG into the chicken IgM heavy-chain locus of DT40 cells by homologous gene targeting. By a mechanism of alternative splicing, the resulting DT40 strain simultaneously expresses chimeric human IgG that contain the same Ig variable region sequences as the membrane-bound chicken IgM displayed at the cell surface. Application of the ADLib system to this human Ig-inserted DT40 strain enables the one-step isolation of human chimeric IgG that is specific for any antigen of interest and can be easily purified for immediate use.

  2. Antibody biotechnology

    African Journals Online (AJOL)

    STORAGESEVER

    2009-07-06

    Jul 6, 2009 ... from somatic recombination between variable genes, was made. This topic has preoccupied immunologists includ- ing Ehrlich (side chain theory), Jerne .... natural naïve libraries, syn- thetic naïve and semi-synthetic libraries. Immune antibody libraries. These libraries are constructed with VH (VDJ) and VL.

  3. Catalytic Antibodies

    Indian Academy of Sciences (India)

    systemic lupus erythematosus, multiple sclerosis and rheumatoid arthritis. The importance of natural immunological mechanisms in pro- ducing artificial catalysts is exemplified by the reports describing increased synthesis of esterase antibodies in autoimmune mice compared to normal mice in response to transition-state ...

  4. Steroid-Responsive Chronic Schizophreniform Syndrome in the Context of Mildly Increased Antithyroid Peroxidase Antibodies

    Directory of Open Access Journals (Sweden)

    Ludger Tebartz van Elst

    2017-04-01

    Full Text Available BackgroundSchizophreniform syndromes can be divided into primary forms from polygenic causes or secondary forms due to immunological, epileptiform, monogenic, or degenerative causes. Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT is a secondary immunological form associated with increased thyroid antibodies, such as antithyroid peroxidase antibodies and shows a good response to corticosteroids.Case presentationWe present the case of a 41-year-old woman suffering from a schizophreniform syndrome. Starting at the age of 35, she developed psychotic exacerbations with formal thought disorder, acoustic hallucinations, cenesthopathic experiences, and loss of ego boundaries. At the same time, she began to suffer from chronic sexual delusions and olfactory hallucinations, which did not respond to neuroleptic medication. Her levels of antithyroid peroxidase antibodies were slightly increased, and the blood–brain barrier was disturbed. An electroencephalogram (EEG showed intermittent generalized slowing, and cerebral magnetic resonance imaging (cMRI depicted mild temporolateral atrophy. High-dose corticosteroid treatment led to convincing improvement of attentional performance and the disappearance of delusions and olfactory hallucinations.ConclusionSREAT can mimic typical symptoms of schizophreniform syndromes. The increased titer of antithyroid peroxidase antibodies in combination with the EEG slowing, blood–brain barrier dysfunction, and the cMRI alterations were the basis for suspecting an immunological cause in our patient. Chronic delusions, olfactory hallucinations, and cognitive deficits were successfully treated with corticosteroids. The occurrence of secondary immunological forms of schizophreniform syndromes demonstrates the need for innovative immunosuppressive treatment options.

  5. Congenital Malaria Among Newborns Admitted for Suspected ...

    African Journals Online (AJOL)

    Background: Signs and symptoms of congenital malaria do not differ much from those of neonatal sepsis: both can co-exist, and most times very difficult to differentiate clinically. Objective: To document the prevalence, risk factors for congeni tal malar ia among neonates admitted for suspected neonatal sepsis, and ...

  6. Congenital Malaria Among Newborns Admitted for Suspected ...

    African Journals Online (AJOL)

    None of the clinical feature had good sensitivity, specificity or predictive value for congenital malaria, and only 1.6% death was recorded in a baby with high parasite density. Conclusion: Congenital malaria is common in newborns with suspected neonatal sepsis. History of peripartum pyrexia, prematurity and intrauterine ...

  7. MRI for clinically suspected appendicitis during pregnancy.

    NARCIS (Netherlands)

    Cobben, L.P.; Groot, I.; Haans, L.; Blickman, J.G.; Puylaert, J.

    2004-01-01

    OBJECTIVE: The purpose of this study was to evaluate whether MRI can be used to accurately diagnose or exclude appendicitis in pregnant patients with clinically suspected appendicitis. CONCLUSION: Our results suggest that MRI is helpful in the examination and diagnosis of acute appendicitis in

  8. Biomechanical properties of keratoconus suspect eyes.

    Science.gov (United States)

    Saad, Alain; Lteif, Yara; Azan, Elodie; Gatinel, Damien

    2010-06-01

    Measuring corneal biomechanical properties may help detect keratoconus suspect corneas and eliminate the risk of ectasia after LASIK. Data of 504 eyes separated into three groups were retrospectively reviewed: normal (n = 252), keratoconus suspect (n = 80), and keratoconus (n = 172). Corneal hysteresis (CH) and corneal resistance factor (CRF) were measured with an ocular biomechanics analyzer. Mean corneal hysteresis was 10.6 +/- 1.4 (SD) mm Hg in the normal group, compared with 10.0 +/- 1.6 mm Hg in the keratoconus suspect group and 8.1 +/- 1.4 mm Hg in the keratoconus group. The mean CRF was 10.6 +/- 1.6 mm Hg in the normal group compared with 9.7 +/- 1.7 in the keratoconus suspect group and 7.1 +/- 1.6 mm Hg in the keratoconus group. Mean CH and CRF were significantly different between the three groups (P corneas. Analyzing signal curves obtained with the biomechanics analyzer may provide additional valuable information for selecting qualified patients for refractive surgery.

  9. Characterization of suspected illegal skin whitening cosmetics.

    Science.gov (United States)

    Desmedt, B; Van Hoeck, E; Rogiers, V; Courselle, P; De Beer, J O; De Paepe, K; Deconinck, E

    2014-03-01

    An important group of suspected illegal cosmetics consists of skin bleaching products, which are usually applied to the skin of the face, hands and décolleté for local depigmentation of hyper pigmented regions or more importantly, for a generalized reduction of the skin tone. These cosmetic products are suspected to contain illegal active substances that may provoke as well local as systemic toxic effects, being the reason for their banning from the EU market. In that respect, illegal and restricted substances in cosmetics, known to have bleaching properties, are in particular hydroquinone, tretinoin and corticosteroids. From a legislative point of view, all cosmetic products containing a prohibited whitening agent are illegal and must be taken off the EU market. A newly developed screening method using ultra high performance liquid chromatography-time off flight-mass spectrometry allows routine analysis of suspected products. 163 suspected skin whitening cosmetics, collected by Belgian inspectors at high risk sites such as airports and so-called ethnic cosmetic shops, were analyzed and 59% were classified as illegal. The whitening agents mostly detected were clobetasol propionate and hydroquinone, which represent a serious health risk when repeatedly and abundantly applied to the skin. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Suspecting Neurological Dysfunction From E Mail Messages ...

    African Journals Online (AJOL)

    A non medical person suspected and confirmed neurological dysfunction in an individual, based only on e mail messages sent by the individual. With email communication becoming rampant “peculiar” email messages may raise the suspicion of neurological dysfunction. Organic pathology explaining the abnormal email ...

  11. Prevalence of IgG autoantibody against F-actin in patients suspected of having autoimmune or acute viral hepatitis.

    Science.gov (United States)

    Jaskowski, Troy D; Konnick, Eric Q; Ashwood, Edward R; Litwin, Christine M; Hill, Harry R

    2007-01-01

    Our objectives in this study were to compare results obtained by an enzyme immunoassay (EIA) for F-actin antibody (FAA) immunoglobulin G (IgG) to those determined by an indirect fluorescent antibody (IFA) assay for smooth muscle antibody (SMA) IgG, and to determine the prevalence of FAA in patient sera having serologic evidence of acute viral hepatitis. Sera from 415 patients suspected of having autoimmune hepatitis (AIH), 208 patients suspected of having acute viral hepatitis A, B, or C, and 100 healthy blood donors (HBD) were included in the study. Only one of 100 HBD showed low levels (20-30 Units) of F-actin IgG. In patients suspected of having AIH, the prevalence of FAA increased as SMA titers increased and all sera with SMA titers of >or=1:160 were FAA-positive. In contrast, there were many sera with negative (30 Units) of FAA; many exceeding 80 Units. Moreover, 51.4% of these sera were also positive for anti-nuclear antibody (ANA), which is also utilized in diagnosing type 1 AIH. FAA was detected in 25% of viral hepatitis antibody-positive sera, with the majority (59.3%) containing low levels, and all were ANA-negative. Copyright (c) 2007 Wiley-Liss, Inc.

  12. Role of type-specific herpes simplex virus-1 and 2 serology as a diagnostic modality in patients with clinically suspected genital herpes: A comparative study in Indian population from a tertiary care hospital.

    Science.gov (United States)

    Patwardhan, Vrushali; Bhalla, Preena

    2016-01-01

    Type-specific serology (TSS) test for herpes simplex virus (HSV) have been used as a research tool in seroepidemiological studies for some years. However, TSS as a diagnostic modality for diagnosis of current episode of genital herpes is not well documented. To measure the seroprevalence of type-specific HSV Type 1 (HSV-1) and Type 2 (HSV-2) IgG antibodies in cases provisionally diagnosed as primary and recurrent genital herpes and to evaluate the role of TSS as a diagnostic modality for diagnosis of genital herpes versus polymerase chain reaction (PCR). A cross-sectional study was performed over a period of 10 months in which 44 adult patients with clinically suspected genital herpes were recruited. An in-house glycoprotein G gene base PCR was performed directly from the genital lesion specimen for simultaneous detection and typing of HSV. TSS was performed to detect IgG antibody against HSV-1 and 2 in all patients using commercially available kits, and the results were compared. Seroprevalence of HSV-1 IgG was 43% among primary and 65% among recurrent genital herpes cases (P = 0.22). Whereas that of HSV-2 IgG was found to be 14% and 83% in respective patient group (P = 0.0001). When compared to PCR results HSV-1 IgG detection in both primary and recurrent genital herpes diagnosis had poor specificity, positive predictive value, and sensitivity. Whereas, HSV-2 serology had a sensitivity of 13.33% and 73.33% in primary and recurrent genital herpes and specificity of 83.33% and 85.71%, respectively. HSV-2 IgG detection helps in strengthening the diagnosis of recurrent HSV-2 disease, whereas the absence of HSV-2 IgG antibody helps in excluding genital herpes as a likely cause of recurrent genital ulceration. However, detection of HSV-1 IgG antibody may not be useful for diagnosis in patients of genital ulcer disease.

  13. Reduction in serum levels of antimitochondrial (M2) antibodies following immunoglobulin therapy in severe combined immunodeficient (SCID) mice reconstituted with lymphocytes from patients with primary biliary cirrhosis (PBC)

    Science.gov (United States)

    ABEDI, M R; HAMMARSTRÖM, L; BROOMÉ, U; ANGELIN, B; EDVARD SMITH, C I; CHRISTENSSON, B

    1996-01-01

    The effect of gammaglobulin treatment on autoantibody production was investigated in SCID mice reconstituted with human peripheral blood mononuclear cells (PBMC) obtained from patients with PBC. All reconstituted mice displayed the presence of human antimitochondrial antibodies (αM2Ab) of both IgG and IgM types before treatment with human immunoglobulin. Two weeks after i.p. injection of 20 ×106 PBMC into SCID mice, i.p. treatment with various preparations of human immunoglobulin was initiated. In control animals treated with saline, serum levels of human αM2Ab of the IgG type increased with time, peaking around 4 weeks after reconstitution. In contrast, human IgG autoantibodies rapidly decreased in all animals treated with human IgG. Treatment with a human IgM preparation had no effect on serum levels of αM2Ab of the IgG type. The results may suggest that the pronounced reduction of specific IgG autoantibodies was due to an increased catabolism of human IgG, including the autoantibodies, in the gammaglobulin-treated mice. Although the production of human αM2Ab in reconstituted mice could be easily shown, PBC-specific liver lesions or bile duct destruction were not observed, irrespective of treatment protocol. PMID:8706332

  14. Antiparietal cell antibody test

    Science.gov (United States)

    APCA; Anti-gastric parietal cell antibody; Atrophic gastritis - anti-gastric parietal cell antibody; Gastric ulcer - anti-gastric parietal cell antibody; Pernicious anemia - anti-gastric parietal cell antibody; ...

  15. Características estructurales del disco óptico y la capa de fibras neurorretinianas mediante tomografía confocal láser en la sospecha de cierre angular primario Structural characteristics of the optic disc and the neuroretinal nerve fiber layer observed by confocal laser tomography in suspected primary angle closure

    Directory of Open Access Journals (Sweden)

    Liamet Fernández Argones

    2012-01-01

    layer in the suspected primary angle closure, the performance of glaucomatous discriminant functions, and the influence of the optic disc size in the results. Methods: a cross-sectional case series study in 47 eyes (30 patients with suspected primary angle-closure, for which the confocal laser tomography (HRT 3, Heidelberg Engineering, Germany, was used to obtain the images. The influence of the optic disc size was analized in 3 groups: 2,0 mm². Results: the disc area was positively related to the cup area, the rim area, the cup volume, the retinal nerve fiber layer cross sectional area, and the cup size (p=0,023, p=0,009, p=0,022, p=0,026, p=0,020 respectively and negatively related with the horizontal curvature of the retinal nerve fiber layer (p=0,019. There was a significant relation to the variation of contour height (p=0,008, particularly to differences between small and medium size discs. Discriminant functions such as MRA, GPS and FSM performed better in small discs (approximately 92 % of agreement with the normal discs for each one. The RB function obtained the greater coincidence (100, 96 and 100 % for respective groups of disc areas, whereas GPS obtained the smallest (92, 72 and 55,6 % respectively. Conclusions: the disc area is related to cup area, rim area, cup volume, retinal nerve fiber layer cross sectional area, retinal nerve fiber layer horizontal curvature, cup size and the variation of contour height. The MRA, GPS and FSM discriminant functions identify better the normal optic disc when it is small. The RB function performs the best whereas the GPS performs the worst, regardless of the disc area.

  16. [Association between time spent on physical exercise, sleep, homework and suspected myopia among students].

    Science.gov (United States)

    Xu, S J; Wan, Y H; Xu, Z H; Zhang, H; Xu, L; Wang, B; Tao, F B

    2016-02-01

    To investigate the prevalence of suspected myopia among students and to examine the relationship between time spent on physical exercise, sleep, homework and suspected myopia. A total of 8 030 primary and secondary school students from 4(th) to 12(th) grades were selected from the National Student Constitution and Health Survey (NSCHS) in Anhui province in 2014. Time spent on exercise, sleep and homework per day were collected using a self-administrated questionnaire. Visual acuity was examined using the Standard Logarithmic Visual Acuity Chart. The overall prevalence of suspected myopia was 69.03%. Prevalence rates of suspected myopia appeared higher in girls, in urban students, with the highest in the 16 to 18 year-old groups. RESULTS from the multiple logistic regression analysis showed that the amount of time spent on physical exercise, sleep and homework per day were all significantly associated with suspected myopia. Suspected myopia was associated with longer time on physical exercise among students aged 8 to 12 years (OR=0.80, 95%CI: 0.64-0.99), and longer sleep time among students in the age groups of 13 to 15 years and 16 to 18 years (OR=0.73, 95% CI: 0.56-0.94;OR=0.38, 95% CI: 0.21-0.68, respectively). Longer time spent on homework significantly increased the risk of suspected myopia among students in the age groups of 8 to 12 years and 13 to 15 years (OR=1.41, 95%CI: 1.11-1.79; OR=1.74, 95% CI: 1.36-2.23, respectively). Suspected myopia appeared common among students. Comprehensive intervention programs focusing on sufficient physical exercise and sleep but less homework might help to prevent myopia among students at different ages.

  17. The evaluation of suspected child physical abuse.

    Science.gov (United States)

    Christian, Cindy W

    2015-05-01

    Child physical abuse is an important cause of pediatric morbidity and mortality and is associated with major physical and mental health problems that can extend into adulthood. Pediatricians are in a unique position to identify and prevent child abuse, and this clinical report provides guidance to the practitioner regarding indicators and evaluation of suspected physical abuse of children. The role of the physician may include identifying abused children with suspicious injuries who present for care, reporting suspected abuse to the child protection agency for investigation, supporting families who are affected by child abuse, coordinating with other professionals and community agencies to provide immediate and long-term treatment to victimized children, providing court testimony when necessary, providing preventive care and anticipatory guidance in the office, and advocating for policies and programs that support families and protect vulnerable children. Copyright © 2015 by the American Academy of Pediatrics.

  18. Neurohormonal activation and diagnostic value of cardiac peptides in patients with suspected mild heart failure

    DEFF Research Database (Denmark)

    Mikkelsen, Kirsten V.; Bie, Peter; Møller, Jacob E.

    2006-01-01

    accuracy of cardiac peptides to detect any left ventricular dysfunction (LVD) in patients referred from primary care with suspected HF before institution of medical therapy. METHODS: Of 166 referred patients 150 were consecutively included (14 were excluded and two refused consent). Echocardiography...

  19. Suspects in criminal investigations of rape

    Directory of Open Access Journals (Sweden)

    Marinković Darko

    2014-01-01

    Full Text Available Investigations of sexual assaults mostly focus on victims and their credibility, which may cause lack of firm evidence in relation to suspects. Given the fact that the criminal offence of rape is characterised by a high incidence of false reports and accusations, frequently indicating specific persons as the perpetrators, certain caution is necessary in the investigation in order to avoid false accusations and/or convictions. As regards the personality of the rapist and motives for committing a forcible sexual act, certain types or rather certain categories of perpetrators can be distinguished, although it should be noted that a large number of rapists do not belong to one category only, but rather combine characteristics of several different types. During a criminal investigation it is of vital importance to differentiate between a rape as a surprise attack and a rape as abuse of trust, as they are compatible with the nature of the suspect's defence. The suspect shall be subjected to a forensic examination in the course of the investigation in order to find traces which prove vaginal, anal or oral penetration, coerced sexual intercourse and identity of the rapist. While conducting an interrogation of a suspected rapist, a crime investigating officer shall use either factual or emotional approach to his interviewee, depending on his psychological and motivational characteristics. In this regard, the factual approach is believed to be more efficient with anger rapists and sadistic rapists, whereas the compassionate approach gives good results with the gentlemen-rapists and partly with the power asserting rapists.

  20. Tocolytics for suspected intrapartum fetal distress.

    Science.gov (United States)

    Kulier, R; Hofmeyr, G J

    2000-01-01

    Prophylactic tocolysis with betamimetics and other agents has become widespread as a treatment for fetal distress. Uterine relaxation may improve placental blood flow and therefore fetal oxygenation. However there may also be adverse maternal cardiovascular effects. The objective of this review was to assess the effects of tocolytic therapy for suspected fetal distress on fetal, maternal and perinatal outcomes. We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. Date of last search: February 1999. Randomised trials comparing tocolytic therapy with no treatment or treatment with another tocolytic agent for suspected fetal distress. Two reviewers assessed trial quality and extracted data. Three studies were included. Compared with no treatment, there were fewer failed improvements in fetal heart rate abnormalities with tocolytic therapy (relative risk 0.26, 95% 0.13 to 0.53). Betamimetic therapy compared with magnesium sulphate showed a non-significant trend towards reduced uterine activity (relative risk 0.07, 95% confidence interval 0.00 to 1.10). Betamimetic therapy appears to be able to reduce the number of fetal heart rate abnormalities and perhaps reduce uterine activity. However there is not enough evidence based on clinically important outcomes to evaluate the use of betamimetics for suspected fetal distress.

  1. Investigation of suspected chronic fatigue syndrome/myalgic encephalopathy.

    Science.gov (United States)

    Owe, Jone Furlund; Næss, Halvor; Gjerde, Ivar Otto; Bødtker, Jørn Eilert; Tysnes, Ole-Bjørn

    2016-02-09

    Chronic fatigue is a frequently occurring problem in both the primary and specialist health services. The Department of Neurology at Haukeland University Hospital has established a standard assessment for patients referred with suspected CFS/ME. This study reports diagnoses and findings upon assessment, and considers the benefit of supplementary examinations. Diagnoses and findings from examinations of 365 patients assessed for suspected CFS/ME are retrospectively reported. A total of 48 patients (13.2%) were diagnosed with CFS/ME, while a further 18 patients (4.9%) were diagnosed with post-infectious fatigue. Mental and behavioural disorders were diagnosed in 169 patients (46.3%), and these represented by far the largest group. Serious, but unrecognised somatic illness was discovered in two patients, while changes of uncertain significance were identified by MRI and lumbar puncture in a few patients. Fatigue is a frequently occurring symptom in the population. Thorough somatic and psychiatric investigation is necessary before referral to the specialist health services. Mental disorders and reactions to life crises are common and important differential diagnoses for CFS/ME. Long waiting times in the specialist health services may result in delayed diagnosis for these patients.

  2. Perioperative sexual interest in women with suspected gynecologic malignancies.

    Science.gov (United States)

    Bretschneider, C E; Bensen, Jeannette T; Geller, Elizabeth J; Gehrig, Paola A; Wu, Jennifer M; Doll, Kemi M

    2017-07-01

    For women with gynecologic cancer, the impact of surgery on sexual interest and desire in the immediate and later postoperative period is not well characterized. The objective of this study was to report the perioperative trends of changing sexual interest and desire in a cohort of women undergoing surgery for suspected gynecologic malignancies. This is an ancillary analysis of a cohort study analyzing health-related outcomes in women who underwent primary surgical management of a suspected gynecologic malignancy between 10/2013 and 10/2014. Subjects completed the Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction Questionnaire (PROMIS-SFQ) preoperatively and questions on sexual interest and desire at one, three, and six months postoperatively. Bivariate tests and multiple linear regression were used to analyze data. Of 231 women who completed a baseline PROMIS-SFQ, 187 (81%) completed one-month, 170 (74%) three-month, and 174 (75%) six-month follow-up interviews. Following surgery, 71% of enrolled subjects were diagnosed with a malignancy. Women age women age >55 (-5.5±1.0 vs -2.3±0.9, p=0.02). In a multivariable analysis, age women of all ages (-5.6, 95% CI: -9.6, -1.5). This study provides new data regarding the timing and magnitude of changes in sexual interest following gynecologic oncology procedures. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Antibody Engineering and Therapeutics

    Science.gov (United States)

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul WHI; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates. PMID:24589717

  4. A new surface plasmon resonance system with the function transforming freely from wavelength to angle modulation and the primary application in real time detection of antibody-antigen interaction

    Science.gov (United States)

    Yang, L. Q.; Zhang, H. Y.; Wang, X. L.

    2011-11-01

    Surface plasmon resonance (SPR) sensor has been widely investigated as an exceedingly powerful tool for biological and chemical detection in the past decay. As an essential component of both academic and commercial laboratories, several methods have been employed to monitor the excitation of SPR by measuring the light reflected from the sensor interface including modulation of angle, wavelength, intensity, phase and polarization. Among these methods, angle modulation (AM) and wavelength modulation (WM) are the most widely adopted in practice. However, the normal sensors system of the angle modulation was built by two ratable stages with a flow cell attaching a prism, and the angle of incidence rottingθ, the angle of reflect rotting 2θ. The mechanical structure can only be used in the angle modulation SPR sensor. In the present study, a new SPR is designed by a mechanical structure which can transform freely from wavelength to angle modulation. The different concentration Ethanol solution is tested by this system, and the linear range is very well from the volume ratio 0% to 60%. The primary application is done in real time detection of human IgG and antibody interaction, and the experimental results indicate that the new SPR system can detect human antibody at low concentration 1x10-11g/ml with highly sensitivity and flexibility. The new SPR system is of great importance for potentially practical application in biosensor and life science with the extended the functions of the conventional SPR sensor, and provides the real-time and in-situ detection of the biomolecules.

  5. The optimal diagnostic workup for children with suspected food allergy.

    Science.gov (United States)

    Berni Canani, Roberto; Di Costanzo, Mara; Troncone, Riccardo

    2011-10-01

    Food allergy is defined as an abnormal immunologic reaction to food proteins that causes an adverse clinical reaction. In addition to well-known acute allergic reactions and anaphylaxis triggered by immunoglobulin E antibody-mediated immune responses to food proteins, there is an increasing recognition of cell-mediated disorders such as eosinophilic esophagitis and food protein-induced enterocolitis syndrome. More than 90% of food allergies in childhood are caused by eight foods: cow's milk, hen's egg, soy, peanuts, tree nuts, wheat, fish, and shellfish. The diagnostic workup for a child with suspected food allergy includes a detailed medical history, physical examination, food allergy screening tests, and responses to an elimination diet and an oral food challenge. None of the screening tests, alone or in combination, can definitely diagnose or exclude a food allergy. Novel diagnostic methods including those that focus on immune responses to specific food proteins or epitopes of specific proteins are under active study. Unconventional diagnostic methods are increasingly used, but they lack scientific rationale, standardization, and reproducibility. In selected cases, such as eosinophilic esophageal gastroenteropathies or food protein-induced gastroesophageal reflux disease, invasive procedures are mandatory for an accurate diagnosis. Properly done, an oral food challenge is still the gold standard in the diagnostic workup. An incorrect diagnosis is likely to result in unnecessary dietary restrictions, which, if prolonged, may adversely affect the child's nutritional status and growth. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Comparison of cortisol and thyroid hormones between tuberculosis-suspect and healthy elephants of Nepal.

    Science.gov (United States)

    Paudel, Sarad; Brown, Janine L; Thapaliya, Sharada; Dhakal, Ishwari P; Mikota, Susan K; Gairhe, Kamal P; Shimozuru, Michito; Tsubota, Toshio

    2016-12-01

    We compared cortisol and thyroid hormone (T3 and T4) concentrations between tuberculosis (TB)-suspected (n=10) and healthy (n=10) elephants of Nepal. Whole blood was collected from captive elephants throughout Nepal, and TB testing was performed using the ElephantTB STAT-PAK® and DPP VetTB® serological assays that detect antibodies against Mycobacterium tuberculosis and M. bovis in elephant serum. Cortisol, T3 and T4 were quantified by competitive enzyme immunoassays, and the results showed no significant differences in hormone concentrations between TB-suspect and healthy elephants. These preliminary data suggest neither adrenal nor thyroid function is altered by TB disease status. However, more elephants, including those positively diagnosed for TB by trunk wash cultures, need to be evaluated over time to confirm results.

  7. Prevalence of glaucoma suspects and pattern of intra-ocular ...

    African Journals Online (AJOL)

    Background: Glaucoma is the commonest cause of irreversible blindness in the world. Some glaucoma patients start out as glaucoma suspects for years. Aim: To determine the prevalence of glaucoma suspects and pattern of intra-ocular pressure distribution in glaucoma suspects. Methods: This survey was carried out in ...

  8. Nuclear Pedigree Criteria of Suspected HNPCC

    Directory of Open Access Journals (Sweden)

    Kładny Józef

    2003-01-01

    Full Text Available Abstract The criteria for the diagnosis of HNPCC established by the ICG-HNPCC are very restrictive as they do not allow for the diagnosis of a large number of "suspected HNPCC" cases - these are families which do no fulfill the strict diagnostic "Amsterdam criteria", but do present with several pedigree and clinical features characteristic for HNPCC. Several series of families suspected of harboring germline mutations in DNA mismatch repair genes have been studied for germline changes in DNA mismatch repair genes and a mutation rate of somewhere between 8-60% was found. Therefore a subgroup of members of the ICG-HNPCC has been working on pedigree/clinical diagnostic criteria for suspected HNPCC. Materials and methods Part I The study was based on two series of colorectal cancer (CRC cases: 1 HNPCC - this group comprised 190 patients affected by CRC from randomly selected families which fulfilled the Amsterdam II criteria registered in Düsseldorf, Germany (102 cases of CRC, Denmark (18 CRCs, Leiden, Holland (23 CRCs and Szczecin, Poland (47 CRCs. 2 Consecutive CRCs - this group comprised 629 (78.0% of 806 individuals with CRC diagnosed in 1991-1997 in the city of Szczecin (ca. 400,000 of inhabitants, Poland. Nuclear pedigrees in both groups were compared for frequency of occurrence of clinical features, that have been shown to be associated with HNPCC. Part II 52 consecutive CRC cases from Szczecin, matching the criteria recognized in part I as appropriate for diagnosis of cases "suspected of HNPCC" were studied for the occurrence of germline hMSH2/hMLH1 constitutional mutations using "exon by exon" sequencing. Results The combination of features - i.e. the occurrence of an HNPCC associated cancer (CRC or cancer of the endometrium, small bowel or urinary tract in a 1st degree relative of a CRC patient; at least one of the patients being diagnosed under age of 50 - appeared to be strongly associated to HNPCC with an OR - 161. Constitutional

  9. Association between QRS duration on prehospital ECG and mortality in patients with suspected STEMI

    DEFF Research Database (Denmark)

    Hansen, Rikke; Frydland, Martin; Møller-Helgestad, Ole Kristian

    2017-01-01

    BACKGROUND: QRS duration has previously shown association with mortality in patients with acute myocardial infarction treated with thrombolytics, less is known in patients with suspected ST segment elevation myocardial infarction (STEMI) when assessing QRS duration on prehospital ECG. Thus......, the objective was to investigate the prognostic effect of QRS duration on prehospital ECG and presence of classic left and right bundle branch block (LBBB/RBBB) for all-cause mortality in patients with suspected STEMI. METHOD: In total 2105 consecutive patients (mean age 64±13years, 72% men) with suspected...... STEMI were prospectively included. QRS duration was registered from automated QRS measurement on prehospital ECG and patients were divided according to quartiles of QRS duration (111ms). Primary endpoint was all-cause 30-day mortality. Predictors of all-cause mortality were...

  10. Added value of interpreter experience in occult and suspect hip fractures: a retrospective analysis of 254 patients.

    Science.gov (United States)

    Collin, David; Göthlin, Jan H; Nilsson, Martin; Hellström, Mikael; Geijer, Mats

    2016-06-01

    The influence of experience in categorizing suspect and occult fractures on radiography compared to MRI and clinical outcome has not been studied. The aim of this study is to evaluate the importance of experience in diagnosing normal or suspect hip radiographs compared to MRI. Primarily reported normal or suspect radiography in 254 patients with low-energy hip trauma and subsequent MRI was re-evaluated by two experienced reviewers. Primary readings and review were compared. The prevalence of fractures among normal and suspect radiographic studies was assessed. Clinical outcome was used as reference. At review of radiography, 44 fractures (17 %) were found. Significantly more fractures were found among suspect cases than among normal cases. At MRI, all 44 fractures were confirmed, and further 64 fractures were detected (25 %). MRI detected all fractures with no missed fractures revealed at follow-up. There were a significantly higher proportion of fractures at MRI among the suspect radiographic diagnoses for both the primary report and at review than among occult cases. The more experienced reviewers classified radiography examinations with higher accuracy than primary reporting general radiologists. There was almost complete agreement on MRI diagnoses.

  11. RBC Antibody Screen

    Science.gov (United States)

    ... products and services. Advertising & Sponsorship: Policy | Opportunities RBC Antibody Screen Share this page: Was this page helpful? ... Indirect Coombs Test; Indirect Anti-human Globulin Test; Antibody Screen Formal name: Red Blood Cell Antibody Screen ...

  12. PET imaging of osteosarcoma in dogs using a fluorine-18-labeled monoclonal antibody fab fragment

    Energy Technology Data Exchange (ETDEWEB)

    Page, R.L.; Garg, P.K.; Gard, S. [North Carolina State Univ., Raleigh, NC (United States)]|[Duke Univ. Medical Center, Durham, NC (United States)]|[North Carolina and Norke Radium Hospital, Oslo (Norway)] [and others

    1994-09-01

    Four dogs with histologically confirmed osteogenic sarcoma were studied with PET following intravenous injection of the {sup 18}F-labeled Fab fragment of TP-3, a monoclonal antibody specific for human and canine osteosarcomas. The antibody fragment was labeled using the N-succinimidyl (8-(4{prime}-({sup 18}F)fluorobenzyl)amino)suberate acylation agent. Blood clearance of activity was biphasic in all dogs but half-times were variable (T{sub 1/2{beta}} = 2-13 hr). Catabolism of labeled Fab was reflected by the decrease in protein-associated activity in serum from more than 90% at 1 min to 60%-80% at 4 hr. PET images demonstrated increased accumulation of {sup 18}F at the primary tumor site relative to normal contralateral bone in one dog as early as 15 min after injection. Biopsies obtained after euthanasia indicated higher uptake at the edges of the tumor as observed on the PET scans. Tumor uptake was 1-3 x 10{sup -3}% injected dose/g, a level similar to that reported for other Fab fragments in human tumors. In the three dogs with metastatic disease, early PET images reflected activity in the blood pool but later uptake was observed in suspected metastatic sites. These results, although preliminary, suggest that PET imaging of {sup 18}F-labeled antibody fragments is feasible and that dogs with spontaneous tumors could be a valuable model for preclinical research with radioimmunoconjugates. 34 refs., 6 figs., 2 tabs.

  13. Facing suspected child abuse--what keeps Swedish general practitioners from reporting to child protective services?

    Science.gov (United States)

    Talsma, Marijke; Bengtsson Boström, Kristina; Östberg, Anna-Lena

    2015-03-01

    The aim of this study was to examine the reporting of suspected child abuse among Swedish general practitioners (GPs), and to investigate factors influencing them in their decision whether or not to report to child protective services (CPS). A cross-sectional questionnaire study. Primary health care centres in western Sweden. 177 GPs and GP trainees. Demographic and educational background, education on child abuse, attitudes to reporting and CPS, previous experience of reporting suspected child abuse, and need of support. Despite mandatory reporting, 20% of all physicians had at some point suspected but not reported child abuse. Main reasons for non-reporting were uncertainty about the suspicion and use of alternative strategies; for instance, referral to other health care providers or follow-up of the family by the treating physician. Only 30% of all physicians trusted CPS's methods of investigating and acting in cases of suspected child abuse, and 44% of all physicians would have wanted access to expert consultation. There were no differences in the failure to report suspected child abuse that could be attributed to GP characteristics. However, GPs educated abroad reported less frequently to CPS than GPs educated in Sweden. This study showed that GPs see a need for support from experts and that the communication and cooperation between GPs and CPS needs to be improved. The low frequency of reporting indicates a need for continued education of GPs and for updated guidelines including practical advice on how to manage child abuse.

  14. Aflatoxin B1 Suppressed T-Cell Response to Anti-pig-CD3 Monoclonal Antibody Stimulation in Primary Porcine Splenocytes: A Role for the Extracellular Regulated Protein Kinase (ERK1/2) MAPK Signaling Pathway.

    Science.gov (United States)

    Hao, Shu; Pan, Shengchi; Hu, Junfa; Qian, Gang; Gan, Fang; Huang, Kehe

    2015-07-08

    The aim of the present study is to investigate whether aflatoxin B1 (AFB1)-induced immunotoxicity is associated with oxidative stress and the expression of extracellular regulated protein kinases (ERK) 1/2. The primary splenocytes isolated from healthy pigs were activated and proliferated by anti-pig-CD3 monoclonal antibodies (mAb) in the present experiment, which is an antigen-specific stimulant. Results indicated that cell proliferation and interleukin-2 (IL-2) production were significantly suppressed by AFB1 from 4 to 8 μg/mL in a dose-dependent manner compared to the control group. Furthermore, AFB1 significantly increased malondialdehyde (MDA) levels, decreased reduced glutathione (GSH) and total superoxide dismutase levels, and up-regulated p-ERK1/2 expression in the activated splenocytes. N-Acetyl-l-cysteine blocked anti-CD3-induced T-cell suppression by AFB1 through increasing intracellular concentrations of GSH levels, decreasing MDA levels, and down-regulated p-ERK1/2 expression, respectively. Inhibition of the ERK1/2 expression by ERK-specific iRNA attenuated the decrease of T-cell proliferation and IL-2 production induced by AFB1. It was concluded that AFB1 inhibits anti-CD3-induced lymphocyte proliferation and IL-2 production by the oxidative stress mediated ERK1/2 MAPK signaling pathway.

  15. A Comparative Study Of The Indirect Fluorescent Antibody Assay And Culture Method In Symptomatic Pulmonary Nocardiosis

    Directory of Open Access Journals (Sweden)

    Eshraghi S

    2004-09-01

    Full Text Available Background: Pulmonary Nocardiosis is an infrequent infection whose incidence seems to be on the rise due to a higher degree of clinical suspicion and to an increasing number of immunosuppressive factors. The present investigation was carried out to detect Nocardiosis in immunocompromised patients confined in the pulmonary ward of Tehran’s Shariati Training Hospital through the use of indirect immunofluorescence assay (IFA and bacterial culture methods. The comparison of the two methods and the correlation between the antibody titer and the statistical and epidemiological data were also investigated. Materials and Methods: 101 patients with advanced symptomatic pulmonary infection were studied in the course of a twenty-month period. Individual patients’ sputum, BAL (bronchoalveolar lavage and blood sera were tested. From each sample three thin smears were prepared for microscopic observations. The samples were cultured in Sabouraud’s dextrose, blood and paraffin agar. The detection of antibody against Nocardia asteroides was carried out in all study groups, using the IFA method. The medical history of patients was also obtained through questionnaires for further analysis. Results: Nocardia asteroides was isolated from only one patient suffering from Wagner vasculitis with an antibody titer of in serum. The 41 patients suspected for Nocardiosis with an antibody titer ranging from to , detected by IFA method, included 26 (63.4% men and 15 (14.8% women. The age of the patients varied from 7-80 years. Those with reasonable antibody titers included 15 (36.5% housewives and 9 (21.9% workers. Furthermore, in-vitro investigation for the differentiation of the isolates was performed and confirmed the notion that the organism which grew on the primary media was, indeed, the Nocardia asteroids complex. Conclusion: Our results revealed that the broncho-pulmonary infections, which occur in high-risk patients -T-cell deficiencies, long term

  16. Usefulness of antibodies and minor salivary gland biopsy in the study of sicca syndrome in daily clinical practice.

    Science.gov (United States)

    Santiago, Maria Lida; Seisdedos, Maria Renata; Garcia Salinas, Rodrigo Nicolás; Catalán Pellet, Antonio; Villalón, Liliana; Secco, Anastasia

    2015-01-01

    To assess the association between histologic findings in the minor salivary gland biopsy (MSGB) and anti La (La/SS-B)y antiRo antibodies (Ro/SS-A), antinuclear antibodies (ANA) and Rheumatoid Factor (RF),and compare the value of the latter as diagnostic tests with MSGB, considered as the gold standard. Patients with suspected Primary Sjögren Syndrome (PSS) referred for MSGB were included. Antibody measurements were performed. Grade III and IV biopsy results were considered positive. Two hundred and eighteen (218) patients were included, 95% females, with a median age of 54 years and 12 months median duration of sicca symptoms. 36 of the biopsies were positive. 33% of patients had positive anti Ro/SS-A anti La/SS-B antibodies, 62% had positive ANA, and 31% positive RF. A statistically significant association was found between MSGB and anti Ro/SS-A anti La/SS-B, ANA and RF. ANA were the most sensitive antibodies (84%. 95% CI: 75- 92), and the most specific were: Anti Ro/ SS-A and/or anti La/ SS-B (78%. 95% CI: 71-85) and RF (78%. 95% CI: 69-87). On PSS clinical suspicion, anti Ro/ SS-A y anti La/ SS-B antibodies have a great value to achieve the diagnosis, with MSGB useful for diagnosis of seronegative patients. The results also suggest the importance of ANA and RF for PSS classification. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  17. A Clinical Approach for Defining the Threshold between Low and Medium Anti-Cardiolipin Antibody Levels for QUANTA Flash Assays

    Directory of Open Access Journals (Sweden)

    Gabriella Lakos

    2016-05-01

    Full Text Available The threshold between low and medium antibody levels for anticardiolipin (aCL and anti-β2 glycoprotein I antibodies (aβ2GPI for the diagnosis of antiphospholipid syndrome (APS remains a matter of discussion. Our goal was to create a protocol for determining the low/medium antibody cut-off for aCL antibody methods based on a clinical approach, and utilize it to establish the clinically-relevant low/medium threshold for QUANTA Flash aCL chemiluminescent immunoassay (CIA results. The study included 288 samples from patients with primary APS (n = 70, secondary APS (n = 42, suspected APS (n = 36, systemic lupus erythematosus (SLE without APS (n = 96 and other connective tissue diseases (n = 44. All samples were tested for IgG and IgM aCL antibodies with QUANTA Flash CIA, along with traditional enzyme-linked immunosorbent assays (ELISAs (QUANTA Lite. The assay specific low/medium threshold for QUANTA Flash aCL IgG and IgM assays (i.e., the equivalent of 40 GPL and MPL units was established as 95 and 31 chemiluminescent units (CU, respectively, based on clinical performance and comparison to QUANTA Lite ELISAs. Agreement between CIA and ELISA assay results improved substantially when the platform-specific low/medium antibody threshold was used, as compared to agreement obtained on results generated with the assay cutoff: Cohen’s kappa increased from 0.85 to 0.91 for IgG aCL, and from 0.59 to 0.75 for IgM aCL results. This study describes a clinical approach for establishing the low/medium antibody threshold for aPL antibody assays, and successfully employs it to define 95 and 31 CU, respectively, as the low/medium cut point for QUANTA Flash aCL IgG and IgM results. This study can serve as a model for labs wishing to establish the appropriate low/medium aPL antibody threshold when implementing new aPL antibody assays.

  18. Prevalence and Correlates of Suspected Nonalcoholic Fatty Liver Disease in Chinese Children

    Directory of Open Access Journals (Sweden)

    Peige Song

    2017-04-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD has become a serious public health problem worldwide; however, the availability of information on the prevalence of NAFLD in the general pediatric population is still limited. The primary aim of this study was to reveal the prevalence and correlates of suspected NAFLD in Chinese children at the national level. Data from the China Health and Nutrition Surveys (CHNS was used. Weight, height, waist circumference (WC, blood pressure (BP were measured for children aged 7–18 years. Blood samples were collected and analyzed. Children were classified as having suspected NAFLD if common causes of liver disease were excluded, and serum alanine aminotransferase (ALT values were above the established thresholds (>22.1 IU/L for girls and >25.8 IU/L for boys. A percentage of 9.03% (75 out of 831 of Chinese children was found to have suspected NAFLD. Overweight and obesity according to BMI percentiles, abdominal obesity, hyperuricemia (uric acid (UA > 327 μmol/L, and elevated total cholesterol (TC were all detected as the correlates of childhood suspected NAFLD when adjusting for other factors. Our study revealed the prevalence of suspected NAFLD in general Chinese children at the national level for the first time. Our findings indicate that suspected NAFLD in children is associated with increasing childhood morbidities, further studies are needed to better understand the prevalence of childhood NAFLD and its correlates, and large-scale programs should be launched to screen NAFLD in the pediatric population in China.

  19. What does the antimitochondrial antibody mean?

    Science.gov (United States)

    Triger, D R; Charlton, C A; Ward, A M

    1982-01-01

    In a prospective survey positive antimitochondrial antibodies have been detected in 69/4200 (1.64%) of all sera submitted to a routine immunology laboratory. Of the 69, only nine patients had uniquivocal primary biliary cirrhosis, six others had chronic active hepatitis, 10 had abnormal liver function tests without evidence of primary biliary cirrhosis, while the remaining 44 had no clinical or biochemical evidence of liver disease. Outside the context of liver disease antimitochondrial antibodies were observed with similar frequency in patients with autoimmune disorders as in other conditions. It was not possible to distinguish primary biliary cirrhosis from patients without liver disease by antibody titre or by immunoglobulin subclass. The positive antimitochondrial antibody patients without liver disease were uniformly distributed throughout the city of Sheffield, in contrast with the marked clustering of cases of primary biliary cirrhosis. We conclude that, in the absence of clinical liver disease, the antimitochondrial antibody test alone (as detected by routine immunofluorescent techniques) does not appear to be a specific screening test for primary biliary cirrhosis. While we cannot exclude the possibility that the autoantibody indicates a predisposition to develop primary biliary cirrhosis, further prospective studies are needed to determine which patients will progress in this manner. The possibility that environmental factors may be implicated cannot be discounted. PMID:7117900

  20. Adrenoleukodystrophy: a forgotten diagnosis in children with primary Addison's disease.

    Science.gov (United States)

    Nascimento, Marta; Rodrigues, Nádia; Espada, Filipa; Fonseca, Marcelo

    2012-08-21

    The X linked adrenoleukodystrophy (X-ALD) is a peroxisomal disease caused by defects of the ABCD1 gene on chromosome Xq28 leading to accumulation of very long chain fatty acids (VLCFA), progressive demyelination and adrenal insufficiency. An 8-year-old boy was referred to our paediatric endocrinology clinic due to fatigue and hyperpigmentation with onset at 2-years old. Blood tests revealed mineralocorticoid insufficiency. Serum adrenocorticotropic hormone and cortisol concentrations were compatible with adrenal insufficiency. Adrenal antibodies were negative. The elevated plasmatic concentration of VLCFA and the genotype analysis with sequencing of ABCD1 gene established the diagnosis of X-ALD. Brain MRI showed demyelination of white matter in the peritrigonal regions. Steroid replacement was started with good response. He initiated restriction of VLCFA by reducing the intake of fatty foods. The authors highlight the importance of suspecting of X-ALD in the aetiology of primary adrenal insufficiency as the first sign of the disease.

  1. Adrenoleukodystrophy: a forgotten diagnosis in children with primary Addison's disease

    Science.gov (United States)

    Nascimento, Marta; Rodrigues, Nádia; Espada, Filipa; Fonseca, Marcelo

    2012-01-01

    The X linked adrenoleukodystrophy (X-ALD) is a peroxisomal disease caused by defects of the ABCD1 gene on chromosome Xq28 leading to accumulation of very long chain fatty acids (VLCFA), progressive demyelination and adrenal insufficiency. An 8-year-old boy was referred to our paediatric endocrinology clinic due to fatigue and hyperpigmentation with onset at 2-years old. Blood tests revealed mineralocorticoid insufficiency. Serum adrenocorticotropic hormone and cortisol concentrations were compatible with adrenal insufficiency. Adrenal antibodies were negative. The elevated plasmatic concentration of VLCFA and the genotype analysis with sequencing of ABCD1 gene established the diagnosis of X-ALD. Brain MRI showed demyelination of white matter in the peritrigonal regions. Steroid replacement was started with good response. He initiated restriction of VLCFA by reducing the intake of fatty foods. The authors highlight the importance of suspecting of X-ALD in the aetiology of primary adrenal insufficiency as the first sign of the disease. PMID:22914231

  2. Antibodies and Selection of Monoclonal Antibodies.

    Science.gov (United States)

    Hanack, Katja; Messerschmidt, Katrin; Listek, Martin

    Monoclonal antibodies are universal binding molecules with a high specificity for their target and are indispensable tools in research, diagnostics and therapy. The biotechnological generation of monoclonal antibodies was enabled by the hybridoma technology published in 1975 by Köhler and Milstein. Today monoclonal antibodies are used in a variety of applications as flow cytometry, magnetic cell sorting, immunoassays or therapeutic approaches. First step of the generation process is the immunization of the organism with appropriate antigen. After a positive immune response the spleen cells are isolated and fused with myeloma cells in order to generate stable, long-living antibody-producing cell lines - hybridoma cells. In the subsequent identification step the culture supernatants of all hybridoma cells are screened weekly for the production of the antibody of interest. Hybridoma cells producing the antibody of interest are cloned by limited dilution till a monoclonal hybridoma is found. This is a very time-consuming and laborious process and therefore different selection strategies were developed since 1975 in order to facilitate the generation of monoclonal antibodies. Apart from common automation of pipetting processes and ELISA testing there are some promising approaches to select the right monoclonal antibody very early in the process to reduce time and effort of the generation. In this chapter different selection strategies for antibody-producing hybridoma cells are presented and analysed regarding to their benefits compared to conventional limited dilution technology.

  3. MR enterography versus capsule endoscopy in paediatric patients with suspected Crohn's disease

    Energy Technology Data Exchange (ETDEWEB)

    Casciani, Emanuele; Masselli, Gabriele; Polettini, Elisabetta; Bertini, Luca; Gualdi, Gianfranco [University, Radiology DEA, Azienda Policlinico Umberto I, Rome (Italy); Di Nardo, Giovanni; Oliva, Salvatore; Cucchiara, Salvatore [University, Pediatric Gastroenterology, Rome (Italy); Floriani, Irene [Istituto di Ricerche Farmacologiche ' ' Mario Negri' ' , Milan (Italy)

    2011-04-15

    The aim of this prospective study was to compare the diagnostic yield of MR enterography (MRE) with small-bowel capsule endoscopy (SBCE) in paediatric patients with suspected Crohn's disease (CD). Paediatric patients with suspected CD were considered eligible to be enrolled in the study. All patients underwent diagnostic work-up including 1.5-T MRE, ileo-colonoscopy and oesophagogastroduodenoscopy. SBCE was not performed if MRE showed SB stricture or extra-intestinal findings consistent with symptoms. Sixty consecutive paediatric patients (36 male; average age 14) were enrolled into the study. A positive diagnosis for CD was made in 19 patients, 29 had a negative result and 12 were affected by other gastro-intestinal conditions. SBCE was performed in 37 patients (61.7%); 23 patients were excluded (strictures in five, extra-intestinal findings in 11 and parents' refusal in seven cases). The accuracy, sensitivity, and specificity of MRE and SBCE were 98.3%, 100%, 97.6%, and 91.9%, 90.9%, 92.3%, respectively. Both MRE and SBCE are accurate methods for patients with suspected CD. MRE can be used as a primary imaging technique in suspected CD, in that it allows access to the ileal stricture, which forms a contra-indication for SBCE and provides extra-intestinal information. (orig.)

  4. Study of topical corticosteroid response in glaucoma suspects and family members of established glaucoma patients

    Directory of Open Access Journals (Sweden)

    Jilani F

    1987-01-01

    Full Text Available The present study was conducted to study the topical steroid response in glaucoma suspects and family members of established glaucoma patients and its hereditary pattern The cases understudy were divided into three groups, namely normal (25 cases, suspected open angle glaucoma cases (20 and family members of established open angle glaucoma cases (33. After preliminary examination each patient was advised to put dexamethasone drop 1 % in one eye and a placebo in other eye. The IOP was noted after three weeks It was found that 80% of all eyes under study showed a rise in IOP after use of topical dexamethasone. The highest mean IOP was found in primary open angle glaucoma suspects, and the highest mean post-corticosteroid rise in IOP of 8.91 mm Hg was found among family members of established open angle glaucoma patients. The lOP response to topical corticosteroids was found to be of three phenotypical types viz., poor responders (nn, moderate responders (ng and high responders (gg. Normal subjects were generally poor responders. Suspected open angle glaucoma cases were generally high responders. However, family members of established open angle glaucoma cases showed the highest percentage of presence of responder gene.

  5. Mitochondrial DNA haplogroup background affects LHON, but not suspected LHON, in Chinese patients.

    Science.gov (United States)

    Zhang, A-Mei; Jia, Xiaoyun; Bi, Rui; Salas, Antonio; Li, Shiqiang; Xiao, Xueshan; Wang, Panfeng; Guo, Xiangming; Kong, Qing-Peng; Zhang, Qingjiong; Yao, Yong-Gang

    2011-01-01

    Recent studies have shown that mtDNA background could affect the clinical expression of Leber hereditary optic neuropathy (LHON). We analyzed the mitochondrial DNA (mtDNA) variation of 304 Chinese patients with m.11778G>A (sample #1) and of 843 suspected LHON patients who lack the three primary mutations (sample #2) to discern mtDNA haplogroup effect on disease onset. Haplogroup frequencies in the patient group was compared to frequencies in the general Han Chinese population (n = 1,689; sample #3). The overall matrilineal composition of the suspected LHON population resembles that of the general Han Chinese population, suggesting no association with mtDNA haplogroup. In contrast, analysis of these LHON patients confirms mtDNA haplogroup effect on LHON. Specifically, the LHON sample significantly differs from the general Han Chinese and suspected LHON populations by harboring an extremely lower frequency of haplogroup R9, in particular of its main sub-haplogroup F (#1 vs. #3, P-value = 1.46×10(-17), OR = 0.051, 95% CI: 0.016-0.162; #1 vs. #2, P-value = 4.44×10(-17), OR = 0.049, 95% CI: 0.015-0.154; in both cases, adjusted P-value LHON in Chinese patients with m.11778G>A but not suspected LHON. Haplogroup F has a protective effect against LHON, while M7b is a risk factor.

  6. Mitochondrial DNA haplogroup background affects LHON, but not suspected LHON, in Chinese patients.

    Directory of Open Access Journals (Sweden)

    A-Mei Zhang

    Full Text Available Recent studies have shown that mtDNA background could affect the clinical expression of Leber hereditary optic neuropathy (LHON. We analyzed the mitochondrial DNA (mtDNA variation of 304 Chinese patients with m.11778G>A (sample #1 and of 843 suspected LHON patients who lack the three primary mutations (sample #2 to discern mtDNA haplogroup effect on disease onset. Haplogroup frequencies in the patient group was compared to frequencies in the general Han Chinese population (n = 1,689; sample #3. The overall matrilineal composition of the suspected LHON population resembles that of the general Han Chinese population, suggesting no association with mtDNA haplogroup. In contrast, analysis of these LHON patients confirms mtDNA haplogroup effect on LHON. Specifically, the LHON sample significantly differs from the general Han Chinese and suspected LHON populations by harboring an extremely lower frequency of haplogroup R9, in particular of its main sub-haplogroup F (#1 vs. #3, P-value = 1.46×10(-17, OR = 0.051, 95% CI: 0.016-0.162; #1 vs. #2, P-value = 4.44×10(-17, OR = 0.049, 95% CI: 0.015-0.154; in both cases, adjusted P-value A but not suspected LHON. Haplogroup F has a protective effect against LHON, while M7b is a risk factor.

  7. PET/MR Outperforms PET/CT in Suspected Occult Tumors.

    Science.gov (United States)

    Sekine, Tetsuro; Barbosa, Felipe de Galiza; Sah, Bert-Ram; Mader, Cäcilia E; Delso, Gaspar; Burger, Irene A; Stolzmann, Paul; Ter Voert, Edwin E; von Schulthess, Gustav K; Veit-Haibach, Patrick; Huellner, Martin W

    2017-02-01

    To compare the diagnostic accuracy of PET/MR and PET/CT in patients with suspected occult primary tumors. This prospective study was approved by the institutional review board. Sequential PET/CT-MR was performed in 43 patients (22 male subjects; median age, 58 years; range, 20-86 years) referred for suspected occult primary tumors. Patients were assessed with PET/CT and PET/MR for the presence of a primary tumor, lymph node metastases, and distant metastases. Wilcoxon signed-rank test was performed to compare the diagnostic accuracy of PET/CT and PET/MR. According to the standard of reference, a primary lesion was found in 14 patients. In 16 patients, the primary lesion remained occult. In the remaining 13 patients, lesions proved to be benign. PET/MR was superior to PET/CT for primary tumor detection (sensitivity/specificity, 0.85/0.97 vs 0.69/0.73; P = 0.020) and comparable to PET/CT for the detection of lymph node metastases (sensitivity/specificity, 0.93/1.00 vs 0.93/0.93; P = 0.157) and distant metastases (sensitivity/specificity, 1.00/0.97 vs 0.82/1.00; P = 0.564). PET/CT tended to misclassify physiologic FDG uptake as malignancy compared with PET/MR (8 patients vs 1 patient). PET/MR outperforms PET/CT in the workup of suspected occult malignancies. PET/MR may replace PET/CT to improve clinical workflow.

  8. Antibody-mediated immune suppression is improved when blends of anti-RBC monoclonal antibodies are used in mice.

    Science.gov (United States)

    Bernardo, Lidice; Amash, Alaa; Marjoram, Danielle; Lazarus, Alan H

    2016-08-25

    Although the prevention of hemolytic disease of the fetus and newborn is highly effective using polyclonal anti-D, a recombinant alternative is long overdue. Unfortunately, anti-D monoclonal antibodies have been, at best, disappointing. To determine the primary attribute defining an optimal antibody, we assessed suppression of murine red blood cell (RBC) immunization by single-monoclonal antibodies vs defined blends of subtype-matched antibodies. Allogeneic RBCs expressing the HOD antigen (hen egg lysozyme [HEL]-ovalbumin-human transmembrane Duffy(b)) were transfused into naïve mice alone or together with selected combinations of HEL-specific antibodies, and the resulting suppressive effect was assessed by evaluating the antibody response. Polyclonal HEL antibodies dramatically inhibited the antibody response to the HOD antigen, whereas single-monoclonal HEL antibodies were less effective despite the use of saturating doses. A blend of monoclonal HEL-specific antibodies reactive with different HEL epitopes significantly increased the suppressive effect, whereas a blend of monoclonal antibodies that block each other's binding to the HEL protein did not increase suppression. In conclusion, these data show that polyclonal antibodies are superior to monoclonal antibodies at suppressing the immune response to the HOD cells, a feature that can be completely recapitulated using monoclonal antibodies to different epitopes. © 2016 by The American Society of Hematology.

  9. Etiology of maculopapular rash in measles and rubella suspected patients from Belarus.

    Directory of Open Access Journals (Sweden)

    Marina A Yermalovich

    Full Text Available As a result of successful implementation of the measles/rubella elimination program, the etiology of more and more double negative cases remains elusive. The present study determined the role of different viruses as causative agents in measles or rubella suspected cases in Belarus. A total of 856 sera sent to the WHO National Laboratory between 2009 and 2011 were tested for specific IgM antibodies to measles virus (MV, rubella virus (RV and human parvovirus B19 (B19V. The negatives were further investigated for antibodies to enterovirus (EV and adenovirus (AdV. Children of up to 3 years were tested for IgM antibodies to human herpesvirus 6 (HHV6. A viral etiology was identified in 451 (52.7% cases, with 6.1% of the samples being positive for MV; 2.6% for RV; 26.2% for B19V; 9.7% for EV; 4.6% for AdV; and 3.6% for HHV6. Almost all measles and rubella cases occurred during limited outbreaks in 2011 and nearly all patients were at least 15 years old. B19V, EV and AdV infections were prevalent both in children and adults and were found throughout the 3 years. B19V occurred mainly in 3-10 years old children and 20-29 years old adults. EV infection was most common in children up to 6 years of age and AdV was confirmed mainly in 3-6 years old children. HHV6 infection was mostly detected in 6-11 months old infants. Laboratory investigation of measles/rubella suspected cases also for B19V, EV, AdV and HHV6 allows diagnosing more than half of all cases, thus strengthening rash/fever disease surveillance in Belarus.

  10. Detection of Rabies antigen in brains of suspected Rabid dogs ...

    African Journals Online (AJOL)

    Objective: To detect the presence of rabies antigen in brains of suspected rabid dogs. Materials and Methods: Ninety six (96) brain specimens from suspected rabid dogs were examined for the presence of rabies antigen using Seller's staining technique and enzyme immunoassay. Results: The two techniques were both ...

  11. 48 CFR 803.806 - Processing suspected violations.

    Science.gov (United States)

    2010-10-01

    ... GENERAL IMPROPER BUSINESS PRACTICES AND PERSONAL CONFLICTS OF INTEREST Limitation on the Payment of Funds to Influence Federal Transactions 803.806 Processing suspected violations. A VA employee must report suspected violations of 31 U.S.C. 1352, Limitation on Use of Appropriated Funds to Influence Certain Federal...

  12. The clinical course of patients with suspected pulmonary embolism

    NARCIS (Netherlands)

    van Beek, E. J.; Kuijer, P. M.; Büller, H. R.; Brandjes, D. P.; Bossuyt, P. M.; ten Cate, J. W.

    1997-01-01

    BACKGROUND: The outcome of patients with suspected pulmonary embolism is known to a limited extent only. OBJECTIVE: To address this limited knowledge in a cohort in whom pulmonary embolism was proved or ruled out. METHODS: Consecutive patients with clinically suspected pulmonary embolism underwent

  13. The antibody approach of labeling blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1991-12-31

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated.

  14. The antibody approach of labeling blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1991-01-01

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated.

  15. The antibody approach of labeling blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1992-12-31

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are critically assessed and evaluated.

  16. Seasonal variation among tuberculosis suspects in four countries

    DEFF Research Database (Denmark)

    Mabaera, Biggie; Naranbat, Nymadawa; Katamba, Achilles

    2009-01-01

    The objective of the study was to analyze monthly trends across a calendar year in tuberculosis suspects and sputum smear-positive cases based on nationally representative samples of tuberculosis laboratory registers from Moldova, Mongolia, Uganda and Zimbabwe. Out of the 47 140 suspects registered...... in the tuberculosis laboratory registers, 13.4% (6312) were cases. The proportion varied from country to country, Moldova having the lowest (9%) and Uganda the highest (21%). From the monthly proportion of suspects and cases among total suspects and cases, seasonal variations were most marked in Mongolia which, among...... attendance to diagnostic laboratory services, evidenced by the contrasting findings of Mongolia (extreme continental northern climate) compared to Uganda (equatorial climate). A combination of external and possibly endogenous factors seems to determine whether tuberculosis suspects and cases present...

  17. Acetylcholine receptor antibody

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood ...

  18. Antinuclear antibody panel

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003535.htm Antinuclear antibody panel To use the sharing features on this page, please enable JavaScript. The antinuclear antibody panel is a blood test that looks at ...

  19. Platelet antibodies blood test

    Science.gov (United States)

    This blood test shows if you have antibodies against platelets in your blood. Platelets are a part of the blood ... Chernecky CC, Berger BJ. Platelet antibody - blood. In: Chernecky ... caused by platelet destruction, hypersplenism, or hemodilution. ...

  20. Suspected vitreous seeding of uveal melanoma: relevance of diagnostic vitrectomy.

    Science.gov (United States)

    Metz, Claudia H D; Bornfeld, Norbert; Metz, Klaus A; Gök, Mete

    2016-05-01

    To review all cases of suspected vitreous seeding of treated or untreated uveal melanoma at our clinic and to compare clinical, cytological and histological findings with patients' survival. Retrospective non-randomised study of 23 patients with consecutive uveal melanoma who underwent diagnostic vitrectomy in our clinic between January 2000 and November 2013. Reason for vitrectomy was suspected dissemination of tumour cells inside the eye. Treated as well as treatment-naïve primary uveal melanomas were included in this study. Follow-up data of all patients were collected. The study included 23 patients with a mean age of 66 years. Four patients presented pigmented vitreous debris at initial presentation prior to treatment of the uveal melanoma. All but one of these four patients has been enucleated as a consequence of cytology-proven vitreous spreading of vital melanoma cells. The remaining 19 patients presented pigmented vitreous debris at a mean of 60 months following local tumour treatment. Thirteen of these patients had been treated with a ruthenium plaque (mean scleral dose 1295 Gy, mean apex dose 152 Gy), three with binuclid plaque (mean scleral dose 1005 Gy, mean apex dose 70 Gy) and three with proton beam radiation. Of the 19 patients, 10 showed only melanophages in the vitreous specimen, while the remaining 9 patients had vital tumour cells in vitreous cytology. Four out of these nine patients have been enucleated in the course of follow-up. During follow-up of our cohort of 23 patients, 4 patients died, but only 1 of them due to metastatic disease. The outcome of this small cohort study shows that obtaining a vitreous specimen helps to distinguish melanophages from vital tumour cells. We could not observe an increased risk of metastasis in patients who showed melanoma cell dissemination inside the eye, compared with those patients only showing melanophages. We therefore suggest to carefully re-evaluate the necessity of enucleation in every

  1. MINOR HUMAN-ANTIBODY RESPONSE TO A MOUSE AND CHIMERIC MONOCLONAL-ANTIBODY AFTER A SINGLE IV INFUSION IN OVARIAN-CARCINOMA PATIENTS - A COMPARISON OF 5 ASSAYS

    NARCIS (Netherlands)

    BUIST, MR; KENEMANS, P; VANKAMP, GJ; Haisma, Hidde

    The human anti-(mouse Ig) antibody (HAMA) response was measured in serum of 52 patients suspected of having ovarian carcinoma who had received an i.v. injection of either the murine monoclonal antibody (mAb) OV-TL 3 F(ab')(2) (n = 28, 1 mg) or the chimeric mouse/human mAb MOv18 (cMOv18; n = 24, 3

  2. An Unusual Suspect Causing Hypoxemic Respiratory Failure

    Directory of Open Access Journals (Sweden)

    Masooma Aqeel MD

    2017-01-01

    Full Text Available Introduction: Antisynthetase syndrome (ASS is characterized by the presence of anti-Jo-1 antibodies in conjunction with clinical findings of fever, polymyositis-dermatomyositis, and interstitial lung disease (ILD. Inflammatory myopathies carry a high risk of malignancy, but this association is less well outlined in ASS. We present the case of a patient with ASS who developed non-Hodgkin’s lymphoma with acute hypoxemic respiratory failure. Case Presentation: A 44-year-old female with ASS presented with acute hypoxemic respiratory failure. She was empirically treated with broad-spectrum antibiotics for a health care–associated pneumonia; however, she failed to improve. Chest computed tomography revealed extensive bilateral ground glass opacities as well as extensive mediastinal and axillary lymphadenopathy. Infectious workup was negative. A surgical lung biopsy revealed peripheral T-cell lymphoma (PTCL. The patient was started on chemotherapy with complete resolution of hypoxemic respiratory failure. Conclusions: Malignancy is very rare in the setting of ASS; and our case illustrates the unique presentation of PTCL in ASS. In addition, lung involvement in PTCL is variable (incidence ranging from 8% to 20%; and in this case, bilateral multifocal consolidation was biopsied and proven to be PTCL involving the lungs. This case highlights the rare noninfectious conditions that can present as acute hypoxemic respiratory failure in the setting of ASS.

  3. Heavy chain only antibodies

    DEFF Research Database (Denmark)

    Moghimi, Seyed Moein; Rahbarizadeh, Fatemeh; Ahmadvand, Davoud

    2013-01-01

    Unlike conventional antibodies, heavy chain only antibodies derived from camel contain a single variable domain (VHH) and two constant domains (CH2 and CH3). Cloned and isolated VHHs possess unique properties that enable them to excel conventional therapeutic antibodies and their smaller antigen...

  4. Antibodies Against Melanin

    African Journals Online (AJOL)

    1973-01-06

    Jan 6, 1973 ... This study reports on unsuccessful attempts to produce antibodies against melanoprotein in rabbits. Available evidence suggests antibodies against melanocytes in the aetiology of vitiligo, but there is no convincing evidence for antibodies against melanin per se. It is suggested that the demonstration of ...

  5. Utilization of serology for the diagnosis of suspected Lyme borreliosis in Denmark: Survey of patients seen in general practice

    Directory of Open Access Journals (Sweden)

    Skarphedinsson Sigurdur

    2010-11-01

    Full Text Available Abstract Background Serological testing for Lyme borreliosis (LB is frequently requested by general practitioners for patients with a wide variety of symptoms. Methods A survey was performed in order to characterize test utilization and clinical features of patients investigated for serum antibodies to Borrelia burgdorferi sensu lato. During one calendar year a questionnaire was sent to the general practitioners who had ordered LB serology from patients in three Danish counties (population 1.5 million inhabitants. Testing was done with a commercial ELISA assay with purified flagella antigen from a Danish strain of B. afzelii. Results A total of 4,664 patients were tested. The IgM and IgG seropositivity rates were 9.2% and 3.3%, respectively. Questionnaires from 2,643 (57% patients were available for analysis. Erythema migrans (EM was suspected in 38% of patients, Lyme arthritis/disseminated disease in 23% and early neuroborreliosis in 13%. Age 0-15 years and suspected EM were significant predictors of IgM seropositivity, whereas suspected acrodermatitis was a predictor of IgG seropositivity. LB was suspected in 646 patients with arthritis, but only 2.3% were IgG seropositive. This is comparable to the level of seropositivity in the background population indicating that Lyme arthritis is a rare entity in Denmark, and the low pretest probability should alert general practitioners to the possibility of false positive LB serology. Significant predictors for treating the patient were a reported tick bite and suspected EM. Conclusions A detailed description of the utilization of serology for Lyme borreliosis with rates of seropositivity according to clinical symptoms is presented. Low rates of seropositivity in certain patient groups indicate a low pretest probability and there is a notable risk of false positive results. 38% of all patients tested were suspected of EM, although this is not a recommended indication due to a low sensitivity of

  6. Antibody-dependent enhancement of severe dengue disease in humans.

    Science.gov (United States)

    Katzelnick, Leah C; Gresh, Lionel; Halloran, M Elizabeth; Mercado, Juan Carlos; Kuan, Guillermina; Gordon, Aubree; Balmaseda, Angel; Harris, Eva

    2017-11-17

    For dengue viruses 1 to 4 (DENV1-4), a specific range of antibody titer has been shown to enhance viral replication in vitro and severe disease in animal models. Although suspected, such antibody-dependent enhancement of severe disease has not been shown to occur in humans. Using multiple statistical approaches to study a long-term pediatric cohort in Nicaragua, we show that risk of severe dengue disease is highest within a narrow range of preexisting anti-DENV antibody titers. By contrast, we observe protection from all symptomatic dengue disease at high antibody titers. Thus, immune correlates of severe dengue must be evaluated separately from correlates of protection against symptomatic disease. These results have implications for studies of dengue pathogenesis and for vaccine development, because enhancement, not just lack of protection, is of concern. Copyright © 2017, American Association for the Advancement of Science.

  7. Facing suspected child abuse – what keeps Swedish general practitioners from reporting to child protective services?

    Science.gov (United States)

    Bengtsson Boström, Kristina; Östberg, Anna-Lena

    2015-01-01

    Abstract Objective. The aim of this study was to examine the reporting of suspected child abuse among Swedish general practitioners (GPs), and to investigate factors influencing them in their decision whether or not to report to child protective services (CPS). Design. A cross-sectional questionnaire study. Setting. Primary health care centres in western Sweden. Subjects. 177 GPs and GP trainees. Main outcome measures. Demographic and educational background, education on child abuse, attitudes to reporting and CPS, previous experience of reporting suspected child abuse, and need of support. Results. Despite mandatory reporting, 20% of all physicians had at some point suspected but not reported child abuse. Main reasons for non-reporting were uncertainty about the suspicion and use of alternative strategies; for instance, referral to other health care providers or follow-up of the family by the treating physician. Only 30% of all physicians trusted CPS's methods of investigating and acting in cases of suspected child abuse, and 44% of all physicians would have wanted access to expert consultation. There were no differences in the failure to report suspected child abuse that could be attributed to GP characteristics. However, GPs educated abroad reported less frequently to CPS than GPs educated in Sweden. Conclusions. This study showed that GPs see a need for support from experts and that the communication and cooperation between GPs and CPS needs to be improved. The low frequency of reporting indicates a need for continued education of GPs and for updated guidelines including practical advice on how to manage child abuse. PMID:25676563

  8. Routine deferred computed tomography for patients with suspected urolithiasis is low-value healthcare.

    Science.gov (United States)

    Rosenlund, Ingvild M; Førde, Olav H; Revhaug, Arthur

    2017-02-01

    The aim of this study was to investigate the benefits of deferred routine computed tomography of the kidneys, ureters and bladder (CT KUB) for patients with a self-limiting episode of suspected urolithiasis. The study comprised a case series of consecutive patients examined with deferred routine CT KUB for control of suspected urolithiasis. Patients examined with CT KUB at the University Hospital of North Norway, between 1 January 2010 and 31 December 2013, were included. The final analysis included 189 CT KUBs (response rate 48%). All data were extracted from the patient case files. The primary endpoint was the proportion of asymptomatic patients with a confirmed diagnosis of urolithiasis on CT KUB that led to surgical intervention within 1 year from the initial CT scan. At the time of CT KUB, 171 patients (90%) were asymptomatic, of whom three (1.8%) were treated. Urolithiasis was confirmed on CT KUB in 23% of asymptomatic patients. Deferred CT KUB did not alter the clinical outcome for the great majority of asymptomatic patients. The majority of patients who received adequate pain relief in primary care remained asymptomatic, and did not need specialized healthcare. Refraining from CT KUB involves little risk. Deferred CT KUB for patients with suspected urolithiasis is a low-value healthcare service.

  9. [Rare differential diagnosis on suspected liver tumor].

    Science.gov (United States)

    Kinkel, B; Walgenbach-Brünagel, G; Risse, J H; Pauleit, D O

    2009-05-01

    This case report describes a 77-year old woman with a leiomyosarcoma of subhepatic inferior caval vein. The presented symptom was unspecific abdominal pain. Ultrasound and CT suggested a primary liver tumor. MRI revealed retroperitoneal location of the neoplasm. The tumor was resected completely and ICV was replaced by a PTF-graft. Vascular leiomyosarcoma is a rare tumor entity, which often is diagnosed in advanced stage. Depending on location it can be mistaken for neoplasms of other organs.

  10. Anti-HIV-1 antibody-dependent cellular cytotoxicity: is there more to antibodies than neutralization?

    Science.gov (United States)

    Lee, Wen Shi; Kent, Stephen J

    2017-11-30

    An increasing body of evidence suggests that nonneutralizing Fc effector functions including antibody-dependent cellular cytotoxicity (ADCC) contribute to protection against HIV-1 acquisition. We discuss recent advances in anti-HIV-1 ADCC research with a particular focus on ADCC mediated by Env-specific antibodies in vitro and in vivo, the curative potential of HIV-1-specific ADCC antibodies and the mechanisms of HIV-1 resistance to ADCC. ADCC activities of broadly neutralizing and nonneutralizing monoclonal antibody panels were recently characterized in vitro against several lab-adapted and primary isolates of HIV-1. ADCC activity of these monoclonal antibodies generally correlated with binding to infected cells and were greater against the lab-adapted strains compared with primary HIV-1 isolates. Several recent studies in mouse and macaque models of HIV-1 infection suggest Fc-mediated effector functions contribute to the protective efficacy of broadly neutralizing antibodies and exert immune pressure on HIV-1 in vivo. An increasing body of evidence suggests that ADCC-mediating antibodies, particularly when combined with neutralizing functions, can facilitate prevention and control of HIV-1. The precise mechanisms of partial protection conferred by nonneutralizing antibodies in vivo remain unclear and will need to be fully investigated in order to realize their full potential for HIV-1 vaccines.

  11. Diagnostic relevance and clinical significance of the new enhanced performance M2 (MIT3) ELISA for the detection of IgA and IgG antimitochondrial antibodies in primary biliary cirrhosis.

    Science.gov (United States)

    Gabeta, Stella; Norman, Gary L; Liaskos, Christos; Papamichalis, Panagiotis A; Zografos, Theodoros; Garagounis, Athanasios; Rigopoulou, Eirini I; Dalekos, George N

    2007-07-01

    Antimitochondrial antibodies (AMAs) are the serological hallmark of primary biliary cirrhosis (PBC). We evaluated the sensitivity and specificity of a new M2 enhanced performance enzyme-linked immunosorbent assay (ELISA) (MIT3) for the detection of IgG- and IgA-specific isotypes of AMA in PBC patients including a number of PBC patients negative for AMA by indirect immunofluorescence (IIF) as well as in patients with diverse, non-PBC disorders. We also investigated the clinical significance of IgG and IgA AMA in PBC. One hundred and three Greek PBC patients including 27 with AMA IIF-negative at the time of the investigation, 29 with autoimmune hepatitis-1 (AIH-1), 12 with primary sclerosing cholangitis (PSC), 26 with hepatitis C virus (HCV), 15 with hepatitis B virus (HBV), and 29 healthy were investigated for AMA (IgG and IgA) using the MIT3-based ELISAs (INOVA Diagnostics, San Diego, CA). The samples were also tested by conventional anti-M2 ELISA (INOVA Diagnostics, Inc.). The IgG MIT3-based ELISA significantly increased AMA detection in the cohort of PBC patients, over 26% of whom were AMA IIF-negative, from 63.1% by the conventional anti-M2, and 73.7% by IIF to 79.6% by MIT3-based ELISA (p<0.001). IgA AMAs were detected in 47.6% patients. Overall, IgG/IgA AMAs were detected in 84/103 (81.6%). IgG MIT3-based ELISA detected 12/27 IIF AMA-negative samples (44.4%), while IgG/IgA MIT3-based ELISAs detected 13/27 IIF AMA-negative patients (48.1%). The specificities of MIT3-based ELISAs (IgG and IgA) were 82.8% and 89.7%, respectively, in AIH-1, 100% and 93.3%, respectively, in HBV, 100% in PSC, and 96% and 93.3%, respectively, in HCV. Patients positive for IgG AMA had significantly more severe disease as shown by worse histology and elevated biochemical markers; IgG and IgA AMA titers were associated positively with the Mayo risk score but none of the isotypes were able to predict disease outcome. The new IgG and IgA MIT3-based ELISAs seem to have higher specificity

  12. Management of primary biliary cirrhosis

    NARCIS (Netherlands)

    Jansen, PLM; Farthing, MJG; Misiewicz, JJ

    1997-01-01

    Primary biliary cirrhosis is a slowly progressive cholestatic liver disease with autoimmune features. Antimitochondrial antibodies are detected in the serum of 95 percent of patients. The antibodies are directed against the E2 component of the pyruvate dyhydrogenase complex on the inner

  13. Effectiveness of a fluid chart in outpatient management of suspected dengue fever: A pilot study.

    Science.gov (United States)

    Nasir, Nazrila Hairin; Mohamad, Mohazmi; Lum, Lucy Chai See; Ng, Chirk Jenn

    2017-01-01

    Dengue infection is the fastest spreading mosquito-borne viral disease in the world. One of the complications of dengue is dehydration which, if not carefully monitored and treated, may lead to shock, particularly in those with dengue haemorrhagic fever. WHO has recommended oral fluid intake of five glasses or more for adults who are suspected to have dengue fever. However, there have been no published studies looking at self-care intervention measures to improve oral fluid intake among patients suspected of dengue fever. To assess the feasibility and effectiveness of using a fluid chart to improve oral fluid intake in patients with suspected dengue fever in a primary care setting. This feasibility study used a randomized controlled study design. The data was collected over two months at a primary care clinic in a teaching hospital. The inclusion criteria were: age > 12 years, patients who were suspected to have dengue fever based on the assessment by the primary healthcare clinician, fever for > three days, and thrombocytopenia (platelets chart and a cup (200ml). Baseline clinical and laboratory data, 24-hour fluid recall (control group), and fluid chart were collected. The main outcomes were: hospitalization rates, intravenous fluid requirement and total oral fluid intake. Among the 138 participants who were included in the final analysis, there were fewer hospital admissions in the intervention group (n = 7, 10.0%) than the control group (n = 12, 17.6%) (p = 0.192). Similarly, fewer patients (n = 9, 12.9%) in the intervention group required intravenous fluid compared to the control group (n = 15, 22.1%), (p = 0.154). There was an increase in the amount of daily oral fluid intake in the intervention group (about 3,000 ml) compared to the control group (about 2,500 ml, p = 0.521). However, these differences did not reach statistical significance. This is a feasible and acceptable study to perform in a primary care setting. The fluid chart is a simple, inexpensive

  14. Prediction of Suspect Location Based on Spatiotemporal Semantics

    Directory of Open Access Journals (Sweden)

    Lian Duan

    2017-06-01

    Full Text Available The prediction of suspect location enables proactive experiences for crime investigations and offers essential intelligence for crime prevention. However, existing studies have failed to capture the complex social location transition patterns of suspects and lack the capacity to address the issue of data sparsity. This paper proposes a novel location prediction model called CMoB (Crime Multi-order Bayes model based on the spatiotemporal semantics to enhance the prediction performance. In particular, the model groups suspects with similar spatiotemporal semantics as one target suspect. Then, their mobility data are applied to estimate Markov transition probabilities of unobserved locations based on a KDE (kernel density estimating smoothing method. Finally, by integrating the total transition probabilities, which are derived from the multi-order property of the Markov transition matrix, into a Bayesian-based formula, it is able to realize multi-step location prediction for the individual suspect. Experiments with the mobility dataset covering 210 suspects and their 18,754 location records from January to June 2012 in Wuhan City show that the proposed CMoB model significantly outperforms state-of-the-art algorithms for suspect location prediction in the context of data sparsity.

  15. Distinct Therapeutic Mechanisms of Tau Antibodies

    Science.gov (United States)

    Funk, Kristen E.; Mirbaha, Hilda; Jiang, Hong; Holtzman, David M.; Diamond, Marc I.

    2015-01-01

    Tauopathies are neurodegenerative diseases characterized by accumulation of Tau amyloids, and include Alzheimer disease and certain frontotemporal dementias. Trans-neuronal propagation of amyloid mediated by extracellular Tau may underlie disease progression. Consistent with this, active and passive vaccination studies in mouse models reduce pathology, although by unknown mechanisms. We previously reported that intracerebroventricular administration of three anti-Tau monoclonal antibodies (HJ8.5, HJ9.3, and HJ9.4) reduces pathology in a model overexpressing full-length mutant (P301S) human Tau. We now study effects of these three antibodies and a negative control antibody (HJ3.4) on Tau aggregate uptake into BV2 microglial-like cells and primary neurons. Antibody-independent Tau uptake into BV2 cells was blocked by heparin, consistent with a previously described role for heparan sulfate proteoglycans. Two therapeutic antibodies (HJ8.5 and HJ9.4) promoted uptake of full-length Tau fibrils into microglia via Fc receptors. Surprisingly, HJ9.3 promoted uptake of fibrils composed of the Tau repeat domain or Alzheimer disease-derived Tau aggregates, but failed to influence full-length recombinant Tau fibrils. Size fractionation of aggregates showed that antibodies preferentially promote uptake of larger oligomers (n ≥∼20-mer) versus smaller oligomers (n ∼10-mer) or monomer. No antibody inhibited uptake of full-length recombinant fibrils into primary neurons, but HJ9.3 blocked neuronal uptake of Tau repeat domain fibrils and Alzheimer disease-derived Tau. Antibodies thus have multiple potential mechanisms, including clearance via microglia and blockade of neuronal uptake. However these effects are epitope- and aggregate size-dependent. Establishing specific mechanisms of antibody activity in vitro may help in design and optimization of agents that are more effective in vivo. PMID:26126828

  16. Radioimmunoimaging of subacute infective endocarditis using a technetium-99m monoclonal granulocyte-specific antibody

    Energy Technology Data Exchange (ETDEWEB)

    Munz, D.L.; Sandrock, D.; Emrich, D. (Goettingen Univ. (Germany). Abt. fuer Nuklearmedizin); Morguet, A.J.; Heim, A.; Sold, G.; Figulla, H.R.; Kreuzer, H. (Goettingen Univ. (Germany). Abt. fuer Kardiologie und Pulmonologie)

    1991-12-01

    Immunoscintigraphy with a technetium-99m murine monoclonal IgG{sub 1} antibody directed against non-specific cross-reacting antigen (NCA-95) and carcinoembryonic antigen was performed with 20 patients with suspected subacute infective endocarditis (SIE) and 6 controls with suspected inflammatory/infectious disease elsewhere in the body. Immunoscintigraphy and echocardiography localised SIE in 11 of 15 patients in whom the disease could be confirmed. In 4 patients with validated SIE, the immunoscan was abnormal, and the echocardiogram was normal. In another 4 patients, the result was exactly the opposite. These findings suggest that the combination of immunoscintigraphy and echocardiography improves diagnostic efficacy in patients with suspected SIE. (orig.).

  17. [Serological Investigation of Toxoplasma gondii on Pregnant Women and Toxoplasmosis Suspected Patients Between 2012-2014 Years on a Tertiary Training Hospital].

    Science.gov (United States)

    Selek, Mehmet Burak; Bektöre, Bayhan; Baylan, Orhan; Özyurt, Mustafa

    2015-09-01

    Toxoplasmosis is a zoonotic disease which is still an important health issue in both developing and developed countries. We aimed to evaluate Toxoplasma gondii (T. gondii) seropositivity on toxoplasmosis suspected patients and pregnant women, retrospectively. Blood samples taken from toxoplasmosis suspected patients (n=1296) and pregnant women (1737) on our tertiary training hospital between 2012-2014 years. Anti-T. gondii IgG and IgM seropositivity analyzed with chemiluminescent microparticle immunological assay (CMIA) method. Also IgG avidity index were evaluated on patients who had both antibodies. Of 1269 toxoplasmosis suspected patients, 37% (n=479) had only T. gondii IgG positive while 1.9% (n=25) had both IgG and IgM antibodies. Of 1737 pregnant women, 24.2% (n=421) had only T. gondii IgG positive while 0.7% (n=13) of women were found positive for both antibodies. None of the total 3033 patients were seropositive for sole IgG antibody. Avidity tests were applied to the double positive patients and low avidity were detected on only one person from each group. Nationwide, high throughput, systemic seroprevalance studies is needed in order to take precautions for the public health to protect sensitive groups and pregnant women especially because of congenital toxoplasmosis risk.

  18. B Plant/WESF suspect/counterfeit parts identification program

    Energy Technology Data Exchange (ETDEWEB)

    Mertz, D.W.

    1996-01-12

    This document describes a suspect/counterfeit parts inspection program required by DOE conducted in accordance with Internal Memo 16710-94-DWM-048, J.A. O`Brien to J. N. Nansen, B Plant Suspect/ Counterfeit Parts Action Plan, dated May 24, 1994. The program included: physical inspection of all spare parts inventories within the plant; screening of installed B Plant/WESF (Waste Encapsulation and Storage Facility) systems for applications where the use and subsequent potential failure of suspect/counterfeit parts could have critical consequences; and a physical inspection based upon this screening.

  19. Antibody or Antibody Fragments: Implications for Molecular Imaging and Targeted Therapy of Solid Tumors

    Directory of Open Access Journals (Sweden)

    Katerina T. Xenaki

    2017-10-01

    Full Text Available The use of antibody-based therapeutics has proven very promising for clinical applications in cancer patients, with multiple examples of antibodies and antibody–drug conjugates successfully applied for the treatment of solid tumors and lymphomas. Given reported recurrence rates, improvements are clearly still necessary. A major factor limiting the efficacy of antibody-targeted cancer therapies may be the incomplete penetration of the antibody or antibody–drug conjugate into the tumor. Incomplete tumor penetration also affects the outcome of molecular imaging, when using such targeting agents. From the injection site until they arrive inside the tumor, targeting molecules are faced with several barriers that impact intratumoral distribution. The primary means of antibody transport inside tumors is based on diffusion. The diffusive penetration inside the tumor is influenced by both antibody properties, such as size and binding affinity, as well as tumor properties, such as microenvironment, vascularization, and targeted antigen availability. Engineering smaller antibody fragments has shown to improve the rate of tumor uptake and intratumoral distribution. However, it is often accompanied by more rapid clearance from the body and in several cases also by inherent destabilization and reduction of the binding affinity of the antibody. In this perspective, we discuss different cancer targeting approaches based on antibodies or their fragments. We carefully consider how their size and binding properties influence their intratumoral uptake and distribution, and how this may affect cancer imaging and therapy of solid tumors.

  20. The child with suspected hearing loss

    Directory of Open Access Journals (Sweden)

    Rajan P

    2013-10-01

    Full Text Available An 8-year-old girl was noticed by her parents to be less attentive and she would respond only after being called several times. She had just recovered from an upper respiratory tract infection two weeks before. The parents brought her to see a primary care physician. The patient had no other complaints, and the rest of the history was unremarkable. Physical examination was normal except for the otoscopic findings shown below (Figure 1 Tuning fork tests indicated conductive deafness.

  1. Computed tomography compared to magnetic resonance imaging in occult or suspect hip fractures. A retrospective study in 44 patients

    Energy Technology Data Exchange (ETDEWEB)

    Collin, David; Goethlin, Jan H. [Sahlgrenska University Hospital, Department of Radiology, Moelndal (Sweden); Geijer, Mats [Lund University, Department of Medical Imaging and Physiology, Skaane University Hospital, Lund (Sweden)

    2016-11-15

    Computed tomography (CT) for evaluation of occult and suspect hip fractures has been proposed as a good second-line investigation. The diagnostic precision compared to magnetic resonance imaging (MRI) is unclear. To compare the diagnostic performance of CT and MRI in a retrospective study on patients with suspect and occult hip fractures. Forty-four elderly consecutive patients with low-energy trauma to the hip were identified where negative or suspect CT was followed by MRI. Primary reporting and review by two observers as well as the diagnostic performance of the two modalities were compared. Surgical treatment and clinical course were used as outcomes. Compared to the primary reports, the CT reviewers found fewer normal and no suspect cases. MRI changed the primary diagnoses in 27 cases, and in 14 and 15 cases, respectively, at review. There was no disagreement on MRI diagnoses. In our patient population, MRI was deemed a more reliable modality for hip fracture diagnosis in comparison to CT. For clinical decision making, MRI seems to have a higher accuracy than CT. A negative CT finding cannot completely rule out a hip fracture in patients where clinical findings of hip fracture persevere. (orig.)

  2. Stopping and Questioning Suspected Shoplifters Without Creating Civil Liability

    Science.gov (United States)

    Reed, Jack R., Jr.

    1977-01-01

    Legal problems concerned with shoplifting suspects are addressed, including common law, criminal penalties, and the merchant's liability. Tangential questions and answers are presented along with discussion of pertinent court cases. (LBH)

  3. ALGORITHM OF MANAGEMENT OF PATIENTS WITH SUSPECTED BLUNT CARDIAC TRAUMA

    Directory of Open Access Journals (Sweden)

    S. R. Gilarevsky

    2013-01-01

    Full Text Available Abstract. Contemporary algorithm of diagnostic examination of patients with suspected blunt cardiac trauma is presented. General aspects of monitoring and treatment of such patients are also discussed. 

  4. Suspect confession of child sexual abuse to investigators.

    Science.gov (United States)

    Lippert, Tonya; Cross, Theodore P; Jones, Lisa; Walsh, Wendy

    2010-05-01

    Increasing the number of suspects who give true confessions of sexual abuse serves justice and reduces the burden of the criminal justice process on child victims. With data from four communities, this study examined confession rates and predictors of confession of child sexual abuse over the course of criminal investigations (final N = 282). Overall, 30% of suspects confessed partially or fully to the crime. This rate was consistent across the communities and is very similar to the rates of suspect confession of child sexual abuse found by previous research, although lower than that from a study focused on a community with a vigorous practice of polygraph testing. In a multivariate analysis, confession was more likely when suspects were younger and when more evidence of abuse was available, particularly child disclosure and corroborative evidence. These results suggest the difficulty of obtaining confession but also the value of methods that facilitate child disclosure and seek corroborative evidence, for increasing the odds of confession.

  5. [Characterisation of a monoclonal antibody against Trypanosoma evansi and its application for detecting circulating antibodies].

    Science.gov (United States)

    Monzón, C M

    2006-12-01

    Monoclonal antibodies were obtained against Trypanosoma evansi. The 2-4F6 IgM monoclonal antibody (Mab) was chosen for the study because of its ability to detect antigens and its specificity (as it did not recognise T. cruzi, T. equiperdum, Babesia equi or B. caballi). The immunoblot test revealed that the 2-4F6 IgM Mab recognises epitopes in two antigenic bands, one measuring 85 kDa and the other 122 kDa. An immunoassay for antigen detection in serum using polyclonal antibodies for capture, the Mab 2-4F6 as primary antibody and an antimouse IgM as secondary antibody gave positive results in 10 of the 11 equidae infected with T. evansi, whereas 20 controls gave negative results. These research results show that the Mab 2-4F6 and the antigen it recognises are useful in identifying equidae infected with T. evansi.

  6. Suspect aggression and victim resistance in multiple perpetrator rapes.

    Science.gov (United States)

    Woodhams, Jessica; Cooke, Claire

    2013-11-01

    Several research studies have reported an elevated level of aggression in rapes committed by multiple perpetrators compared to rapes committed by lone suspects. Several factors that have been linked to elevated aggression in generic samples of rape were examined for the first time with a sample of multiple perpetrator rapes. Factors that might be associated with victim resistance were also investigated. Victim and offender characteristics, as well as the behaviors displayed by victims and offenders, were extracted from the police files of 89 multiple perpetrator stranger rapes perpetrated against female victims in the United Kingdom. These behaviors were rated for their level of suspect (non-sexual) aggression and victim resistance, respectively. Degree of victim resistance was significantly and positively associated with suspect aggression. Older victims were the recipients of significantly higher levels of suspect aggression. Victims who were incapacitated from drugs and/or alcohol were less likely to be the recipients of suspect aggression. Group leaders displayed more aggression towards the victim than the followers in the groups. The number of perpetrators was significantly related to the degree of resistance displayed by the victim with offences perpetrated by fewer suspects being characterized by more victim resistance. Research regarding cognitive appraisal during criminal interactions and the respective roles of offenders is referred to in considering these relationships.

  7. Interviewing strategically to elicit admissions from guilty suspects.

    Science.gov (United States)

    Tekin, Serra; Granhag, Pär Anders; Strömwall, Leif; Giolla, Erik Mac; Vrij, Aldert; Hartwig, Maria

    2015-06-01

    In this article we introduce a novel interviewing tactic to elicit admissions from guilty suspects. By influencing the suspects' perception of the amount of evidence the interviewer holds against them, we aimed to shift the suspects' counterinterrogation strategies from less to more forthcoming. The proposed tactic (SUE-Confrontation) is a development of the Strategic Use of Evidence (SUE) framework and aims to affect the suspects' perception by confronting them with statement-evidence inconsistencies. Participants (N = 90) were asked to perform several mock criminal tasks before being interviewed using 1 of 3 interview techniques: (a) SUE-Confrontation, (b) Early Disclosure of Evidence, or (c) No Disclosure of Evidence. As predicted, the SUE-Confrontation interview generated more statement-evidence inconsistencies from suspects than the Early Disclosure interview. Importantly, suspects in the SUE-Confrontation condition (vs. Early and No disclosure conditions) admitted more self-incriminating information and also perceived the interviewer to have had more information about the critical phase of the crime (the phase where the interviewer lacked evidence). The findings show the adaptability of the SUE-technique and how it may be used as a tool for eliciting admissions. (c) 2015 APA, all rights reserved).

  8. ABO genotyping of suspects from sperm DNA isolated from postcoital samples in sex crimes.

    Science.gov (United States)

    Sasaki, M; Shiono, H

    1996-03-01

    In sexual assaults against women, one key to identifying the suspect is ABO phenotyping or the typing of other polymorphic markers of the seminal fluid in the victim's vagina. However, ABO phenotyping is frequently unsuccessful, since mixtures of fluids cannot be separated to be subjected to conventional methods for the detection of antibody or antigen material. We therefore studied ABO blood group genotyping of sperm DNA isolated from contaminating vaginal fluid by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Seminal samples of genotypes OO, AO, BO and AB were experimentally mixed with vaginal fluid (OO, AO, BO and AB), and were successfully separated and genotyped by this method. In practice, we also separated and genotyped the seminal DNA of suspects from contaminated postcoital vaginal fluid obtained in 4 sexual assaults. These forensic samples were easily separated and completely genotyped. This reliable ABO genotyping method by PCR-RFLP, using separated sperm DNA, should be of value in forensic identification in sexual assaults.

  9. Presumed prevalence analysis on suspected and highly suspected breast cancer lesions in São Paulo using BIRADS® criteria

    Directory of Open Access Journals (Sweden)

    Vivian Milani

    Full Text Available CONTEXT AND OBJECTIVE: Breast cancer screening programs are critical for early detection of breast cancer. Early detection is essential for diagnosing, treating and possibly curing breast cancer. Since there are no data on the incidence of breast cancer, nationally or regionally in Brazil, our aim was to assess women by means of mammography, to determine the prevalence of this disease. DESIGN AND SETTING: The study protocol was designed in collaboration between the Department of Diagnostic Imaging (DDI, Institute of Diagnostic Imaging (IDI and São Paulo Municipal Health Program. METHODS: A total of 139,945 Brazilian women were assessed by means of mammography between April 2002 and September 2004. Using the American College of Radiology (ACR criteria (Breast Imaging Reporting and Data System, BIRADS®, the prevalence of suspected and highly suspected breast lesions were determined. RESULTS: The prevalence of suspected (BIRADS® 4 and highly suspected (BIRADS® 5 lesions increased with age, especially after the fourth decade. Accordingly, BIRADS® 4 and BIRADS® 5 lesions were more prevalent in the fourth, fifth, sixth and seventh decades. CONCLUSION: The presumed prevalence of suspected and highly suspected breast cancer lesions in the population of São Paulo was 0.6% and it is similar to the prevalence of breast cancer observed in other populations.

  10. Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses

    Science.gov (United States)

    McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T.; Dennison, S. Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S. Munir; Haynes, Barton F.; Tomaras, Georgia D.

    2016-01-01

    Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine

  11. A Comparative Analysis of Polymerase Chain Reaction and Direct Fluorescent Antibody Test for Diagnosis of Genital Herpes.

    Science.gov (United States)

    Patwardhan, Vrushali; Bhalla, Preena; Rawat, Deepti; Garg, Vijay Kumar; Sardana, Kabir; Sethi, Sumit

    2017-01-01

    To compare laboratory tests that can simultaneously detect and type herpes simplex virus (HSV) directly from the genital ulcer specimens in clinically suspected cases of genital herpes. A study was conducted over 10 months and 44 adult male and female patients clinically suspected with genital herpes were recruited. Genital ulcer swab specimens were subjected to glycoprotein-G gene-based conventional polymerase chain reaction (PCR) and commercially available direct fluorescent antibody (DFA) test and the results were compared. PCR for HSV was positive in 82% (36/44) cases. DFA was positive in 68.2% (30/44) cases. There was 100% agreement between HSV types detected by DFA and PCR. The strength of agreement between the results was better in primary genital herpes than recurrent cases. PCR was found to be better in the detection of HSV in recurrent genital herpes patients. It is a better modality, especially when genital herpes clinically presents with ulcerative or crusted lesions, and is also a cheaper alternative as compared to DFA.

  12. When the Child is Suspected to Have Autism Spectrum Disorder: Recommendation for Parents

    Directory of Open Access Journals (Sweden)

    Borodina L.G.

    2015-12-01

    Full Text Available Experts in the area of treatment and intervention for autism spectrum disorders provide parents with recommenda¬tions for situations when their children are suspected to have autism or have been diagnosed. These recommenda¬tions are universal and are appropriate for raising a child with any spectrum disorder. Following these recommenda¬tions will allow parents to comprehend the situation with the child’s development, access approaches, that are used by professionals, and will help them to not waste precious time on finding primary information after the diagnosis.

  13. Autologous HIV-1 neutralizing antibodies: emergence of neutralization-resistant escape virus and subsequent development of escape virus neutralizing antibodies

    DEFF Research Database (Denmark)

    Arendrup, M; Nielsen, C; Hansen, J E

    1992-01-01

    of neutralizing antibodies to the primary virus isolates was detected 13-45 weeks after seroconversion. Emergence of escape virus with reduced sensitivity to neutralization by autologous sera was demonstrated. The patients subsequently developed neutralizing antibodies against the escape virus but after a delay...... escape virus may be part of the explanation of the apparent failure of the immune system to control HIV infection....

  14. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  15. Expression of recombinant Antibodies

    Directory of Open Access Journals (Sweden)

    André eFrenzel

    2013-07-01

    Full Text Available Recombinant antibodies are highly specific detection probes in research, diagnostics and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines and transgenic plants are promising to obtain antibodies with human-like post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications.

  16. Expression of Recombinant Antibodies

    Science.gov (United States)

    Frenzel, André; Hust, Michael; Schirrmann, Thomas

    2013-01-01

    Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines, and transgenic plants are promising to obtain antibodies with “human-like” post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications. PMID:23908655

  17. Molecular, serological and epidemiological observations after a suspected outbreak of plague in Nyimba, eastern Zambia.

    Science.gov (United States)

    Nyirenda, Stanley S; Hang'ombe, Bernard M; Kilonzo, Bukheti S; Kabeta, Mathews N; Cornellius, Mundia; Sinkala, Yona

    2017-01-01

    Plague is a re-emerging zoonotic disease caused by the bacterium Yersinia pestis. The disease has caused periodic global devastation since the first outbreak in the 6th century. Two months after a suspected plague outbreak in Nyimba district, samples were collected from 94 livestock (goats and pigs), 25 rodents, 6 shrews and 33 fleas. Enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) techniques were used to investigate the presence of Y. pestis, which showed that 16.0% (4/25) of rodents, 16.7% (1/6) of shrews (Crocidura spp) and 6.0% (5/83) of goats were positive for IgG antibodies against Fraction 1 antigen of Y. pestis. Plasminogen activator (Pla) gene (DNA) of Y. pestis was detected in five pools containing 36.4% (12/33) fleas collected from pigs (n = 4), goats (n = 5) and rodents (n = 3). The detection of Pla gene in fleas and IgG antibodies against Fraction1 antigen in rodents, shrews and goats suggest that Y. pestis had been present in the study area in the recent past. © The Author(s) 2016.

  18. Antibody persistence after a primary series of a new DTaP-IPV-Hep B-PRP-T combined vaccine or separate DTaP-IPV//PRP-T and hepatitis B vaccines at 2, 4, and 6 months of age and the effect of a subsequent DTaP-IPV//PRP-T booster vaccination at 18 months of age in healthy Argentinean infants.

    Science.gov (United States)

    Tregnaghi, Marcelo; Zambrano, Betzana; Santos-Lima, Eduardo

    2012-01-01

    To assess antibody persistence after vaccination with a new, fully liquid, hexavalent DTaP-IPV-Hep B-PRP-T vaccine at 18 months of age versus licensed DTaP-IPV//PRP-T and hepatitis B (Hep B) vaccines, and to assess the immunogenicity and safety of a subsequent DTaP-IPV//PRP-T booster. A phase III, open-label, single-center study was conducted. Infants previously primed with 3 doses of DTaP-IPV-Hep B-PRP-T (Hexaxim: N = 232 [group 1]) or DTaP-IPV//PRP-T and hepatitis B vaccine (Pentaxim + Engerix B Pediatrico: N = 226 [group 2]) at 2, 4, and 6 months of age received a DTaP-IPV//PRP-T booster at 18 months of age. Antibodies were measured before and 1 month after booster vaccination. Safety was evaluated from parental reports. Analyses were descriptive. Antibody persistence was high and similar in each group for each antigen except for Hep B, for which the percentage (95% confidence interval) of participants with a titer of ≥ 10 mIU/mL was higher in group 2 (99.5% [97.5%, 100.0%]) than in group 1 (85.5% [80.3%, 89.8%]). Postbooster seroprotection (diphtheria, tetanus, inactivated poliovirus, polyribosyl-ribitol phosphate) and serconversion (pertussis toxoid, filamentous hemagglutinin) rates were high and similar in each group, and geometric mean antibody concentrations increased markedly in both groups. Safety after the booster vaccination was good and independent of the primary-series vaccine, although one serious adverse event of convulsions was considered to be vaccine related. The DTaP-IPV/PRP-T booster vaccination at 18 months of age was similarly immunogenic and well tolerated after primary-series vaccination with either the investigational hexavalent vaccine or the reference pentavalent vaccine. This confirms the suitability of a booster vaccination of DTaP-IPV//PRP-T after a primary series of the new DTaP-IPV-Hep B-PRP-T vaccine.

  19. Hypertrophic Pulmonary Osteoarthropathy with Positive Antinuclear Antibodies: Case Report

    Directory of Open Access Journals (Sweden)

    C. Cruz

    2012-06-01

    Full Text Available A male Afro-descendant patient, 57 years old, complaining of polyarticular involvement and weight loss for 18 months, with a load of 13.5 pack years of smoking. On physical examination there was pain on palpation of the right knee and right leg, with signs of inflammation on the knee. We also observed digital clubbing in all fingers. Antinuclear antibodies (ANA and anti-Sm antibodies were positive. X-rays of the legs and arm showed cortical thickening of long bones. The computed tomography demonstrated a large mass located in the middle lobe of the right lung. The anatomopathological study revealed a bronchial adenocarcinoma. The history of polyarticular involvement associated with positive anti-Sm and ANA antibodies could lead to an erroneous diagnosis of systemic lupus erythematosus. Considering the bad consequences of delayed diagnosis in this patient, the medical team should be alerted for suspecting and look for a lung cancer under these circumstances.

  20. Anti-gliadin antibodies identify celiac patients overlooked by tissue transglutaminase antibodies.

    Science.gov (United States)

    Benson, Brian C; Mulder, Christopher J; Laczek, Jeffrey T

    2013-09-01

    For patients with suspected celiac disease, the American Gastroenterological Association recommends initial screening with anti-tissue transglutaminase antibody (tTG) and confirmation testing with small bowel biopsy. However, at Tripler Army Medical Center we routinely screen patients with both tTG and anti-gliadin antibodies (AGA) in combination. The purpose of this study was to evaluate whether this dual screening method adds to the evaluation of patients with suspected celiac disease or results in more false-positive results than tTG screening alone. A retrospective chart review of all tTG and AGA screening serologies at Tripler Army Medical Center between September 2008 and March 2012 was performed. For patients with positive serologic testing, small bowel biopsy results or reasoning for deferring biopsy were investigated. tTG was found to have a higher positive predictive value for celiac disease than AGA, however AGA identified 5 patients (19% of biopsy confirmed celiac disease) that had a negative tTG and would not have been identified by tTG screening alone. Using AGA in combination with tTG should be considered if the goal of screening is to identify all patients with celiac disease, with the understanding that this strategy will generate more false positive tests and result in additional patients undergoing small bowel biopsy.

  1. The use of psychoactive prescription drugs among DUI suspects.

    Science.gov (United States)

    Karjalainen, Karoliina; Haukka, Jari; Lintonen, Tomi; Joukamaa, Matti; Lillsunde, Pirjo

    2015-10-01

    The study seeks to increase understanding of the use of psychoactive prescription drugs among persons suspected of driving under the influence (DUI). We studied whether the use of prescribed psychoactive medication was associated with DUI, and examined the difference in the use of prescription drugs between DUI recidivists and those arrested only once. In this register-based study, persons suspected of DUI (n=29470) were drawn from the Register of DUI suspects, and an age- and gender-matched reference population (n=30043) was drawn from the Finnish general population. Data on prescription drug use was obtained by linkage to the National Prescription Register. The associations of DUI arrest and use of psychoactive prescription drugs in different DUI groups (findings for alcohol only, prescription drugs, prescription drugs and alcohol, illicit drugs) were estimated by using mixed-effect logistic regression. The use of psychoactive prescription drugs and DUI appeared to be strongly associated, with DUI suspects significantly more likely to use psychoactive prescription drugs compared to the reference population. Gender differences existed, with the use of benzodiazepines being more common among female DUI suspects. Moreover, DUI recidivists were more likely to use psychoactive prescription drugs compared to those arrested only once. In addition to alcohol and/or illicit drug use, a significant proportion of DUI suspects were using psychoactive prescription drugs. When prescribing psychoactive medication, especially benzodiazepines, physicians are challenged to screen for possible substance use problems and also to monitor for patients' alcohol or illicit drug use while being medicated. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Book Review: Placing the Suspect behind the Keyboard: Using Digital Forensics and Investigative Techniques to Identify Cybercrime Suspects

    Directory of Open Access Journals (Sweden)

    Thomas Nash

    2013-06-01

    Full Text Available Shavers, B. (2013. Placing the Suspect behind the Keyboard: Using Digital Forensics and Investigative Techniques to Identify Cybercrime Suspects. Waltham, MA: Elsevier, 290 pages, ISBN-978-1-59749-985-9, US$51.56. Includes bibliographical references and index.Reviewed by Detective Corporal Thomas Nash (tnash@bpdvt.org, Burlington Vermont Police Department, Internet Crime against Children Task Force. Adjunct Instructor, Champlain College, Burlington VT.In this must read for any aspiring novice cybercrime investigator as well as the seasoned professional computer guru alike, Brett Shaver takes the reader into the ever changing and dynamic world of Cybercrime investigation.  Shaver, an experienced criminal investigator, lays out the details and intricacies of a computer related crime investigation in a clear and concise manner in his new easy to read publication, Placing the Suspect behind the Keyboard. Using Digital Forensics and Investigative techniques to Identify Cybercrime Suspects. Shaver takes the reader from start to finish through each step of the investigative process in well organized and easy to follow sections, with real case file examples to reach the ultimate goal of any investigation: identifying the suspect and proving their guilt in the crime. Do not be fooled by the title. This excellent, easily accessible reference is beneficial to both criminal as well as civil investigations and should be in every investigator’s library regardless of their respective criminal or civil investigative responsibilities.(see PDF for full review

  3. Antibody engineering: methods and protocols

    National Research Council Canada - National Science Library

    Chames, Patrick

    2012-01-01

    "Antibody Engineering: Methods and Protocols, Second Edition was compiled to give complete and easy access to a variety of antibody engineering techniques, starting from the creation of antibody repertoires and efficient...

  4. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... You appear to have an allergic response to insulin Insulin no longer seems to control your diabetes

  5. Induction of labour for suspected macrosomia at term in non-diabetic women: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Magro-Malosso, E R; Saccone, G; Chen, M; Navathe, R; Di Tommaso, M; Berghella, V

    2017-02-01

    Several randomized controlled trials (RCTs) compared induction of labour with expectant management in non-diabetic women with suspected fetal macrosomia. To evaluate the effects of labour induction for suspected fetal macrosomia. Literature search in electronic databases. We included all RCTs of suspected fetal macrosomia comparing labour induction with expectant management in term pregnancy. The primary outcome was the incidence of caesarean delivery. Four RCTs, including 1190 non-diabetic women with suspected fetal macrosomia at term, were analysed. Pooled data did not show a significant difference in incidence of caesarean delivery [relative risk (RR) 0.91, 95% confidence interval (CI) 0.76-1.09], operative and spontaneous vaginal delivery, shoulder dystocia, intracranial haemorrhage, brachial plexus palsy, Apgar score macrosomia is associated with a significant decrease in fetal fractures, and therefore can be considered as a reasonable option. TWEETABLE ABSTRACT: #Induction of labour for #macrosomia improves neonatal outcome. © 2016 Royal College of Obstetricians and Gynaecologists.

  6. Primary Newcastle disease vaccination of broilers: comparison of the antibody seroresponse and adverse vaccinal reaction after eye-nose drop or coarse spray application, and implication of the results for a previously developed coarse dry powder vaccine.

    Science.gov (United States)

    Landman, W J M; Vervaet, C; Remon, J P; Huyge, K; van Eck, J H H

    2017-08-01

    To compare antibody seroresponse and adverse vaccinal reaction induced by Newcastle disease (ND) vaccination after eye-nose drop or coarse spray, groups of SPF broiler hens were vaccinated at day 4 (day of hatch is day 0) and intratracheally inoculated with Escherichia coli at day 11. Body weight gain (BWG) was assessed between day 4 and day 18; colibacillosis lesions and serum antibodies were determined at day 18. Meaningful comparison requires similar vaccine uptake. Vaccine virus loss during spray relative to eye-nose drop, which was assessed by comparing the results of endpoint titrations, was 3 log10. Colibacillosis lesions in birds spray vaccinated with 106.4 EID50/chicken were significantly more severe (P drop vaccinated with 103.4 EID50/chicken, while the seroresponse was slightly but significantly (P < 0.05) stronger. Colibacillosis lesion scores inversely paralleled BWG. It is concluded that: (1) There is room to improve the coarse ND vaccine spray used regarding adverse vaccinal reaction, while maintaining a sufficient immune response. This is also applicable to the coarse ND powder vaccine studied in previous research, which induced similar antibody response and adverse vaccinal reaction as the spray vaccine used here. (2) The vaccine virus dose influences the colibacillosis susceptibility at seven days post vaccination, as the dynamics of the vaccine virus infection is likely dose-dependent. (3) Low vaccine virus doses likely result in heterogeneous vaccine-take followed by vaccine virus spread from vaccine shedding birds to their non-vaccine virus infected flock mates ("rolling vaccinal reaction").

  7. Enzyme inhibition assay for pyruvate dehydrogenase complex: Clinical utility for the diagnosis of primary biliary cirrhosis

    Science.gov (United States)

    Omagari, Katsuhisa; Hazama, Hiroaki; Kohno, Shigeru

    2005-01-01

    Primary biliary cirrhosis (PBC) is usually diagnosed by the presence of characteristic histopathological features of the liver and/or antimitochondrial antibodies (AMA) in the serum traditionally detected by immunofluorescence. Recently, new and more accurate serological assays for the detection of AMA, such as enzyme-linked immunosorbent assay (ELISA), immunoblotting, and enzyme inhibition assay, have been developed. Of these, the enzyme inhibition assay for the detection of anti- pyruvate dehydrogenase complex (PDC) antibodies offers certain advantages such as objectivity, rapidity, simplicity, and low cost. Since this assay has almost 100% specificity, it may have particular applicability in screening the at-risk segment of the population in developing countries. Moreover, this assay could be also used for monitoring the disease course in PBC. Almost all sera of PBC-suspected patients can be confirmed for PBC or non-PBC by the combination results of immunoblotting and enzyme inhibition assay without histopathological examination. For the development of a “complete” or "gold standard" diagnostic assay for PBC, similar assays of the enzyme inhibition for anti-2-oxoglutarate dehydrogenase complex (OGDC) and anti-branched chain oxo-acid dehydrogenase complex (BCOADC) antibodies will be needed in future. PMID:16425376

  8. Fragmentation of monoclonal antibodies

    Science.gov (United States)

    Vlasak, Josef

    2011-01-01

    Fragmentation is a degradation pathway ubiquitously observed in proteins despite the remarkable stability of peptide bond; proteins differ only by how much and where cleavage occurs. The goal of this review is to summarize reports regarding the non-enzymatic fragmentation of the peptide backbone of monoclonal antibodies (mAbs). The sites in the polypeptide chain susceptible to fragmentation are determined by a multitude of factors. Insights are provided on the intimate chemical mechanisms that can make some bonds prone to cleavage due to the presence of specific side-chains. In addition to primary structure, the secondary, tertiary and quaternary structures have a significant impact in modulating the distribution of cleavage sites by altering local flexibility, accessibility to solvent or bringing in close proximity side chains that are remote in sequence. This review focuses on cleavage sites observed in the constant regions of mAbs, with special emphasis on hinge fragmentation. The mechanisms responsible for backbone cleavage are strongly dependent on pH and can be catalyzed by metals or radicals. The distribution of cleavage sites are different under acidic compared to basic conditions, with fragmentation rates exhibiting a minimum in the pH range 5–6; therefore, the overall fragmentation pattern observed for a mAb is a complex result of structural and solvent conditions. A critical review of the techniques used to monitor fragmentation is also presented; usually a compromise has to be made between a highly sensitive method with good fragment separation and the capability to identify the cleavage site. The effect of fragmentation on the function of a mAb must be evaluated on a case-by-case basis depending on whether cleavage sites are observed in the variable or constant regions, and on the mechanism of action of the molecule. PMID:21487244

  9. Suspected Rhinolithiasis Associated With Endodontic Disease in a Cat.

    Science.gov (United States)

    Ng, Kevin; Fiani, Nadine; Peralta, Santiago

    2017-12-01

    Rhinoliths are rare, intranasal, mineralized masses formed via the precipitation of mineral salts around an intranasal nidus. Clinical signs are typically consistent with inflammatory rhinitis and nasal obstruction, but asymptomatic cases are possible. Rhinoliths may be classified as exogenous or endogenous depending on the origin of the nidus, with endogenous rhinoliths reportedly being less common. This case report describes a suspected case of endogenous rhinolithiasis in a cat which was detected as an incidental finding during radiographic assessment of a maxillary canine tooth with endodontic disease. Treatment consisted of removal of the suspected rhinolith via a transalveolar approach after surgical extraction of the maxillary canine tooth.

  10. Cholescintigraphy and ultrasonography in patients suspected of having acute cholecystitis

    DEFF Research Database (Denmark)

    Lauritsen, K B; Sommer, W; Hahn, L

    1988-01-01

    The diagnostic power of combined cholescintigraphy and ultrasonography was tested in 67 patients suspected of having acute cholecystitis; of these, 42 (63%) had acute cholecystitis. The predictive value of a positive scintigraphy (PVpos) was 95% and that of a negative (PVneg) was 91% (n = 67...... that in patients suspected of having acute cholecystitis cholescintigraphy should be the first diagnostic procedure performed. If the scintigraphy is positive, additional ultrasonographic detection of gallstones makes the diagnosis almost certain. If one diagnostic modality is inconclusive, the other makes a fair...

  11. Symptomatic Patency Capsule Retention in Suspected Crohn's Disease

    DEFF Research Database (Denmark)

    Rasmussen, Bjørn; Nathan, Torben; Jensen, Michael Dam

    2016-01-01

    The main limitation of capsule endoscopy is the risk of capsule retention. In patients with suspected Crohn's disease, however, this complication is rare, and if a small bowel stenosis is not reliably excluded, small bowel patency can be confirmed with the Pillcam patency capsule. We present two...... patients examined for suspected Crohn's disease who experienced significant symptoms from a retained patency capsule. Both patients had Crohn's disease located in the terminal ileum. In one patient, the patency capsule caused abdominal pain and vomiting and was visualized at magnetic resonance enterography...

  12. Monoclonal antibody "gold rush".

    Science.gov (United States)

    Maggon, Krishan

    2007-01-01

    The market, sales and regulatory approval of new human medicines, during the past few years, indicates increasing number and share of new biologics and emergence of new multibillion dollar molecules. The global sale of monoclonal antibodies in 2006 were $20.6 billion. Remicade had annual sales gain of $1 billion during the past 3 years and five brands had similar increase in 2006. Rituxan with 2006 sales of $4.7 billion was the best selling monoclonal antibody and biological product and the 6th among the top selling medicinal brand. It may be the first biologic and monoclonal antibody to reach $10 billion annual sales in the near future. The strong demand from cancer and arthritis patients has surpassed almost all commercial market research reports and sales forecast. Seven monoclonal antibody brands in 2006 had sales exceeding $1 billion. Humanized or fully human monoclonal antibodies with low immunogenicity, enhanced antigen binding and reduced cellular toxicity provide better clinical efficacy. The higher technical and clinical success rate, overcoming of technical hurdles in large scale manufacturing, low cost of market entry and IND filing, use of fully human and humanized monoclonal antibodies has attracted funds and resources towards R&D. Review of industry research pipeline and sales data during the past 3 years indicate a real paradigm shift in industrial R&D from pharmaceutical to biologics and monoclonal antibodies. The antibody bandwagon has been joined by 200 companies with hundreds of new projects and targets and has attracted billions of dollars in R&D investment, acquisitions and licensing deals leading to the current Monoclonal Antibody Gold Rush.

  13. B cells contribute to MS pathogenesis through antibody-dependent and antibody-independent mechanisms

    Directory of Open Access Journals (Sweden)

    Wilson HL

    2012-05-01

    Full Text Available Heather L Wilson1,21Vaccine and Infectious Disease Organization-International Vaccine Center, 2Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan, CanadaAbstract: For many years, central dogma defined multiple sclerosis (MS as a T cell-driven autoimmune disorder; however, over the past decade there has been a burgeoning recognition that B cells contribute to the pathogenesis of certain MS disease subtypes. B cells may contribute to MS pathogenesis through production of autoantibodies (or antibodies directed at foreign bodies, which unfortunately cross-react with self-antigens, through promotion of T cell activation via antigen presentation, or through production of cytokines. This review highlights evidence for antibody-dependent and antibody-independent B cell involvement in MS pathogenesis.Keywords: autoantibodies, antibody targets, clinically isolated MS, primary progressive MS, secondary progressive MS, relapsing and remitting MS, T cells, T regulatory cells

  14. Comparative efficacy of antigen and antibody detection tests for human trichinellosis

    Energy Technology Data Exchange (ETDEWEB)

    Ivanoska, D.; Cuperlovic, K.; Gamble, H.R.; Murrell, K.D.

    1989-02-01

    Sera collected from patients with suspected or confirmed exposure to Trichinella spiralis were tested for circulating parasite antigens and antiparasite antibodies. Using an immunoradiometric assay, excretory--secretory antigens from muscle-stage larvae of T. spiralis were detected in the sera of 47% of 62 patients with clinical trichinellosis and 13% of 39 patients without clinical signs but suspected of exposure to infected meat. In comparison, antibodies were detected using an indirect immunofluorescent test in the circulation of 100% of the 62 patients with clinical trichinellosis and 46% of the 39 patients with suspected exposure. The presence of antibodies specific to excretory-secretory products of T. spiralis muscle larvae was confirmed in the majority of the samples tested by a monoclonal antibody-based competitive inhibition assay. These results indicate that antibody detection is a more sensitive diagnostic method for human trichinellosis, but that antigen detection might be a useful confirmatory test because it is a direct demonstration of parasite products in the circulation.

  15. Clinical correlation of antimitochondrial antibodies.

    Science.gov (United States)

    Zuber, M A; Recktenwald, C

    2003-02-21

    Antimitochondrial antibodies (AMA) are a hallmark of primary biliary cirrhosis (PBC). They are believed to be absolutely disease specific. It does occur that patients with positive AMA are diagnosed with PBC in the absence of liver specific signs and symptoms. The aim of the present study was to examine the disease spectrum of unselected AMA positive patients of an university hospital. All of the AMA tests performed in the immunological laboratory of the hospital between 1992 and 1998 were examined for positivity. 100 patients with a positive result were analyzed retrospectively for diagnosis, clinical and laboratory features. 61 patients suffered from liver diseases and 39 from non-liver diseases. The patients with liver diseases were 36 patients with PBC, 2 patients with PBC/PSC-overlap syndrome, 4 patients with autoimmune hepatitis and 19 patients with different liver diseases of other than autoimmune origin. The 39 patients with non-liver diseases included 9 patients with systemic autoimmune diseases, 3 patients with organ-specific autoimmune diseases, 8 patients with carcinoma and 19 patients with different diseases. 97 patients had an ELISA test for antibodies to the mitochondrial antigen M2 performed in addition to the immunofluorescence test for AMA. 73 patients had positive values for anti-M2 antibodies and 24 patients had negative results. Anti-M2 antibody values were divided in negative, low (5-100 U/ml), medium (101-1000 U/ml), high (1001-10000 U/ml) and very high (>10000 U/ml). Very high and high anti-M2 values were present mainly in patients with PBC and some patients with other liver diseases, medium high and low values in patients with different disease groups. In this unselected patient population only one third of AMA positive patients had an established diagnosis of PBC, about 10% a diagnosis of a systemic autoimmune disease and 3 % had other organ-specific autoimmune diseases. It can be concluded that, although high titers of antibodies against

  16. Molecular Dissection of the Human Antibody Response to the Structural Repeat Epitope of Plasmodium falciparum sporozoite from a Protected Donor

    National Research Council Canada - National Science Library

    Chappel, Jonathan A; Rogers, William O; Hoffman, Stephen L; Kang, Angray S

    2004-01-01

    The circumsporozoite surface protein is the primary target of human antibodies against Plasmodium falciparum sporozoites, these antibodies are predominantly directed to the major repetitive epitope (Asn-Pro-Asn-Ala)n, (NPNA)n...

  17. PMS2 Involvement in Patients Suspected of Lynch Syndrome

    NARCIS (Netherlands)

    Niessen, Renee C.; Kleibeuker, Jan H.; Westers, Helga; Jager, Paul O. J.; Rozeveld, Dennie; Bos, Krista K.; Boersma-van Ek, Wytske; Hollema, Harry; Sijmons, Rolf H.; Hofstra, Robert M. W.

    It is well-established that germline mutations in the mismatch repair genes MLH1, MSH2, and MSH6 cause Lynch syndrome. However, mutations in these three genes do not account for all Lynch syndrome (suspected) families. Recently, it was shown that germline mutations in another mismatch repair gene,

  18. Faecal Calprotectin in Suspected Paediatric Inflammatory Bowel Disease

    NARCIS (Netherlands)

    Degraeuwe, Pieter L. J.; Beld, Monique P. A.; Ashorn, Merja; Canani, Roberto Berni; Day, Andrew S.; Diamanti, Antonella; Fagerberg, Ulrika L.; Henderson, Paul; Kolho, Kaija-Leena; Van de Vijver, Els; van Rheenen, Patrick F.; Wilson, David C.; Kessels, Alfons G. H.

    Objectives: The diagnostic accuracy of faecal calprotectin (FC) concentration for paediatric inflammatory bowel disease (IBD) is well described at the population level, but not at the individual level. We reassessed the diagnostic accuracy of FC in children with suspected IBD and developed an

  19. Stabilization of the spine in patients with suspected cervical spine ...

    African Journals Online (AJOL)

    Stabilization of the spine in patients with suspected cervical spine injury in Mulago Hospital. BM Ndeleva, T Beyeza. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/eaoj.v5i1.67487 · AJOL African Journals ...

  20. Talking heads : interviewing suspects from a cultural perspective

    NARCIS (Netherlands)

    Beune, K.

    2009-01-01

    Although the literature on the interviewing of suspects has increased over the past decade, research on the use and effectiveness of police strategies and their boundary conditions is very rare. The present dissertation aims to fill this void by identifying behaviors that appeal to and persuade

  1. Nonreferral of Nursing Home Patients With Suspected Breast Cancer

    NARCIS (Netherlands)

    Hamaker, Marije E.; Hamelinck, Victoria C.; van Munster, Barbara C.; Bastiaannet, Esther; Smorenburg, Carolien H.; Achterberg, Wilco P.; Liefers, Gerrit-Jan; de Rooij, Sophia E.

    2012-01-01

    Introduction: People with suspected breast cancer who are not referred for diagnostic testing remain unregistered and are not included in cancer statistics. Little is known about the extent of and motivation for nonreferral of these patients. Methods: A Web-based survey was sent to all elderly care

  2. DNA typing from vaginal smear slides in suspected rape cases

    Directory of Open Access Journals (Sweden)

    Dayse Aparecida da Silva

    Full Text Available In an investigation of suspected rape, proof of sexual assault with penetration is required. In view of this, detailed descriptions of the genitalia, the thighs and pubic region are made within the forensic medical service. In addition, vaginal swabs are taken from the rape victim and some of the biological material collected is then transferred to glass slides. In this report, we describe two rape cases solved using DNA typing from cells recovered from vaginal smear slides. In 1999, two young women informed the Rio de Janeiro Police Department that they had been victims of sexual assaults. A suspect was arrested and the victims identified him as the offender. The suspect maintained that he was innocent. In order to elucidate these crimes, vaginal smear slides were sent to the DNA Diagnostic Laboratory for DNA analysis three months after the crimes, as unique forensic evidence. To get enough epithelial and sperm cells to perform DNA analysis, we used protocols modified from the previously standard protocols used for DNA extraction from biological material fixed on glass slides. The quantity of cells was sufficient to perform human DNA typing using nine short tandem repeat (STR loci. It was 3.3 billion times more probable that it was the examined suspect who had left sperm cells in the victims, rather than any other individual in the population of Rio de Janeiro.

  3. Cognitive Linguistic Performances of Multilingual University Students Suspected of Dyslexia

    Science.gov (United States)

    Lindgren, Signe-Anita; Laine, Matti

    2011-01-01

    High-performing adults with compensated dyslexia pose particular challenges to dyslexia diagnostics. We compared the performance of 20 multilingual Finnish university students with suspected dyslexia with 20 age-matched and education-matched controls on an extensive test battery. The battery tapped various aspects of reading, writing, word…

  4. Differential Diagnosis of Children with Suspected Childhood Apraxia of Speech

    Science.gov (United States)

    Murray, Elizabeth; McCabe, Patricia; Heard, Robert; Ballard, Kirrie J.

    2015-01-01

    Purpose: The gold standard for diagnosing childhood apraxia of speech (CAS) is expert judgment of perceptual features. The aim of this study was to identify a set of objective measures that differentiate CAS from other speech disorders. Method: Seventy-two children (4-12 years of age) diagnosed with suspected CAS by community speech-language…

  5. Is extended biopsy protocol justified in all patients with suspected ...

    African Journals Online (AJOL)

    Objective: To determine the significance of an extended 10-core transrectal biopsy protocol in different categories of patients with suspected prostate cancer using digital guidance. Materials and Methods: We studied 125 men who were being evaluated for prostate cancer. They all had an extended 10-core digitally guided ...

  6. Correlates and Suspected Causes of Obesity in Children

    Science.gov (United States)

    Crothers, Laura M.; Kehle, Thomas J.; Bray, Melissa A.; Theodore, Lea A.

    2009-01-01

    The correlates and suspected causes of the intractable condition obesity are complex and involve environmental and heritable, psychological and physical variables. Overall, the factors associated with and possible causes of it are not clearly understood. Although there exists some ambiguity in the research regarding the degree of happiness in…

  7. Medical Evaluation of Suspected Child Sexual Abuse: 2011 Update

    Science.gov (United States)

    Adams, Joyce A.

    2011-01-01

    The medical evaluation of children with suspected sexual abuse includes more than just the physical examination of the child. The importance of taking a detailed medical history from the parents and a history from the child about physical sensations following sexual contact has been emphasized in other articles in the medical literature. The…

  8. Selective screening in neonates suspected to have inborn errors of ...

    African Journals Online (AJOL)

    Background: Inborn errors of metabolism (IEM) have a high morbidity and mortality in neonates. Unfortunately, there is no nationwide neonatal screen in Egypt, so several cases may be missed. Objective: The aim of this work was to detect the prevalence of IEM among neonates with suspected IEM, and to diagnose IEM as ...

  9. Sexual Health Before Treatment in Women with Suspected Gynecologic Malignancy.

    Science.gov (United States)

    Bretschneider, C Emi; Doll, Kemi M; Bensen, Jeannette T; Gehrig, Paola A; Wu, Jennifer M; Geller, Elizabeth J

    2017-08-22

    Sexual health in survivors of gynecologic cancer has been studied; however, sexual health in these women before treatment has not been thoroughly evaluated. The objective of our study was to describe the pretreatment characteristics of sexual health of women with suspected gynecologic cancer before cancer treatment. We performed a cross-sectional analysis of women with a suspected gynecologic cancer, who were prospectively enrolled in a hospital-based cancer survivorship cohort from August 2012 to June 2013. Subjects completed the validated Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction Questionnaire. Pretreatment sexual health was assessed in terms of sexual interest, desire, lubrication, discomfort, orgasm, enjoyment, and satisfaction. Of 186 eligible women with suspected gynecologic cancer, 154 (82%) completed the questionnaire pretreatment. Mean age was 58.1 ± 13.3 years. Sexual health was poor: 68.3% reported no sexual activity, and 54.7% had no interest in sexual activity. When comparing our study population to the general U.S. population, the mean pretreatment scores for the subdomains of lubrication and vaginal discomfort were similar, while sexual interest was significantly lower and global satisfaction was higher. In a linear regression model, controlling for cancer site, age remained significantly associated with sexual function while cancer site did not. Problems with sexual health are prevalent in women with suspected gynecologic malignancies before cancer treatment. Increasing awareness of the importance of sexual health in this population will improve quality of life for these women.

  10. Use of budesonide Turbuhaler in young children suspected of asthma

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, S; Nikander, K

    1994-01-01

    The question addressed in this study was the ability of young children to use a dry-powder inhaler, Turbuhaler. One hundred and sixty five children suspected of asthma, equally distributed in one year age-groups from 6 months to 8 yrs, inhaled from a Pulmicort Turbuhaler, 200 micrograms budesonid...

  11. Doppler ultrasound in the assessment of suspected intra-uterine ...

    African Journals Online (AJOL)

    Ramakantb

    obesity with hypertension and non-insulin-dependent diabetes mellitus.[3] In this review, a brief discussion about the ultrasound diagnosis of suspected IUGR, and thereafter about the use of Doppler ultrasound in the diagnosis of IUGR, will be ... before that, all fetuses have relatively larger heads, which will mask the brain-.

  12. Candida meningitis in a suspected immunosuppressive patient - A ...

    African Journals Online (AJOL)

    Candida meningitis in a suspected immunosuppressive patient - A case report. EO Sanya, NB Ameen, BA Onile. Abstract. No Abstract. West African Journal of Medicine Vol. 25 (1) 2006: pp.79-81. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

  13. Ajmaline challenge in young individuals with suspected Brugada syndrome

    NARCIS (Netherlands)

    Sorgente, A.; Sarkozy, A.; Asmundis, C. de; Chierchia, G.B.; Capulzini, L.; Paparella, G.; Henkens, S.; Brugada, P.

    2011-01-01

    BACKGROUND: The clinical characteristics and the results of ajmaline challenge in young individuals with suspected Brugada syndrome (BS) have not been systematically investigated. METHODS: Among a larger series of patients included in the BS database of our Department, 179 patients undergoing

  14. A Diagnostic Program for Patients Suspected of Having Lung Cancer

    NARCIS (Netherlands)

    Stigt, Jos A.; Uil, Steven M.; Oostdijk, Ad H.; Boers, James E.; van den Berg, Jan-Willem K.; Groen, Harry J. M.

    2012-01-01

    In 297 patients suspected of having lung cancer, invasive diagnostic procedures followed positron emission tomography/computed tomography (PET-CT) on the same day. For patients with a diagnosis of malignancy (215/297), investigations were finalized on 1 day in 85%, and bronchoscopy was performed in

  15. Use of Chest Radiography In Patients Suspected of Pulmonary ...

    African Journals Online (AJOL)

    may be rushed into treatfng all cases of cough, fever and weight loss with negative sputums as PTB, and other diagnoses may be overlooked. A cheaper, quicker way of screening TB suspects would help con- siderably in this common problem. In Febuary 1991, the Norwegian Government do- nated two Odelka camer;l,s to ...

  16. Opioid analgesic administration in patients with suspected drug use.

    Science.gov (United States)

    Kreling, Maria Clara Giorio Dutra; Mattos-Pimenta, Cibele Andrucioli de

    2017-01-01

    To identify the prevalence of patients suspected of drug use according to the nursing professionals' judgement, and compare the behavior of these professionals in opioid administration when there is or there is no suspicion that patient is a drug user. A cross-sectional study with 507 patients and 199 nursing professionals responsible for administering drugs to these patients. The Chi-Square test, Fisher's Exact and a significance level of 5% were used for the analyzes. The prevalence of suspected patients was 6.7%. The prevalence ratio of administration of opioid analgesics 'if necessary' is twice higher among patients suspected of drug use compared to patients not suspected of drug use (p = 0.037). The prevalence of patients suspected of drug use was similar to that of studies performed in emergency departments. Patients suspected of drug use receive more opioids than patients not suspected of drug use. Identificar a prevalência de pacientes com suspeita de uso de drogas conforme opinião de profissionais de enfermagem e comparar a conduta desses profissionais na administração de opioides quando há ou não suspeita de que o paciente seja usuário de drogas. Estudo transversal com 507 pacientes e 199 profissionais de enfermagem responsáveis pela administração de medicamentos a esses pacientes. Para as análises foram utilizados os testes de Qui-Quadrado, Exato de Fisher e um nível de significância de 5%. A prevalência de pacientes suspeitos foi 6,7%. A razão de prevalência de administração de analgésicos opioides "se necessário" é duas vezes maior entre os pacientes suspeitos em relação aos não suspeitos (p=0,037). A prevalência de suspeitos foi semelhante à de estudos realizados em departamentos de emergência. Os suspeitos de serem usuários de drogas recebem mais opioides do que os não suspeitos.

  17. Antithyroid microsomal antibody

    Science.gov (United States)

    ... to confirm the cause of thyroid problems, including Hashimoto thyroiditis . The test is also used to find ... positive test may be due to: Granulomatous thyroiditis Hashimoto thyroiditis High levels of these antibodies have also ...

  18. Serum herpes simplex antibodies

    Science.gov (United States)

    ... causes cold sores (oral herpes). HSV-2 causes genital herpes. How the Test is Performed A blood sample ... person has ever been infected with oral or genital herpes . It looks for antibodies to herpes simplex virus ...

  19. ANA (Antinuclear Antibody Test)

    Science.gov (United States)

    ... Testing Leptin Levetiracetam Lipase Lipid Profile Lipoprotein (a) Lithium Liver Panel Lp-PLA2 Lupus Anticoagulant Testing Luteinizing ... Scleroderma Elsewhere On The Web Lupus Foundation of America American College of Rheumatology: Antinuclear Antibodies (ANA) American ...

  20. Anti-sulfotyrosine antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Bertozzi, Carolyn R [Berkeley, CA; Kehoe, John [Saint Davids, PA; Bradbury, Andrew M [Santa Fe, NM

    2009-09-15

    The invention provides anti-sulfotyrosine specific antibodies capable of detecting and isolating polypeptides that are tyrosine-sulfated. The sulfotyrosine antibodies and antibody fragments of the invention may be used to discriminate between the non-sulfated and sulfated forms of such proteins, using any number of immunological assays, such ELISAs, immunoblots, Western Blots, immunoprecipitations, and the like. Using a phage-display system, single chain antibodies (scFvs) were generated and screened against tyrosine-sulfated synthetic peptide antigens, resulting in the isolation of scFvs that specifically recognize sulfotyrosine-containing peptides and/or demonstrate sulfotyrosine-specific binding in tyrosine sulfated proteins. The VH and VL genes from one such sulfotyrosine-specific scFv were employed to generate a full length, sulfotyrosine-specific immunoglobulin.

  1. Antibody Blood Tests

    Science.gov (United States)

    Antibody Blood Tests Researchers have discovered that people with celiac disease who eat gluten have higher than normal levels of ... do I do if I have a negative blood test (or panel) but I’m still having symptoms? ...

  2. Magnetic resonance imaging versus bone scintigraphy in suspected scaphoid fracture

    Energy Technology Data Exchange (ETDEWEB)

    Tiel-van Buul, M.M.C. [Dept. of Nuclear Medicine, Academic Medical Center, Univ. of Amsterdam (Netherlands); Roolker, W. [Dept. of Nuclear Medicine, Academic Medical Center, Univ. of Amsterdam (Netherlands); Verbeeten, B.W.B. Jr. [Dept. of Radiology, Academic Medical Center, Univ. of Amsterdam (Netherlands); Broekhuizen, A.H. [Dept. of Traumatology, Academic Medical Center, Univ. of Amsredam (Netherlands)

    1996-08-01

    Magnetic resonance imaging (MRI) has become increasingly useful in the evaluation of musculoskeletal problems, including those of the wrist. In patients with a wrist injury, MRI is used mainly to assess vascularity of scaphoid non-union. However, the use of MRI in patients in the acute phase following carpal injury is not common. Three-phase bone scintigraphy is routinely performed from at least 72 h after injury in patients with suspected scaphoid fracture and negative initial radiographs. We evaluated MRI in this patient group. The bone scan was used as the reference method. Nineteen patients were included. Bone scintigraphy was performed in all 19 patients, but MRI could be obtained in only 16 (in three patients, MRI was stopped owing to claustrophobia). In five patients, MRI confirmed a scintigraphically suspected scaphoid fracture. In one patient, a perilunar luxation, without a fracture, was seen on MRI, while bone scintigraphy showed a hot spot in the region of the lunate bone, suspected for fracture. This was confirmed by surgery. In two patients, a hot spot in the scaphoid region was suspected for scaphoid fracture, and immobilization and employed for a period of 12 weeks. MRI was negative in both cases; in one of them a scaphoid fracture was retrospectively proven on the initial X-ray series. In another two patients, a hot spot in the region of MCP I was found with a negative MRI. In both, the therapy was adjusted. In the remaining six patients, both modalities were negative. We conclude that in the diagnostic management of patients with suspected scaphoid fracture and negative initial radiographs, the use of MRI may be promising, but is not superior to three-phase bone scintigraphy. (orig.)

  3. Expression of Recombinant Antibodies

    OpenAIRE

    André eFrenzel; Michael eHust; Thomas eSchirrmann

    2013-01-01

    Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transg...

  4. Specificity of anti-phospholipid antibodies in infectious mononucleosis: a role for anti-cofactor protein antibodies

    Science.gov (United States)

    Sorice, M; Pittoni, V; Griggi, T; Losardo, A; Leri, O; Magno, M S; Misasi, R; Valesini, G

    2000-01-01

    The antigen specificity of anti-phospholipid antibodies in infectious mononucleosis (IM) was studied using ELISA for the detection of anti-β2-glycoprotein I (β2-GPI), anti-annexin V, anti-protein S and anti-prothrombin antibodies and TLC immunostaining for the detection of anti-phospholipid antibodies. This technique enabled us to look at antibodies reacting to ‘pure’ phospholipid antigens in the absence of protein contamination. Sera from 46 patients with IM, 18 with systemic lupus erythematosus (SLE), 21 with primary anti-phospholipid antibody syndrome (PAPS), 50 with Helicobacter pylori infection and 30 healthy blood donors were tested. This study highlights anti-phospholipid antibodies in patients with IM as specific ‘pure’ anti-cardiolipin antibodies, while in PAPS and SLE patients anti-phosphatidylserine and anti-phosphatidylethanolamine antibodies were also found. This investigation also shows that the anti-cardiolipin antibodies found in IM can be present with anti-cofactor protein antibodies. The higher prevalence of anti-cofactor antibodies found in IM sera than in Helicobacter pylori sera may be due to the immunostimulatory effect and/or the polyclonal activation often observed in course of Epstein–Barr virus infection. However, anti-β2-GPI and, to a lesser extent, anti-prothrombin antibodies occur with a significantly lower prevalence in IM than in PAPS patients. This finding suggests that these antibodies should be regarded as the expression of the broad autoimmune syndrome involving the phospholipid-binding plasma proteins. PMID:10792380

  5. Warm antibody autoimmune hemolytic anemia.

    Science.gov (United States)

    Kalfa, Theodosia A

    2016-12-02

    Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disease that affects 1 to 3/100 000 patients per year. AIHA caused by warm autoantibodies (w-AIHA), ie, antibodies that react with their antigens on the red blood cell optimally at 37°C, is the most common type, comprising ∼70% to 80% of all adult cases and ∼50% of pediatric cases. About half of the w-AIHA cases are called primary because no specific etiology can be found, whereas the rest are secondary to other recognizable underlying disorders. This review will focus on the postulated immunopathogenetic mechanisms in idiopathic and secondary w-AIHA and report on the rare cases of direct antiglobulin test-negative AIHA, which are even more likely to be fatal because of inherent characteristics of the causative antibodies, as well as because of delays in diagnosis and initiation of appropriate treatment. Then, the characteristics of w-AIHA associated with genetically defined immune dysregulation disorders and special considerations on its management will be discussed. Finally, the standard treatment options and newer therapeutic approaches for this chronic autoimmune blood disorder will be reviewed. © 2016 by The American Society of Hematology. All rights reserved.

  6. Peripapillary retinal splitting visualized on OCT in glaucoma and glaucoma suspect patients.

    Directory of Open Access Journals (Sweden)

    Dilraj S Grewal

    Full Text Available To identify the risk factors for development of peripapillary retinal splitting (schisis in patients with glaucoma or suspicion of glaucoma.Glaucoma Clinic, Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, IL.In this institutional cross-sectional study, 495 patients (990 eyes who had undergone spectral-domain optical coherence tomography (OCT Spectralis HRA-OCT, Heidelberg Engineering optic nerve head (ONH imaging and did not have identifiable optic nerve pits, pseudopits or coloboma were included. OCT scans were reviewed by two observers.Presence of peripapillary retinal splitting identified on OCT raster scans.Eleven of 990 glaucoma and glaucoma suspect eyes (1.1% of 7 patients (2 females, 5 males, mean age 64.5 ± 9.2 years had peripapillary retinal splitting. Two of these 11 eyes had extension of the splitting into the macula but none to the fovea. Of these 11 patients, 2 (28.6% were glaucoma suspects, 3 (42.9% had primary open-angle glaucoma, 1 (14.3% had chronic angle-closure glaucoma and 1 (14.3% had pigmentary glaucoma. 7/11 (63.6% eyes had vitreous traction to the disc visualized on OCT and 6/11 eyes (54.5% had beta-zone peripapillary atrophy.We observed peripapillary retinal splitting in 1.1% of a series of 990 glaucoma and glaucoma-suspect eyes. Evidence of adherent vitreous with traction and peripapillary atrophy was found in a majority of the involved eyes. A comparison to an age and axial length matched cohort is required to determine if this is a condition that is associated with glaucoma.

  7. Rivaroxaban for treatment of suspected or confirmed heparin-induced thrombocytopenia study.

    Science.gov (United States)

    Linkins, L A; Warkentin, T E; Pai, M; Shivakumar, S; Manji, R A; Wells, P S; Wu, C; Nazi, I; Crowther, M A

    2016-06-01

    Essentials Heparin-induced thrombocytopenia (HIT) is a thrombogenic condition that is difficult to treat. We evaluated rivaroxaban as a treatment option in patients with suspected or confirmed HIT. One patient had recurrent thrombosis and 9/10 patients with thrombocytopenia had platelet recovery. Rivaroxaban may be an effective and safe treatment option for HIT. Background Rivaroxaban is a direct oral anti-Xa inhibitor that has the potential to greatly simplify treatment of heparin-induced thrombocytopenia (HIT). Objectives To evaluate the efficacy and safety of rivaroxaban in this patient population, we conducted a multicenter, single-arm, prospective cohort study of patients with suspected or confirmed HIT. Patients/Methods Twenty-two consecutive adults with suspected or confirmed HIT received rivaroxaban 15 mg bid until a local HIT assay result was available. Participants with a positive local assay result continued rivaroxaban 15 mg bid until platelet recovery (or until day 21 if they had acute thrombosis at study entry), then stepped down to rivaroxaban 20 mg daily until day 30. Results and Conclusions The primary outcome measure, incidence of new symptomatic, objectively-confirmed venous and arterial thromboembolism at 30 days, occurred in one HIT-positive participant (4.5%; 95% confidence interval [CI], 0-23.5%) and one HIT-positive participant required limb amputation despite platelet recovery. Platelet recovery was achieved in nine out of 10 HIT-positive patients with thrombocytopenia. Rivaroxaban appears to be effective for treating patients with confirmed HIT, although the small number of patients enrolled limits precision. © 2016 International Society on Thrombosis and Haemostasis.

  8. Medical History for Prognostic Risk Assessment and Diagnosis of Stable Patients with Suspected Coronary Artery Disease

    Science.gov (United States)

    Min, James K.; Dunning, Allison; Gransar, Heidi; Achenbach, Stephan; Lin, Fay Y.; Al-Mallah, Mouaz; Budoff, Matthew J.; Callister, Tracy Q.; Chang, Hyuk-Jae; Cademartiri, Filippo; Chinnaiyan, Kavitha; Chow, Benjamin J. W.; D’Agostino, Ralph; DeLago, Augustin; Friedman, John; Hadamitzky, Martin; Hausleiter, Joerg; Hayes, Sean; Kaufmann, Philipp; Raff, Gilbert L.; Shaw, Leslee J.; Thomson, Louise; Villines, Todd; Cury, Ricardo C.; Feuchtner, Gudrun; Kim, Yong-Jin; Leipsic, Jonathon; Berman, Daniel S.; Pencina, Michael

    2014-01-01

    Aims To develop a clinical cardiac risk algorithm for stable patients with suspected CAD based upon angina typicality and CAD risk factors. Methods and Results Between 2004 and 2011, 14,004 adults with suspected CAD referred for cardiac imaging were followed: 1) 9,093 patients for CCTA (CCTA-1) followed for 2.0 years; 2) 2,132 patients for CCTA (CCTA-2) followed for 1·6 years, and 3) 2,779 patients for exercise myocardial perfusion scintigraphy followed for 5.0 years. A best-fit model from CCTA-1 for prediction of death or myocardial infarction (MI) was developed, with integer values proportional to regression coefficients. Discrimination was assessed using C-statistic. The validated model was also tested for estimation of the likelihood of obstructive CAD, defined as ≥50% stenosis, as compared to method of Diamond and Forrester (D-F). Primary outcomes included all-cause mortality and non-fatal MI. Secondary outcomes included prevalence of angiographically obstructive CAD. In CCTA-1, best-fit model discriminated individuals at risk of death or MI (C-statistic 0·76). The integer model ranged from 3-13, and corresponded to 3-year death risk or MI of 0·25% to 53·8%. When applied to the CCTA-2 and MPS, the model demonstrated C-statistics of 0·71 and 0·77. Both best-fit (C=0·76, 95% CI 0·746-0·771) and integer model (C=0·71, 95% CI 0·693-0·719) performed better than D-F (C=0·64; 95% CI, 0·628-0·659) for estimating obstructive CAD. Conclusions For stable symptomatic patients with suspected CAD, we developed a history-based method for prediction of death and obstructive CAD. PMID:25865923

  9. Peripapillary retinal splitting visualized on OCT in glaucoma and glaucoma suspect patients.

    Science.gov (United States)

    Grewal, Dilraj S; Merlau, Daniel J; Giri, Pushpanjali; Munk, Marion R; Fawzi, Amani A; Jampol, Lee M; Tanna, Angelo P

    2017-01-01

    To identify the risk factors for development of peripapillary retinal splitting (schisis) in patients with glaucoma or suspicion of glaucoma. Glaucoma Clinic, Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, IL. In this institutional cross-sectional study, 495 patients (990 eyes) who had undergone spectral-domain optical coherence tomography (OCT Spectralis HRA-OCT, Heidelberg Engineering) optic nerve head (ONH) imaging and did not have identifiable optic nerve pits, pseudopits or coloboma were included. OCT scans were reviewed by two observers. Presence of peripapillary retinal splitting identified on OCT raster scans. Eleven of 990 glaucoma and glaucoma suspect eyes (1.1%) of 7 patients (2 females, 5 males, mean age 64.5 ± 9.2 years) had peripapillary retinal splitting. Two of these 11 eyes had extension of the splitting into the macula but none to the fovea. Of these 11 patients, 2 (28.6%) were glaucoma suspects, 3 (42.9%) had primary open-angle glaucoma, 1 (14.3%) had chronic angle-closure glaucoma and 1 (14.3%) had pigmentary glaucoma. 7/11 (63.6%) eyes had vitreous traction to the disc visualized on OCT and 6/11 eyes (54.5%) had beta-zone peripapillary atrophy. We observed peripapillary retinal splitting in 1.1% of a series of 990 glaucoma and glaucoma-suspect eyes. Evidence of adherent vitreous with traction and peripapillary atrophy was found in a majority of the involved eyes. A comparison to an age and axial length matched cohort is required to determine if this is a condition that is associated with glaucoma.

  10. Primary biliary cirrhosis.

    Science.gov (United States)

    Carey, Elizabeth J; Ali, Ahmad H; Lindor, Keith D

    2015-10-17

    Primary biliary cirrhosis is a chronic cholestatic liver disease characterised by destruction of small intrahepatic bile ducts, leading to fibrosis and potential cirrhosis through resulting complications. The serological hallmark of primary biliary cirrhosis is the antimitochondrial antibody, a highly disease-specific antibody identified in about 95% of patients with primary biliary cirrhosis. These patients usually have fatigue and pruritus, both of which occur independently of disease severity. The typical course of primary biliary cirrhosis has changed substantially with the introduöction of ursodeoxycholic acid (UDCA). Several randomised placebo-controlled studies have shown that UDCA improves transplant-free survival in primary biliary cirrhosis. However, about 40% of patients do not have a biochemical response to UDCA and would benefit from new therapies. Liver transplantation is a life-saving surgery with excellent outcomes for those with decompensated cirrhosis. Meanwhile, research on nuclear receptor hormones has led to the development of exciting new potential treatments. This Seminar will review the current understanding of the epidemiology, pathogenesis, and natural history of primary biliary cirrhosis, discuss management of the disease and its sequelae, and introduce research on new therapeutic options. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Natural and Man-made Antibody Repertories for Antibody Discovery

    Directory of Open Access Journals (Sweden)

    Juan C eAlmagro

    2012-11-01

    Full Text Available Antibodies are the fastest-growing segment of the biologics market. The success of antibody-based drugs resides in their exquisite specificity, high potency, stability, solubility, safety and relatively inexpensive manufacturing process in comparison with other biologics. We outline here the structural studies and fundamental principles that define how antibodies interact with diverse targets. We also describe the antibody repertoires and affinity maturation mechanisms of human, mice and chickens, plus the use of novel single-domain antibodies in camelids and sharks. These species all utilize diverse evolutionary solutions to generate specific and high affinity antibodies and illustrate the plasticity of natural antibody repertoires. In addition, we discuss the multiple variations of man-made antibody repertoires designed and validated in the last two decades, which have served as tools to explore how the size, diversity and composition of a repertoire impact the antibody discovery process.

  12. A rational clinical approach to suspected insulin allergy

    DEFF Research Database (Denmark)

    Bødtger, Uffe; Wittrup, M

    2005-01-01

    AIMS: Allergy to recombinant human (rDNA) insulin preparations is a rare complication of insulin therapy. However, insulin preparations contain several allergens, and several disorders can resemble insulin allergy. Studies evaluating the diagnostic procedures on suspected insulin allergy...... technique (n = 5), skin disease (n = 3) and other systemic allergy (n = 1). Nine other patients were found to be allergic to protamine (n = 3) or rDNA insulin (n = 6), and specific treatment was associated with relief in 8 patients (89%). Four patients had local reactions of unknown causes but symptom...... relief was obtained in three cases by unspecific therapy. Overall, 20 (91%) reported relief of symptoms. CONCLUSION: Our standardized investigative procedure of suspected insulin preparation (IP) allergy was associated with relief of symptoms in > 90% of patients. IP allergy was diagnosed in 41...

  13. Interdisciplinary action of nurses to children with suspected sexual abuse

    Directory of Open Access Journals (Sweden)

    Lia Leão Ciuffo

    2014-04-01

    Full Text Available Objective. Understanding the role of nurses as members of interdisciplinary teams in the care of children with suspected sexual abuse. Methodology. This is a qualitative research based on the sociological phenomenology of Alfred Schutz. In 2008 were interviewed eleven nurses who worked in reference institutions for the care of child victims of sexual abuse in Rio de Janeiro. Results. The category called 'Interacting with other professionals in child care' emerged from the analysis of performance of professionals. The intersubjective relations between the nurses and the interdisciplinary team will enable to understand the intent of care from the perspective of social, emotional and psychological needs of children and their families. Conclusion. Interdisciplinarity favored the development of actions based on acceptance, listening and agreements on possible solutions in the care of children with suspected sexual abuse.

  14. Suspected side effects to the quadrivalent human papilloma vaccine

    DEFF Research Database (Denmark)

    Brinth, Louise; Theibel, Ann Cathrine; Pors, Kirsten

    2015-01-01

    INTRODUCTION: The quadrivalent vaccine that protects against human papilloma virus types 6, 11, 16 and 18 (Q-HPV vaccine, Gardasil) was included into the Danish childhood vaccination programme in 2009. During the past years, a collection of symptoms primarily consistent with sympathetic nervous...... system dysfunction have been described as suspected side effects to the Q-HPV vaccine. METHODS: We present a description of suspected side effects to the Q-HPV vaccine in 53 patients referred to our Syncope Unit for tilt table test and evaluation of autonomic nervous system function. RESULTS: All...... consistency in the reported symptoms as well as between our findings and those described by others. Our findings neither confirm nor dismiss a causal link to the Q-HPV vaccine, but they suggest that further research is urgently warranted to clarify the pathophysiology behind the symptoms experienced...

  15. Radiological (scintigraphic) evaluation of patients with suspected pulmonar thromboembolism

    Energy Technology Data Exchange (ETDEWEB)

    Biello, D.R.

    1987-06-19

    The optimal strategy for diagnostic evaluation of patients with suspected pulmonary thromboembolism (PE) is subject of controversial and often conflicting opinions. If untreated, as many as 30% of patients with PE may die. Conversely, anticoagulant therapy significantly decreases mortality from PE, but bleeding complications occur. Underdiagnosis may result in a preventable death, and overdiagnosis may lead to significant hemorrhage from unnecessary anticoagulant therapy. This article outlines a practical guide for the use of pulmonary ventilation-perfusion (V-P) scintigraphy in patients with suspected PE. Perfusion imaging involves the intravenous injection of radiolabeled particles ranging from 10 to 60 ..mu..m in diameter (technetium Tc 99m macroaggregated albumin or technetium Tc 99m serum albumin microspheres); these particles are trapped in the capillaries and precapillary arterioles of the lung. The radiolabeled particles are distributed to the lungs in proportion to regional pulmonary blood flow. The correspondence of perfusion defects to bronchopulmonary segments is best appreciated in the posterior oblique views.

  16. Gamma-camera 18F-FDG PET in diagnosis and staging of patients presenting with suspected lung cancer and comparison with dedicated PET

    DEFF Research Database (Denmark)

    Oturai, Peter S; Mortensen, Jann; Enevoldsen, Henriette

    2004-01-01

    It is not clear whether high-quality coincidence gamma-PET (gPET) cameras can provide clinical data comparable with data obtained with dedicated PET (dPET) cameras in the primary diagnostic work-up of patients with suspected lung cancer. This study focuses on 2 main issues: direct comparison betw...

  17. Radiotherapy in three suspect cases of feline thymoma.

    Science.gov (United States)

    Kaser-Hotz, B; Rohrer, C R; Fidel, J L; Nett, C S; Hörauf, A; Hauser, B

    2001-01-01

    Radiation therapy for three cases of suspect feline thymoma is described. The thymoma was controlled for 4 years in case no. 1. Case no. 2 responded well to radiation therapy but was euthanized after 2 months because of a nasal adenocarcinoma. Case no. 3 continues to do well more than 8 months after radiotherapy. Difficulties in diagnosing feline thymomas are discussed, and biological behavior as well as different treatment modalities of feline and human thymomas are compared.

  18. Percutaneous cholecystocentesis in cats with suspected hepatobiliary disease.

    Science.gov (United States)

    Byfield, Victoria L; Callahan Clark, Julie E; Turek, Bradley J; Bradley, Charles W; Rondeau, Mark P

    2017-12-01

    Objectives The objective was to evaluate the safety and diagnostic utility of percutaneous ultrasound-guided cholecystocentesis (PUC) in cats with suspected hepatobiliary disease. Methods Medical records of 83 cats with suspected hepatobiliary disease that underwent PUC were retrospectively reviewed. Results At the time of PUC, at least one additional procedure was performed in 79/83 cats, including hepatic aspiration and/or biopsy (n = 75) and splenic aspiration (n = 18). Complications were noted in 14/83 cases, including increased abdominal fluid (n = 11), needle-tip occlusion (n = 1), failed first attempt to penetrate the gall bladder wall (n = 1) and pneumoperitoneum (n = 1). There were no reports of gall bladder rupture, bile peritonitis or hypotension necessitating treatment with vasopressor medication. Blood products were administered to 7/83 (8%) cats. Seventy-two cats (87%) survived to discharge. Of the cats that were euthanized (9/83) or died (2/83), none were reported as a definitive consequence of PUC. Bacteria were identified cytologically in 10/71 samples (14%); all 10 had a positive aerobic bacterial culture. Bile culture was positive in 11/80 samples (14%). Of the cases with a positive bile culture, cytological description of bacteria corresponded to the organism cultured in fewer than 50% of cases. The most common cytologic diagnosis was hepatic lipidosis (49/66). The most common histopathologic diagnosis was cholangitis (10/21). Conclusions and relevance PUC was safe in this group of cats with suspected hepatobiliary disease. Complications were likely associated with ancillary procedures performed at the time of PUC. Bile analysis yielded an abnormal result in nearly one-third of cats with suspected hepatobiliary disease. Complete agreement between bile cytology and culture was lacking. Further evaluation of the correlation between bile cytology and bile culture is warranted.

  19. Interviewing strategically to elicit admissions from guilty suspects

    OpenAIRE

    Tekin, Serra; Granhag, Pär Anders; Strömwall, Leif; Giolla, Erik Mac; Vrij, Aldert; Hartwig, Maria

    2015-01-01

    In this article we introduce a novel interviewing tactic to elicit admissions from guilty suspects. By influencing the suspects’ perception of the amount of evidence the interviewer holds against them, we aimed to shift the suspects’ counterinterrogation strategies from less to more forthcoming. The proposed tactic (SUE-Confrontation) is a development of the Strategic Use of Evidence (SUE) framework and aims to affect the suspects’ perception by confronting them with statement-evidence incons...

  20. MRI for clinically suspected pediatric appendicitis: case interpretation

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Michael M.; Brian, James M.; Methratta, Sosamma T.; Hulse, Michael A.; Choudhary, Arabinda K.; Eggli, Kathleen D.; Boal, Danielle K.B. [Penn State Milton S. Hershey Medical Center, Division of Pediatric Radiology, Department of Radiology, Hershey, PA (United States)

    2014-05-15

    As utilization of MRI for clinically suspected pediatric appendicitis becomes more common, there will be increased focus on case interpretation. The purpose of this pictorial essay is to share our institution's case interpretation experience. MRI findings of appendicitis include appendicoliths, tip appendicitis, intraluminal fluid-debris level, pitfalls of size measurements, and complications including abscesses. The normal appendix and inguinal appendix are also discussed. (orig.)

  1. Epidemiology of suspected wrist joint infection versus inflammation.

    Science.gov (United States)

    Skeete, Kshamata; Hess, Erik P; Clark, Tod; Moran, Steven; Kakar, Sanjeev; Rizzo, Marco

    2011-03-01

    To determine the cumulative prevalence of septic arthritis presenting to the emergency department of an academic medical center and evaluate the use of clinical data to diagnose infection versus inflammation. We conducted a records review of a single institution with 80,000 annual emergency room visits. We included a consecutive series of patients with suspected wrist infection from January 1, 2007, to December 31, 2008. Adults complaining of atraumatic wrist pain with either erythema or swelling on physical examination or a final diagnosis of septic arthritis, gout, pseudogout, cellulitis, wrist hematoma/edema, or wrist arthritic flare were suspected to have infection. We collected data using a standardized data abstraction form. We reviewed 804 patient records. A total of 104 patients meeting inclusion criteria for suspected wrist joint infection during the 2-year study period were included. Mean age was 62.5 years (SD, 20.2 y); 63 were men. There were 12 patients with a history of gout, 4 with a history of pseudogout, and 19 with a history of diabetes. Wrist arthrocentesis was performed in 31 patients, and 11 underwent surgical treatment. There were 16 patients with a final diagnosis of gout, 11 with pseudogout, 43 with cellulitis, 13 with upper extremity hematoma/edema, and 15 with wrist arthritic flare. The cumulative prevalence of septic arthritis was 5%. In this series of emergency department patients with suspected wrist joint infection, gout, pseudogout, and cellulitis were the most common etiologies. The cumulative incidence of septic wrist arthritis was low. Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  2. Suspected spinocellular carcinoma of the inferior eyelid resulted multiple chalazion.

    Science.gov (United States)

    Onesti, Maria Giuseppina; Troccola, Antonietta; Maruccia, Michele; Conversi, Andrea; Scuderi, Gianluca

    2013-01-01

    Chalazion is a subacute granulomatous inflammation of the eyelid caused by retention of tarsal gland secretions and it's the most common inflammatory lesion of the eyelid. In cases of doubtful clinical presentation the diagnosis with a biopsy and a histopathological examination is important because it can orientate an appropriate surgical treatment. We report a case of a 64-years-old diabetic man, suspected for a spinocellular lesion of the inferior eyelid of the left eye, it resulted unexpectedly a chalazion.

  3. CT-guided biopsy of suspected malignancy: A potential pitfall

    Directory of Open Access Journals (Sweden)

    Steven Henderson

    2013-11-01

    Full Text Available Paragangliomas are rare catecholamine-secreting neuro-endocrine tumours that can arise from sympathetic or parasympathetic tissue. Any manipulation of these tumours, without appropriate medical therapy, can result in excess catecholamine release leading to a catecholamine crisis. Neuro-endocrine tumours must be considered prior to interventional biopsy of an unknown soft-tissue mass, and appropriate biochemical investigations should be performed in suspected cases to prevent catastrophic complications.

  4. MR delayed enhancement imaging findings in suspected acute myocarditis

    Energy Technology Data Exchange (ETDEWEB)

    Gahide, Gerald [CHU de Montpellier, Radiologie centrale - Pole Cardiovasculaire et Thoracique, Montpellier (France); Centre Hospitalo-Universitaire de Montpellier, Hopital A de Villeneuve, Montpellier (France); Bertrand, D.; Dacher, J.N. [CHU de Rouen, Radiologie centrale - Hopital Charles Nicolle, Rouen (France); Roubille, F.; Skaik, S.; Piot, C.; Leclerq, F. [CHU de Montpellier, Departement de Cardiologie - Pole Cardiovasculaire et Thoracique, Montpellier (France); Tron, C.; Cribier, A. [CHU de Rouen, Departement de Cardiologie - Hopital Charles Nicolle, Rouen (France); Vernhet, H. [CHU de Montpellier, Radiologie centrale - Pole Cardiovasculaire et Thoracique, Montpellier (France)

    2010-01-15

    The purpose of the study was to prospectively assess the clinical impact of routinely performed delayed enhancement imaging in suspected acute myocarditis. A two-centre prospective study was performed in patients with suspected acute myocarditis. The protocol included horizontal long axis, vertical long axis and short axis cine MR and delayed enhancement imaging after Gd-DTPA infusion (0.2 mmol/kg). Sixty consecutive patients were enrolled (aged 49.4{+-}17.8 years). MRI demonstrated delayed enhancement sparing the subendocardicardial layer in 51.6% of patients, concordant with the diagnosis of acute myocarditis; 16.7% of patients exhibited delayed enhancement involving the subendocardial layer with irregular margins, concordant with the diagnosis of acute myocardial infarction; 31.7% of patients had delayed enhancement imaging that was considered normal. Routine imaging to identify delayed enhancement provided crucial information in suspected acute myocarditis by reinforcing the diagnosis in 51.6% of patients and correcting a misdiagnosed acute myocardial infarction in 16.7% of patients. (orig.)

  5. Low dose computed tomography in suspected acute renal colic.

    Science.gov (United States)

    Meagher, T; Sukumar, V P; Collingwood, J; Crawley, T; Schofield, D; Henson, J; Lakin, K; Connolly, D; Giles, J

    2001-11-01

    To evaluate whether computed tomography (CT) of the renal tract in suspected renal colic using reduced exposure factors maintains diagnostic accuracy. Prospective multi-centre cohort study. Patients with suspected renal colic were examined using computed tomography (CT) of the renal tract followed by intravenous urography (IVU) in four different centres with five different CT systems. Sixty-nine patients with suspected renal colic had CT of the renal tract followed by IVU. CT was performed with reduced exposure factors, giving a mean CT effective dose of 3.5 (range 2.8-4.5) mSv compared with 1.5 mSv for IVU. Ureteric calculi were detected in 43 patients: CT and IVU detected 40 (93%) ureteric calculi. CT identified other lesions causing symptoms in five patients and identified renal calculi in 24 patients. IVU identified renal calculi in six patients and made false positive diagnosis of renal calculi in seven patients. Mean examination time for CT was 5 minutes and for IVU was 80 minutes. CT examination at reduced exposure factors maintains the diagnostic accuracy recorded in other series. Copyright 2001 The Royal College of Radiologists.

  6. The economics of cardiac biomarker testing in suspected myocardial infarction.

    Science.gov (United States)

    Goodacre, Steve; Thokala, Praveen

    2015-03-01

    Suspected myocardial infarction (MI) is a common reason for emergency hospital attendance and admission. Cardiac biomarker measurement is an essential element of diagnostic assessment of suspected MI. Although the cost of a routinely available biomarker may be small, the large patient population and consequences in terms of hospital admission and investigation mean that the economic impact of cardiac biomarker testing is substantial. Economic evaluation involves comparing the estimated costs and effectiveness (outcomes) of two or more interventions or care alternatives. This process creates some difficulties with respect to cardiac biomarkers. Estimating the effectiveness of cardiac biomarkers involves identifying how they help to improve health and how we can measure this improvement. Comparison to an appropriate alternative is also problematic. New biomarkers may be promoted on the basis of reducing hospital admission or length of stay, but hospital admission for low risk patients may incur significant costs while providing very little benefit, making it an inappropriate comparator. Finally, economic evaluation may conclude that a more sensitive biomarker strategy is more effective but, by detecting and treating more cases, is also more expensive. In these circumstances it is unclear whether we should use the more effective or the cheaper option. This article provides an introduction to health economics and addresses the specific issues relevant to cardiac biomarkers. It describes the key concepts relevant to economic evaluation of cardiac biomarkers in suspected MI and highlights key areas of uncertainty and controversy. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  7. Limitation of personal freedom by detention of suspect

    Directory of Open Access Journals (Sweden)

    Knežević Saša

    2011-01-01

    Full Text Available The right of personal freedom is one of the most important right from the set of basic human rights and freedoms, contained in the most important acts of international legal character, and the constitutions of states based on the rule of law. This right is directly related to the very human existence, and, therefore, it is necessary to make its legal articulation. Personal freedom means the right to security of the citizen, that he will not be arrested and detained in prison by the state authorities, as well as the right to be free to move and inhabit. However, from the very nature of Criminal Law protection of social values, arises the need to limit the right to personal freedom in exceptional circumstances, including the detention of the suspect. Keeping the suspect is a measure of procedural compulsion, by which, through the police decision, detained prison is temporarily imprisoned, for gathering information and hearing. The basic principles of humanity require that the detained suspect retains all the rights, derived from the principle of personal liberty.

  8. MIBG in the evaluation of suspected pheochromocytoma: Mayo Clinic experience

    Energy Technology Data Exchange (ETDEWEB)

    Brown, M.L.; Sheps, S.G.; Sizemore, G.; Swensen, S.J.; Gharib, H.; Grant, C.S.; van Heerden, J.A.

    1984-01-01

    Work done at the University of Michigan has shown that I-131 metaiodobenzylguanidine (MIBG) is an effective agent for the diagnosis and localization of pheochromocytoma. A recent report questioned the sensitivity of this test. In 1983, 40 patients at Mayo Clinic had 42 scans during the workup of suspected spontaneous pheochromocytoma or metastatic pheochromocytoma. All patients were given 500 ..mu..Ci I-131 MIBG supplied by the University of Michigan. The final diagnosis of pheochromocytoma (true positive (TP) and false negative (FN) and false positive (FP)) was made by surgery and pathology. True negative (TN) diagnosis was made by normal plasma and urinary catecholamines, and in many patients CT. There were 15 TP studies (six spontaneous pheochrocytoma, nine metastatic or recurrent pheochromoctyoma), and 22 TN studies. There was one FP study of recurrent paraganglioma near the bladder (CT was also FP) and four FN studies (two spontaneous and two metastatic) where one CT was also FN. This results in a sensitivity of 79%, specificity of 96%, and accuracy of 88%. MIBG is very useful in the workup of patients with known or suspected recurrent or metastatic pheochromocytoma and is helpful in the evaluation of the patient suspected of having a spontaneous pheochromocytoma when CT is normal.

  9. Association Between Baseline Iris Thickness and Prophylactic Laser Peripheral Iridotomy Outcomes in Primary Angle Closure Suspects

    Science.gov (United States)

    Lee, Roland Y.; Kasuga, Toshimitsu; Cui, Qi N.; Porco, Travis C.; Huang, Guofu; He, Mingguang; Lin, Shan C.

    2014-01-01

    Objective To evaluate the association between baseline measurements of iris thickness at three positions and change in anterior segment biometric parameters after prophylactic laser peripheral iridotomy (LPI). Design Prospective clinical cohort study. Participants Fifty-two eyes of 52 nonglaucomatous subjects with anatomically narrow angles. Methods Anterior segment optical coherence tomography images captured before and after LPI were analyzed using customized software, the Zhongshan Angle Assessment Program. Differences in preoperative and postoperative measurements for anterior segment biometric parameters were compared by paired Student’s t-tests. Multivariate linear regression models, adjusted for age, sex, ethnicity, and preoperative pupil diameter, were used to examine the association between the baseline measurements of iris thickness at three positions and the change in anterior segment biometric parameters after LPI. Main Outcome Measures Baseline iris thickness measured at 750μm (IT750) and 2000μm (IT2000) from the scleral spur and maximal iris thickness (ITM). Changes in iris curvature (ICURV) and trabecular–iris space area at 500μm (TISA500) and 750μm (TISA750) from the scleral spur after LPI. Results ICURV significantly decreased, while TISA500 and TISA750 significantly increased following LPI (all Piris thickness are associated with greater decrease in ICURV and increases in TISA500 and TISA750 after LPI. This suggests that eyes with thinner irides undergoing LPI were more likely to exhibit greater magnitude of change in terms of flattening of the iris convexity (i.e., ICURV) and widening of the anterior chamber angle (i.e., TISA500 and TISA750). PMID:24534754

  10. Monoclonal Antibodies production technology

    Directory of Open Access Journals (Sweden)

    Flávia Rocha

    2011-02-01

    Full Text Available Since the first cells were capable of maintain a continuous antibody supply, developed by Köhler and Milstein in 1975, its use in medicine and industry showed a great potential. New researches were developed to enhance the use of such cells, including immunizations, mieloma cells, fusion methodology, screening techniques, cloning, culture media, among several details which enable and optimizes its use. Nowadays, monoclonal antibodies are a well-established tool for proteomics research and it have countless applications on several knowledge areas, mainly human and/or animal disease diagnostic, identification and tracking of allergenic compounds in food and residues in the environment. This review can be used by professionals, researches and students searching for a compiled papers contributing to the improvement of the monoclonal antibodies technology, used at different knowledge areas such as human diseases and diseases and disorders in agriculture and livestock chain.

  11. Antibody affinity maturation

    DEFF Research Database (Denmark)

    Skjødt, Mette Louise

    fragments by in vivo homologous recombination large combinatorial antibody libraries can easily be generated. We have optimized ordered assembly of three CDR fragments into a gapped vector and observed increased transformation efficiency in a yeast strain carrying a deletion of the SGS1 helicase...... surface expression of various antibody formats in the generated knockout strain. Functional scFv and scFab fragments were efficiently displayed on yeast whereas impaired chain assembly and heavy chain degradation was observed for display of full-length IgG molecules. To identify the optimal polypeptide...... linker for yeast surface display of scFv and scFab fragments, we compared a series of different Gly-Ser-based linkers in display and antigen binding proficiency. We show that these formats of the model antibody can accommodate linkers of different lengths and that introduction of alanine or glutamate...

  12. Factors associated with late presentation of suspected tuberculosis cases to tuberculosis management facilities: The case in Dagoretti district, Nairobi, Kenya

    Science.gov (United States)

    Njau, Irene Wambui; Karanja, Simon Muturi; Wanzala, Peter; Omolo, Jared Odhiambo

    2012-01-01

    Background Tuberculosis is a highly contagious disease accounting for a high number of deaths in the developing countries; its control can be effectively achieved if individuals with the disease receive adequate and timely treatment. The objective of this study was to determine the factors associated with late presentation of suspects to tuberculosis management facilities in Dagoretti district in Nairobi, Kenya. Method A cross sectional study was conducted on patients aged 18 years and above attending TB clinics in Dagoretti District, Nairobi Kenya. A total of 426 TB suspects were interviewed. The study covered 8 clinics in Dagoretti district. Analysis was done using SPSS version 16.0 and Epi info version 6, this included Chi Square for Bivariate analysis and Binary Logistic Regression for Multivariate Analysis. Results Out of the 426 tuberculosis suspects, 248 (58.2%) suspects had delayed in seeking medical care. In Bivariate analysis male gender (P = 0.039, O.R = 1.51; 95% Confidence Interval; 1.00- 2.27), level of education (Primary class 5-8) (P = 0.001, O.R= 2.06; 95% C.I 1.34-3.19) and place of first medical care (drug store) (P= 0.013, O.R = 1.63; 95% C.I 1.09-2.46) were all significantly associated with late presentation. After multivariate logistic regression, gender (P = 0,019, OR = 1.6), level of education (p = 0.029, OR = 1.26) and place of first medical care (P= 0.01 OR = 1.27), were found to be significantly associated with late presentation. Conclusion This study shows that age, level of education and place of first medical care are the factors associated with late presentation of suspects to tuberculosis management facilities. PMID:23077714

  13. Adherence to standard of care in the diagnosis and treatment of suspected bacterial meningitis.

    Science.gov (United States)

    Chia, David; Yavari, Youness; Kirsanov, Eugeny; Aronin, Steven I; Sadigh, Majid

    2015-01-01

    Acute bacterial meningitis (ABM) is a rare but deadly neurological emergency. Accordingly, Infectious Diseases Society of America (IDSA) guidelines summarize current evidence into a straightforward algorithm for its management. The goal of this study is to evaluate the overall compliance with these guidelines in patients with suspected ABM. A retrospective cross-sectional study was conducted of adult patients who underwent lumbar puncture for suspected ABM to ascertain local adherence patterns to IDSA guidelines for bacterial meningitis. Primary outcomes included appropriate utilization of neuroimaging, blood cultures, antibiotics, corticosteroids, and lumbar puncture. In all, 160 patients were included in the study. Overall IDSA compliance was only 0.6%. Neuroimaging and blood cultures were appropriately utilized in 54.3% and 47.5% of patients, respectively. Steroids and antibiotics were appropriately administered in only 7.5% and 5.6% of patients, respectively. Adherence to IDSA guidelines is poor. Antibiotic choice is often incorrect, corticosteroids are rarely administered, and there is an overutilization of neuroimaging. © The Author(s) 2014.

  14. Antibody informatics for drug discovery

    DEFF Research Database (Denmark)

    Shirai, Hiroki; Prades, Catherine; Vita, Randi

    2014-01-01

    to the antibody science in every project in antibody drug discovery. Recent experimental technologies allow for the rapid generation of large-scale data on antibody sequences, affinity, potency, structures, and biological functions; this should accelerate drug discovery research. Therefore, a robust bioinformatic...... infrastructure for these large data sets has become necessary. In this article, we first identify and discuss the typical obstacles faced during the antibody drug discovery process. We then summarize the current status of three sub-fields of antibody informatics as follows: (i) recent progress in technologies...... for antibody rational design using computational approaches to affinity and stability improvement, as well as ab-initio and homology-based antibody modeling; (ii) resources for antibody sequences, structures, and immune epitopes and open drug discovery resources for development of antibody drugs; and (iii...

  15. Prediction of Antibody Epitopes

    DEFF Research Database (Denmark)

    Nielsen, Morten; Marcatili, Paolo

    2015-01-01

    Antibodies recognize their cognate antigens in a precise and effective way. In order to do so, they target regions of the antigenic molecules that have specific features such as large exposed areas, presence of charged or polar atoms, specific secondary structure elements, and lack of similarity...... to self-proteins. Given the sequence or the structure of a protein of interest, several methods exploit such features to predict the residues that are more likely to be recognized by an immunoglobulin.Here, we present two methods (BepiPred and DiscoTope) to predict linear and discontinuous antibody...

  16. Imaging trends in suspected appendicitis-a Canadian perspective.

    Science.gov (United States)

    Tan, Victoria F; Patlas, Michael N; Katz, Douglas S

    2017-06-01

    The purpose of our study was to assess trends in the imaging of suspected appendicitis in adult patients in emergency departments of academic centers in Canada. A questionnaire was sent to all 17 academic centers in Canada to be completed by a radiologist who works in emergency radiology. The questionnaires were sent and collected over a period of 4 months from October 2015 to February 2016. Sixteen centers (94%) responded to the questionnaire. Eleven respondents (73%) use IV contrast-enhanced computed tomography (CT) as the imaging modality of choice for all patients with suspected appendicitis. Thirteen respondents (81%) use ultrasound as the first modality of choice in imaging pregnant patients with suspected appendicitis. Eleven respondents (69%) use ultrasound (US) as the first modality of choice in patients younger than 40 years of age. Ten respondents (67%) use ultrasound as the first imaging modality in female patients younger than 40 years of age. When CT is used, 81% use non-focused CT of the abdomen and pelvis, and 44% of centers use oral contrast. Thirteen centers (81%) have ultrasound available 24 h a day/7 days a week. At 12 centers (75%), ultrasound is performed by ultrasound technologists. Four centers (40%) perform magnetic resonance imaging (MRI) in suspected appendicitis in adult patients at the discretion of the attending radiologist. Eleven centers (69%) have MRI available 24/7. All 16 centers (100%) use unenhanced MRI. Various imaging modalities are available for the work-up of suspected appendicitis. Although there are North American societal guidelines and recommendations regarding the appropriateness of the multiple imaging modalities, significant heterogeneity in the first-line modalities exist, which vary depending on the patient demographics and resource availability. Imaging trends in the use of the first-line modalities should be considered in order to plan for the availability of the imaging examinations and to consider plans for

  17. Predictors of bacteremia in emergency department patients with suspected infection.

    Science.gov (United States)

    Chase, Maureen; Klasco, Richard S; Joyce, Nina R; Donnino, Michael W; Wolfe, Richard E; Shapiro, Nathan I

    2012-11-01

    The goal of this study is to identify clinical variables associated with bacteremia. Such data could provide a rational basis for blood culture testing in emergency department (ED) patients with suspected infection. This is a secondary analysis of a prospective cohort of ED patients with suspected infection. Data collected included demographics, vital signs, medical history, suspected source of infection, laboratory and blood culture results and outcomes. Bacteremia was defined as a positive blood culture by Centers for Disease Control criteria. Clinical variables associated with bacteremia on univariate logistic regression were entered into a multivariable model. There were 5630 patients enrolled with an average age of 59.9 ± 19.9 years, and 54% were female. Blood cultures were obtained on 3310 (58.8%). There were 409 (12.4%) positive blood cultures, of which 68 (16.6%) were methicillin-resistant Staphylococcus aureus (MRSA) and 161 (39.4%) were Gram negatives. Ten covariates (respiratory failure, vasopressor use, neutrophilia, bandemia, thrombocytopenia, indwelling venous catheter, abnormal temperature, suspected line or urinary infection, or endocarditis) were associated with all-cause bacteremia in the final model (c-statistic area under the curve [AUC], 0.71). Additional factors associated with MRSA bacteremia included end-stage renal disease (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.9-7.8) and diabetes (OR, 2.0; 95% CI, 1.1-3.6) (AUC, 0.73). Factors strongly associated with Gram-negative bacteremia included vasopressor use in the ED (OR, 2.8; 95% CI, 1.7-4.6), bandemia (OR, 3.5; 95% CI, 2.3-5.3), and suspected urinary infection (OR, 4.0; 95% CI, 2.8-5.8) (AUC, 0.75). This study identified several clinical factors associated with bacteremia as well as MRSA and Gram-negative subtypes, but the magnitude of their associations is limited. Combining these covariates into a multivariable model moderately increases their predictive value. Copyright

  18. Abdominal CT Does Not Improve Outcome for Children with Suspected Acute Appendicitis

    Directory of Open Access Journals (Sweden)

    Danielle I. Miano

    2015-12-01

    Full Text Available Introduction: Acute appendicitis in children is a clinical diagnosis, which often requires preoperative confirmation with either ultrasound (US or computed tomography (CT studies. CTs expose children to radiation, which may increase the lifetime risk of developing malignancy. US in the pediatric population with appropriate clinical follow up and serial exam may be an effective diagnostic modality for many children without incurring the risk of radiation. The objective of the study was to compare the rate of appendiceal rupture and negative appendectomies between children with and without abdominal CTs; and to evaluate the same outcomes for children with and without USs to determine if there were any associations between imaging modalities and outcomes. Methods: We conducted a retrospective chart review including emergency department (ED and inpatient records from 1/1/2009–2/31/2010 and included patients with suspected acute appendicitis. Results: 1,493 children, aged less than one year to 20 years, were identified in the ED with suspected appendicitis. These patients presented with abdominal pain who had either a surgical consult or an abdominal imaging study to evaluate for appendicitis, or were transferred from an outside hospital or primary care physician office with the stated suspicion of acute appendicitis. Of these patients, 739 were sent home following evaluation in the ED and did not return within the subsequent two weeks and were therefore presumed not to have appendicitis. A total of 754 were admitted and form the study population, of which 20% received a CT, 53% US, and 8% received both. Of these 57%, 95% CI [53.5,60.5] had pathology-proven appendicitis. Appendicitis rates were similar for children with a CT (57%, 95% CI [49.6,64.4] compared to those without (57%, 95% CI [52.9,61.0]. Children with perforation were similar between those with a CT (18%, 95% CI [12.3,23.7] and those without (13%, 95% CI [10.3,15.7]. The proportion of

  19. Fixed Dosing of Monoclonal Antibodies in Oncology.

    Science.gov (United States)

    Hendrikx, Jeroen J M A; Haanen, John B A G; Voest, Emile E; Schellens, Jan H M; Huitema, Alwin D R; Beijnen, Jos H

    2017-10-01

    Most monoclonal antibodies in oncology are administered in body-size-based dosing schedules. This is believed to correct for variability in both drug distribution and elimination between patients. However, monoclonal antibodies typically distribute to the blood plasma and extracellular fluids only, which increase less than proportionally with the increase in body weight. Elimination takes place via proteolytic catabolism, a nonspecific immunoglobulin G elimination pathway, and intracellular degradation after binding to the target. The latter is the primary route of elimination and is related to target expression levels rather than body size. Taken together, the minor effects of body size on distribution and elimination of monoclonal antibodies and their usually wide therapeutic window do not support body-size-based dosing. We evaluated effects of body weight on volume of distribution and clearance of monoclonal antibodies in oncology and show that a fixed dose for most of these drugs is justified based on pharmacokinetics. A survey of the savings after fixed dosing of monoclonal antibodies at our hospital showed that fixed dosing can reduce costs of health care, especially when pooling of preparations is not possible (which is often the case in smaller hospitals). In conclusion, based on pharmacokinetic parameters of monoclonal antibodies, there is a rationale for fixed dosing of these drugs in oncology. Therefore, we believe that fixed dosing is justified and can improve efficiency of the compounding. Moreover, drug spillage can be reduced and medication errors may become less likely. The currently available knowledge of elimination of monoclonal antibodies combined with the publicly available data from clinical trials and extensive population pharmacokinetic (PopPK) modeling justifies fixed dosing. Interpatient variation in exposure is comparable after body weight and fixed dosing and most monoclonal antibodies show relatively flat dose-response relationships

  20. Child Mortality after Discharge from a Health Facility following Suspected Pneumonia, Meningitis or Septicaemia in Rural Gambia: A Cohort Study.

    Science.gov (United States)

    Chhibber, Aakash Varun; Hill, Philip C; Jafali, James; Jasseh, Momodou; Hossain, Mohammad Ilias; Ndiaye, Malick; Pathirana, Jayani C; Greenwood, Brian; Mackenzie, Grant A

    2015-01-01

    To measure mortality and its risk factors among children discharged from a health centre in rural Gambia. We conducted a cohort study between 12 May 2008 and 11 May 2012. Children aged 2-59 months, admitted with suspected pneumonia, sepsis, or meningitis after presenting to primary and secondary care facilities, were followed for 180 days after discharge. We developed models associating post-discharge mortality with clinical syndrome on admission and clinical risk factors. One hundred and five of 3755 (2.8%) children died, 80% within 3 months of discharge. Among children aged 2-11 and 12-59 months, there were 30 and 29 deaths per 1000 children per 180 days respectively, compared to 11 and 5 respectively in the resident population. Children with suspected pneumonia unaccompanied by clinically severe malnutrition (CSM) had the lowest risk of post-discharge mortality. Mortality increased in children with suspected meningitis or septicaemia without CSM (hazard ratio [HR] 2.6 and 2.2 respectively). The risk of mortality greatly increased with CSM on admission: CSM with suspected pneumonia (HR 8.1; 95% confidence interval (CI) 4.4 to 15), suspected sepsis (HR 18.4; 95% CI 11.3 to 30), or suspected meningitis (HR 13.7; 95% CI 4.2 to 45). Independent associations with mortality were: mid-upper arm circumference (MUAC) of 11.5-13.0 cm compared to >13.0 cm (HR 7.2; 95% CI 3.0 to 17.0), MUAC 10.5-11.4 cm (HR 24; 95% CI 9.4 to 62), and MUAC <10.5 cm (HR 44; 95% CI 18 to 108), neck stiffness (HR 10.4; 95% CI 3.1 to 34.8), non-medical discharge (HR 4.7; 95% CI 2.0 to 10.9), dry season discharge (HR 2.0; 95% CI 1.2 to 3.3), while greater haemoglobin (HR 0.82; 0.73 to 0.91), axillary temperature (HR 0.71; 95% CI 0.58 to 0.87), and oxygen saturation (HR 0.96; 95% CI 0.93 to 0.99) were associated with reduced mortality. Gambian children experience increased mortality after discharge from primary and secondary care. Interventions should target both moderately and severely

  1. Antimitochondrial antibodies in patients with chronic hepatitis C.

    Science.gov (United States)

    Grimbert, S; Johanet, C; Bendjaballah, F; Homberg, J C; Poupon, R; Beaugrand, M

    1996-06-01

    Although autoantibodies have been found in the serum of patients with chronic hepatitis C virus (HCV) there has been no convincing evidence of the presence of antimitochondrial antibodies, until now. Sera from 460 untreated patients with chronic hepatitis C were tested for antimitochondrial antibodies, using an indirect immunofluorescence technique; and if they tested positive for the antibodies (titer more than 1:50), they also were treated by Western blot analysis. Seven (1.5%) sera were positive. None of the patients had biological or histological evidence of primary biliary cirrhosis. Antimitochondrial antibodies recognized one of the oxo-dehydrogenase multienzyme complexe's epitopes by Western blot assay in three patients only. All seven patients were then treated by interferon alpha for six months. None showed exacerbation of liver disease during treatment. HCV-RNA disappeared from the serum in one patient who became negative for anti-M2 antibodies. The four patients who did not respond to interferon-alpha therapy, and the two who relapsed after treatment withdrawal, had sustained positive antimitochondrial antibodies. These data suggest that: 1) antimitochondrial antibodies present in patients with chronic hepatitis C do not always recognize the same epitopes as in primary biliary cirrhosis; 2) these antibodies may disappear after eradication of HCV, suggesting that the production of antimitochondrial antibodies is linked to the presence of the virus and 3) the clinical and biological course of chronic hepatitis C, and the response to interferon-alpha therapy, does not seem to be different in patients who are positive for antimitochondrial antibodies.

  2. Compositions, antibodies, asthma diagnosis methods, and methods for preparing antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Hongjun; Zangar, Richard C.

    2017-01-17

    Methods for preparing an antibody are provided with the method including incorporating 3-bromo-4-hydroxy-benzoic acid into a protein to form an antigen, immunizing a mammalian host with the antigen, and recovering an antibody having an affinity for the antigen from the host. Antibodies having a binding affinity for a monohalotyrosine are provided as well as composition comprising an antibody bound with monohalotyrosine. Compositions comprising a protein having a 3-bromo-4-hydroxy-benzoic acid moiety are also provided. Methods for evaluating the severity of asthma are provide with the methods including analyzing sputum of a patient using an antibody having a binding affinity for monohalotyrosine, and measuring the amount of antibody bound to protein. Methods for determining eosinophil activity in bodily fluid are also provided with the methods including exposing bodily fluid to an antibody having a binding affinity for monohalotyrosine, and measuring the amount of bound antibody to determine the eosinophil activity.

  3. Human germline antibody gene segments encode polyspecific antibodies.

    Science.gov (United States)

    Willis, Jordan R; Briney, Bryan S; DeLuca, Samuel L; Crowe, James E; Meiler, Jens

    2013-04-01

    Structural flexibility in germline gene-encoded antibodies allows promiscuous binding to diverse antigens. The binding affinity and specificity for a particular epitope typically increase as antibody genes acquire somatic mutations in antigen-stimulated B cells. In this work, we investigated whether germline gene-encoded antibodies are optimal for polyspecificity by determining the basis for recognition of diverse antigens by antibodies encoded by three VH gene segments. Panels of somatically mutated antibodies encoded by a common VH gene, but each binding to a different antigen, were computationally redesigned to predict antibodies that could engage multiple antigens at once. The Rosetta multi-state design process predicted antibody sequences for the entire heavy chain variable region, including framework, CDR1, and CDR2 mutations. The predicted sequences matched the germline gene sequences to a remarkable degree, revealing by computational design the residues that are predicted to enable polyspecificity, i.e., binding of many unrelated antigens with a common sequence. The process thereby reverses antibody maturation in silico. In contrast, when designing antibodies to bind a single antigen, a sequence similar to that of the mature antibody sequence was returned, mimicking natural antibody maturation in silico. We demonstrated that the Rosetta computational design algorithm captures important aspects of antibody/antigen recognition. While the hypervariable region CDR3 often mediates much of the specificity of mature antibodies, we identified key positions in the VH gene encoding CDR1, CDR2, and the immunoglobulin framework that are critical contributors for polyspecificity in germline antibodies. Computational design of antibodies capable of binding multiple antigens may allow the rational design of antibodies that retain polyspecificity for diverse epitope binding.

  4. Prediction of antibody persistency from antibody titres to natalizumab

    DEFF Research Database (Denmark)

    Jensen, Poul Erik H; Koch-Henriksen, Nils; Sellebjerg, Finn Thorup

    2012-01-01

    In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients.......In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients....

  5. Human monoclonal antibodies: the residual challenge of antibody immunogenicity.

    Science.gov (United States)

    Waldmann, Herman

    2014-01-01

    One of the major reasons for seeking human monoclonal antibodies has been to eliminate immunogenicity seen with rodent antibodies. Thus far, there has yet been no approach which absolutely abolishes that risk for cell-binding antibodies. In this short article, I draw attention to classical work which shows that monomeric immunoglobulins are intrinsically tolerogenic if they can be prevented from creating aggregates or immune complexes. Based on these classical studies two approaches for active tolerization to therapeutic antibodies are described.

  6. Monoclonal antibodies in haematopathology

    Energy Technology Data Exchange (ETDEWEB)

    Grignani, F.; Martelli, M.F.; Mason, D.Y.

    1985-01-01

    This book contains over 40 selections. Some of the titles are: Oncogene (c-myc, c-myb) amplification in acute myelogenous leukaemia; Ultrastructural characterization of leukaemic cells with monoloclonal antibodies; Origin of B-cell malignancies; Immunohistology of gut lymphomas; and Spurious evidence of lineage infidelity in monocytic leukaemia.

  7. Monoclonal antibodies in myeloma

    DEFF Research Database (Denmark)

    Sondergeld, P.; van de Donk, N. W. C. J.; Richardson, P. G.

    2015-01-01

    The development of monoclonal antibodies (mAbs) for the treatment of disease goes back to the vision of Paul Ehrlich in the late 19th century; however, the first successful treatment with a mAb was not until 1982, in a lymphoma patient. In multiple myeloma, mAbs are a very recent and exciting add...

  8. Antibodies Targeting EMT

    Science.gov (United States)

    2015-10-01

    biomarkers. We have developed a new technique allowing for discovery of new antibodies that disrupt a key process in cancer progression termed...14 post Twist induction to trigger EMT. 7 within CDRH3s, the RGD motif could be indicative of ligand mimetic integrin binding properties of these

  9. Donepezil decreases annual rate of hippocampal atrophy in suspected prodromal Alzheimer's disease.

    Science.gov (United States)

    Dubois, Bruno; Chupin, Marie; Hampel, Harald; Lista, Simone; Cavedo, Enrica; Croisile, Bernard; Louis Tisserand, Guy; Touchon, Jacques; Bonafe, Alain; Ousset, Pierre Jean; Ait Ameur, Amir; Rouaud, Olivier; Ricolfi, Fréderic; Vighetto, Alain; Pasquier, Florence; Delmaire, Christine; Ceccaldi, Mathieu; Girard, Nadine; Dufouil, Carole; Lehericy, Stéphane; Tonelli, Isabelle; Duveau, Françoise; Colliot, Olivier; Garnero, Line; Sarazin, Marie; Dormont, Didier

    2015-09-01

    The purpose of this study was to study the effect of donepezil on the rate of hippocampal atrophy in prodromal Alzheimer's disease (AD). A double-blind, randomized, placebo-controlled parallel group design using donepezil (10 mg/day) in subjects with suspected prodromal AD. Subjects underwent two brain magnetic resonance imaging scans (baseline and final visit). The primary efficacy outcome was the annualized percentage change (APC) of total hippocampal volume (left + right) measured by an automated segmentation method. Two-hundred and sixteen only subjects were randomized across 28 French expert clinical sites. In the per protocol population (placebo = 92 and donepezil = 82), the donepezil group exhibited a significant reduced rate of hippocampal atrophy (APC = -1.89%) compared with the placebo group (APC = -3.47%), P donepezil compared with placebo. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  10. A case suspected for yellow fever vaccine-associated viscerotropic disease in the Netherlands.

    Science.gov (United States)

    van de Pol, Eva M; Gisolf, Elizabeth H; Richter, Clemens

    2014-01-01

    Yellow fever (YF) 17D vaccine is one of the most successful vaccines ever developed. Since 2001, 56 cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) have been published in the peer-reviewed literature. Here, we report a new case suspected for YEL-AVD in the Netherlands. Further research is needed to determine the true incidence of YEL-AVD and to clarify host and vaccine-associated factors in the pathogenesis of YEL-AVD. Because of the potential adverse events, healthcare providers should carefully consider vaccination only in people who are truly at risk for YF infection, especially in primary vaccine recipients. © 2014 International Society of Travel Medicine.

  11. Prognostic importance of quantitative echocardiographic evaluation in patients suspected of first non-massive pulmonary embolism

    DEFF Research Database (Denmark)

    Kjaergaard, Jesper; Schaadt, Bente Krogsgaard; Lund, Jens Otto

    2008-01-01

    AIMS: Patients suspected of acute pulmonary embolism (PE) frequently undergo echocardiography as a part of the initial work-up. Prognostic implication of routine echocardiography in patients suspected of PE remain to be established. METHODS AND RESULTS: Transthoracic echocardiography, including...

  12. Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study.

    Science.gov (United States)

    van der Hulle, Tom; Cheung, Whitney Y; Kooij, Stephanie; Beenen, Ludo F M; van Bemmel, Thomas; van Es, Josien; Faber, Laura M; Hazelaar, Germa M; Heringhaus, Christian; Hofstee, Herman; Hovens, Marcel M C; Kaasjager, Karin A H; van Klink, Rick C J; Kruip, Marieke J H A; Loeffen, Rinske F; Mairuhu, Albert T A; Middeldorp, Saskia; Nijkeuter, Mathilde; van der Pol, Liselotte M; Schol-Gelok, Suzanne; Ten Wolde, Marije; Klok, Frederikus A; Huisman, Menno V

    2017-07-15

    Validated diagnostic algorithms in patients with suspected pulmonary embolism are often not used correctly or only benefit subgroups of patients, leading to overuse of computed tomography pulmonary angiography (CTPA). The YEARS clinical decision rule that incorporates differential D-dimer cutoff values at presentation, has been developed to be fast, to be compatible with clinical practice, and to reduce the number of CTPA investigations in all age groups. We aimed to prospectively evaluate this novel and simplified diagnostic algorithm for suspected acute pulmonary embolism. We did a prospective, multicentre, cohort study in 12 hospitals in the Netherlands, including consecutive patients with suspected pulmonary embolism between Oct 5, 2013, to July 9, 2015. Patients were managed by simultaneous assessment of the YEARS clinical decision rule, consisting of three items (clinical signs of deep vein thrombosis, haemoptysis, and whether pulmonary embolism is the most likely diagnosis), and D-dimer concentrations. In patients without YEARS items and D-dimer less than 1000 ng/mL, or in patients with one or more YEARS items and D-dimer less than 500 ng/mL, pulmonary embolism was considered excluded. All other patients had CTPA. The primary outcome was the number of independently adjudicated events of venous thromboembolism during 3 months of follow-up after pulmonary embolism was excluded, and the secondary outcome was the number of required CTPA compared with the Wells' diagnostic algorithm. For the primary outcome regarding the safety of the diagnostic strategy, we used a per-protocol approach. For the secondary outcome regarding the efficiency of the diagnostic strategy, we used an intention-to-diagnose approach. This trial is registered with the Netherlands Trial Registry, number NTR4193. 3616 consecutive patients with clinically suspected pulmonary embolism were screened, of whom 151 (4%) were excluded. The remaining 3465 patients were assessed of whom 456 (13%) were

  13. Individual serological follow-up of patients with suspected or confirmed abdominal angiostrongyliasis

    Directory of Open Access Journals (Sweden)

    Penélope E Palominos

    2008-02-01

    Full Text Available Abdominal angiostrongyliasis (AA is a zoonotic nematode infection caused by Angiostrongylus costaricensis, with widespread occurrence in the Americas. Although the human infection may be highly prevalent, morbidity is low in Southern Brazil. Confirmed diagnosis is based on finding parasitic structures in pathological examination of biopsies or surgical resections. Serology stands as an important diagnostic tool in the less severe courses of the infection. Our objective is to describe the follow up of humoral reactivity every 2-4 weeks up to one year, in six individuals with confirmed (C and ten suspected (S AA. Antibody (IgG detection was performed by ELISA and resulted in gradually declining curves of reactivity in nine subjects (56% (4C + 5S, that were consistently negative in only three of them (2C + 1S after 221, 121 and 298 days. Three individuals (2C + 1S presented with low persistent reacitivity, other two (1C + 1S were serologically negative from the beginning, but also presenting a declining tendency. The study shows indications that abdominal angiostrongyliasis is usually not a persistent infection: although serological negativation may take many months, IgG reactivity is usually declining along time and serum samples pairing may add valuable information to the diagnostic workout.

  14. Cancer of unknown primary

    DEFF Research Database (Denmark)

    Dyrvig, Anne-Kirstine; Yderstræde, Knud Bonnet; Gerke, Oke

    2017-01-01

    Cancer of unknown primary (CUP) ranges within top 10 cancers in both incidence and mortality. As primary identification is crucial to choosing treatment, guidelines on CUP emphasize the diagnostic strategy. Whether guidelines are complied with, or if they are indeed helpful, is however unclear. We...... to procedures and patient survival. The cohort was investigated in terms of validity of diagnosis through cross-referencing with the Cancer Registry (CR), which served as gold standard for cancer diagnoses and patients' cancer histories.The NPR cohort consisted of 542 patients (275 males, 264 females) of whom...... after 4 years.The validity of a CUP diagnosis in NPR was low when using data from CR as reference. More than half the suspected CUP patients had a previous cancer diagnosis with CUP being the most frequent. Patients were diagnosed in compliance with guidelines indicating high external validity, but less...

  15. Structural Characterization of Peptide Antibodies

    DEFF Research Database (Denmark)

    Chailyan, Anna; Marcatili, Paolo

    2015-01-01

    can be modified to obtain desired properties or conformation, tagged for purification, isotopically labeled for protein quantitation or conjugated to immunogens for antibody production. The antibodies that bind to these peptides represent an invaluable tool for biological research and discovery...

  16. Sputum direct fluorescent antibody (DFA)

    Science.gov (United States)

    ... ency/article/003553.htm Sputum direct fluorescent antibody (DFA) test To use the sharing features on this page, please enable JavaScript. Sputum direct fluorescent antibody (DFA) is a lab test that looks for micro- ...

  17. Comparative study of Widal test against stool culture for typhoid fever suspected cases in southern Ethiopia

    Directory of Open Access Journals (Sweden)

    Ameya G

    2017-01-01

    Full Text Available Gemechu Ameya,1 Edemew Atalel,2 Berhanu Kebede,3 Bethel Yohannes4 1Department of Medical Laboratory Science, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, 2Department of Medical Laboratory Science, Durbetie Primary Hospital, Amahara, 3Department of Medical Laboratory Science, Dalifage Primary Hospital, Afar, 4Department of Medical Laboratory Science, Hayilemariyam Hospital, Adama, Ethiopia Introduction: Infection caused by Salmonella enterica subsp. serotype Typhi remains an important public health problem in developing countries. Culture is an effective diagnostic method of confirming this infection. Diagnosis in developing countries is mostly done by Widal test, which is nonreliable. The aim of this study was to compare the Widal test against stool culture in typhoid-suspected cases and to evaluate the agreement between test methods.Methodology: A cross-sectional study design was conducted on typhoid-suspected cases in southern Ethiopia. Collected data were entered into Epi-Info version 3.5.1 and exported to SPSS version 20.0 for further analysis. Kappa test was used to assess the agreement between the tests. Sensitivity, specificity, positive predictive value (PPV, and negative predictive value (NPV were calculated to compare the Widal test against stool culture.Results: A total of 95 patients participated in the study, of whom 49 (51.6% were females and 46 (48.4% were males. The age range of the suspected cases were between 10 and 62 years, with mean age of 27.9 years. Of the examined cases, 65 (68.4% were positive for slide agglutination Widal test, whereas only 19 (20.0% were positive for S. enterica serotype Typhi by stool culture. The sensitivity, specificity, PPV, and NPV of slide agglutination test against stool culture were 84.2%, 35.5%, 24.6%, and 90.0%, respectively. Slide agglutination test has a poor agreement with the stool culture (kappa = 0.103, but tube titration test has a fair agreement with the

  18. Antibody and B cell responses to Plasmodium sporozoites

    Directory of Open Access Journals (Sweden)

    Johanna N Dups

    2014-11-01

    Full Text Available Antibodies are capable of blocking infection of the liver by Plasmodium sporozoites. Accordingly the induction of anti-sporozoite antibodies is a major aim of various vaccine approaches to malaria. In recent years our knowledge of the specificity and quantities of antibodies required for protection has been greatly expanded by clinical trials of various whole sporozoite and subunit vaccines. Moreover, the development of humanized mouse models and transgenic parasites have also aided our ability to assess the specificity of antibodies and their ability to block infection. Nonetheless, considerable gaps remain in our knowledge - in particular in understanding what antigens are recognized by infection blocking antibodies and in knowing how we can induce robust, long-lived antibody responses. Maintaining high levels of circulating antibodies is likely to be of primary importance, as antibodies must block infection in the short time it takes for sporozoites to reach the liver from the skin. It is clear that a better understanding of the development of protective B cell-mediated immunity will aid the development and refinement of malaria vaccines.

  19. Icare rebound tonometry in children with known and suspected glaucoma.

    Science.gov (United States)

    Flemmons, Meghan S; Hsiao, Ya-Chuan; Dzau, Jacqueline; Asrani, Sanjay; Jones, Sarah; Freedman, Sharon F

    2011-04-01

    Accurate intraocular pressure (IOP) measurement, important in managing pediatric glaucoma, often presents challenges. The Icare rebound tonometer shows promise for screening healthy children and has been reported comparable with Goldmann applanation in adults with glaucoma. The purpose of this study was to evaluate the Icare tonometer against Goldmann applanation for clinic IOP measurement in pediatric glaucoma. This was a prospective study comparing Icare versus Goldmann tonometry in pediatric glaucoma. Children with known or suspected glaucoma were recruited from scheduled clinic visits. IOP was measured with the Icare tonometer by a clinician and subsequently measured with Goldmann applanation tonometry (GAT) by a different single masked clinician. A total of 71 eyes of 71 children with known or suspected glaucoma were included. IOP by GAT ranged from 9 to 36 mm Hg. Icare readings ranged from 11 to 44 mm Hg. Mean difference between Icare and GAT was 2.3 ± SD 3.7 mm Hg, p IOPs were within ± 3 mm Hg of GAT in 63%. Icare IOPs were ≥GAT IOPs in 75%. The following factors were not associated with Icare IOPs greater than GAT: child's age, glaucoma diagnosis, strabismus, nystagmus, central corneal thickness, Icare instrument-reported reliability, number of glaucoma surgeries or medications, corneal abnormalities, and visual acuity. IOP by Icare tonometry was within 3 mm Hg of IOP by GAT in 63% and greater than GAT in 75%. This device may be reasonable to estimate IOP in selected children with known or suspected glaucoma whose IOP cannot otherwise be obtained in clinic; however, correlation of Icare IOPs with clinical findings must continue to be considered in each case. Copyright © 2011 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

  20. Herbal hepatotoxicity: suspected cases assessed for alternative causes.

    Science.gov (United States)

    Teschke, Rolf; Schulze, Johannes; Schwarzenboeck, Alexander; Eickhoff, Axel; Frenzel, Christian

    2013-09-01

    Alternative explanations are common in suspected drug-induced liver injury (DILI) and account for up to 47.1% of analyzed cases. This raised the question of whether a similar frequency may prevail in cases of assumed herb-induced liver injury (HILI). We searched the Medline database for the following terms: herbs, herbal drugs, herbal dietary supplements, hepatotoxic herbs, herbal hepatotoxicity, and herb-induced liver injury. Additional terms specifically addressed single herbs and herbal products: black cohosh, Greater Celandine, green tea, Herbalife products, Hydroxycut, kava, and Pelargonium sidoides. We retrieved 23 published case series and regulatory assessments related to hepatotoxicity by herbs and herbal dietary supplements with alternative causes. The 23 publications comprised 573 cases of initially suspected HILI; alternative causes were evident in 278/573 cases (48.5%). Among them were hepatitis by various viruses (9.7%), autoimmune diseases (10.4%), nonalcoholic and alcoholic liver diseases (5.4%), liver injury by comedication (DILI and other HILI) (43.9%), and liver involvement in infectious diseases (4.7%). Biliary and pancreatic diseases were frequent alternative diagnoses (11.5%), raising therapeutic problems if specific treatment is withheld; pre-existing liver diseases including cirrhosis (9.7%) were additional confounding variables. Other diagnoses were rare, but possibly relevant for the individual patient. In 573 cases of initially assumed HILI, 48.5% showed alternative causes unrelated to the initially incriminated herb, herbal drug, or herbal dietary supplement, calling for thorough clinical evaluations and appropriate causality assessments in future cases of suspected HILI.

  1. Antineurofilament antibodies in postpolio syndrome.

    Science.gov (United States)

    Drory, V E; Shapira, A; Korczyn, A D; Shavit, S; Kushnir, M; Michaelson, D M; Chapman, J

    1998-10-01

    We determined the levels of antineurofilament antibodies in 29 patients with postpolio syndrome (PPS), 26 stable postpolio (PP) patients, 22 patients with ALS, and 20 normal controls (NCs). Patients with PPS had higher antibody levels to cholinergic neurofilaments than did all other groups. PP patients and those with ALS had antibody levels similar to those of NCs. The antibody binding level showed no relation to the age of the patients, duration of disease, or motor score.

  2. Benefits of sonography in diagnosing suspected uncomplicated acute diverticulitis.

    Science.gov (United States)

    King, Welfur C; Shuaib, Waqas; Vijayasarathi, Arvind; Fajardo, Carlos G; Cabrera, Waldo E; Costa, Juan L

    2015-01-01

    Despite evidence demonstrating equivalent accuracy of sonography and computed tomography (CT) in the workup of mild/uncomplicated acute diverticulitis, CT is overwhelmingly performed as the initial diagnostic test, particularly in the acute setting. Our study evaluated potential radiation and turnaround time savings associated with performing sonography instead of CT as the initial diagnostic examination in the workup of suspected uncomplicated acute diverticulitis. We retrospectively reviewed medical records from January 2010 to December 2012 for patients presenting with clinical symptoms of acute diverticulitis. Patients were categorized as a whole and subgrouped by age (>40 and 40 years and 121 diverticulitis. © 2015 by the American Institute of Ultrasound in Medicine.

  3. A Suspected Pelvic Aneurysmal Bone Cyst in Pregnancy

    Directory of Open Access Journals (Sweden)

    Rayan Elkattah

    2013-01-01

    Full Text Available Albeit rare, the majority of identified bone lesions in pregnancy spare the pelvis. Once encountered with a pelvic bone lesion in pregnancy, the obstetrician may face a challenging situation as it is difficult to determine and predict the effects that labor and parturition impart on the pelvic bones. Bone changes and pelvic bone fractures have been well documented during childbirth. The data regarding clinical outcomes and management of pregnancies complicated by pelvic ABCs is scant. Highly suspected to represent an aneurysmal bone cyst, the clinical evaluation of a pelvic lesion in the ilium of a pregnant individual is presented, and modes of delivery in such a scenario are discussed.

  4. Patch Testing in Suspected Allergic Contact Dermatitis to Cosmetics

    OpenAIRE

    Pramod Kumar; Rekha Paulose

    2014-01-01

    Background. Increasing use of cosmetics has contributed to a rise in the incidence of allergic contact dermatitis (ACD) to cosmetics. It is estimated that 1–5.4% of the population is sensitized to a cosmetic ingredient. Patch testing helps to confirm the presence of an allergy and to identify the actual allergens which are chemical mixtures of various ingredients. Objectives. The aims of this study are to perform patch testing in suspected ACD to cosmetics and to identify the most common alle...

  5. Coinfection with EBV/CMV and other respiratory agents in children with suspected infectious mononucleosis

    Directory of Open Access Journals (Sweden)

    Wei Cong

    2010-09-01

    Full Text Available Abstract Background Numerous studies have shown that Epstein-Barr virus (EBV and cytomegalovirus (CMV can infect immunocompetent patients simultaneously with other agents. Nonetheless, multiple infections with other agents in EBV/CMV-infected children have received little attention. We conducted a retrospective study of children with suspected infectious mononucleosis. Peripheral blood samples were analyzed by indirect immunofluorescence to detect EBV, CMV and other respiratory agents including respiratory syncytial virus; adenovirus; influenza virus types A and B; parainfluenza virus types 1, 2 and 3; Chlamydia pneumoniae and Mycoplasma pneumoniae. A medical history was collected for each child. Results The occurrence of multipathogen infections was 68.9%, 81.3% and 63.6% in the children with primary EBV, CMV or EBV/CMV, respectively, which was significantly higher than that in the past-infected group or the uninfected group (p C. pneumoniae in children with primary infection was as high as 50%, significantly higher than in the other groups (p Conclusion Our study suggests that there is a high incidence of multipathogen infections in children admitted with EBV/CMV primary infection and that the distribution of these pathogens is not random.

  6. Developing a Salivary Antibody Multiplex Immunoassay to ...

    Science.gov (United States)

    The etiology and impacts of human exposure to environmental pathogens are of major concern worldwide and, thus, the ability to assess exposure and infections using cost effective, high-throughput approaches would be indispensable. The principal objective of this work is to develop an immunoassay capable of measuring the presence of antibodies in human saliva to multiple pathogens simultaneously. Saliva is particularly attractive in this application because it is noninvasive, cheaper and easier to collect than serum. Antigens from environmental pathogens were coupled to carboxylated microspheres (beads) and used to measure antibodies in very small volumes of human saliva samples using the Luminex xMAP solution-phase assay. Beads were coupled to antigens from Campylobacter jejuni, Helicobacter pylori, Toxoplasma gondii, noroviruses (G I.1 and G II.4) and hepatitis A virus. To ensure that the antigens were sufficiently coupled to the beads, coupling was confirmed using species-specific, animal-derived primary detection antibodies, followed by incubation with biotinylated anti-species secondary detection antibodies and streptavidin-R-phycoerythrin reporter (SAPE). As a control to measure non-specific binding, one bead set was treated identically to the others except it was not coupled to any antigen. The antigen coupled and control beads were then incubated with prospectively-collected human saliva samples, analyzed on a Luminex 100 platform, and the presence

  7. Hashimoto encephalopathy in pediatric patients: Homogeneity in clinical presentation and heterogeneity in antibody titers.

    Science.gov (United States)

    Lee, Jiwon; Yu, Hee Joon; Lee, Jeehun

    2018-01-01

    Hashimoto encephalopathy is an autoimmune encephalopathy characterized by elevated antithyroid antibodies and a favorable response to corticosteroid. This study delineated the clinical characteristics of pediatric Hashimoto encephalopathy and the significance of low antithyroid antibody titers in diagnosis and treatment. Clinical manifestations, antibody titers, and treatment responses were retrospectively reviewed in six consecutive children diagnosed with Hashimoto encephalopathy between August 2008 and July 2016. Age at diagnosis was 10-17years. Presenting symptoms were seizures, altered consciousness, behavioral changes, psychosis, tremor, and dystonia. Thyroid function was normal in five patients, and one had hypothyroidism prior to the encephalopathy. Antithyroid antibody titer was increased at presentation in five patients and one week later in the other. Antibody levels were extremely varied (anti-thyroglobulin, 20.5-2318.0U/ml; anti-thyroid peroxidase, 12.5-2231.0U/ml; reference range, Hashimoto encephalopathy were similar, irrespective of antithyroid antibody titer. Because the initial antithyroid antibody titers can be normal or mildly-elevated, follow-up testing of antithyroid antibodies is required in patients who are clinically suspect for Hashimoto encephalopathy. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  8. Monkeypox-specific antibodies in human and simian sera from the Ivory Coast and Nigeria.

    Science.gov (United States)

    Gispen, R; Brand-Saathof, B B; Hekker, A C

    1976-01-01

    A test for monkeypox-specific antibodies is described. Monkeypox immune sera can be made type-specific by immunoabsorption with heterotypic poxvirus extracts. Monkeypox-specific antibodies were demonstrated in sera from 9 cynomolgus monkeys (Macaca fascicularis) that had previously been experimentally infected with monkeypox. Monkeypox-specific antibodies were found in 3 wild-caught African monkeys (Cercopithecus spp.) and in 3 human sera collected from Africans in the Ivory Coast and Nigeria 3(1/2)-4 years after they had suffered a pox-like infection. Monkeypox had been recognized in one of the patients by virus isolation, and had been suspected in the others for epidemiological reasons. Vaccinia-specific antibodies were found in 4 human sera collected 6 weeks after smallpox vaccination.The serological results provide the first laboratory evidence of a monkeypox reservoir in wild monkeys.

  9. Monkeypox-specific antibodies in human and simian sera from the Ivory Coast and Nigeria*

    Science.gov (United States)

    Gispen, R.; Brand-Saathof, B.; Hekker, A. C.

    1976-01-01

    A test for monkeypox-specific antibodies is described. Monkeypox immune sera can be made type-specific by immunoabsorption with heterotypic poxvirus extracts. Monkeypox-specific antibodies were demonstrated in sera from 9 cynomolgus monkeys (Macaca fascicularis) that had previously been experimentally infected with monkeypox. Monkeypox-specific antibodies were found in 3 wild-caught African monkeys (Cercopithecus spp.) and in 3 human sera collected from Africans in the Ivory Coast and Nigeria 3½-4 years after they had suffered a pox-like infection. Monkeypox had been recognized in one of the patients by virus isolation, and had been suspected in the others for epidemiological reasons. Vaccinia-specific antibodies were found in 4 human sera collected 6 weeks after smallpox vaccination. The serological results provide the first laboratory evidence of a monkeypox reservoir in wild monkeys. PMID:186210

  10. KADAR ANTIBODI-TIROPEROKSIDASE DAN ANTIBODI-TIROGLOBULIN PADA WANITA USIA SUBUR DI DAERAH ENDEMlS GAKI

    Directory of Open Access Journals (Sweden)

    Agus Wibowo

    2012-10-01

    Full Text Available Background: Thyroid hormones play a critical role in human. Disorders of the thyroid gland result primary from autoimmune processes that either stimulate the over production of thyroid hormones (hyperthyroid or causes glandular destruction and hormones deficiency (hypothyroid. Autoimmune Thyroid Disease (AITD a common organ specific autoimmune disorder is seen mostly in women. AITD are complex disease that are caused by an interaction between susceptibility genes and environmental trigger such dietary iodine. The development of antibodies to Thyroid peroxidase (TPO and Thyroglobulin (TG is the main hall mark of AITD. Method: 'Thirty respondents from were analyzed. The blood were collected for TSH, FreeT4, Tyroglobulin Antibody and Tyroperoxidase Antibody analyzed and DNA isolation. Circulating TSH, FreeT4, autoantibodies to TPO and TG are measured by ELISA. Result: 50% respondent in normal thyroid hormones and 50% in hypothyroid and hyperthyroid status. TPO antibodies  and thyroglobulin antibodies found in all of respondent with thyroid disorder. Conclusion: Antibodies to TPO and TG is seen in respondent with thyroid disorder   Keywords: AITD, TSH, FreeT4, TPO antibodies, TG antibodies.

  11. Comparison of a rapid immunochromatographic assay with an immunofluorescent antibody test for detection of Leishmania infantum antibodies in dogs.

    Science.gov (United States)

    Proverbio, Daniela; Spada, Eva; Perego, Roberta; Baggiani, Luciana; Bagnagatti De Giorgi, Giada; Migliazzo, Antonella; Vitale, Fabrizio

    2016-12-01

    Identification of Leishmania infantum-infected dogs is crucial for control of canine leishmaniosis. In particular, in areas where access to specialized laboratories is limited, the availability of reliable and rapid in-clinic serologic tests may support immediate diagnosis in suspected cases and permit detection of asymptomatic canine carriers of L infantum infection. The purpose of the study was to validate the immunochromatographic test (ICT) Anigen Rapid Leishmania Ab Test kit for detection of L infantum antibodies in naturally exposed dogs in comparison with the immunofluorescence antibody test (IFAT). Serum samples from 66 dogs, including 20 healthy control dogs and 46 dogs suspected or confirmed with canine leishmaniosis, were measured by both tests. Anti-Leishmania IgG titers ≥ 1:40 by IFAT were considered positive. Kappa statistic with a 95% CI was calculated to evaluate agreement between the 2 testing methods, and sensitivity, specificity, and positive and negative likelihood ratio were calculated. Anti-L infantum IgG antibodies were found in 35 of 66 samples using the IFAT test (titers 1:40-1:5120). Thirty-one out of 66 samples tested positive with the qualitative ICT. Four IFAT-positive (titers ICT-negative. The Kappa value of 0.853 demonstrated very good agreement between the 2 tests. The Anigen Rapid Leishmania Ab Test kit reliably identified canine sera with anti-L infantum IgG antibody titers ≥ 1:40. The ICT requires neither special preparation of the serum nor specialized equipment and can be stored at ambient temperature. The test is applicable as a field test because it is easy to use and provides rapid results. © 2016 American Society for Veterinary Clinical Pathology.

  12. Production of antibodies and antibody fragments in plants.

    Science.gov (United States)

    Peeters, K; De Wilde, C; De Jaeger, G; Angenon, G; Depicker, A

    2001-03-21

    Our current knowledge allows the generation of transgenic plants that efficiently produce heterologous proteins from plant, bacterial, fungal or animal origin. Among all types of recombinant proteins, antibodies are particularly attractive because of their ability to specifically recognize and bind virtually any type of antigen. Plants show several advantages as a large-scale antibody production system: they can be grown easily and inexpensively in large quantities that can be harvested, stored and processed by using existing infrastructures. Isolation and purification of plant-made antibodies, if necessary, allow fundamental, industrial, and therapeutical applications. In the past, we and others have successfully generated antibody-producing plants. The maximal accumulation levels of antibodies and antibody fragments that we observed are 1-5% of the extracted proteins. Currently, several biotechnological companies grow field crops to produce antibodies for ex planta applications on an industrial scale.

  13. Serum Dried Samples to Detect Dengue Antibodies: A Field Study

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    Angelica Maldonado-Rodríguez

    2017-01-01

    Full Text Available Background. Dried blood and serum samples are useful resources for detecting antiviral antibodies. The conditions for elution of the sample need to be optimized for each disease. Dengue is a widespread disease in Mexico which requires continuous surveillance. In this study, we standardized and validated a protocol for the specific detection of dengue antibodies from dried serum spots (DSSs. Methods. Paired serum and DSS samples from 66 suspected cases of dengue were collected in a clinic in Veracruz, Mexico. Samples were sent to our laboratory, where the conditions for optimal elution of DSSs were established. The presence of anti-dengue antibodies was determined in the paired samples. Results. DSS elution conditions were standardized as follows: 1 h at 4°C in 200 µl of DNase-, RNase-, and protease-free PBS (1x. The optimal volume of DSS eluate to be used in the IgG assay was 40 µl. Sensitivity of 94%, specificity of 93.3%, and kappa concordance of 0.87 were obtained when comparing the antidengue reactivity between DSSs and serum samples. Conclusion. DSS samples are useful for detecting anti-dengue IgG antibodies in the field.

  14. Prevalence of Entamoeba spp. in Stool Samples of Patients with Amebiasis Suspect by Native-Lugol and ELISA.

    Science.gov (United States)

    Beyhan, Yunus Emre; Yılmaz, Hasan; Taş Cengiz, Zeynep

    2016-06-01

    This study aimed to determine the prevalence of Entamoeba spp. in suspected stool samples submitted to our laboratory. In this retrospective study, stool samples of 998 patients with suspected amebiasis were sent from various clinics and services to our laboratory and were investigated by native-Lugol and enzyme-linked immunosorbent assay (ELISA) [for Entamoeba spp. antigen (Ridascreen® Entamoeba)] between January 2010 and December 2014. By the end of the study, it was shown that 8.5% (85) of 997 patients, 7.45% (39) of males and 9.8% (46) of females whom amoeba antigen inspected in their stool samples, were positive. No parasite was identified by the saline-Lugol method. The highest antigen positivity was detected in the 25-44-year-old group with 11% positivity, and a high positivity of 23.2% was seen in March. These results demonstrate that amebiasis is still a major health concern for our region. Although no parasite was detected during microscopic examinations, the detection of antigen positivity by ELISA reveals that microscopic examinations require experience and utilizing only microscopic examinations may lead to overlooks. To obtain more reliable results in diagnosis, ELISA analyses that use E. histolytica-specific monoclonal antibodies should be applied in addition to microscopic methods.

  15. MRI diagnosis of suspected atlanto-occipital dissociation in childhood

    Energy Technology Data Exchange (ETDEWEB)

    Grabb, B.C.; Frye, T.A.; Hedlund, G.L.; Vaid, Y.N.; Royal, S.A. [Department of Radiology, The Children`s Hospital of Alabama, Birmingham (United States); Grabb, P.A. [Department of Neurosurgery, University of Alabama at Birmingham (United States)

    1999-04-01

    Objective. To demonstrate the utility of magnetic resonance (MR) imaging in the diagnosis of complete and partial ligamentous injuries in patients with suspected atlanto-occipital dissociation (AOD). Materials and methods. Five patients with suspected AOD had MR imaging performed within an average of 4 days after injury. MR scans were reviewed with specific analysis of craniocervical ligamentous structures. Charts were reviewed to obtain clinical information regarding presentation, treatment, hospital course, and outcome. Results. Two patients demonstrated MR evidence of complete AOD. One had disruption of all visualized major ligamentous structures at the craniocervical junction with anterolisthesis and evidence of cord damage. The second had injuries to the tectorial membrane, superior band of the cruciform ligament, apical ligament, and interspinous ligament at C 1-2. The remaining three patients sustained incomplete severance of the ligamentous structures at the craniocervical junction. All patients demonstrated subtle radiographic findings suggestive of AOD, including soft tissue swelling at the craniocervical junction without fracture. The two patients with complete AOD died. The three patients with partial AOD were treated with stabilization. On follow-up, these three children were asymptomatic following their craniocervical injury. Conclusion. MR imaging of acute AOD provides accurate identification of the craniocervical ligaments injured, classification of full versus partial ligamentous disruption, and analysis of accompanying spinal cord injury. This information is important for early appropriate neurosurgical management and preservation of neurologic function in survivors. (orig.) With 7 figs., 1 tab., 14 refs.

  16. MRI diagnosis of suspected atlanto-occipital dissociation in childhood.

    Science.gov (United States)

    Grabb, B C; Frye, T A; Hedlund, G L; Vaid, Y N; Grabb, P A; Royal, S A

    1999-04-01

    To demonstrate the utility of magnetic resonance (MR) imaging in the diagnosis of complete and partial ligamentous injuries in patients with suspected atlanto-occipital dissociation (AOD). Five patients with suspected AOD had MR imaging performed within an average of 4 days after injury. MR scans were reviewed with specific analysis of craniocervical ligamentous structures. Charts were reviewed to obtain clinical information regarding presentation, treatment, hospital course, and outcome. Two patients demonstrated MR evidence of complete AOD. One had disruption of all visualized major ligamentous structures at the craniocervical junction with anterolisthesis and evidence of cord damage. The second had injuries to the tectorial membrane, superior band of the cruciform ligament, apical ligament, and interspinous ligament at C 1-2. The remaining three patients sustained incomplete severance of the ligamentous structures at the craniocervical junction. All patients demonstrated subtle radiographic findings suggestive of AOD, including soft tissue swelling at the craniocervical junction without fracture. The two patients with complete AOD died. The three patients with partial AOD were treated with stabilization. On follow-up, these three children were asymptomatic following their craniocervical injury. MR imaging of acute AOD provides accurate identification of the craniocervical ligaments injured, classification of full versus partial ligamentous disruption, and analysis of accompanying spinal cord injury. This information is important for early appropriate neurosurgical management and preservation of neurologic function in survivors.

  17. CT Pulmonary Angiography and Suspected Acute Pulmonary Embolism

    Energy Technology Data Exchange (ETDEWEB)

    Enden, T.; Kloew, N.E. [Ullevaal Univ. Hospital, Oslo (Norway). Dept. of Cardiovascular Radiology

    2003-05-01

    Purpose: To evaluate the use and quality of CT pulmonary angiography in our department, and to relate the findings to clinical parameters and diagnoses. Material and Methods: A retrospective study of 324 consecutive patients referred to CT pulmonary angiography with clinically suspected pulmonary embolism (PE). From the medical records we registered clinical parameters, blood gases, D-dimer, risk factors and the results of other relevant imaging studies. Results: 55 patients (17%) had PE detected on CT. 39 had bilateral PE, and 8 patients had isolated peripheral PE. 87% of the examinations showing PE had satisfactory filling of contrast material including the segmental pulmonary arteries, and 60% of the subsegmental arteries. D-dimer test was performed in 209 patients, 85% were positive. A negative D-dimer ruled out PE detected at CT. Dyspnea and concurrent symptoms or detection of deep vein thrombosis (DVT), contraceptive pills and former venous thromboembolism (VTE) were associated with PE. The presence of only one clinical parameter indicated a negative PE diagnosis (p < 0.017), whereas two or more suggested a positive PE diagnosis (p < 0.002). CT also detected various ancillary findings such as consolidation, pleural effusion, nodule or tumor in nearly half of the patients; however, there was no association with the PE diagnosis. Conclusion: The quality of CT pulmonary angiography was satisfactory as a first-line imaging of PE. CT also showed additional pathology of importance in the chest. Our study confirmed that a negative D-dimer ruled out clinically suspected VTE.

  18. Ocular lesions following suspected lightning injury in a horse.

    Science.gov (United States)

    Evans, Paige M; Armour, Micki D; Dubielzig, Richard R

    2012-07-01

      To describe the gross and histopathological ocular findings in a horse following suspected lightning injury.   The eyes of a 2-year-old thoroughbred gelding were clinically and histopathologically evaluated following a severe lightning storm following euthanasia because of visual impairment.   Severe corneal edema and hydrops were noted clinically oculus dexter. Indirect ophthalmoscopy revealed bilateral symmetrical raised hyporeflective peripapillary geographic lesions. Histopathologic evaluation revealed corneal edema in the right eye with normal corneal endothelium. Posterior segment evaluation revealed localized, pericentral choroidal lesions characterized by the presence of hemorrhage, early fibrosis, and minimal lymphoplasmacytic, neutrophilic, and histiocytic inflammation with spindle cell proliferation. The retinas overlying the choroidal lesions were necrotic and mostly absent. Peripheral to the focal lesion, the retina abruptly returned to normal architecture peripheral to a zone of apoptotic photoreceptors. Centrally, swollen axons extended into the optic disc.   There have been few descriptions of ocular lesions in animals following suspected lightning injury. We believe these findings to be unique because of the type of thermal injury that may be characteristic of lightening injury. We do not know whether these lesions would have progressed over time. © 2011 American College of Veterinary Ophthalmologists.

  19. Suspected side effects to the quadrivalent human papilloma vaccine.

    Science.gov (United States)

    Brinth, Louise; Theibel, Ann Cathrine; Pors, Kirsten; Mehlsen, Jesper

    2015-04-01

    The quadrivalent vaccine that protects against human papilloma virus types 6, 11, 16 and 18 (Q-HPV vaccine, Gardasil) was included into the Danish childhood vaccination programme in 2009. During the past years, a collection of symptoms primarily consistent with sympathetic nervous system dysfunction have been described as suspected side effects to the Q-HPV vaccine. We present a description of suspected side effects to the Q-HPV vaccine in 53 patients referred to our Syncope Unit for tilt table test and evaluation of autonomic nervous system function. All patients had symptoms consistent with pronounced autonomic dysfunction including different degrees of orthostatic intolerance, severe non-migraine-like headache, excessive fatigue, cognitive dysfunction, gastrointestinal discomfort and widespread pain of a neuropathic character. We found consistency in the reported symptoms as well as between our findings and those described by others. Our findings neither confirm nor dismiss a causal link to the Q-HPV vaccine, but they suggest that further research is urgently warranted to clarify the pathophysiology behind the symptoms experienced in these patients and to evaluate the possibility and the nature of any causal link and hopefully establish targeted treatment options. not relevant. not relevant.

  20. Patch Testing in Suspected Allergic Contact Dermatitis to Cosmetics

    Science.gov (United States)

    Paulose, Rekha

    2014-01-01

    Background. Increasing use of cosmetics has contributed to a rise in the incidence of allergic contact dermatitis (ACD) to cosmetics. It is estimated that 1–5.4% of the population is sensitized to a cosmetic ingredient. Patch testing helps to confirm the presence of an allergy and to identify the actual allergens which are chemical mixtures of various ingredients. Objectives. The aims of this study are to perform patch testing in suspected ACD to cosmetics and to identify the most common allergen and cosmetic product causing dermatitis. Methods. Fifty patients with suspected ACD to cosmetics were patch-tested with 38 antigens of the Indian Cosmetic Series and 12 antigens of the Indian Standard Series. Results. The majority (58%) of patients belonged to the 21–40 years age group. The presence of ACD to cosmetics was confirmed in 38 (76%) patients. Face creams (20%), hair dyes (14%), and soaps (12%) were the most commonly implicated. The most common allergens identified were gallate mix (40%), cetrimide (28%), and thiomersal (20%). Out of a total of 2531 patches applied, positive reactions were obtained in 3.75%. Conclusion. Incidence of ACD to cosmetics was greater in females. Face creams and hair dyes were the most common cosmetic products implicated. The principal allergens were gallate mix, cetrimide, and thiomersal. PMID:25295057

  1. Feline toxicological emergencies: when to suspect and what to do.

    Science.gov (United States)

    Grave, Tobias W; Boag, Amanda K

    2010-11-01

    Confirmed or suspected intoxications with a wide variety of agents represent a small but important group of feline emergency cases. Generally it is thought that toxicities are less common in cats compared with dogs, with a higher proportion relating to dermal as opposed to oral exposure. Once toxicity is suspected or diagnosed, it must be recognised that treatment regimes may need modification compared with those established for dogs. Different drugs or different dosages may be warranted and the choice of available drugs may be reduced. This review draws on published studies, case reports and clinical experience to summarise key features of the general management of the intoxicated feline patient before describing some of the more serious and common intoxications in more detail. The focus throughout the review is on the peculiarities of feline metabolism and how they may impact on presentation and treatment. The aim is to assist companion animal and feline practitioners, who are in the frontline when it comes to managing these emergency cases. Copyright © 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

  2. Plant antibodies for immunotherapy.

    Science.gov (United States)

    Ma, J K; Hein, M B

    1995-01-01

    The original report of Hiatt (1989) initiated a wave of excitement at the realization that a complex mammalian protein such as immunoglobulin could be assembled within a plant cell. The general reaction was one of amazement, but interest in exploiting the possibilities arising from the discovery, for example to make antibodies of therapeutic value, has taken a considerable time to develop. In the meantime, other recombinant expression systems and traditional cell culture techniques have advanced and overcome some of their problems, particularly those associated with yields. Plants, however, still offer unique advantages, especially in their ability to match the protein assembly capabilities of mammalian cells (as demonstrated by the assembly of SIgA molecules), as well as to provide antibodies in bulk at low cost. In addition, the area of "immunization" of plants holds great promise and will surely be a field of enormous growth for the future. PMID:7480334

  3. Influenza Illness among Case-Patients Hospitalized for Suspected Dengue, El Salvador, 2012.

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    Rafael Chacon

    Full Text Available We estimate the proportion of patients hospitalized for suspected dengue that tested positive for influenza virus in El Salvador during the 2012 influenza season. We tested specimens from 321 hospitalized patients: 198 patients with SARI and 123 patients with suspected dengue. Among 121 hospitalized suspected dengue (two co-infected excluded patients, 28% tested positive for dengue and 19% positive for influenza; among 35 with suspected dengue and respiratory symptoms, 14% were positive for dengue and 39% positive for influenza. One percent presented co-infection between influenza and dengue. Clinicians should consider the diagnosis of influenza among patients with suspected dengue during the influenza season.

  4. Influenza Illness among Case-Patients Hospitalized for Suspected Dengue, El Salvador, 2012.

    Science.gov (United States)

    Chacon, Rafael; Clara, Alexey Wilfrido; Jara, Jorge; Armero, Julio; Lozano, Celina; El Omeiri, Nathalie; Widdowson, Marc-Alain; Azziz-Baumgartner, Eduardo

    2015-01-01

    We estimate the proportion of patients hospitalized for suspected dengue that tested positive for influenza virus in El Salvador during the 2012 influenza season. We tested specimens from 321 hospitalized patients: 198 patients with SARI and 123 patients with suspected dengue. Among 121 hospitalized suspected dengue (two co-infected excluded) patients, 28% tested positive for dengue and 19% positive for influenza; among 35 with suspected dengue and respiratory symptoms, 14% were positive for dengue and 39% positive for influenza. One percent presented co-infection between influenza and dengue. Clinicians should consider the diagnosis of influenza among patients with suspected dengue during the influenza season.

  5. A Case Report on Suspected Levamisole-Induced Pseudovasculitis.

    Science.gov (United States)

    Fan, Tiffany; Macaraeg, Jeffrey; Haddad, Toufik Mahfood; Bacon, Holly; Le, Duc; Mirza, Mohsin; Valenta, Carrie; Wichman, Tammy

    2017-02-01

    Levamisole-induced pseudovasculitis should be considered in patients with inconsistent anti-neutrophil cytoplasmic antibodies (ANCA) pattern and history of cocaine use. A 50-year-old man presented to the emergency department with symptoms of bilateral pulmonary emboli. His hospital course was complicated by multiple end organ failure, which improved dramatically with prednisone. Although he was diagnosed previously with granulomatosis with polyangiitis due to positive proteinase 3 (PR3), myeloperoxidase (MPO), perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) and cytoplasmic anti-neutrophil cytoplasmic antibodies (C-ANCA) markers, his longstanding cocaine use and history of skin ulcers, thrombotic events, and febrile illnesses suggested a diagnosis of levamisole-induced pseudovasculitis instead. Differentiating between vasculitides can be challenging due to similar clinical and laboratory findings. To differentiate the two, biopsies should be obtained. The absence of granulomas or leukocytoclasia, and the presence of vasculopathic purpura, should guide clinicians toward pseudovasculitis. It is important to maintain a high index of suspicion for pseudovasculitis because long-term corticosteroid use to treat granulomatosis with polyangiitis can lead to detrimental effects.

  6. [The benefit from mumps virus IgG antibody avidity testing in the population with high vaccine coverage in the context of other serological methods for laboratory diagnosis of mumps and the current epidemiological].

    Science.gov (United States)

    Limberková, R; Smíšková, D; Havlíčková, M; Herrmannová, K; Lexová, P; Marešová, V

    2016-01-01

    Regular vaccination against mumps resulted in a significant reduction in epidemic mumps in the Czech Republic. However, mumps cases have recently shown an upward trend, even in the vaccinated population where a considerable proportion of cases have occurred. The aim of this study was to find out, by mumps virus IgG antibody avidity testing, whether the high incidence of mumps in the vaccinated population is a result of primary or secondary vaccine failure and whether the vaccinated differ from the naturally immunised in anamnestic antibody avidity. Given the problematic laboratory diagnosis of mumps in the population with high vaccination coverage, the informative value of the detected IgM, IgA, and IgG antibodies was also considered as well as the potential of antibody avidity testing for improving laboratory diagnosis from a single sample of blood, the most commonly analysed clinical material, in patients with suspected mumps. Sixty-four patients laboratory confirmed with mumps, whose vaccination status was known, were included in the study (groups 1 and 2). Other study groups were 30 healthy naturally immunised subjects (group 3) and 22 vaccinated children 2-4-years of age with no etiological link to the mumps virus (group 4). The avidity index (AI) was determined using the Siemens Enzygnost Anti-Mumps/IgG kit and 6M urea, able to induce the dissociation of antigen-antibody bonds proportionally to the antibody avidity. IgM, IgG, and IgA antibodies were tested using the Siemens Enzygnost Anti-Mumps/IgM and /IgG, and Mast Diagnostica Mastazyme Mumps IgA kits. The EPIDAT system served as the data source. The results showed that the mumps virus induces antibodies with a low AI after both vaccination, even recent, and natural immunisation. Antibodies with a high AI were only detected in convalescent sera of the vaccinated patients or in re-infected, naturally immunised persons, as a result of recent contact with the mumps virus. The comparison of the results of acute

  7. An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity

    Science.gov (United States)

    2014-01-01

    Background Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome with several unsettled issues despite the increasing awareness of its existence. We carried out a prospective survey on NCGS in Italian centers for the diagnosis of gluten-related disorders, with the aim of defining the clinical picture of this new syndrome and to establish roughly its prevalence compared with celiac disease. Methods From November 2012 to October 2013, 38 Italian centers (27 adult gastroenterology, 5 internal medicine, 4 pediatrics, and 2 allergy) participated in this prospective survey. A questionnaire was used in order to allow uniform and accurate collection of clinical, biochemical, and instrumental data. Results In total, 486 patients with suspected NCGS were identified in this 1-year period. The female/male ratio was 5.4 to 1, and the mean age was 38 years (range 3–81). The clinical picture was characterized by combined gastrointestinal (abdominal pain, bloating, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and systemic manifestations (tiredness, headache, fibromyalgia-like joint/muscle pain, leg or arm numbness, 'foggy mind,' dermatitis or skin rash, depression, anxiety, and anemia). In the large majority of patients, the time lapse between gluten ingestion and the appearance of symptoms varied from a few hours to 1 day. The most frequent associated disorders were irritable bowel syndrome (47%), food intolerance (35%) and IgE-mediated allergy (22%). An associated autoimmune disease was detected in 14% of cases. Regarding family history, 18% of our patients had a relative with celiac disease, but no correlation was found between NCGS and positivity for HLA-DQ2/-DQ8. IgG anti-gliadin antibodies were detected in 25% of the patients tested. Only a proportion of patients underwent duodenal biopsy; for those that did, the biopsies showed normal intestinal mucosa (69%) or mild increase in intraepithelial

  8. Using Internet Artifacts to Profile a Child Pornography Suspect

    Directory of Open Access Journals (Sweden)

    Marcus K. Rogers

    2014-03-01

    Full Text Available Digital evidence plays a crucial role in child pornography investigations. However, in the following case study, the authors argue that the behavioral analysis or “profiling” of digital evidence can also play a vital role in child pornography investigations. The following case study assessed the Internet Browsing History (Internet Explorer Bookmarks, Mozilla Bookmarks, and Mozilla History from a suspected child pornography user’s computer. The suspect in this case claimed to be conducting an ad hoc law enforcement investigation. After the URLs were classified (Neutral; Adult Porn; Child Porn; Adult Dating sites; Pictures from Social Networking Profiles; Chat Sessions; Bestiality; Data Cleaning; Gay Porn, the Internet history files were statistically analyzed to determine prevalence and trends in Internet browsing. First, a frequency analysis was used to determine a baseline of online behavior. Results showed 54% (n = 3205 of the URLs were classified as “neutral” and 38.8% (n = 2265 of the URLs were classified as a porn website. Only 10.8% of the URLs were classified as child pornography websites. However when the IE history file was analyzed by visit, or “hit,” count, the Pictures/Profiles (31.5% category had the highest visit count followed by Neutral (19.3%, Gay Porn (17%, and Child Porn (16.6%. When comparing the frequency of URLs to the Hit Count for each pornography type, it was noted that the accused was accessing gay porn, child porn, chat rooms, and picture profiles (i.e., from Facebook more often than adult porn and neutral websites. The authors concluded that the suspect in this case was in fact a child pornography user and not an ad hoc investigator, and the findings from the behavioral analysis were admitted as evidence in the sentencing hearing for this case. The authors believe this case study illustrates the ability to conduct a behavioral analysis of digital evidence. More work is required to further validate the

  9. Teicoplanin versus vancomycin for proven or suspected infection.

    Science.gov (United States)

    Cavalcanti, Alexandre B; Goncalves, Anderson R; Almeida, Claudia S; Bugano, Diogo Dg; Silva, Eliezer

    2010-06-16

    Vancomycin and teicoplanin are commonly used to treat gram-positive infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA). There is uncertainty regarding the effects of teicoplanin compared to vancomycin on kidney function with some previous studies suggesting teicoplanin is less nephrotoxic than vancomycin. To investigate the efficacy and safety of vancomycin versus teicoplanin in patients with proven or suspected infection. We searched the Cochrane Renal Group's Specialised Register, CENTRAL, MEDLINE, EMBASE, reference lists of nephrology textbooks, review articles with relevant studies and sent letters seeking information about unpublished or incomplete studies to investigators involved in previous studies. We searched for randomised controlled trials (RCTs) in any language comparing teicoplanin to vancomycin for patients with proven or suspected infection. Two authors independently evaluated methodological quality and extracted data using standardised data extraction forms. Study investigators were contacted for information not available in the original manuscripts. Random effects model was used to estimate the pooled risk ratio (RR) with 95% confidence interval (CI). We included 24 studies (2,610 patients) in this review. Teicoplanin reduced the risk of nephrotoxicity compared to vancomycin (RR 0.66, 95% CI 0.48 to 0.90).The effects of teicoplanin or vancomycin were similar for clinical cure (RR 1.03, 95% CI 0.98 to 1.08), microbiological cure (RR 0.98, 95% CI 0.93 to 1.03) and mortality (RR 1.02, 95% CI 0.79 to1.30). Six studies reported no cases of acute kidney injury (AKI) needing dialysis. Adverse events were less frequent with teicoplanin including cutaneous rash (RR 0.57, 95% CI 0.35 to 0.92), red man syndrome (RR 0.21, 95% CI 0.08 to 0.59) and total adverse events (RR 0.73, 95% CI 0.53 to 1.00). A lower risk of nephrotoxicity with teicoplanin was observed in patients either with (RR 0.51, 95% CI 0.30 to 0.88) or

  10. Secondary Mechanisms of Affinity Maturation in the Human Antibody Repertoire

    Directory of Open Access Journals (Sweden)

    Bryan S. Briney

    2013-03-01

    Full Text Available V(DJ recombination and somatic hypermutation (SHM are the primary mechanisms for diversification of the human antibody repertoire. These mechanisms allow for rapid humoral immune responses to a wide range of pathogenic challenges. V(DJ recombination efficiently generate a virtually limitless diversity through random recombination of variable (V, diversity (D and joining (J genes with diverse nontemplated junctions between the selected gene segments. Following antigen stimulation, affinity maturation by SHM produces antibodies with refined specificity mediated by mutations typically focused in complementarity determining regions (CDRs, which form the bulk of the antigen recognition site. While V(DJ recombination and SHM are responsible for much of the diversity of the antibody repertoire, there are several secondary mechanisms that, while less frequent, make substantial contributions to antibody diversity including V(DDJ recombination (or D-D fusion, somatic-hypermutation-associated insertions and deletions, and affinity maturation and antigen contact by non-CDR regions of the antibody. In addition to enhanced diversity, these mechanisms allow the production of antibodies that are critical to response to a variety of viral and bacterial pathogens but that would be difficult to generate using only the primary mechanisms of diversification.

  11. Progressive lesions of central nervous system in microcephalic fetuses with suspected congenital Zika virus syndrome.

    Science.gov (United States)

    Sarno, M; Aquino, M; Pimentel, K; Cabral, R; Costa, G; Bastos, F; Brites, C

    2017-12-01

    To describe the pattern and progression of central nervous system (CNS) lesions in microcephalic fetuses with suspected Zika virus (ZIKV) infection. In this prospective study in Salvador, Brazil, we analyzed fetuses diagnosed with microcephaly and suspected ZIKV infection after a routine primary care ultrasound scan between July 2015 and February 2016 raised suspicion of fetal microcephaly. The pregnancies were followed with serial ultrasound scans until delivery at one of the three main referral centers for fetal abnormalities in Salvador, Brazil. Microcephaly was diagnosed when the head circumference was two or more SDs below the mean for gestational age and its relationship with ZIKV infection was defined according to the World Health Organization's criteria. All women were interviewed, to assess potential factors associated with fetal microcephaly. Serology test results for toxoplasmosis, cytomegalovirus, rubella, syphilis and human immunodeficiency virus (HIV) were recorded, as were previous routine ultrasound results. Signs/symptoms of infection during the pregnancy were noted. Of 60 cases of suspected ZIKV-related fetal microcephaly seen during the study period, eight were excluded due to serological evidence of other congenital infection