WorldWideScience

Sample records for human immunoglobulin offers

  1. A 10% ready-to-use intravenous human immunoglobulin offers potential economic advantages over a lyophilized product in the treatment of primary immunodeficiency

    NARCIS (Netherlands)

    Kallenberg, C. G. M.

    2007-01-01

    Intravenous immunoglobulin (IVIg) replacement therapy is the standard of care for patients with primary humoral immunodeficiencies. This study evaluated differences in infusion time between a 10% IVIg ready-to-use solution and a 6% IVIg lyophilized product and addressed potential cost implications.

  2. HPLC chromatofocusing of human immunoglobulins.

    Science.gov (United States)

    Waldrep, J C; Schulte, J R

    1989-03-31

    A method is described for fractionation and analysis of IgA, IgM, and IgG and antibodies in human serum and/or plasma using a combination of HPLC chromatofocusing and immunoassay. A pH 9.0-3.2 gradient is utilized to separate the major proteins in the complex biological samples and monoclonal antibody based ELISAs used to determine the isotype profiles. Antigen-specific ELISAs are subsequently utilized to determine the distribution of antibody species within the chromatofocused specimens. This method is versatile since multiple simultaneous assays can easily be run on each fraction generating extensive qualitative information regarding immunoglobulin classes, subclasses, and antibodies and their distribution profiles. Such spectra will prove useful for experimental kinetic analysis of the humoral immune status of humans and experimental animals.

  3. Prognostic Value Of Immunoglobulin Profile In Human Papilloma Virus Infection

    National Research Council Canada - National Science Library

    Chattopadhyay S P

    2001-01-01

    Present study aimed at defining the prognostic value of immunoglobulin profile in human papilloma virus infection by assessing and correlating the levels of immunoglobulin with type, number, duration...

  4. Translocations affecting human immunoglobulin heavy chain locus

    Directory of Open Access Journals (Sweden)

    Sklyar I. V.

    2014-03-01

    Full Text Available Translocations involving human immunoglobulin heavy chain (IGH locus are implicated in different leukaemias and lymphomas, including multiple myeloma, mantle cell lymphoma, Burkitt’s lymphoma and diffuse large B cell lymphoma. We have analysed published data and identified eleven breakpoint cluster regions (bcr related to these cancers within the IgH locus. These ~1 kbp bcrs are specific for one or several types of blood cancer. Our findings could help devise PCR-based assays to detect cancer-related translocations, to identify the mechanisms of translocations and to help in the research of potential translocation partners of the immunoglobulin locus at different stages of B-cell differentiation.

  5. Gene conversion in human rearranged immunoglobulin genes.

    Science.gov (United States)

    Darlow, John M; Stott, David I

    2006-07-01

    Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V(H) segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V(H) replacements with no addition of untemplated nucleotides at the V(H)-V(H) joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V(H) replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion.

  6. Intravenous polyclonal human immunoglobulins in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Per Soelberg

    2008-01-01

    Intravenous immunoglobulin (IVIG) is an established therapy for demyelinating diseases of the peripheral nervous system. IVIG exerts a number of effects that may be beneficial in multiple sclerosis (MS). Four double-blind IVIG trials have been performed in relapsing-remitting MS. A meta...

  7. Offers

    CERN Multimedia

    Staff Association

    2011-01-01

    Special offers for our members       Go Sport in Val Thoiry is offering 15% discount on all purchases made in the shop upon presentation of the Staff Association membership card (excluding promotions, sale items and bargain corner, and excluding purchases using Go Sport  and Kadéos gift cards. Only one discount can be applied to each purchase).  

  8. Offers

    CERN Multimedia

    Staff Association

    2012-01-01

    L'Occitane en Provence proposes the following offer: 10 % discount on all products in all L'Occitane shops in Metropolitan France upon presentation of your Staff Association membership card and a valid ID. This offer is valid only for one person, is non-transferable and cannot be combined with other promotions.

  9. Offers

    CERN Multimedia

    Staff Association

    2014-01-01

    New offers : Discover the theater Galpon in Geneva. The Staff Association is happy to offer to its members a discount of 8.00 CHF on a full-price ticket (tickets of 15.00 CHF instead of 22.00 CHF) so do not hesitate anymore (mandatory reservation by phone + 4122 321  21 76 as tickets are quickly sold out!). For further information, please see our website: http://staff-association.web.cern.ch/fr/content/th%C3%A9%C3%A2tre-du-galpon  

  10. Offer

    CERN Multimedia

    Staff Association

    2016-01-01

    CERN was selected and participated in the ranking "Best Employers" organized by the magazine Bilan. To thank CERN for its collaboration, the magazine offers a reduction to the subscription fee for all employed members of personnel. 25% off the annual subscription: CHF 149.25 instead of CHF 199 .— The subscription includes the magazine delivered to your home for a year, every other Wednesday, as well as special editions and access to the e-paper. To benefit from this offer, simply fill out the form provided for this purpose. To get the form, please contact the secretariat of the Staff Association (Staff.Association@cern.ch).

  11. Offers

    CERN Multimedia

    Staff Association

    2013-01-01

    SPECIAL OFFER FOR OUR MEMBERS Prices Spring and Summer 2013 Day ticket: same price weekends, public holidays and weekdays: Children from 5 to 15 years old: 30 CHF instead of 39 CHF Adults from 16 years old: 36 CHF instead of 49 CHF Bonus! Free for children under 5 Tickets available at the Staff Association Secretariat.

  12. Offers

    CERN Multimedia

    Association du personnel

    2013-01-01

    SPECIAL OFFER FOR OUR MEMBERS Prices Spring and Summer 2013 Day ticket: same price weekends, public holidays and weekdays: – Children from 5 to 15 years old: 30 CHF instead of 39 CHF – Adults from 16 years old: 36 CHF instead of 49 CHF – Bonus! Free for children under 5 Tickets available at the Staff Association Secretariat.

  13. Offers

    CERN Multimedia

    Staff Association

    2013-01-01

    The theater season will start again, so do not hesitate to benefit from our discount: Théâtre de Carouge : Discount for all shows and on various season tickets. La Comédie : reduction on various tickets, on annual subscriptions and on discounted card. For further information, see our website: http://staff-association.web.cern.ch/sociocultural/offers

  14. Offers

    CERN Multimedia

    Staff Association

    2012-01-01

    proposes the following offer: 15% discount for the Staff Association members who enroll their children in summer FUTUREKIDS activities. Extracurricular Activities For Your Children The FUTUREKIDS Geneva Learning Center is open 6 days a week and offers a selection of after-school extracurricular activities for children and teenagers (ages 5 to 16). In addition to teaching in its Learning Centers, Futurekids collaborates with many private schools in Suisse Romande (Florimont, Moser, Champittet, Ecole Nouvelle, etc.) and with the Département de l'Instruction Publique (DIP) Genève. Courses and camps are usually in French but English groups can be set up on demand. FUTUREKIDS Computer Camps (during school holidays) FUTUREKIDS Computer Camps are a way of having a great time during vacations while learning something useful, possibly discovering a new hobby or even, why not, a future profession. Our computer camps are at the forefront of technology. Themes are diverse and suit all ...

  15. Offers

    CERN Multimedia

    Staff Association

    2015-01-01

    New offer for our members. The Staff Association CERN staff has recently concluded a framework agreement with AXA Insurance Ltd, General-Guisan-Strasse 40, 8401 Winterthur. This contract allows you to benefit from a preferential tariff and conditions for insurances: Motor vehicles for passenger cars and motorcycles of the product line STRADA: 10% discount Household insurance (personal liability and household contents) the product line BOX: 10% discount Travel insurance: 10% discount Buildings: 10% discount Legal protection: 10% discount AXA is number one on the Swiss insurance market. The product range encompasses all non-life insurance such as insurance of persons, property, civil liability, vehicles, credit and travel as well as innovative and comprehensive solutions in the field of occupational benefits insurance for individuals and businesses. Finally, the affiliate AXA-ARAG (legal expenses insurance) completes the offer. Armed with your staff association CERN card, you can always get the offe...

  16. Offer

    CERN Multimedia

    Staff Association

    2010-01-01

      Special offer for members of the Staff Association and their families 10% reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Plus 20% reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * Next “vente privée” from 22th to 29th November 2010

  17. Offer

    CERN Multimedia

    Staff Association

    2011-01-01

      Special offer for members of the Staff Association and their families 10% reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Plus 20% reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * Next “vente privée” from 25th to 27th March 2011  

  18. Offer

    CERN Multimedia

    CARLSON WAGONLIT TRAVEL

    2011-01-01

    Special offer   From 14th to 28th February 2011: no CWT service fee! For any new reservation of a holiday package (flight + hotel/apartment) from a catalog “summer 2011” For any additional information our staff is at your disposal from Monday – Friday, from 8h30 to 16h30. Phone number 72763 or 72797 Carlson Wagonlit Tavel, Agence du CERN  

  19. Offers

    CERN Multimedia

    Staff Association

    2012-01-01

    SPECIAL OFFER FOR OUR MEMBERS Prices Spring and Summer 2012 Half-day ticket: 5 hours, same price weekends, public holidays and weekdays. Children from 5 to 15 years old: 26 CHF instead of 35 CHF Adults from 16 years old: 32 CHF instead of 43 CHF Bonus! Free for children under 5. Aquaparc Les Caraïbes sur Léman 1807 Le Bouveret (VS)

  20. Offers

    CERN Document Server

    Staff Association

    2012-01-01

    SPECIAL OFFER FOR OUR MEMBERS Single tariff Adulte/Enfant Tickets “Zone terrestre” 20 euros instead of 25 euros. Access to Aqualibi: 5 euros instead of 8 euros on presentation of your ticket SA member. Free for children under 3, with limited access to the attractions. More information on our website : http://association.web.cern.ch/association/en/OtherActivities/Walibi.html

  1. Offers

    CERN Multimedia

    Staff Association

    2011-01-01

    Banque cantonale de Genève (BCGE) The BCGE Business partner programme devised for members of the CERN Staff Association offers personalized banking solutions with preferential conditions. The advantages are linked to salary accounts (free account keeping, internet banking, free Maestro and credit cards, etc.), mortgage lending, retirement planning, investment, credit, etc. The details of the programme and the preferential conditions are available on our website: http://association.web.cern.ch/association/en/OtherActivities/BCGE.html.  

  2. Offers

    CERN Multimedia

    Staff Association

    2013-01-01

    Special offer for members of the Staff Association and their families 10 % reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Plus 20 % reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * Next “vente privée” from 11th to 23rd November 2013 Please contact the Staff Association Secretariat to get the discount voucher.  

  3. Offers

    CERN Multimedia

    Staff Association

    2012-01-01

    Special offer for members of the Staff Association and their families 10% reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Plus 20% reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * Next “vente privée” from 21st to 26th May 2012 Please contact the Staff Association Secretariat to get the discount voucher  

  4. Offers

    CERN Multimedia

    Staff Association

    2012-01-01

    Special offer for members of the Staff Association and their families 10 % reduction on all products in the Sephora shop (sells perfume, beauty products etc.) in Val Thoiry all year round. Plus 20 % reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * next “vente privée” from 21st November to 1st December 2012 Please contact the Staff Association Secretariat to get the discount voucher.

  5. Offers

    CERN Multimedia

    Staff Association

    2014-01-01

    Passeport Gourmand   Are you dying for a nice meal? The “Passeport Gourmand” offers discounted prices to the members of the Staff Association (available until April 2015 and on sale in the Staff Association Secretariat): Passeport gourmand Ain / Savoie/ Haute Savoie: 56 CHF instead of 79 CHF. Passeport gourmand Geneva / neighbouring France:72 CHF instead of 95 CHF. To the members of the Staff Association: Benefit of reduced tickets: CHF 10 (instead of  18 CHF at the desk) on sale to the secretariat of the Staff Association, Building 510-R010 (in front of the Printshop).

  6. Offers

    CERN Multimedia

    Staff Association

    2014-01-01

    Special offer for members of the Staff Association and their families 10 % reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Simply present your Staff Association membership card when you make your purchase. Plus 20 % reduction during their “vente privée”* three or four times a year. * Next “vente privée” from 24th September to 6th November 2014 Please contact the Staff Association Secretariat to get the discount voucher.  

  7. Offers

    CERN Multimedia

    Staff Association

    2013-01-01

    The « Théâtre de Carouge » offers a 5.- CHF discount for all shows (30.- CHF instead of 35.- CHF) and for the season tickets "Premières représentations" (132.- CHF instead of 162.- CHF) and "Classique" (150.- CHF instead of 180.- CHF). Please send your reservation by email to smills@tcag.ch via your professional email address. Please indicate the date of your reservation, your name and firstname and your telephone number A confirmation will be sent by email. Your membership card will be asked when you collect the tickets. More information on www.tcag.ch and www.tcag.ch/blog/

  8. Prognostic Value Of Immunoglobulin Profile In Human Papilloma Virus Infection

    OpenAIRE

    Chattopadhyay S P

    2001-01-01

    Present study aimed at defining the prognostic value of immunoglobulin profile in human papilloma virus infection by assessing and correlating the levels of immunoglobulin with type, number, duration and response to therapy in 54 randomly selected cases from age group 8 to 42 years (male â€"35, female â€" 19). Raised IgG levels were seen maximally in all spectrum of warts (59.25%) followed by IgM (40.74%) and IgA (25.92%). It was also...

  9. Offers

    CERN Multimedia

    Staff Association

    2015-01-01

    New season 2015-2016 The new season was revealed in May, and was warmly welcomed by the press, which is especially enthusiastic about the exceptional arrival of Fanny Ardand in September in the framework of Cassandre show. Discover the programme 2015-2016. The theatre La Comédie proposes different offers to our members Benefit from a reduction of 20 % on a full price ticket during all the season: from 38 CHF to 23 CHF ticket instead of 50 CHF to 30 CHF depending on the show. Buy two seasonal tickets at the price of one (offers valid upon availability, and until 30 september 2015) 2 Cards Libertà for 240 CHF instead of 480 CHF. Cruise freely through the season with 8 perfomances of your choice per season. These cards are transferrable, and can be shared with one or more accompanying persons. 2 Abo Piccolo for 120 CHF instead of 240 CHF. Let yourself be surprised a theatre performance with our discovery seasonal tickets, which includes 4 flagship perfomances for the season. ...

  10. Offer

    CERN Multimedia

    Staff Association

    2015-01-01

    RRP Communication organizes cultural events such as concerts, shows, sporting events. The members of the Staff Association profits from a reduction of 10 CHF per ticket. How to proceed: The ticket reservation is made by mail info@rrp.ch. You need to give the following information: Name of the show, and which date chosen Number of tickets, and category Name and surname Address Telephone number Mention “offer CERN”, and attach a photocopy of your Staff Association member card. After your reservation, you will be sent a copy with a payslip to the address mentioned above. Once paid, the members have the possibility to: pick up their ticket(s) from the cash register the evening of the show (opens 1 hour before the show) by showing their member card; receive the ticket(s) to the address indicated above, by registered mail, subject to an extra cost of 10CHF. Next show : More information at http://www.rrp.ch/

  11. Offers

    CERN Document Server

    Staff Association

    2013-01-01

    FUTUREKIDS proposes 15% discount for the Staff Association members who enroll their children in FUTUREKIDS activities. New workshop for 12-15 year olds, on how to develop applications for Android phones. Easter activities calendar Extracurricular Activities For Your Children The FUTUREKIDS Geneva Learning Center is open 6 days a week and offers a selection of after-school extracurricular activities for children and teenagers (ages 5 to 16). In addition to teaching in its Learning Centers, Futurekids collaborates with many private schools in Suisse Romande (Florimont, Moser, Champittet, Ecole Nouvelle, etc.) and with the Département de l'Instruction Publique (DIP) Genève. Courses and camps are usually in French but English groups can be set up on demand. FUTUREKIDS Computer Camps (during school holidays) FUTUREKIDS Computer Camps are a way of having a great time during vacations while learning something useful, possibly discovering a new hobby or even, why not, a fut...

  12. Offers

    CERN Multimedia

    Association du personnel

    2010-01-01

    THEATRE FORUM DE MEYRIN 1, place des Cinq-Continents 1217 Meyrin    Special offer for members of the Staff Association: Reduced ticket prices for the play Love is my sin (in English) from 15 to 17 March at 8.30pm http://www.forum-meyrin.ch/main.php?page=119&s=12   First category: 37 CHF instead of 46 CHF Second category (seats towards the sides): 30 CHF instead of 38 CHF Please present your CERN card and your Staff Association membership card at the ticket office. Ticket reservation: tel. 022 989 34 34 (from Monday to Friday 2pm to 6pm) or e-mail : billetterie@forum-meyrin.ch  

  13. Offer

    CERN Multimedia

    Staff Association

    2011-01-01

    DETAILS OF THE AGREEMENT WITH BCGE The BCGE Business partner programme devised for members of the CERN Staff Association offers personalized banking solutions with preferential conditions. The advantages are linked to salary accounts (free account keeping, internet banking, free Maestro and credit cards, etc.), mortgage lending, retirement planning, investment, credit, etc. The details of the programme and the preferential conditions are available on the Staff Association web site and from the secretariat (http://cern.ch/association/en/OtherActivities/BCGE.html). To benefit from these advantages, you will need to fill in the form available on our site, which must then be stamped by the Staff Association as proof that you are a paid-up member.  

  14. Offers

    CERN Multimedia

    Staff Association

    2013-01-01

    Do not hesitate to benefit of our offers in our partners: Théâtre de Carouge Discount of 5 CHF for all shows (30 CHF instead of 35 CHF) and on season tickets « first performance » ( 132 CHF instead 162 CHF) and also on « classical » ( 150 CHF instead of 180 CHF) upon presentation of your Staff Association membership card before payment. Théâtre La Comédie de Genève  20% off on tickets (full price – also available for partner): from 24 to 32 CHF a ticket instead of 30 to 40 CHF depending on the shows. 40% off on annual subscriptions (access to the best seats, pick up tickets at the last minute): 200 CHF for 9 shows (about 22 CHF a ticket instead of 30 to 40 CHF. Discounted card: 60 CHF and single price ticket of 16 CHF.

  15. Offers

    CERN Document Server

    Staff Association

    2011-01-01

    At the UN Cultural kiosk (door C6) This offer is meant for international civil servants, members of diplomatic missions as well as official delegates under presentation of their accreditation card. Matthew Lee & 5 musiciens Du Blues, du Boogie, du Rock’n’Roll 28 octobre 2011 à 20h30 Théâtre du Léman Quai du Mont-Blanc 19 Hôtel Kempinski Genève Matthew Lee is an exciting pianist singer combining classic Rock’n’Roll with timeless ballads. He revisits the standards, being alternately Jerry Lee Lewis, Chuck Berry, Little Richards and many others... He is a showman with a soulful voice and displays virtuosity during his piano solos. Simply amazing! 20 % reduction Tickets from 32 to 68 CHF Kiosque Culturel ONU Palais des Nations Porte 6 Avenue de la Paix 8-14 1211 Genève 10 Tél. 022 917 11 11 info@kiosqueonu.ch

  16. Digital Humanities: What Can Libraries Offer?

    Science.gov (United States)

    Wong, Shun Han Rebekah

    2016-01-01

    The collaborative aspect of digital humanities is one of the core values of the field. Specialists and organizations involved in digital humanities partnerships may include individual scholars focusing on a particular area, multiple scholars across disciplines, computer scientists, or digital humanities centers. Through a quantitative analysis of…

  17. Offer

    CERN Multimedia

    Staff Association

    2016-01-01

    The “La Comédie” theatre unveiled its programme for the season 2016–2017 in late May, and it was met with great enthusiasm by the press. Leading names of the European and Swiss theatre scenes, such as director Joël Pommerat who recently won four Molière awards, will make an appearance! We are delighted to share this brand new, rich and varied programme with you. The “La Comédie” theatre has various discounts for our members Buy 2 subscriptions for the price of 1 : 2 cards “Libertà” for CHF 240.- instead of CHF 480.- Cruise freely through the season with an 8-entry card valid for the shows of your choice. These cards are transferable and can be shared with one or more accompanying persons. 2 cards “Piccolo” for CHF 120 instead of CHF 240.- This card lets you discover 4 shows which are suitable for all audiences (offers valid while stock lasts and until October 31, 201...

  18. Offers

    CERN Multimedia

    Staff Association

    2011-01-01

    Special offer for members of the Staff Association and their families 10% reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Plus 20% reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * Next “vente privée” from 21st to 26th November 2011 New BCGE Business partner benefits As you may remember thanks to our BCGE business partner agreement you benefit from various advantages such as free annual subscription on your Silver or Gold credit card both for yourself and your partner (joint account). Please be informed that as of October 1st  2011 the below mentioned features will be added to your annual credit card subscription : MasterCard/Visa Silver and Gold: travel cancellation as well as related services such as holiday interruption best guaranteed price Only for Ma...

  19. Polyomavirus BK Neutralizing Activity in Human Immunoglobulin Preparations

    Science.gov (United States)

    Randhawa, Parmjeet S; Schonder, Kristine; Shapiro, Ron; Farasati, Nousha; Huang, Yuchen

    2011-01-01

    Background Polyomavirus BK (BKV) infection can cause nephropathy in the allograft kidney. No well-established drug treatment is available at this time. Human intravenous immunoglobulins (IVIG) have been used as an empiric therapy without proof of effectiveness. Methods We tested five lots of commercially available IVIG preparations from two different suppliers for polyomavirus neutralizing activity. BKV and mouse polyomavirus were used to infect human and murine host cells, respectively, with or without prior treatment with IVIG. Neutralization activity was measured by quantitation of viral DNA after 7 days in culture. Results Coincubation of BKV but not mouse polyomavirus with clinically relevant concentrations of IVIG derived from healthy and hepatitis B vaccinated subjects caused more than 90% inhibition of viral DNA yield after 7 days in culture. Consistent with a direct neutralizing mechanism, this effect was significantly diminished if viral infection was performed in immunoglobulin pretreated cells or if immunoglobulin treatment was delayed 2 hr after addition of infectious virus. Conclusion Human IVIG preparations contain BKV neutralizing antibodies. Data on neutralizing capacity of these antibodies are presented to aid dose exploration in clinical trials seeking to validate the use of IVIG in patients with BKV infection. PMID:20568674

  20. 21 CFR 1270.42 - Human tissue offered for import.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Human tissue offered for import. 1270.42 Section...) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN TISSUE INTENDED FOR TRANSPLANTATION Inspection of Tissue Establishments § 1270.42 Human tissue offered for import. (a...

  1. Prognostic Value Of Immunoglobulin Profile In Human Papilloma Virus Infection

    Directory of Open Access Journals (Sweden)

    Chattopadhyay S P

    2001-01-01

    Full Text Available Present study aimed at defining the prognostic value of immunoglobulin profile in human papilloma virus infection by assessing and correlating the levels of immunoglobulin with type, number, duration and response to therapy in 54 randomly selected cases from age group 8 to 42 years (male â€"35, female â€" 19. Raised IgG levels were seen maximally in all spectrum of warts (59.25% followed by IgM (40.74% and IgA (25.92%. It was also seen that 82% of cases with elevated IgM and IgA were free from lesions with no recurrence at 6 months follow up with any form of treatment (electrodessication, 25% podophyllin, 50% trichloroacetic acid,50% 5-fluorouracil. On the contrary, patients with elevated IgG level showed poor response (64% and partial response (16% with recurrence of 38% at the end of 6 months. Cure rate was 54% with combined elevation of IgG, IgA and IgM with recurrence rate of 24%.

  2. Purification of human immunoglobulins by sequential precipitation with caprylic acid and ammonium sulphate.

    Science.gov (United States)

    Perosa, F; Carbone, R; Ferrone, S; Dammacco, F

    1990-03-27

    We have tested the usefulness of sequential precipitation with caprylic acid and ammonium sulfate to purify human monoclonal and polyclonal immunoglobulins from sera of 11 patients with monoclonal gammapathy (4 IgG kappa, 2 IgG lambda, 2 IgM kappa, 1 IgA kappa, 2 IgA lambda), four patients with autoimmune diseases and four healthy donors. In terms of purity and activity of Ig as well as execution time and cost, this two-step non-chromatographic procedure is highly efficient for the purification of IgG, IgA and IgM, thus offering several advantages over other methods of purification. Therefore, this procedure may have useful application in the preparation of human Ig for structural studies and therapeutic purposes.

  3. A micro amperometric immunosensor for detection of human immunoglobulin

    Institute of Scientific and Technical Information of China (English)

    XU Yuanyuan; XIA Shanhong; BIAN Chao; CHEN Shaofeng

    2006-01-01

    A novel amperometric immunosensor based on the micro electromechanical systems (MEMS) technology, using protein A and self-assembled monolayers (SAMs) for the orientation-controlled immobilization of antibodies, has been developed. Using MEMS technology, an "Au, Pt, Pt" three-microelectrode system enclosed in a SU-8 micro pool was fabricated. Employing SAMs, a monolayer of protein A was immobilized on the cysteamine modified Au electrode to achieve the orientation-controlled immobilization of the human immunoglobulin (HIgG) antibody. The immunosensor aimed at low unit cost, small dimension, high level of integration and the prospect of a biosensor system-on-a-chip. Cyclic voltammetry and chronoamperometry were conducted to characterize the immunosensor. Compared with the traditional immunosensor using bulky gold electrode or screen-printed electrode and the procedure directly binding protein A to electrode for immobilization of antibodies, it had attractive advantages, such as miniaturization, compatibility with CMOS technology, fast response (30 s), broad linear range (50-400μg/L) and low detection limit (10μg/L) for HIgG. In addition, this immunosensor was easy to be designed into micro array and to realize the simultaneously multi-parameter detection.

  4. Somatic hypermutation of immunoglobulin genes in human neonates.

    Science.gov (United States)

    Ridings, J; Nicholson, I C; Goldsworthy, W; Haslam, R; Roberton, D M; Zola, H

    1997-05-01

    The antibody response in the young infant is limited in several ways; in particular, responses generally are of low affinity and restricted to IgM. This raises the question whether the affinity maturation process, consisting of somatic mutation of immunoglobulin genes coupled with selection of high-affinity variants, is operative in the neonate. Re-arranged V(H)6 genes were amplified by polymerase chain reaction (PCR) from cord blood and from peripheral blood of infants. Heteroduplex analysis detected mutation in only 2/18 cord blood samples, while mutations were seen from about 10 days of age onwards. Cloning and sequencing of mutated neonatal V(H)6 genes showed that mutated sequences contained relatively few mutations (one to three mutations per sequence) compared with published values of about 10 in adult IgM sequences. Selection was not evident in the majority of neonatal samples. Thus mutation can occur in the human neonate, but is minimal and generally not accompanied by selection. The age at which affinity maturation develops effectively is yet to be defined.

  5. Immunoglobulin Free Light Chain Dimers in Human Diseases

    Directory of Open Access Journals (Sweden)

    Batia Kaplan

    2011-01-01

    Full Text Available Immunoglobulin free light chain (FLC kappa (κ and lambda (λ isotypes exist mainly in monomeric and dimeric forms. Under pathological conditions, the level of FLCs as well as the structure of monomeric and dimeric FLCs and their dimerization properties might be significantly altered. The abnormally high fractions of dimeric FLCs were demonstrated in the serum of patients with multiple myeloma (MM and primary systemic amyloidosis (AL, as well as in the serum of anephric patients. The presence of tetra- and trimolecular complexes formed due to dimer-dimer and dimer-monomer interactions was detected in the myeloma serum. Analysis of the amyloidogenic light chains demonstrated mutations within the dimer interface, thus raising the possibility that these mutations are responsible for amyloidogenicity. Increased κ monomer and dimer levels, as well as a high κ/λ monomer ratio, were typically found in the cerebrospinal fluid from patients with multiple sclerosis (MS. In many MS cases, the elevation of κ FLCs was accompanied by an abnormally high proportion of λ dimers. This review focuses on the disease-related changes of the structure and level of dimeric FLCs, and raises the questions regarding their formation, function, and role in the pathogenesis and diagnosis of human diseases.

  6. Introduction of human gamma 1 immunoglobulin genes into fertilized mouse eggs.

    Science.gov (United States)

    Yamamura, K; Kikutani, H; Takahashi, N; Taga, T; Akira, S; Kawai, K; Fukuchi, K; Kumahara, Y; Honjo, T; Kishimoto, T

    1984-08-01

    A rearranged human gamma 1 immunoglobulin gene was introduced into fertilized mouse eggs. The phage Ch4A-VCE-gamma 1 was constructed by ligating an EcoRI and BglII fragment of pBR322-CESSV(CE-1) containing the VDJ region with an EcoRI and BamHI fragment of Ch4A-HIg gamma 1-10 containing the gamma 1 constant region. About 200 copies of Ch4A-VCE-gamma 1 genes were introduced into fertilized mouse eggs. Of 489 eggs injected with these genes, 319 survived and were transferred to oviducts of foster mothers. Thirtyeight mice were born and were screened for the presence of human gamma 1 immunoglobulin genes by Southern blot hybridization. Five of these 38 mice had integrated human gamma 1 immunoglobulin genes. None of the human gamma 1 copies in each mouse had undergone deletions or rearrangements as judged by the Southern blotting patterns for several restriction enzymes. Human gamma 1 gene was present in several different tissues. All the mice tested so far transmit the human gamma 1 gene to a fraction of their offspring in an autosomal dominant manner. Spleen cells from transgenic mice were analyzed for immunoglobulin production by reverse plaque assay or immunofluorescence staining of cytoplasmic immunoglobulin, but synthesis and secretion of human gamma 1 chains could not be detected. No human gamma 1 immunoglobulin mRNA was detected in the liver and spleen of a transgenic mouse. The presence of the human gamma 1 immunoglobulin gene appeared to have no effect on the expression of endogenous mouse immunoglobulin genes.

  7. Cloning and sequencing of human lambda immunoglobulin genes by the polymerase chain reaction.

    Science.gov (United States)

    Songsivilai, S; Bye, J M; Marks, J D; Hughes-Jones, N C

    1990-12-01

    Universal oligonucleotide primers, designed for amplifying and sequencing genes encoding the rearranged human lambda immunoglobulin variable region, were validated by amplification of the lambda light chain genes from four human heterohybridoma cell lines and in the generation of a cDNA library of human V lambda sequences from Epstein-Barr virus-transformed human peripheral blood lymphocytes. This technique allows rapid cloning and sequencing of human immunoglobulin genes, and has potential applications in the rescue of unstable human antibody-producing cell lines and in the production of human monoclonal antibodies.

  8. Rescue and expression of human immunoglobulin genes to generate functional human monoclonal antibodies.

    Science.gov (United States)

    Lewis, A P; Parry, N; Peakman, T C; Crowe, J S

    1992-07-01

    Human monoclonal antibody production has been hampered for many years by the instability of cell lines and low levels of expression of the antibodies. We describe here the rescue of human immunoglobulin genes utilizing micro-mRNA preparation from a small number of human hybridoma cells and conventional cDNA cloning. This allows cloning and immediate high-level expression from full-length human heavy and light chain cDNA molecules and provides a mechanism to rescue whole human monoclonal antibodies of proven efficacy.

  9. [10 years' of production and use of human rabies immunoglobulin in Yugoslavia].

    Science.gov (United States)

    Romić, M; Tomović, O; Medić, P; Pelević, S; Sindić, M; Popović, M; Gligorović, V; Bogdanović, G; Mitrović, M; Petrović, M; Stankov, S; Lazarević-Ivanc, L; Lalosević, V; Lalosević, D

    2001-01-01

    Application of the rabies immunoglobuline is a compulsory part of the prophylaxis of rabies in all severe, transdermal lesions caused by rabies infected animals. Sylvatic rabies has spread in the past few years throughout the whole Yugoslavia, and human cases of rabies have also been reported in other East European countries. In order to achieve the highest level of rabies prophylaxis, apart from postinfective rabies vaccination, it is necessary to provide passive immunization using specific antibodies against rabies. After successful immunization of the young, healthy volunteers in 1990, National Blood Transfusion Institute, in cooperation with the Pasteur Institute from Novi Sad, prepared the first quantities of immunized plasma by plasmapheresis procedure and human rabies immunoglobuline. Without national production, sufficient quantities of human rabies immunoglobuline could not be provided, since the price on the world market is rather high (over $1000 per patient).

  10. Functional in vitro studies of recombinant human immunoglobulin G and immunoglobulin A anti-D

    DEFF Research Database (Denmark)

    Nielsen, Leif Kofoed; Green, Trine Hefsgaard; Norderhaug, Lars;

    2007-01-01

    The use of anti-D purified from human serum to prevent hemolytic disease of the fetus and newborn due to D is well established. Owing to supply and safety reasons, however, an unlimited and non-plasma-derived source of antibodies for Rhesus prophylaxis is needed.......The use of anti-D purified from human serum to prevent hemolytic disease of the fetus and newborn due to D is well established. Owing to supply and safety reasons, however, an unlimited and non-plasma-derived source of antibodies for Rhesus prophylaxis is needed....

  11. The physiological effects of human immunoglobulin on severe bronchiolitis patients before and after treatment.

    Science.gov (United States)

    Shan, Yan-Hua; Zhang, Yong-Gang; Zhang, Jian-Hua; Wang, Dong; Li, Xiao-Xia; Zhang, Jie; Wang, Xi-Mei; Luo, Song-Yuan

    2015-01-01

    The goal of the present study is to explore the physiological effects of injected human immunoglobulin on patients with severe bronchiolitis before and after treatment. 86 young children with severe bronchiolitis were randomly divided into the observation group (43 cases) and the treatment group (43 cases). On the basis of conventional therapy, the children in the treatment group were given human immunoglobulin (400 mg/kg, 1-3 times) via intravenous injection. 60 healthy young children, as determined by a physical examination given at the Zhumadian Central Hospital, were enrolled as the control group. The T lymphocytes, cytokines, IgA, IgG, and IgM immunoglobulins in the peripheral blood of all 3 groups were measured. The clinical efficacy of the immunoglobulins to mitigate the effects of bronchiolitis and the amount of time for the reduction of symptoms to occur were observed. The serum Ca, Fe, and Zn levels of children with severe bronchiolitis were significantly lower than those of the healthy control group (p bronchiolitis than in the children in the healthy control group (p bronchiolitis children was significantly shorter for those in the treatment group than for those in the observation group. Human immunoglobulin via intravenous injection showed active therapeutical effects on trace elements, T lymphocytes, and cytokines in patients with severe bronchiolitis.

  12. Somatic mutation of immunoglobulin VH6 genes in human infants

    Science.gov (United States)

    Ridings, J; Dinan, L; Williams, R; Roberton, D; Zola, H

    1998-01-01

    Infants respond to antigen by making antibody that is generally of low affinity for antigen. Somatic hypermutation of immunoglobulin genes, and selection of cells expressing mutations with improved affinity for antigen, are the molecular and cellular processes underlying the maturation of antibody affinity. We have reported previously that neonates and infants up to 2 months of age, including individuals undergoing strong immunological challenge, show very few mutated VH6 sequences, with low mutation frequencies in mutated sequences, and little evidence of selection. We have now examined immunoglobulin genes from healthy infants between 2 and 10 months old for mutation and evidence of selection. In this age group, the proportion of VH6 sequences which are mutated and the mutation frequency in mutated sequences increase with age. There is evidence of selection from 6 months old. These results indicate that the process of affinity maturation, which depends on cognate T–B cell interaction and functional germinal centres, is approaching maturity from 6 months old. PMID:9764600

  13. Somatic hypermutations in the immunoglobulin genes of two new human lymphoma lines of lymphatic follicle origin.

    Science.gov (United States)

    Wu, H Y; Tuomikoski, T; Eray, M; Mattila, P; Knuutila, S; Kaartinen, M

    1994-03-01

    Variable immunoglobulin heavy-chain regions (VDJ) of two newly established human lymphoma cell lines (HF-1 and HF-4) were sequenced. The most homologous germline VH gene found for both the HF-1 and HF-4 sequences was VH26 of the VH3a (V gene) family (82% and 91% homologies, respectively). The JH region of the HF-4 heavy-chain sequence contained two nucleotide differences compared to the published germline JH3 gene. The DHJH region of the HF-1 gene had a record high number (20%) of somatic mutations. The numerous hypermutations found in the HF-1 cell line support the hypothesis that in some human follicular lymphomas, mutations continue to accumulate in immunoglobulin genes during the malignant growth. Follicular lymphoma cell lines, which have an active mutational machinery, in future may help to solve the molecular events behind the somatic hypermutations modifying immunoglobulin genes of B lymphocytes.

  14. Computer models of the human immunoglobulins shape and segmental flexibility.

    Science.gov (United States)

    Pumphrey, R

    1986-06-01

    At present there is interest in the design and deployment of engineered biosensor molecules. Antibodies are the most versatile of the naturally occurring biosensors and it is important to understand their mechanical properties and the ways in which they can interact with their natural ligands. Two dimensional representations are clearly inadequate, and three dimensional representations are too complicated to manipulate except as numerical abstractions in computers. Recent improvements in computer graphics allow these coordinate matrices to be seen and more easily comprehended, and interactive programs permit the modification and reassembly of molecular fragments. The models which result have distinct advantages both over those of lower resolution, and those showing every atom, which are limited to the few fragments(2-5) or mutant molecules for which the X-ray crystallographic coordinates are known. In this review Richard Pumphrey describes the shape and flexibility of immunoglobulin molecules in relation to the three dimensional structure. Copyright © 1986. Published by Elsevier B.V.

  15. Binding analysis of carbon nanoparticles to human immunoglobulin G: Elucidation of the cytotoxicity of CNPs and perturbation of immunoglobulin conformations

    Science.gov (United States)

    Zhang, Shengrui; Yang, Haitao; Ji, Xiaohui; Wang, Qin

    2016-02-01

    The chemical compositions, sizes and fluorescent properties of synthesized carbon nanoparticles (CNPs) were characterized. Escherichia coli (E. coli) cells were used as a model to study the cytotoxicity of CNPs, and the results of the cellular uptake of CNPs yielded excellent results: the CNPs demonstrated good biocompatibility and were non-toxic to the growth of the E. coli cells. Moreover, to assess the potential toxicity of CNPs to human health, the binding behavior of CNPs with human immunoglobulin G (HIgG) was examined by fluorescence quenching spectroscopy, synchronous fluorescence spectroscopy and circular dichroism spectroscopy under physiological conditions. The fluorescence quenching constants and parameters for the interaction at different temperatures had been calculated according to Scatchard. The thermodynamic parameters, such as enthalpy change (ΔH), entropy change (ΔS) and free energy change (ΔG), were calculated, and the results indicated strong static quenching and showed that van der Waals forces, hydrogen bonds and hydrophobic interactions were the predominant intermolecular forces stabilizing the CNP-HIgG complex. Synchronous fluorescence and circular dichroism spectra provided information regarding the conformational alteration of HIgG in the presence of CNPs. These findings help to characterize the interactions between CNPs and HIgG, which may clarify the potential risks and undesirable health effects of CNPs, as well as the related cellular trafficking and systemic translocation.

  16. Pooled human immunoglobulins reduce adhesion of Pseudomonas aeruginosa in a parallel plate flow chamber

    NARCIS (Netherlands)

    Poelstra, KA; van der Mei, HC; Gottenbos, B; Grainger, DW; van Horn, [No Value; Busscher, HJ

    2000-01-01

    The influence of pooled polyclonal immunoglobulin (IgG) interactions with both bacteria and model substrates in altering Pseudomonas aeruginosa surface adhesion is reported. Opsonization of this pathogen by polyclonal human IgG and preadsorption of IgG to glass surfaces both effectively reduce initi

  17. Non-immunoglobulin fraction of human milk protects rabbits against enterotoxin-induced intestinal fluid secretion.

    OpenAIRE

    Otnaess, A B; Svennerholm, A M

    1982-01-01

    Human milk was fractionated by ammonium sulphate precipitation and column chromatography. A milk fraction depleted of secretory immunoglobulin A and with an apparent molecular weight of greater than 400,000 inhibited fluid secretion induced by cholera toxin and Escherichia coli heat-labile toxin in rabbit ileal loops.

  18. Demonstration of immunoglobulin G in normal human epidermis by peroxidase-labeled antibody.

    Directory of Open Access Journals (Sweden)

    Yamada,Mariko

    1980-04-01

    Full Text Available Cytoplasmic immunoglobulin G (IgG in normal human epidermis was defined by a peroxidase-labeled antibody method. A correlation between cytoplasmic staining and the serum level of IgG was found. Epidermal cells containing IgG were not present when the serum level of IgG was less than 1000 microgram/ml.

  19. Pooled human immunoglobulins reduce adhesion of Pseudomonas aeruginosa in a parallel plate flow chamber

    NARCIS (Netherlands)

    Poelstra, KA; van der Mei, HC; Gottenbos, B; Grainger, DW; van Horn, [No Value; Busscher, HJ

    The influence of pooled polyclonal immunoglobulin (IgG) interactions with both bacteria and model substrates in altering Pseudomonas aeruginosa surface adhesion is reported. Opsonization of this pathogen by polyclonal human IgG and preadsorption of IgG to glass surfaces both effectively reduce

  20. Multi-scale modeling of the phase diagram of Human Immunoglobulin

    Science.gov (United States)

    Tuchman, Mark; Buldyrev, Sergey; Wang, Ying; Lomakin, Aleksey; Benedek, George B.

    2014-03-01

    Human Immunoglobulin antibodies IGg is a Y-shape trimer consisting of three folded protein globules, connected by two polypeptide hinges in random conformations linked by disulfide bonds. The solubility and crystallization phase diagrams of immunoglobulin are crucial in understanding various pathological conditions. It is experimentally known that the critical volume fraction of immunoglobulin is three times smaller than for typical globular proteins. In order to explain this phenomenon, we perform a multi-scale molecular dynamic (MD) simulations. First we produce all atom simulations of the hinges and compute the distribution of their end-to-end distances. Using these results we construct a simple effective bond potential and study a phase diagram of a system of three sticky hard-spheres linked by these bonds by discrete MD simulations. The results are in good agreement with the experiment.

  1. Cerebellar Purkinje cells incorporate immunoglobulins and immunotoxins in vitro: implications for human neurological disease and immunotherapeutics

    Directory of Open Access Journals (Sweden)

    Rose John W

    2009-10-01

    Full Text Available Abstract Background Immunoglobulin G (IgG antibodies reactive with intracellular neuronal proteins have been described in paraneoplastic and other autoimmune disorders. Because neurons have been thought impermeable to immunoglobulins, however, such antibodies have been considered unable to enter neurons and bind to their specific antigens during life. Cerebellar Purkinje cells - an important target in paraneoplastic and other autoimmune diseases - have been shown in experimental animals to incorporate a number of molecules from cerebrospinal fluid. IgG has also been detected in Purkinje cells studied post mortem. Despite the possible significance of these findings for human disease, immunoglobulin uptake by Purkinje cells has not been demonstrated in living tissue or studied systematically. Methods To assess Purkinje cell uptake of immunoglobulins, organotypic cultures of rat cerebellum incubated with rat IgGs, human IgG, fluorescein-conjugated IgG, and rat IgM were studied by confocal microscopy in real time and following fixation. An IgG-daunorubicin immunotoxin was used to determine whether conjugation of pharmacological agents to IgG could be used to achieve Purkinje cell-specific drug delivery. Results IgG uptake was detected in Purkinje cell processes after 4 hours of incubation and in Purkinje cell cytoplasm and nuclei by 24-48 hours. Uptake could be followed in real time using IgG-fluorochrome conjugates. Purkinje cells also incorporated IgM. Intracellular immunoglobulin did not affect Purkinje cell viability, and Purkinje cells cleared intracellular IgG or IgM within 24-48 hours after transfer to media lacking immunoglobulins. The IgG-daunomycin immunotoxin was also rapidly incorporated into Purkinje cells and caused extensive, cell-specific death within 8 hours. Purkinje cell death was not produced by unconjugated daunorubicin or control IgG. Conclusion Purkinje cells in rat organotypic cultures incorporate and clear host (rat and non

  2. Use of human intravenous immunoglobulin in lower motor neuron syndromes

    Science.gov (United States)

    Ellis, C; Leary, S; Payan, J; Shaw, C; Hu, M; O'Brien, M; Leigh, P

    1999-01-01

    OBJECTIVE—To determine whether patients with the clinical phenotype of multifocal motor neuropathy but without the electrophysiological criteria for conduction block would respond to intravenous immunoglobulin (IVIg).
METHODS—Ten patients were selected with a slowly progressive, asymmetric, lower motor neuron disorder, and were treated prospectively with IVIg at a dose of 2g/kg over 5 days. All subjects had neurophysiological testing to look for evidence of conduction block before treatment. Muscle strength was assessed by MRC grades and hand held myometry, measuring pinch and grip strength. A 20% increase in both pinch and grip myometry was considered a positive response.
RESULTS—In no patient was conduction block detected. Four of the 10 patients showed a positive response to IVIg, with the best response occurring in two patients who presented with weakness but without severe muscle wasting. Three of the four responders have continued to receive IVIg for a mean period of 17 months (range 15-24 months), with continued effect. The response to IVIg was not related to the presence of anti-GM1 antiganglioside antibodies, but responders had a selective pattern of muscle weakness and normal (>90% predicted) vital capacity.
CONCLUSION—The findings suggest that a course of IVIg should be considered in patients with the clinical phenotype of multifocal motor neuropathy but without neurophysiological evidence of conduction block.

 PMID:10369816

  3. Does lycopene offer human LDL any protection against myeloperoxidase activity?

    Science.gov (United States)

    Chew, Poh Yeong; Riley, Lucy; Graham, Daniel L; Rahman, Khalid; Lowe, Gordon M

    2012-02-01

    Lycopene is a lipophilic antioxidant that is largely transported in human blood by Low Density Lipoproteins (LDL). One of the early events in the aetiology of atherosclerosis is thought to be the oxidation of LDL. Myeloperoxidase an enzyme secreted by neutrophils and macrophages is thought to oxidise human LDL particles. In this study, isolated human LDL was challenged with myeloperoxidase or copper, and the LDL was screened for lipoperoxidation and oxidation of apolipoprotein B100, depletion of lycopene and oxidation of cholesterol. Myeloperoxidase induced oxidation of LDL through direct interaction with apolipoprotein B100. No lipoperoxidation was observed following myeloperoxidase treatment; however, 7-ketocholesterol was detected indicating the products of myeloperoxidase interact with the surface of the LDL particles. Lycopene does react with the products of myeloperoxidase in solvent, but played no role in protecting against enzyme derived oxidation of human LDL.

  4. Physiological level production of antigen-specific human immunoglobulin in cloned transchromosomic cattle.

    Science.gov (United States)

    Sano, Akiko; Matsushita, Hiroaki; Wu, Hua; Jiao, Jin-An; Kasinathan, Poothappillai; Sullivan, Eddie J; Wang, Zhongde; Kuroiwa, Yoshimi

    2013-01-01

    Therapeutic human polyclonal antibodies (hpAbs) derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH) and kappa-chain (hIGK) germline loci (named as κHAC) are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO). However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM) and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ) in the pre-B cell receptor (pre-BCR) complex, we partially replaced (bovinized) the hIgM constant domain with the counterpart of bovine IgM (bIgM) that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO), the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype) in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG) can be produced from such Tc cattle.

  5. Physiological level production of antigen-specific human immunoglobulin in cloned transchromosomic cattle.

    Directory of Open Access Journals (Sweden)

    Akiko Sano

    Full Text Available Therapeutic human polyclonal antibodies (hpAbs derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc cattle carrying a human artificial chromosome (HAC comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH and kappa-chain (hIGK germline loci (named as κHAC are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO. However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ in the pre-B cell receptor (pre-BCR complex, we partially replaced (bovinized the hIgM constant domain with the counterpart of bovine IgM (bIgM that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO, the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG can be produced from such Tc cattle.

  6. What Can Human Geography Offer Climate Change Modelling?

    DEFF Research Database (Denmark)

    Grindsted, Thomas Skou

    2014-01-01

    The discipline of Geography may be one of the most prominent and oldest disciplines in the conceptualization of human–environment interactions that integrates elements from both natural and social sciences. Yet, much research on society–environment interactions on climate change reduces human...... conceptual modelling of climate change adaption and mitigation. In other words, geographical representations do matter. In the following we will first reflect upon what I shall call spatio-temporal tides and waves of the human environment theme to examine the methodological grounds on which climate change...

  7. Do Human Arts Really Offer a Lower Return to Education?

    DEFF Research Database (Denmark)

    Dalgaard, Carl-Johan Lars; Sørensen, Anders; Schultz, Esben

    Is the wage gap between majors in human arts and other fields caused by the education?  If the educational choice is endogenous, the wage gap may instead be caused by selection. We  document that individuals' educational choice is correlated with that of older students and by  the concentration...

  8. Do Human Arts Really Offer a Lower Return to Education?

    DEFF Research Database (Denmark)

    Dalgaard, Carl-Johan; Schultz, Esben Anton; Sørensen, Anders

    Is the wage gap between majors in human arts and other fields caused by their education per se? If the educational choice is endogenous, the gap may instead be caused by selection. We document that individuals’ educational choice is correlated with that of older students, and argue that it should...

  9. [Thyroid stimulating immunoglobulin bioassay using cultured normal human thyroid cells].

    Science.gov (United States)

    Ando, M; Yamauchi, K; Tanaka, H; Mori, Y; Takatsuki, K; Yamamoto, M; Matsui, N; Tomita, A

    1985-08-20

    It is currently believed that the thyroid stimulating immunoglobulin (TSI) of Graves' disease is involved in the pathogenesis of hyperthyroidism through the stimulation of the adenylate cyclase-cyclic AMP system. To evaluate this mechanism, TSI in the serum of patients with Graves' disease was determined by its ability to generate cyclic AMP (cAMP) in monolayer cells prepared from a normal thyroid gland. The thyroid tissue was digested with collagenase, and the liberated follicles were collected from the supernatant and cultured for 7 days. One gram of thyroid tissue yielded more than 1 X 10(7) monolayer cells which were stored in aliquots at -80C. Cells (1 approximately 2 X 10(4)/0.28 cm2 microtiter well) were incubated for 4 hours in 0.2 ml Hanks solution poor in NaCl, with various amounts of bovine TSH (bTSH) or 1.5 mg/ml Graves' serum IgG extracted by polyethylene glycol. cAMP accumulated in medium and cells was measured by RIA. Total cAMP (both medium and cells) was about 4 times higher when NaCl was deleted from Hanks solution. Moreover, as more than 90% of the cAMP was released into the medium, it was possible to omit the measurement of cellular cAMP, which requires extraction. The increase in medium cAMP concentration was dependent upon the number of cells, incubation time, and dose of bTSH. Time course and dose response curves in medium cAMP stimulated by IgG from 3 Graves' patients paralleled those of bTSH equivalent units. Accordingly, TSI activity could be expressed in bTSH equivalent units (bTSH microUeq). The assay could detect 1.0 or 3.3 microU/ml of bTSH and was highly reproducible. TSI activity in all of 16 IgGs from normal subjects was under 3.3 bTSH microUeq/ml, while it was greater than 3.3 bTSH microUeq/ml in IgGs from 33 of 37 (89%) untreated patients with Graves disease. Of the 13 patients followed for 2 to 7 months while on antithyroid drugs, 12 had greater than 3.3 bTSH microUeq/ml and, with the exception of one, all showed a decrease in

  10. Expression of SNC73, a transcript of the immunoglobulin α-1 gene, in human epithelial carcinomas

    Institute of Scientific and Technical Information of China (English)

    Li-Yi Geng; Shu Zheng; Zheng-Zhen Shi; Qi Dong; Xin-Han Cai; Yan-Ming Zhang; Wei Cao; Jia-Ping Peng; Yong-Ming Fang; Lei Zheng

    2007-01-01

    AIM: To investigate the expression of SNC73, a transcript of the immunoglobulin α-1 gene (IgA1-H chain), in human epithelia-derived tumor cells.METHODS: Total RNAs and cell lysates were prepared from five different human epithelial cell lines derived from lung, stomach, liver, skin, and breast, respectively. RT-PCR and immunoblot analysis of these five cell lines were done. Both RT-PCR and immunochemistry were used to detect the expression of SNC73 in these cell lines. We also examined the expression of SNC73 in normal epithelial cells of colon mucosa by in situ hybridization. RT-PCR and immunoblot analysis were used to determine whether the recombination activating gene1/2 (RAG1 and RAG2) is present. The expression of three immunoglobulin transcription factors, EBF, E2A and Pax5, and the heavy chain of IgA1 and two types of light chains of immunoglobulin (κ and λ) in the aforementioned cell lines were analyzed by RT-PCR and immunochemistry, respectively. All the RT-PCR products were analyzed by sequencing.RESULTS: The results of RT-PCR and immunochemistry showed that both mRNA and protein of SNC73 were expressed in five human epithelia-derived cancer cell lines. These data were further confirmed in the normal epithelial cells of colon mucosa by in situ hybridization. Also, the heavy chain of IgA1 and κ light chain were detected in these cells, but no λ light chain was observed. Both RAG1 and RAG2 were expressed in these human epithelia-derived cancer cell lines and the sequence was identical to that expressed in pre-B and pre-T cells. In addition to RAG1 and RAG2, the mRNA in one of the immunoglobulin transcription factors, EBF, was also detected in these cell lines, and Pax5 was only expressed in SW480 cells, but no expression of E2A was observed in all the five cell lines.CONCLUSION: Immunoglobulin A1 is originally expressed and V(D)J recombination machine is also present in non-lymphoid cells, suggesting that V(D)J recombination machine mediates the

  11. Co-localization of the heat shock protein and human immunoglobulin G in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    DUAN Chun-guang; LIU Yan-fang; LI Kai-nan; YU Lu; CUI Ji-hong; LI Jing; YANG Shou-jing

    2005-01-01

    @@ Elevated levels of serum immunoglobulin observed in patients with cancers of epithelial origin, including carcinomas of breast, colon, and liver1,2 have been interpreted as humoral responses of host to cancer growth.3 Recently, Qiu et al4 described in detail that human cancers of epithelial origin, including carcinomas of breast, colon, liver, lung, established epithelial cancer lines, produce immunoglobulin G (IgG) in their cytoplasm. Under normal conditions, heat shock proteins (HSPs) have multiple cellular functions, such as folding and translocating newly synthesized proteins. When a cell is injured or under stress, HSPs refold damaged protein or facilitate degradation of proteins. In most cancers, heat shock proteins can capture tumour specific peptide to inhibit the growth of cancer. This study demonstrated that human IgG and HSPs are co-localized in hepatocellular carcinoma.

  12. Plasmonic Enhancement of Luminescence of Fluorscein Isothiocyanate and Human Immunoglobulin Conjugates

    Science.gov (United States)

    Ramanenka, A. A.; Vaschenko, S. V.; Stankevich, V. V.; Lunevich, A. Ya.; Glukhov, Yu. F.; Gaponenko, S. V.

    2014-05-01

    Plasmonic enhancement of the luminescence of fl uorescein isothiocyanate and human immunoglobulin conjugates near silver nanoparticles was investigated as functions of the nanoparticle-conjugate distance and the excitation polarization. The maximum luminescence enhancement of 7.4 was achieved for p-polarized excitation and nanoparticle-conjugate distance 3.3 nm. The luminescence enhancement factor increased experimentally for p-polarized excitation and decreased for s-polarized excitation as compared with unpolarized excitation.

  13. Mannosylerythritol lipid, a yeast extracellular glycolipid, shows high binding affinity towards human immunoglobulin G

    Directory of Open Access Journals (Sweden)

    Ikegami Toru

    2001-09-01

    Full Text Available Abstract Background There have been many attempts to develop new materials with stability and high affinity towards immunoglobulins. Some of glycolipids such as gangliosides exhibit a high affinity toward immunoglobulins. However, it is considerably difficult to develop these glycolipids into the practical separation ligand due to their limited amounts. We thus focused our attention on the feasible use of "mannosylerythritol lipid A", a yeast glycolipid biosurfactant, as an alternative ligand for immunoglobulins, and undertook the investigation on the binding between mannosylerythritol lipid A (MEL-A and human immunoglobulin G (HIgG. Results In ELISA assay, MEL-A showed nearly the same binding affinity towards HIgG as that of bovine ganglioside GM1. Fab of human IgG was considered to play a more important role than Fc in the binding of HIgG by MEL-A. The bound amount of HIgG increased depending on the attached amount of MEL-A onto poly (2-hydroxyethyl methacrylate (polyHEMA beads, whereas the amount of human serum albumin slightly decreased. Binding-amount and -selectivity of HIgG towards MEL-A were influenced by salt species, salt concentration and pH in the buffer solution. The composite of MEL-A and polyHEMA, exhibited a significant binding constant of 1.43 × 106 (M-1 for HIgG, which is approximately 4-fold greater than that of protein A reported. Conclusions MEL-A shows high binding-affinity towards HIgG, and this is considered to be due to "multivalent effect" based on the binding molar ratio. This is the first report on the binding of a natural human antibody towards a yeast glycolipid.

  14. Humanity at the crossroads: does sri aurobindo offer an alternative?

    Science.gov (United States)

    Singh, Shakuntala A; Singh, Ajai R

    2009-01-01

    In the light of Sri Aurobindo's philosophy, this paper looks into some of the problems of contemporary man as an individual, a member of society, a citizen of his country, a component of this world, and of nature itself. Concepts like Science; Nature,;Matter; Mental Being; Mana-purusa; Prana-purusa; Citta-purusa; Nation-ego and Nation-soul; True and False Subjectivism; World-state and World-union; Religion of Humanism are the focus of this paper. NATURE: Beneath the diversity and uniqueness of the different elements in Nature there is an essential unity that not only allows for this diversity but even supports it. Nature is both a benefactor and a force: a benefactor, because it acts to carry out the evolution of mankind; a force, because it also supplies the necessary energy and momentum to achieve it. NATURAL CALAMITIES: If mankind can quieten the tsunamis and cyclones and droughts and earthquakes that rage within, and behave with care and compassion towards Nature, not exploiting, denuding, or denigrating it, there is a strong possibility that Nature too will behave with equal care and compassion towards man and spare him the natural calamities than rend him asunder. SCIENCE: The limitation of science become obvious, according to Sri Aurobindo, when we realize that it has mastered knowledge of processes and helped in the creation of machinery but is ignorant of the foundations of being and, therefore, cannot perfect our nature or our life. SCIENCE AND PHILOSOPHY: The insights of philosophy could become heuristic and algorithmic models for scientific experimentation. MATTER: An interesting aspect of Sri Aurobindo's philosophy is his acceptance of the reality of matter even while highlighting its inadequacies; the ultimate goal, according to him, is the divination of matter itself. PURUSA: If the mana-purusa (mental being) were to log on to the genuine citta-purusa (psychic formation), without necessarily logging off from the prana-purusa (frontal formation), it

  15. Humanity at the Crossroads: Does Sri Aurobindo offer an alternative?

    Directory of Open Access Journals (Sweden)

    Singh Shakuntala

    2009-01-01

    Full Text Available In the light of Sri Aurobindo′s philosophy, this paper looks into some of the problems of contemporary man as an individual, a member of society, a citizen of his country, a component of this world, and of nature itself. Concepts like Science; Nature,;Matter; Mental Being; Mana-purusa; Prana-purusa; Citta-purusa; Nation-ego and Nation-soul; True and False Subjectivism; World-state and World-union; Religion of Humanism are the focus of this paper. Nature: Beneath the diversity and uniqueness of the different elements in Nature there is an essential unity that not only allows for this diversity but even supports it. Nature is both a benefactor and a force: a benefactor, because it acts to carry out the evolution of mankind; a force, because it also supplies the necessary energy and momentum to achieve it. Natural calamities: If mankind can quieten the tsunamis and cyclones and droughts and earthquakes that rage within, and behave with care and compassion towards Nature, not exploiting, denuding, or denigrating it, there is a strong possibility that Nature too will behave with equal care and compassion towards man and spare him the natural calamities than rend him asunder. Science: The limitation of science become obvious, according to Sri Aurobindo, when we realize that it has mastered knowledge of processes and helped in the creation of machinery but is ignorant of the foundations of being and, therefore, cannot perfect our nature or our life. Science and philosophy: The insights of philosophy could become heuristic and algorithmic models for scientific experimentation. Matter: An interesting aspect of Sri Aurobindo′s philosophy is his acceptance of the reality of matter even while highlighting its inadequacies; the ultimate goal, according to him, is the divination of matter itself. Purusa: If the mana-purusa (mental being were to log on to the genuine citta-purusa (psychic formation, without necessarily logging off from the prana

  16. Selective removal, recovery, and characterization of immunoglobulins from human colostrum.

    Science.gov (United States)

    Hutchens, T W; Magnuson, J S; Yip, T T

    1989-12-01

    Investigations into the mechanisms by which Ig in human colostrum influence the development and maturation of both the gastrointestinal and the immune systems of human milk-fed term and preterm infants have been restricted by the paucity of purified human milk Ig. We have developed a simple adsorption procedure for the selective removal and quantitative recovery (95-100%) of intact Ig (secretory IgA, IgG, and IgM) present in human colostral whey. The procedure exploits the rapid, ionic-strength dependent, thiophilic adsorption of Ig during a single pass of colostral whey through a column of beaded agarose with immobilized thioether-sulfone ligands (Anal Biochem 1986;159:217-226). The purity and composition of the adsorbed Ig were verified by SDS-PAGE and sensitive silver-staining protein detection procedures; proteins of approximately 78-80 kD (secretory component), 50-60 kD (heavy chain), and 25 kD (light chain) were observed. The identity, structural integrity, and relative concentrations of the recovered Ig were confirmed by high-performance size-exclusion chromatography, Ouchterlony immunodiffusion, rocket immunoelectrophoresis and ELISA. These results were analyzed and compared with reported values for the concentration of human milk Ig. Thus, the use of thiophilic adsorption appears to facilitate 1) selective removal of Ig from colostrum, enabling the evaluation of remaining components for growth- and immune-potentiating properties, and 2) selective immobilization and recovery of Ig from colostrum under conditions consistent with preserved biologic activity.

  17. Immunoglobulin M

    DEFF Research Database (Denmark)

    Pleass, Richard J; Moore, Shona C; Stevenson, Liz

    2016-01-01

    Immunoglobulin M (IgM) is an ancient antibody class that is found in all vertebrates, with the exception of coelacanths, and is indispensable in both innate and adaptive immunity. The equally ancient human malaria parasite, Plasmodium falciparum, formed an intimate relationship with IgM with which...

  18. Characterization of immunoglobulin variable regions of two human pathogenic monoclonal cryocrystalglobulins.

    Science.gov (United States)

    Navazza, Valentina; Gabba, Silvia; Alfieri, Andrea; Giorgetti, Sofia; Marchese, Loredana; Palladini, Giovanni; Mattevi, Andrea; Ascari, Edoardo; Caporali, Roberto; Montecucco, Carlomaurizio; Merlini, Giampaolo; Perfetti, Vittorio

    2008-03-01

    Cold-precipitating monoclonal immunoglobulins can rarely aggregate in form of crystals (cryocrystalglobulins) and cause serious clinical manifestations. The structural basis underlying this phenomenon remains to be defined. This study was undertaken to provide the first characterization of the heavy (VH) and light chain (VL) variable regions of two human pathogenic cryocrystalglobulins. The immunoglobulins used different heavy and light chain constant regions and germline gene fragments, underwent high degrees of somatic hypermutation, and showed distributions of replacement and silent nucleotide changes suggestive of antigenic selection. Primary sequences analyses and computer-generated modeling identified a positive charge and the introduction of unusual hydrophobic residues in exposed areas of VH and VL. In particular, a rare replacement of a polar residue with proline is shared at the beginning of the VH complementarity-determining region 2, and this residue might be involved in intermolecular contacts.

  19. EXPERIENCE OF INTRAVENOUS INJECTION OF NORMAL HUMAN IMMUNOGLOBULIN IN A PATIENT WITH KAWASAKI SYNDROME

    Directory of Open Access Journals (Sweden)

    T. V. Sleptsova

    2014-01-01

    Full Text Available The article presents a case of late diagnosis of cutaneomucosal lymphonodular syndrome (Kawasaki syndrome. The child featured fever, mucosal lesion (conjunctivitis, stomatitis, rash, thick edemas on arms and feet, arthritis and coronaritis. Initial therapy proved ineffective. Pathogenetic therapy, which proved to be rather effective, was prescribed after diagnosis was confirmed. The authors present a case of successful use of normal human immunoglobulin for intravenous injections in the dose of 2 g/kg of body weight per course in combination with acetylsalicylic acid in the dose of 80 mg/kg per day. Body temperature decreased down to subfebrile figures and foot pain attenuated as early as after 1 day of treatment. Fever, rash, stomatitis and conjunctivitis terminated, edemas of limbs and arthritic manifestations attenuated considerably and laboratory parameters of disease activity normalized after 1 week (ESR and CRP. Inflammation of coronary arteries terminated after 3 weeks. No adverse events in the setting of immunoglobulin therapy were observed.  

  20. Activation of human complement by immunoglobulin G antigranulocyte antibody.

    Science.gov (United States)

    Rustagi, P K; Currie, M S; Logue, G L

    1982-01-01

    The ability of antigranulocyte antibody to fix the third component of complement (C3) to the granulocyte surface was investigated by an assay that quantitates the binding of monoclonal anti-C3 antibody to paraformaldehyde-fixed cells preincubated with Felty's syndrome serum in the presence of human complement. The sera from 7 of 13 patients with Felty's syndrome bound two to three times as much C3 to granulocytes as sera from patients with uncomplicated rheumatoid arthritis. The complement-activating ability of Felty's syndrome serum seemed to reside in the monomeric IgG-containing serum fraction. For those sera capable of activating complement, the amount of C3 fixed to granulocytes was proportional to the amount of granulocyte-binding IgG present in the serum. Thus, complement fixation appeared to be a consequence of the binding of antigranulocyte antibody to the cell surface. These studies suggest a role for complement-mediated injury in the pathophysiology of immune granulocytopenia, as has been demonstrated for immune hemolytic anemia and immune thrombocytopenia. PMID:7174786

  1. Competitive Protein Adsorption of Albumin and Immunoglobulin G from Human Serum onto Polymer Surfaces

    DEFF Research Database (Denmark)

    Holmberg, Maria; Hou, Xiaolin

    2010-01-01

    Competitive protein adsorption from human serum onto unmodified polyethylene terephthalate (PET) surfaces and plasma-polymerized PET surfaces, using the monomer diethylene glycol vinyl ether (DEGVE), has been investigated using radioactive labeling. Albumin and immunoglobulin G (IgG) labeled...... with two different iodine isotopes have been added to human serum solutions of different concentrations, and adsorption has been performed using adsorption times from approximately 5 s to 24 h. DEGVE surfaces showed indications of being nonfouling regarding albumin and IgG adsorption during competitive...

  2. Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human complement produces neuromyelitis optica lesions in mice

    Science.gov (United States)

    Saadoun, Samira; Waters, Patrick; Bell, B. Anthony; Vincent, Angela; Verkman, A. S.

    2010-01-01

    Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system associated with autoantibodies against the glial water channel protein aquaporin-4. It has recently been reported that immunoglobulin from neuromyelitis optica patients injected peripherally does not cause lesions in naive rats, but only when pre-existing central nervous system inflammation is present. Here, we investigated whether immunoglobulin G from aquaporin-4-autoantibody-positive neuromyelitis optica patients has the potential to damage the central nervous system either alone or in the presence of human complement. Immunoglobulin G from neuromyelitis optica patients did not activate mouse complement and was not pathogenic when injected into mouse brain. However, co-injection of immunoglobulin G from neuromyelitis optica patients with human complement produced neuromyelitis optica-like lesions in mice. Within 12 h of co-injecting immunoglobulin G from neuromyelitis optica patients and human complement, there was a striking loss of aquaporin-4 expression, glial cell oedema, myelin breakdown and axonal injury, but little intra-parenchymal inflammation. At 7 days, there was extensive inflammatory cell infiltration, perivascular deposition of activated complement components, extensive demyelination, loss of aquaporin-4 expression, loss of reactive astrocytes and neuronal cell death. In behavioural studies, mice injected with immunoglobulin G from neuromyelitis optica patients and human complement into the right hemisphere preferentially turned to the right at 7 days. No brain inflammation, demyelination or right-turning behaviour was seen in wild-type mice that received immunoglobulin G from non-neuromyelitis optica patients with human complement, or in aquaporin-4-null mice that received immunoglobulin G from neuromyelitis optica patients with human complement. We conclude that co-injection of immunoglobulin G from neuromyelitis optica patients with human complement

  3. Purification of human immunoglobulin G autoantibodies to tumor necrosis factor using affinity chromatography and magnetic separation.

    Science.gov (United States)

    Sennikov, S V; Golikova, E A; Kireev, F D; Lopatnikova, J A

    2013-04-30

    Autoantibodies to cytokines are important biological effector molecules that can regulate cytokine activities. The aim of the study was to develop a protocol to purify autoantibodies to tumor necrosis factor from human serum, for use as a calibration material to determine the absolute content of autoantibodies to tumor necrosis factor by enzyme-linked immunosorbent assay. The proposed protocol includes a set of affinity chromatography methods, namely, Bio-Gel P6DG sorbent to remove albumin from serum, Protein G Sepharose 4 Fast Flow to obtain a total immunoglobulin G fraction of serum immunoglobulins, and Affi-Gel 15 to obtain specifically antibodies to tumor necrosis factor. The addition of a magnetic separation procedure to the protocol eliminated contaminant tumor necrosis factor from the fraction of autoantibodies to tumor necrosis factor. The protocol generated a pure fraction of autoantibodies to tumor necrosis factor, and enabled us to determine the absolute concentrations of different subclasses of immunoglobulin G autoantibodies to tumor necrosis factor in apparently healthy donors.

  4. Triple Immunoglobulin Gene Knockout Transchromosomic Cattle: Bovine Lambda Cluster Deletion and Its Effect on Fully Human Polyclonal Antibody Production

    OpenAIRE

    Hiroaki Matsushita; Akiko Sano; Hua Wu; Jin-An Jiao; Poothappillai Kasinathan; Eddie J. Sullivan; Zhongde Wang; Yoshimi Kuroiwa

    2014-01-01

    Towards the goal of producing fully human polyclonal antibodies (hpAbs or hIgGs) in transchromosomic (Tc) cattle, we previously reported that Tc cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin (Ig) heavy-chain (hIGH), kappa-chain (hIGK), and lambda-chain (hIGL) germline loci produced physiological levels of hIgGs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, were homozygously inactivated (bIGHM−/− , bIGHM...

  5. Triple Immunoglobulin Gene Knockout Transchromosomic (Tc) Cattle: Bovine Lambda Cluster Deletion and its Effect on Fully Human Polyclonal Antibody Production

    OpenAIRE

    Matsushita, H.; Sano, A.; Wu, H.; J. Jiao; Kasinathan, P.; Sullivan, E. J.; Wang, Zhongde; Kuroiwa, K

    2014-01-01

    Towards the goal of producing fully human polyclonal antibodies (hpAbs or hIgGs) in transchromosomic (Tc) cattle, we previously reported that Tc cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin (Ig) heavy-chain (hIGH), kappa-chain (hIGK), and lambda-chain (hIGL) germline loci produced physiological levels of hIgGs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, were homozygously inactivated (bIGHM-/-, bIGHML...

  6. Brown Norway rat ovalbumin-specific immunoglobulin E antibodies increase the human basophil expression of CD63 marker

    NARCIS (Netherlands)

    Bellou, A.; Saint-Laudy, J.; Knippels, L.; Montémont, C.; Vauthier, E.; Gerard, P.; Pellegrom, H.; Koerkamp, E.K.; Lesesve, J.F.; Guéant, J.L.; Lambert, H.; Mallié, J.P.

    2003-01-01

    Anaphylactic shock is an immunoglobulin E (IgE)-dependent hypersensitivity. Biological tests like leucocyte histamine release (LHR) and human basophil activation (HBA), frequently used in human allergy, reflect both the amount of IgE fixed on cells and the cellular reactivity. To assess whether

  7. Brown Norway rat ovalbumin-specific immunoglobulin E antibodies increase the human basophil expression of CD63 marker

    NARCIS (Netherlands)

    Bellou, A.; Saint-Laudy, J.; Knippels, L.; Montémont, C.; Vauthier, E.; Gerard, P.; Pellegrom, H.; Koerkamp, E.K.; Lesesve, J.F.; Guéant, J.L.; Lambert, H.; Mallié, J.P.

    2003-01-01

    Anaphylactic shock is an immunoglobulin E (IgE)-dependent hypersensitivity. Biological tests like leucocyte histamine release (LHR) and human basophil activation (HBA), frequently used in human allergy, reflect both the amount of IgE fixed on cells and the cellular reactivity. To assess whether seru

  8. Detection of orchitis and sacroiliitis due to brucellosis by 99mTc polyclonal human immunoglobulin scintigraphy.

    Science.gov (United States)

    Kadanali, Ayten; Uslu, Hatice; Bayraktar, Rezan; Varoglu, Erhan

    2012-07-01

    Here, we report 1 case of Brucella orchitis detected by 99mTc human immunoglobulin scintigraphy and confirmed by testicular ultrasound. A 29-year-old farmer was admitted to our hospital with fever, fatigue, arthralgia, and painful scrotal swelling that had appeared 12 days before admission. Clinically, right sacroiliitis was recorded through the Fabere test Unilateral sacroiliitis and orchitis were detected by 99mTc human immunoglobulin scintigraphy. Hypoechoic left testicular lesions and swelling of the concurrent epididymis were seen on a testicular ultrasound examination. Wright agglutination test and blood specimen culture for Brucella species were positive.

  9. Physical map and one-megabase sequencing of the human immunoglobulin lambda locus

    Directory of Open Access Journals (Sweden)

    Geraldo A.S. Passos Jr.

    1998-06-01

    Full Text Available The human immunoglobulin lambda (IGL locus is located on chromosome 22q11.1-q11.2 and contains the genes responsible for the immunoglobulin lambda light chains. This locus was recently mapped (physical map and its 1-Mb DNA totally sequenced. In this review we focus on the characterization of the v-lambda genes, its chromosomal location, genomics and sequencing of the IGL locus.O locus IGL humano está localizado no cromosomo 22q11.1-q11.2 e contém os genes responsáveis pelas cadeias leves de imunoglobulina tipo lambda. Este locus foi recentemente mapeado (mapa físico e seu 1 Mb DNA totalmente sequenciado. Nesta revisão focamos os principais resultados de caracterização dos genes v-lambda, sua localização cromossômica, a genômica e seqüenciamento do locus IGL.

  10. The influence of sodium perfluorooctanoate on the conformational transitions of human immunoglobulin.

    Science.gov (United States)

    Messina, Paula V; Prieto, Gerardo; Salgado, Francisco; Varela, Carla; Nogueira, Montserrat; Dodero, Verónica; Ruso, Juan M; Sarmiento, Félix

    2007-07-19

    In the field of bioscience, the study of the interactions between blood proteins and fluorinated materials is very important from both theoretical and applied points of view. Fluorinated materials have potential use in drug delivery, as blood substitutes, and in biotechnology. Using a combination of ultraviolet-visible (UV-vis) and ultraviolet-circular dichroism (UV-CD) spectroscopies and ion-selective electrodes, the complete interaction of sodium perfluorooctanoate (SPFO) and the most important immunoglobulin (on a quantitative basis) in human serum, immunoglobulin G (IgG), has been evaluated. The study has been focused on bulk solution. By the application of an SPFO selective electrode, it was determined that there were true specific unions between surfactant molecules and IgG structure. The experimental data were presented as Koltz and Scatchard plots and analyzed on the basis of an empirical Hill equation. The conformational changes at the bulk solution were well characterized by UV-vis and UV-CD spectroscopies. As a consequence of these changes, the protein structure was affected.

  11. Correlation between parity and concentration of immunoglobulins A, G and M in human colostrum

    Directory of Open Access Journals (Sweden)

    Gabriel André João Striker

    2003-06-01

    Full Text Available Objective: To study the relationship between parity andimmunoglobulin concentrations in human colostrum. Methods:82 puerperas aged 21-41 years were selected, with gestationalage ≥ 37 weeks, up to the fourth parity, good nutritional status andno gestational or puerperal diseases. The inclusion criteria for thenewborn were: weight > 2,500 g, Apgar score > 7 in the firstminute and exclusive maternal breastfeeding until discharge fromthe nursery. The mothers were divided into 2 groups: A -primiparous, B - multiparous. Colostrum was collected manuallyfrom 48 to 72 hours after delivery and the immunoglobulins weremeasured by ELISA technique. Results: No differences wereobserved regarding timing to collect colostrum; the earliercolostrum was collected, the higher the concentration of immunoglobulinA; primiparous women showed higher concentrations of IgA andIgM in their colostrum than multiparous women; there were nodifferences regarding IgG concentrations in the two groups.Conclusion: Primiparous women presented higher concentrationsof IgA and IgM in their colostrum than multiparous women.

  12. Protein-G-based human immunoglobulin G biosensing by electrochemical impedance spectroscopy

    Science.gov (United States)

    Tsugimura, Kaiki; Ohnuki, Hitoshi; Endo, Hideaki; Tsuya, Daijyu; Izumi, Mitsuru

    2016-02-01

    A highly sensitive biosensor based on electrochemical impedance spectroscopy (EIS) was developed for the determination of human immunoglobulin G (IgG). Protein G, which specifically binds to IgG, was employed as the molecular receptor. Protein G was covalently immobilized on interdigitated electrodes through a mixed self-assembled monolayer (SAM) composed of 11-mercaptoundecanoic acid (MUA) and 6-mercaptohexanol. It was found that the mixing ratio of the SAM markedly affected the sensor performance. The sample prepared on 25% MUA SAM exhibited a linear behavior in the concentration range of 0.01-10 ng/mL, which is a record low detection for EIS-based IgG sensors. On the other hand, the sample on 100% MUA SAM showed no IgG-sensing action. A possible mechanism of the mixing ratio that affects the sensing performance was proposed.

  13. The role of the interleukin-10 subfamily members in immunoglobulin production by human B cells

    DEFF Research Database (Denmark)

    Hummelshoj, L; Ryder, L P; Poulsen, Lars K.

    2006-01-01

    Interleukin (IL)-10 has been shown to have various effects on B cells, including positively affecting the production of immunoglobulin A (IgA) and IgG. Several human IL-10-related molecules have been identified. These include IL-19, IL-20, IL-22, IL-24, IL-26, IL-28 and IL-29. To determine...... the effects of the IL-10 analogues on the class switch recombination in B cells, we analysed Ig production from naïve B cells stimulated with these cytokines in the presence of anti-CD40. None of the cytokines were found to induce Ig production by themselves in the presence of anti-CD40 Ab. However, all...... involved in the Ig regulation in B cells. However, some of the analogues might have regulatory effects on CSR induced by CD40-ligation in combination with IL-4 or TGF-beta....

  14. A Double-Blind, Placebo-Controlled Trial of Oral Human Immunoglobulin for Gastrointestinal Dysfunction in Children with Autistic Disorder

    Science.gov (United States)

    Handen, Benjamin L.; Melmed, Raun D.; Hansen, Robin L.; Aman, Michael G.; Burnham, David L.; Bruss, Jon B.; McDougle, Christopher J.

    2009-01-01

    Controversy exists regarding the extent and possible causal relationship between gastrointestinal symptoms and autism. A randomized, double-blind, placebo-controlled, parallel groups, dose-ranging study of oral, human immunoglobulin (IGOH 140, 420, or 840 mg/day) was utilized with 125 children (ages 2-17 years) with autism and persistent GI…

  15. II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies.

    Science.gov (United States)

    Goudouris, Ekaterini Simões; Rego Silva, Almerinda Maria do; Ouricuri, Aluce Loureiro; Grumach, Anete Sevciovic; Condino-Neto, Antonio; Costa-Carvalho, Beatriz Tavares; Prando, Carolina Cardoso; Kokron, Cristina Maria; Vasconcelos, Dewton de Moraes; Tavares, Fabíola Scancetti; Silva Segundo, Gesmar Rodrigues; Barreto, Irma Cecília; Dorna, Mayra de Barros; Barros, Myrthes Anna; Forte, Wilma Carvalho Neves

    2017-01-01

    In the last few years, new primary immunodeficiencies and genetic defects have been described. Recently, immunoglobulin products with improved compositions and for subcutaneous use have become available in Brazil. In order to guide physicians on the use of human immunoglobulin to treat primary immunodeficiencies, based on a narrative literature review and their professional experience, the members of the Primary Immunodeficiency Group of the Brazilian Society of Allergy and Immunology prepared an updated document of the 1st Brazilian Consensus, published in 2010. The document presents new knowledge about the indications and efficacy of immunoglobulin therapy in primary immunodeficiencies, relevant production-related aspects, mode of use (routes of administration, pharmacokinetics, doses and intervals), adverse events (major, prevention, treatment and reporting), patient monitoring, presentations available and how to have access to this therapeutic resource in Brazil. RESUMO Nos últimos anos, novas imunodeficiências primárias e defeitos genéticos têm sido descritos. Recentemente, produtos de imunoglobulina, com aprimoramento em sua composição e para uso por via subcutânea, tornaram-se disponíveis em nosso meio. Com o objetivo de orientar o médico no uso da imunoglobulina humana para o tratamento das imunodeficiências primárias, os membros do Grupo de Assessoria em Imunodeficiências da Associação Brasileira de Alergia e Imunologia produziram um documento que teve por base uma revisão narrativa da literatura e sua experiência profissional, atualizando o I Consenso Brasileiro publicado em 2010. Apresentam-se novos conhecimentos sobre indicações e eficácia do tratamento com imunoglobulina nas imunodeficiências primárias, aspectos relevantes sobre a produção, forma de utilização (vias de administração, farmacocinética, doses e intervalos), efeitos adversos (principais efeitos, prevenção, tratamento e notificação), monitorização do

  16. Analysis and comparison of the mouse and human immunoglobulin heavy chain JH-Cmu-Cdelta locus.

    Science.gov (United States)

    Koop, B F; Richards, J E; Durfee, T D; Bansberg, J; Wells, J; Gilliam, A C; Chen, H L; Clausell, A; Tucker, P W; Blattner, F R

    1996-02-01

    We report here 23,686 bases of contiguous DNA sequences from the mouse germline immunoglobulin heavy chain (H) constant (C) mu delta region. The sequence spans the joining (JH) regions, the mu constant region (C mu), the delta constant region (C delta) coding regions, a domain relic, the mu switch region (S mu), seven blocks of simple sequence repeats, a large unique sequence inverted repeat, a large unique sequence forward repeat, and all of the intervening material. A comparison of this 23.7-kb region with the corresponding human C mu/C delta region reveals clear homology in the coding and introns of C mu but not in the 5' flanking J gene segments nor in the intergenic and C delta regions. This mixed pattern of similarity between the human and the mouse sequences contrasts with high levels of similarity found in the T-cell receptor C alpha/C delta region and alpha and beta myosin genes and the very low levels found in the gamma-crystallin, XRCC1, and beta-globin gene clusters. The human and mouse comparison further suggests the incorporation of novel sequences into expressed genes of IgD.

  17. Editing of mouse and human immunoglobulin genes by CRISPR-Cas9 system.

    Science.gov (United States)

    Cheong, Taek-Chin; Compagno, Mara; Chiarle, Roberto

    2016-03-09

    Applications of the CRISPR-Cas9 system to edit the genome have widely expanded to include DNA gene knock-out, deletions, chromosomal rearrangements, RNA editing and genome-wide screenings. Here we show the application of CRISPR-Cas9 technology to edit the mouse and human immunoglobulin (Ig) genes. By delivering Cas9 and guide-RNA (gRNA) with retro- or lenti-virus to IgM(+) mouse B cells and hybridomas, we induce class-switch recombination (CSR) of the IgH chain to the desired subclass. Similarly, we induce CSR in all human B cell lines tested with high efficiency to targeted IgH subclass. Finally, we engineer mouse hybridomas to secrete Fab' fragments instead of the whole Ig. Our results indicate that Ig genes in mouse and human cells can be edited to obtain any desired IgH switching helpful to study the biology of normal and lymphoma B cells. We also propose applications that could transform the technology of antibody production.

  18. Oral Human Immunoglobulin for Children with Autism and Gastrointestinal Dysfunction: A Prospective, Open-Label Study

    Science.gov (United States)

    Schneider, Cindy K.; Melmed, Raun D.; Barstow, Leon E.; Enriquez, F. Javier; Ranger-Moore, James; Ostrem, James A.

    2006-01-01

    Immunoglobulin secretion onto mucosal surfaces is a major component of the mucosal immune system. We hypothesized that chronic gastrointestinal (GI) disturbances associated with autistic disorder (AD) may be due to an underlying deficiency in mucosal immunity, and that orally administered immunoglobulin would be effective in alleviating chronic GI…

  19. Serum or breast milk immunoglobulins mask the self-reactivity of human natural IgG antibodies.

    Science.gov (United States)

    Djoumerska-Alexieva, Iglika; Manoylov, Iliyan; Dimitrov, Jordan D; Tchorbanov, Andrey

    2014-04-01

    B cells producing IgG antibodies specific to a variety of self- or foreign antigens are a normal constituent of the immune system of all healthy individuals. These naturally occurring IgG antibodies are found in the serum, external secretions, and pooled human immunoglobulin preparations. They bind with low affinity to antigens, which can also be targets for pathologic autoantibodies. An enhancement of naturally occurring IgG autoantibody activity was observed after treatment of human IgG molecules with protein-destabilizing agents. We have investigated the interactions of human immunoglobulins that were obtained from serum or from breast milk of healthy individuals or IVIg with human liver antigens. Proteins from an individual serum or milk were isolated by two methods, one of which included exposure to low pH and the other did not. Purified serum, mucosal IgM, IgA, and the fraction containing immunoglobulin G F(ab')2 fragments each inhibited the binding of a single donor or pooled IgG to human liver antigens. Our study presents findings regarding the role of the breast milk or serum antibodies in blocking the self-reactivity of IgG antibodies. It supports the suggestion that not IVIg only, but also the pooled human IgM and IgA might possess a potent beneficial immunomodulatory activity in autoimmune patients.

  20. Evaluation of capillary zone electrophoresis for the determination of protein composition in therapeutic immunoglobulins and human albumins.

    Science.gov (United States)

    Christians, Stefan; van Treel, Nadine Denise; Bieniara, Gabriele; Eulig-Wien, Annika; Hanschmann, Kay-Martin; Giess, Siegfried

    2016-07-01

    Capillary zone electrophoresis (CZE) provides an alternative means of separating native proteins on the basis of their inherent electrophoretic mobilities. The major advantage of CZE is the quantification by UV detection, circumventing the drawbacks of staining and densitometry in the case of gel electrophoresis methods. The data of this validation study showed that CZE is a reliable assay for the determination of protein composition in therapeutic preparations of human albumin and human polyclonal immunoglobulins. Data obtained by CZE are in line with "historical" data obtained by the compendial method, provided that peak integration is performed without time correction. The focus here was to establish a rapid and reliable test to substitute the current gel based zone electrophoresis techniques for the control of protein composition of human immunoglobulins or albumins in the European Pharmacopoeia. We believe that the more advanced and modern CZE method described here is a very good alternative to the procedures currently described in the relevant monographs.

  1. Significant differences in physicochemical properties of human immunoglobulin kappa and lambda CDR3 regions

    Directory of Open Access Journals (Sweden)

    Catherine L Townsend

    2016-09-01

    Full Text Available Antibody variable regions are composed of a heavy and a light chain and in humans there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain CDR-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 - light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains, and probed the Protein Data Bank (PDB to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda and heavy chain gene rearrangements are correlated within donors, but can differ between donors. This indicates that TdT may work with differing efficiencies between different people, but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response.

  2. Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions.

    Science.gov (United States)

    Townsend, Catherine L; Laffy, Julie M J; Wu, Yu-Chang Bryan; Silva O'Hare, Joselli; Martin, Victoria; Kipling, David; Fraternali, Franca; Dunn-Walters, Deborah K

    2016-01-01

    Antibody variable regions are composed of a heavy and a light chain, and in humans, there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain complementarity-determining region (CDR)-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains and probed the Protein Data Bank to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda, and heavy chain gene rearrangements are correlated within donors but can differ between donors. This indicates that terminal deoxynucleotidyl transferase may work with differing efficiencies between different people but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response.

  3. Utility of the indium 111-labeled human immunoglobulin G scan for the detection of focal vascular graft infection

    Energy Technology Data Exchange (ETDEWEB)

    LaMuraglia, G.M.; Fischman, A.J.; Strauss, H.W.; Keech, F.; Wilkinson, R.; Callahan, R.J.; Khaw, B.A.; Rubin, R.H.

    1989-07-01

    The ability to diagnose and localize vascular graft infections has been a major challenge. Recent studies in animal models and humans with focal bacterial infection have shown that radiolabeled, polyclonal, human immunoglobulin G accumulates at the site of inflammation and can serve as the basis for an imaging technique. This study investigated this new technique for the diagnosis and localization of vascular graft infections. Twenty-five patients with suspected vascular infections involving grafts (22), atherosclerotic aneurysms (2), and subclavian vein thrombophlebitis (1) were studied. Gamma camera images of the suspected area were obtained between 5 and 48 hours after intravenous administration of 1.5 to 2.0 mCi (56 to 74 mBq) of indium 111-labeled, human, polyclonal immunoglobulin G. Scan results were interpreted without clinical information about the patient and were subsequently correlated with surgical findings, other imaging modalities, and/or clinical follow-up. In 10 of 10 patients found to have positive scan results, localized infections were confirmed at the involved sites. In 14 of 15 patients whose scan results were interpreted as negative, no vascular infections were identified at follow-up. The patient with false-negative results and recurrent bacteremia from an aortoduodenal fistula was found to have a negative scan outcome at a time when his disease was quiescent. These data suggest that nonspecific, human, indium 111-labeled immunoglobulin G scanning can be a useful noninvasive means of localizing vascular infections.

  4. Potent neutralizing serum immunoglobulin A (IgA) in human immunodeficiency virus type 2-exposed IgG-seronegative individuals

    DEFF Research Database (Denmark)

    Lizeng, Q; Nilsson, C; Sourial, S

    2004-01-01

    Links Potent neutralizing serum immunoglobulin A (IgA) in human immunodeficiency virus type 2-exposed IgG-seronegative individuals.Lizeng Q, Nilsson C, Sourial S, Andersson S, Larsen O, Aaby P, Ehnlund M, Bjorling E. Research Center, South Hospital, Stockholm, Sweden. The mechanisms behind...... the resistance to human immunodeficiency virus type 2 (HIV-2) infection are still not fully understood. In the present study, we explored the HIV-2-specific humoral serum immunoglobulin A (IgA) immune response in HIV-2-exposed IgG-seronegative (EGSN) individuals. Serum samples from heterosexual EGSN individuals...... and their known HIV-2-infected partners, as well as controls originating from Guinea-Bissau in Africa, were studied. Antibody reactivity to native and recombinant envelope glycoproteins was investigated, and the capacity of purified serum IgA to neutralize HIV-2(SBL6669) was tested. Our results showed that 16...

  5. Pooled human immunoglobulins reduce adhesion of Pseudomonas aeruginosa in a parallel plate flow chamber.

    Science.gov (United States)

    Poelstra, K A; van der Mei, H C; Gottenbos, B; Grainger, D W; van Horn, J R; Busscher, H J

    2000-08-01

    The influence of pooled polyclonal immunoglobulin (IgG) interactions with both bacteria and model substrates in altering Pseudomonas aeruginosa surface adhesion is reported. Opsonization of this pathogen by polyclonal human IgG and preadsorption of IgG to glass surfaces both effectively reduce initial deposition rates and surface growth of P. aeruginosa IFO3455 from dilute nutrient broth in a parallel plate flow chamber. Polyclonal IgG depleted of P. aeruginosa-specific antibodies reduces the initial deposition rate or surface growth to levels intermediate between exposed and nonexposed IgG conditions. Bacterial surface properties are changed in the presence of opsonizing IgG. Plateau contact angle analysis via sessile drop technique shows a drop in P. aeruginosa surface hydrophobicity after IgG exposure consistent with a more hydrophilic IgG surface coat. Zeta potential values for opsonized versus nonopsonized bacteria exhibit little change. X-ray photoelectron spectroscopy measurements provide surface compositional evidence for IgG attachment to bacterial surfaces. Surface elemental ratios attributed to IgG protein signals versus those attributed primarily to bacterial polysaccharide surface or lipid membrane change with IgG opsonization. Direct evidence for antibody-modified P. aeruginosa surface properties correlates both with reduction of bacterial adhesion to glass surfaces under flow in nutrient medium reported and previous reports of IgG efficacy against P. aeruginosa motility in vitro and infection in vivo.

  6. Impact of killer immunoglobulin-like receptor-human leukocyte antigens ligand incompatibility among renal transplantation.

    Science.gov (United States)

    Alam, S; Rangaswamy, D; Prakash, S; Sharma, R K; Khan, M I; Sonawane, A; Agrawal, S

    2015-01-01

    Killer immunoglobulin-like receptor (KIR) gene shows a high degree of polymorphism. Natural killer cell receptor gets activated once they bind to self-human leukocyte antigens (HLAs) with specific ligand. KIR gene and HLA ligand incompatibility due to the presence/absence of KIR in the recipient and the corresponding HLA ligand in the allograft may impact graft survival in solid organ transplantation. This study evaluates the effect of matches between KIR genes and known HLA ligands. KIR genotypes were determined using sequence specific primer polymerase chain reaction. Presence of certain KIR in a recipient, where the donor lacked the corresponding HLA ligand was considered a mismatch. The allograft was considered matched when both KIR receptor and HLA alloantigen reveald compatibility among recipient and donor. The data revealed better survival among individuals with matched inhibitory KIR receptors and their corresponding HLA ligands (KIR2DL2/DL3-HLAC2, KIR3DL1-HLABw4). On the contrary, no adverse effect was seen for matched activating KIR receptors and their corresponding HLA ligands. One of the activating gene KIR2DS4 showed risk (P = 0.0413, odds ratio = 1.91, 95% confidence interval = 1.02-3.57) association with renal allograft rejection. We conclude that the presence of inhibitory KIR gene leads to better survival; whereas activating motifs show no significant role in renal allograft survival.

  7. Protecting contacts of hepatitis A: what's the difference between vaccine and human normal immunoglobulin?

    Science.gov (United States)

    Crowcroft, N S

    2008-01-01

    The efficacy of vaccine when time since exposure is prolonged (more than 1 week from onset of illness in the index case) is unknown, but is likely to be significantly lower than human normal immunoglobulin (HNIG). We estimated the number of additional secondary cases that may occur through giving vaccine instead of HNIG to contacts of cases of hepatitis A who are identified more than 1 week after onset in the index case. This was calculated for different levels of vaccine efficacy, assuming HNIG efficacy to be 80-90%. The number of households that need to be treated to prevent one secondary case was calculated using estimates of secondary attack ratios (AR). If more than 1 week has elapsed from onset of illness in the index case, for an average household size of 2.3 people, a vaccine efficacy of 50% and an AR of 10-25%, 8-26 households would need to be treated with vaccine before one additional secondary case would be observed. As UK public health professionals manage around one hepatitis A case per month, it would take from 8 months to over 2 years for them to observe one additional case amongst contacts using vaccine rather than HNIG. It is unlikely that an average practitioner would notice if vaccine were 30% less effective than HNIG. Public health practice and advice to patients and contacts should be based on evidence as well as experience.

  8. A baboon syndrome induced by intravenous human immunoglobulins: report of a case and immunological analysis.

    Science.gov (United States)

    Barbaud, A; Tréchot, P; Granel, F; Lonchamp, P; Faure, G; Schmutz, J L; Béné, M C

    1999-01-01

    Following the second series of intravenous human immunoglobulins (IVIg; 0.4 g/kg) prescribed to treat a sensorimotor polyneuritis, a 28-year-old woman developed pompholyx that recurred after each of the following monthly treatments with IVIg. During the administration of the 10th series, the patient developed a typical baboon syndrome. Immunohistochemical studies of a skin biopsy revealed an unexpected epidermal expression of P-selectin, usually expressed by endothelial cells. Patch, prick and intradermal tests performed with IVIg on the back, arms and buttocks gave negative results on immediate and delayed readings. IVIg were re-administered, with the informed consent of the patient, and induced a generalized maculopapular rash. This is the first reported case of baboon syndrome induced by IVIg. Although extensive skin testing was performed, all test sites remained negative. We wonder whether IVIg could reproduce immunological mechanisms involved in the 3 types of systemic contact dermatitis (pompholyx, baboon syndrome and maculopapular rash), including the epidermal expression of P-selectin.

  9. Carbon nanotube field effect transistors for the fast and selective detection of human immunoglobulin G.

    Science.gov (United States)

    Cid, Cristina C; Riu, Jordi; Maroto, Alicia; Rius, F Xavier

    2008-08-01

    We report a field effect transistor (FET) based on a network of single-walled carbon nanotubes (SWCNTs) which can selectively detect human immunoglobulin G (HIgG). HIgG antibodies, which are strongly adsorbed onto the walls of the SWCNTs, are the basic elements of the recognition layer. The non-specific binding of proteins and the effects of other interferences are avoided by covering the non-adsorbed areas of the SWCNTs with Tween 20. The selectivity of the sensor has been tested against bovine serum albumin (BSA), the most abundant protein in plasma. HIgG in aqueous solution with concentrations from 1.25 mg L(-1) (8 nM) can be readily detected with response times of about 10 min. The SWCNT networks that form the basis of the sensor are easily grown by chemical vapour deposition. Silver screen-printed electrodes make the sensor quick to build. The sensitivity obtained with this sensor is similar to other FET devices based on SWCNTs built using much more complicated lithography processes. Moreover, the sensor is a reagentless device that does not need labels to detect HIgG.

  10. Aberrant and unstable expression of immunoglobulin genes in persons infected with human immunodeficiency virus.

    Science.gov (United States)

    Bessudo, A; Rassenti, L; Havlir, D; Richman, D; Feigal, E; Kipps, T J

    1998-08-15

    We examined the IgM VH gene subgroup use-distribution in serial blood samples of 37 human immunodeficiency virus (HIV)-infected patients and a group of HIV-seronegative healthy adults. The IgM VH gene repertoires of healthy adults were relatively similar to one another and were stable over time. In contrast, individuals infected with HIV had IgM VH gene repertoires that were significantly more heterogeneous and unstable. Persons at early stages of HIV infection generally had abnormal expression levels of Ig VH3 genes and frequently displayed marked fluctuations in the relative expression levels of this VH gene subgroup over time. In contrast, persons with established acquired immunodeficiency syndrome (AIDS) had a significantly lower incidence of abnormalities in Ig VH3 expression levels, although continued to display abnormalities and instability in the expression levels of the smaller Ig VH gene subgroups. Moreover, the skewing and/or fluctuations in the expressed-IgM VH gene repertoire appeared greatest for persons at earlier stages of HIV infection. These studies show that persons infected with HIV have aberrant and unstable expression of immunoglobulin genes suggestive of a high degree humoral immune dysregulation and ongoing humoral immune responses to HIV-associated antigens and superantigens.

  11. A chromatographic method for the production of a human immunoglobulin G solution for intravenous use

    Directory of Open Access Journals (Sweden)

    K. Tanaka

    1998-11-01

    Full Text Available Immunoglobulin G (IgG of excellent quality for intravenous use was obtained from the cryosupernatant of human plasma by a chromatographic method based on a mixture of ion-exchange, DEAE-Sepharose FF and arginine Sepharose 4B affinity chromatography and a final purification step by Sephacryl S-300 HR gel filtration. The yield of 10 experimental batches produced was 3.5 g IgG per liter of plasma. A solvent/detergent combination of 1% Tri (n-butyl phosphate and 1% Triton X-100 was used to inactivate lipid-coated viruses. Analysis of the final product (5% liquid IgG based on the mean for 10 batches showed 94% monomers, 5.5% dimers and 0.5% polymers and aggregates. Anticomplementary activity was 0.3 CH50/mg IgG and prekallikrein activator levels were less than 5 IU/ml. Stability at 37ºC for 30 days in the liquid state was satisfactory. IgG was stored in flasks (2.5 g/flask at 4 to 8ºC. All the characteristics of the product were consistent with the requirements of the 1997 Pharmacopée Européenne.

  12. Production of intravenous human dengue immunoglobulin from Brazilian-blood donors

    Directory of Open Access Journals (Sweden)

    Frederico Leite Gouveia

    2013-12-01

    Full Text Available Dengue represents an important health problem in Brazil and therefore there is a great need to develop a vaccine or treatment. The neutralization of the dengue virus by a specific antibody can potentially be applied to therapy. The present paper describes, for the first time, the preparation of Immunoglobulin specific for the dengue virus (anti-DENV IgG, collected from screened Brazilian blood-donations. Production was performed using the classic Cohn-Oncley process with minor modifications. The anti-DENV IgG was biochemically and biophysically characterized and fulfilled the requirements defined by the European Pharmacopoeia. The finished product was able to neutralize different virus serotypes (DENV-1, DENV-2, and DENV-3, while a commercial IgG collected from American blood donations was found to have low anti-dengue antibody titers. Overall, this anti-DENV IgG represents an important step in the study of the therapeutic potential and safety of a specific antibody that neutralizes the dengue virus in humans.

  13. Mannosylerythritol lipid, a yeast extracellular glycolipid, shows high binding affinity towards human immunoglobulin G

    OpenAIRE

    Ikegami Toru; Yanagishita Hiroshi; Nakane Takashi; Im Jae Hong; Kitamoto Dai

    2001-01-01

    Abstract Background There have been many attempts to develop new materials with stability and high affinity towards immunoglobulins. Some of glycolipids such as gangliosides exhibit a high affinity toward immunoglobulins. However, it is considerably difficult to develop these glycolipids into the practical separation ligand due to their limited amounts. We thus focused our attention on the feasible use of "mannosylerythritol lipid A", a yeast glycolipid biosurfactant, as an alternative ligand...

  14. Computational study on the interactions and orientation of monoclonal human immunoglobulin G on a polystyrene surface

    Science.gov (United States)

    Javkhlantugs, Namsrai; Bayar, Hexig; Ganzorig, Chimed; Ueda, Kazuyoshi

    2013-01-01

    Having a theoretical understanding of the orientation of immunoglobulin on an immobilized solid surface is important in biomedical pathogen-detecting systems and cellular analysis. Despite the stable adsorption of immunoglobulin on a polystyrene (PS) surface that has been applied in many kinds of immunoassays, there are many uncertainties in antibody-based clinical and biological experimental methods. To understand the binding mechanism and physicochemical interactions between immunoglobulin and the PS surface at the atomic level, we investigated the binding behavior and interactions of the monoclonal immunoglobulin G (IgG) on the PS surface using the computational method. In our docking simulation with the different arrangement of translational and rotational orientation of IgG onto the PS surface, three typical orientation patterns of the immunoglobulin G on the PS surface were found. We precisely analyzed these orientation patterns and clarified how the immunoglobulin G interacts with the PS surface at atomic scale in the beginning of the adsorption process. Major driving forces for the adsorption of IgG onto the PS surface come from serine (Ser), aspartic acid (Asp), and glutamic acid (Glu) residues. PMID:23874096

  15. Immunohistochemical localization of human immunoglobulins and lysozyme in epoxy-embedded lymph nodes: effect of different fixatives and of proteolytic digestion.

    Science.gov (United States)

    Dell'Orto, P; Viale, G; Colombi, R; Braidotti, P; Coggi, G

    1982-07-01

    The postembedding immunoperoxidase staining technique for the localization of immunoglobulins (light and heavy chains) and of lysozyme has been successfully applied to epoxy-embedded human lymph nodes, after removal of the resin. Glutaraldehyde-containing fixatives appear to be suitable for the immunohistochemical localization of human immunoglobulins and lysozyme, provided that the masked antigenicity of these proteins is recovered by proteolytic digestion of the tissue sections using 0.4% pepsin or 0.1% trypsin. Nonglutaraldehyde-containing fixatives allow the immunolocalization of human immunoglobulins without any enzymatic pretreatment. This study shows that tissues routinely fixed in glutaraldehyde and embedded for ultrastructural investigations are actually suitable for immunohistochemical studies on human immunoglobulins and lysozyme.

  16. Hinge-Region O-Glycosylation of Human Immunoglobulin G3 (IgG3)*

    Science.gov (United States)

    Plomp, Rosina; Dekkers, Gillian; Rombouts, Yoann; Visser, Remco; Koeleman, Carolien A.M.; Kammeijer, Guinevere S.M.; Jansen, Bas C.; Rispens, Theo; Hensbergen, Paul J.; Vidarsson, Gestur; Wuhrer, Manfred

    2015-01-01

    Immunoglobulin G (IgG) is one of the most abundant proteins present in human serum and a fundamental component of the immune system. IgG3 represents ∼8% of the total amount of IgG in human serum and stands out from the other IgG subclasses because of its elongated hinge region and enhanced effector functions. This study reports partial O-glycosylation of the IgG3 hinge region, observed with nanoLC-ESI-IT-MS(/MS) analysis after proteolytic digestion. The repeat regions within the IgG3 hinge were found to be in part O-glycosylated at the threonine in the triple repeat motif. Non-, mono- and disialylated core 1-type O-glycans were detected in various IgG3 samples, both poly- and monoclonal. NanoLC-ESI-IT-MS/MS with electron transfer dissociation fragmentation and CE-MS/MS with CID fragmentation were used to determine the site of IgG3 O-glycosylation. The O-glycosylation site was further confirmed by the recombinant production of mutant IgG3 in which potential O-glycosylation sites had been knocked out. For IgG3 samples from six donors we found similar O-glycan structures and site occupancies, whereas for the same samples the conserved N-glycosylation of the Fc CH2 domain showed considerable interindividual variation. The occupancy of each of the three O-glycosylation sites was found to be ∼10% in six serum-derived IgG3 samples and ∼13% in two monoclonal IgG3 allotypes. PMID:25759508

  17. Functionalized gold nanoclusters as fluorescent labels for immunoassays: Application to human serum immunoglobulin E determination.

    Science.gov (United States)

    Alonso, María Cruz; Trapiella-Alfonso, Laura; Fernández, José M Costa; Pereiro, Rosario; Sanz-Medel, Alfredo

    2016-03-15

    A quantitative immunoassay for the determination of immunoglobulin E (IgE) in human serum using gold nanoclusters (AuNCs) as fluorescent label was developed. Water soluble AuNCs were synthesized using lipoic acid and then thoroughly characterized. The obtained AuNCs have a particle size of 2.7 ± 0.1 nm and maximum fluorescence emission at 710 nm. The synthesized AuNCs showed very good stability of the fluorescent signal with light exposure and at neutral and slightly basic media. A covalent bioconjugation of these AuNCs with the desired antibody was carried out by the carbodiimide reaction. After due optimization of such bioconjugation reaction, a molar ratio 1:3 (antibody:AuNCs) was selected. The bioconjugate maintained an intense luminescence emission, slightly red-shifted as compared to the free AuNCs. Two typical immunoassay configurations, competitive and sandwich, were assayed and their performance for IgE determination critically compared. After the different immunoassay steps were accomplished, the fluorescence emission of the bioconjugate was measured. While the sandwich format provided a detection limit (DL) of 10 ng/mL and a linear range between 25 and 565 ng/mL of IgE, the competitive format revealed a DL of 0.2 ng/mL with a linear range between 0.3 and 7.1 ng/mL The applicability of the more sensitive competitive fluorescent immunoassay was assessed by successful analysis of the IgE in human serum and comparison of results with those from a commercial kit. The main advantages of the proposed AuNCs-based fluorimetric method include a low DL and a simple immunoassay protocol involving few reagents.

  18. A new method for radiolabeling of human immunoglobulin-G and its biological evaluation

    Directory of Open Access Journals (Sweden)

    Thakuri Singh

    2012-01-01

    Full Text Available Background: Radiolabeled human Immunoglobulin-G (hIgG has demonstrated its utility in inflammation and infection imaging. However, the present method of radiolabeling hIgG is time-consuming and complex. Objective: To develop a simplified method of radiolabeling hIgG with technetium-99m (99mTc via a nicotinyl hydrazine derivative (99mTc-HYNIC-hIgG and its biological evaluation. Results: In vitro and in vivo studies showed that 99mTc-hIgG prepared by this method was fairly stable in physiological saline and human serum till 24 h. Only 4.3% degradation of the radiolabeled drug was seen till 24 h. Blood clearance pattern of the radiopharmaceutical exhibited biphasic exponential pattern. Biodistribution of 99mTc-HYNIC-hIgG in mice was observed up to 24 h. Significant accumulation of the radiotracer was found in liver (4.93 %, kidney (3.67% and intestine (2.12 % at 4 h interval by 24 h interval, it was reduced to 1.99%, 2.18% and 1.93 % respectively. Significant amount of radioactivity in liver, kidney and intestine suggest hepatobilliary as well as renal route of clearance for 99mTc-HYNIC-hIgG. The anterior whole body and spot scintigraphy images showed increased uptake of 99mTc-HYNIC-hIgG, with the area seen as a focal hot spot, indicating good localization of the radiolabeled hIgG at the site of infection. Conclusion: The present findings indicate that 99mTc-HYNIC-hIgG holds great potential for the scintigraphy localization of inflammation. The shelf life of the developed kit, when stored at (- 20°C was found to be at least 3 months.

  19. Disodium cromoglycate enhances ongoing immunoglobulin production in vitro in human B cells.

    Science.gov (United States)

    Kimata, H; Yoshida, A; Ishioka, C; Mikawa, H

    1991-01-01

    The effect of disodium cromoglycate (DSCG) upon human immunoglobulin (Ig) isotypes and IgG subclasses production by purified B cells was studied. DSCG enhanced IgM, IgG1, IgG2, IgG3, IgG4 and IgA production in a dose-dependent fashion, while DSCG failed to induce IgE production at any concentrations tested by purified B cells. When B cells were separated into small resting and large activated B cells, DSCG failed to induce Ig production from small resting B cells in the presence or absence of Staphylococcus aureus Cowan strain I (SAC). In contrast, in large activated B cells DSCG significantly enhanced all types of Ig production (two-to threefold), especially IgG4 production (seven-to 11-fold), except IgE, which large B cells did not produce. The enhancement of IgG subclass production was not subclass switching, since DSCG failed to enhance IgG1 production in B cells depleted of surface IgG1+ cells (sIgG1+ cells). Similarly, DSCG did not enhance IgG2, IgG3 or IgG4 production from sIgG2-, sIgG3- or sIgG4- B cells, respectively, Interleukin-4 (IL-4) or interleukin-6 (IL-6) also enhanced Ig production except IgG4 from large activated B cells. The enhancing effect of DSCG was not mediated by IL-4 or IL-6 since anti-IL-4 or anti-IL-6 antibody failed to block the DSCG-induced enhancement. DSCG also enhanced IgG2 and IgM production from human B-cell lines GM-1500 and CBL, respectively. These results suggest that DSCG directly and preferentially stimulates activated B cells which are producing Ig and, in addition, enhances their Ig production. PMID:1904400

  20. High Efficiency of Human Normal Immunoglobulin for Intravenous Administration in a Patient with Kawasaki Syndrome Diagnosed in the Later Stages

    Directory of Open Access Journals (Sweden)

    T. V. Sleptsova

    2016-01-01

    Full Text Available The article describes a case of late diagnosis of mucocutaneous lymphonodular syndrome (Kawasaki syndrome. At the beginning of the therapy, the child had fever, conjunctivitis, stomatitis, rash, solid swelling of hands and feet, and coronaritis with the development of aneurysms. The article describes the successful use of normal human immunoglobulin for intravenous administration at a dose of 2 g/kg body weight per course in combination with acetylsalicylic acid at the dose of 80 mg/kg per day. After 3 days of treatment, the rash disappeared; limb swelling and symptoms of conjunctivitis significantly reduced; and laboratory parameters of disease activity became normal (erythrocyte sedimentation rate, C-reactive protein concentration. After 3 months, inflammation in the coronary arteries was stopped. After 6 months, a regression of coronary artery aneurysms was recorded. No adverse effects during the immunoglobulin therapy were observed.

  1. Intravenous human immunoglobulins for refractory recurrent pericarditis: a systematic review of all published cases.

    Science.gov (United States)

    Imazio, Massimo; Lazaros, George; Picardi, Elisa; Vasileiou, Panagiotis; Carraro, Mara; Tousoulis, Dimitrios; Belli, Riccardo; Gaita, Fiorenzo

    2016-04-01

    Refractory recurrent pericarditis is a major clinical challenge after colchicine failure, especially in corticosteroid-dependent patients. Human intravenous immunoglobulins (IVIGs) have been proposed as possible therapeutic options for these cases. The goal of this systematic review is to assess the efficacy and safety of IVIGs in this context. Studies reporting the use of IVIG for the treatment of recurrent pericarditis and published up to October 2014 were searched in several databases. All references found, upon initial assessment at title and abstract level for suitability, were consequently retrieved as full reports for further appraisal. Among the 18 citations retrieved, 17 reports (4 case series and 13 single case reports, with an overall population of 30 patients) were included. The mean disease duration was 14 months and the mean number of recurrences before IVIG was 3. Approximately 47% of patients had idiopathic recurrent pericarditis, 10% had an infective cause, and the remainder a systemic inflammatory disease. Nineteen out of the 30 patients (63.3%) were on corticosteroids at IVIG commencement. IVIGs were generally administered at a dose of 400-500 mg/kg/day for 5 consecutive days with repeated cycles according to the clinical response. Complications were uncommon (headache in ~3%) and not life-threatening. After a mean follow-up of approximately 33th months, recurrences occurred in 26.6% of cases after the first IVIG cycle, and 22 of the 30 patients (73.3%) were recurrence-free. Five patients (16.6%) were on corticosteroids at the end of the follow-up. IVIGs are rapidly acting, well tolerated, and efficacious steroid-sparing agents in refractory pericarditis.

  2. Usefulness of high-dose intravenous human immunoglobulins treatment for refractory recurrent pericarditis.

    Science.gov (United States)

    Moretti, Michele; Buiatti, Alessandra; Merlo, Marco; Massa, Laura; Fabris, Enrico; Pinamonti, Bruno; Sinagra, Gianfranco

    2013-11-01

    The management of refractory recurrent pericarditis is challenging. Previous clinical reports have noted a beneficial effect of high-dose intravenous human immunoglobulins (IvIgs) in isolated and systemic inflammatory disease-related forms. In this article, we analyzed retrospectively our clinical experience with IvIg therapy in a series of clinical cases of pericarditis refractory to conventional treatment. We retrospectively analyzed 9 patients (1994 to 2010) with refractory recurrent pericarditis, who received high-dose IvIg as a part of their medical treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or colchicine treatment was not discontinued during IvIg treatment. No patients had a history of autoimmune or connective tissue diseases. During an average period of 11 months from the first recurrence, patients had experienced a mean of 5 relapses before the first IvIg treatment. In 4 cases, patients showed complete clinical remission with no further relapse after the first IvIg cycle. Two patients experienced a single minor relapse, responsive to short-term nonsteroidal anti-inflammatory drugs. In 2 patients, we performed a second cycle of IvIg after a recurrence of pericarditis, with subsequent complete remission. One patient did not respond to 3 cycles of IvIg and subsequently underwent pericardial window and long-term immunosuppressive treatment. No major adverse effect was observed in consequence of IvIg administration in all the cases. In conclusion, although IvIg mode of action is still poorly understood in this setting, this treatment can be considered as an option in patients with recurrent pericarditis refractory to conventional medical treatment and, in our small series, has proved to be effective in 8 of 9 cases. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Computational study on the interactions and orientation of monoclonal human immunoglobulin G on a polystyrene surface

    Directory of Open Access Journals (Sweden)

    Javkhlantugs N

    2013-07-01

    Full Text Available Namsrai Javkhlantugs,1,2 Hexig Bayar,3 Chimed Ganzorig,1 Kazuyoshi Ueda2 1Center for Nanoscience and Nanotechnology and Department of Chemical Technology, School of Chemistry and Chemical Engineering, National University of Mongolia, Ulaanbaatar, Mongolia; 2Department of Advanced Materials Chemistry, Graduate School of Engineering, Yokohama National University, Yokohama, Japan; 3The Key Laboratory of Mammalian Reproductive Biology and Biotechnology of the Ministry of Education, Inner Mongolia University, Hohhot, Inner Mongolia Autonomous Region, People's Republic of China Abstract: Having a theoretical understanding of the orientation of immunoglobulin on an immobilized solid surface is important in biomedical pathogen-detecting systems and cellular analysis. Despite the stable adsorption of immunoglobulin on a polystyrene (PS surface that has been applied in many kinds of immunoassays, there are many uncertainties in antibody-based clinical and biological experimental methods. To understand the binding mechanism and physicochemical interactions between immunoglobulin and the PS surface at the atomic level, we investigated the binding behavior and interactions of the monoclonal immunoglobulin G (IgG on the PS surface using the computational method. In our docking simulation with the different arrangement of translational and rotational orientation of IgG onto the PS surface, three typical orientation patterns of the immunoglobulin G on the PS surface were found. We precisely analyzed these orientation patterns and clarified how the immunoglobulin G interacts with the PS surface at atomic scale in the beginning of the adsorption process. Major driving forces for the adsorption of IgG onto the PS surface come from serine (Ser, aspartic acid (Asp, and glutamic acid (Glu residues. Keywords: bionano interface, immunoassay, polystyrene, IgG, physical adsorption, simulation

  4. A novel human immunoglobulin Fcγ–Fcε bifunctional fusion protein inhibits FcεRI-mediated degranulation

    OpenAIRE

    Zhu, Daocheng; Kepley, Christopher L.; Zhang, Min; Zhang, Ke; Saxon, Andrew

    2002-01-01

    Human mast cells and basophils that express the high-affinity immunoglobulin E (IgE) receptor, Fcε receptor 1 (FcεRI), have key roles in allergic diseases. FcεRI cross-linking stimulates the release of allergic mediators1. Mast cells and basophils co-express FcγRIIb, a low affinity receptor containing an immunoreceptor tyrosine-based inhibitory motif and whose co-aggregation with FcεRI can block FcεRI-mediated reactivity2–4. Here we designed, expressed and tested the human basophil and mast-c...

  5. Rabbit anti-rabies immunoglobulins production and evaluation.

    Science.gov (United States)

    Liu, Xinjian; Liu, Qiongqiong; Feng, Xiaomin; Tang, Qi; Wang, Zhongcan; Li, Suqing; Feng, Zhenqing; Zhu, Jin; Guan, Xiaohong

    2011-04-01

    Due to the disadvantages of human and equine rabies immunoglobulin, it is necessary to develop a substitute for HRIG and ERIG, especially for those people living in the developing countries. Because of higher affinity and lower immunogenicity of rabbit's immunoglobulins, anti-rabies immunoglobulins specific to rabies virus were produced in rabbits as a bioreactor, and had been characterized by ELISA, affinity assay, immunofluorescence assay (IFA), immunocytochemistry, rapid fluorescent focus inhibition test (RFFIT). ELISA, affinity assay and IFA showed that rabbit RIG (RRIG) bound specifically to rabies virions. RFFIT result showed that RRIG has neutralization activity. This result was confirmed in vivo in a Kunming mouse challenge model and the protection rate of the treatment with RRIG was higher (25%) than that offered by HRIG when mice were challenged with a lethal RV dose. Our results demonstrate that RRIG is safe and efficacious as a candidate drug to replace rabies immunoglobulin in post-exposure prophylaxis.

  6. A human follicular lymphoma B cell line hypermutates its functional immunoglobulin genes in vitro.

    Science.gov (United States)

    Wu, H; Pelkonen, E; Knuutila, S; Kaartinen, M

    1995-12-01

    The functional immunoglobulin (Ig) genes of B lymphocytes undergo somatic mutations during immune responses. These mutations modify the antigen binding site of the immunoglobulins, thereby enhancing the average affinity of the antibodies produced. The molecular mechanism underlying these B cell hypermutations remains unresolved, partly because it is difficult to grow normal B cells in long-term cell cultures and because there is no suitable transformed or malignant B cell line which generates mutations in its immunoglobulin genes in vitro. Here, we show that the recently established follicular lymphoma line HF-1.3.4 generates somatic hypermutations in vitro at a high frequency of 0.7 x 10(-6) mutations per base pair per generation in standard cell cultures (RPMI 1640 + 5% fetal calf serum). This shows for the first time that B cell hypermutation can occur without T cells or T cell factors. The mutation frequency increased approximately tenfold to 1 x 10(-5) mutations/base pair/generation with B cell-specific growth factors (interleukins-2 and -4 and three antibodies stimulatory to HF-1.3.4 cells). This HF-1.3.4 lymphoma line may help to elucidate the molecular mechanism of Ig gene hypermutation.

  7. Anti-Human Platelet Antigen-1a Immunoglobulin G Preparation Intended to Prevent Fetal and Neonatal Alloimmune Thrombocytopenia

    Science.gov (United States)

    Weng, Ying-Jan; Husebekk, Anne; Skogen, Björn; Kjaer, Mette; Lin, Liang-Tzung; Burnouf, Thierry

    2016-01-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a severe disease that is caused by maternal alloantibodies generated during pregnancy or at delivery as a result of incompatibility between maternal and fetal human platelet antigens (HPAs) inherited from the father. Antibody-mediated immune suppression using anti-HPA-1a immunoglobulins is thought to be able to prevent FNAIT caused by HPA-1a. A fractionation process to prepare anti-HPA-1a immunoglobulin (Ig) G (IgG) from human plasma was therefore developed. Anti-HPA-1a plasma was obtained from volunteer mothers who underwent alloimmunization against HPA-1a during a previous pregnancy. Plasma was cryoprecipitated and the supernatant treated with caprylic acid and solvent/detergent (S/D), purified by chromatography, nanofiltered, concentrated, and sterile-filtered. The anti-HPA-1a immunoglobulin fraction was characterized for purity and safety. PAK12 and quantitative monoclonal antibody immobilization of platelet antigen (MAIPA) assays were used to detect anti-HPA-1a IgG. Hepatitis C virus (HCV) removal during nanofiltration was assessed by spiking experiments, using cell culture-derived reporter HCV and luciferase analysis. The caprylic acid treatment precipitated non-Ig proteins yielding a 90% pure Ig supernatant. S-HyperCel chromatography of the S/D-treated supernatant followed by HyperCel STAR AX provided high IgG recovery (>80%) and purity (>99.5%), and efficient IgA and IgM removal. Concentrations of complement factors C3 and C4 were HPA-1a throughout the process. Clinical-grade HPA-1a IgG can be prepared using a process compliant with current quality requirements opening perspectives for the prevention of FNAIT. PMID:27627660

  8. Unusual patterns of immunoglobulin gene rearrangement and expression during human B cell ontogeny: human B cells can simultaneously express cell surface kappa and lambda light chains

    OpenAIRE

    1993-01-01

    Immunoglobulin gene rearrangement during mammalian B cell development generally follows an ordered progression, beginning with heavy (H) chain genes and proceeding through kappa and lambda light (L) chain genes. To determine whether the predicted kappa-->lambda hierarchy was occurring in vitro, we generated Epstein-Barr virus-transformed cell lines from cultures undergoing human pre-B cell differentiation. A total of 143 cell lines were established. 24 expressed cell surface mu/lambda by flow...

  9. Efficacy of Polyvalent Human Immunoglobulins in an Animal Model of Neuromyelitis Optica Evoked by Intrathecal Anti-Aquaporin 4 Antibodies

    Science.gov (United States)

    Grünewald, Benedikt; Bennett, Jeffrey L.; Toyka, Klaus V.; Sommer, Claudia; Geis, Christian

    2016-01-01

    Neuromyelitis Optica Spectrum Disorders (NMOSD) are associated with autoantibodies (ABs) targeting the astrocytic aquaporin-4 water channels (AQP4-ABs). These ABs have a direct pathogenic role by initiating a variety of immunological and inflammatory processes in the course of disease. In a recently-established animal model, chronic intrathecal passive-transfer of immunoglobulin G from NMOSD patients (NMO-IgG), or of recombinant human AQP4-ABs (rAB-AQP4), provided evidence for complementary and immune-cell independent effects of AQP4-ABs. Utilizing this animal model, we here tested the effects of systemically and intrathecally applied pooled human immunoglobulins (IVIg) using a preventive and a therapeutic paradigm. In NMO-IgG animals, prophylactic application of systemic IVIg led to a reduced median disease score of 2.4 on a 0–10 scale, in comparison to 4.1 with sham treatment. Therapeutic IVIg, applied systemically after the 10th intrathecal NMO-IgG injection, significantly reduced the disease score by 0.8. Intrathecal IVIg application induced a beneficial effect in animals with NMO-IgG (median score IVIg 1.6 vs. sham 3.7) or with rAB-AQP4 (median score IVIg 2.0 vs. sham 3.7). We here provide evidence that treatment with IVIg ameliorates disease symptoms in this passive-transfer model, in analogy to former studies investigating passive-transfer animal models of other antibody-mediated disorders. PMID:27571069

  10. Efficacy of Polyvalent Human Immunoglobulins in an Animal Model of Neuromyelitis Optica Evoked by Intrathecal Anti-Aquaporin 4 Antibodies

    Directory of Open Access Journals (Sweden)

    Benedikt Grünewald

    2016-08-01

    Full Text Available Neuromyelitis Optica Spectrum Disorders (NMOSD are associated with autoantibodies (ABs targeting the astrocytic aquaporin-4 water channels (AQP4-ABs. These ABs have a direct pathogenic role by initiating a variety of immunological and inflammatory processes in the course of disease. In a recently-established animal model, chronic intrathecal passive-transfer of immunoglobulin G from NMOSD patients (NMO-IgG, or of recombinant human AQP4-ABs (rAB-AQP4, provided evidence for complementary and immune-cell independent effects of AQP4-ABs. Utilizing this animal model, we here tested the effects of systemically and intrathecally applied pooled human immunoglobulins (IVIg using a preventive and a therapeutic paradigm. In NMO-IgG animals, prophylactic application of systemic IVIg led to a reduced median disease score of 2.4 on a 0–10 scale, in comparison to 4.1 with sham treatment. Therapeutic IVIg, applied systemically after the 10th intrathecal NMO-IgG injection, significantly reduced the disease score by 0.8. Intrathecal IVIg application induced a beneficial effect in animals with NMO-IgG (median score IVIg 1.6 vs. sham 3.7 or with rAB-AQP4 (median score IVIg 2.0 vs. sham 3.7. We here provide evidence that treatment with IVIg ameliorates disease symptoms in this passive-transfer model, in analogy to former studies investigating passive-transfer animal models of other antibody-mediated disorders.

  11. Surface Plasmon Resonance Studies of the Specific Interactions of Hexamer Peptide Ligands with Human Immunoglobulin G

    Science.gov (United States)

    Islam, Nafisa

    This study characterizes the human immunoglobulin G (IgG) binding on peptides grafted onto self-assembled monolayers (SAMs) and the binding events are studied primarily using surface plasmon resonance (SPR) technology. The dissertation also seeks to determine the optimum surface preparation and surface chemistry approaches for grafting the peptide so that the sensor surfaces demonstrate enhanced selectivity and sensitivity in both laboratory and industrial settings. Peptide covalent grafting was performed on pure and mixed SAMs, the surfaces were characterized and the peptide densities were quantified. Theoretical models were developed and implemented to describe the binding mechanism of IgG with grafted ligands. Protein A was grafted onto SPR sensors and subsequent IgG binding characteristics were compared side-by-side to those of peptide-IgG binding. It was found that Protein A-based sensors showed much higher selectivities and higher binding capacities than their peptides based counterparts. Oligo(ethylene glycol) alkanethiol-based pure and mixed SAMs were grafted with peptides in order to determine the optimal surface among these, for enhanced selectivity. Among the mixed SAMs formed from different precursor solutions, a surface with peptides grafted onto mixed SAMs formulated from 10% amine-terminated/90% hydroxyl-terminated alkanethiols showed optimum selectivity. Studies were carried out to increase the peptide density via grafting of branched amines onto surfaces. The branched amine-based peptide surfaces displayed improved sensitivities and similar selectivities to the surfaces based on un-branched amine termini. Kinetic analyses were carried out to determine the characteristics of IgG binding to ligands grafted in the abovementioned methods. Kinetic analysis of binding indicated that Protein A-IgG interactions have concentrationdependent affinity properties that could be attributed to the allosteric effects of the interaction. The lack of tertiary

  12. Treatment with human immunoglobulin G improves the early disease course in a mouse model of Duchenne muscular dystrophy.

    Science.gov (United States)

    Zschüntzsch, Jana; Zhang, Yaxin; Klinker, Florian; Makosch, Gregor; Klinge, Lars; Malzahn, Dörthe; Brinkmeier, Heinrich; Liebetanz, David; Schmidt, Jens

    2016-01-01

    Duchenne muscular dystrophy (DMD) is a severe hereditary myopathy. Standard treatment by glucocorticosteroids is limited because of numerous side effects. The aim of this study was to test immunomodulation by human immunoglobulin G (IgG) as treatment in the experimental mouse model (mdx) of DMD. 2 g/kg human IgG compared to human albumin was injected intraperitoneally in mdx mice at the age of 3 and 7 weeks. Advanced voluntary wheel running parameters were recorded continuously. At the age of 11 weeks, animals were killed so that blood, diaphragm, and lower limb muscles could be removed for quantitative PCR, histological analysis and ex vivo muscle contraction tests. IgG compared to albumin significantly improved the voluntary running performance and reduced muscle fatigability in an ex vivo muscle contraction test. Upon IgG treatment, serum creatine kinase values were diminished and mRNA expression levels of relevant inflammatory markers were reduced in the diaphragm and limb muscles. Macrophage infiltration and myopathic damage were significantly ameliorated in the quadriceps muscle. Collectively, this study demonstrates that, in the early disease course of mdx mice, human IgG improves the running performance and diminishes myopathic damage and inflammation in the muscle. Therefore, IgG may be a promising approach for treatment of DMD. Two monthly intraperitoneal injections of human immunoglobulin G (IgG) improved the early 11-week disease phase of mdx mice. Voluntary running was improved and serum levels of creatine kinase were diminished. In the skeletal muscle, myopathic damage was ameliorated and key inflammatory markers such as mRNA expression of SPP1 and infiltration by macrophages were reduced. The study suggests that IgG could be explored as a potential treatment option for Duchenne muscular dystrophy and that pre-clinical long-term studies should be helpful.

  13. Triple immunoglobulin gene knockout transchromosomic cattle: bovine lambda cluster deletion and its effect on fully human polyclonal antibody production.

    Directory of Open Access Journals (Sweden)

    Hiroaki Matsushita

    Full Text Available Towards the goal of producing fully human polyclonal antibodies (hpAbs or hIgGs in transchromosomic (Tc cattle, we previously reported that Tc cattle carrying a human artificial chromosome (HAC comprising the entire unrearranged human immunoglobulin (Ig heavy-chain (hIGH, kappa-chain (hIGK, and lambda-chain (hIGL germline loci produced physiological levels of hIgGs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, were homozygously inactivated (bIGHM-/-, bIGHML1-/-; double knockouts or DKO. However, because endogenous bovine immunoglobulin light chain loci are still intact, the light chains are produced both from the hIGK and hIGL genomic loci on the HAC and from the endogenous bovine kappa-chain (bIGK and lambda-chain (bIGL genomic loci, resulting in the production of fully hIgGs (both Ig heavy-chains and light-chains are of human origin: hIgG/hIgκ or hIgG/hIgλ and chimeric hIgGs (Ig heavy-chains are of human origin while the Ig light-chains are of bovine origin: hIgG/bIgκ or hIgG/bIgλ. To improve fully hIgG production in Tc cattle, we here report the deletion of the entire bIGL joining (J and constant (C gene cluster (bIGLJ1-IGLC1 to bIGLJ5-IGLC5 by employing Cre/loxP mediated site-specific chromosome recombination and the production of triple knockout (bIGHM-/-, bIGHML1-/- and bIGL-/-; TKO Tc cattle. We further demonstrate that bIGL cluster deletion greatly improves fully hIgGs production in the sera of TKO Tc cattle, with 51.3% fully hIgGs (hIgG/hIgκ plus hIgG/hIgλ.

  14. Human epidermal Langerhans cells express the high affinity receptor for immunoglobulin E (Fc epsilon RI)

    OpenAIRE

    1992-01-01

    It has been suggested that epidermal Langerhans cells (LC) bearing immunoglobulin E (IgE) may be involved in the genesis of atopic disease. The identity of the IgE receptor(s) on LC remained unclear, although it represents a crucial point in understanding cellular events linked to the binding of allergens to LC via IgE. In this report, we demonstrate that epidermal LC express the high affinity receptor for the Fc fragment of IgE (Fc epsilon RI) which has, so far, only been described on mast c...

  15. Somatic mutation of immunoglobulin V(H)6 genes in human infants.

    Science.gov (United States)

    Ridings, J; Dinan, L; Williams, R; Roberton, D; Zola, H

    1998-10-01

    Infants respond to antigen by making antibody that is generally of low affinity for antigen. Somatic hypermutation of immunoglobulin genes, and selection of cells expressing mutations with improved affinity for antigen, are the molecular and cellular processes underlying the maturation of antibody affinity. We have reported previously that neonates and infants up to 2 months of age, including individuals undergoing strong immunological challenge, show very few mutated V(H)6 sequences, with low mutation frequencies in mutated sequences, and little evidence of selection. We have now examined immunoglobulin genes from healthy infants between 2 and 10 months old for mutation and evidence of selection. In this age group, the proportion of V(H)6 sequences which are mutated and the mutation frequency in mutated sequences increase with age. There is evidence of selection from 6 months old. These results indicate that the process of affinity maturation, which depends on cognate T-B cell interaction and functional germinal centres, is approaching maturity from 6 months old.

  16. Immunofluorescent study of immunoglobulins and complement components in human brain tumors.

    Directory of Open Access Journals (Sweden)

    Kawakami,Yasuto

    1981-04-01

    Full Text Available Using a direct immunofluorescent method, histological locations of immunoglobulins (IgG, IgM, IgA and IgD of heavy chain, and kappa and lambda of light chain and complement components (C3 and C4 were studied in 78 brain tumors, which included 24 astrocytomas, 6 metastatic tumors, 5 medulloblastomas, 4 malignant lymphomas, 15 meningiomas, 8 schwannomas, 8 pituitary adenomas, and 8 other miscellaneous brain tumors. IgG-positive cells were observed in the perivascular regions of astrocytomas, but were more marked in those of high grade, metastatic tumors and meningiomas. Malignant lymphomas demonstrated IgG and IgM-positive cells accompanied by either kappa of lambda light chains. C3 and C4 were much less evident in these tumors. Pituitary adenomas showed slight positive stains for both immunoglobulins and complement components on the blood vessel walls, Immune reactions against brain tumors were discussed including the clinical application of autologous lymphocyte infusion in malignant gliomas and combination chemotherapy in intracranial malignant lymphomas.

  17. Rapid infusions of human normal immunoglobulin 50g/l are safe and well tolerated in immunodeficiencies and immune thrombocytopenia.

    Science.gov (United States)

    Spadaro, Giuseppe; Vultaggio, Alessandra; Alberto Bosi, A; Reichert, Dietmar; Janssen, Jan; Lamacchia, Donatella; Nappi, Liliana; Pecoraro, Antonio; Milito, Cinzia; Ferraro, Andrea; Matucci, Andrea; Bacchiarri, Francesca; Carrai, Valentina; Hibbeler, Azra; Speckman, Elisabet; Guarnieri, Chiara; Bongiovanni, Serena; Quinti, Isabella

    2017-03-01

    Intravenous immunoglobulin (IVIg) is accepted as an effective and well-tolerated treatment for primary and secondary immunodeficiencies (ID) and immune thrombocytopenia (ITP). Adverse reactions of IVIg are usually mild, comprising transient flu-like symptoms, change in blood pressure and tachycardia. However IVIg therapy can be burdensome for both patients and healthcare facilities, since the infusion may take up to 4h to administer. The objective of our multicentre, prospective, open-label phase III trial was to evaluate the tolerability and safety of human normal immunoglobulin 50g/l (Ig VENA) at high intravenous infusion rates in adult patients with ID and ITP who had previously tolerated IVIg treatment, by progressively increasing infusion rate up to 8ml/kg/hr. 39 ID patients received three infusions, 5 ITP patients received up to a maximum of 5 infusions for a maximum of 5days. Overall 55 adverse events were reported in 18 patients, and all were mild and self-limiting. Two serious adverse events occurred in ID patients and 1 in an ITP patient; none was fatal or treatment-related. No clinically significant changes or abnormalities were observed in vital signs, laboratory results and HRQoL. In summary, in this study, more rapid IVIg infusions were well tolerated by ID and ITP patients, while maintaining their quality of life, helping to minimise the time spent in outpatient hospital visiting to potentially optimise adherence to treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Fish Immunoglobulins

    Science.gov (United States)

    Mashoof, Sara; Criscitiello, Michael F.

    2016-01-01

    The B cell receptor and secreted antibody are at the nexus of humoral adaptive immunity. In this review, we summarize what is known of the immunoglobulin genes of jawed cartilaginous and bony fishes. We focus on what has been learned from genomic or cDNA sequence data, but where appropriate draw upon protein, immunization, affinity and structural studies. Work from major aquatic model organisms and less studied comparative species are both included to define what is the rule for an immunoglobulin isotype or taxonomic group and what exemplifies an exception. PMID:27879632

  19. [A New Approach to the Depletion of Albumin and Immunoglobulin G from Human Serum].

    Science.gov (United States)

    Bormotova, E A; Mil'man, B L; Gupalova, T V

    2015-01-01

    The use of proteomic analysis to find potential diagnostic biomarkers is limited by the presence of serum albumin (HSA) and immunoglobulin (IgG) at high concentrations in patients' blood; these substances impede the detection of serum proteins with similar molecular weights. Recombinant HSA- and IgG-binding polypeptides are used as ligands in creating sorbents for complete removal of the proteins by affinity chromatography. The binding specificity of the sorbents for HAS and IgG is higher than that of the conventionally used antibodies. A composite sorbent enabling the depletion of HSA and IgG from serum by single-step affinity chromatography is obtained. The. developed sorbents were used to prepare serum for proteomic analysis.

  20. Anti-Human Platelet Antigen-1a Immunoglobulin G Preparation Intended to Prevent Fetal and Neonatal Alloimmune Thrombocytopenia.

    Science.gov (United States)

    Weng, Ying-Jan; Husebekk, Anne; Skogen, Björn; Kjaer, Mette; Lin, Liang-Tzung; Burnouf, Thierry

    2016-01-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a severe disease that is caused by maternal alloantibodies generated during pregnancy or at delivery as a result of incompatibility between maternal and fetal human platelet antigens (HPAs) inherited from the father. Antibody-mediated immune suppression using anti-HPA-1a immunoglobulins is thought to be able to prevent FNAIT caused by HPA-1a. A fractionation process to prepare anti-HPA-1a immunoglobulin (Ig) G (IgG) from human plasma was therefore developed. Anti-HPA-1a plasma was obtained from volunteer mothers who underwent alloimmunization against HPA-1a during a previous pregnancy. Plasma was cryoprecipitated and the supernatant treated with caprylic acid and solvent/detergent (S/D), purified by chromatography, nanofiltered, concentrated, and sterile-filtered. The anti-HPA-1a immunoglobulin fraction was characterized for purity and safety. PAK12 and quantitative monoclonal antibody immobilization of platelet antigen (MAIPA) assays were used to detect anti-HPA-1a IgG. Hepatitis C virus (HCV) removal during nanofiltration was assessed by spiking experiments, using cell culture-derived reporter HCV and luciferase analysis. The caprylic acid treatment precipitated non-Ig proteins yielding a 90% pure Ig supernatant. S-HyperCel chromatography of the S/D-treated supernatant followed by HyperCel STAR AX provided high IgG recovery (>80%) and purity (>99.5%), and efficient IgA and IgM removal. Concentrations of complement factors C3 and C4 were < 0.5 and < 0.4 mg/dL, respectively. The final IgG could be nanofiltered on Planova 20N under conditions removing more than 3 log HCV infectivity to baseline mock infection level, and concentrated to ca. 30 g/L. Proteolytic activity and thrombin generation were low in the final fraction. The Pak12 and MAIPA assays showed good recovery of anti-HPA-1a throughout the process. Clinical-grade HPA-1a IgG can be prepared using a process compliant with current quality requirements

  1. Defensins, lectins, mucins, and secretory immunoglobulin A: microbe-binding biomolecules that contribute to mucosal immunity in the human gut.

    Science.gov (United States)

    Chairatana, Phoom; Nolan, Elizabeth M

    2017-02-01

    In the intestine, the mucosal immune system plays essential roles in maintaining homeostasis between the host and microorganisms, and protecting the host from pathogenic invaders. Epithelial cells produce and release a variety of biomolecules into the mucosa and lumen that contribute to immunity. In this review, we focus on a subset of these remarkable host-defense factors - enteric α-defensins, select lectins, mucins, and secretory immunoglobulin A - that have the capacity to bind microbes and thereby contribute to barrier function in the human gut. We provide an overview of the intestinal epithelium, describe specialized secretory cells named Paneth cells, and summarize our current understanding of the biophysical and functional properties of these select microbe-binding biomolecules. We intend for this compilation to complement prior reviews on intestinal host-defense factors, highlight recent advances in the field, and motivate investigations that further illuminate molecular mechanisms as well as the interplay between these molecules and microbes.

  2. Multiplex genotype determination at a DNA sequence polymorphism cluster in the human immunoglobulin heavy-chain region

    Energy Technology Data Exchange (ETDEWEB)

    Li, H.; Hood, L. [California Institute of Technology, Pasadena, CA (United States)

    1995-03-20

    We have developed a method for multilocus genotype determination. The method involves using restriction fragment length polymorphisms (RFLPs) for allele discrimination. If a polymorphism is not an RFLP, it is converted into an RFLP during the polymerase chain reaction (PCR). After amplification and restriction enzyme digestion, samples are analyzed by sequential gel loading during electrophoresis. The efficiency of this method was demonstrated by determining the genotypes of 108 semen samples at seven DNA sequence polymorphic sites identified in the human immunoglobulin heavy-chain variable region. It was shown that more than 1000 PCR products could be easily analyzed per day per investigator. To show the reliability of this method, some of the typing results were confirmed by DNA sequence analysis. By computer simulation, most (98%) polymorphisms were shown to be natural or convertible (by changing 1 bp close to or next to each polymorphic site) RFLPs for the commercially available 4-base cutters. 47 refs., 4 figs., 3 tabs.

  3. Similarities in the immunoglobulin response and VH gene usage in rhesus monkeys and humans exposed to porcine hepatocytes

    Directory of Open Access Journals (Sweden)

    Borie Dominic C

    2006-03-01

    Full Text Available Abstract Background The use of porcine cells and organs as a source of xenografts for human patients would vastly increase the donor pool; however, both humans and Old World primates vigorously reject pig tissues due to xenoantibodies that react with the polysaccharide galactose α (1,3 galactose (αGal present on the surface of many porcine cells. We previously examined the xenoantibody response in patients exposed to porcine hepatocytes via treatment(s with bioartficial liver devices (BALs, composed of porcine cells in a support matrix. We determined that xenoantibodies in BAL-treated patients are predominantly directed at porcine αGal carbohydrate epitopes, and are encoded by a small number of germline heavy chain variable region (VH immunoglobulin genes. The studies described in this manuscript were designed to identify whether the xenoantibody responses and the IgVH genes encoding antibodies to porcine hepatocytes in non-human primates used as preclinical models are similar to those in humans. Adult non-immunosuppressed rhesus monkeys (Macaca mulatta were injected intra-portally with porcine hepatocytes or heterotopically transplanted with a porcine liver lobe. Peripheral blood leukocytes and serum were obtained prior to and at multiple time points after exposure, and the immune response was characterized, using ELISA to evaluate the levels and specificities of circulating xenoantibodies, and the production of cDNA libraries to determine the genes used by B cells to encode those antibodies. Results Xenoantibodies produced following exposure to isolated hepatocytes and solid organ liver grafts were predominantly encoded by genes in the VH3 family, with a minor contribution from the VH4 family. Immunoglobulin heavy-chain gene (VH cDNA library screening and gene sequencing of IgM libraries identified the genes as most closely-related to the IGHV3-11 and IGHV4-59 germline progenitors. One of the genes most similar to IGHV3-11, VH3-11cyno, has

  4. 特异性人免疫球蛋白与传染性疾病的防治%Specific human immunoglobulin in prevention and treatment of infectious diseases

    Institute of Scientific and Technical Information of China (English)

    马玉媛; 向思龙; 王卓; 吕茂民; 章金刚

    2015-01-01

    特异性人免疫球蛋白是指针对某一特定病原体或生物毒素等的一类高免疫球蛋白制剂,是血液制品的重要品种,多用于预防和治疗一些发病率高、感染后果严重、无特效治疗方法的病原体感染,在传染性疾病的防治中具有其他药物不可比拟的优点。国外特异性人免疫球蛋白上市品种较多,而国内由于技术瓶颈约束、经济效益有限等原因,新型特异性人免疫球蛋白的研发进展缓慢。该文对多种特异性人免疫球蛋白及其对于传染病的防治作用进行了综述。%The specific human immunoglobulin is a hyperimmune globulin against a particular pathogen or biotoxin .It′s an important variety in plasma derivatives .Specific human immunoglobulin is usually used to prevent and treat pathogen in -fections with high morbidity , severe outcomes and no efficient treatment available .Thus it has unique advantages in preven-tion and management of infectious diseases .A variety of specific human immunoglobulins have been licensed abroad , but the development of new specific human immunoglobulins is slow in China due to technical constraints , limited economic benefits or for other reasons .Here we reviewed some specific human immunoglobulins and their preventive and therapeutic effect on infectious diseases .

  5. Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes.

    Science.gov (United States)

    Macdonald, Lynn E; Karow, Margaret; Stevens, Sean; Auerbach, Wojtek; Poueymirou, William T; Yasenchak, Jason; Frendewey, David; Valenzuela, David M; Giallourakis, Cosmas C; Alt, Frederick W; Yancopoulos, George D; Murphy, Andrew J

    2014-04-01

    Genetic humanization, which involves replacing mouse genes with their human counterparts, can create powerful animal models for the study of human genes and diseases. One important example of genetic humanization involves mice humanized for their Ig genes, allowing for human antibody responses within a mouse background (HumAb mice) and also providing a valuable platform for the generation of fully human antibodies as therapeutics. However, existing HumAb mice do not have fully functional immune systems, perhaps because of the manner in which they were genetically humanized. Heretofore, most genetic humanizations have involved disruption of the endogenous mouse gene with simultaneous introduction of a human transgene at a new and random location (so-called KO-plus-transgenic humanization). More recent efforts have attempted to replace mouse genes with their human counterparts at the same genetic location (in situ humanization), but such efforts involved laborious procedures and were limited in size and precision. We describe a general and efficient method for very large, in situ, and precise genetic humanization using large compound bacterial artificial chromosome-based targeting vectors introduced into mouse ES cells. We applied this method to genetically humanize 3-Mb segments of both the mouse heavy and κ light chain Ig loci, by far the largest genetic humanizations ever described. This paper provides a detailed description of our genetic humanization approach, and the companion paper reports that the humoral immune systems of mice bearing these genetically humanized loci function as efficiently as those of WT mice.

  6. Association of respiratory complications and elevated serum immunoglobulins with drinking water arsenic toxicity in human.

    Science.gov (United States)

    Islam, Laila N; Nabi, A H M Nurun; Rahman, M Mahfuzur; Zahid, M Shamim H

    2007-10-01

    We assessed the relationship between chronic arsenic exposure through drinking water with respiratory complications and humoral immune response by measuring serum immunoglobulin profiles in the affected subjects (arsenicosis patients) living in the arsenic endemic rural villages of Bangladesh. The duration of exposure was determined through detailed history of the patients (n=125) and the levels of arsenic in the drinking water and urine samples were determined. The mean duration of exposure in the patients was 7.4+/-5.3 y, and the levels of arsenic in the drinking water and urine samples were 216+/-211 and 223+/-302 micro g/L, respectively, compared to 11+/-20 and 29+/-19 microg/L, respectively, in the unexposed subjects. There was high prevalence of respiratory complications like breathing problems including chest sound, asthma, bronchitis and cough associated with drinking water arsenic toxicity. Arsenicosis patients had significantly elevated levels of IgG (Pdiseases, rather it could be due to direct effects of arsenic. We found significant linear relationships between the levels of serum IgE and inorganic phosphorus (Pcaused respiratory complications, induced changes in the humoral as well as mucosal immune responses.

  7. Assessment by Southern blot analysis of UV-induced damage and repair in human immunoglobulin genes.

    Science.gov (United States)

    Bianchi, M S; Bianchi, N O; de la Chapelle, A

    1990-09-01

    Irradiation of DNA with UV light induces pyrimidine dimers and (6-4) photoproducts. The presence of one of these photolesions in the restriction site of a given endonuclease inhibits DNA cleavage and induces the formation of fragments by incomplete DNA digestion which appear as additional, facultative bands in Southern hybridization autoradiograms. The number and size of these fragments show a positive correlation with the UV dose. The response to UV light of immunoglobulin light-chain constant kappa and heavy-chain constant mu genes was analyzed with 2 specific probes. Constant kappa and mu genes when irradiated as part of the chromatin of living lymphocytes showed a UV sensitivity similar to that of naked DNA. The same genes from granulocytes had 50-60 times lower UV sensitivity. When cells were allowed to repair photolesions for 24 h the facultative bands from granulocytes disappeared indicating that these cells were able to remove photolesions from constant kappa and mu genes. Facultative bands from lymphocytes showed a smaller decrease of density after 24 h repair. This suggests that lymphocytes are less efficient than granulocytes in removing UV damage from constant kappa and mu genes.

  8. A novel human immunoglobulin Fc gamma Fc epsilon bifunctional fusion protein inhibits Fc epsilon RI-mediated degranulation.

    Science.gov (United States)

    Zhu, Daocheng; Kepley, Christopher L; Zhang, Min; Zhang, Ke; Saxon, Andrew

    2002-05-01

    Human mast cells and basophils that express the high-affinity immunoglobulin E (IgE) receptor, Fc epsilon receptor 1 (Fc epsilon RI), have key roles in allergic diseases. Fc epsilon RI cross-linking stimulates the release of allergic mediators. Mast cells and basophils co-express Fc gamma RIIb, a low affinity receptor containing an immunoreceptor tyrosine-based inhibitory motif and whose co-aggregation with Fc epsilon RI can block Fc epsilon RI-mediated reactivity. Here we designed, expressed and tested the human basophil and mast-cell inhibitory function of a novel chimeric fusion protein, whose structure is gamma Hinge-CH gamma 2-CH gamma 3-15aa linker-CH epsilon 2-CH epsilon 3-CH epsilon 4. This Fc gamma Fc epsilon fusion protein was expressed as the predicted 140-kappa D dimer that reacted with anti-human epsilon- and gamma-chain specific antibodies. Fc gamma Fc epsilon bound to both human Fc epsilon RI and Fc gamma RII. It also showed dose- and time-dependent inhibition of antigen-driven IgE-mediated histamine release from fresh human basophils sensitized with IgE directed against NIP (4-hydroxy-3-iodo-5-nitrophenylacetyl). This was associated with altered Syk signaling. The fusion protein also showed increased inhibition of human anti-NP (4-hydroxy-3-nitrophenylacetyl) and anti-dansyl IgE-mediated passive cutaneous anaphylaxis in transgenic mice expressing human Fc epsilon RI alpha. Our results show that this chimeric protein is able to form complexes with both Fc epsilon RI and Fc gamma RII, and inhibit mast-cell and basophil function. This approach, using a Fc gamma Fc epsilon fusion protein to co-aggregate Fc epsilon RI with a receptor containing an immunoreceptor tyrosine-based inhibition motif, has therapeutic potential in IgE- and Fc epsilon RI-mediated diseases.

  9. Physiological level Production of Antigen-Specific Human Immunoglobulin in Cloned Transchromosomic Cattle

    OpenAIRE

    Akiko Sano; Hiroaki Matsushita; Hua Wu; Jin-An Jiao; Poothappillai Kasinathan; Eddie J. Sullivan; Zhongde Wang; Yoshimi Kuroiwa

    2013-01-01

    Therapeutic human polyclonal antibodies (hpAbs) derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human...

  10. Aberrant heparan sulfate profile in the human diabetic kidney offers new clues for therapeutic glycomimetics.

    NARCIS (Netherlands)

    Wijnhoven, T.J.M.; Lensen, J.F.M.; Rops, A.L.; Vlag, J. van der; Kolset, S.O.; Bangstad, H.J.; Pfeffer, P.; Hoven, M.J.W. van den; Berden, J.H.M.; Heuvel, L.P.W.J. van den; Kuppevelt, A.H.M.S.M. van

    2006-01-01

    BACKGROUND: Diabetic nephropathy poses an increasing health problem in the Western world, and research to new leads for diagnosis and therapy therefore is warranted. In this respect, heparan sulfates (HSs) offer new possibilities because crude mixtures of these polysaccharides are capable of amelior

  11. Survival and digestibility of orally-administered immunoglobulin preparations containing IgG through the gastrointestinal tract in humans.

    Science.gov (United States)

    Jasion, Victoria S; Burnett, Bruce P

    2015-03-07

    Oral immunoglobulin (Ig) preparations are prime examples of medicinal nutrition from natural sources. Plasma products containing Ig have been used for decades in animal feed for intestinal disorders to mitigate the damaging effects of early weaning. These preparations reduce overall mortality and increase feed utilization in various animal species leading to improved growth. Oral administration of Ig preparations from human serum as well as bovine colostrum and serum have been tested and proven to be safe as well as effective in human clinical trials for a variety of enteric microbial infections and other conditions which cause diarrhea. In infants, children, and adults, the amount of intact IgG recovered in stool ranges from trace amounts up to 25% of the original amount ingested. It is generally understood that IgG can only bind to antigens within the GI tract if the Fab structure is intact and has not been completely denatured through acidic pH or digestive proteolytic enzymes. This is a comprehensive review of human studies regarding the survivability of orally-administered Ig preparations, with a focus on IgG. This review also highlights various biochemical studies on IgG which potentially explain which structural elements are responsible for increased stability against digestion.

  12. Specific, sensitive, and quantitative enzyme-linked immunosorbent assay for human immunoglobulin G antibodies to anthrax toxin protective antigen.

    Science.gov (United States)

    Quinn, Conrad P; Semenova, Vera A; Elie, Cheryl M; Romero-Steiner, Sandra; Greene, Carolyn; Li, Han; Stamey, Karen; Steward-Clark, Evelene; Schmidt, Daniel S; Mothershed, Elizabeth; Pruckler, Janet; Schwartz, Stephanie; Benson, Robert F; Helsel, Leta O; Holder, Patricia F; Johnson, Scott E; Kellum, Molly; Messmer, Trudy; Thacker, W Lanier; Besser, Lilah; Plikaytis, Brian D; Taylor, Thomas H; Freeman, Alison E; Wallace, Kelly J; Dull, Peter; Sejvar, Jim; Bruce, Erica; Moreno, Rosa; Schuchat, Anne; Lingappa, Jairam R; Martin, Sandra K; Walls, John; Bronsdon, Melinda; Carlone, George M; Bajani-Ari, Mary; Ashford, David A; Stephens, David S; Perkins, Bradley A

    2002-10-01

    The bioterrorism-associated human anthrax epidemic in the fall of 2001 highlighted the need for a sensitive, reproducible, and specific laboratory test for the confirmatory diagnosis of human anthrax. The Centers for Disease Control and Prevention developed, optimized, and rapidly qualified an enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) antibodies to Bacillus anthracis protective antigen (PA) in human serum. The qualified ELISA had a minimum detection limit of 0.06 micro g/mL, a reliable lower limit of detection of 0.09 micro g/mL, and a lower limit of quantification in undiluted serum specimens of 3.0 micro g/mL anti-PA IgG. The diagnostic sensitivity of the assay was 97.8%, and the diagnostic specificity was 97.6%. A competitive inhibition anti-PA IgG ELISA was also developed to enhance diagnostic specificity to 100%. The anti-PA ELISAs proved valuable for the confirmation of cases of cutaneous and inhalational anthrax and evaluation of patients in whom the diagnosis of anthrax was being considered.

  13. Analysis of the structural integrity of YACs comprising human immunoglobulin genes in yeast and in embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Mendez, M.J.; Abderrahim, H.; Noguchi, M. [Cell Genesys, Inc., Foster City, CA (United States)] [and others

    1995-03-20

    With the goal of creating a strain of mice capable of producing human antibodies, we are cloning and reconstructing the human immunoglobulin germline repertoire in yeast artificial chromosomes (YACs). We describe the identification of YACs containing variable and constant region sequences from the human heavy chain (IgH) and kappa light chain (IgK) loci and the characterization of their integrity in yeast and in mouse embryonic stem (ES) cells. The IgH locus-derived YAC contains five variable (V{sub H}) genes, the major diversity (D) gene cluster, the joining (J{sub H}) genes, the intronic enhancer (E{sub H}), and the constant region genes, mu (C{mu}) and delta (C{delta}). Two IgK locus-derived YACs each contain three variable (V{kappa}) genes, the joining (J{kappa}) region, the intronic enhancer (E{kappa}), the constant gene (C{kappa}), and the kappa deleting element (kde). The IgH YAC was unstable in yeast, generating a variety of deletion derivatives, whereas both IgK YACs were stable. YACs encoding heavy chain and kappa light chain, retrofitted with the mammalian selectable marker, hypoxanthine phosphoribosyltransferase (HPRT), were each introduced into HPRT-deficient mouse ES cells. Analysis of YAC integrity in ES cell lines revealed that the majority of DNA inserts were integrated in substantially intact form. 78 refs., 7 figs.

  14. A strategy for synthesis of pathogenic human immunoglobulin free light chains in E. coli.

    Science.gov (United States)

    Rognoni, Paola; Lavatelli, Francesca; Casarini, Simona; Palladini, Giovanni; Verga, Laura; Pedrazzoli, Paolo; Valentini, Giovanna; Merlini, Giampaolo; Perfetti, Vittorio

    2013-01-01

    Monoclonal immunoglobulin light chains are normally synthesized in excess compared to the heavy chain partners and can be detected in serum and urine ("free" LC). Occasionally free LC are per se cause of organ toxicity, as in free LC-related disorders. In AL amyloidosis, the most common of these conditions, free LC with peculiar biophysical properties related to their primary structure damage target organs and organize in amyloid fibrils. Unlimited availability of well-characterized free LC is instrumental to investigate the toxic effect of these proteins and to study their interactions with targets. We present a straightforward strategy to obtain recombinant monoclonal free LC by using a bacterial system. These proteins, expressed as inclusion bodies, were subjected to solubilization and refolding procedures to recover them in native form. To minimize differences from the circulating natural LC, full-length recombinant LC were expressed, i.e. complete of variable and constant regions, with the original amino acid sequence along the entire protein, and with no purification tags. The strategy was exploited to generate free LC from three AL amyloidosis patients. After purification, recombinant proteins were biochemically characterized and compared to the natural Bence Jones protein isolated from one of the patients. Results showed that the recombinant free LC were properly folded and formed homodimers in solution, similar to the natural Bence Jones protein used for comparison. Furthermore, as proof of pathogenicity, recombinant proteins formed amyloid fibrils in vitro. We believe that the present strategy represents a valuable tool to speed research in free LC-related disorders.

  15. A Strategy for Synthesis of Pathogenic Human Immunoglobulin Free Light Chains in E. coli

    Science.gov (United States)

    Rognoni, Paola; Lavatelli, Francesca; Casarini, Simona; Palladini, Giovanni; Verga, Laura; Pedrazzoli, Paolo; Valentini, Giovanna; Merlini, Giampaolo; Perfetti, Vittorio

    2013-01-01

    Monoclonal immunoglobulin light chains are normally synthesized in excess compared to the heavy chain partners and can be detected in serum and urine (“free” LC). Occasionally free LC are per se cause of organ toxicity, as in free LC-related disorders. In AL amyloidosis, the most common of these conditions, free LC with peculiar biophysical properties related to their primary structure damage target organs and organize in amyloid fibrils. Unlimited availability of well-characterized free LC is instrumental to investigate the toxic effect of these proteins and to study their interactions with targets. We present a straightforward strategy to obtain recombinant monoclonal free LC by using a bacterial system. These proteins, expressed as inclusion bodies, were subjected to solubilization and refolding procedures to recover them in native form. To minimize differences from the circulating natural LC, full-length recombinant LC were expressed, i.e. complete of variable and constant regions, with the original amino acid sequence along the entire protein, and with no purification tags. The strategy was exploited to generate free LC from three AL amyloidosis patients. After purification, recombinant proteins were biochemically characterized and compared to the natural Bence Jones protein isolated from one of the patients. Results showed that the recombinant free LC were properly folded and formed homodimers in solution, similar to the natural Bence Jones protein used for comparison. Furthermore, as proof of pathogenicity, recombinant proteins formed amyloid fibrils in vitro. We believe that the present strategy represents a valuable tool to speed research in free LC-related disorders. PMID:24086679

  16. A strategy for synthesis of pathogenic human immunoglobulin free light chains in E. coli.

    Directory of Open Access Journals (Sweden)

    Paola Rognoni

    Full Text Available Monoclonal immunoglobulin light chains are normally synthesized in excess compared to the heavy chain partners and can be detected in serum and urine ("free" LC. Occasionally free LC are per se cause of organ toxicity, as in free LC-related disorders. In AL amyloidosis, the most common of these conditions, free LC with peculiar biophysical properties related to their primary structure damage target organs and organize in amyloid fibrils. Unlimited availability of well-characterized free LC is instrumental to investigate the toxic effect of these proteins and to study their interactions with targets. We present a straightforward strategy to obtain recombinant monoclonal free LC by using a bacterial system. These proteins, expressed as inclusion bodies, were subjected to solubilization and refolding procedures to recover them in native form. To minimize differences from the circulating natural LC, full-length recombinant LC were expressed, i.e. complete of variable and constant regions, with the original amino acid sequence along the entire protein, and with no purification tags. The strategy was exploited to generate free LC from three AL amyloidosis patients. After purification, recombinant proteins were biochemically characterized and compared to the natural Bence Jones protein isolated from one of the patients. Results showed that the recombinant free LC were properly folded and formed homodimers in solution, similar to the natural Bence Jones protein used for comparison. Furthermore, as proof of pathogenicity, recombinant proteins formed amyloid fibrils in vitro. We believe that the present strategy represents a valuable tool to speed research in free LC-related disorders.

  17. Novel region within the V kappa gene promoter is responsible for tissue and stage-specific expression of immunoglobulin genes in human lymphoid neoplasms.

    Science.gov (United States)

    Kossakowska, A E; Urbanski, S J

    1989-03-01

    Immunoglobulin gene-specific transacting factors have been shown to play a role in lymphoid tissue-specific expression of immunoglobulin genes. The role of these factors in B-cell differentiation and stage-specific expression of these genes is, however, not fully understood. We have used a model of human lymphoid neoplasia to address this question. Different fragments of unrearranged human variable region of immunoglobulin kappa gene (V kappa) were used for cell-free in vitro transcription and DNA mobility shift assays. Previously described enhancement of in vitro transcription that was only seen with nuclear extracts derived from B-cell neoplasms corresponding to the late stages of B-cell differentiation was shown to be dependent on the actions of these factor(s) on the DNA region within the V kappa gene promoter. This region is located within the 920 bp fragment located 210 bp upstream from the coding region and this fragment represents a possible novel DNA region, which plays a role in the stage- and tissue-specific expression of immunoglobulin genes.

  18. Use of human immunodeficiency virus (HIV) human hyperimmune immunoglobulin in HIV type 1-infected children (Pediatric AIDS clinical trials group protocol 273).

    Science.gov (United States)

    Stiehm, E R; Fletcher, C V; Mofenson, L M; Palumbo, P E; Kang, M; Fenton, T; Sapan, C V; Meyer, W A; Shearer, W T; Hawkins, E; Fowler, M G; Bouquin, P; Purdue, L; Sloand, E M; Nemo, G J; Wara, D; Bryson, Y J; Starr, S E; Petru, A; Burchett, S

    2000-02-01

    The clinical, immunologic, and virologic effects and the pharmacokinetics of human immunodeficiency virus (HIV) human hyperimmune immunoglobulin (HIVIG) were assessed in 30 HIV-infected children aged 2-11 years. All had moderately advanced disease with an immune complex-dissociated (ICD) p24 antigen >70 pg/mL and were on stable antiviral therapy. Three groups of 10 children received 6 monthly infusions of 200, 400, or 800 mg/kg of HIVIG, and serial immunologic and virologic assays were performed. HIVIG doses as high as 800 mg/kg were safe and well tolerated. The half-life of HIVIG, determined by serial p24 antibody titers, was 13-16 days, the volume of distribution was 102-113 mL/kg, and clearance was 5.6-6.0 mL/kg/day. Plasma ICD p24 decreased during the infusions, but CD4 cell levels, plasma RNA copy number, cellular virus, immunoglobulin levels, and neutralizing antibody titers were minimally affected by the infusions. Clinical status did not change during the 6-month infusion and 3-month follow-up periods.

  19. The interactions of calreticulin with immunoglobulin G and immunoglobulin Y

    DEFF Research Database (Denmark)

    Møllegaard, Karen Mai; Duus, Karen; Træholt, Sofie Dietz;

    2011-01-01

    accumulating in support of calreticulin as a polypeptide binding chaperone. In contrast to mammalian immunoglobulin G (IgG), which has complex type N-glycans, chicken immunoglobulin Y (IgY) possesses a monoglucosylated high mannose N-linked glycan, which is a ligand for calreticulin. Here, we have used solid...... and solution-phase assays to analyze the in vitro binding of calreticulin, purified from human placenta, to human IgG and chicken IgY in order to compare the interactions. In addition, peptides from the respective immunoglobulins were included to further probe the binding specificity of calreticulin....... The experiments demonstrate the ability of calreticulin to bind to denatured forms of both IgG and IgY regardless of the glycosylation state of the proteins. Furthermore, calreticulin exhibits binding to peptides (glycosylated and non-glycosylated) derived from trypsin digestion of both immunoglobulins...

  20. Philosophy for Welders: Colleges Offer Innovative Humanities Curricula for Liberal Arts and Career Track Students Alike

    Science.gov (United States)

    Finkel, Ed

    2016-01-01

    Does America needs more welders and fewer philosophers? Community college humanities professors and administrators say it benefits all students, whether liberal arts or career track, to take courses in philosophy, history, political science, language arts, and other liberal arts subjects. And they're developing innovative humanities curricula to…

  1. 77 FR 43337 - Drugs for Human Use; Drug Efficacy Study Implementation; Certain Prescription Drugs Offered for...

    Science.gov (United States)

    2012-07-24

    ..., functional diarrhea, drug- induced diarrhea, ulcerative colitis, urinary bladder spasm, and urethral spasm... HUMAN SERVICES Food and Drug Administration [Docket Nos. FDA-1975-N-0336 (Formerly 75N-0184), FDA-1975-N... Hydrocortisone Acetate and Pramoxine Hydrochloride] Drugs for Human Use; Drug Efficacy Study...

  2. Two dimensional gel human protein databases offer a systematic approach to the study of cell proliferation and differentiation

    DEFF Research Database (Denmark)

    Celis, J E; Gesser, B; Dejgaard, K;

    1989-01-01

    Human cellular protein databases have been established using computer-analyzed 2D gel electrophoresis. These databases, which include information on various properties of proteins, offer a global approach to the study of regulation of cell proliferation and differentiation. Furthermore, thanks...

  3. Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice.

    Science.gov (United States)

    Murphy, Andrew J; Macdonald, Lynn E; Stevens, Sean; Karow, Margaret; Dore, Anthony T; Pobursky, Kevin; Huang, Tammy T; Poueymirou, William T; Esau, Lakeisha; Meola, Melissa; Mikulka, Warren; Krueger, Pamela; Fairhurst, Jeanette; Valenzuela, David M; Papadopoulos, Nicholas; Yancopoulos, George D

    2014-04-01

    Mice genetically engineered to be humanized for their Ig genes allow for human antibody responses within a mouse background (HumAb mice), providing a valuable platform for the generation of fully human therapeutic antibodies. Unfortunately, existing HumAb mice do not have fully functional immune systems, perhaps because of the manner in which their genetic humanization was carried out. Heretofore, HumAb mice have been generated by disrupting the endogenous mouse Ig genes and simultaneously introducing human Ig transgenes at a different and random location; KO-plus-transgenic humanization. As we describe in the companion paper, we attempted to make mice that more efficiently use human variable region segments in their humoral responses by precisely replacing 6 Mb of mouse Ig heavy and kappa light variable region germ-line gene segments with their human counterparts while leaving the mouse constant regions intact, using a unique in situ humanization approach. We reasoned the introduced human variable region gene segments would function indistinguishably in their new genetic location, whereas the retained mouse constant regions would allow for optimal interactions and selection of the resulting antibodies within the mouse environment. We show that these mice, termed VelocImmune mice because they were generated using VelociGene technology, efficiently produce human:mouse hybrid antibodies (that are rapidly convertible to fully human antibodies) and have fully functional humoral immune systems indistinguishable from those of WT mice. The efficiency of the VelocImmune approach is confirmed by the rapid progression of 10 different fully human antibodies into human clinical trials.

  4. IMMUNOMETRIC ASSAY TO DETERMINE FREE LIGHT CHAIN CONCENTRATIONS OF HUMAN IMMUNOGLOBULINS

    Directory of Open Access Journals (Sweden)

    M. P. Samoylovich

    2016-01-01

    Full Text Available Detection of total free light chains (FLC of immunoglobulins and their ratio (kappa/lambda quotient are used in diagnostics and monitoring of multiple myeloma and other gammapathies, primary amyloidosis and multiple sclerosis. Previously described immunoassays with monoclonal antibodies (Mabs against cryptic and constantly exposed epitopes of FLC failed to recognize rare variants of lambda Bence-Jones proteins and a significant proportion of lambda chains excreted with urine. Aiming to improve this approach, a novel murine Mab (IgG2b coded as 1C8 was employed, which specifically binds free lambda chains but doesn’t interact with native IgA, IgG, and IgM. The novel Mab recognized an epitope exposed at free lambda chains in peripheral blood of healthy donors and patients with multiple myeloma. It is not destroyed or masked upon renal filtration.The aim of this study was to determine basic features of improved assay system, and to estimate its potential in diagnostics of monoclonal gammapathies. The mixtures of three Bence-Jones proteins of either kappa- or lambda- types purified from the urine of multiple myeloma patients were used as calibrator samples.Improved immunometric assay is able to detect free kappa and lambda chains in serum and urine at a scale of 1 to 100 ng/ml, thus being three orders more sensitive than, e.g., detection levels of Freelite method based on polyclonal antibodies.A novel assay allows to detect free kappa and lambda chains at comparable levels in serum or urine, and to deduce kappa/lambda ratio. The proposed assay is able to detect FLC in 10,000-fold excess of whole IgG molecules. The calibrating plots for both antigens are linear on log-log scales, with very similar slopes. Detection thresholds for kappa or lambda chains proved to be 5 and 3 ng/ml, respectively. Mean concentrations of free kappa chains in sera of healthy donors were 6.7±2.1, in urine, 4.2±3.8 mcg/ml. Mean concentrations of free lambda chains were 4

  5. Experience with Subgam, a Subcutaneously Administered Human Normal Immunoglobulin (ClinicalTrials.gov--NCT02247141.

    Directory of Open Access Journals (Sweden)

    Clive Dash

    Full Text Available A multi-centre, non-comparative study examining the efficacy and safety of Subgam, a normal immunoglobulin (IgG given weekly as a rapid subcutaneous infusion to patients with primary immune deficiency (PID, is reported. Also included is a summary of adverse drug reactions associated with the use of marketed Subgam in the UK.50 patients with stable PID on IgG therapy were enrolled: Stage 1 included three infusions with prior IgG product followed by 6 months with Subgam, Stage 2 involved long-term Subgam therapy up to 4 years.Stage 1, 85% of the subjects aged >12 years and 93% of the subjects aged <12 years achieved IgG levels ≥6 and ≥4 g/L, respectively at all observations. There were 3.62 infections/patient/year during Subgam treatment. The most common product-related events were infusion site reactions (50% of patients. Recent post-hoc pharmacokinetics analysis of the post-infusion serum total IgG concentration indicated that the mean dose-normalised incremental IgG AUCτ following intravenous dosing (120.5 g.day/L was 1.64-fold that of the dose-normalised mean incremental IgG AUCτ following subcutaneous dosing (73.6 g.day/L, corresponding to an estimated IgG bioavailability for subcutaneous dosing of 61%. Only 34 post-licensing adverse reactions have been received in 30 patients over a period of 10 years; fourteen were classed as serious as defined by the ICH guidelines on good clinical practice. The most common post-licensing adverse reaction was infusion site reaction (7 reports. There were 7 reports of flu-like symptoms (pyrexia/shivering/rigors/feeling hot or cold, 2 other reports of combined flu-like symptoms and infusion site reactions, 5 reports of generalised skin reactions, and 3 reports of combined infusion site and skin reactions. There were also reports of anaphylaxis (2 reports and 8 other adverse events (including headache. In conclusion, Subgam is effective and well tolerated in the treatment of PID.ClinicalTrials.gov NCT

  6. Thermal expression of intersubjectivity offers new possibilities to human-machine and technologically mediated interactions.

    Science.gov (United States)

    Merla, Arcangelo

    2014-01-01

    The evaluation of the psychophysiological state of the interlocutor is an important element of interpersonal relationships and communication. Thermal infrared (IR) imaging has proved to be a reliable tool for non-invasive and contact-less evaluation of vital signs, psychophysiological responses, and emotional states. This technique is quickly spreading in many fields, from psychometrics to social and developmental psychology; and from the touch-less monitoring of vital signs and stress, up to the human-machine interaction. In particular, thermal IR imaging promises to be of use for gathering information about affective states in social situations. This paper presents the state of the art of thermal IR imaging in psychophysiology and in the assessment of affective states. The goal is to provide insights about its potentialities and limits for its use in human-artificial agent interaction in order to contribute to a major issue in the field: the perception by an artificial agent of human psychophysiological and affective states.

  7. Immunoglobulins in nasal secretions of healthy humans: structural integrity of secretory immunoglobulin A1 (IgA1) and occurrence of neutralizing antibodies to IgA1 proteases of nasal bacteria

    DEFF Research Database (Denmark)

    Kirkeby, L; Rasmussen, TT; Reinholdt, Jesper

    2000-01-01

    Certain bacteria, including overt pathogens as well as commensals, produce immunoglobulin A1 (IgA1) proteases. By cleaving IgA1, including secretory IgA1, in the hinge region, these enzymes may interfere with the barrier functions of mucosal IgA antibodies, as indicated by experiments in vitro....... Previous studies have suggested that cleavage of IgA1 in nasal secretions may be associated with the development and perpetuation of atopic disease. To clarify the potential effect of IgA1 protease-producing bacteria in the nasal cavity, we have analyzed immunoglobulin isotypes in nasal secretions of 11...... healthy humans, with a focus on IgA, and at the same time have characterized and quantified IgA1 protease-producing bacteria in the nasal flora of the subjects. Samples in the form of nasal wash were collected by using a washing liquid that contained lithium as an internal reference. Dilution factors and...

  8. Characterization of upFc, a fragment of human immunoglobulin G1 produced by pepsin in urea.

    Science.gov (United States)

    Parr, D M; Hofmann, T; Connell, G E

    1976-09-01

    The digestion of human IgG1/K myeloma proteins with pepsin in the presence of 8 M-urea produces fragments that differ from those produced by aqueous peptic digestion, and from other characteristic immunoglobulin fragments. Fb'2, the larger urea/pepsin fragment, was previously shown to consist of the constant regions of the light chains, and the CH1 domains and hinge regions of the heavy chains. The smaller fragment, upFc, has now been characterized. After reduction, three peptides were released from fragment upFc. Amino acid sequencing, N- and C-terminal determinations and amino acid compositions have enabled these peptides to be identified as residues Ile-253 to Leu-306, residues Thr-307 to Asp-376 and residues Thr-411 to Gly-446 of the heavy chain. Fragment upFc therefore contains the entire Fc region, beginning at residue Ile-253, except for a 34-residue section from within the CH3-domain disulphide loop. Peptic digestion of IgG1/K proteins in 8M-urea therefore provides a method for isolating from gamma1 heavy chains five homogeneous peptides in good yield, which account for almost the entire constant region. Characterization of fragments Fb'2 and upFc has shown that the action of pepsin in urea is entirely different from that of aqueous pepsin. Two gamma1 heavy chains have been shown to differ in sequence at three positions from the sequence reported for protein Eu.

  9. PCR amplification and high throughput sequencing of immunoglobulin heavy chain genes from formalin-fixed paraffin-embedded human biopsies.

    Science.gov (United States)

    Tabibian-Keissar, Hilla; Schibby, Ginette; Michaeli, Miri; Rakovsky-Shapira, Aviya; Azogui-Rosenthal, Noemie; Dunn-Walters, Deborah K; Rosenblatt, Kinneret; Mehr, Ramit; Barshack, Iris

    2013-02-01

    The use of high throughput sequencing (HTS) technologies in biomedicine is expanding in a variety of fields in recent years. The 454 system is an HTS platform that is ideally suited to characterize B cell receptor (BCR) repertoires by sequencing of immunoglobulin (Ig) genes, as it is able to sequence stretches of several hundred nucleotides. Most studies that used this platform for antibody repertoire analyses have started from fresh or frozen tissues or peripheral blood samples, and rely on starting with optimal quality DNA. In this paper we demonstrate that BCR repertoire analysis can be done using DNA from formalin-fixed paraffin-embedded (FFPE) human tissue samples. The heterogeneity of BCR repertoires we obtained confirms the plausibility of HTS of DNA from FFPE specimens. The establishment of experimental protocols and computational tools that enable sequence data analysis from the low quality DNA of FFPE tissues is important for enabling research, as it would enable the use of the rich source of preserved samples in clinical biobanks and biopsy archives.

  10. Thermal expression of intersubjectivity offers new possibilities to human-machine and technologically mediated interactions

    Directory of Open Access Journals (Sweden)

    Arcangelo eMerla

    2014-07-01

    Full Text Available The evaluation of the psychophysiological state of the interlocutor is an important element of interpersonal relationships and communication. Thermal infrared imaging has proved to be a reliable tool for non-invasive and contact-less evaluation of vital signs, psychophysiological responses and emotional states. This technique is quickly spreading in many fields, from psychometrics to social and developmental psychology; and from the touch-less monitoring of vital signs and stress, up to the human-machine interaction. In particular, thermal IR imaging promises to be of use for gathering information about affective states in social situations. This paper presents the state of the art of thermal infrared imaging in psychophysiology and in the assessment of affective states. The goal is to provide insights about its potentialities and limits for its use in human-artificial agent interaction in order to contribute to a major issue in the field: the perception by an artificial agent of human psychophysiological and affective states.

  11. Spatial mapping by imaging mass spectrometry offers advancements for rapid definition of human skin proteomic signatures.

    Science.gov (United States)

    Taverna, Domenico; Nanney, Lillian B; Pollins, Alonda C; Sindona, Giovanni; Caprioli, Richard

    2011-08-01

    Investigations into the human skin proteome by classical analytical procedures have not addressed spatial molecular distributions in whole-skin biopsies. The aim of this study was to develop methods for the detection of protein signatures and their spatial disposition in human skin using advanced molecular imaging technology based on mass spectrometry technologies. This technology allows for the generation of protein images at specific molecular weight values without the use of antibody while maintaining tissue architecture. Two experimental approaches were employed: MALDI-MS profiling, where mass spectra were taken from discrete locations based on histology, and MALDI-IMS imaging, where complete molecular images were obtained at various MW values. In addition, proteins were identified by in situ tryptic digestion, sequence analysis of the fragment peptides and protein database searching. We have detected patterns of protein differences that exist between epidermis and dermis as well as subtle regional differences between the papillary and reticular dermis. Furthermore, we were able to detect proteins that are constitutive features of human skin as well as those associated with unique markers of individual variability.

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  13. A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Weiguo; Che, Wenti; Guimai, Zuo; Chen, Jiejing [181st Hospital Guangxi, Central Laboratory, Laboratory of Metabolic Diseases Research, Guangxi Province (China); Li, Liping [Guangxi Normal University, The Life Science College, Guangxi Province (China); Li, Wuxian [Key Laboratory of Laboratory Medical Diagnostics of Education Ministry, Chongqiong Medical University, Chongqing (China); Dai, Yong [Clinical Medical Research Center, the Second Clinical Medical College of Jinan University (Shenzhen People' s Hospital), Shenzhen, Guangdong Province (China)

    2012-07-01

    Objectives: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. Methods: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23), low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23), and high-risk patients with nephropathies of grades IV-V (N = 12). Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. Results: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-inositol, lactate, L6 lipids ( CH-CH{sub 2}-CH = O), L5 lipids (-CH{sub 2}-C = O), and L3 lipids (-CH{sub 2}-CH{sub 2}-C = O) as well as lower levels of {beta}-glucose, {alpha}-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. Conclusions: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high

  14. A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

    Directory of Open Access Journals (Sweden)

    Weiguo Sui

    2012-01-01

    Full Text Available OBJECTIVES: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. METHODS: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23, low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23, and high-risk patients with nephropathies of grades IV-V (N = 12. Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. RESULTS: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-Inositol, lactate, L6 lipids ( = CH-CH2-CH = O, L5 lipids (-CH2-C = O, and L3 lipids (-CH2-CH2-C = O as well as lower levels of β -glucose, α-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. CONCLUSIONS: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high-risk groups in our

  15. Feline immunoglobulins.

    Science.gov (United States)

    Schultz, R D; Scott, F W; Duncan, J R; Gillespie, J H

    1974-02-01

    Immunoglobulins (Ig) in feline sera and secretions were identified by immuno-electrophoresis and immunodiffusion with rabbit antisera prepared to feline IgG, IgA, IgM, and whole serum. Adult cat sera, colostral whey, postcolostral sera, tears, and nasal secretions contained IgG, IgA, and IgM. IgG was the only Ig identified in precolostral sera and cerebrospinal fluid. Milk, intestinal contents, pooled allantoic and amniotic fluids, and saliva from adult cats and urine from suckling kittens contained IgG and IgA. Ig were not detected in urine from adult cats. Bile was unique in that IgA and IgM were the predominant Ig.

  16. Clinical applications of immunoglobulin: update

    Directory of Open Access Journals (Sweden)

    Marcia Cristina Zago Novaretti

    2011-06-01

    Full Text Available Human immunoglobulin is the most used blood product in the clinical practice. Immunoglobulin applications have increased quickly since the elucidation of its immunomodulatory and antiinflammatory properties which turned this blood product into a precious tool in the treatment of numerous diseases that present with humoral immune deficiency or that cause immune system dysfunction. Currently, the approved indications for Ig are: primary immunodeficiencies, secondary immunodeficiencies (multiple myeloma or chronic lymphoid leukemia, Kawasaki syndrome, immune thrombocytopenic purpura, Guillain Barré syndrome, graft-versus-host disease following bone marrow transplantation and repeat infections in HIV children. On the other hand, there are numerous "off-label" indications of immunoglobulin, which represent 20-60% of all clinical applications of this drug. It is important to study all these indications and, above all, the scientific evidence for its use, in order to provide patients with a new therapeutic option without burdening the health system. This review results from a wide selection of papers identified in the Pubmed and Lilacs scientific electronic databases. A group of descriptors were used from human immunoglobulin to the names of each disease that immunoglobulin is clinically applied. Our main objective is to list the numerous indications of immunoglobulin, both authorized and "off-label" and to analyze these indications in the light of the most recent scientific evidence.

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  20. Inhibitory potential of Buffalo (Bubalus bubalis) colostrum immunoglobulin G on Klebsiella pneumoniae.

    Science.gov (United States)

    L S, Mamatha Bhanu; Nishimura, S-I; H S, Aparna

    2016-07-01

    The unique components of colostrum like free oligosaccharides and glycoconjugates are known to offer resistance to enzymatic digestion in the gastrointestinal tract and have the ability to inhibit the localized adherence of enteropathogens to the digestive tract of the neonates. In this context, we have evaluated the in vitro effect of buffalo colostrum immunoglobulin G on human pathogen Klebsiella pneumoniae, a predominant multidrug resistant pathogen associated with nasocomial infections. The investigation revealed growth inhibitory potential of immunoglobulin G in a dose dependent manner supported by scanning electron microscopic studies. The N-glycan enriched fraction of immunoglobulin G after PNGase treatment was found more effective, comparable to ampicillin than native immunoglobulin G supporting the fact that colostrum derived oligosaccharides is crucial and act as ideal substrates for undesirable and pathogenic bacteria. The MALDI TOF/TOF analysis confirmed the glycostructures of abundant N-glycans of immunoglobulin G exerting antibacterial activity. The proteomic analysis revealed variations between control and treated cells and expression of chemotaxis-CheY protein (14kDa) was evidenced in response to immunoglobulin G treatment. Hence, it would be interesting to investigate the mode of inhibition of multidrug-resistant K. pneumoniae by buffalo colostrum immunoglobulin G with the identification of a newly expressed signalling protein.

  1. A human T cell lymphoma secreting an immunoglobulin E specific helper factor.

    Science.gov (United States)

    Young, M C; Harfi, H; Sabbah, R; Leung, D Y; Geha, R S

    1985-06-01

    An 8-yr-old nonallergic girl with non-Hodgkin's lymphoma had markedly elevated serum IgE at presentation (greater than 10,000 IU/ml), negative skin tests to a battery of 24 common allergens, and no evidence of parasitic infestation. Serum levels of IgG, IgA, and IgM were normal. Remission after cytotoxic chemotherapy was accompanied by a marked reduction in serum IgE levels (to less than 200 IU/ml) with no change in the level of serum IgG, IgM, or IgA. Recurrence of the lymphoma 7 mo after remission was accompanied by an isotype specific rise in serum IgE (to 3,850 IU/ml). Isoelectric focusing revealed that the IgE was polyclonal. Phenotypic analysis of the lymphoma obtained during relapse revealed all (greater than 98%) cells to be T3+, T4+, and T8+. Incubation of lymphoma cells with human myeloma IgE followed by immunosorbent purified fluorescein tagged goat anti-human IgE (anti-IgE PS-adsorbed over IgE ADZ) stained 25% of the cells. In contrast, less than 1% of the cells were stained after incubation with human IgG followed by fluorescein conjugated goat anti-human IgE. Supernatants from lymphoma cells (5 X 10(6)/ml, 48 h) enhanced IgE production in B cells derived from four patients with allergic rhinitis (mean +/- SD picograms per milliliter of net IgE 930 +/- 320 in unstimulated cultures versus 2,450 +/- 650 in cultures stimulated with lymphoma supernatants; P less than 0.01) but did not induce IgE synthesis in B cells from two normal subjects that synthesized no IgE spontaneously. Lymphoma supernatants failed to enhance IgG synthesis by B cells of both allergic and nonallergic subjects. These results indicate that a T cell lymphoma comprised of cells bearing Fc receptors for IgE with a phenotype characteristic of immature T cells (i.e., T3+, T4+, T8+) exhibited IgE specific helper function. This lymphoma may represent the monoclonal expansion of a subpopulation of IgE specific helper T cells.

  2. Human Toxoplasma gondii-specific secretory immunoglobulin A reduces T. gondii infection of enterocytes in vitro.

    Science.gov (United States)

    Mack, D G; McLeod, R

    1992-12-01

    Whey from 17 women (four acutely infected with Toxoplasma gondii, eight chronically infected, and five uninfected) was studied. T. gondii-specific secretory IgA antibodies were demonstrated by ELISA in whey from acutely infected and one of eight chronically infected women. Such antibodies to tachyzoite proteins of 100 kD (eliminated by protease but not periodate or neuraminidase treatment) were demonstrated in whey from acutely infected subjects when Western blots were probed with their whey and antibodies to human secretory IgA or IgA or secretory piece. Secretory IgA from four of eight chronically infected women recognized the 46- and 69-kD epitopes. Other whey samples were negative. Incubation of T. gondii tachyzoites with whey or purified secretory IgA from acutely infected (but not seronegative) women caused 50-75% reduction in infection of enterocytes in vitro. Whey reactive with the 46-kD epitope from three of six chronically infected women caused less (> or = 40%) inhibition. Whey and purified secretory IgA from two of three acutely infected women agglutinated tachyzoites. Whey did not result in complement-dependent lysis of T. gondii. These results indicate that it may be possible to produce human secretory IgA to T. gondii capable of reducing initial infection of enterocytes, as such IgA is present during natural infection. They also demonstrate candidate epitopes for such protection.

  3. Brown Norway rat ovalbumin-specific immunoglobulin E antibodies increase the human basophil expression of CD63 marker.

    Science.gov (United States)

    Bellou, A; Saint-Laudy, J; Knippels, L; Montémont, C; Vauthier, E; Gerard, P; Pellegrom, H; Koerkamp, E K; Lesesve, J F; Guéant, J L; Lambert, H; Mallié, J P

    2003-03-01

    Anaphylactic shock is an immunoglobulin E (IgE)-dependent hypersensitivity. Biological tests like leucocyte histamine release (LHR) and human basophil activation (HBA), frequently used in human allergy, reflect both the amount of IgE fixed on cells and the cellular reactivity. To assess whether serum-specific IgE from Brown Norway (BN) rats prepared for ovalbumin (OVA)-induced anaphylactic shocks can activate human basophils which has a potential interest in experimental allergy: such a test could rapidly assert an IgE sensitization in laboratory animals genetically T-helper 2 (Th2)-predisposed. Rats (n = 39) were immunized three times (day 0, day 5 and day 21) with OVA injected subcutaneously. One week after the third immunization, a shock was induced with an intravenous (i.v.) bolus of OVA. Sensitization was assessed by passive cutaneous anaphylaxis (PCA) test and dosages of serum IgE antibodies anti-OVA by enzyme-linked immunosorbent assay. Blood basophils were counted before and during the shock. Before the shock induction (at day 21), an LHR test was performed on rat blood, and human basophils were sensitized with rat sera. HBA was demonstrated by the increase in the percentage of cells expressing CD63 antigen membrane, measured by flow cytometry. Twenty-one days after the first subcutaneous (s.c.) immunization, the rat serum induced a significant HBA. HBA was observed neither with the same serum previously heated nor with the serum from nonimmunized rats (NIRs). OVA-specific IgEs were significantly increased in immunized rat (IR) serum. The PCA test was negative when the serum was previously heated (56 degrees C). We never observed any circulating basophils, and LHR test was negative. After OVA i.v. administration, all IRs died rapidly. HBA testing strongly suggests a mediation by specific IgE in the increase of CD63 in BN rats. Thus, HBA test seems useful in assessing whether an experimental allergy was induced in animals genetically predisposed to an immune

  4. Aberrant recombination and repair during immunoglobulin class switching in BRCA1-deficient human B cells

    DEFF Research Database (Denmark)

    Björkman, Andrea; Qvist, Per; Du, Likun

    2015-01-01

    machinery. A shift to the use of microhomology-based, alternative end-joining (A-EJ) and increased frequencies of intra-S region deletions as well as insertions of inverted S sequences were observed at the recombination junctions amplified from BRCA1-deficient human B cells. Furthermore, increased use...... underlying BRCA1’s function in maintaining genome stability and tumor suppression but may also point to a previously unrecognized role of BRCA1 in B-cell lymphomagenesis....... of long microhomologies was found at recombination junctions derived from E3 ubiquitin-protein ligase RNF168-deficient, Fanconi anemia group J protein (FACJ, BRIP1)-deficient, or DNA endonuclease RBBP8 (CtIP)-compromised cells, whereas an increased frequency of S-region inversions was observed in breast...

  5. Immunoglobulin V(H) gene sequence analysis of spontaneous murine immunoglobulin secreting B-cell tumours with clinical features of human disease

    NARCIS (Netherlands)

    Zhu, D.; Arkel, C. van; King, C.A.; Meirvenne, S. van; Greef, C. de; Thielemans, K.; Radl, J.; Stevenson, F.K.

    1998-01-01

    The 5T series of multiple myelomas (MM) and Waldenstrsom's macroglobulinaemia-like lymphomas (WM), which developed spontaneously in ageing mice of the C57BL/KaLwRij strain, shows clinical and biological features that closely resemble their corresponding human diseases. In order to compare the patter

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    Are you a member of the Staff Association? Did you know that as a member you can benefit from the following special offers: BCGE (Banque Cantonale de Genève): personalized banking solutions with preferential conditions.     TPG: reduced rates on annual transport passes for all active and retired staff.     Aquaparc: reduced ticket prices for children and adults at this Swiss waterpark in Le Bouveret.     Walibi: reduced prices for children and adults at this French attraction park in Les Avenières.       FNAC: 5% reduction on FNAC vouchers.       For more information about all these offers, please consult our web site: http://association.web.cern.ch/association/en/OtherActivities/Offers.html

  8. Human Lyme arthritis and the immunoglobulin G antibody response to the 37-kilodalton arthritis-related protein of Borrelia burgdorferi.

    Science.gov (United States)

    Salazar, Carlos A; Rothemich, Monika; Drouin, Elise E; Glickstein, Lisa; Steere, Allen C

    2005-05-01

    In Borrelia burgdorferi-infected C3H-scid mice, antiserum to a differentially expressed, 37-kDa spirochetal outer-surface protein, termed arthritis-related protein (Arp), has been shown to prevent or reduce the severity of arthritis. In this study, we determined the immunoglobulin G (IgG) antibody responses to this spirochetal protein in single serum samples from 124 antibiotic-treated human patients with early or late manifestations of Lyme disease and in serial serum samples from 20 historic, untreated patients who were followed longitudinally from early infection through the period of arthritis. These 20 patients were representative of the spectrum of the severity and duration of Lyme arthritis. Among the 124 antibiotic-treated patients, 53% with culture-proven erythema migrans (EM) had IgG responses to recombinant glutathione S-transferase (GST)-Arp, as did 59% of the patients with facial palsy and 68% of those with Lyme arthritis. In addition, 75 to 80% of the 20 past, untreated patients had reactivity with this protein when EM was present, during initial episodes of joint pain, or during the maximal period of arthritis. There was no association at any of these three time points between GST-Arp antibody levels and the severity of the maximal attack of arthritis or the total duration of arthritis. Thus, after the first several weeks of infection, 60 to 80% of patients had IgG antibody responses to GST-Arp, but this response did not correlate with the severity or duration of Lyme arthritis.

  9. Receptor-binding properties of the peptides corresponding to the beta-endorphin-like sequence of human immunoglobulin G.

    Science.gov (United States)

    Zav'yalov, V P; Zaitseva, O R; Navolotskaya, E V; Abramov, V M; Volodina EYu; Mitin, Y V

    1996-01-01

    The decapeptide H2N-Ser-Leu-Thr-Cys-Leu-Val-Lys-Gly-Phe-Tyr-COOH (termed immunorphin) corresponding to the sequence 364-373 of the CH3 domain of the human immunoglobulin G1 Eu heavy chain and displaying a 43% identity with the antigenic determinant of beta-endorphin was synthesized. Immunorphin was found to compete with 125I-beta-endorphin for high-affinity receptors on murine peritoneal macrophages (K = 2.5 +/- 0.9 x 10(-9) M) and with 3H-morphin for receptors on murine thymocytes (Ki = 2.7 +/- 0.6 x 10(-9) M) and murine macrophages (Ki = 5.9 +/- 0.7 x 10(-9) M). In particular two types of receptors to 125I-beta-endorphin with Kd1 = 6.1 +/- 0.6 x 10(-9) M and Kd2 = 3.1 +/- 0.2 x 10(-8) M were revealed on macrophages. The second type of receptors interacted with 125I-beta-endorphin, 3H-Met-enkephalin, 3H-Leu-enkephalin and 3H-morphin; the first displayed reactivity with 125I-beta-endorphin, 3H-morphin and immunorphin. The first type receptors are not present on murine brain cells nor are inhibited by naloxone. A minimum fragment of immunorphin practically completely retaining its inhibitory activity in the competition tests with 125I-beta-endorphin for common receptors on thymocytes was found to correspond to the tetrapeptide H2N-Lys-Gly-Phe-Tyr-COOH (Ki = 5.6 +/- 0.5 x 10(-9) M).

  10. Why natural killer cells are not enough: a further understanding of killer immunoglobulin-like receptor and human leukocyte antigen.

    Science.gov (United States)

    Alecsandru, Diana; García-Velasco, Juan A

    2017-06-01

    The immune system's role in recurrent reproductive failure is a controversial issue in assisted reproduction. Most studies into immune system implication in reproduction have focused on finding markers of peripheral blood and less on the uterine environment. Peripheral blood natural killer cells have become an "immune study core" for women with recurrent miscarriage or recurrent implantation failure, based on the mistaken notion that they cause reproductive failure by killing or "rejecting" the embryo. Maternal-fetal tolerance begins at the uterine level, so successful adaptation to the fetus occurs after a complicated process. Insufficient uterine lining invasion by an invading extravillous trophoblast is the primary defect in pregnancy disorders such as recurrent miscarriage. This process is regulated by the interaction between maternal killer immunoglobulin-like receptors (KIRs), expressed by uterine natural killer cells (uNK), and their ligand human leukocyte antigen (HLA) C, expressed by the extravillous trophoblast. Pregnancies are an increased risk of disorders in mothers with KIR AA when the fetus has paternal HLA-C2. A recent report has indicated that the expression of more than one paternal HLA-C by the extravillous trophoblast in assisted reproduction may affect placentation in mothers with KIR AA. This review provides insight into the immune system's role in assisted reproductive treatments. These insights can have an impact on the selection of single-embryo transfer and/or oocyte/sperm donor according to HLA-C in patients with recurrent implantation failure and recurrent miscarriage depending on their KIR haplotype. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  11. Offer/Acceptance Ratio.

    Science.gov (United States)

    Collins, Mimi

    1997-01-01

    Explores how human resource professionals, with above average offer/acceptance ratios, streamline their recruitment efforts. Profiles company strategies with internships, internal promotion, cooperative education programs, and how to get candidates to accept offers. Also discusses how to use the offer/acceptance ratio as a measure of program…

  12. Natural and Immune Human Antibodies Reactive with Antigens of Virulent Neisseria gonorrhoeae: Immunoglobulins G, M, and A

    Science.gov (United States)

    Cohen, Irun R.

    1967-01-01

    Natural and immune human antibodies reactive with heat-labile and heat-stable antigens of virulent Neisseria gonorrhoeae were studied by use of an indirect fluorescent-antibody (IFA) procedure. The immunoglobulin class of the reactive antibodies was identified by using fluorescein-conjugated antisera specific for human IgG, IgA, or IgM in the IFA procedure. The effects of heat and mercaptoethanol on IFA reactivities were also studied. It appeared that antibodies of the IgG, IgM, and IgA classes present in the sera of both infected persons (immune antibodies) and normal persons with no history of gonococcal infection (natural antibodies) react with heat-stable somatic antigens. Immune IgG antibodies, however, were distinguishable from natural IgG antibodies by their ability to recognize heat-labile surface antigens. The distinction between natural and immune IgM antibodies was less obvious. IgM antibodies from both infected and normal persons appeared to react with heat-labile antigens. Some, but not all, infected persons had immune IgA antibodies to heat-labile as well as to heat-stable antigens. Treatment of sera with mercaptoethanol had no effect on IgG antibodies. The IFA activity of IgM antibodies was decreased, but not abolished. The effects of mercaptoethanol on IgA antibodies were variable. Some sera showed a decrease in IgA titer, and others showed an increase in IgA activity to certain antigens. Immune IgG antibodies were more resistant to heating than were natural IgG antibodies. Natural and immune IgM antibodies appeared equally sensitive to heating. IgA activity, on the other hand, was increased by heating sera at 60 C, but was decreased at higher temperatures. Thus, it appears that natural and immune human IgG antibodies to N. gonorrhoeae may be distinguished by their interactions with heat-labile antigens and by their resistance to heating. Images PMID:4961630

  13. Persistent oral human papillomavirus infection is associated with smoking and elevated salivary immunoglobulin G concentration.

    Science.gov (United States)

    Haukioja, Anna; Asunta, Maribel; Söderling, Eva; Syrjänen, Stina

    2014-09-01

    Prevalence and risk factors for human papillomavirus (HPV) persistence in oral mucosa are largely unknown. Furthermore, the antiviral effects of saliva in the outcome of oral HPV infections are unexplored. To compare the levels of selected salivary defence proteins in women with a persistent oral HPV infection and in those without any signs of oral HPV. Lifestyle factors including the use of oral contraceptives, oral sex, smoking and alcohol drinking habits were also assessed. This nested case-control study of the Finnish Family HPV Study included 60 women with a persistent oral HPV infection and 117 women who remained HPV DNA negative throughout a 6-year follow-up. Whole saliva samples and oral scrapings for HPV testing were collected at the same visit. The oral HPV status was related to salivary concentrations of lactoferrin, lysozyme, IgA, IgG, total protein and sodium as well as to the use of oral contraceptives, oral sex, smoking and alcohol drinking habits. Women with a persistent oral HPV infection had higher salivary levels of IgG (p=0.007) and lysozyme (p=0.002, when adjusted to the total protein concentration), than those without an HPV infection. Lactoferrin and IgA concentrations were not related to the HPV-status. Smoking increased the risk of a persistent oral HPV infection (p=0.020), but the oral HPV status was not related to other life-style factors studied. Smoking is a risk factor for a persistent oral HPV infection. Oral HPV infection may be associated with increased concentrations of salivary IgG and lysozyme. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Induction of maturation of human B-cell lymphomas in vitro. Morphologic changes in relation to immunoglobulin and DNA synthesis.

    Science.gov (United States)

    Beiske, K.; Ruud, E.; Drack, A.; Marton, P. F.; Godal, T.

    1984-01-01

    In vitro stimulation of cells from 8 non-Hodgkin's lymphomas comprising several histologic types with a tumor promotor (TPA) and with or without anti-immunoglobulins directed against the surface immunoglobulin of the tumor cells is reported. Morphologic transformation to immunoblastic and plasmablastic cells, but not to plasma cells, and induction of Ig and DNA synthesis were observed. A comparative analysis, including flow cytofluorometry, light microscopy combined with immunocytochemistry, and electron microscopy, suggests that the three events may not always be associated phenomena at the single-cell level even in monoclonal cell populations. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 PMID:6375389

  15. A cross-reacting human idiotype (B17) associated with antibodies to N-acetyl-D-glucosamine. Specificity, immunoglobulin class association, and distribution in the population.

    Science.gov (United States)

    Emmrich, F; Greger, B; Eichmann, K

    1983-04-01

    This report describes the study of the expression of an idiotype in the human population which is associated with antibodies to N-acetyl-D-glucosamine (GlcNAc) present in most human sera presumably due to streptococcal infections. The idiotype is identified with antisera and monoclonal antibodies prepared against the IgM (kappa) antibody secreted by the Epstein-Barr virus-transformed human B cell line B17. At least 90% of 207 individuals tested had immunoglobulin with B17 idiotypic determinants in their sera, as demonstrated with conventional and one monoclonal anti-idiotypic antibody. Another monoclonal anti-idiotypic antibody reacted with antibodies in only a few of the sera. No correlation was found between the level of expression of different idiotopes in individual human sera, suggesting molecular heterogeneity of the B17-positive antibody population. B17-positive immunoglobulins are to a large extent specific for GlcNAc but represent only a minor population of all GlcNAc-specific antibodies in human sera. B17 determinants are on IgM (kappa) in all human sera and on IgG and IgA in some. In addition, some lambda-bearing Ig was found to react with anti-B17 antisera, suggesting the detection of VH-associated idiotypic determinants in this experimental system.

  16. The concept of milk kinship in Islam: issues raised when offering preterm infants of Muslim families donor human milk.

    Science.gov (United States)

    El-Khuffash, Afif; Unger, Sharon

    2012-05-01

    Research has documented health benefits associated with donor human milk (DHM). Offering DHM to people of the Muslim faith raises important religious concerns for these families. Knowledge of these beliefs and an understanding of the rationale for these beliefs enable the health care team to establish rapport and build a foundation of trust with patients and their families, thereby paving the way to developing a treatment plan that is in the best interest of the patients without compromising care. This article describes the issues and a rationale for them and provides physicians caring for preterm infants of Muslim families with information to facilitate advocating DHM to those families.

  17. Ultrastructural localization of intracellular immunoglobulins in Epon-embedded human lymph nodes. An immunoelectron microscopic investigation using the immunogold staining (IGS) and the avidin-biotin-peroxidase complex (ABC) methods.

    Science.gov (United States)

    Viale, G; Dell'Orto, P; Braidotti, P; Coggi, G

    1985-05-01

    The ultrastructural localization of intracellular immunoglobulins on ultrathin sections of glutaraldehyde-fixed, postosmicated, and Epon-embedded human lymph nodes has been achieved using such highly sensitive immunocytochemical techniques as immunogold staining and avidin-biotin-peroxidase complex. These immunoelectron microscopic techniques allow the identification of intracellular immunoglobulins without affecting the ultrastructural morphology of the tissue, since they do not require any pretreatment of the sections with proteolytic enzymes or deresinating agents. Therefore, immunoglobulins can be precisely localized in the cell organelles; structures whose morphology is well preserved. The availability of a reliable postembedding staining procedure for the ultrastructural localization of immunoglobulins is of definite value for investigations on human lymphoid tissue, both normal and pathological.

  18. Human intravenous immunoglobulin provides protection against Aβ toxicity by multiple mechanisms in a mouse model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Goldsteins Gundars

    2010-12-01

    Full Text Available Abstract Background Purified intravenous immunoglobulin (IVIG obtained from the plasma of healthy humans is indicated for the treatment of primary immunodeficiency disorders associated with defects in humoral immunity. IVIG contains naturally occurring auto-antibodies, including antibodies (Abs against β-amyloid (Aβ peptides accumulating in the brains of Alzheimer's disease (AD patients. IVIG has been shown to alleviate AD pathology when studied with mildly affected AD patients. Although its mechanisms-of-action have been broadly studied, it remains unresolved how IVIG affects the removal of natively formed brain Aβ deposits by primary astrocytes and microglia, two major cell types involved in the neuroinflammatory responses. Methods We first determined the effect of IVIG on Aβ toxicity in primary neuronal cell culture. The mechanisms-of-action of IVIG in reduction of Aβ burden was analyzed with ex vivo assay. We studied whether IVIG solubilizes natively formed Aβ deposits from brain sections of APP/PS1 mice or promotes Aβ removal by primary glial cells. We determined the role of lysosomal degradation pathway and Aβ Abs in the IVIG-promoted reduction of Aβ. Finally, we studied the penetration of IVIG into the brain parenchyma and interaction with brain deposits of human Aβ in a mouse model of AD in vivo. Results IVIG was protective against Aβ toxicity in a primary mouse hippocampal neuron culture. IVIG modestly inhibited the fibrillization of synthetic Aβ1-42 but did not solubilize natively formed brain Aβ deposits ex vivo. IVIG enhanced microglia-mediated Aβ clearance ex vivo, with a mechanism linked to Aβ Abs and lysosomal degradation. The IVIG-enhanced Aβ clearance appears specific for microglia since IVIG did not affect Aβ clearance by astrocytes. The cellular mechanisms of Aβ clearance we observed have potential relevance in vivo since after peripheral administration IVIG penetrated to mouse brain tissue reaching highest

  19. Special offer

    CERN Multimedia

    Staff Association

    2010-01-01

    Special offer for members of the Staff Association and their families 10% reduction on all products in the SEPHORA shop (sells perfume, beauty products etc.) in Val Thoiry ALL YEAR ROUND. Plus 20% reduction during their “vente privée”* three or four times a year. Simply present your Staff Association membership card when you make your purchase. * next “vente privée” from 24th to 29th May 2010  

  20. Special offer

    CERN Multimedia

    Staff Association

    2011-01-01

    SPECIAL OFFER FOR OUR MEMBERS Tarif unique Adulte/Enfant Entrée Zone terrestre 19 euros instead of 23 euros Entrée “Zone terrestre + aquatique” 24 euros instead of 31 euros Free for children under 3, with limited access to the attractions. Walibi Rhône-Alpes is open daily from 22 June to 31 August, and every week end from 3 September until 31 October. Closing of the “zone aquatique” 11 September.

  1. Special offer

    CERN Multimedia

    Staff Association

    2011-01-01

    SPECIAL OFFER FOR OUR MEMBERS Tarif unique Adulte/Enfant Entrée Zone terrestre 19 euros instead of 23 euros Entrée “Zone terrestre + aquatique” 24 euros instead of 31 euros Free for children under 3, with limited access to the attractions. Walibi Rhône-Alpes is open daily from 22 June to 31 August, and every week end from 3 September until 31 October. Closing of the “zone aquatique” 11 September.

  2. Distribution of kappa and lambda light chain isotypes among human blood immunoglobulin-secreting cells after vaccination with pneumococcal polysaccharides

    DEFF Research Database (Denmark)

    Heilmann, C; Barington, T

    1989-01-01

    The light chain isotype of immunoglobulin-secreting blood cells was investigated by means of monolayer plaque-forming cell assays allowing direct immunofluorescence staining for cytoplasmic kappa and lambda light chains in centre cells. The study revealed that cultured, polyclonally activated pok...

  3. N-terminal truncated human RAG1 proteins can direct T-cell receptor but not immunoglobulin gene rearrangements

    NARCIS (Netherlands)

    J.G. Noordzij; N.S. Verkaik (Nicole); N.G. Hartwig (Nico); R. de Groot (Ronald); D.C. van Gent (Dik); J.J.M. van Dongen (Jacques)

    2000-01-01

    textabstractThe proteins encoded by RAG1 and RAG2 can initiate gene recombination by site-specific cleavage of DNA in immunoglobulin and T-cell receptor (TCR) loci. We identified a new homozygous RAG1 gene mutation (631delT) that leads to a premature stop codon in the 5

  4. Leptospira Immunoglobulin-Like Protein B Interacts with the 20th Exon of Human Tropoelastin Contributing to Leptospiral Adhesion to Human Lung Cells

    Directory of Open Access Journals (Sweden)

    Ching-Lin Hsieh

    2017-05-01

    Full Text Available Leptospira immunoglobulin-like protein B (LigB, a surface adhesin, is capable of mediating the attachment of pathogenic leptospira to the host through interaction with various components of the extracellular matrix (ECM. Human tropoelastin (HTE, the building block of elastin, confers resilience and elasticity to lung, and other tissues. Previously identified Ig-like domains of LigB, including LigB4 and LigB12, bind to HTE, which is likely to promote Leptospira adhesion to lung tissue. However, the molecular mechanism that mediates the LigB-HTE interaction is unclear. In this study, the LigB-binding site on HTE was further pinpointed to a N-terminal region of the 20th exon of HTE (HTE20N. Alanine mutants of basic and aromatic residues on HTE20N significantly reduced binding to the LigB. Additionally, HTE-binding site was narrowed down to the first β-sheet of LigB12. On this binding surface, residues F1054, D1061, A1065, and D1066 were critical for the association with HTE. Most importantly, the recombinant HTE truncates could diminish the binding of LigB to human lung fibroblasts (WI-38 by 68%, and could block the association of LigA-expressing L. biflexa to lung cells by 61%. These findings should expand our understanding of leptospiral pathogenesis, particularly in pulmonary manifestations of leptospirosis.

  5. CIG-DB: the database for human or mouse immunoglobulin and T cell receptor genes available for cancer studies.

    Science.gov (United States)

    Nakamura, Yoji; Komiyama, Tomoyoshi; Furue, Motoki; Gojobori, Takashi; Akiyama, Yasuto

    2010-07-27

    Immunoglobulin (IG or antibody) and the T-cell receptor (TR) are pivotal proteins in the immune system of higher organisms. In cancer immunotherapy, the immune responses mediated by tumor-epitope-binding IG or TR play important roles in anticancer effects. Although there are public databases specific for immunological genes, their contents have not been associated with clinical studies. Therefore, we developed an integrated database of IG/TR data reported in cancer studies (the Cancer-related Immunological Gene Database [CIG-DB]). This database is designed as a platform to explore public human and murine IG/TR genes sequenced in cancer studies. A total of 38,308 annotation entries for IG/TR proteins were collected from GenBank/DDBJ/EMBL and the Protein Data Bank, and 2,740 non-redundant corresponding MEDLINE references were appended. Next, we filtered the MEDLINE texts by MeSH terms, titles, and abstracts containing keywords related to cancer. After we performed a manual check, we classified the protein entries into two groups: 611 on cancer therapy (Group I) and 1,470 on hematological tumors (Group II). Thus, a total of 2,081 cancer-related IG and TR entries were tabularized. To effectively classify future entries, we developed a computational method based on text mining and canonical discriminant analysis by parsing MeSH/title/abstract words. We performed a leave-one-out cross validation for the method, which showed high accuracy rates: 94.6% for IG references and 94.7% for TR references. We also collected 920 epitope sequences bound with IG/TR. The CIG-DB is equipped with search engines for amino acid sequences and MEDLINE references, sequence analysis tools, and a 3D viewer. This database is accessible without charge or registration at http://www.scchr-cigdb.jp/, and the search results are freely downloadable. The CIG-DB serves as a bridge between immunological gene data and cancer studies, presenting annotation on IG, TR, and their epitopes. This database

  6. CIG-DB: the database for human or mouse immunoglobulin and T cell receptor genes available for cancer studies

    Directory of Open Access Journals (Sweden)

    Furue Motoki

    2010-07-01

    Full Text Available Abstract Background Immunoglobulin (IG or antibody and the T-cell receptor (TR are pivotal proteins in the immune system of higher organisms. In cancer immunotherapy, the immune responses mediated by tumor-epitope-binding IG or TR play important roles in anticancer effects. Although there are public databases specific for immunological genes, their contents have not been associated with clinical studies. Therefore, we developed an integrated database of IG/TR data reported in cancer studies (the Cancer-related Immunological Gene Database [CIG-DB]. Description This database is designed as a platform to explore public human and murine IG/TR genes sequenced in cancer studies. A total of 38,308 annotation entries for IG/TR proteins were collected from GenBank/DDBJ/EMBL and the Protein Data Bank, and 2,740 non-redundant corresponding MEDLINE references were appended. Next, we filtered the MEDLINE texts by MeSH terms, titles, and abstracts containing keywords related to cancer. After we performed a manual check, we classified the protein entries into two groups: 611 on cancer therapy (Group I and 1,470 on hematological tumors (Group II. Thus, a total of 2,081 cancer-related IG and TR entries were tabularized. To effectively classify future entries, we developed a computational method based on text mining and canonical discriminant analysis by parsing MeSH/title/abstract words. We performed a leave-one-out cross validation for the method, which showed high accuracy rates: 94.6% for IG references and 94.7% for TR references. We also collected 920 epitope sequences bound with IG/TR. The CIG-DB is equipped with search engines for amino acid sequences and MEDLINE references, sequence analysis tools, and a 3D viewer. This database is accessible without charge or registration at http://www.scchr-cigdb.jp/, and the search results are freely downloadable. Conclusions The CIG-DB serves as a bridge between immunological gene data and cancer studies, presenting

  7. Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.

    Directory of Open Access Journals (Sweden)

    Gordan Lauc

    Full Text Available Glycosylation of immunoglobulin G (IgG influences IgG effector function by modulating binding to Fc receptors. To identify genetic loci associated with IgG glycosylation, we quantitated N-linked IgG glycans using two approaches. After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC in 2,247 individuals from four European discovery populations. In parallel, we measured IgG N-glycans using MALDI-TOF mass spectrometry (MS in a replication cohort of 1,848 Europeans. Meta-analysis of genome-wide association study (GWAS results identified 9 genome-wide significant loci (P<2.27 × 10(-9 in the discovery analysis and two of the same loci (B4GALT1 and MGAT3 in the replication cohort. Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3, while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3. However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma. Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842. Our study shows that it is possible to identify new loci that control glycosylation of a single plasma protein

  8. Cleavage of a Recombinant Human Immunoglobulin A2 (IgA2)-IgA1 Hybrid Antibody by Certain Bacterial IgA1 Proteases

    OpenAIRE

    Senior, Bernard W.; Dunlop, James I.; Batten, Margaret R.; Kilian, Mogens; Woof, Jenny M.

    2000-01-01

    To understand more about the factors influencing the cleavage of immunoglobulin A1 (IgA1) by microbial IgA1 proteases, a recombinant human IgA2/IgA1 hybrid molecule was generated. In the hybrid, termed IgA2/A1 half hinge, a seven-amino-acid sequence corresponding to one half of the duplicated sequence making up the IgA1 hinge was incorporated into the equivalent site in IgA2. Insertion of the IgA1 half hinge into IgA2 did not affect antigen binding capacity or the functional activity of the h...

  9. The impact of the cardiopulmonary bypass on the infant immunoglobulin and the method of the human immunoglobulin supplementary%体外循环对婴幼儿免疫球蛋白的影响及临床补充人免疫球蛋白的方法

    Institute of Scientific and Technical Information of China (English)

    郭士勇; 崔传玉; 王为民; 李青

    2009-01-01

    Objective To explore the effect of the cardiopulmonary bypass (CPB) on the infant immunoglobulin and the method.of the human immunoglobulin supplementary. Methods Thirty cases of infant congenital heart disease were mean divided into 3 groups (A, B and C). Group A and B were the CPB cases, group C was comparison group. All the infants had been detected the blood immunoglobulin level before and after the cardiotic operation. Results The CPB can decline the infant blood immuno-globulin significantly and the supplementary of the human immunoglobulin after the operation can increase the infant blood immunoglobulin level rapidly. Conclusions The CPB operation can make the infant blood immunoglobulin decline for a week and supply the human immunoglobulin early can make the infant blood immunoglobulin level restore normal rapidly and increase the body immunity.%目的 探讨体外循环对婴幼儿免疫球蛋白的影响及临床补充人免疫球蛋白的方法.方法 选取先天性心脏病婴幼儿30例,均分成三组,A、B二组为体外循环组,A组为术后补充人免疫球蛋白组,B组则不补充.C组为非体外循环对照组.三组病人均在术前、术后检测免疫球蛋白.结果 体外循环可引起婴幼儿免疫球蛋白显著下降,术后补充人免疫球蛋白可快速提升患儿免疫球蛋白水平.结论 婴幼儿体外循环心脏术后可使免疫球蛋白下降1周,术后早期补充人免疫球蛋白能使患儿术后免疫球蛋白水平快速恢复正常,提高机体免疫力.

  10. Affinity composite cryogel discs functionalized with Reactive Red 120 and Green HE 4BD dye ligands: Application on the separation of human immunoglobulin G subclasses

    Energy Technology Data Exchange (ETDEWEB)

    Huseynli, Sabina; Baydemir, Gözde; Sarı, Esma [Department of Chemistry, Biochemistry Division, Hacettepe University, Ankara (Turkey); Elkak, Assem [Laboraory of “Valorisation des Ressources Naturelles et Produits de Santé (VRNPS)”, Doctoral School of Sciences and Technology, Lebanese University, Rafic Hariri University Campus, Hadath (Lebanon); Denizli, Adil, E-mail: denizli@hacettepe.edu.tr [Department of Chemistry, Biochemistry Division, Hacettepe University, Ankara (Turkey)

    2015-01-01

    Naturally produced by the human immune system, immunoglobulin nowadays is widely used for in vivo and in vitro purposes. The increased needs for pure immunoglobulin have prompted researchers to find new immunoglobulin chromatographic separation processes. Cryogels as chromatographic adsorbents, congregate several mechanical features including good compatibility, large pore structure, flexibility, short diffusion pathway and stability. These different characteristics make them a good alternative to conventional chromatographic methods and allowing their potential use in separation technology. In the present study, two sets of poly(2-hydroxyethyl methacrylate) (PHEMA) based beads were prepared and functionalized with Reactive Red 120 (RR) and Reactive Green HE 4BD (RG) dyes, and then embedded into supermacroporous cryogels. The morphology, physical and chemical features of the prepared bead embedded composite cryogel discs (CCDs) were performed by scanning electron microscopy (SEM), swelling test, elemental analysis and Fourier transform infrared spectroscopy (FTIR). The results showed that the embedded composite cryogel discs have a specific surface area of 192.0 m{sup 2}/g with maximum adsorption capacity of HIgG 239.8 mg/g for the RR functionalized CCD and 170 mg/g for RG functionalized CCD columns, both at pH 6.2. - Highlights: • Dye attached composite cryogel discs were prepared to separate HIgG subclasses. • Composite cryogels characterized by swelling, FTIR, SEM and elemental analysis. • Reactive Green HE 4B and Reactive Red 120 dyes were used as the affinity ligand. • HIgG and subclasses were separate from both aqueous solution and human plasma.

  11. Subcutaneous immunoglobulin replacement therapy in the treatment of patients with primary immunodeficiency disease

    Directory of Open Access Journals (Sweden)

    Suzanne Skoda-Smith

    2009-12-01

    Full Text Available Suzanne Skoda-Smith, Troy R Torgerson, Hans D OchsSeattle Children’s Research Institute and Department of Pediatrics, University of Washington, Seattle, WashingtonAbstract: Antibody deficiency is the most frequently encountered primary immunodeficiency disease (PIDD and patients who lack the ability to make functional immunoglobulin require life-long replacement therapy to prevent serious bacterial infections. Human serum immunoglobulin manufactured from pools of donated plasma can be administered intramuscularly, intravenously or subcutaneously. With the advent of well-tolerated preparations of intravenous immunoglobulin (IVIg in the 1980s, the suboptimal painful intramuscular route of administration is no longer used. However, some patients continued to experience unacceptable adverse reactions to the intravenous preparations, and for others, vascular access remained problematic. Subcutaneously administered immunoglobulin (SCIg provided an alternative delivery method to patients experiencing difficulties with IVIg. By 2006, immunoglobulin preparations designed exclusively for subcutaneous administration became available. They are therapeutically equivalent to intravenous preparations and offer patients the additional flexibility for the self-administration of their product at home. SCIg as replacement therapy for patients with primary antibody deficiencies is a safe and efficacious method to prevent serious bacterial infections, while maximizing patient satisfaction and improving quality of life.Keywords: subcutaneous immunoglobulin, primary immunodeficiency disease, antibody deficiency, X-linked agammaglobulinemia, common variable immune deficiency

  12. Quantitative immunoglobulins in adulthood.

    Science.gov (United States)

    Crisp, Howard C; Quinn, James M

    2009-01-01

    Although age-related changes in serum immunoglobulins are well described in childhood, alterations in immunoglobulins in the elderly are less well described and published. This study was designed to better define expected immunoglobulin ranges and differences in adults of differing decades of life. Sera from 404 patients, aged 20-89 years old were analyzed for quantitative immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA). The patients with diagnoses or medications known to affect immunoglobulin levels were identified while blinded to their immunoglobulin levels. A two-factor ANOVA was performed using decade of life and gender on both the entire sample population as well as the subset without any disease or medication expected to alter immunoglobulin levels. A literature review was also performed on all English language articles evaluating quantitative immunoglobulin levels in adults >60 years old. For the entire population, IgM was found to be higher in women when compared with men (p immunoglobulin levels, the differences in IgM with gender and age were maintained (p immunoglobulin levels have higher serum IgA levels and lower serum IgM levels. Women have higher IgM levels than men throughout life. IgG levels are not significantly altered in an older population.

  13. Segmental duplication as one of the driving forces underlying the diversity of the human immunoglobulin heavy chain variable gene region

    Directory of Open Access Journals (Sweden)

    Gao Richeng

    2011-01-01

    Full Text Available Abstract Background Segmental duplication and deletion were implicated for a region containing the human immunoglobulin heavy chain variable (IGHV gene segments, 1.9III/hv3005 (possible allelic variants of IGHV3-30 and hv3019b9 (a possible allelic variant of IGHV3-33. However, very little is known about the ranges of the duplication and the polymorphic region. This is mainly because of the difficulty associated with distinguishing between allelic and paralogous sequences in the IGHV region containing extensive repetitive sequences. Inability to separate the two parental haploid genomes in the subjects is another serious barrier. To address these issues, unique DNA sequence tags evenly distributed within and flanking the duplicated region implicated by the previous studies were selected. The selected tags in single sperm from six unrelated healthy donors were amplified by multiplex PCR followed by microarray detection. In this way, individual haplotypes of different parental origins in the sperm donors could be analyzed separately and precisely. The identified polymorphic region was further analyzed at the nucleotide sequence level using sequences from the three human genomic sequence assemblies in the database. Results A large polymorphic region was identified using the selected sequence tags. Four of the 12 haplotypes were shown to contain consecutively undetectable tags spanning in a variable range. Detailed analysis of sequences from the genomic sequence assemblies revealed two large duplicate sequence blocks of 24,696 bp and 24,387 bp, respectively, and an incomplete copy of 961 bp in this region. It contains up to 13 IGHV gene segments depending on haplotypes. A polymorphic region was found to be located within the duplicated blocks. The variants of this polymorphism unusually diverged at the nucleotide sequence level and in IGHV gene segment number, composition and organization, indicating a limited selection pressure in general. However

  14. Expression and sub-cellular localization of leucine-rich repeats and immunoglobulin-like domains are related to antioxidant enzymes in human ependymoma and oligodendroglioma

    Institute of Scientific and Technical Information of China (English)

    Wei Yi; Lin Liu; Okechi Humphrey; Qianxue Chen; Shulan Huang

    2011-01-01

    The current study investigated correlations between the expression of leucine-rich repeats and immunoglobulin-like domain 1 (LRIG1) and antioxidant enzymes and related proteins, including manganese superoxide dismutase, glutamate cysteine ligase catalytic or regulatory subunit, thioredoxin and thioredoxin reductase, in both human ependymoma and oligodendroglioma. Results revealed that the cytoplasmic expression of LRIG1 was associated with expression of glutamate cysteine ligase catalytic subunit in the human ependymoma, while the nuclear expression of LRIG1 was associated with expression of thioredoxin reductase. In human oligodendroglioma, the cytoplasmic expression of LRIG1 was associated with expression of the glutamate cysteine ligase catalytic subunit. Both the nuclear and perinuclear expressions of LRIG1 were associated with expression of glutamate cysteine ligase regulatory subunit. These results indicated that several antioxidant enzymes and related proteins contributed to LRIG1 expression, and that these may participate in the antioxidation of the cells.

  15. A human Fab fragment specific for thyroid peroxidase generated by cloning thyroid lymphocyte-derived immunoglobulin genes in a bacteriophage lambda library.

    Science.gov (United States)

    Portolano, S; Seto, P; Chazenbalk, G D; Nagayama, Y; McLachlan, S M; Rapoport, B

    1991-08-30

    A human Fab fragment (SP2) which binds specifically to human thyroid peroxidase has been generated by expressing random combinations of heavy and light chain immunoglobulin genes (derived from Graves' thyroid cDNA) in a bacteriophage lambda library. In common with many serum TPO autoantibodies, the cloned Fab fragment is IgG1 kappa and has a high affinity for TPO (approximately 10(-9) M). On the basis of their nucleotide sequences, the heavy and light chain genes coding for SP2 belong to families VHI, (D), JH3 and VKI, JK2, respectively. These data provide the first characterization at a molecular level of a human thyroid peroxidase antibody associated with autoimmune thyroid disease.

  16. Effect of yoghurt containing Bifidobacterium lactis Bb12® on faecal excretion of secretory immunoglobulin A and human beta-defensin 2 in healthy adult volunteers.

    Science.gov (United States)

    Kabeerdoss, Jayakanthan; Devi, R Shobana; Mary, R Regina; Prabhavathi, D; Vidya, R; Mechenro, John; Mahendri, N V; Pugazhendhi, Srinivasan; Ramakrishna, Balakrishnan S

    2011-12-23

    Probiotics are used to provide health benefits. The present study tested the effect of a probiotic yoghurt on faecal output of beta-defensin and immunoglobulin A in a group of young healthy women eating a defined diet. 26 women aged 18-21 (median 19) years residing in a hostel were given 200 ml normal yoghurt every day for a week, followed by probiotic yoghurt containing Bifidobacterium lactis Bb12® (10⁹ in 200 ml) for three weeks, followed again by normal yoghurt for four weeks. Stool samples were collected at 0, 4 and 8 weeks and assayed for immunoglobulin A and human beta-defensin-2 by ELISA. All participants tolerated both normal and probiotic yoghurt well. Human beta-defensin-2 levels in faeces were not altered during the course of the study. On the other hand, compared to the basal sample, faecal IgA increased during probiotic feeding (P = 0.0184) and returned to normal after cessation of probiotic yoghurt intake. Bifidobacterium lactis Bb12® increased secretory IgA output in faeces. This property may explain the ability of probiotics to prevent gastrointestinal and lower respiratory tract infections.

  17. Effect of yoghurt containing Bifidobacterium lactis Bb12® on faecal excretion of secretory immunoglobulin A and human beta-defensin 2 in healthy adult volunteers

    Directory of Open Access Journals (Sweden)

    Kabeerdoss Jayakanthan

    2011-12-01

    Full Text Available Abstract Background Probiotics are used to provide health benefits. The present study tested the effect of a probiotic yoghurt on faecal output of beta-defensin and immunoglobulin A in a group of young healthy women eating a defined diet. Findings 26 women aged 18-21 (median 19 years residing in a hostel were given 200 ml normal yoghurt every day for a week, followed by probiotic yoghurt containing Bifidobacterium lactis Bb12® (109 in 200 ml for three weeks, followed again by normal yoghurt for four weeks. Stool samples were collected at 0, 4 and 8 weeks and assayed for immunoglobulin A and human beta-defensin-2 by ELISA. All participants tolerated both normal and probiotic yoghurt well. Human beta-defensin-2 levels in faeces were not altered during the course of the study. On the other hand, compared to the basal sample, faecal IgA increased during probiotic feeding (P = 0.0184 and returned to normal after cessation of probiotic yoghurt intake. Conclusions Bifidobacterium lactis Bb12® increased secretory IgA output in faeces. This property may explain the ability of probiotics to prevent gastrointestinal and lower respiratory tract infections.

  18. New low-flux mixed matrix membranes that offer superior removal of protein-bound toxins from human plasma

    Science.gov (United States)

    Pavlenko, Denys; van Geffen, Esmée; van Steenbergen, Mies J.; Glorieux, Griet; Vanholder, Raymond; Gerritsen, Karin G. F.; Stamatialis, Dimitrios

    2016-10-01

    Hemodialysis is a widely available and well-established treatment for patients with End Stage Renal Disease (ESRD). However, although life-sustaining, patient mortality rates are very high. Several recent studies corroborated the link between dialysis patients’ outcomes and elevated levels of protein-bound uremic toxins (PBUT) that are poorly removed by conventional hemodialysis. Therefore, new treatments are needed to improve their removal. Recently, our group showed that the combination of dialysis and adsorption on one membrane, the mixed matrix membrane (MMM), can effectively remove those toxins from human plasma. However, these first MMMs were rather large in diameter and their mass transport characteristics needed improvement before application in the clinical setting. Therefore, in this study we developed a new generation of MMMs that have a smaller diameter and optimized characteristics offering superior ability in removing the PBUT indoxyl sulfate (IS) and p-cresyl sulfate (pCS) in comparison to first generation MMMs (30 and 125% respectively), as well as, a commercial dialysis membrane (more than 100% better removal).

  19. Leukocyte-associated immunoglobulin-like receptor-1 is expressed on human megakaryocytes and negatively regulates the maturation of primary megakaryocytic progenitors and cell line

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Jiangnan, E-mail: xuejinagnan@263.net [Department of Immunology, Binzhou Medical University, Yantai 264003 (China); Zhang, Xiaoshu; Zhao, Haiya; Fu, Qiang; Cao, Yanning; Wang, Yuesi; Feng, Xiaoying; Fu, Aili [Department of Immunology, Binzhou Medical University, Yantai 264003 (China)

    2011-02-04

    Research highlights: {yields} LAIR-1 is expressed on human megakaryocytes from an early stage. {yields} Up-regulation of LAIR-1 negatively regulates megakaryocytic differentiation of cell line. {yields} LAIR-1 negatively regulates the differentiation of primary megakaryocytic progenitors. -- Abstract: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an inhibitory collagen receptor which belongs to the immunoglobulin (Ig) superfamily. Although the inhibitory function of LAIR-1 has been extensively described in multiple leukocytes, its role in megakaryocyte (MK) has not been explored so far. Here, we show that LAIR-1 is expressed on human bone marrow CD34{sup +}CD41a{sup +} and CD41a{sup +}CD42b{sup +} cells. LAIR-1 is also detectable in a fraction of human cord blood CD34{sup +} cell-derived MK that has morphological characteristics of immature MK. In megakaryoblastic cell line Dami, the membrane protein expression of LAIR-1 is up-regulated significantly when cells are treated with phorbol ester phorbol 12-myristate 13-acetate (PMA). Furthermore, cross-linking of LAIR-1 in Dami cells with its natural ligand or anti-LAIR-1 antibody leads to the inhibition of cell proliferation and PMA-promoted differentiation when examined by the MK lineage-specific markers (CD41a and CD42b) and polyploidization. In addition, we also observed that cross-linking of LAIR-1 results in decreased MK generation from primary human CD34{sup +} cells cultured in a cytokines cocktail that contains TPO. These results suggest that LAIR-1 is a likely candidate for an early marker of MK differentiation, and provide initial evidence indicating that LAIR-1 serves as a negative regulator of megakaryocytopoiesis.

  20. An electrochemical quartz crystal impedance study on anti-human immunoglobulin G immobilization in the polymer grown during dopamine oxidation at an Au electrode.

    Science.gov (United States)

    He, Hua; Xie, Qingji; Yao, Shouzhuo

    2005-09-15

    The polymeric film grown during dopamine oxidation at an Au electrode was studied as a novel matrix for immobilizing anti-human immunoglobulin G (IgG) via the electrochemical quartz crystal impedance analysis (EQCIA) method. The growth of the polymeric films at Au electrodes during dopamine oxidation in neutral phosphate buffer (pH 7.4) and the immobilization of anti-human IgG into the polymeric films during their growth have been traced at real time. Lysozyme control experiments suggested that anti-human IgG was electrostatically incorporated into the polymeric film. Also, the porosity of the polymeric films has been discussed by measuring the "wet" and "dry" frequency shifts. Compared with a polypyrrole film immobilized with anti-human IgG, the proposed matrix possessed a larger amount of specific binding sites for human IgG by subsequent immunoreaction tests. The association constant of the anti-human IgG immunoreaction was obtained with satisfactory results.

  1. 21 CFR 310.534 - Drug products containing active ingredients offered over-the-counter (OTC) for human use as oral...

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Drug products containing active ingredients offered over-the-counter (OTC) for human use as oral wound healing agents. 310.534 Section 310.534 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR...

  2. Polyclonal immunoglobulins from a chronic hepatitis C virus patient protect human liver-chimeric mice from infection with a homologous hepatitis C virus strain

    DEFF Research Database (Denmark)

    Vanwolleghem, Thomas; Bukh, Jens; Meuleman, Philip

    2008-01-01

    The role of the humoral immune response in the natural course of hepatitis C virus (HCV) infection is widely debated. Most chronically infected patients have immunoglobulin G (IgG) antibodies capable of neutralizing HCV pseudoparticles (HCVpp) in vitro. It is, however, not clear whether these Ig...... were loaded with chronic phase polyclonal IgG and challenged 3 days later with a 100% infectious dose of the acute phase H77C virus, both originating from patient H. Passive immunization induced sterilizing immunity in five of eight challenged animals. In the three nonprotected animals, the HCV...... chimeric mice, the inoculum was pre-incubated in vitro at an IgG concentration normally observed in humans. Conclusion: Polyclonal IgG from a patient with a long-standing HCV infection not only displays neutralizing activity in vitro using the HCVpp system, but also conveys sterilizing immunity toward...

  3. Fundamental characteristics of the expressed immunoglobulin VH and VL repertoire in different canine breeds in comparison with those of humans and mice.

    Science.gov (United States)

    Steiniger, Sebastian C J; Dunkle, William E; Bammert, Gary F; Wilson, Thomas L; Krishnan, Abhiram; Dunham, Steven A; Ippolito, Gregory C; Bainbridge, Graeme

    2014-05-01

    Complementarity determining regions (CDR) are responsible for binding antigen and provide substantial diversity to the antibody repertoire, with VH CDR3 of the immunoglobulin variable heavy (VH) domain playing a dominant role. In this study, we examined 1200 unique canine VH and 500 unique variable light (VL) sequences of large and small canine breeds derived from peripheral B cells. Unlike the human and murine repertoire, the canine repertoire is heavily dominated by the Canis lupus familiaris IGHV1 subgroup, evolutionarily closest to the human IGHV3 subgroup. Our studies clearly show that the productive canine repertoire of all analyzed breeds shows similarities to both human and mouse; however, there are distinct differences in terms of VH CDR3 length and amino acid paratope composition. In comparison with the human and murine antibody repertoire, canine VH CDR3 regions are shorter in length than the human counterparts, but longer than the murine VH CDR3. Similar to corresponding human and mouse VH CDR3, the amino acids at the base of the VH CDR3 loop are strictly conserved. For identical CDR positions, there were significant changes in chemical paratope composition. Similar to human and mouse repertoires, the neutral amino acids tyrosine, glycine and serine dominate the canine VH CDR3 interval (comprising 35%) although the interval is nonetheless relatively depleted of tyrosine when compared to human and mouse. Furthermore, canine VH CDR3 displays an overrepresentation of the neutral amino acid threonine and the negatively charged aspartic acid while proline content is similar to that in the human repertoire. In general, the canine repertoire shows a bias towards small, negatively charged amino acids. Overall, this analysis suggests that functional canine therapeutic antibodies can be obtained from human and mouse sequences by methods of speciation and affinity maturation.

  4. Perspectives on Immunoglobulins in colostrum and milk

    DEFF Research Database (Denmark)

    Hurley, W L; Theil, Peter Kappel

    2011-01-01

    Immunoglobulins form an important component of the immunological activity found in milk and colostrum. They are central to the immunological link that occurs when the mother transfers passive immunity to the offspring. The mechanism of transfer varies among mammalian species. Cattle provide...... a readily available immune rich colostrum and milk in large quantities, making those secretions important potential sources of immune products that may benefit humans. Immune milk is a term used to describe a range of products of the bovine mammary gland that have been tested against several human diseases....... The use of colostrum or milk as a source of immunoglobulins, whether intended for the neonate of the species producing the secretion or for a different species, can be viewed in the context of the types of immunoglobulins in the secretion, the mechanisms by which the immunoglobulins are secreted...

  5. Monomeric Immunoglobulin A from Plasma Inhibits Human Th17 Responses In Vitro Independent of FcαRI and DC-SIGN

    Science.gov (United States)

    Saha, Chaitrali; Das, Mrinmoy; Patil, Veerupaxagouda; Stephen-Victor, Emmanuel; Sharma, Meenu; Wymann, Sandra; Jordi, Monika; Vonarburg, Cédric; Kaveri, Srini V.; Bayry, Jagadeesh

    2017-01-01

    Circulating immunoglobulins including immunoglobulin G (IgG) and IgM play a critical role in the immune homeostasis by modulating functions of immune cells. These functions are mediated in part by natural antibodies. However, despite being second most abundant antibody in the circulation, the immunoregulatory function of IgA is relatively unexplored. As Th17 cells are the key mediators of a variety of autoimmune, inflammatory, and allergic diseases, we investigated the ability of monomeric IgA (mIgA) isolated from pooled plasma of healthy donors to modulate human Th17 cells. We show that mIgA inhibits differentiation and amplification of human Th17 cells and the production of their effector cytokine IL-17A. mIgA also suppresses IFN-γ responses under these experimental conditions. Suppressive effect of mIgA on Th17 responses is associated with reciprocal expansion of FoxP3-positive regulatory T cells. The effect of mIgA on Th17 cells is dependent on F(ab′)2 fragments and independent of FcαRI (CD89) and DC-SIGN. Mechanistically, the modulatory effect of mIgA on Th17 cells implicates suppression of phosphorylation of signal transducer and activator of transcription 3. Furthermore, mIgA binds to CD4+ T cells and recognizes in a dose-dependent manner the receptors for cytokines (IL-6Rα and IL-1RI) that mediate Th17 responses. Our findings thus reveal novel anti-inflammatory functions of IgA and suggest potential therapeutic utility of mIgA in autoimmune and inflammatory diseases that implicate Th17 cells. PMID:28352269

  6. Primary structure of the major glycans of the N-acetyllactosamine type derived from the human immunoglobulins M from two patients with Waldenström’s macroglobulinemia

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Cahour, A.; Debeire, P.; Hartmann, L.; Montreuil, J.; Halbeek, H. van

    1984-01-01

    The carbohydrate chains of the pathological human immunoglobulins M from two patients with Waldenström's macroglobulinemia were released by hydrazinolysis. The N-acetyllactosamine-type glycans were obtained by affinity chromatography on concanavalin A and fractionated by high-voltage paper electroph

  7. Magnetically-assisted surface enhanced raman spectroscopy (MA-SERS) for label-free determination of human immunoglobulin G (IgG) in blood using Fe3O4@Ag nanocomposite.

    Science.gov (United States)

    Balzerova, Anna; Fargasova, Ariana; Markova, Zdenka; Ranc, Vaclav; Zboril, Radek

    2014-11-18

    Development of methods allowing determination of even ultralow levels of immunoglobulins in various clinical samples including whole human blood and plasma is a particular scientific challenge, especially due to many essential discoveries in the fields of immunology and medicine in the past few decades. The determination of IgG is usually performed using an enzymatic approach, followed by colorimetric or fluorimetric detection. However, limitations of these methods relate to their complicated setup and stringent requirements concerning the sample purity. Here, we present a novel approach based on magnetically assisted surface enhanced Raman spectroscopy (MA/SERS), which utilizes a Fe3O4@Ag@streptavidin@anti-IgG nanocomposite with strong magnetic properties and an efficient SERS enhancement factor conferred by the Fe3O4 particles and silver nanoparticles, respectively. Such a nanocomposite offers the possibility of separating a target efficiently from a complex matrix by simple application of an external magnetic force, followed by direct determination using SERS. High selectivity was achieved by the presence of anti-IgG on the surface of silver nanoparticles coupled with their further inactivation by ethylamine. Compared to many recently developed sandwich methods, application of single nanocomposites showed many advantages, including simplicity of use, direct control of the analytic process, and elimination of errors caused by possible nonspecific interactions. Moreover, incorporation of advanced spectral processing methods led to a considerable decrease in the relative error of determination to below 5%.

  8. Immunoglobulins and immunoglobulin genes of the horse.

    Science.gov (United States)

    Wagner, Bettina

    2006-01-01

    Antibodies of the horse were studied intensively by many notable immunologists throughout the past century until the early 1970's. After a large gap of interest in horse immunology, additional basic studies on horse immunoglobulin genes performed during the past 10 years have resulted in new insights into the equine humoral immune system. These include the characterization of the immunoglobulin lambda and kappa light chain genes, the immunoglobulin heavy chain constant (IGHC) gene regions, and initial studies regarding the heavy chain variable genes. Horses express predominately lambda light chains and seem to have a relatively restricted germline repertoire of both lambda and kappa chain variable genes. The IGHC region contains eleven constant heavy chain genes, seven of which are gamma heavy chain genes. It is suggested that all seven genes encoding IgG isotypes are expressed and have distinct functions in equine immune responses.

  9. Circulating human CD27-IgA+ memory-B cells recognize bacteria with polyreactive immunoglobulins1

    Science.gov (United States)

    Berkowska, Magdalena A.; Schickel, Jean-Nicolas; Grosserichter-Wagener, Christina; de Ridder, Dick; Ng, Yen Shing; van Dongen, Jacques J.M.; Meffre, Eric; van Zelm, Menno C.

    2015-01-01

    The vast majority of immunoglobulin (Ig)A production occurs in mucosal tissue following T-cell dependent and T-cell independent antigen responses. To study the nature of each of these responses, we analyzed the gene expression and Ig reactivity profiles of T-cell dependent CD27+IgA+ and T-cell independent CD27−IgA+ circulating memory-B cells. Gene expression profiles of IgA+ subsets were highly similar to each other and to IgG+ memory-B-cell subsets with typical upregulation of activation markers and downregulation of inhibitory receptors. However, we identified the mucosa-associated CCR9 and RUNX2 genes to be specifically upregulated in CD27−IgA+ B cells. We also found that CD27−IgA+ B cells expressed antibodies with distinct Ig repertoire and reactivity than those from CD27+IgA+ B cells. Indeed, antibodies from CD27−IgA+ B cells were weakly mutated, often utilized Igλ chain and were enriched in polyreactive clones recognizing various bacterial species. Hence, T-cell independent IgA responses are likely involved in the maintenance of gut homeostasis through the production of polyreactive mutated IgA antibodies with crossreactive anti-commensal reactivity. PMID:26150533

  10. In this issue: Nef, a lingering problem; are there better immunoglobulins for human use; and Takayasu arteritis, still a mystery.

    Science.gov (United States)

    Bot, Adrian

    2012-12-01

    The current issue of the International Reviews of Immunology brings the latest in three different areas of basic and clinical immunology. First, there is the lingering question of residual HIV-related pathology in patients on chronic antiretroviral therapy. The specific role of Nef in the macrophage-mediated disease manifested through lymphoma, metabolic disease and neurological disorder, is extensively discussed. A second topic is a clinical immunology one, a critical perspective on the efficacy and safety profile of various preparations of immunoglobulin products currently prescribed for a range of immunodeficiencies. Surprisingly, the authors showed that while the available preparations are equivalent from efficacy standpoint, they differ from the standpoint of toxicity. The third subject is again, in the arena of clinical immunology and deals with a relatively rare yet extremely puzzling disease -Takayasu arteritis -with a pathogenesis that needs elucidation and a dire need for better treatments. The authors provide a state of the art in terms of genetic association, other factors possibly involved in the onset and progression of this unusual inflammatory disease of large arteries, and provide a perspective on current standard of care and potential usefulness of TNF-α blockade as therapy for Takayasu arteritis.

  11. Double electrophoretic separation and lectin analyses of the component chains of secretory immunoglobulin A from human saliva.

    Science.gov (United States)

    Carpenter, G H; Proctor, G B

    2000-05-01

    A new method is presented for the separation of secretory immunoglobulin A (SIgA) from salivary samples. Salivary proteins (from parotid or stimulated whole mouth saliva) were precipitated with methanol to concentrate SIgA from salivary samples whilst removing other salivary proteins. SIgA purified from breast milk and salivary proteins was separated by 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under nonreducing conditions. Following completion of electrophoresis the top strip of gel was removed and the proteins present reduced with dithiothreitol. The gel strip was then applied to the top of a second 10% SDS gel, and the proteins were electrophoresed and then stained by Coomassie Brilliant Blue R-250. Three major protein bands were stained in all samples corresponding in molecular mass to secretory component, alpha-heavy chain and light chains of SIgA. Separated proteins were also electroblotted onto nitrocellulose and stained by fluorescein isothiocyanate (FITC). Lectin analysis was then used to detect the O-glycans present on IgA1. Lectins from Helix aspersa and Arachis hypogaea were used to determine the amount of terminal N-acetyl galactosamine and nonsialylated O-glycans, respectively. Maclura pomifera lectin was used to determine the total amount of IgA1 present on the blots. The results indicate that SlgA in stimulated whole mouth saliva, stimulated parotid saliva and purified from breast milk contain similar O-glycans.

  12. The interactions of calreticulin with immunoglobulin G and immunoglobulin Y.

    Science.gov (United States)

    Møllegaard, Karen Mai; Duus, Karen; Træholt, Sofie Dietz; Thaysen-Andersen, Morten; Liu, Yan; Palma, Angelina S; Feizi, Ten; Hansen, Paul R; Højrup, Peter; Houen, Gunnar

    2011-07-01

    Calreticulin is a chaperone of the endoplasmic reticulum (ER) assisting proteins in achieving the correctly folded structure. Details of the binding specificity of calreticulin are still a matter of debate. Calreticulin has been described as an oligosaccharide-binding chaperone but data are also accumulating in support of calreticulin as a polypeptide binding chaperone. In contrast to mammalian immunoglobulin G (IgG), which has complex type N-glycans, chicken immunoglobulin Y (IgY) possesses a monoglucosylated high mannose N-linked glycan, which is a ligand for calreticulin. Here, we have used solid and solution-phase assays to analyze the in vitro binding of calreticulin, purified from human placenta, to human IgG and chicken IgY in order to compare the interactions. In addition, peptides from the respective immunoglobulins were included to further probe the binding specificity of calreticulin. The experiments demonstrate the ability of calreticulin to bind to denatured forms of both IgG and IgY regardless of the glycosylation state of the proteins. Furthermore, calreticulin exhibits binding to peptides (glycosylated and non-glycosylated) derived from trypsin digestion of both immunoglobulins. Additionally, calreticulin peptide binding was examined with synthetic peptides covering the IgG Cγ2 domain demonstrating interaction with approximately half the peptides. Our results show that the dominant binding activity of calreticulin in vitro is toward the polypeptide moieties of IgG and IgY even in the presence of the monoglucosylated high mannose N-linked oligosaccharide on IgY.

  13. Use of human immunoglobulins as an anti-infective treatment: the experience so far and their possible re-emerging role.

    Science.gov (United States)

    Bozzo, Jordi; Jorquera, Juan I

    2017-06-01

    Pooled human immunoglobulins (IGs) are prepared from plasma obtained from healthy donors as a concentrated antibody-containing solution. In addition, high-titer IGs (hyperimmune) against a specific pathogen can be obtained from vaccinated or convalescing donors. Currently, IGs can be used for the treatment of a variety of infections for which no specific therapy exists or that remain difficult to treat. Moreover, the recent pathogen outbreaks for which there is no approved treatment have renewed attention to the role of convalescent plasma and IGs. Areas covered: In this review, a historical perspective of the use of sera and IGs in humans as anti-infective agents (any viral, bacterial, parasitic infection), excluding immunodeficient patients, is presented from early development to the latest clinical studies. A Medline search was conducted to examine the peer-reviewed literature, with no date limits. Expert commentary: Human pooled plasma-derived IG products benefit from the polyclonal response of every individual donor and from the interindividual variability in such response. The trend to increased availability of vaccines for infectious diseases also opens new potential applications of hyperimmune IGs for emerging or re-emerging infectious diseases (e.g.: Ebola, Zika, Dengue), for the prevention and treatment in the general population, healthcare personnel and caregivers.

  14. Salivary Secretory Immunoglobulin a secretion increases after 4-weeks ingestion of chlorella-derived multicomponent supplement in humans: a randomized cross over study

    Directory of Open Access Journals (Sweden)

    Iemitsu Motoyuki

    2011-09-01

    Full Text Available Abstract Background Chlorella, a unicellular green alga that grows in fresh water, contains high levels of proteins, vitamins, minerals, and dietary fibers. Some studies have reported favorable immune function-related effects on biological secretions such as blood and breast milk in humans who have ingested a chlorella-derived multicomponent supplement. However, the effects of chlorella-derived supplement on mucosal immune functions remain unclear. The purpose of this study was to investigate whether chlorella ingestion increases the salivary secretory immunoglobulin A (SIgA secretion in humans using a blind, randomized, crossover study design. Methods Fifteen men took 30 placebo and 30 chlorella tablets per day for 4 weeks separated by a 12-week washout period. Before and after each trial, saliva samples were collected from a sterile cotton ball that was chewed after overnight fasting. Salivary SIgA concentrations were measured using ELISA. Results Compliance rates for placebo and chlorella ingestions were 97.0 ± 1.0% and 95.3 ± 1.6%, respectively. No difference was observed in salivary SIgA concentrations before and after placebo ingestion (P = 0.38. However, salivary SIgA concentrations were significantly elevated after chlorella ingestion compared to baseline (P P = 0.36, it significantly increased after 4-week chlorella ingestion than before intake (P Conclusions These results suggest 4-week ingestion of a chlorella-derived multicomponent supplement increases salivary SIgA secretion and possibly improves mucosal immune function in humans.

  15. Rapid amplification of cDNA ends (RACE) improves the PCR-based isolation of immunoglobulin variable region genes from murine and human lymphoma cells and cell lines.

    Science.gov (United States)

    Doenecke, A; Winnacker, E L; Hallek, M

    1997-10-01

    The isolation of rearranged immunoglobulin (Ig) variable region (V) genes is usually performed by PCR with consensus primers binding to conserved regions within the V sequences. However, the isolation of Ig genes by this method is hampered in 15-35% by technical difficulties, mostly mismatches of oligonucleotide primers to V sequences. In order to obtain DNA sequences from V heavy chain (VH) genes which could not be amplified with consensus primers, we used a modified PCR technique, the rapid amplification of cDNA ends (RACE) PCR in combination with new heavy chain constant region primers for the isolation of human and murine VH genes. In comparison, consensus primer PCR with different sets of previously published oligonucleotide primers was used. Both methods were applied to isolate VH genes from murine B cell lymphoma (A20 and BCL1), myeloma (NS1) and hybridoma (SP6) cell lines and from freshly isolated human chronic lymphocytic leukemia and lymphoma cells. RACE PCR allowed the amplification and subsequent cloning of the complete VH gene in all cases. In contrast, consensus primer PCR failed to isolate the VH sequence of the murine A20 cell line; this was explained by a mismatch of consensus primers with VH sequences. When both PCR methods amplified VH sequences, the DNA sequences obtained were identical. Taken together, RACE PCR represents a reliable and versatile method for the isolation of VH genes from human and murine lymphoma cells, in particular if consensus primer PCR fails.

  16. Use of intravenous immunoglobulin in pediatric practice

    Science.gov (United States)

    Zülfikar, Bülent; Koç, Başak

    2014-01-01

    In recent years, human-driven intravenous immunoglobulins (IVIG) administered intravenously have been widely used in treatment of many diseases. Intravenous immunoglobulin is obtained from human-driven plasma pools as in other plasma-driven products and IVIG preperations contain structurally and functionally intact immunoglobulin. Intravenous immunoglobulin was approved by FDA (Food and Drug Administration) in USA in 1981 for the first time and was started to be primarily used in patients with immune deficiency with hypogammaglobulinemia. The effects of intravenous immunoglobulin include complex mechanisms, but it exerts its essential action by eliminating the non-specific Fc receptors found in the mononuclear phagocytic system or by inhibiting binding of immune complexes to Fc receptors in the cells. Their areas of usage include conditions where their anti-inflammatory and immunomudulator effects are utilized in addition to replacement of deficient immunoglobulin. Although the definite indications are limited, it has been shown that it is useful in many diseases in clinical practice. Its side effects include fever, sweating, nausea, tachycardia, eczematous reactions, aseptic meningitis, renal failure and hematological-thromboembolic events. In this article, use of IVIG, its mechanisms of action, indications and side effects were discussed. PMID:26078679

  17. Atypical antigen recognition mode of a shark immunoglobulin new antigen receptor (IgNAR) variable domain characterized by humanization and structural analysis.

    Science.gov (United States)

    Kovalenko, Oleg V; Olland, Andrea; Piché-Nicholas, Nicole; Godbole, Adarsh; King, Daniel; Svenson, Kristine; Calabro, Valerie; Müller, Mischa R; Barelle, Caroline J; Somers, William; Gill, Davinder S; Mosyak, Lidia; Tchistiakova, Lioudmila

    2013-06-14

    The immunoglobulin new antigen receptors (IgNARs) are a class of Ig-like molecules of the shark immune system that exist as heavy chain-only homodimers and bind antigens by their single domain variable regions (V-NARs). Following shark immunization and/or in vitro selection, V-NARs can be generated as soluble, stable, and specific high affinity monomeric binding proteins of ∼12 kDa. We have previously isolated a V-NAR from an immunized spiny dogfish shark, named E06, that binds specifically and with high affinity to human, mouse, and rat serum albumins. Humanization of E06 was carried out by converting over 60% of non-complementarity-determining region residues to those of a human germ line Vκ1 sequence, DPK9. The resulting huE06 molecules have largely retained the specificity and affinity of antigen binding of the parental V-NAR. Crystal structures of the shark E06 and its humanized variant (huE06 v1.1) in complex with human serum albumin (HSA) were determined at 3- and 2.3-Å resolution, respectively. The huE06 v1.1 molecule retained all but one amino acid residues involved in the binding site for HSA. Structural analysis of these V-NARs has revealed an unusual variable domain-antigen interaction. E06 interacts with HSA in an atypical mode that utilizes extensive framework contacts in addition to complementarity-determining regions that has not been seen previously in V-NARs. On the basis of the structure, the roles of various elements of the molecule are described with respect to antigen binding and V-NAR stability. This information broadens the general understanding of antigen recognition and provides a framework for further design and humanization of shark IgNARs.

  18. Interactive Effects of Immunoglobulin Gamma and Human Leucocyte Antigen Genotypes on Response to Interferon Based Therapy of Hepatitis C Virus

    Directory of Open Access Journals (Sweden)

    Howayda E. Gomaa

    2015-04-01

    Full Text Available AIM: We examined the role that immunoglobulin GM 23 and KM allotypes—genetic markers of γ and κ chains, respectively—play in response to treatment of hepatitis C virus (HCV infection in Egyptian patients. MATERIAL AND METHODS: A total of 120 persons who had responded to HCV treatment and 125 with persistent HCV infection were genotyped for the presence of GM23 and KM determinants. HLA –C genotyping was also done. RESULTS: Association of GM 23+ and KM3 was significantly associated with non response to treatment (P < 0.0001. Individuals who lacked this GM genotype (but were positive for KM1,2 and 3 were likely to respond to treatment (P=0.045. Association of heterozygous GM23 (+/- with KM 1,2 and 3 or KM3 alone was significantly associated with SVR (P = 0.001 and (P = 0.0001 respectively. Particular combinations of HLA and GM genotypes were associated significantly with the response to HCV treatment. The combination of HLAC2C2 and GM23+ was associated with persistence of infection (P = 0.027 while the association of HLAC2C2 and heterozygous GM23+/- was associated with SVR (P = 0.001.The association of HLAC1C1 and heterozygous GM23+/- was significantly associated with SVR (P = 0.001 and also subjects with HLA C1/C2 and heterozygous GM23+/- were likely to respond to treatment (P = 0.003 while subjects with HLA C1/C2 and GM23+ show tendency to resist to treatment (P = 0.0001. CONCLUSION: Our results didn’t support a role for KM allotypes, GM23 allotype plays a role in the persistence of HCV infection in the presence or absence of KM1,3. Interaction between certain GM and HLA-C genotypes may favor adequate response to interferon based therapies.

  19. 人力资源管理专业课程设置与人才培养%The Course Offering and Personnel Training of Human Resource Management Major

    Institute of Scientific and Technical Information of China (English)

    吴友军; 汪荟萃; 潘天意

    2016-01-01

    以人力资源管理专业为研究对象,分析比较了国内外人力资源管理专业课程设置情况,探讨了企业对人力资源管理人才的需求,提出了关于课程设置与人才培养的建议,希望对国内高校人力资源管理专业的发展有所帮助。%Taking the human resource management major as a study object, this paper conducts a analytic comparison of the offering status of the human resource management major at home and abroad, probes into the demand of enterprises on the human resource management personnel, and puts forward some suggestions on the course offering and personnel training, hoping to be helpful to the development of human resources management major of universities in China.

  20. Seroprevalence of human papillomavirus immunoglobulin G antibodies among women presenting at the reproductive health clinic of a university teaching hospital in Nigeria

    Directory of Open Access Journals (Sweden)

    Aminu M

    2014-05-01

    Full Text Available M Aminu,1 JZ Gwafan,1 HI Inabo,1 AO Oguntayo,2 EE Ella,1 AK Koledade21Department of Microbiology, Faculty of Science, Ahmadu Bello University, 2Department of Obstetrics and Gynaecology, Ahmadu Bello University Teaching Hospital, Zaria, NigeriaBackground: Human papillomavirus (HPV is the cause of 90%–95% of squamous cell cancers. Persistent infection with high-risk HPV can lead to development of precancerous lesions of the cervix in 5%–10% of infected women, and can progress to invasive cervical cancer 15–20 years later. This study was conducted to determine the seroprevalence of HPV immunoglobulin G (IgG antibodies among women of reproductive age attending a reproductive health clinic at Ahmadu Bello University Teaching Hospital, Zaria, Nigeria.Methods: The study was descriptive, cross-sectional, and experimental, combining the use of a structured questionnaire and analysis of serum samples obtained from 350 consecutive consenting women. The serum samples were analyzed for IgG antibodies to HPV by enzyme-linked immunosorbent assay.Results: We found a seroprevalence of 42.9% (150/350 for IgG antibodies to HPV in these women. Women aged 45–49 years and those who had their sexual debut aged 20–23 years had the highest HPV seroprevalence, ie, 50% (57/114 and 51.1% (46/90, respectively. Presence of antibodies varied according to sociodemographic factors, but was significantly associated with educational status, tribe, and religion (P<0.05. Human papillomavirus infection was not significantly associated with the reproductive characteristics and sexual behavior of the women. Antibodies to HPV were detected in 50.0% (9/18 of women with a family history of cervical cancer and in 30.8% (4/13 of those with a history or signs of WHIM (warts, hypogammaglobulinemia, immunodeficiency, myelokathexis syndrome as a genetic disorder (P>0.05.Conclusion: Further studies are needed to determine the HPV serotypes and evaluate the risk of natural development

  1. Human CD72 splicing isoform responsible for resistance to systemic lupus erythematosus regulates serum immunoglobulin level and is localized in endoplasmic reticulum

    Directory of Open Access Journals (Sweden)

    Hitomi Yuki

    2012-12-01

    Full Text Available Abstract Background CD72 is an inhibitory co-receptor expressed on B cells. We previously demonstrated significant association of the polymorphism of the CD72 gene with susceptibility to human systemic lupus erythematosus (SLE in individuals carrying a SLE-susceptible FCGR2B genotype (FCGR2B-232Thr/Thr. The human CD72 locus generates a splicing isoform that lacks exon 8 (CD72Δex8 as well as full-length CD72 (CD72fl, and the CD72 polymorphism regulates exon 8 skipping. Results Here we demonstrated that individuals carrying the disease-protective CD72 genotype exhibit significantly lower serum immunoglobulin levels than do individuals carrying other CD72 genotypes (P CD72 genotype, the protein level of CD72Δex8 was increased in individuals carrying the disease-protective CD72 genotype, suggesting a crucial role of CD72Δex8 in regulation of antibody production. By expressing these human CD72 isoforms in mouse cell lines, we further demonstrated that CD72Δex8 is accumulated in endoplasmic reticulum (ER and fails to regulate BCR signaling whereas human CD72fl is efficiently transported to the cell surface and inhibits signaling through the B cell antigen receptor (BCR, as is the case for mouse CD72. Conclusion Human CD72 polymorphism appears to regulate antibody production as well as susceptibility to SLE by regulating expression of ER-localizing CD72Δex8.

  2. Rationale for the development of IMC-3G3, a fully human immunoglobulin G subclass 1 monoclonal antibody targeting the platelet-derived growth factor receptor alpha.

    Science.gov (United States)

    Shah, Gaurav D; Loizos, Nick; Youssoufian, Hagop; Schwartz, Jonathan D; Rowinsky, Eric K

    2010-02-15

    A large body of evidence suggests that the platelet-derived growth factor (PDGF) family and associated receptors are potential targets in oncology therapeutic development because of their critical roles in the proliferation and survival of various cancers and in the regulation and growth of the tumor stroma and blood vessels. Several small molecules that nonspecifically target the PDGF signaling axis are in current use or development as anticancer therapies. However, for the majority of these agents, PDGF and its receptors are neither the primary targets nor the principal mediators of anticancer activity. IMC-3G3, a fully human monoclonal antibody of the immunoglobulin G subclass 1, specifically binds to the human PDGF receptor alpha (PDGFRalpha) with high affinity and blocks PDGF ligand binding and PDGFRalpha activation. The results of preclinical studies and the frequent expression of PDGFRalpha in many types of cancer and in cancer-associated stroma support a rationale for the clinical development of IMC-3G3. Currently, IMC-3G3 is being evaluated in early clinical development for patients with several types of solid malignancies.

  3. Human NK cells maintain licensing status and are subject to killer immunoglobulin-like receptor (KIR) and KIR-ligand inhibition following ex vivo expansion.

    Science.gov (United States)

    Wang, Wei; Erbe, Amy K; Alderson, Kory A; Phillips, Emily; Gallenberger, Mikayla; Gan, Jacek; Campana, Dario; Hank, Jacquelyn A; Sondel, Paul M

    2016-09-01

    Infusion of allogeneic NK cells is a potential immunotherapy for both hematopoietic malignancies and solid tumors. Interactions between killer immunoglobulin-like receptors (KIR) on human NK cells and KIR-ligands on tumor cells influence the magnitude of NK function. To obtain sufficient numbers of activated NK cells for infusion, one potent method uses cells from the K562 human erythroleukemia line that have been transfected to express activating 41BB ligand (41BBL) and membrane-bound interleukin 15 (mbIL15). The functional importance of KIRs on ex vivo expanded NK cells has not been studied in detail. We found that after a 12-day co-culture with K562-mbIL15-41BBL cells, expanded NK cells maintained inhibition specificity and prior in vivo licensing status determined by KIR/KIR-ligand interactions. Addition of an anti-CD20 antibody (rituximab) induced NK-mediated antibody-dependent cellular cytotoxicity and augmented killing of CD20+ target cells. However, partial inhibition induced by KIR/KIR-ligand interactions persisted. Finally, we found that extended co-cultures of NK cells with stimulatory cells transduced to express various KIR-ligands modified both the inhibitory and activating KIR repertoires of the expanded NK cell product. These studies demonstrate that the licensing interactions known to occur during NK ontogeny also influence NK cell function following NK expansion ex vivo with HLA-null stimulatory cells.

  4. Amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by streptococcal IgA1 proteases

    DEFF Research Database (Denmark)

    Batten, MR; Senior, BW; Kilian, Mogens

    2003-01-01

    The amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by IgA1 proteases of different species of Streptococcus were investigated. Recombinant IgA1 antibodies were generated with point mutations at proline 227 and threonine 228, the residues lying on either...... side of the peptide bond at which all streptococcal IgA1 proteases cleave wild-type human IgA1. The amino acid substitutions produced no major effect upon the structure of the mutant IgA1 antibodies or their functional ability to bind to Fcalpha receptors. However, the substitutions had a substantial...... effect upon sensitivity to cleavage with some streptococcal IgA1 proteases, with, in some cases, a single point mutation rendering the antibody resistant to a particular IgA1 protease. This effect was least marked with the IgA1 protease from Streptococcus pneumoniae, which showed no absolute requirement...

  5. Equine immunoglobulins and organization of immunoglobulin genes.

    Science.gov (United States)

    Walther, Stefanie; Rusitzka, Tamara V; Diesterbeck, Ulrike S; Czerny, Claus-Peter

    2015-12-01

    Our understanding of how equine immunoglobulin genes are organized has increased significantly in recent years. For equine heavy chains, 52 IGHV, 40 IGHD, 8 IGHJ and 11 IGHC are present. Seven of these IGHCs are gamma chain genes. Sequence diversity is increasing between fetal, neonatal, foal and adult age. The kappa light chain contains 60 IGKV, 5 IGKJ and 1 IGKC, whereas there are 144 IGLV, 7 IGLJ, and 7 IGLC for the lambda light chain, which is expressed predominantly in horses. Significant transcriptional differences for IGLV and IGLC are identified in different breeds. Allotypic and allelic variants are observed for IGLC1, IGLC5, and IGLC6/7, and two IGLV pseudogenes are also transcribed. During age development, a decrease in IGLVs is noted, although nucleotide diversity and significant differences in gene usage increased. The following paper suggests a standardization of the existing nomenclature of immunoglobulin genes.

  6. CANCEROUS IMMUNOGLOBULINS AND CA215: IMPLICATIONS IN CANCER IMMUNOLOGY

    Directory of Open Access Journals (Sweden)

    Gregory Lee

    2012-01-01

    Full Text Available Immunoglobulins are typically expressed by B cells in our normal immune system. However, certain normal human tissues, such as hyperplastic epithelial cells, cells of the immunologically privileged sites and the majority of cancer cells, have also been found to be sites of immunoglobulin production. Current research is lacking in regards to the differential immunoglobulin expression, the underling mechanisms of action and the biological implications of these cancerous immunoglobulins in cancer immunology. This article reviews the etiology of atypical immunoglobulin expression in normal non-B cells and cancer cells, with emphasis on the exploration of the possible mechanisms of action and biological function of these atypical immunoglobulins, by means of specific biological probes. In contrast to immunoglobulins of B cell origins, atypical immunoglobulins were found to carry additional post-translational modifications, including a unique carbohydrateassociated epitope recognized by RP215 monoclonal antibody. This unique RP215-specific epitope enables us to differentiate between these two types of immunoglobulins. Atypical immunoglobulins expressed by cancer cells have been a common subject of interest in cancer immunology. Furthermore, the recent accumulation of experimental evidence has indicated that these atypical immunoglobulins are essential for the growth and proliferation of cancer cells under our normal immune environment. RP215 monoclonal antibody also reacts with many other cancer cell-expressed glycoproteins, known as CA215, on the cancer cell surface. Apoptosis of cultured cancer cells can be induced and growth inhibition of implanted tumors can be observed in nude mouse animal models. Therefore, humanized RP215 monoclonal antibody, which reacts mainly with surface bound CA215, may have the potential to be developed as an anti-cancer drug for the treatment of human cancers. A better understanding of cancer cell

  7. Melanin offers protection against induction of cyclobutane pyrimidine dimers and 6-4 photoproducts by UVB in cultured human melanocytes

    NARCIS (Netherlands)

    Smit, N.P.M.; Vink, A.A.; Kolb, R.M.; Steenwinkel, M.J.S.T.; Berg, P.T.M. van den; Nieuwpoort, F. van; Roza, L.; Pavel, S.

    2001-01-01

    The goal of this investigation was to correlate the melanin content in human pigmentary cells with the generation of UVB-induced photoproducts and to examine the relationship between the melanin content and the removal of the photoproducts. Cultured melanocytes from light-skinned individuals

  8. Melanin offers protection against induction of cyclobutane pyrimidine dimers and 6-4 photoproducts by UVB in cultured human melanocytes

    NARCIS (Netherlands)

    Smit, N.P.M.; Vink, A.A.; Kolb, R.M.; Steenwinkel, M.J.S.T.; Berg, P.T.M. van den; Nieuwpoort, F. van; Roza, L.; Pavel, S.

    2001-01-01

    The goal of this investigation was to correlate the melanin content in human pigmentary cells with the generation of UVB-induced photoproducts and to examine the relationship between the melanin content and the removal of the photoproducts. Cultured melanocytes from light-skinned individuals synthes

  9. Successful treatment of systemic lupus erythematosus with subcutaneous immunoglobulin.

    Science.gov (United States)

    Brasileiro, A; Fonseca Oliveira, J; Pinheiro, S; Paiva-Lopes, M J

    2016-05-01

    The therapeutic efficacy of high-dose intravenous immunoglobulin in systemic lupus erythematosus (SLE) patients is well established. However, side effects might limit its use and lead to the consideration of therapeutic alternatives, such as the subcutaneous formulation of immunoglobulin, which has been used in some patients with other autoimmune diseases. We report a case of SLE refractory to classical therapies. High-dose intravenous immunoglobulin was effective, but gave rise to significant side effects. The patient was successfully treated with subcutaneous human immunoglobulin, achieving and maintaining clinical and laboratory remission. A lower immunoglobulin dose was needed and no side effects were observed, compared to the intravenous administration. Subcutaneous immunoglobulin could be a better-tolerated and cost-saving therapeutic option for select SLE patients.

  10. Dynamics in enzymatic protein complexes offer a novel principle for the regulation of melatonin synthesis in the human pineal gland.

    Science.gov (United States)

    Maronde, Erik; Saade, Anastasia; Ackermann, Katrin; Goubran-Botros, Hany; Pagan, Cecile; Bux, Roman; Bourgeron, Thomas; Dehghani, Faramarz; Stehle, Jörg H

    2011-08-01

    Time of day is communicated to the body through rhythmic cues, including pineal gland melatonin synthesis, which is restricted to nighttime. Whereas in most rodents transcriptional regulation of the arylalkylamine N-acetyltransferase (Aanat) gene is essential for rhythmic melatonin synthesis, investigations into nonrodent mammalian species have shown post-transcriptional regulation to be of central importance, with molecular mechanisms still elusive. Therefore, human pineal tissues, taken from routine autopsies were allocated to four time-of-death groups (night/dawn/day/dusk) and analyzed for daytime-dependent changes in phosphorylated AANAT (p31T-AANAT) and in acetyl-serotonin-methyltransferase (ASMT) expression and activity. Protein content, intracellular localization, and colocalization of p31T-AANAT and ASMT were assessed, using immunoblotting, immunofluorescence, and immunoprecipitation techniques. Fresh sheep pineal gland preparations were used for comparative purposes. The amount of p31T-AANAT and ASMT proteins as well as their intracellular localization showed no diurnal variation in autoptic human and fresh sheep pineal glands. Moreover, in human and sheep pineal extracts, AANAT could not be dephosphorylated, which was at variance to data derived from rat pineal extracts. P31T-AANAT and ASMT were often found to colocalize in cellular rod-like structures that were also partly immunoreactive for the pinealocyte process-specific marker S-antigen (arrestin) in both, human and sheep pinealocytes. Protein-protein interaction studies with p31T-AANAT, ASMT, and S-antigen demonstrated a direct association and formation of robust complexes, involving also 14-3-3. This work provides evidence for a regulation principle for AANAT activity in the human pineal gland, which may not be based on a p31T-AANAT phosphorylation/dephosphorylation switch, as described for other mammalian species.

  11. Effect of yoghurt containing Bifidobacterium lactis Bb12® on faecal excretion of secretory immunoglobulin A and human beta-defensin 2 in healthy adult volunteers

    National Research Council Canada - National Science Library

    Kabeerdoss, Jayakanthan; Devi, R Shobana; Mary, R Regina; Prabhavathi, D; Vidya, R; Mechenro, John; Mahendri, N V; Pugazhendhi, Srinivasan; Ramakrishna, Balakrishnan S

    2011-01-01

    Probiotics are used to provide health benefits. The present study tested the effect of a probiotic yoghurt on faecal output of beta-defensin and immunoglobulin A in a group of young healthy women eating a defined diet...

  12. Significant neutralizing activities against H2N2 influenza A viruses in human intravenous immunoglobulin lots manufactured from 1993 to 2010

    Directory of Open Access Journals (Sweden)

    Ikuta K

    2012-07-01

    Full Text Available Ritsuko Kubota-Koketsu,1,2 Mikihiro Yunoki,2,3 Yoshinobu Okuno,1 Kazuyoshi Ikuta21Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kagawa; 2Department of Virology, Research Institute for Microbial Diseases, Osaka University, 3Pathogenic Risk Management, Benesis Corporation, Osaka, JapanAbstract: Influenza A H2N2 virus, also known as the Asian flu, spread worldwide from 1957 to 1967, although there have been no cases reported in humans in the past 40 years. A vaccination program was introduced in Japan in the 1960s. Older Japanese donors could have been naturally infected with the H2N2 virus or vaccinated in the early 1960s. Human intravenous immunoglobulin (IVIG reflects the epidemiological status of the donating population in a given time period. Here, the possible viral neutralizing (VN activities of IVIG against the H2N2 virus were examined. Hemagglutination inhibition (HI and VN activities of IVIG lots manufactured from 1993 to 2010 in Japan and the United States were evaluated against H2N2 viruses. High HI and VN activities against H2N2 viruses were found in all the IVIG lots investigated. HI titers were 32–64 against the isolate in 1957 and 64–128 against the isolates in 1965. VN titers were 80–320 against the isolate in 1957 and 1280–5120 against the isolates in 1965. Both the HI and VN titers were higher against the isolate in 1965 than in 1957. Thus, antibody titers of IVIG against influenza viruses are well correlated with the history of infection and the vaccine program in Japan. Therefore, evaluation of antibody titers provides valuable information about IVIGs, which could be used for immune stimulation when a new influenza virus emerges in the human population.Keywords: IVIG, influenza, H2N2, neutralization

  13. Adsorption of human immunoglobulin G to poly ( β-hydroxybutyrate (PHB, poly (L- lactic Acid (PLLA and PHB/PLLA blends

    Directory of Open Access Journals (Sweden)

    M. V. S. Lima

    2009-06-01

    Full Text Available Biodegradable polymeric materials can be used as temporary implants and may be able to carry out specific functions for a pre-determined period prior to their degradation in vivo. In order to be used they must present characteristics of biocompatibility. When a material comes into contact with blood, the instantaneous adsorption of protein occurs on its surface. Coverage of the surface by γ-globulins causes the adhesion of platelets and, consequently, provokes the process of blood coagulation. In this context, the objective of the present paper was to quantify the adsorption of human Immunoglobulin G (HIgG to poly ( β-hydroxybutyrate (PHB, poly (L-lactic acid (PLLA and PHB/PLLA blends using the FTIR/ATR technique. The results showed the occurrence of HlgG adsorption for all three systems, PHB having the highest adsorption density, about Γmax =2.57 µg/cm², followed by PHB/PLLA blends (Γmax=0.85 µg/cm² and PLLA with the lowest values (Γmax=0.25 µg/cm².

  14. Interaction Study of 2,6-Bis[4-(4-amino-2-trifluoromethyl phenoxy)benzoyl] Pyridine with Human Immunoglobulin by Optical Spectroscopy and Molecular Modeling

    Institute of Scientific and Technical Information of China (English)

    HE Wenying; ZHANG Qiongmei; GAO Wenhua; DONG Yuming; YAO Xiaojun

    2009-01-01

    The interaction between human immunoglobulin (HIgG) and BAFP (2,6-bis[4-(4-amino-2-trifluoromethyl phenoxy)benzoyl] pyridine was studied by fluorescence quenching, Fourier transform infrared (FT-IR) spectra and molecule modeling. The synchronous fluorescence spectra indicated the information on qualitative changes of the pro-tein secondary structure in the presence of BAFP in aqueous solution. The quantitative alterations of the protein sec-ondary structure were estimated by the evidences from FT-IR spectra with increases of α helices by about 2.6%-10.2%, increases of β-sheet structure by about 13.6%-27.7%, and reductions of β-turn structure by about 23.8%-30.3%. Molecular docking suggests that BAFP can strongly bind to HIgG. There are four hydrogen bond interac-tions between the drug and the residues Trp 170, Val 105, Met 139 and Asn 52. It was also considered that BAFP bound to HIgG mainly by a hydrophobic interaction, which is in good agreement with the results from the experi-mental thermodynamic parameters (the enthalpy change △Hθ and the entropy change △Sθ were calculated to be-6.70 kJ·mol-1 and 71.93 J·mol-1·K-1,respectively, according to the Van't Holf equation).

  15. Immunohistochemical characterization of the lymphocyte and the immunoglobulin-containing cell in the epithelium and the lamina propria of normal human intestines.

    Directory of Open Access Journals (Sweden)

    Matsueda,Kazuhiro

    1991-06-01

    Full Text Available In order to clarify difference of the mucosal immunity in various sites of normal large and small intestines, we studied the population of lymphocyte subsets and immunoglobulin (Ig-containing cells in situ in biopsy specimens taken from various sites (ascending colon, sigmoid colon and rectum of the large intestine and from the duodenum using an immunohistochemical method. Monoclonal antibodies against pan-T (Leu 1, cytotoxic/suppressor T (Leu2a, helper/inducer T (Leu3a, suppressor T (Leu15 and natural killer/K (Leu7 cells, and polyclonal antibodies to human IgG, IgA and IgM were used. In the duodenum, intraepithelial lymphocytes (IELs were more prominent than in the large intestine. Immunoelectron microscopic observation revealed that some Leu2a+ IELs possessed pseudopods extending into intestinal epithelial cells, indicating that some IELs belong to the cytotoxic T cell subset. Leu7+ IELs were scarcely observed and Leu7+/Leu1+ ratio was higher in the large intestine than in the duodenum. Furthermore, the number of Leu7+ cells were more in the distal than the proximal colon. In the lamina propria Ig-containing cells tended to be fewer in the rectum than in the duodenum and the proximal colon. Our findings may suggest the variation of local immune responses and the difference of assigned immunological functions among the various sites of the intestines.

  16. Human immunoglobulin G recognizing fibrinogen-binding surface proteins is protective against both Staphylococcus aureus and Staphylococcus epidermidis infections in vivo.

    Science.gov (United States)

    Vernachio, John H; Bayer, Arnold S; Ames, Brenda; Bryant, Dawn; Prater, Bradley D; Syribeys, Peter J; Gorovits, Elena L; Patti, Joseph M

    2006-02-01

    A human donor-selected immunoglobulin G for intravenous injection (IGIV) product with elevated titers against the staphylococcal fibrinogen-binding MSCRAMM proteins ClfA and SdrG (INH-A21) was tested in vitro and in vivo. INH-A21 contained a significantly increased ability to inhibit the fibrinogen-binding activity of recombinant forms of both ClfA and SdrG. Evaluation of the opsonizing potential of INH-A21 was evaluated using fluorescently labeled bacteria; this assay indicated an increase in phagocytic activity compared to normal IGIV. The prophylactic efficacy of INH-A21 against an intraperitoneal challenge of methicillin-resistant Staphylococcus epidermidis (MRSE) was evaluated in a neonatal rat model. INH-A21 was also evaluated for prophylactic and therapeutic efficacy in a rabbit model of catheter-induced aortic valve infective endocarditis caused by either MRSE or methicillin-resistant Staphylococcus aureus (MRSA). Results from the in vivo models demonstrated potent prophylactic and therapeutic efficacy against both MRSE and MRSA. These data suggest that INH-A21 may be an important tool for the prevention and treatment of staphylococcal infections, especially in high-risk populations.

  17. Immunoglobulin genes undergo legitimate repair in human B cells not only after cis- but also frequent trans-class switch recombination.

    Science.gov (United States)

    Laffleur, B; Bardet, S M; Garot, A; Brousse, M; Baylet, A; Cogné, M

    2014-01-01

    Immunoglobulin (Ig) genes specifically recruit activation-induced deaminase (AID) for 'on-target' DNA deamination, initiating either variable (V) region somatic hypermutation, or double-strand break intermediates of class switch recombination (CSR). Such breaks overwhelmingly undergo legitimate intra-Ig repair rather than rare illegitimate and potentially oncogenic junctions outside of Ig loci. We show that in human B cells, legitimate synapsis and repair efficiently join Ig genes whether physically linked on one chromosome or located apart on both alleles. This indicates mechanisms faithfully recognizing and/or pairing loci with homology in structure and accessibility, thus licensing interchromosomal trans-CSR junctions while usually preventing illegitimate interchromosomal recombination with AID off-target genes. Physical linkage of IgH genes in cis on the same allele just increases the likelihood of legitimate repair by another fourfold. The strongest force driving CSR might thus be recognition of legitimate target genes. Formation of IgH intra-allelic loops along this process would then constitute a consequence rather than a pre-requisite of this gene-pairing process.

  18. Expression of E-selectin, integrin β1 and immunoglobulin superfamily member in human gastric carcinoma cells and its clinicopathologic significance

    Institute of Scientific and Technical Information of China (English)

    Jin-Jing Ke; Qin-Shu Shao; Zhi-Qiang Ling

    2006-01-01

    AIM: To study the expression levels of E- selectin, integrin β1 and immunoglobulin supperfamily memberintercellular adhesion molecule-1 (ICAM-1) in human gastric carcinoma cells, and to explore the relationship between these three kinds of cell adhesion molecules and gastric carcinoma.METHODS: The serum contents of E-selectin, integrin β1 and ICAM-1 were detected by enzyme-linked immunosorbent assay (ELISA), in 47 healthy individuals (control group) and in 57 patients with gastric carcinoma (gastric carcinoma group) respectively prior to operation and 7 d after operation.RESULTS: The serum E-selectin, ECAM-1 and integrin β1were found to be expressed in both control and gastric carcinoma groups. However, they were highly expressed in patients with gastric carcinoma patients before operation or with unresectable tumours. The expression levels of ICAM-1 and integrin β1 were significantly higher in gastric carcinoma patients than in controls (P <0.01). A comparison of the E-selectin levels between the two groups showed statistically insignificant differnce (P = 0.64) In addition, the expression levels were all decreased substantially in the postoperative patients subjected to radical resection of the tumours, indicating that the high level expressions of these compounds might be the important factor for predicting the prognosis of these patients.CONCLUSION: Serum E-selectin, ICAM-1 and integrin β1 expression levels are probably related to the metastasis and relapse of gastric cancer.

  19. A prospective comparison of sup 99m Tc-labeled polyclonal human immunoglobulin and sup 111 In granulocytes for localization of inflammatory bowel disease

    Energy Technology Data Exchange (ETDEWEB)

    Arndt, J.W.; Sluys Veer, A. van der; Blok, D.; Griffioen, G.; Verspaget, H.W.; Salvador Pena, A.; Lamers, C.B.H.W.; Pauwels, E.K.J. (Leiden Univ. Hospital (Netherlands). Div. of Nuclear Medicine, Dept. of Diagnostic Radiology, and Dept. of Gastroenterology)

    1992-03-01

    There is a need for an easily prepared radiopharmaceutical agent for the detection of inflammation and infection. In a group of 14 patients with inflammatory bowel disease (IBD), the detection of actively involved intestinal segments by nonspecific human polyclonal immunoglobulin (IgG) labeled with {sup 99m}Tc was compared with that of {sup 111}In granulocytes. To determine the specificity of {sup 99m}Tc-IgG scintigraphy, 8 control patients without clinical indications of intestinal inflammation were examined. {sup 99m}Tc-IgG was found in the left colon in 8 and in the right colon in 7 of the 8 controls 4 hours after the injection. At that time of scintigraphy only 4 IBD patients exhibited a more intensive accumulation at the site of the intestinal segments with active disease. In contrast, in a randomized comparison with {sup 111}In granulocytes scintigraphy was positive in 11 patients with the latter technique. Moreover, fewer diseased segments were seen in the 4 patients with positive {sup 99m}Tc-IgG scintigraphy (6 versus 12 with {sup 111}In granulocytes). In view of the low sensitivity and specificity, it is concluded that {sup 99m}Tc-IgG is not suitable for the scintigraphy staging of IBD patients. (orig.).

  20. Homogenous electrogenerated chemiluminescence immunoassay for human immunoglobulin G using N-(aminobutyl)-N-ethylisoluminol as luminescence label at gold nanoparticles modified paraffin-impregnated graphite electrode.

    Science.gov (United States)

    Qi, Honglan; Zhang, Yi; Peng, Yage; Zhang, Chengxiao

    2008-05-15

    A homogeneous electrogenerated chemiluminescence (ECL) immunoassay for human immunoglobulin G (hIgG) has been developed using a N-(aminobutyl)-N-ethylisoluminol (ABEI) as luminescence label at gold nanoparticles modified paraffin-impregnated graphite electrode (PIGE). ECL emission was electrochemically generated from the ABEI-labeled anti-hIgG antibody and markedly increased in the presence of hIgG antigen due to forming a more rigid structure of the ABEI moiety. The concentration of hIgG antigen was determined by the increase of ECL intensity at a gold nanoparticles modified PIGE. It was found that the ECL intensity of ABEI in presence of hydrogen peroxide was dramatically enhanced at gold nanoparticles modified PIGE in neutral aqueous solution and the detection limit of ABEI was 2 x 10(-14)mol/L (S/N=3). The integral ECL intensity was linearly related to the concentration of hIgG antigen from 3.0 x 10(-11) to 1.0 x 10(-9)g/mL with a detection limit of 1 x 10(-11)g/mL (S/N=3). The relative standard deviation was 3.1% at 1.0 x 10(-10)g/mL (n=11). This work demonstrates that the enhancement of the sensitivity of ECL and ECL immunoassay at a nanoparticles modified electrode is a promising strategy.

  1. E6 and E7 fusion immunoglobulin from human papilloma virus 16 induces dendritic cell maturation and antigen specific activation of T helper 1 response.

    Science.gov (United States)

    Kim, Sang-Hoon; Hur, Yu Jin; Lee, Suk Jun; Kim, Sang Joon; Park, Chung-Gyu; Oh, Yu-Koung; Jung, Woon-Won; Seo, Jong Bok; Nam, Myung Hee; Choi, Inho; Chun, Taehoon

    2011-04-01

    Human papilloma virus (HPV) 16 causes cervical cancer. Induction of oncogenesis by HPV 16 is primarily dependent on the function of E6 and E7 proteins, which inactivate the function of p53 and pRB, respectively. Thus, blocking the activity of the E6 and E7 proteins from HPV 16 is critical to inhibiting oncogenesis during infection. We have expressed and purified soluble HPV 16 E6 and E7 fusion immunoglobulin (Ig), which were combined with the constant region of an Ig heavy chain, in a mammalian system. To assess whether soluble E6 and E7 fusion Igs induce effective cellular immune responses, immature dendritic cells (DCs) were treated with these fusion proteins. Soluble E6 and E7 fusion Igs effectively induced maturation of DCs. Furthermore, immunization with soluble E6 and E7 fusion Igs in mice resulted in antigen-specific activation of T helper 1 (Th1) cells. This is the first comprehensive study to show the molecular basis of how soluble HPV 16 E6 or E7 fusion Igs induces Th1 responses through the maturation of DCs. In addition, we show that DC therapy using soluble HPV E6 and E7 fusion Igs may be a valuable tool for controlling the progress of cervical cancer.

  2. Cleavage of a recombinant human immunoglobulin A2 (IgA2)-IgA1 hybrid antibody by certain bacterial IgA1 proteases

    DEFF Research Database (Denmark)

    Senior, B; Dunlop, JI; Batten, MR

    2000-01-01

    To understand more about the factors influencing the cleavage of immunoglobulin A1 (IgA1) by microbial IgA1 proteases, a recombinant human IgA2/IgA1 hybrid molecule was generated. In the hybrid, termed IgA2/A1 half hinge, a seven-amino-acid sequence corresponding to one half of the duplicated...... sequence making up the IgA1 hinge was incorporated into the equivalent site in IgA2. Insertion of the IgA1 half hinge into IgA2 did not affect antigen binding capacity or the functional activity of the hybrid molecule, as judged by its ability to bind to IgA Fcalpha receptors and trigger respiratory bursts...... in neutrophils. Although the IgA2/A1 hybrid contained only half of the IgA1 hinge, it was found to be cleaved by a variety of different bacterial IgA1 proteases, including representatives of those that cleave IgA1 in the different duplicated halves of the hinge, namely, those of Prevotella melaninogenica...

  3. Expression of human AID in yeast induces mutations in context similar to the context of somatic hypermutation at G-C pairs in immunoglobulin genes

    Directory of Open Access Journals (Sweden)

    Kunkel Thomas A

    2005-06-01

    Full Text Available Abstract Background Antibody genes are diversified by somatic hypermutation (SHM, gene conversion and class-switch recombination. All three processes are initiated by the activation-induced deaminase (AID. According to a DNA deamination model of SHM, AID converts cytosine to uracil in DNA sequences. The initial deamination of cytosine leads to mutation and recombination in pathways involving replication, DNA mismatch repair and possibly base excision repair. The DNA sequence context of mutation hotspots at G-C pairs during SHM is DGYW/WRCH (G-C is a hotspot position, R = A/G, Y = T/C, W = A/T, D = A/G/T. Results To investigate the mechanisms of AID-induced mutagenesis in a model system, we studied the genetic consequences of AID expression in yeast. We constructed a yeast vector with an artificially synthesized human AID gene insert using codons common to highly expressed yeast genes. We found that expression of the artificial hAIDSc gene was moderately mutagenic in a wild-type strain and highly mutagenic in an ung1 uracil-DNA glycosylase-deficient strain. A majority of mutations were at G-C pairs. In the ung1 strain, C-G to T-A transitions were found almost exclusively, while a mixture of transitions with 12% transversions was characteristic in the wild-type strain. In the ung1 strain mutations that could have originated from deamination of the transcribed stand were found more frequently. In the wild-type strain, the strand bias was reversed. DGYW/WRCH motifs were preferential sites of mutations. Conclusion The results are consistent with the hypothesis that AID-mediated deamination of DNA is a major cause of mutations at G-C base pairs in immunoglobulin genes during SHM. The sequence contexts of mutations in yeast induced by AID and those of somatic mutations at G-C pairs in immunoglobulin genes are significantly similar. This indicates that the intrinsic substrate specificity of AID itself is a primary determinant of mutational hotspots at G

  4. Overexpression of Human Senescence Marker Protein 30 in Mice Fails to Offer Protection Against Challenge with Organophosphorus Compounds

    Science.gov (United States)

    2011-09-01

    organophosphate poisoning . Proc Natl Acad Sci U S A 104: 13603-13608. 8. Ashani Y, Pistinner S (2004) Estimation of the upper limit of human...life-threatening risk to both soldiers and civilians [1]. Current antidotal regimen for OP poisoning includes anticholinergic drugs to counteract the...Eyer P, Felgenhauer N, Zilker T, Worek F. (2007) Lessons to be learnt from organophosphorus pesticide poisoning for the treatment of nerve agent

  5. Identification of a human immunodominant B-cell epitope within the immunoglobulin A1 protease of Streptococcus pneumoniae

    Directory of Open Access Journals (Sweden)

    Felici Franco

    2007-12-01

    Full Text Available Abstract Background The IgA1 protease of Streptococcus pneumoniae is a proteolytic enzyme that specifically cleaves the hinge regions of human IgA1, which dominates most mucosal surfaces and is the major IgA isotype in serum. This protease is expressed in all of the known pneumococcal strains and plays a major role in pathogen's resistance to the host immune response. The present work was focused at identifying the immunodominant regions of pneumococcal IgA1 protease recognized by the human antibody response. Results An antigenic sequence corresponding to amino acids 420–457 (epiA of the iga gene product was identified by screening a pneumococcal phage display library with patients' sera. The epiA peptide is conserved in all pneumococci and in two out of three S. mitis strains, while it is not present in other oral streptococci so far sequenced. This epitope was specifically recognized by antibodies present in sera from 90% of healthy adults, thus representing an important target of the humoral response to S. pneumoniae and S. mitis infection. Moreover, sera from 68% of children less than 4 years old reacted with the epiA peptide, indicating that the human immune response against streptococcal antigens occurs during childhood. Conclusion The broad and specific recognition of the epiA polypeptide by human sera demonstrate that the pneumococcal IgA1 protease contains an immunodominant B-cell epitope. The use of phage display libraries to identify microbe or disease-specific antigens recognized by human sera is a valuable approach to epitope discovery.

  6. Characterization of Human and Murine T-Cell Immunoglobulin Mucin Domain 4 (TIM-4) IgV Domain Residues Critical for Ebola Virus Entry.

    Science.gov (United States)

    Rhein, Bethany A; Brouillette, Rachel B; Schaack, Grace A; Chiorini, John A; Maury, Wendy

    2016-07-01

    Phosphatidylserine (PtdSer) receptors that are responsible for the clearance of dying cells have recently been found to mediate enveloped virus entry. Ebola virus (EBOV), a member of the Filoviridae family of viruses, utilizes PtdSer receptors for entry into target cells. The PtdSer receptors human and murine T-cell immunoglobulin mucin (TIM) domain proteins TIM-1 and TIM-4 mediate filovirus entry by binding to PtdSer on the virion surface via a conserved PtdSer binding pocket within the amino-terminal IgV domain. While the residues within the TIM-1 IgV domain that are important for EBOV entry are characterized, the molecular details of virion-TIM-4 interactions have yet to be investigated. As sequences and structural alignments of the TIM proteins suggest distinct differences in the TIM-1 and TIM-4 IgV domain structures, we sought to characterize TIM-4 IgV domain residues required for EBOV entry. Using vesicular stomatitis virus pseudovirions bearing EBOV glycoprotein (EBOV GP/VSVΔG), we evaluated virus binding and entry into cells expressing TIM-4 molecules mutated within the IgV domain, allowing us to identify residues important for entry. Similar to TIM-1, residues in the PtdSer binding pocket of murine and human TIM-4 (mTIM-4 and hTIM-4) were found to be important for EBOV entry. However, additional TIM-4-specific residues were also found to impact EBOV entry, with a total of 8 mTIM-4 and 14 hTIM-4 IgV domain residues being critical for virion binding and internalization. Together, these findings provide a greater understanding of the interaction of TIM-4 with EBOV virions. With more than 28,000 cases and over 11,000 deaths during the largest and most recent Ebola virus (EBOV) outbreak, there has been increased emphasis on the development of therapeutics against filoviruses. Many therapies under investigation target EBOV cell entry. T-cell immunoglobulin mucin (TIM) domain proteins are cell surface factors important for the entry of many enveloped viruses

  7. Killer cell immunoglobulin-like receptor and human leukocyte antigen gene profiles in a cohort of HIV-infected Mexican Mestizos.

    Science.gov (United States)

    Garrido-Rodríguez, Daniela; Ávila-Ríos, Santiago; García-Morales, Claudia; Valenzuela-Ponce, Humberto; Ormsby, Christopher; Reyes-Gopar, Helena; Fernandez-Lopez, Juan Carlos; Reyes-Terán, Gustavo

    2016-10-01

    Killer cell immunoglobulin-like receptors (KIRs) represent the most polymorphic genes responsible for natural killer cell function, while human leukocyte antigen (HLA) class I molecules define and restrict cytotoxic T lymphocyte responses. Specific KIR, HLA, or KIR-HLA combinations have been implicated in the outcome of human immunodeficiency virus (HIV) disease. The remarkable polymorphism of KIR and HLA genes warrants descriptive gene frequency studies in different populations, as well as their impact on HIV disease progression in different immunogenetic contexts. We report KIR and HLA class I gene profiles of 511 unrelated HIV-infected Mexican Mestizo individuals from 18 states for whom genetic ancestry proportions were assessed. KIR and HLA gene profiles were compared between individuals from the north and central-south regions of the country and between individuals with higher European (EUR) or Amerindian (AMI) genetic ancestry component. A total of 65 KIR genotypes were observed, 11 harboring novel KIR gene combinations. A total of 164 HLA alleles were observed: 43 HLA-A, 87 HLA-B, and 34 HLA-C. Differences in the distribution of 12 HLA alleles were observed between individuals with higher AMI or EUR ancestry components (p < 0.05, q < 0.2). After correcting for genetic ancestry, only individual HLA alleles were associated with HIV disease progression, including a novel association with A*02:06, an Amerindian HLA allele associated with lower CD4+ T cell counts. No KIR effects were significant. Our results highlight the advantages of considering a detailed genetic stratification within populations when studying genetic profiles that could be implicated in disease-association studies.

  8. Study of Humoral Immunity to Commensal Oral Bacteria in Human Infants Demonstrates the Presence of Secretory Immunoglobulin A Antibodies Reactive with Actinomyces naeslundii Genospecies 1 and 2 Ribotypes

    Science.gov (United States)

    Cole, Michael F.; Evans, Mishell K.; Kirchherr, Jennifer L.; Sheridan, Michael J.; Bowden, G. H. W.

    2004-01-01

    The mouths of three human infants were examined from birth to age 2 years to detect colonization of Actinomyces naeslundii genospecies 1 and 2. These bacteria did not colonize until after tooth eruption. The diversity of posteruption isolates was determined by ribotyping. Using immunoblotting and enzyme-linked immunosorbent assay, we determined the reactivity of secretory immunoglobulin A (SIgA) antibodies in saliva samples collected from each infant before and after colonization against cell wall proteins from their own A. naeslundii strains and carbohydrates from standard A. naeslundii genospecies 1 and 2 strains. A. naeslundii genospecies 1 and 2 carbohydrate-reactive SIgA antibodies were not detected in any saliva sample. However, SIgA antibodies reactive with cell wall proteins were present in saliva before these bacteria colonized the mouth. These antibodies could be almost completely removed by absorption with A. odontolyticus, a species known to colonize the human mouth shortly after birth. However, after colonization by A. naeslundii genospecies 1 and 2, specific antibodies were induced that could not be removed by absorption with A. odontolyticus. Cluster analysis of the patterns of reactivity of postcolonization salivary antibodies from each infant with antigens from their own strains showed that not only could these antibodies discriminate among strains but antibodies in saliva samples collected at different times showed different reactivity patterns. Overall, these data suggest that, although much of the salivary SIgA antibodies reactive with A. naeslundii genospecies 1 and 2 are directed against genus-specific or more broadly cross-reactive antigens, species, genospecies, and possibly strain-specific antibodies are induced in response to colonization. PMID:15138172

  9. Molecular evolution of the human immunoglobulin E response: high incidence of shared mutations and clonal relatedness among epsilon VH5 transcripts from three unrelated patients with atopic dermatitis

    Science.gov (United States)

    1993-01-01

    We have analyzed the nucleotide sequences of 19 epsilon VH5 transcripts derived from in vivo isotype switched peripheral blood B cells of three patients with atopic dermatitis. Comparison with the patients' own germline VH5 gene segments revealed that the epsilon transcripts were derived from both functional members of the human VH5 gene family and harbored numerous somatic mutations (range 5-36 per VH5 gene). In two patients, we detected clonally related but diverged transcripts, permitting the construction of a genealogical tree in one patient. We observed a high proportion of shared silent (S) and replacement (R) mutations among epsilon VH5 sequences derived from all three individuals, even among transcripts descending from the two different germline VH5 gene segments. A remarkably high number of these mutations is shared with previously reported VH5 genes encoding antibodies with defined specificities. The shared S mutations, and likely a fraction of the R mutations, appear to mark preferential sites ("hot spots") of somatic hypermutations in human VH5 genes. The distribution of R and S mutations over complementarity determining region and framework regions in the majority of VH regions deviated from that characteristic of antigen-driven immune response. We hypothesize that the V regions of immunoglobulin E-bearing B cells have accumulated "selectively neutral" mutations over extended periods of clonal expansion, resulting in unusual R/S ratios. We propose that the molecular characteristics of the epsilon VH regions in atopic dermatitis may be representative of antigens that recurrently or chronically stimulate the immune system. PMID:8418213

  10. Intravenous immunoglobulin therapy for pure red cell aplasia related to human parvovirus b19 infection: a retrospective study of 10 patients and review of the literature.

    Science.gov (United States)

    Crabol, Yoann; Terrier, Benjamin; Rozenberg, Flore; Pestre, Vincent; Legendre, Christophe; Hermine, Olivier; Montagnier-Petrissans, Catherine; Guillevin, Loïc; Mouthon, Luc

    2013-04-01

    We evaluated the efficacy of intravenous immunoglobulin (IVIG) therapy in patients with pure red cell aplasia (PRCA) related to human parvovirus B19 (HPV-B19) infection. We retrospectively reviewed all HPV-B19 PRCA cases treated with IVIG between January 2000 and December 2005 in the Assistance Publique-Hôpitaux de Paris hospitals and reviewed all cases of HPV-B19 PRCA cases treated with IVIG in the literature. Among our 36 patients, PRCA was confirmed in 22, including 10 with proven HPV-B19 infection. Nine patients were immunocompromised, including 4 who had undergone transplant. All patients had severe anemia (mean hemoglobin level, 5.0 ± 1.9 g/dL). Seven patients who underwent bone-marrow aspiration had positive HPV-B19 polymerase chain reaction (PCR) results at diagnosis. Patients received a mean of 2.7 ± 2.1 IVIG courses (1.3 ± 0.5 g/kg/course). Hemoglobin level was corrected in 9 of the 10 patients within a mean of 80 ± 54 days. The only nonresponsive patient had underlying myelodysplasia. Blood HPV-B19 PCR results were negative from 35 to 159 days after treatment. Four patients showed side effects of IVIG treatment: acute reversible renal failure (n = 2) and pulmonary edema (n = 2). Among 133 patients with HPV-B19 PRCA who received IVIG (our 10 patients and 123 from the literature), 63 had undergone solid-organ transplant and 39 had human immunodeficiency virus infection. Hemoglobin level was corrected after the first IVIG course in 124 patients (93%); disease relapsed in 42 (33.9%), at a mean of 4.3 months. IVIG therapy appears to be effective in the short term in immunocompromised patients with HPV-B19 PRCA.

  11. Human Leukocyte Antigen C*12:02:02 and Killer Immunoglobulin-Like Receptor 2DL5 are Distinctly Associated with Ankylosing Spondylitis in the Taiwanese.

    Science.gov (United States)

    Wang, Chin-Man; Wang, Sheng-Hung; Jan Wu, Yeong-Jian; Lin, Jing-Chi; Wu, Jianming; Chen, Ji-Yih

    2017-08-16

    Human leukocyte antigen (HLA) class I ligands and Killer immunoglobulin-like receptors (KIRs) regulate the cytolytic activity of natural killer (NK) cells and certain T cells. We examined their genetic predisposition to disease susceptibility and clinical phenotypes in Taiwanese ankylosing spondylitis (AS) patients. KIR genotyping and Human Leucocyte Antigen C (HLA-C) sequencing were performed in 653 Taiwanese AS patients and 952 healthy controls. KIR genotype distributions and HLA-C allele frequencies were compared in patients and controls and among patients with and without HLA-B27 positivity, early age onset and spinal syndesmophytes. HLA-C alleles were functionally characterized using 3D structural modelling with peptide simulation. This study discovered that the HLA-C*12:02:02 allele (43.42% vs. 3.31%; p C*12:02:02 allele. KIR2DL5 (p = 0.0047; pFDR = 0.0423) and the KIR Bx haplotype (p = 0.0000275) were protective against Taiwanese AS, while KIR 2DS4/1D (22 base pair truncated deletion; p = 0.0044; pFDR = 0.1998) appeared to be a risk factor for it. KIR2DL5 combined with the HLA-C1/C2 heterozygous genotype showed a protective effect (AS 5.97% vs. normal 11.66%; p = 0.002; pFDR = 0.0127, OR, 0.48 95% CI: 0.33-0.70); in contrast, KIR 2DS4/1D combined with the HLA-C1C1 homozygous genotype (AS 45.33% vs. normal 35.92%; p = 0.002; pFDR = 0.0127, OR, 1.48 95% CI: 1.21-1.81) represented a risk factor for AS development. Our data suggested that interactions between KIRs and their cognate HLA-C ligands may contribute to the pathogenesis of AS.

  12. Exchanging murine and human immunoglobulin constant chains affects the kinetics and thermodynamics of antigen binding and chimeric antibody autoreactivity.

    Directory of Open Access Journals (Sweden)

    Marcela Torres

    Full Text Available Mouse-human chimeric antibodies composed of murine variable (V and human (C chains are useful therapeutic reagents. Consequently, we investigated whether heterologous C-regions from mice and humans affected specificity and affinity, and determined the contribution of C(H glycosylation to antigen binding. The interaction of a 12-mer peptide mimetic with monoclonal antibody (mAb 18B7 to Cryptococcus neoformans glucuronoxylomannan, and its chimeric (ch and deglycosylated forms were studied by surface plasmon resonance. The equilibrium and rate association constants for the chAb were higher than for mAb 18B7. V region affinity was not affected by C(H region glycosylation whereas heterologous C region of the same isotype altered the Ab binding affinity and the specificity for self-antigens. Structural models displayed local differences that implied changes on the connectivity of residues. These findings suggest that V region conformational changes can be dictated by the C(H domains through an allosteric effect involving networks of highly connected amino acids.

  13. Effect of thermal pasteurisation and high-pressure processing on immunoglobulin content and lysozyme and lactoperoxidase activity in human colostrum.

    Science.gov (United States)

    Sousa, Sílvia G; Delgadillo, Ivonne; Saraiva, Jorge A

    2014-05-15

    Human milk, and particularly human colostrum, is the gold standard for newborn nourishment. Colostrum contains the highest concentration of immune factors, being the most potent immune booster known to science. In this work, we investigated Holder pasteurisation and high-pressure processing (HPP) effects on colostral IgA, IgM, IgG, lysozyme and lactoperoxidase. The amount of Igs was significantly decreased after Holder pasteurisation (20%, 51% and 23% for IgA, IgM and IgG, respectively), but fully preserved after HPP at 200 and 400 MPa. HPP at 600 MPa for 2.5 min resulted in the maintenance of IgA and losses of IgM and IgG (21% for both). The pressure treatments at 600 MPa for 15 and 30 min led to similar or higher losses than pasteurisation. D-values (min) for Igs ranged from 4941 to 452 at 400 MPa and from 235 to 40 at 600 MPa. Lysozyme activity was lost after pasteurisation (decreased 44%) and maintained after HPP. Lactoperoxidase activity was not detected. As far as the authors are aware, this is the first study evaluating HPP effects on human colostrum.

  14. Bovine immunoglobulin protein isolates for the nutritional management of enteropathy.

    Science.gov (United States)

    Petschow, Bryon W; Blikslager, Anthony T; Weaver, Eric M; Campbell, Joy M; Polo, Javier; Shaw, Audrey L; Burnett, Bruce P; Klein, Gerald L; Rhoads, J Marc

    2014-09-07

    The gastrointestinal tract is responsible for a multitude of digestive and immune functions which depend upon the balanced interaction of the intestinal microbiota, diet, gut barrier function, and mucosal immune response. Disruptions in one or more of these factors can lead to intestinal disorders or enteropathies which are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Enteropathy is frequently associated with human immunodeficiency virus (HIV) infection, inflammatory bowel disease, autoimmune enteropathy, radiation enteritis, and irritable bowel syndrome (IBS), where pathologic changes in the intestinal tract lead to abdominal discomfort, bloating, abnormal bowel function (e.g., diarrhea, urgency, constipation and malabsorption). Unfortunately, effective therapies for the management of enteropathy and restoring intestinal health are still not available. An accumulating body of preclinical studies has demonstrated that oral administration of plasma- or serum-derived protein concentrates containing high levels of immunoglobulins can improve weight, normalize gut barrier function, and reduce the severity of enteropathy in animal models. Recent studies in humans, using serum-derived bovine immunoglobulin/protein isolate, demonstrate that such protein preparations are safe and improve symptoms, nutritional status, and various biomarkers associated with enteropathy. Benefits have been shown in patients with HIV infection or diarrhea-predominant IBS. This review summarizes preclinical and clinical studies with plasma/serum protein concentrates and describes the effects on host nutrition, intestinal function, and markers of intestinal inflammation. It supports the concept that immunoglobulin-containing protein preparations may offer a new strategy for restoring functional homeostasis in the intestinal tract of patients with enteropathy.

  15. Mannose-containing oligosaccharides of non-specific human secretory immunoglobulin A mediate inhibition of Vibrio cholerae biofilm formation.

    Directory of Open Access Journals (Sweden)

    Ashlesh K Murthy

    Full Text Available The role of antigen-specific secretory IgA (SIgA has been studied extensively, whereas there is a limited body of evidence regarding the contribution of non-specific SIgA to innate immune defenses against invading pathogens. In this study, we evaluated the effects of non-specific SIgA against infection with Vibrio cholerae O139 strain MO10 and biofilm formation. Seven day old infant mice deficient in IgA (IgA(-/- mice displayed significantly greater intestinal MO10 burden at 24 hr post-challenge when compared to IgA(+/+ pups. Importantly, cross-fostering of IgA(-/- pups with IgA(+/+ nursing dams reversed the greater susceptibility to MO10 infection, suggesting a role for non-specific SIgA in protection against the infection. Since biofilm formation is associated with virulence of MO10, we further examined the role of human non-specific SIgA on this virulence phenotype of the pathogen. Human non-specific SIgA, in a dose-dependent fashion, significantly reduced the biofilm formation by MO10 without affecting the viability of the bacterium. Such an inhibitory effect was not induced by human serum IgA, IgG, or IgM, suggesting a role for the oligosaccharide-rich secretory component (SC of SIgA. This was supported by the demonstration that SIgA treated with endoglycosidase H, to cleave the high-mannose containing terminal chitobiose residues, did not induce a reduction in biofilm formation by MO10. Furthermore, the addition of free mannose per se, across a wide dose range, induced significant reduction in MO10 biofilm formation. Collectively, these results suggest that mannose containing oligosaccharides within human non-specific secretory IgA can alter important virulence phenotypes of Vibrio cholerae such as biofilm formation, without affecting viability of the microorganism. Such effects may contribute significantly to innate immune defenses against invading pathogens in vivo in the gastrointestinal tract.

  16. Organization of immunoglobulin genes.

    Science.gov (United States)

    Tonegawa, S; Brack, C; Hozumi, N; Pirrotta, V

    1978-01-01

    The nucleotide-sequence determination of a cloned, embryonic Vlambda gene directly demonstrated that V genes are separate from a corresponding C gene in embryonic cells. Analysis by restriction enzymes of total cellular DNA from various sources strongly suggested that the two separate immunoglobulin genes become continuous during differentiation of B lymphocytes. There seems to be a strict correlation between the joining event and activation of the joined genes. Cloning of more immunoglobulin genes from embryo and plasma cells will not only provide direct demonstration of such a gene-joining event but also help in the elucidation of a possible relationship of the event to gene activation mechanisms.

  17. Placental transfer of (125)Iodinated humanized immunoglobulin G2Δa in the Sprague Dawley rat.

    Science.gov (United States)

    Coder, P S; Thomas, J A; Stedman, D B; Bowman, C J

    2013-07-01

    Antibody-like biopharmaceuticals cross the placenta by utilizing transport pathways available for transfer of maternal antibodies to the conceptus. To characterize the timing and magnitude of this transfer in the rat, embryo/fetal biodistribution of maternally administered radiolabeled humanized IgG2 was quantified over the course of gestation using gamma counting and whole body autoradiography. The result was humanized IgG2 found in rat embryo/fetal tissues as early as gestation day 11 with a >1000-fold increase in the amount of total IgG2 by day 21. The concentration of IgG2 in rat embryo/fetal tissues generally remained unchanged from gestation day 11 to 17 with a slight increase from day 17 to 21. In addition, fetal-maternal tissue concentration ratios remained stable during organogenesis with a slight increase from gestation day 17 to 21. Based on the empirical amount of antibody present in the embryo/fetus during specific developmental windows, direct antibody binding to biological targets could potentially result in adverse developmental outcomes.

  18. Identification of a macromolecule containing an anticarcinoembryonic antigen-reactive substance and immunoglobulin M in human pancreatic cancer.

    Science.gov (United States)

    Harvey, S R; Van Dusen, L R; Douglass, H O; Holyoke, E D; Chu, T M

    1978-11-01

    Ascitic fluid from a patient with carcinoma of the pancreas was fractionated by ammonium sulfate precipitation. The fraction precipitated between 25 and 50% saturation of ammonium sulfate was sequentially chromatographed on Sephadex G-200 and Sepharose 6B. A macromolecular fraction (greater than 10(6) daltons) obtained was found to react with both antihuman IgM and antiserum to carcinoembryonic antigen (CEA). This fraction was further purified by adsorption with protein A-Sepharose CL-4B and chromatography on DEAE-Sephacel. The purified macromolecular fraction had a sedimentation value of 28S as determined by ultracentrifugation. Upon dissociation of the purified macromolecule at pH 2.3 and purification of the dissociated components on Sepharose CL-2B and BioGel A 1.5M, a 19S protein and a 5S protein were recovered. The 19S protein showed a complete line of identity with a reference human IgM when reacted with antihuman IgM in gel diffusion, whereas the 5S protein showed a partial immunologic identity with colon CEA against anti-CEA. These results indicated the existence of an IgM-containing macromolecular complex with an anti-CEA cross-reactive substance in the extracellular fluid of human pancreatic cancer.

  19. A combined experimental and theoretical study on the immunoassay of human immunoglobulin using a quartz crystal microbalance.

    Science.gov (United States)

    Liao, Po-Jen; Chang, Jeng-Shian; Chao, Sheng D; Chang, Hung-Chi; Huang, Kuan-Rong; Wu, Kuang-Chong; Wung, Tzong-Shyan

    2010-01-01

    We investigate a immunoassay biosensor that employs a Quartz Crystal Microbalance (QCM) to detect the specific binding reaction of the (Human IgG1)-(Anti-Human IgG1) protein pair under physiological conditions. In addition to experiments, a three dimensional time domain finite element method (FEM) was used to perform simulations for the biomolecular binding reaction in microfluidic channels. In particular, we discuss the unsteady convective diffusion in the transportation tube, which conveys the buffer solution containing the analyte molecules into the micro-channel where the QCM sensor lies. It is found that the distribution of the analyte concentration in the tube is strongly affected by the flow field, yielding large discrepancies between the simulations and experimental results. Our analysis shows that the conventional assumption of the analyte concentration in the inlet of the micro-channel being uniform and constant in time is inadequate. In addition, we also show that the commonly used procedure in kinetic analysis for estimating binding rate constants from the experimental data would underestimate these rate constants due to neglected diffusion processes from the inlet to the reaction surface. A calibration procedure is proposed to supplement the basic kinetic analysis, thus yielding better consistency with experiments.

  20. A Combined Experimental and Theoretical Study on the Immunoassay of Human Immunoglobulin Using a Quartz Crystal Microbalance

    Directory of Open Access Journals (Sweden)

    Jeng-Shian Chang

    2010-12-01

    Full Text Available We investigate a immunoassay biosensor that employs a Quartz Crystal Microbalance (QCM to detect the specific binding reaction of the (Human IgG1-(Anti-Human IgG1 protein pair under physiological conditions. In addition to experiments, a three dimensional time domain finite element method (FEM was used to perform simulations for the biomolecular binding reaction in microfluidic channels. In particular, we discuss the unsteady convective diffusion in the transportation tube, which conveys the buffer solution containing the analyte molecules into the micro-channel where the QCM sensor lies. It is found that the distribution of the analyte concentration in the tube is strongly affected by the flow field, yielding large discrepancies between the simulations and experimental results. Our analysis shows that the conventional assumption of the analyte concentration in the inlet of the micro-channel being uniform and constant in time is inadequate. In addition, we also show that the commonly used procedure in kinetic analysis for estimating binding rate constants from the experimental data would underestimate these rate constants due to neglected diffusion processes from the inlet to the reaction surface. A calibration procedure is proposed to supplement the basic kinetic analysis, thus yielding better consistency with experiments.

  1. Efficacy of zidovudine and human immunodeficiency virus (HIV) hyperimmune immunoglobulin for reducing perinatal HIV transmission from HIV-infected women with advanced disease: results of Pediatric AIDS Clinical Trials Group protocol 185.

    Science.gov (United States)

    Stiehm, E R; Lambert, J S; Mofenson, L M; Bethel, J; Whitehouse, J; Nugent, R; Moye, J; Glenn Fowler, M; Mathieson, B J; Reichelderfer, P; Nemo, G J; Korelitz, J; Meyer, W A; Sapan, C V; Jimenez, E; Gandia, J; Scott, G; O'Sullivan, M J; Kovacs, A; Stek, A; Shearer, W T; Hammill, H

    1999-03-01

    Pediatric AIDS Clinical Trials Group protocol 185 evaluated whether zidovudine combined with human immunodeficiency virus (HIV) hyperimmune immunoglobulin (HIVIG) infusions administered monthly during pregnancy and to the neonate at birth would significantly lower perinatal HIV transmission compared with treatment with zidovudine and intravenous immunoglobulin (IVIG) without HIV antibody. Subjects had baseline CD4 cell counts /=200/microL) but not with time of zidovudine initiation (5.6% vs. 4.8% if started before vs. during pregnancy; P=. 75). The Kaplan-Meier transmission rate for HIVIG recipients was 4. 1% (95% confidence interval, 1.5%-6.7%) and for IVIG recipients was 6.0% (2.8%-9.1%) (P=.36). The unexpectedly low transmission confirmed that zidovudine prophylaxis is highly effective, even for women with advanced HIV disease and prior zidovudine therapy, although it limited the study's ability to address whether passive immunization diminishes perinatal transmission.

  2. Targeting FMS-related tyrosine kinase receptor 3 with the human immunoglobulin G1 monoclonal antibody IMC-EB10.

    Science.gov (United States)

    Youssoufian, Hagop; Rowinsky, Eric K; Tonra, James; Li, Yiwen

    2010-02-15

    FMS-related tyrosine kinase receptor 3 (FLT3) is a class III receptor tyrosine kinase that holds considerable promise as a therapeutic target in hematologic malignancies. Current efforts directed toward the development of small-molecule tyrosine kinase inhibitors of FLT3 may be limited by off-target toxicities and the development of drug resistance. Target-specific antibodies could overcome these hurdles and provide additional mechanisms to enhance the antitumor efficacy of FLT3 inhibitors. IMC-EB10 is a novel antibody directed against FLT3. The binding of IMC-EB10 to FLT3 results in antiproliferative effects in vitro and in mouse models engrafted with human leukemia cells that harbor wild-type or constitutively activated FLT3. Future clinical trials will test these notions formally and will identify the most appropriate opportunities for this member of a new generation of antileukemic therapies.

  3. The Agreement Between Blood Pool - Delayed Bone Scintigraphy and Tc-99m Human Immunoglobulin G (HIG Scintigraphy in the Determination of the Presence and Severity of Inflammatory Arthritis

    Directory of Open Access Journals (Sweden)

    Gulizar Kacar

    2011-08-01

    Full Text Available Objective: In this study, it was aimed to investigate the agreement between early phase of bone scintigraphy – human immunoglobulin scintigraphy (EPBS-HIG and late phase bone scintigraphy – HIG (LPBS-HIG in the determination of the presence and also the severity of inflammatory arthritis. Material and Methods: Twenty-eight patients (23 female, 5 male; between 19 to 80 years of age with inflammatory arthritis were included in the study. Tc-99m HIG and blood pool/late phase bone scintigraphies were performed in all patients. In scintigraphic examinations, the joints were scored with the degree of accumulation of the radiopharmaceutical by the semiquantitative analysis (0=Background activity, 1=Faint uptake, 2=Moderate uptake, 3=Marked uptake which is called as visually active joint score as severity index of the disease. To estimate the agreement between EPBS – HIG and LPBS - HIG in the determination of the presence and severity of inflammatory arthritis, 2x2 kappa coefficients were calculated. Results: Our results showed good agreement between EPBS - HIG for the presence of inflammation (kappa: 0.72 but not for the severity of the disease (kappa: 0.29, poor agreement between LPBS - HIG for both the presence (kappa: 0.51 and severity (kappa: 0.01 of inflammatory arthritis. Conclusion: The blood pool scintigraphy could be used in the investigation of the presence of inflammatory arthritis because the good agreement with HIG and the lower cost but not for the severity of the disease. (MIRT 2011;20:45-51

  4. Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2.

    Science.gov (United States)

    Spratlin, Jennifer L; Cohen, Roger B; Eadens, Matthew; Gore, Lia; Camidge, D Ross; Diab, Sami; Leong, Stephen; O'Bryant, Cindy; Chow, Laura Q M; Serkova, Natalie J; Meropol, Neal J; Lewis, Nancy L; Chiorean, E Gabriela; Fox, Floyd; Youssoufian, Hagop; Rowinsky, Eric K; Eckhardt, S Gail

    2010-02-10

    PURPOSE To evaluate the safety, maximum-tolerated dose (MTD), pharmacokinetics (PKs), pharmacodynamics, and preliminary anticancer activity of ramucirumab (IMC-1121B), a fully human immunoglobulin G(1) monoclonal antibody targeting the vascular endothelial growth factor receptor (VEGFR)-2. PATIENTS AND METHODS Patients with advanced solid malignancies were treated once weekly with escalating doses of ramucirumab. Blood was sampled for PK studies throughout treatment. The effects of ramucirumab on circulating vascular endothelial growth factor-A (VEGF-A), soluble VEGFR-1 and VEGFR-2, tumor perfusion, and vascularity using dynamic contrast-enhanced magnetic resonance imaging were assessed. Results Thirty-seven patients were treated with 2 to 16 mg/kg of ramucirumab. After one patient each developed dose-limiting hypertension and deep venous thrombosis at 16 mg/kg, the next lower dose (13 mg/kg) was considered the MTD. Nausea, vomiting, headache, fatigue, and proteinuria were also noted. Four (15%) of 27 patients with measurable disease had a partial response (PR), and 11 (30%) of 37 patients had either a PR or stable disease lasting at least 6 months. PKs were characterized by dose-dependent elimination and nonlinear exposure consistent with saturable clearance. Mean trough concentrations exceeded biologically relevant target levels throughout treatment at all dose levels. Serum VEGF-A increased 1.5 to 3.5 times above pretreatment values and remained in this range throughout treatment at all dose levels. Tumor perfusion and vascularity decreased in 69% of evaluable patients. CONCLUSION Objective antitumor activity and antiangiogenic effects were observed over a wide range of dose levels, suggesting that ramucirumab may have a favorable therapeutic index in treating malignancies amenable to VEGFR-2 inhibition.

  5. Expression of Immunoglobulin Receptors with Distinctive Features Indicating Antigen Selection by Marginal Zone B Cells from Human Spleen

    Science.gov (United States)

    Colombo, Monica; Cutrona, Giovanna; Reverberi, Daniele; Bruno, Silvia; Ghiotto, Fabio; Tenca, Claudya; Stamatopoulos, Kostas; Hadzidimitriou, Anastasia; Ceccarelli, Jenny; Salvi, Sandra; Boccardo, Simona; Calevo, Maria Grazia; De Santanna, Amleto; Truini, Mauro; Fais, Franco; Ferrarini, Manlio

    2013-01-01

    Marginal zone (MZ) B cells, identified as surface (s)IgMhighsIgDlowCD23low/−CD21+CD38− B cells, were purified from human spleens, and the features of their V(D)J gene rearrangements were investigated and compared with those of germinal center (GC), follicular mantle (FM) and switched memory (SM) B cells. Most MZ B cells were CD27+ and exhibited somatic hypermutations (SHM), although to a lower extent than SM B cells. Moreover, among MZ B-cell rearrangements, recurrent sequences were observed, some of which displayed intraclonal diversification. The same diversifying sequences were detected in very low numbers in GC and FM B cells and only when a highly sensitive, gene-specific polymerase chain reaction was used. This result indicates that MZ B cells could expand and diversify in situ and also suggested the presence of a number of activation-induced cytidine deaminase (AID)-expressing B cells in the MZ. The notion of antigen-driven expansion/selection in situ is further supported by the VH CDR3 features of MZ B cells with highly conserved amino acids at specific positions and by the finding of shared (“stereotyped”) sequences in two different spleens. Collectively, the data are consistent with the notion that MZ B cells are a special subset selected by in situ antigenic stimuli. PMID:23877718

  6. [Cloning and expression of a single human immunoglobulin heavy-chain variable domain with vascular endothelial growth factor binding activity].

    Science.gov (United States)

    Liu, Heng; Liu, Siguo; Wu, Yi; Zili, M; Liu, Yu; Zhang, Aimin; Chen, Jianquan; Cheng, Guoxiang

    2010-11-01

    In the application of therapeutic antibodies, large molecular weight of antibodies is always a problem that prevents them from penetrating into tissues or binding to antigenic determinants. To overcome this problem, we investigated the function of the heavy chain variable domain of a monoclonal anti-VEGF human IgM antibody derived from the Five-Feature Translocus Mice. We cloned the cDNA of the heavy chain variable domain, which was then inserted into pET28a vector and expressed in Escherichia coli. After purification and renaturation of the denatured recombinant protein, we obtained a 16 kDa antibody fragment, which is named as rhVVH. By immunoassaying its VEGF-binding capability in vitro, we proved that rhVVH retains this activity as the complete IgM. Importantly, rhVVH is shown to inhibit the HUVEC cell proliferation in a concentration-dependent manner. Our results indicate that the single heavy chain variable domain might inherit part of the biological function of the complete IgM antibody, which provided a valuable potential in further research on antibody miniaturisation.

  7. Immunoglobulin and fatty acids

    DEFF Research Database (Denmark)

    2009-01-01

    The present invention relates to a composition comprising 0.1-10 w/w % immunoglobulin (Ig), 4-14 w/w % saturated fatty acids, 4-14 w/w % mono-unsaturated fatty acids and 0-5 w/w % poly-unsaturated fatty acids, wherein the weight percentages are based on the content of dry matter in the composition...

  8. Molecular characterization of a human immunoglobulin G4 antibody specific for the major birch pollen allergen, Bet v 1.

    Science.gov (United States)

    Flicker, S; Steinberger, P; Eibensteiner, P B; Lebecque, S; Kraft, D; Valenta, R

    2008-02-01

    Allergen-specific IgG4 antibodies induced by specific immunotherapy are thought to represent a protective immune response. Objective Our aim was the molecular characterization of a human IgG4 antibody (BAB5) specific for the major birch pollen allergen Bet v 1 that was derived from an immunotherapy-treated patient. The cDNA coding for BAB5 was obtained by reverse transcriptase-PCR from the BAB5-producing cell line, compared with the germ line sequences and was expressed as a soluble antibody fragment in Escherichia coli. The epitope specificity and cross-reactivity of BAB5 were investigated with recombinant and synthetic Bet v 1 fragments and Bet v 1 homologous allergens from pollen. The ability of BAB5 to block allergic patients IgE was determined by competition experiments and sandwich ELISA. BAB5 is an affinity-matured Bet v 1-specific IgG4 antibody that reacts exclusively with Bet v 1 but not with Bet v 1-related allergens. Unlike an earlier-described monoclonal IgG1-blocking antibody, BAB1, which had been isolated from the same patient, BAB5 did not block allergic patients' IgE reactivity to Bet v 1. Our study demonstrates that not all allergen-specific IgG antibodies inhibit IgE recognition of allergens and can contribute to the success of immunotherapy. The epitope specificity and affinity of IgG antibodies but not their isotype are decisive for their protective activity.

  9. [Using the preparation "human immunoglobulin against herpes simplex virus type 1 for intramuscular injections" in the complex therapy of nervous system diseases].

    Science.gov (United States)

    Rudenko, A O; Diachenko, N S; Nesterova, N V; Kurishchuk, K V; Berestova, T H; Zahorodnia, S D; Riads'ka, L S; Muravs'ka, L V; Andrieieva, O H; Baranova, H V

    2004-01-01

    The technology of obtaining of specific immunoglobulin for serotherapy of neuroinfection caused by virus herpes simplex 1 type was developed. The patients presented with the following diseases: arachnoencephalitis, encephalopolyradiculoneuritis, encephalomyelitis, encephalitis, arachnoiditis, polyneuropathy, encephalomyelopolyradiculoneuritis, meningoencephalitis. The study showed good tolerance and safety of the medicine, no adverse effects registered during the study. The assessed median score of the efficacy was 2.8 from 3. The obtained results suggest using the liquid form preparation for intramuscular injection "Immunoglobulin for treatment of neuroinfection caused by virus herpes simplex type 1". The Close corporation "Biofarma" located in Kyiv produces this medicine.

  10. Recombinant human immunoglobulin (Ig)A1 and IgA2 anti-D used for detection of IgA deficiency and anti-IgA

    DEFF Research Database (Denmark)

    Nielsen, Leif K; Dziegiel, Morten Hanefeld

    2008-01-01

    To avoid anaphylactic reactions, immunoglobulin (Ig)A-deficient patients with anti-IgA should be transfused with IgA-deficient blood components. There is a need for fast and robust assays for demonstration of IgA deficiency and for detection of anti-IgA.......To avoid anaphylactic reactions, immunoglobulin (Ig)A-deficient patients with anti-IgA should be transfused with IgA-deficient blood components. There is a need for fast and robust assays for demonstration of IgA deficiency and for detection of anti-IgA....

  11. Safety and pharmacokinetics of hyperimmune anti-human immunodeficiency virus (HIV) immunoglobulin administered to HIV-infected pregnant women and their newborns. Pediatric AIDS Clinical Trials Group Protocol 185 Pharmacokinetic Study Group.

    Science.gov (United States)

    Lambert, J S; Mofenson, L M; Fletcher, C V; Moye, J; Stiehm, E R; Meyer, W A; Nemo, G J; Mathieson, B J; Hirsch, G; Sapan, C V; Cummins, L M; Jimenez, E; O'Neill, E; Kovacs, A; Stek, A

    1997-02-01

    The pharmacokinetics and safety of hyperimmune anti-human immunodeficiency virus (HIV) intravenous immunoglobulin (HIVIG) were evaluated in the first 28 maternal-infant pairs enrolled in a randomized, intravenous immunoglobulin (IVIG)-controlled trial of HIVIG maternal-infant HIV transmission prophylaxis. Using 200 mg/kg, mean half-life and volume of distribution (Vd) in women were 15 days and 72 mL/kg, respectively, after one and 32 days and 154 mL/kg after three monthly infusions, with stable 4 mL/kg/day clearance. Transplacental passage occurred. Newborn single-dose half-life, Vd, and clearance were 30 days, 143 mL/kg, and 4 mL/kg/day, respectively. HIVIG rapidly cleared maternal serum immune complex-dissociated p24 antigen, and plasma HIV-1 RNA levels were stable. Mild to moderate adverse clinical effects occurred in 2 of 103 maternal and 2 of 25 infant infusions. No adverse hematologic, blood chemistry, or immunologic effects were seen. HIVIG is well-tolerated in HIV-infected pregnant women and their newborns, clears antigenemia, crosses the placenta, and exhibits pharmacokinetics similar to those of other immunoglobulin preparations.

  12. [Selective immunoglobulin A deficiency].

    Science.gov (United States)

    Binek, Alicja; Jarosz-Chobot, Przemysława

    2012-01-01

    Immunoglobulin class A is the main protein of the mucosal immune system. Selective immunoglobulin A deficiency (sIgAD) is the most common primary immunodeficiency in Caucasians. sIGAD is strongly associated with the certain major histocompatibility complex region. Most individuals with sIgAD are asymptomatic and identified coincidentally. However, some patients may present with recurrent infections, allergic disorders and autoimmune manifestations. Several autoimmune diseases, such as systemic lupus erythematosus, diabetes mellitus type 1, Graves disease and celiac disease, are associated with an increased prevalence of sIgAD. Screening for sIgAD in coeliac disease is essential. Patients need treatment of associated diseases. It is also known that IgA deficiency may progress into a common variable immunodeficiency (CVID). Pathogenesis and molecular mechanism involved in sIgAD should be elucidated in the future.

  13. The flexibility of a generic LC-MS/MS method for the quantitative analysis of therapeutic proteins based on human immunoglobulin G and related constructs in animal studies.

    Science.gov (United States)

    Lanshoeft, Christian; Wolf, Thierry; Walles, Markus; Barteau, Samuel; Picard, Franck; Kretz, Olivier; Cianférani, Sarah; Heudi, Olivier

    2016-11-30

    An increasing demand of new analytical methods is associated with the growing number of biotherapeutic programs being prosecuted in the pharmaceutical industry. Whilst immunoassay has been the standard method for decades, a great interest in assays based on liquid chromatography tandem mass spectrometry (LC-MS/MS) is evolving. In this present work, the development of a generic method for the quantitative analysis of therapeutic proteins based on human immunoglobulin G (hIgG) in rat serum is reported. The method is based on four generic peptides GPSVFPLAPSSK (GPS), TTPPVLDSDGSFFLYSK (TTP), VVSVLTVLHQDWLNGK (VVS) and FNWYVDGVEVHNAK (FNW) originating from different parts of the fraction crystallizable (Fc) region of a reference hIgG1 (hIgG1A). A tryptic pellet digestion of rat serum spiked with hIgG1A and a stable isotope labeled protein (hIgG1B) used as internal standard (ISTD) was applied prior LC-MS/MS analysis. The upper limit of quantification was at 1000μg/mL. The lower limit of quantitation was for GPS, TTP and VVS at 1.00μg/mL whereas for FNW at 5.00μg/mL. Accuracy and precision data met acceptance over three days. The presented method was further successfully applied to the quantitative analysis of other hIgG1s (hIgG1C and hIgG1D) and hIgG4-based therapeutic proteins on spiked quality control (QC) samples in monkey and rat serum using calibration standards (Cs) prepared with hIgG1A in rat serum. In order to extend the applicability of our generic approach, a bispecific-bivalent hIgG1 (bb-hIgG1) and two lysine conjugated antibody-drug conjugates (ADC1 and ADC2) were incorporated as well. The observed values on spiked QC samples in monkey serum were satisfactory with GPS for the determination of bb-hIgG1 whereas the FNW and TTP peptides were suitable for the ADCs. Moreover, comparable mean concentration-time profiles were obtained from monkeys previously dosed intravenously with ADC2 measured against Cs samples prepared either with hIgG1A in rat serum

  14. Immunoglobulin genes of the turtles.

    Science.gov (United States)

    Magadán-Mompó, Susana; Sánchez-Espinel, Christian; Gambón-Deza, Francisco

    2013-03-01

    The availability of reptile genomes for the use of the scientific community is an exceptional opportunity to study the evolution of immunoglobulin genes. The genome of Chrysemys picta bellii and Pelodiscus sinensis is the first one that has been reported for turtles. The scanning for immunoglobulin genes resulted in the presence of a complex locus for the immunoglobulin heavy chain (IGH). This IGH locus in both turtles contains genes for 13 isotypes in C. picta bellii and 17 in P. sinensis. These correspond with one immunoglobulin M, one immunoglobulin D, several immunoglobulins Y (six in C. picta bellii and eight in P. sinensis), and several immunoglobulins that are similar to immunoglobulin D2 (five in C. picta belli and seven in P. sinensis) that was previously described in Eublepharis macularius. It is worthy to note that IGHD2 are placed in an inverted transcriptional orientation and present sequences for two immunoglobulin domains that are similar to bird IgA domains. Furthermore, its phylogenetic analysis allows us to consider about the presence of IGHA gene in a primitive reptile, so we would be dealing with the memory of the gene that originated from the bird IGHA. In summary, we provide a clear picture of the immunoglobulins present in a turtle, whose analysis supports the idea that turtles emerged from the evolutionary line from the differentiation of birds and the presence of the IGHA gene present in a common ancestor.

  15. Competencia Cultural: Una forma humanizada de ofrecer Cuidados de Enfermería Cultural competence: a humane form of offering Nursing Care

    Directory of Open Access Journals (Sweden)

    Teresa Ximena Ibarra Mendoza

    2006-03-01

    Full Text Available La actual dinámica social, hace que el cuidado de Enfermería se convierta en un desafío permanente, pues debe considerar los valores, creencias y prácticas de individuos que tiene bajo su cuidado, así como manifestar el respeto por la diferencia cuando ofrece dicho cuidado. El presente trabajo muestra las dimensiones que el profesional de Enfermería debería considerar al ofrecer cuidado, dada la incidencia en la diversidad cultural de los grupos humanos bajo la perspectiva de la competencia cultural. En el desarrollo del trabajo se define la diversidad cultural como elemento de valoración en Enfermería y los constructos que el modelo incluye para adquirir la competencia cultural. Es a partir del desarrollo de estos puntos cuando se puede llegar a entender el papel del profesional de enfermería bajo la dimensión transcultural, siempre teniendo como referencia que para propiciar Cuidados de Enfermería de calidad, el profesional debe tener conocimiento, sensibilidad y disposición para colaborar en ello. La aceptación y respeto por las diferencias culturales, la sensibilidad para entender cómo esas diferencias influyen en las relaciones con las personas, y la habilidad para ofrecer estrategias que mejoren los encuentros culturales, son requisitos indispensables para que el cuidado transcultural en enfermería se pueda consolidar.The current social dynamics require that the Nursing treatment becomes a permanent challenge, as it has to consider the values, beliefs and practices of the individuals that are under its care, as much as it has to manifest respect for the differences when the attention is being offered. The present paper is intended to expose the dimensions that the Nursing Professional should consider when offering treatment, given the incidence in the cultural diversity of the human groups under the perspective of the cultural competence. In the development of this work, cultural diversity is defined as a valuation element

  16. Measuring Immunoglobulin G Antibodies to Tetanus Toxin, Diphtheria Toxin, and Pertussis Toxin with Single-Antigen Enzyme-Linked Immunosorbent Assays and a Bead-Based Multiplex Assay▿

    OpenAIRE

    Reder, Sabine; Riffelmann, Marion; Becker, Christian; Wirsing von König, Carl Heinz

    2008-01-01

    Bead-based assay systems offer the possibility of measuring several specific antibodies in one sample simultaneously. This study evaluated a vaccine panel of a multianalyte system that measures antibodies to tetanus toxin, diphtheria toxin, and pertussis toxin (PT) from Bordetella pertussis. The antibody concentrations of human immunoglobulin G (IgG) to PT, tetanus toxin, and diphtheria toxin were measured in 123 serum pairs (total of 246 sera) from a vaccine study. The multianalyte bead assa...

  17. Neutralizing activities of human immunoglobulin derived from donors in Japan against mosquito-borne flaviviruses, Japanese encephalitis virus, West Nile virus, and dengue virus

    Directory of Open Access Journals (Sweden)

    Yunoki M

    2016-07-01

    Full Text Available Mikihiro Yunoki,1-3 Takeshi Kurosu,2 Ritsuko Kubota Koketsu,2,4 Kazuo Takahashi,5 Yoshinobu Okuno,4 Kazuyoshi Ikuta2,4 1Research and Development Division, Japan Blood Products Organization, Tokyo, 2Department of Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, 3Pathogenic Risk Evaluation, Graduate School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, 4Research and Development Division, The Research Foundation for Microbial Diseases of Osaka University, Kagawa, 5Osaka Prefectural Institute of Public Health, Osaka, Japan Abstract: Japanese encephalitis virus (JEV, West Nile virus (WNV, and dengue virus (DenV are causal agents of Japanese encephalitis, West Nile fever, and dengue fever, respectively. JEV is considered to be indigenized and widespread in Japan, whereas WNV and DenV are not indigenized in Japan. Globulin products seem to reflect the status of the donor population according to antivirus neutralization activity. However, the anti-JEV, -WNV, and -DenV neutralization activities of globulin products derived from donors in Japan have not been clarified. Furthermore, potential candidates for the development of an effective immunotherapeutic drug for encephalitis caused by JEV, WNV, or DenV have also not been identified. Therefore, the aim of this study was to determine the overall status of the donor population in Japan based on globulin products by evaluating anti-JEV, -WNV, and -DenV neutralizing activities of intravenous immunoglobulin. Overall, intravenous immunoglobulin products showed stable neutralizing activity against JEV but showed no or only weak activity against WNV or DenV. These results suggest that the epidemiological level against WNV and DenV in the donor population of Japan is still low, suggesting that these viruses are not yet indigenized. In addition, JEV vaccinations and/or infections in the donor population do not induce a cross-reactive antibody against WNV. Keywords

  18. Cytomegalovirus Immunoglobulin After Thoracic Transplantation

    Science.gov (United States)

    Grossi, Paolo; Mohacsi, Paul; Szabolcs, Zoltán; Potena, Luciano

    2016-01-01

    Abstract Cytomegalovirus (CMV) is a highly complex pathogen which, despite modern prophylactic regimens, continues to affect a high proportion of thoracic organ transplant recipients. The symptomatic manifestations of CMV infection are compounded by adverse indirect effects induced by the multiple immunomodulatory actions of CMV. These include a higher risk of acute rejection, cardiac allograft vasculopathy after heart transplantation, and potentially bronchiolitis obliterans syndrome in lung transplant recipients, with a greater propensity for opportunistic secondary infections. Prophylaxis for CMV using antiviral agents (typically oral valganciclovir or intravenous ganciclovir) is now almost universal, at least in high-risk transplants (D+/R−). Even with extended prophylactic regimens, however, challenges remain. The CMV events can still occur despite antiviral prophylaxis, including late-onset infection or recurrent disease, and patients with ganciclovir-resistant CMV infection or who are intolerant to antiviral therapy require alternative strategies. The CMV immunoglobulin (CMVIG) and antiviral agents have complementary modes of action. High-titer CMVIG preparations provide passive CMV-specific immunity but also exert complex immunomodulatory properties which augment the antiviral effect of antiviral agents and offer the potential to suppress the indirect effects of CMV infection. This supplement discusses the available data concerning the immunological and clinical effects of CMVIG after heart or lung transplantation. PMID:26900989

  19. The comparison of the WHO standard rabies immunoglobulin and the national standard Human rabies immunogiobulin used in the rapid fluorescent focus inhibition test (RFFIT)%狂犬病抗血清WHO标准品和国家标准品用于RFFIT方法的比较

    Institute of Scientific and Technical Information of China (English)

    于鹏程; 申辛欣; 吕新军; 单虎; 唐青

    2010-01-01

    目的 比较狂犬病快速荧光灶抑制试验(RFFIT)方法中狂犬病免疫球蛋白WHO标准品和狂犬患者免疫球蛋白国家标准品为参照所得结果的差异.方法 在同一次RFFIT试验中同时设置WHO标准品参照和国家标准品参照,同时测定12份待测人血清,比较两种标准品所产生荧光灶的百分比;按照中和抗体滴度计算公式计算不同标准品参照所得12份待测血清抗体滴度,比较其差异.结果 结果显示WHO标准品和国家标准品的50%感染量均出现在第5孔和第6孔之间,但国家标准品荧光灶百分比低于WHO标准品;以WHO标准品做参照所得到的同一份血清滴度略高于国家标准品.结论 WHO标准品和国家标准品在RFFIT方法中存在差异,但不影响结果判定.%Objective Compare the difference of the results referred to the WHO standard rabies immunoglobulin and the national standard human rabies immunoglobulin used in the rapid fluorescent focus inhibition test (RFFIT).Methods Setting the WHO standard immunoglobulin and the national standard immunoglobulin in the same system and testing 12 human serum at the same time.Compare the fluorescence percentage of the two different standard immunoglobulin;compare the 12 serum results calculated from the two different standard immunoglobulin used the calculation formula of neutralization antibody titer.Results The Results display that the 50% percent of the two standard immunoglobulin are all between the fifth and the sixth well,but the percentage of the national standard immunoglobulin is lower than the WHO one.The same testserum result calculated from the WHO standard immunoglobulin is little higher than the national one.Conclusion There is difference in the WHO standard immunoglobulin and the national one,but there is no influence in the results.

  20. Milk immunoglobulins and complement factors.

    Science.gov (United States)

    Korhonen, H; Marnila, P; Gill, H S

    2000-11-01

    The importance of colostrum for the growth and health of newborn offspring is well known. In bovine colostrum, the antibody (immunoglobulin) complement system provides a major antimicrobial effect against a wide range of microbes and confers passive immunity until the calf's own immune system has matured. Bovine serum and lacteal secretions contain three major classes of immunoglobulins: IgG, IgM and IgA. The immunoglobulins are selectively transported from the serum into the mammary gland, as a result of which the first colostrum contains very high concentrations of immunoglobulins (40-200 mg/ml). IgG1 accounts for over 75 % of the immunoglobulins in colostral whey, followed by IgM, IgA and IgG2. All these immunoglobulins decrease within a few days to a total immunoglobulin concentration of 0.7-1.0 mg/ml, with IgG1 representing the major Ig class in milk throughout the lactation period. Together with the antibodies absorbed from colostrum after birth, the complement system plays a crucial role in the passive immunisation of the newborn calf. The occurrence of haemolytic or bactericidal complement activity in bovine colostrum and milk has been demonstrated in several studies. This review deals with the characteristics of bovine Igs and the complement system to be exploited as potential ingredients for health-promoting functional foods.

  1. Initial Public Offering

    OpenAIRE

    Veselý, Marek

    2009-01-01

    Thesis describes initial public offering on the stock markets. There are mentioned basic phases of this process. In this thesis is named pros & cons of this source of financing. Recommends also other ways how to gain capital for own company business acitivities. Thesis is interested about main conditions for successfull "going public". Initial Public Offering of bonds is described too. Practical part of this thesis is concern IPO in the Czech Republic -- historical data, IPO in the past on Pr...

  2. Laser-based microdissection of single cells from tissue sections and PCR analysis of rearranged immunoglobulin genes from isolated normal and malignant human B cells.

    Science.gov (United States)

    Küppers, Ralf; Schneider, Markus; Hansmann, Martin-Leo

    2013-01-01

    Normal and malignant B cells carry rearranged immunoglobulin (Ig) variable region genes, which due to their practically limitless diversity represent ideal clonal markers for these cells. We describe here an approach to isolate single cells from frozen tissue sections by microdissection using a laser-based method. From the isolated cells rearranged IgH and Igκ genes are amplified in a semi-nested PCR approach, using a collection of V gene family-specific primers recognizing nearly all V gene segments together with primers for the J gene segments. By sequence analysis of V genes from distinct cells, the clonal relationship of the B lineage cells can unequivocally be determined and related to the histological distribution of the cells. The approach is also useful to determine V, D, and J gene usage. Moreover, the presence and pattern of somatic Ig V gene mutations give valuable insight into the stage of differentiation of the B cells.

  3. Protamine coated proliposomes of recombinant human insulin encased in Eudragit S100 coated capsule offered improved peptide delivery and permeation across Caco-2 cells.

    Science.gov (United States)

    Sharma, Shiva; Jyoti, Kiran; Sinha, Richa; Katyal, Anju; Jain, Upendra Kumar; Madan, Jitender

    2016-10-01

    In present investigation, recombinant human insulin loaded proliposomes and protamine sulphate coated proliposomes (rh insulin-proliposomes and Pt-rh insulin proliposomes) were encased in Eudragit S100 coated capsule to offer peptide release in simulated intestinal conditions. The particle size and zeta potential of Pt-rh insulin proliposomes were measured to be 583.2±10.2nm/+28.3±3.7mV significantly (P<0.05) higher than 569.7±14.9nm/-37.9±4.3mV and 534.6±24.6nm/-42.7±2.8mV of rh insulin proliposomes and proliposomes, respectively. Next, shape and surface morphology analysis pointed out the successful transformation of proliposomes in to spherical shaped liposomes. Furthermore, in vitro release study specified that free rh insulin solution encapsulated in uncoated gelatine capsule released 97.8% of peptide within 1h in SGF (pH~1.2). On other hand, rh insulin-proliposomes and Pt-rh insulin proliposomes encased in Eudragit S100 coated capsule released 93.2% and 81.6% of peptide, up to 24 h in SIF (pH~7.2). SDS-PAGE and circular dichroism (CD) ascertained the stability and intactness of isolated rh insulin from tailored dosage forms. In last, cellular uptake in Caco-2 cells indicating the superiority of Pt-rh insulin proliposomes in comparison to rh-insulin proliposomes and free rh insulin solution, respectively. In conclusion, Pt-rh insulin proliposomes displayed promising results and may be considered for further investigations.

  4. [BIOLOGICAL AND IMMUNOCHEMICAL PROPERTIES OF POLYREACTIVE IMMUNOGLOBULINS].

    Science.gov (United States)

    Bobrovnik, S A; Demchenko, M A; Komisarenko, S V

    2015-01-01

    A previously unknown phenomenon of acquired polyreactivity for serum immunoglobulins, which were subjected either to solutions of KSCN (3.0-5.0 M), low/high pH (pH 2.2-3.0), or heating to 58-60 degrees C, was described by us in 1990 year. Much later, eleven years after that, similar data were published by others, which completely confirmed our results concerning the influence of either chaotropic ions or the drastic shift of pH on immunoglobulins polyreactive properties. Our further investigations of polyreactive serum immunoglobulins (PRIG) properties have shown that the mechanism of non-specific interaction between PRIG and antigens much differs from the mechanism of interaction between specific antibodies and corresponding antigens. Later we have shown that the increasing of PRIG reactivity could be induced in vivo, and PRIG are one of serum components for human or animal sera. Then, it could be suggested that PRIG can perform certain biological functions. Studying of PRIG's effect on the phagocytosis of microbes by peritoneal cells or the tumor growth have shown that PRIG can play a certain role in protecting the body from infections and probably can influence on the development of various pathological processes. Recently we have also found that PRIG IgG contents significantly increases in aged people. These data demonstrate that further investigations of PRIG's immunochemical properties and studying of their biological role in organism protection from various diseases is very intriguing and important.

  5. Characterization of antibodies against ferret immunoglobulins, cytokines and CD markers

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Aasted, Bent

    2009-01-01

    immunoglobulins, we identified and characterized polyclonal antibodies towards ferret IgG, IgM and IgA. We also identified 22 monoclonal antibodies (mAbs) raised mostly against human CD markers which cross-reacted with ferret leukocytes. These antibodies were originally specific against human CD8, CD9, CD14, CD18...

  6. Pasteurization of IgM-enriched Immunoglobulin

    Directory of Open Access Journals (Sweden)

    Kamran Mousavi Hosseini

    2004-06-01

    Full Text Available Human plasma proteins are important for therapy or prophylaxis of human diseases. Due to the preparation of human plasma proteins from human plasma pools and risk of contamination with human viruses, different viral reduction treatments such as: pasteurization, solvent/detergent, dry heat treatment, steam treatment, beta-propiolactone/UV and nanofiltration have been implemented. As pasteurization can be performed for liquid protein, this method (a 10-hour heat treatment of the aqueous solutions at 60°C was introduced into the manufacturing procedure of IgM-enriched immunoglobulin, to improve its safety further. The efficiency of this method for inactivation of viruses was evaluated by the use of Foot-and-Mouth Disease Virus (a non-enveloped virus and Infectious Bovine Rhinotracheitis (IBR Virus (a lipid-enveloped virus. Pasteurization inactivated Foot-and-Mouth Disease Virus by 7 log10 and for IBR Virus by 5log10. These findings show a significant added measure of virus safety associated with pasteurization of IgM-enriched immunoglobulin preparation.

  7. VIP Programs Offer More

    Institute of Scientific and Technical Information of China (English)

    ISABELDING

    2005-01-01

    When choosing a hotel, service standards are a high priority for customers, with the quality of service often reflecting a hotel's standing.While most hotels try to provide the beststandard possible to their guest, many also offer special VIP programs that provide vale-added service and reward customer loyalty.

  8. Validation of the World Health Organization Enzyme-Linked Immunosorbent Assay for the Quantitation of Immunoglobulin G Serotype-Specific Anti-Pneumococcal Antibodies in Human Serum.

    Science.gov (United States)

    Lee, Hyunju; Lim, Soo Young; Kim, Kyung Hyo

    2017-10-01

    The World Health Organization (WHO) enzyme-linked immunosorbent assay (ELISA) guideline is currently accepted as the gold standard for the evaluation of immunoglobulin G (IgG) antibodies specific to pneumococcal capsular polysaccharide. We conducted validation of the WHO ELISA for 7 pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) by evaluating its specificity, precision (reproducibility and intermediate precision), accuracy, spiking recovery test, lower limit of quantification (LLOQ), and stability at the Ewha Center for Vaccine Evaluation and Study, Seoul, Korea. We found that the specificity, reproducibility, and intermediate precision were within acceptance ranges (reproducibility, coefficient of variability [CV] ≤ 15%; intermediate precision, CV ≤ 20%) for all serotypes. Comparisons between the provisional assignments of calibration sera and the results from this laboratory showed a high correlation > 94% for all 7 serotypes, supporting the accuracy of the ELISA. The spiking recovery test also fell within an acceptable range. The quantification limit, calculated using the LLOQ, for each of the serotypes was 0.05-0.093 μg/mL. The freeze-thaw stability and the short-term temperature stability were also within an acceptable range. In conclusion, we showed good performance using the standardized WHO ELISA for the evaluation of serotype-specific anti-pneumococcal IgG antibodies; the WHO ELISA can evaluate the immune response against pneumococcal vaccines with consistency and accuracy. © 2017 The Korean Academy of Medical Sciences.

  9. Simultaneous administration of {sup 111}In-human immunoglobulin and {sup 99m}Tc-HMPAO labelled leucocytes in inflammatory bowel disease

    Energy Technology Data Exchange (ETDEWEB)

    Mairal, L. [Dept. of Nuclear Medicine, CSUB, Hospital Princeps d`Espanya, Barcelona (Spain); Lima, P.A. de [Bolsista do Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Brazil); Martin-Comin, J. [Dept. of Nuclear Medicine, CSUB, Hospital Princeps d`Espanya, Barcelona (Spain); Baliellas, C. [Dept. of Gastroenterology, CSUB, Hospital Princeps d`Espanya, Barcelona (Spain); Xiol, X. [Dept. of Gastroenterology, CSUB, Hospital Princeps d`Espanya, Barcelona (Spain); Roca, M. [Dept. of Nuclear Medicine, CSUB, Hospital Princeps d`Espanya, Barcelona (Spain); Ricart, Y. [Dept. of Nuclear Medicine, CSUB, Hospital Princeps d`Espanya, Barcelona (Spain); Ramos, M. [Dept. of Nuclear Medicine, CSUB, Hospital Princeps d`Espanya, Barcelona (Spain)

    1995-07-01

    Technetium-99m hexamethylpropylene amine oxime (HMPAO) labelled leucocytes and indium-111 polyclonal immunoglobulin (IgG) were simultaneously injected into a group of 27 patients routinely referred for the investigation of inflammatory bowel disease (IBD). Ten-minute anterior abdomen and tail on detector views were obtained at 30 min, 4 h and 24 h p.i. of both tracers. The diagnosis of IBD was obtained in all cases by endoscopy with biopsy and/or surgery. Images were blindly evaluated by two experienced observers who only knew of the clinical suspicion of IBD. IBS was confirmed in 20 patients (12 with Crohn`s disease and eight with ulcerative colitis). Sensitivity, specificity and accuracy were 100%, 85% and 96% respectively for labelled leucocytes and 70%, 85% and 74% for IgG. Both IgG and leucocyte scans were normal in six out of seven patients in whom a diagnosis of IBD was excluded; the remaining patient, with ischaemic colitis, was falsely positive with both agents. As far as disease extension is concerned, the IgG study localized 27 diseased segments, whereas 49 were seen with the leucocyte study. Eighty-four segments were normal and 25 showed tracer uptake with both agents. Twenty-four were positive only with the leucocyte study and two were positive only with the IgG study. Agreement between the agents was 80.7%. (orig./UG)

  10. Offers for our members

    CERN Multimedia

    Staff Association

    2013-01-01

    The Courir shops propose the following offer: 15% discount on all articles (not on sales) in the Courir shops (Val Thoiry, Annemasse and Neydens) and 5% discount on sales upon presentation of your Staff Association membership card and an identity card before payment. Summer is here, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 21 € instead of 26 €. Access to Aqualibi: 5 € instead of 8 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12 h 00. Free for children under 3, with limited access to the attractions. Car park free. * * * * * Aquaparc : Day ticket: – Children: 30 CHF instead of 39 CHF – Adults : 36 CHF instead of 49 CHF Bonus! Free for children under 5.

  11. Offers for our members

    CERN Multimedia

    Staff Association

    2017-01-01

    Summer is coming, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 24 € instead of 30 €. Access to Aqualibi: 5 € instead of 6 € on presentation of your SA member ticket. Free for children under 100 cm. Car park free. * * * * * Aquaparc : Day ticket: – Children: 33 CHF instead of 39 CHF – Adults : 33 CHF instead of 49 CHF Bonus! Free for children under 5.

  12. Offers for our members

    CERN Multimedia

    Staff Association

    2017-01-01

    Summer is here, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 24 € instead of 30 €. Access to Aqualibi: 5 € instead of 6 € on presentation of your SA member ticket. Free for children under 100 cm. Car park free. * * * * * Aquaparc : Day ticket: – Children: 33 CHF instead of 39 CHF – Adults : 33 CHF instead of 49 CHF Bonus! Free for children under 5.

  13. Offers for our members

    CERN Multimedia

    Staff Association

    2017-01-01

    Summer is here, enjoy our offers for the water parks! Walibi: Tickets "Zone terrestre": 24 € instead of 30 €. Access to Aqualibi: 5 € instead of 6 € on presentation of your ticket purchased at the Staff Association. Bonus! Free for children under 100 cm, with limited access to the attractions. Free car park. *  *  *  *  *  *  *  * Aquaparc: Day ticket: -  Children: 33 CHF instead of 39 CHF -  Adults : 33 CHF instead of 49 CHF Bonus! Free for children under 5 years old.

  14. Offers for our members

    CERN Multimedia

    Staff Association

    2016-01-01

    Summer is here, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 23 € instead of 29 €. Access to Aqualibi: 5 € instead of 6 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12:00 p.m. Free for children under 3, with limited access to the attractions. Car park free. * * * * * Aquaparc : Day ticket: – Children: 33 CHF instead of 39 CHF – Adults : 33 CHF instead of 49 CHF Bonus! Free for children under 5.

  15. Offers for our members

    CERN Multimedia

    Staff Association

    2016-01-01

    Summer is here, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 23 € instead of 29 €. Access to Aqualibi: 5 € instead of 6 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12:00 p.m. Free for children under 3, with limited access to the attractions. Car park free. * * * * * Aquaparc : Day ticket: – Children: 33 CHF instead of 39 CHF – Adults : 33 CHF instead of 49 CHF Bonus! Free for children under 5.

  16. Offers for our members

    CERN Multimedia

    Staff Association

    2015-01-01

    Summer is here, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 21,50 € instead of 27 €. Access to Aqualibi: 5 € instead of 6 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12:00 p.m. Free for children under 3, with limited access to the attractions. Car park free. * * * * * Aquaparc : Day ticket: – Children: 33 CHF instead of 39 CHF – Adults : 33 CHF instead of 49 CHF Bonus! Free for children under 5.

  17. Offers for our members

    CERN Multimedia

    Staff Association

    2013-01-01

    Summer is here, enjoy our offers for the aquatic parcs! Walibi : Tickets "Zone terrestre": 21 € instead of 26 €. Access to Aqualibi: 5 € instead of 8 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12 h 00. Free for children under 3, with limited access to the attractions. Car park free. * * * * * Aquaparc : Day ticket: – Children: 30 CHF instead of 39 CHF – Adults : 36 CHF instead of 49 CHF Bonus! Free for children under 5.

  18. Hyaluronidase facilitated subcutaneous immunoglobulin in primary immunodeficiency

    Directory of Open Access Journals (Sweden)

    Jolles S

    2013-09-01

    Full Text Available Stephen Jolles Department of Immunology, University Hospital of Wales, Cardiff, UK Abstract: Immunoglobulin (Ig-replacement therapy represents the mainstay of treatment for patients with primary antibody deficiency and is administered either intravenously (IVIg or subcutaneously (SCIg. While hyaluronidase has been used in clinical practice for over 50 years, the development of a high-purity recombinant form of this enzyme (recombinant human hyaluronidase PH20 has recently enabled the study of repeated and more prolonged use of hyaluronidase in facilitating the delivery of SC medicines. It has been used in a wide range of clinical settings to give antibiotics, local anesthetics, insulin, morphine, fluid replacement, and larger molecules, such as antibodies. Hyaluronidase has been used to help overcome the limitations on the maximum volume that can be delivered into the SC space by enabling dispersion of SCIg and its absorption into lymphatics. The rate of facilitated SCIg (fSCIg infusion is equivalent to that of IVIg, and the volume administered at a single site can be greater than 700 mL, a huge increase over conventional SCIg, at 20–40 mL. The use of fSCIg avoids the higher incidence of systemic side effects of IVIg, and it has higher bioavailability than SCIg. Data on the long-term safety of this approach are currently lacking, as fSCIg has only recently become available. fSCIg may help several areas of patient management in primary antibody deficiency, and the extent to which it may be used in future will depend on long-term safety data and cost–benefit analysis. Keywords: enzyme facilitated IgG infusion, recombinant human hyaluronidase PH20, subcutaneous immunoglobulin, intravenous immunoglobulin, primary immunodeficiency disease

  19. Use of intravenous immunoglobulin in neonates with haemolytic disease and immune thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Marković-Sovtić Gordana

    2013-01-01

    Full Text Available Background/Aim. Intravenous immunoglobulin is a blood product made of human polyclonal immunoglobulin G. The mode of action of intravenous immunoglobulin is very complex. It is indicated in treatment of neonatal immune thrombocytopenia and haemolytic disease of the newborn. The aim of the study was to present our experience in the use of intravenous immunoglobulin in a group of term neonates. Methods. We analysed all relevant clinical and laboratory data of 23 neonates who recieved intravenous immunoglobulin during their hospitalization in Neonatal Intensive Care Unit of Mother and Child Health Care Institute over a five year period, from 2006. to 2010. Results. There were 11 patients with haemolytic disease of the newborn and 12 neonates with immune thrombocytopenia. All of them recieved 1-2 g/kg intravenous immunoglobulin in the course of their treatment. There was no adverse effects of intravenous immunoglobulin use. The use of intravenous immunoglobulin led to an increase in platelet number in thrombocytopenic patients, whereas in those with haemolytic disease serum bilirubin level decreased significantly, so that some patients whose bilirubin level was very close to the exchange transfusion criterion, avoided this procedure. Conclusion. The use of intravenous immunoglobulin was shown to be an effective treatment in reducing the need for exchange transfusion, duration of phototherapy and the length of hospital stay in neonates with haemolytic disease. When used in treatment of neonatal immune thrombocytopenia, it leads to an increase in the platelet number, thus decreasing the risk of serious complications of thrombocytopenia.

  20. Offers for our members

    CERN Multimedia

    Staff Association

    2013-01-01

    The warm weather arrives, it's time to take advantage of our offers Walibi and Aquapark! Walibi : Tickets "Zone terrestre": 21 € instead of 26 € Access to Aqualibi: 5 € instead of 8 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12 h 00. Free for children under 3, with limited access to the attractions. Car park free. * * * * * Aquaparc : Half-day ticket (5 hours): – Children: 26 CHF instead of 35 CHF – Adults : 32 CHF instead of 43 CHF Day ticket: – Children: 30 CHF instead of 39 CHF – Adults : 36 CHF instead of 49 CHF Free for children under 5.

  1. Offers for our members

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    Association du personnel

    2013-01-01

    La banque LCL propose aux membres de l’Association du personnel les avantages suivants : – Un barème Privilège sur le Prêt immobilier – Des avantages tarifaires sur l’épargne, notamment l’assurance-vie. – Un taux préférentiel de prêt à la consommation. En outre, jusqu’au 30 septembre 2013, elle offre 50€ à tous les nouveaux clients, membres de l'Association du personnel. Summer is here, enjoy our offers for the aquatic parcs! Tickets "Zone terrestre" : 21 € instead of de 26 €. Access to Aqualibi : 5 euros instead of 8 euros on presentation of your SA member ticket. Free for children (3-11 years old) before 12 h 00. Free for children under 3, with limited access to the attractions. Free car park. * * * * * * * Full day ticket: – Children : 30 CHF instead of 39 CHF &...

  2. Methods for chromatofocusing of cerebrospinal fluid and serum immunoglobulin G.

    Science.gov (United States)

    Gallo, P; Olsson, O; Sidén, A

    1985-06-26

    Chromatofocusing programs were designed for separations of submilligram amounts of normal and abnormal human IgG. The Pharmacia FPLC system, equipped with a Mono P column or a specially designed, small column was used for the separations. Normal IgG in paired cerebrospinal fluid and serum samples, paired samples from patients with intrathecal immunoglobulin G synthesis, as well as sera with IgG M components were examined. Abnormal immunoglobulin G components, especially those with pI values greater than ca. 7.0 pH units, were easily identified.

  3. Efficacy of hepatitis B immunoglobulin in relation to the gene polymorphisms of human leukocyte Fcγ receptor Ⅲ (CD16) in Chinese liver transplant patients

    Institute of Scientific and Technical Information of China (English)

    WANG Wei-lin; ZHENG Shu-sen; ZHANG Guo-liang; WU Li-hua; YAO Min-ya; JIN Jing; JIA Chang-ku; XIE Hai-yang; ZHOU Lin; JIANG Zhi-jun

    2007-01-01

    Background Although the use of hepatitis B immunoglobulin (HBIG) may lead to a significant reduction in recurrent hepatitis B virus (HBV) infection and improve the survival of patients who have undergone liver transplantation (LT) for hepatitis B-related diseases, the recurrence of the disease still remains at a lower level. Different clinical curative effects were observed in patients with the same HBV-related diseases and the same therapy. This study was undertaken to investigate whether the efficacy of HBIG is associated with FCGR3A gene polymorphisms in Chinese liver transplant patients.Methods Altogether 77 patients who had received liver transplantation for hepatitis B-related diseases with more than one-year survival after surgery were studied. The recurrence of HBV was characterized by the appearance of HBsAg in serum after the operation. The FCGR3A genotyping was performed using genomic DNA sequencing (ABI 3037). Single nucleotide polymorphism at nucleotide 559 was detected by Polyphred.Results Of the 77 patients, 14 were complicated with HBV recurrence post-transplant. The FCGR3A at nucleotide 559 TT was observed in 35 (45.5%) subjects, whereas TG in 31(40.3%) and GG in 11(14.3%). In the 559G carrier group (n=42, 54.5%), the risk of HBV recurrence was 9.5%, and 1- and 2-year recurrence-free survival rates were 95.2% and 88.7%, respectively. In the 559G noncarrier group (n=35, 45.5%), the risk of HBV recurrence was 28.6%, and 1- and 2-year recurrence-free survival rates were 74.3% and 69.3%, respectively. The risk of HBV recurrence and the recurrence-free survival rate were both statistically different between the 559G carrier and noncarrier groups (P<0.05).Conclusions A single nucleotide polymorphism (T/G) at position 559 of the FCGR3A gene was found in Chinese patients. The efficacy of HBIG in prophylaxis of HBV recurrence after LT is associated with the gene polymorphism, so detecting FCGR3A genotypes can be a clinical reference of the HBIG

  4. Combination of Human Leukocyte Antigen and Killer Cell Immunoglobulin-Like Receptor Genetic Background Influences the Onset Age of Hepatocellular Carcinoma in Male Patients with Hepatitis B Virus Infection

    Directory of Open Access Journals (Sweden)

    Ning Pan

    2013-01-01

    Full Text Available To investigate whether killer cell immunoglobulin-like receptor (KIR and human leukocyte antigen (HLA genetic background could influence the onset age of hepatocellular carcinoma (HCC in patients with hepatitis B virus (HBV infection, one hundred and seventy-one males with HBV-related HCC were enrolled. The presence of 12 loci of KIR was detected individually. HLA-A, -B, and -C loci were genotyped with high resolution by a routine sequence-based typing method. The effect of each KIR locus, HLA ligand, and HLA-KIR combination was examined individually by Kaplan-Meier (KM analysis. Multivariate Cox hazard regression model was also applied. We identified C1C1-KIR2DS2/2DL2 as an independent risk factor for earlier onset age of HCC (median onset age was 44 for C1C1-KIR2DS2/2DL2 positive patients compared to 50 for negative patients, P=0.04 for KM analysis; HR = 1.70, P=0.004 for multivariate Cox model. We conclude that KIR and HLA genetic background can influence the onset age of HCC in male patients with HBV infection. This study may be useful to improve the current HCC surveillance program in HBV-infected patients. Our findings also suggest an important role of natural killer cells (or other KIR-expressing cells in the progress of HBV-related HCC development.

  5. Mecanismos de acción de la inmunoglobulina humana en las enfermedades dermatológicas pediátricas Action mechanisms of human immunoglobulin in pediatric dermatological diseases

    Directory of Open Access Journals (Sweden)

    Alain R. Rodríguez Orozco

    2007-12-01

    Full Text Available El uso de inmunomoduladores en dermatología pediátrica ha devenido necesidad de la práctica clínica contemporánea. Por otro lado, el continuo descubrimiento de moléculas involucradas en la fisiopatología de muchas enfermedades dermatológicas asociadas a trastornos inmunológicos obliga a revisar continuamente las aplicaciones de estos. El presente trabajo propone mostrar algunos mecanismos de acción que justifican el uso de la inmunoglobulina humana en algunas enfermedades dermatológicas pediátricas y facilita al médico la discusión sobre la conveniencia del uso de estas a la luz de la fisiopatología actual de estas enfermedades y del estado del paciente.The use of immunomodulators in pediatric dermatology has turned into a need of contemporary clinical practice. On the other hand, the continuous discovery of molecules involved in the physiopathology of many dermatological diseases associated with immunological disorders leads to the constant review of the application of these immunomodulators. This paper is aimed at showing some action mechanisms that justify the use of human immunoglobulin in some pediatric dermatological diseases and allows physicians to discuss the convenience of its utilization in the light of the present physiopathology of these diseases and of the patient’s state.

  6. Extracts from Calendula officinalis offer in vitro protection against H2 O2 induced oxidative stress cell killing of human skin cells.

    Science.gov (United States)

    Alnuqaydan, Abdullah M; Lenehan, Claire E; Hughes, Rachel R; Sanderson, Barbara J

    2015-01-01

    The in vitro safety and antioxidant potential of Calendula officinalis flower head extracts was investigated. The effect of different concentrations (0.125, 0.5, 1.0, 2.0 and 5.0% (v/v)) of Calendula extracts on human skin cells HaCaT in vitro was explored. Doses of 1.0% (v/v) (0.88 mg dry weight/mL) or less showed no toxicity. Cells were also exposed to the Calendula extracts for either 4, 24 or 48 h before being exposed to an oxidative insult (hydrogen peroxide H2 O2 ) for 1 h. Using the MTT cytotoxicity assay, it was observed that two independent extracts of C. officinalis gave time-dependent and concentration-dependent H2 O2 protection against induced oxidative stress in vitro using human skin cells. Pre-incubation with the Calendula extracts for 24 and 48 h increased survival relative to the population without extract by 20% and 40% respectively following oxidative challenge. The antioxidant potential of the Calendula extracts was confirmed using a complimentary chemical technique, the DPPH(●) assay. Calendula extracts exhibited free radical scavenging abilities. This study demonstrates that Calendula flower extracts contain bioactive and free radical scavenging compounds that significantly protect against oxidative stress in a human skin cell culture model.

  7. Immunoglobulin K light chain deficiency: A rare, but probably underestimated, humoral immune defect.

    Science.gov (United States)

    Sala, Pierguido; Colatutto, Antonio; Fabbro, Dora; Mariuzzi, Laura; Marzinotto, Stefania; Toffoletto, Barbara; Perosa, Anna R; Damante, Giuseppe

    2016-04-01

    Human immunoglobulin molecules are generated by a pair of identical heavy chains, which identify the immunoglobulin class, and a pair of identical light chains, Kappa or Lambda alternatively, which characterize the immunoglobulin type. In normal conditions, Kappa light chains represent approximately 2/3 of the light chains of total immunoglobulins, both circulating and lymphocyte surface bound. Very few cases of immunoglobulin Kappa or Lambda light chain defects have been reported. Furthermore, the genetic basis of this defect has been extensively explored only in a single case. We report a case of a patient suffering of serious recurrent bacterial infections, which was caused by a very rare form of immunoglobulin disorder, consisting of a pure defect of Kappa light chain. We evaluated major serum immunoglobulin concentrations, as well as total and free Kappa and Lambda light chain concentrations. Lymphocyte phenotyping was also performed and finally we tested the Kappa chain VJ rearrangement as well as the constant Kappa region sequence. Studies performed on VJ rearrangement showed a polyclonal genetic arrangement, whereas the gene sequencing for the constant region of Kappa chain showed a homozygous T to G substitution at the position 1288 (rs200765148). This mutation causes a substitution from Cys to Gly in the protein sequence and, therefore, determines the abnormal folding of the constant region of Kappa chain. We suggest that this defect could lead to an effective reduction of the variability of total antibody repertoire and a consequent defect of an apparently normal immunoglobulin response to common antigens.

  8. Measurement of Acylcarnitine Substrate to Product Ratios Specific to Biotin-Dependent Carboxylases Offers a Combination of Indicators of Biotin Status in Humans12

    Science.gov (United States)

    Bogusiewicz, Anna; Horvath, Thomas D.; Stratton, Shawna L.; Mock, Donald M.; Boysen, Gunnar

    2012-01-01

    This work describes a novel liquid chromatography tandem MS (LC-MS/MS) method for the determination of ratios of acylcarnitines arising from acyl-CoA substrates and products that reflect metabolic disturbances caused by marginal biotin deficiency. The urinary ratios reflecting reduced activities of biotin-dependent enzymes include the following: 1) the ratio of 3-hydroxyisovalerylcarnitine : 3-methylglutarylcarnitine (3HIAc : MGc) for methylcrotonyl-CoA carboxylase; 2) the ratio of propionylcarnitine:methylmalonylcarnitine (Pc : MMc) for propionyl-CoA carboxylase (PCC); and 3) the ratio of acetylcarnitine : malonylcarnitine (Ac : Mc) for acetyl-CoA carboxylase. To demonstrate the suitability of the LC-MS/MS method for biomonitoring, we measured the 3 ratios for 7 healthy adults at various time points (d 0, 14, and 28) during the induction of marginal biotin through the consumption of egg white. The mean change in the Pc : MMc ratio relative to d 0 was 5.3-fold by d 14 (P = 0.0049) and 8.5-fold by d 28 (P = 0.0042). The mean change in the 3HIAc : MGc ratio was 2.8-fold by d 14 (P = 0.0022) and 3.8-fold by d 28 (P = 0.0001). The mean change in the Ac : Mc ratio was 2.9-fold by d 14 (P = 0.03) and 4.7-fold by d 28 (P = 0.02). The results suggest that simultaneous assessment of ratios of multiple biotin-dependent pathways offers insight into the complex metabolic disturbances caused by marginal biotin deficiency. We hypothesize that one or a combination of the ratios might be more sensitive or robust with respect to other nutrient deficiencies or confounding metabolic processes. PMID:22833654

  9. Selective staining of CdS on ZnO biolabel for ultrasensitive sandwich-type amperometric immunoassay of human heart-type fatty-acid-binding protein and immunoglobulin G.

    Science.gov (United States)

    Qin, Xiaoli; Xu, Aigui; Liu, Ling; Sui, Yuyun; Li, Yunlong; Tan, Yueming; Chen, Chao; Xie, Qingji

    2017-05-15

    We report on an ultrasensitive metal-labeled amperometric immunoassay of proteins, which is based on the selective staining of nanocrystalline cadmium sulfide (CdS) on ZnO nanocrystals and in-situ microliter-droplet anodic stripping voltammetry (ASV) detection on the immunoelectrode. Briefly, antibody 1 (Ab1), bovine serum albumin (BSA), antigen and ZnO-multiwalled carbon nanotubes (MWCNTs) labeled antibody 2 (Ab2-ZnO-MWCNTs) were successively anchored on a β-cyclodextrin-graphene sheets (CD-GS) nanocomposite modified glassy carbon electrode (GCE), forming a sandwich-type immunoelectrode (Ab2-ZnO-MWCNTs/antigen/BSA/Ab1/CD-GS/GCE). CdS was selectively grown on the catalytic ZnO surfaces through chemical reaction of Cd(NO3)2 and thioacetamide (ZnO-label/CdS-staining), due to the presence of an activated cadmium hydroxide complex on ZnO surfaces that can decompose thioacetamide. A beforehand cathodic "potential control" in air and then injection of 7μL of 0.1M aqueous HNO3 on the immunoelectrode allow dissolution of the stained CdS and simultaneous cathodic preconcentration of atomic Cd onto the electrode surface, thus the following in-situ ASV detection can be used for immunoassay with enhanced sensitivity. Under optimized conditions, human immunoglobulin G (IgG) and human heart-type fatty-acid-binding protein (FABP) are analyzed by this method with ultrahigh sensitivity, excellent selectivity and small reagent-consumption, and the limits of detection (LODs, S/N=3) are 0.4fgmL(-1) for IgG and 0.3fgmL(-1) for FABP (equivalent to 73 FABP molecules in the 6μL sample employed).

  10. Fusion of Na-ASP-2 with human immunoglobulin Fcγ abrogates histamine release from basophils sensitized with anti-Na-ASP-2 IgE.

    Science.gov (United States)

    Zhan, Bin; Santiago, H; Keegan, B; Gillespie, P; Xue, J; Bethony, J; de Oliveira, L M; Jiang, D; Diemert, D; Xiao, S-H; Jones, K; Feng, X; Hotez, P J; Bottazzi, M E

    2012-01-01

    Na-ASP-2 is a major protein secreted by infective third-stage larvae (L3) of the human hookworm Necator americanus upon host entry. It was chosen as a lead vaccine candidate for its ability to elicit protective immune responses. However, clinical development of this antigen as a recombinant vaccine was halted because it caused allergic reactions among some of human volunteers previously infected with N. americanus. To prevent IgE-mediated allergic reactions induced by Na-ASP-2 but keep its immunogenicity as a vaccine antigen, we designed and tested a genetically engineered fusion protein, Fcγ/Na-ASP-2, composed of full-length Na-ASP-2 and truncated human IgG Fcγ1 that targets the negative signalling receptor FcγRIIb expressed on pro-allergic cells. The chimeric recombinant Fcγ/Na-ASP-2 protein was expressed in Pichia pastoris and shared the similar antigenicity as native Na-ASP-2. Compared to Na-ASP-2, the chimeric fusion protein efficiently reduced the release of histamine in human basophils sensitized with anti-Na-ASP-2 IgE obtained from individuals living in a hookworm-endemic area. In dogs infected with canine hookworm, Fcγ/Na-ASP-2 resulted in significantly reduced immediate-type skin reactivity when injected intradermally compared with Na-ASP-2. Hamsters vaccinated with Fcγ/Na-ASP-2 formulated with Alhydrogel(®) produced specific IgG that recognized Na-ASP-2 and elicited similar protection level against N. americanus L3 challenge as native Na-ASP-2. © 2012 Blackwell Publishing Ltd.

  11. The new generation of liquid intravenous immunoglobulin formulations in patient care: a comparison of intravenous immunoglobulins.

    Science.gov (United States)

    Stein, Mark R

    2010-09-01

    Intravenous immunoglobulin (IGIV) replacement therapy is the standard of care for primary immunodeficiencies with impaired humoral immunity. It is also the immunomodulatory therapy of choice for some types of neuroimmunologic and autoimmune hematologic disorders and for immunomodulation in bone marrow and some solid organ transplants. Currently available IGIV products include older lyophilized formulations, 5% liquid products, and newer, liquid, ready-to-use, 10% formulations. Differences in the formulations, manufacturing processes, excipients, pH, and other physicochemical properties of IGIV products may affect their clinical efficacy and tolerability. Among at-risk patients, the possibility of serious complications such as renal insufficiency, heart failure, thrombotic events, and immunological reactions may be increased if an IGIV formulation has sugar as a stabilizer, has high sodium or immunoglobulin A (IgA) content, or is hyperosmolar. The 10% liquid formulations may offer advantages because of their lower IgA concentrations, optimal pH, glycine or proline stabilizers, low sodium content, and lower osmolality. Liquid formulations are more convenient for patients and health care providers due to shorter infusion times and easier preparation and administration.

  12. Human Leukocyte Antigens and Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma: Old Associations Offer New Clues into the Role of Immunity in Infection-Associated Cancers

    Directory of Open Access Journals (Sweden)

    Wen-Hui eSu

    2013-12-01

    Full Text Available Nasopharyngeal carcinoma (NPC is an Epstein-Barr virus (EBV associated tumor. In addition to EBV, host genetic factors are believed to be important determinants of NPC risk. Of all genes studies to date, human leukocyte antigen (HLA genes have shown the most consistent evidence for association with NPC, both from candidate-gene studies and genome-wide association studies (GWAS. In this report we summarize results from recent studies that evaluated the association between HLA and NPC, and discuss whether findings reflect direct causal associations for HLA genes and/or indirect associations that mark causal associations with other genes in the gene-dense major histocompatibility (MHC region where HLA resides. We also compare GWAS results across cancer sites for which strong hits in the MHC region were observed to generate new hypotheses regarding the role of HLA genes in the development of EBV-associated cancers such as NPC. Of note, we report that MHC associations for EBV-associated cancers (NPC, EBV+ Hodgkin lymphoma are driven by HLA class I genes. In contrast, MHC associations for other viral-associated cancers (cervical cancer, hepatocellular carcinoma or other hematopoetic cancers (EBV- Hodgkin lymphoma, leukemia, non-Hodgkin lymphomas are driven by HLA class II genes, and those for other solid tumors with less clear links to infections (lung, testicular, prostate cancers are driven by non-HLA genes in the MHC region. Future studies should aim to better understand these patterns.

  13. Structural repertoire of immunoglobulin λ light chains

    KAUST Repository

    Chailyan, Anna

    2011-03-01

    The immunoglobulin λ isotype is present in nearly all vertebrates and plays an important role in the human immune system. Despite its importance, few systematic studies have been performed to analyze the structural conformation of its variable regions, contrary to what is the case for κ and heavy chains. We show here that an analysis of the structures of λ chains allows the definition of a discrete set of recurring conformations (canonical structures) of their hypervariable loops and, most importantly, the identification of sequence constraints that can be used to predict their structure. We also show that the structural repertoire of λ chains is different and more varied than that of the κ chains, consistently with the current view of the involvement of the two major light-chain families in complementary strategies of the immune system to ensure a fine tuning between diversity and stability in antigen recognition. © 2011 Wiley-Liss, Inc.

  14. VH Replacement Footprint Analyzer-I, a Java-Based Computer Program for Analyses of Immunoglobulin Heavy Chain Genes and Potential VH Replacement Products in Human and Mouse.

    Science.gov (United States)

    Huang, Lin; Lange, Miles D; Zhang, Zhixin

    2014-01-01

    VH replacement occurs through RAG-mediated secondary recombination between a rearranged VH gene and an upstream unrearranged VH gene. Due to the location of the cryptic recombination signal sequence (cRSS, TACTGTG) at the 3' end of VH gene coding region, a short stretch of nucleotides from the previous rearranged VH gene can be retained in the newly formed VH-DH junction as a "footprint" of VH replacement. Such footprints can be used as markers to identify Ig heavy chain (IgH) genes potentially generated through VH replacement. To explore the contribution of VH replacement products to the antibody repertoire, we developed a Java-based computer program, VH replacement footprint analyzer-I (VHRFA-I), to analyze published or newly obtained IgH genes from human or mouse. The VHRFA-1 program has multiple functional modules: it first uses service provided by the IMGT/V-QUEST program to assign potential VH, DH, and JH germline genes; then, it searches for VH replacement footprint motifs within the VH-DH junction (N1) regions of IgH gene sequences to identify potential VH replacement products; it can also analyze the frequencies of VH replacement products in correlation with publications, keywords, or VH, DH, and JH gene usages, and mutation status; it can further analyze the amino acid usages encoded by the identified VH replacement footprints. In summary, this program provides a useful computation tool for exploring the biological significance of VH replacement products in human and mouse.

  15. Half molecular exchange of IgGs in the blood of healthy humans: chimeric lambda-kappa-immunoglobulins containing HL fragments of antibodies of different subclasses (IgG1-IgG4).

    Science.gov (United States)

    Sedykh, Sergey E; Lekchnov, Evgenii A; Prince, Viktor V; Buneva, Valentina N; Nevinsky, Georgy A

    2016-10-20

    In the classic paradigm, immunoglobulins represent products of clonal B cell populations, each producing antibodies recognizing a single antigen (monospecific). There is a common belief that IgGs in mammalian biological fluids are monospecific molecules having stable structures and two identical antigen-binding sites. But the issue concerning the possibility of exchange by HL-fragments between the antibody molecules in human blood is still unexplored. Different physico-chemical and immunological methods for analysis of half-molecule exchange between human blood IgGs were used. Using eighteen blood samples of healthy humans we have shown unexpected results for the first time: blood antibodies undergo extensive post-transcriptional half-molecule exchange and IgG pools on average consist of 62.4 ± 6.5% IgGs containing kappa light chains (kappa-kappa-IgGs), 29.8.6 ± 5.4% lambda light chains (lambda-lambda-IgGs), and 8.8 ± 2.7% (range 2.6-16.8%) IgGs containing both kappa- and lambda-light chains. Kappa-kappa-IgGs and lambda-lambda-IgGs contained on average (%): IgG1 (36.0 and 32.3), IgG2 (50.9 and 51.4), IgG3 (9.7 and 9.9), and IgG4 (6.5 and 5.7), while chimeric kappa-lambda-IgGs consisted of (%): 25.5 ± 4.2 IgG1, 50.8 ± 3.9 IgG2, 9.1 ± 2.1 IgG3, and 14.5 ± 2.2 IgG4. Our unexpected data are indicative of the possibility of half-molecule exchange between blood IgGs of various subclasses, raised against different antigens. The existence of blood chimeric bifunctional IgGs with different binding sites destroys the classic paradigm. Due to the phenomenon of polyspecificity and cross-reactivity of bifunctional IgGs containing HL-fragments of different types to different antigens, such IgGs may be important in human blood for widening their different biological functions.

  16. Offers

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    To our members 5% discount on Fnac vouchers Vouchers of 50.-, 100.- et 200. - CHF Valid in the 4 shops in Switzerland without restriction on purchases. On sale in the office of Secretariat of the staff Association.

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    12 % discount on football camps and courses for children from 3 to 13 years old, with bilingual coaches.   Now also courses during the autumn holidays! In order to get the discount you need to register online, then send a mail to info@intersoccer.ch with a scan of your membership card to recieve a refund of the discount.

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    Découvrez les plus belles tables de Suisse romande et de France voisine en bénéficiant des réductions suivantes sur chaque repas, pendant une année : 50 % pour 2 personnes / 40 % pour 3 personnes / 30 % pour 4 personnes / 20 % pour 5 à 6 personnes. Comment ça marche ? Faites votre choix parmi les 110 restaurants de votre région et réservez votre table pour 2, 3, 4, 5 ou 6 personnes. Présentez votre Passeport Gourmand dès votre arrivée. Savourez votre repas et profitez d’une réduction exceptionnelle sur votre addition (hors boissons, menu du jour et business lunch). Quels sont vos avantages ? Profitez du prix préférentiel pour les membres de l’association du CERN : – Passeport Gourmand Genève : CHF 75.- (au lieu de CHF 95.-) – Passeport Gourmand Ain/Savoie/Haute-Savoie : CHF 59.- (au lieu de...

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    Découvrez les plus belles tables de Suisse romande et de France voisine en bénéficiant des réductions suivantes sur chaque repas, pendant une année : 50 % pour 2 personnes, 40 % pour 3 personnes, 30 % pour 4 personnes, 20 % pour 5 à 6 personnes. Comment ça marche ? Faites votre choix parmi les 110 restaurants de votre région et réservez votre table pour 2, 3, 4, 5 ou 6 personnes. Présentez votre Passeport Gourmand dès votre arrivée. Savourez votre repas et profitez d’une réduction exceptionnelle sur votre addition (hors boissons, menu du jour et business lunch). Quels sont vos avantages ? Profitez du prix préférentiel pour les membres de l’association du CERN : – Passeport Gourmand Genève : CHF 75.- (au lieu de CHF 95.-) – Passeport Gourmand Ain/Savoie/Haute-Savoie : CHF 59.- (au lieu de CH...

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    Concert Scoop music tour sur le parc Walibi ! Vendredi 12 Juillet Vous trouverez la présentation de l’événement et les vidéos des artistes attendus avec leurs titres faisant vibrer les radios en ce moment sur le site internet http://www.walibi.com/rhone-alpes/fr-fr/evenements/scoop-music-tour. Le concert est gratuit et débute à la fermeture du parc avec une première partie surprise. Profitez donc d’une belle journée sur le parc et finissez en beauté avec le concert de l’été !

  1. Offers

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    LA BÂTIE-FESTIVAL DE GENEVE Offre pour les membres de l'association du personnel du CERN   P r é s e n t a t i o n L a B â t i e-F e s t i v a l d e G e n è v e : Festival pluridisciplinaire et contemporain, souvent qualifié de «tête chercheuse», La Bâtie-Festival de Genève permet durant deux semaines de découvrir plus de 40 spectacles d’artistes emblématiques d’ici ou d’ailleurs, aussi bien pour les grands que les petits (mini-Bâtie). De la danse, du théâtre, de la musique, du 3 au 18 septembre 2010 nous recevrons près de 300 artistes dans une vingtaine de salles à Genève et en France voisine (Annemasse et Divonne). La Bâtie c’est aussi deux lieux de rencontre et d’échange, Le Tampopo, notre restaurant-l...

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        Envie de soirée au théâtre, n’hésitez pas à bénéficier de nos offres pour nos membres ! Théâtre de Carouge : Réduction de 5 CHF pour tous les spectacles (30 CHF au lieu de 35 CHF) Le théâtre de Carouge vous présente sa nouvelle pièce : La double insconstance Du vedredi 21 mars au dimanche 6 avril 2014 De Marivaux Mise en scène de Philippe Mentha Audio-description le mardi 1er avril et le samedi 5 avril 2014 Il règne un doux mélange de révoltes et de séductions, de ruses et de fatalité dans cette Double Inconstance de Marivaux que met en scène Philippe Mentha, membre fondateur du Théâtre de Carouge et directeur depuis plus de trente ans du Théâtre Kléber-Méleau. L’allure d...

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      Bénéficiez du tarif spécial de 35 CHF/personne + 1 accompagnant au Théâtre de Carouge  en étant membre de l’Association du personnel.  Envoyez votre réservation par mail à smills@tcag.ch via votre adresse mail professionnelle. Indiquez la date de votre réservation, votre nom, prénom et numéro de téléphone. Une confirmation de réservation vous sera retournée par mail. La présentation de votre carte de membre sera demandée lors du retrait des billets.   De Molière – Mise en scène de Jean Liermier Argan, veuf, remarié avec Béline qui n’attend que la mort de son mari pour hériter, multiplie saignées, purges et autres ingestions de remèdes. Angélique, sa fille, vuet &a...

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    Tickets "Zone terrestre": 21.50 € instead of 27 €. Access to Aqualibi: 5 € instead of 8 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12 h 00. Free for children under 3, with limited access to the attractions. Car park free.

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    Le parc ouvre ses portes le samedi 4 avril 2015!   La Chasse aux Oeufs du 4 au 26 avril En plus de ses 25 attractions et spectacles, le parc proposera aux enfants de 3 à 12 ans de relever le challenge d’une course aux oeufs dans un jardin de Pâques reconstitué ! Autant de petits oeufs à trouver dans un temps limite ; tout cela au milieu de lapins, poules, fleurs et autres oeufs géants pour repartir avec des gourmandises en chocolat de la marque Revillon Chocolatier.   Profitez de notre offre spéciale pour nos membres : Tarif unique Adulte/Enfant Entrée Zone terrestre 21,50 euros au lieu de 27 euros Accès à l’Aqualibi : 5 euros au lieu de 8 euros sur présentation du billet d’entrée au tarif membre AP. Entrée gratuite pour les enfants de moins de 3 ans, avec accès limité aux attractions. Les billet...

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    Tickets "Zone terrestre": 21 € instead of 27 €. Access to Aqualibi: 5 € instead of 8 € on presentation of your SA member ticket. Free for children (3-11 years old) before 12 h 00. Free for children under 3, with limited access to the attractions. Car park free.

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    Nouveau partenaire - Joy’s Club   Venez profiter des remises au Joy’s Club / Minigolf à Divonne-les-bains en tant que membre de l’Association ! Sur présentation de votre carte membre, vous bénéficierez d’une remise immédiate telle que : - Pour une partie adulte : 6 euros au lieu de 7 euros - Pour une partie enfant : 4 euros au lieu de 5 euros - Pour le mini Park : 6 euros au lieu de 7 euros Pour plus de renseignements, n’hésitez pas à demander au Secrétariat de l’Association ou à consulter notre site web: http://staff-association.web.cern.ch/fr/socioculturel/offres  

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    Si cette offre vous intéresse, merci d’envoyer un mail à mh.boulanger@comedie.ch avec le détail de votre réservation via votre adresse mail professionnelle. Le retrait des places se fait à la billetterie sur présentation de votre carte de membre de l’Association du personnel. Pour toute commande d’abonnement ou de carte de réduction par courrier ou internet, cocher le tarif collectif en indiquant le nom de l’entreprise et en joignant un justificatif nominatif. Pour tout renseignement, n’hésitez pas à contacter Marie-Hélène Boulanger : –  Tel. : 022 809 60 86 –  email : mh.boulanger@comedie.ch

  9. Solvent-Detergent Treatment of IgM-Enriched Immunoglobulin

    Directory of Open Access Journals (Sweden)

    Mojgan Pourmokhtar

    2003-08-01

    Full Text Available Viral safety of human plasma products plays a key role in their safe uses. Solvent- detergent (SD virus-inactivation method has gained widespread popularity in the manufacture of biological products. This treatment which inactivates lipid-enveloped viruses effectively consists of incubation of a plasma protein solution in the presence of a non-volatile organic solvent and a detergent. In this study, IgM-enriched immunoglobulin was incubated at 24 °C for 6 h under slow stirring in the presence of tri(n-butyl phosphate (0.3% w/w as solvent and tween 80 (1% w/w as detergent. After completion of the inactivation process and removal of the solvent-detergent, the ability of SD-treatment to remove Infectious Bovine Rhinotracheitis (IBR virus (a lipid-enveloped virus and Foot-and-Mouth Disease virus (a non-enveloped virus were evaluated by "virus spiking studies" using a scaled down process. Reduction factor of 4 log was obtained for the SD-treatment of IgM-enriched immunoglobulin spiked with IBR virus. No virus inactivation was observed in the SD-treated IgM-enriched immunoglobulin, spiked with Foot-and-Mouth Disease virus. It was concluded that treatment of IgM-enriched immunoglobulin with TNBP-TWEEN 80 may be considered as an efficient lipid-enveloped virus inactivation step in the manufacture of this product.

  10. Potent and synergistic neutralization of human immunodeficiency virus (HIV) type 1 primary isolates by hyperimmune anti-HIV immunoglobulin combined with monoclonal antibodies 2F5 and 2G12.

    Science.gov (United States)

    Mascola, J R; Louder, M K; VanCott, T C; Sapan, C V; Lambert, J S; Muenz, L R; Bunow, B; Birx, D L; Robb, M L

    1997-10-01

    Three antibody reagents that neutralize primary human immunodeficiency virus type 1 (HIV-1) isolates were tested for magnitude and breadth of neutralization when used alone or in double or triple combinations. Hyperimmune anti-HIV immunoglobulin (HIVIG) is derived from the plasma of HIV-1-infected donors, and monoclonal antibodies (MAbs) 2F5 and 2G12 bind to distinct regions of the HIV-1 envelope glycoprotein. The antibodies were initially tested against a panel of 15 clade B HIV-1 isolates, using a single concentration that is achievable in vivo (HIVIG, 2,500 microg/ml; MAbs, 25 microg/ml). Individual antibody reagents neutralized many of the viruses tested, but antibody potency varied substantially among the viruses. The virus neutralization produced by double combinations of HIVIG plus 2F5 or 2G12, the two MAbs together, or the triple combination of HIVIG, 2F5, and 2G12 was generally equal to or greater than that predicted by the effect of individual antibodies. Overall, the triple combination displayed the greatest magnitude and breadth of neutralization. Synergistic neutralization was evaluated by analyzing data from dose-response curves of each individual antibody reagent compared to the triple combination and was demonstrated against each of four viruses tested. Therefore, combinations of polyclonal and monoclonal anti-HIV antibodies can produce additive or synergistic neutralization of primary HIV-1 isolates. Passive immunotherapy for treatment or prophylaxis of HIV-1 should consider mixtures of potent neutralizing antibody reagents to expand the magnitude and breadth of virus neutralization.

  11. Lung scintigraphy with nonspecific human immunoglobulin G ({sup 99m}Tc-HIG) in the evaluation of pulmonary involvement in connective tissue diseases: correlation with pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT)

    Energy Technology Data Exchange (ETDEWEB)

    Kostopoulos, C.; Toubanakis, C.; Mamoulakis, C.; Gialafos, E.; Mavrikakis, M. [Alexandra University Hospital, Department of Clinical Therapeutics, Athens (Greece); Koutsikos, J.; Zerva, C.; Leondi, A. [Alexandra University Hospital, Department of Nuclear Medicine, Athens (Greece); Moulopoulos, L.A. [Areteion University Hospital, Department of Radiology, Athens (Greece); Sfikakis, P.P. [Laikon University Hospital, Department of Propaedeutic Medicine, Athens (Greece)

    2008-02-15

    In patients with connective tissue diseases (CTD), the early detection and evaluation of the severity of the pulmonary involvement is mandatory. High-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) are considered to be valuable noninvasive diagnostic modalities. Radiopharmaceuticals have also been used for this purpose. Our aim was the evaluation of technetium-labeled human polyclonal immunoglobulin G (HIG) lung scintigraphy in the early detection and assessment of the severity of the pulmonary involvement in CTD patients. Fifty-two nonsmoking CTD patients were studied by PFTs, HRCT, and HIG. According to PFTs, patients were divided in group A (impaired PFTs - abnormal pulmonary function) and group B (normal pulmonary function). Semiquantitative analysis was done on HIG and HRCT and corresponding scores were obtained. Significant difference was found between HIG scores in the two groups (0.6 {+-} 0.07 vs 0.51 {+-} 0.08, P < 0.001). There was a statistically significant negative correlation between HIG scores and PFTs results and a positive correlation between HIG and HRCT scores. HIG demonstrated similar clinical performance to HRCT. At the best cut-off levels of their score (0.56 and 7, respectively), HIG had a superior sensitivity (77.5 vs 57.5%) with lower specificity (75 vs 91.7%). The combination of the two methods increased the sensitivity of abnormal findings at the expense of specificity. HIG scintigraphy can be used in the early detection and evaluation of the severity of the pulmonary involvement in CTD, whereas, when used in combination with HRCT, the detection of affected patients can be further improved. (orig.)

  12. Humoral Immunity to Commensal Oral Bacteria in Human Infants: Salivary Secretory Immunoglobulin A Antibodies Reactive with Streptococcus mitis biovar 1, Streptococcus oralis, Streptococcus mutans, and Enterococcus faecalis during the First Two Years of Life

    Science.gov (United States)

    Cole, Michael F.; Bryan, Stacey; Evans, Mishell K.; Pearce, Cheryl L.; Sheridan, Michael J.; Sura, Patricia A.; Wientzen, Raoul L.; Bowden, George H. W.

    1999-01-01

    Secretory immunoglobulin A (SIgA) antibodies reactive with the pioneer oral streptococci Streptococcus mitis biovar 1 and Streptococcus oralis, the late oral colonizer Streptococcus mutans, and the pioneer enteric bacterium Enterococcus faecalis in saliva samples from 10 human infants from birth to age 2 years were analyzed. Low levels of salivary SIgA1 and SIgA2 antibodies reactive with whole cells of all four species were detected within the first month after birth, even though S. mutans and E. faecalis were not recovered from the mouths of the infants during the study period. Although there was a fivefold increase in the concentration of SIgA between birth and age 2 years, there were no differences between the concentrations of SIgA1 and SIgA2 antibodies reactive with the four species over this time period. When the concentrations of SIgA1 and SIgA2 antibodies reactive with all four species were normalized to the concentrations of SIgA1 and SIgA2 in saliva, SIgA1 and SIgA2 antibodies reactive with these bacteria showed a significant decrease from birth to 2 years of age. Adsorption of each infant’s saliva with cells of one species produced a dramatic reduction of antibodies recognizing the other three species. Sequential adsorption of saliva samples removed all SIgA antibody to the bacteria, indicating that the SIgA antibodies were directed to antigens shared by all four species. The induction by the host of a limited immune response to common antigens that are likely not involved in adherence may be among the mechanisms that commensal streptococci employ to persist in the oral cavity. PMID:10085031

  13. Immunoglobulin superantigen protein L induces IL-4 and IL-13 secretion from human Fc epsilon RI+ cells through interaction with the kappa light chains of IgE.

    Science.gov (United States)

    Genovese, Arturo; Borgia, Guglielmo; Björck, Lars; Petraroli, Angelica; de Paulis, Amato; Piazza, Marcello; Marone, Gianni

    2003-02-15

    Peptostreptococcus magnus protein L is a multidomain bacterial surface protein that correlates with virulence. It consists of up to five homologous Ig-binding domains (B1-B5) that interact with the variable domain of Ig kappa L chains. Intact protein L stimulates the synthesis and the release of IL-4 and IL-13 from human basophils in vitro. A protein L fragment covering the Ig-binding domains B1-B4 also induced IL-4 and IL-13 release from basophils. There was an excellent correlation (r(s) = 0.82; p ADZ (kappa chains) blocked both anti-IgE- and protein L-induced secretion. Cyclosporin A, but not cyclosporin H, inhibited protein L-induced release of IL-4 and IL-13 from basophils. Thus, protein L acts as a bacterial Ig superantigen to induce the synthesis and release of IL-4 and IL-13 from basophils by interacting with kappa L chains of the IgE isotype.

  14. Cloning and expression in Escherichia coli of a human gelatinase B-inhibitory single-chain immunoglobulin variable fragment (scFv).

    Science.gov (United States)

    Zhou, N; Paemen, L; Opdenakker, G; Froyen, G

    1997-09-15

    The murine monoclonal antibody REGA-3G12 selectively and specifically inhibits the activity of human gelatinase B. The cDNA fragments which encode the variable regions of the light and heavy chains were isolated by PCR-mediated cloning and sequenced. Single-chain Fv expression constructs for Escherichia coli were generated in which c-myc tag sequences were encoded. Inducible expression of the scFv and secretion to the periplasm were obtained with higher yields when the c-myc tag sequence was positioned at the amino-terminal side. The inhibitory activity of purified scFv on neutrophil gelatinase B was tested in a gelatin degradation assay and it was found to possess a similar specific activity as that of the intact monoclonal antibody and of the pepsin-clipped F(ab')2 derivative. This shows for the first time that inhibition of soluble enzymes with scFv is possible and opens new perspectives for the treatment of diseases with excessive and detrimental enzyme production in the host.

  15. Human placenta: relative content of antibodies of different classes and subclasses (IgG1-IgG4) containing lambda- and kappa-light chains and chimeric lambda-kappa-immunoglobulins.

    Science.gov (United States)

    Lekchnov, Evgenii A; Sedykh, Sergey E; Dmitrenok, Pavel S; Buneva, Valentina N; Nevinsky, Georgy A

    2015-06-01

    The specific organ placenta is much more than a filter: it is an organ that protects, feeds and regulates the growth of the embryo. Affinity chromatography, ELISA, SDS-PAGE and matrix-assisted laser desorption ionization mass spectrometry were used. Using 10 intact human placentas deprived of blood, a quantitative analysis of average relative content [% of total immunoglobulins (Igs)] was carried out for the first time: (92.7), IgA (2.4), IgM (2.5), kappa-antibodies (51.4), lambda-antibodies (48.6), IgG1 (47.0), IgG2 (39.5), IgG3 (8.8) and IgG4 (4.3). It was shown for the first time that placenta contains sIgA (2.5%). In the classic paradigm, Igs represent products of clonal B-cell populations, each producing antibodies recognizing a single antigen. There is a common belief that IgGs in mammalian biological fluids are monovalent molecules having stable structures and two identical antigen-binding sites. However, similarly to human milk Igs, placenta antibodies undergo extensive half-molecule exchange and the IgG pool consists of 43.5 ± 15.0% kappa-kappa-IgGs and 41.6 ± 17.0% lambda-lambda-IgGs, while 15.0 ± 4.0% of the IgGs contained both kappa- and lambda-light chains. Kappa-kappa-IgGs and lambda-lambda-IgGs contained, respectively (%): IgG1 (47.7 and 34.4), IgG2 (36.3 and 44.5), IgG3 (7.4 and 11.8) and IgG4 (7.5 and 9.1), while chimeric kappa-lambda-IgGs consisted of (%): 43.5 IgG1, 41.0 IgG2, 5.6 IgG3 and 7.9 IgG4. Our data are indicative of the possibility of half-molecule exchange between placenta IgGs of various subclasses, raised against different antigens, which explains a very well-known polyspecificity and cross-reactivity of different human IgGs.

  16. Peptide mimetics of immunoglobulin A (IgA) and FcαRI block IgA-induced human neutrophil activation and migration.

    Science.gov (United States)

    Heineke, Marieke H; van der Steen, Lydia P E; Korthouwer, Rianne M; Hage, J Joris; Langedijk, Johannes P M; Benschop, Joris J; Bakema, Jantine E; Slootstra, Jerry W; van Egmond, Marjolein

    2017-07-24

    The cross-linking of the IgA Fc receptor (FcαRI) by IgA induces release of the chemoattractant LTB4, thereby recruiting neutrophils in a positive feedback loop. IgA autoantibodies of patients with autoimmune blistering skin diseases therefore induce massive recruitment of neutrophils, resulting in severe tissue damage. To interfere with neutrophil mobilization and reduce disease morbidity, we developed a panel of specific peptides mimicking either IgA or FcαRI sequences. CLIPS technology was used to stabilize three-dimensional structures and to increase peptides' half-life. IgA and FcαRI peptides reduced phagocytosis of IgA-coated beads, as well as IgA-induced ROS production and neutrophil migration in in vitro and ex vivo (human skin) experiments. Since topical application would be the preferential route of administration, Cetomacrogol cream containing an IgA CLIPS peptide was developed. In the presence of a skin permeation enhancer, peptides in this cream were shown to penetrate the skin, while not diffusing systemically. Finally, epitope mapping was used to discover sequences important for binding between IgA and FcαRI. In conclusion, a cream containing IgA or FcαRI peptide mimetics, which block IgA-induced neutrophil activation and migration in the skin may have therapeutic potential for patients with IgA-mediated blistering skin diseases. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. IMMUNOREGULATORY EFFECTS OF INTRAVENOUS IMMUNOGLOBULINS

    Directory of Open Access Journals (Sweden)

    S. A. Sel'kov

    2013-01-01

    Full Text Available Treatment with intravenous immunoglobulins (IVIG is widely used in modern clinical practice inorder to cure different clinical disorders, including obstetric conditions. Currently, IVIGs have become drugs of  choice  for  treatment of  anti-phospholipid  syndrome  in pregnant women,  like  as  in  cases of  intrauterine cytomegalovirus infection.

  18. The ubiquitous octamer-binding protein(s) is sufficient for transcription of immunoglobulin genes.

    Science.gov (United States)

    Johnson, D G; Carayannopoulos, L; Capra, J D; Tucker, P W; Hanke, J H

    1990-03-01

    All immunoglobulin genes contain a conserved octanucleotide promoter element, ATGCAAAT, which has been shown to be required for their normal B-cell-specific transcription. Proteins that bind this octamer have been purified, and cDNAs encoding octamer-binding proteins have been cloned. Some of these proteins (referred to as OTF-2) are lymphoid specific, whereas at least one other, and possibly more (referred to as OTF-1), is found ubiquitously in all cell types. The exact role of these different proteins in directing the tissue-specific expression of immunoglobulin genes is unclear. We have identified two human pre-B-cell lines that contain extremely low levels of OTF-2 yet still express high levels of steady-state immunoglobulin heavy-chain mRNA in vivo and efficiently transcribe an immunoglobulin gene in vitro. Addition of a highly enriched preparation of OTF-1 made from one of these pre-B cells or from HeLa cells specifically stimulated in vitro transcription of an immunoglobulin gene. Furthermore, OFT-1 appeared to have approximately the same transactivation ability as OTF-2 when normalized for binding activity. These results suggest that OTF-1, without OTF-2, is sufficient for transcription of immunoglobulin genes and that OTF-2 alone is not responsible for the B-cell-specific regulation of immunoglobulin gene expression.

  19. The ubiquitous octamer-binding protein(s) is sufficient for transcription of immunoglobulin genes

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, D.G.; Carayannopoulos, L.; Capra, J.D.; Tucker, P.W. (Dept. of Microbiology, Southwestern Medical Center at Dallas, Dallas, TX (US)); Hanke, J.H. (Central Research, Dept. of Molecular Genetics, Pfizer, Inc., Groton, CT (US))

    1990-03-01

    All immunoglobulin genes contain a conserved octanucleotide promoter element, ATGCAAAT, which has been shown to be required for their normal B-cell-specific transcription. Proteins that bind this octamer have been purified, and cDNAs encoding octamer-binding proteins have been cloned. Some of these proteins (referred to as OTF-2) are lymphoid specific, whereas at least one other, and possibly more (referred to as OTF-1), is found ubiquitously in all cell types. The exact role of these different proteins in directing the tissue-specific expression of immunoglobulin genes is unclear. The authors have identified two human pre-B-cell lines that contain extremely low levels of OTF-2 yet still express high levels of steady-state immunoglobulin heavy-chain mRNA in vivo and efficiently transcribe an immunoglobulin gene in vitro. Addition of a highly enriched preparation of OTF-1 made from one of these pre-B cells or from HeLa cells specifically stimulated in vitro transcription of an immunoglobulin gene. Furthermore, OFT-1 appeared to have approximately the same transactivation ability as OTF-2 when normalized for binding activity. These results suggest that OTF-1, without OTF-2, is sufficient for transcription of immunoglobulin genes and that OTF-2 alone is not responsible for the B-cell-specific regulation of immunoglobulin gene expression.

  20. A double signal electrochemical human immunoglobulin G immunosensor based on gold nanoparticles-polydopamine functionalized reduced graphene oxide as a sensor platform and AgNPs/carbon nanocomposite as signal probe and catalytic substrate.

    Science.gov (United States)

    Zhang, Si; Huang, Na; Lu, Qiujun; Liu, Meiling; Li, Haitao; Zhang, Youyu; Yao, Shouzhuo

    2016-03-15

    In this paper, a double signal electrochemical Human immunoglobulin G (HIgG) immunosensor based on AgNPs/carbon nanocomposite (Ag/C NC) as the signal probe and catalytic substrate was developed for fast and sensitive detection of HIgG. The as-prepared AuNPs-PDA-rGO nanocomposite and Ag/C NC were confirmed by UV-vis, Fourier transform infrared spectroscopy, scanning electron microscopy and transmission electron microscopy. Electrochemical impedance spectroscopy, cyclic voltammetry and differential pulse voltammetry were used to investigate the electrochemical properties of the proposed immunosensor. The AuNPs-PDA-rGO nanocomposite can improve the electron transfer rate and capture more Ab1. In the sandwich-type immunoassay process, the Ag/C NC functionalized bioconjugates were captured on HIgG/Ab1/AuNPs-PDA-rGO surface and the electrochemical double-signal strategy was employed. These double electrochemical detection signals were directly monitored the oxidation current originated from Ag/C NC and indirectly detected the reduction current of benzoquinone which was produced from the reaction of H2O2 and HQ by catalysis of Ag/C NC in electrochemical detection of HIgG. Under the optimized conditions, the current responses were changed with the concentrations of HIgG for the proposed immunosensor with wide linear ranges of 0.1 to 100 ngmL(-1) and 0.01-100 ngmL(-1) with the lowest detection concentration of 0.001 ng mL(-1) in the absence and presence of H2O2 and HQ. The double-signal strategy is used for detection of HIgG, and the results came from the two signals were well consistent with each other. The proposed immunosensor was successfully applied in analysis of human IgG in real samples and this strategy may provide a relative simple and effective method for construction of other immunsensors in detection of other biomarkers in clinical medicine.

  1. Comparison of immunoglobulin E measurements on IMMULITE and ImmunoCAP in samples consisting of allergen-specific mouse-human chimeric monoclonal antibodies towards allergen extracts and four recombinant allergens

    DEFF Research Database (Denmark)

    Szecsi, Pal B; Stender, Steen

    2013-01-01

    Specific immunoglobulin E (IgE) antibody in vitro tests are performed on enzyme immunoassay systems. Poor agreement among systems has been reported and comparisons have been made exclusively with allergen extracts - not with recombinant allergens. Here we compare the ImmunoCAP and the IMMULITE...

  2. Blood Test: Immunoglobulin A (IgA)

    Science.gov (United States)

    ... to 2-Year-Old Blood Test: Immunoglobulin A (IgA) KidsHealth > For Parents > Blood Test: Immunoglobulin A (IgA) Print A A A What's in this article? ... Questions en español Análisis de sangre: inmunoglobulina A (IgA) What It Is An IgA test measures the ...

  3. [Clinical significance of analysis of immunoglobulin A levels in saliva].

    Science.gov (United States)

    Bokor-Bratić, M

    2000-01-01

    plasma cells locally in the salivary glands. There is still little convincing evidence for the origin of predominantly immunoglobulin A secreting plasma cells in salivary glands. DETECTION OF IMMUNOGLOBULIN A IN SALIVA: Radial immunodiffusion (RID) was the most applicable method for detecting salivary immunoglobulin A. However, there are more sensitive and automatic methods such as nephelometry and ELISA. A standard level of immunoglobulin in saliva is still in question since the concentration varies in relation to origin of saliva, method of collection and stimulation of secretion (Table 1). PERIODONTAL DISEASE: Studies of the salivary immunoglobulin A in patients with periodontal disease and healthy persons showed that there are differences which can be used in detection of high-risk groups and individuals. If the bacterial adherence to the mucosa is a prerequisite for bacterial evolution in subgingival or any other region of the oral cavity respectively introduction in periodontitis development, than it is to be presumed that the basic function of salivary immunoglobulin A is inhibition of bacterial adherence rather than antigens destruction. Several bacterial species frequently isolated from the oral cavity of patients with periodontitis have been identified as producers of IgA protease. These enzymes cleave serum IgA and secretory IgA equally well. Additionally, most of the IgA proteases studied have cleaved the A1 and A2 subclass. Several studies have demonstrated that cleavage of human IgA occurs in vivo, resulting in generation of intact Fab alpha and (Fc alpha)2 fragment. Moreover, when bacteria are exposed to Fab alpha fragments released from IgA after cleavage by IgA protease, their surface antigens are likely to be occupied by Fab alpha fragments. These Fab alpha fragments left on the bacterial surface may mediate adhesion. Together, these results indicate that IgA proteases, by promoting adherence, contribute the pathogenic potential of bacteria in the oral

  4. Linear immunoglobulin A bullous dermatosis.

    Science.gov (United States)

    Fortuna, Giulio; Marinkovich, M Peter

    2012-01-01

    Linear immunoglobulin A (IgA) bullous dermatosis, also known as linear IgA disease, is an autoimmune mucocutaneous disorder characterized by subepithelial bullae, with IgA autoantibodies directed against several different antigens in the basement membrane zone. Its immunopathologic characteristic resides in the presence of a continuous linear IgA deposit along the basement membrane zone, which is clearly visible on direct immunofluorescence. This disorder shows different clinical features and distribution when adult-onset of linear IgA disease is compared with childhood-onset. Diagnosis is achieved via clinical, histopathologic, and immunopathologic examinations. Two common therapies are dapsone and sulfapyridine, which reduce the inflammatory response and achieve disease remission in a variable period of time.

  5. [Subcutaneous immunoglobulin. Treatment in chronic inflammatory demyelinating polyradiculo-neuropathy].

    Science.gov (United States)

    Nogués, Martín A; Varela, Francisco J; Seminario, Gisela; Insúa, María C; Bezrodnik, Liliana

    2016-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired disease that may affect nerve roots and peripheral nerves. Despite its low incidence, diagnosis is particularly important because there are different effective treatments. Human immunoglobulin is one of the mainstays of the treatment. Although there are few studies up to date, subcutaneous immunoglobulin (IgSC) has been proposed as an alternative to intravenous administration with similar efficacy. We present three cases with definite CIDP, classified according to the European Federation of Neurological Societies / Peripheral Nerve, Society (EFNS /PNS) criteria in which was used SCIgG as a treatment after success with the intravenous route. The Overall Neuropathy Limitations Scale (ONLS) was used to estimate the changes in the muscular strength before and after treatment.

  6. Comparative analyses of immunoglobulin genes: surprises and portents.

    Science.gov (United States)

    Flajnik, Martin F

    2002-09-01

    The study of immunoglobulin genes in non-mouse and non-human models has shown that different vertebrate groups have evolved distinct methods of generating antibody diversity. By contrast, the development of T cells in the thymus is quite similar in all of the species that have been examined. The three mechanisms by which B cells uniquely modify their immunoglobulin genes -- somatic hypermutation, gene conversion and class switching -- are increasingly believed to share some fundamental mechanisms, which studies in different vertebrate groups have helped (and will continue to help) to resolve. When these mechanisms are better understood, we should be able to look to the constitutive pathways from which they have evolved and perhaps determine whether the rearrangement of variable, diversity and joining antibody gene segments -- V(D)J recombination -- was superimposed on an existing adaptive immune system.

  7. Expression of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1 on osteoclasts and its potential role in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Yuan Zhang

    2013-04-01

    Full Text Available OBJECTIVE: Leukocyte-associated immunoglobulin-like receptor-1 is an inhibitory receptor primarily expressed by immune cells. This study was undertaken to define the role of this molecule in osteoclast differentiation and rheumatoid arthritis. METHODS: In vitro osteoclast assays were performed to characterize the role of Leukocyte-associated immunoglobulin-like receptor-1 in murine and human osteoclastogenesis. Human Leukocyte-associated immunoglobulin-like receptor-1 expression was assessed by immunohistochemistry staining in the synovium of patients with rheumatoid arthritis. The levels of soluble Human Leukocyte-associated immunoglobulin-like receptor-1 were determined by enzyme-linked immunosorbent assay. RESULTS: We found that multinucleated osteoclast formation from mouse bone marrow cells was inhibited by treatment with a monoclonal antibody against mouse Leukocyte-associated immunoglobulin-like receptor-1 in vitro. By immunohistochemistry, we found that Leukocyte-associated immunoglobulin-like receptor-1 was mainly expressed by macrophages in the inflamed synovial tissue of rheumatoid arthritis patients. In addition, serum and synovial fluid levels of soluble Leukocyte-associated immunoglobulin-like receptor-1 were higher in rheumatoid arthritis patients compared to healthy controls or osteoarthritis patients. Moreover, overexpression of Leukocyte-associated immunoglobulin-like receptor-1 in CD14+ monocytes from healthy volunteers also inhibited human osteoclastogenesis. CONCLUSION: Collectively, these data demonstrate for the first time that Leukocyte-associated immunoglobulin-like receptor-1 inhibits osteoclastogenesis. Therefore, these results may have therapeutic implications for the treatment of rheumatoid arthritis.

  8. Immunoglobulin Replacement Therapy for Primary Immunodeficiency.

    Science.gov (United States)

    Sriaroon, Panida; Ballow, Mark

    2015-11-01

    Immunoglobulin replacement therapy has been standard treatment in patients with primary immunodeficiency diseases for the past 3 decades. The goal of therapy is to reduce serious bacterial infections in individuals with antibody function defects. Approximately one-third of patients receiving intravenous immunoglobulin treatment experience adverse reactions. Recent advances in manufacturing processes have resulted in products that are safer and better tolerated. Self-infusion by the subcutaneous route has become popular and resulted in better quality of life. This review summarizes the use of immunoglobulin therapy in primary immunodeficiency diseases including its properties, dosing, adverse effects, and different routes of administration.

  9. 7th International Immunoglobulin Conference: Poster presentations.

    Science.gov (United States)

    Warnatz, K; Ballow, M; Stangel, M; Bril, V

    2014-12-01

    The pan-European survey provides useful information on the accessibility and trends of intravenous and subcutaneous immunoglobulin (IVIg/SCIg) therapy, which is used to treat primary immunodeficiency disorders (PIDs). Although immunoglobulin (Ig) therapy is the first-line treatment for PIDs, the mechanisms of action of Ig therapy may differ according to the condition it is used to treat. Moreover, intriguing presentations suggest that further investigation is required to understand more clearly both the haematological and immunoregulatory effects of therapeutic immunoglobulin. This can ultimately provide more information on optimizing Ig therapy efficacy, and establish whether individualized dosing regimens for patients will be conducive to better clinical outcomes. In addition to treating autoimmune and inflammatory conditions, there is evidence to suggest that immunoglobulins can potentially play a role in transplantation, which warrants further investigation for future use.

  10. Thermodynamic stability contributes to immunoglobulin specificity.

    Science.gov (United States)

    Dimitrov, Jordan D; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien

    2014-05-01

    Antigen-binding specificity of immunoglobulins is important for their function in immune defense. However, immune repertoires contain a considerable fraction of immunoglobulins with promiscuous binding behavior, the physicochemical basis of which is not well understood. Evolution of immunoglobulin specificity occurs through iterative processes of mutation and selection, referred to as affinity maturation. Recent studies reveal that some somatic mutations could compromise the thermodynamic stability of the variable regions of immunoglobulins. By integrating this observation with the wealth of data on the evolution of novel enzyme activities, we propose that antibody specificity is linked to the thermodynamic stability of the antigen-binding regions, which provides a quantitative distinction between highly specific and promiscuous antibodies.

  11. Immunoglobulin class-switch recombination deficiencies.

    Science.gov (United States)

    Durandy, Anne; Kracker, Sven

    2012-07-30

    Immunoglobulin class-switch recombination deficiencies (Ig-CSR-Ds) are rare primary immunodeficiencies characterized by defective switched isotype (IgG/IgA/IgE) production. Depending on the molecular defect in question, the Ig-CSR-D may be combined with an impairment in somatic hypermutation (SHM). Some of the mechanisms underlying Ig-CSR and SHM have been described by studying natural mutants in humans. This approach has revealed that T cell-B cell interaction (resulting in CD40-mediated signaling), intrinsic B-cell mechanisms (activation-induced cytidine deaminase-induced DNA damage), and complex DNA repair machineries (including uracil-N-glycosylase and mismatch repair pathways) are all involved in class-switch recombination and SHM. However, several of the mechanisms required for full antibody maturation have yet to be defined. Elucidation of the molecular defects underlying the diverse set of Ig-CSR-Ds is essential for understanding Ig diversification and has prompted better definition of the clinical spectrum of diseases and the development of increasingly accurate diagnostic and therapeutic approaches.

  12. Immunoglobulin: production, mechanisms of action and formulations

    Directory of Open Access Journals (Sweden)

    Marcia Cristina Zago Novaretti

    2011-10-01

    Full Text Available Human immunoglobulin (Ig began to be applied in the clinical practice with the treatment of primary immunodeficiencies. Quickly, applications of Ig increased, as its anti-inflammatory and immunomodulatory functions were elucidated. Currently, Ig is the most commonly used blood product. Ig is obtained by processing plasma; methods, in particular, techniques to reduce plasma viral loads have been evolving over the years and include: pasteurization, solvent/ detergent treatment, caprylic acid treatment and nanofiltration. These methods contribute to increased safety and quality of blood products. The mechanisms of action of Ig not only involve the blockade of Fc receptors of phagocytes, but also control complement pathways, idiotype-anti-idiotype dimer formation, blockage of superantigen binding to T cells, inhibition of dendritic cells and stimulation of regulatory T cells (Tregs. There are several formulations of Ig available, each one with its own peculiar characteristics. In Brazil, there is stringent legislation regulating the quality of Ig. Only Ig products that completely fulfill the quality control criteria are released for use. These standards involve different tests from visual inspection to determination of anti-complementary activity. This paper will further review the history and current status of Ig, including its production and mechanisms of action. The formulations available in Brazil and also the criteria of quality control currently applied will be presented.

  13. Immunoglobulin A nephropathy: Basic characteristics

    Directory of Open Access Journals (Sweden)

    Petrović Lada

    2003-01-01

    Full Text Available Introduction Immunoglobulin A nephropathy (IgAN is one of the most common forms of primary glomerulonephritis in many countries. Most clinical features of IgAN point to a renal problem, such as recurrent macroscopic hematuria or asymptomatic microscopic hematuria and proteinuria. Pathologic features of IgAN present with different types and different degrees of glomerular tubulointerstitial and vascular lesions. The aim of this study was detailed analysis of clinical and laboratory findings, as well as findings of immunofluorescence and light microscopy. We also investigated associations between these factors. Material and methods We investigated 60 patients who underwent renal biopsy. The study was partly retrospective and partly prospective. Results The average age of patients was 34.19 years. Male female ratio was 2.33:1. IgAN was most frequently asymptomatic (83.33% as microhematuria and proteinuria, while gross hematuria was found in 16.667%. Renal biopsy material was analyzed by light microscopy revealing changes in all glomerular structures. Immunofluorescence microscopy demonstrated dominant IgA deposits. This study established association of glomerulosclerosis with clinical features of disease. Discussion and conclusions IgAN frequently develops in the 4th decade of life, mostly in males and presents as asymptomatic (83.33%. Patohistological changes include all glomerular structures. There is no specific serological test for IgAN, but pathological changes affect clinical features of the disease, as proteinuria and increase of creatinine concentration.

  14. Postgraduates courses offered to nursing

    Directory of Open Access Journals (Sweden)

    Pedro Jorge Araujo

    2011-07-01

    Full Text Available Aim: To know the official masters that the Spanish Universities have offered during the academic course 2010/2011.Material and methods: Descriptive observational and transversal court study, in which it has analysed 170 university official masters and in which it has used a questionnaire with a total of 15 questions elaborated for this work.Results: 52 Spanish Universities of the 75 that there is have offered during the academic course 2010/2011 official masters that can realise for graduated in infirmary. By areas, the official masters more offered have been the ones of nutrition and alimentary security. 76,33% of the official masters have a length of 1 academic year. Almost the half of the official masters have an orientation researcher-professional and almost 40% researcher. 62,65% of the masters give of face-to-face way. In 52,1% of the official masters do not realise external practices and 86,2% has continuity with the doctorate.Conclusions: It has seen that it is necessary that expand the number of masters including other fields of study that contribute to a main specialisation of the professionals of the infirmary. An important percentage of official masters give in face-to-face modality, and there is very few offered on-line or to distance.

  15. Secretory immunoglobulin A and immunoglobulin G in horse saliva.

    Science.gov (United States)

    Palm, Anna-Karin E; Wattle, Ove; Lundström, Torbjörn; Wattrang, Eva

    2016-11-01

    This study aimed to increase the knowledge on salivary antibodies in the horse since these constitute an important part of the immune defence of the oral cavity. For that purpose assays to detect horse immunoglobulin A (IgA) including secretory IgA (SIgA) were set up and the molecular weights of different components of the horse IgA system were estimated. Moreover, samples from 51 clinically healthy horses were tested for total SIgA and IgG amounts in saliva and relative IgG3/5 (IgG(T)) and IgG4/7 (IgGb) content were tested in serum and saliva. Results showed a mean concentration of 74μg SIgA/ml horse saliva and that there was a large inter-individual variation in salivary SIgA concentration. For total IgG the mean concentration was approx. 5 times lower than that of SIgA, i.e. 20μg IgG/ml saliva and the inter-individual variation was lower than that observed for SIgA. The saliva-serum ratio for IgG isotypes IgG3/5 and IgG4/7 was also assessed in the sampled horses and this analysis showed that the saliva-serum ratio of IgG4/7 was in general approximately 4 times higher than that of IgG3/5. The large inter-individual variation in salivary SIgA levels observed for the normal healthy horses in the present study emphasises the need for a large number of observations when studying this parameter especially in a clinical setting. Moreover, our results also indicated that some of the salivary IgG does not originate from serum but may be produced locally. Thus, these results provide novel insight, and a base for further research, into salivary antibody responses of horses. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Cow's milk with active immunoglobulins against Campylobacter jejuni: effects of temperature on immunoglobulin activity.

    Science.gov (United States)

    Riera, Francisco; Alvarez, Alejandro; Espi, Alberto; Prieto, Miguel; de la Roza, Begoña; Vicente, Fernando

    2014-04-01

    Adult Holstein cows were injected with an antiserum against Campylobacter jejuni and immunoglobulin activities in vitro were determined in blood and milk several weeks after injection. The immunoactivity of immunoglobulins in milk was measured by an ELISA after different temperature-time treatments (60-91°C and 4-3600 s) at laboratory and pilot-plant scales. Kinetic and thermodynamic parameters were determined. An increase in immunoglobulin activity in milk was detected several days after injection. Optical densities increased by three- to seven-fold in this period. The activity started to decay 4-5 weeks after injection. Immunoglobulins maintained most of their in vitro activity under pasteurisation conditions (72°C and 15 s) and were denatured following first-order kinetics. The injection protocol applied allows milk with specific immunoglobulins against Campylobacter jejuni to be obtained. Traditional pasteurisation did not reduce this activity. © 2013 Society of Chemical Industry.

  17. The place of intravenous immunoglobulin in rheumatic diseases

    Directory of Open Access Journals (Sweden)

    N. V. Seredavkina

    2015-01-01

    Full Text Available Therapy with intravenous human immunoglobulin (IVIG was and continues to remain essential for a number of diseases. At the same time the evidence base for IVIG use is extremely small in rheumatology. Clinical experience shows that IVIG is effective in treating thrombocytopenic purpura, Guillain–Barre syndrome, and chronic inflammatory demyelinating polyneuropathy, which develop in the presence of rheumatic diseases, such as systemic lupus erythematosus, inflammatory myopathies, and antineutrophil cytoplasmic antibody-associated vasculitides. The review considers indications for the use of IVIG, its dosage regimen, benefits, and adverse reactions and analyzes the Russian and foreign literature on this issue.

  18. WITHDRAWN: Immunoglobulin treatment for respiratory syncytial virus infection.

    Science.gov (United States)

    Fuller, Hannah L; Del Mar, Chris B

    2010-09-08

    Respiratory syncytial virus (RSV) bronchiolitis and pneumonia hospitalise hundreds of thousands of infants every year. Treatment is largely supportive therapy, (for example, oxygen, fluids and occasionally mechanical ventilation). Ribavirin, an antiviral agent, is licensed for severe RSV infection, although systematic reviews find it of no benefit. Passive protection against RSV can be achieved through monthly intramuscular injections of the humanised monoclonal anti-RSV antibody palivizumab (Synagis), and yields a 55% reduction in RSV hospitalisation in susceptible infants. This review assesses immunoglobulin treatment of RSV infection rather than its role as a prophylactic measure. To assess the efficacy of adding human or humanised immunoglobulin therapy to supportive therapy in infants hospitalised with laboratory-determined RSV infection. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2006, issue 1) which contains the Acute Respiratory Infections Group's specialized regsiter, MEDLINE (1966 to Week 4, January 2006) and EMBASE (1980 to September 2005). We also ran searches of reference lists of relevant trials and review articles and searches of personal files. We did not impose any language restrictions. We selected randomised controlled trials (RCTs) that compared immunoglobulin treatment with a placebo control in children hospitalised for RSV infection with bronchiolitis or pneumonia or other lower respiratory tract infection (LRTI) with laboratory-documented RSV infection. The primary outcomes of interest were mortality, length of hospitalisation, length of ventilation and oxygen dependence. Secondary outcome measures were pulmonary function and re-hospitalisations for recurrent breathing difficulties in subsequent years. Any adverse effects of the treatments were also noted, for example, hypersensitivity reactions. Data were extracted but cross-comparison was not possible due to the shortage of studies and

  19. Feasibility of reducing rabies immunoglobulin dosage for passive immunization against rabies: results of In vitro and In vivo studies.

    Science.gov (United States)

    Madhusudana, Shampur Narayan; Ashwin, Belludi Yajaman; Sudarshan, Sampada

    2013-09-01

    Passive immunization is a crucial parameter for prevention of human rabies. Presently as World Health Organization (WHO) strongly advocates local infiltration of rabies immunoglobulin in and around the bite wound, we feel that there is no basis for calculating the dose of immunoglobulin based on body weight. Keeping this in view we conducted both in vitro and in vivo studies to know whether the dose of immunoglobulin can be reduced and still obtain complete neutralization of the virus. In vitro neutralization studies were conducted using CVS strain of virus and BHK 21 cells. In vivo experiments were conducted in 4 weeks old Swiss albino mice by initial challenge with CVS followed by infiltration with increasing dilutions of either human rabies immunoglobulin (HRIG) and equine rabies immunoglobulin (ERIG). In vitro studies showed that a dose of 100 FFD 50 of CVS was neutralized by increasing dilution of both HRIG and ERIG and 100% neutralization was observed with HRIG and ERIG in as low quantities as 0.025 IU. In mice studies there was 100% survival of mice infiltrated with 0.025 IU of both HRIG and ERIG compared with 100% mortality in mice infiltrated with normal saline. These results suggest that it is possible to reduce the dose of rabies immunoglobulins by at least 16 times the presently advocated dose. These findings needs to be further evaluated using larger animal models and street viruses prevalent in nature but cannot serve as recommendations for use of RIG for passive immunization in humans.

  20. Extração de DNA a partir de sangue humano coagulado para aplicação nas técnicas de genotipagem de antígenos leucocitários humanos e de receptores semelhantes à imunoglobulina DNA extraction from coagulated human blood for application in genotyping techniques for human leukocyte antigen and immunoglobulin-like receptors

    Directory of Open Access Journals (Sweden)

    Daniela Maira Cardozo

    2009-12-01

    Full Text Available O objetivo deste estudo foi padronizar uma metodologia de extração de DNA de alta qualidade a partir de amostras de sangue coagulado. Quarenta e oito amostras de sangue humano coagulado foram utilizadas para a extração de DNA pelo kit comercial EZ-DNA® (Biological Industries, Beit Haemek, Israel, pelo kit de coluna Neoscience® (One Lambda Inc., San Diego, CA e pelo método modificado de salting out. Apenas o método de salting out foi capaz de extrair altas concentrações de DNA (média, 180ng/µL, as quais foram medidas pelo detector de fluorescência Qubit® (Invitrogen, USA. Este método permitiu a amplificação dos genes HLA (human leukocyte antigens pela tecnologia PCR-SSO (polymerase chain reaction - specific sequence of oligonucleotides Luminex, a qual exige DNA de boa qualidade, e de genes KIR (killer cell immunoglobulin-like receptors pela técnica made in house PCR-SSP (polymerase chain reaction-sequence specific of primers, a qual demanda uma concentração específica de DNA (10ng/µL. Concluímos que a técnica de salting out modificada foi muito eficiente, simples e rápida para a extração de DNA de amostras de sangue humano coagulado, com o objetivo de realizar a genotipagem de genes HLA e KIR.The objective of this study was to standardize a method for extracting high-quality DNA from samples of coagulated blood. Forty-eight samples of human coagulated blood were used for DNA extraction by means of the EZ-DNA® commercial kit (Biological Industries, Beit Haemek, Israel, the Neoscience® column kit (One Lambda Inc., San Diego, CA, USA and a modified salting-out method. Only the salting-out method was able to extract high concentrations of DNA (mean, 180 ng/¼l, which were measured using the Qubit® fluorescence detector (Invitrogen, USA. This method enabled amplification of HLA (human leukocyte antigen genes using the Luminex PCR-SSO (polymerase chain reaction - sequence-specific oligonucleotide technology, which demands

  1. The effect of chronic ammonia exposure on acute phase proteins, immunoglobulin and cytokines in laying hens

    Science.gov (United States)

    Ammonia is a potential health hazard to both humans and animals, causing systemic low-grade inflammation based on its levels and durations. The objective of this study was to examine the effect of 45 weeks of exposure to 30 ppm NH3 on the concentrations of acute phase proteins, immunoglobulins and c...

  2. Methods for the purification of equine rabies immunoglobulin: Effects on yield and biological activity

    NARCIS (Netherlands)

    H.A. Hong; E.J.M. Rooijakkers; N.T. Ke; J.M. Groen (Jan); A.D.M.E. Osterhaus (Albert)

    1994-01-01

    textabstractSince rabies is still a major cause of human death in many developing countries and the implementation of recommended post-exposure prophylaxis by vaccination and specific immunoglobulin therapy is largely hampered by its high cost, the development of cheap rabies vaccines and immunoglob

  3. Nonimmune immunoglobulin binding and multiple adhesion characterize Plasmodium falciparum-infected erythrocytes of placental origin

    DEFF Research Database (Denmark)

    Rasti, Niloofar; Namusoke, Fatuma; Chêne, Arnaud;

    2006-01-01

    . A P. falciparum erythrocyte membrane protein 1 variant, VAR2CSA, and the placental receptor chondroitin sulfate A (CSA) are currently the focus of PAM research. A role for immunoglobulins (IgG and IgM) from normal human serum and hyaluronic acid as additional receptors in placental sequestration have...

  4. A preliminary analysis of the immunoglobulin genes in the African elephant (Loxodonta africana.

    Directory of Open Access Journals (Sweden)

    Yongchen Guo

    Full Text Available The genomic organization of the IgH (Immunoglobulin heavy chain, Igκ (Immunoglobulin kappa chain, and Igλ (Immunoglobulin lambda chain loci in the African elephant (Loxodonta africana was annotated using available genome data. The elephant IgH locus on scaffold 57 spans over 2,974 kb, and consists of at least 112 V(H gene segments, 87 D(H gene segments (the largest number in mammals examined so far, six J(H gene segments, a single μ, a δ remnant, and eight γ genes (α and ε genes are missing, most likely due to sequence gaps. The Igκ locus, found on three scaffolds (202, 50 and 86, contains a total of 153 V(κ gene segments, three J(κ segments, and a single C(κ gene. Two different transcriptional orientations were determined for these V(κ gene segments. In contrast, the Igλ locus on scaffold 68 includes 15 V(λ gene segments, all with the same transcriptional polarity as the downstream J(λ-C(λ cluster. These data suggest that the elephant immunoglobulin gene repertoire is highly diverse and complex. Our results provide insights into the immunoglobulin genes in a placental mammal that is evolutionarily distant from humans, mice, and domestic animals.

  5. A preliminary analysis of the immunoglobulin genes in the African elephant (Loxodonta africana).

    Science.gov (United States)

    Guo, Yongchen; Bao, Yonghua; Wang, Hui; Hu, Xiaoxiang; Zhao, Zhihui; Li, Ning; Zhao, Yaofeng

    2011-02-25

    The genomic organization of the IgH (Immunoglobulin heavy chain), Igκ (Immunoglobulin kappa chain), and Igλ (Immunoglobulin lambda chain) loci in the African elephant (Loxodonta africana) was annotated using available genome data. The elephant IgH locus on scaffold 57 spans over 2,974 kb, and consists of at least 112 V(H) gene segments, 87 D(H) gene segments (the largest number in mammals examined so far), six J(H) gene segments, a single μ, a δ remnant, and eight γ genes (α and ε genes are missing, most likely due to sequence gaps). The Igκ locus, found on three scaffolds (202, 50 and 86), contains a total of 153 V(κ) gene segments, three J(κ) segments, and a single C(κ) gene. Two different transcriptional orientations were determined for these V(κ) gene segments. In contrast, the Igλ locus on scaffold 68 includes 15 V(λ) gene segments, all with the same transcriptional polarity as the downstream J(λ)-C(λ) cluster. These data suggest that the elephant immunoglobulin gene repertoire is highly diverse and complex. Our results provide insights into the immunoglobulin genes in a placental mammal that is evolutionarily distant from humans, mice, and domestic animals.

  6. Generation of Monoclonal Antibodies against Immunoglobulin Proteins of the Domestic Ferret (Mustela putorius furo)

    Science.gov (United States)

    2017-01-01

    The domestic ferret (Mustela putorius furo) serves as an animal model for the study of several viruses that cause human disease, most notably influenza. Despite the importance of this animal model, characterization of the immune response by flow cytometry (FCM) is severely hampered due to the limited number of commercially available reagents. To begin to address this unmet need and to facilitate more in-depth study of ferret B cells including the identification of antibody-secreting cells, eight unique murine monoclonal antibodies (mAb) with specificity for ferret immunoglobulin (Ig) were generated using conventional B cell hybridoma technology. These mAb were screened for reactivity against ferret peripheral blood mononuclear cells by FCM and demonstrate specificity for CD79β+ B cells. Several of these mAb are specific for the light chain of surface B cell receptor (BCR) and enable segregation of kappa and lambda B cells. Additionally, a mAb that yielded surface staining of nearly all surface BCR positive cells (i.e., pan ferret Ig) was generated. Collectively, these MαF-Ig mAb offer advancement compared to the existing portfolio of polyclonal anti-ferret Ig detection reagents and should be applicable to a wide array of immunologic assays including the identification of antibody-secreting cells by FCM. PMID:28286781

  7. Facilitated subcutaneous immunoglobulin (fSCIg) therapy--practical considerations.

    Science.gov (United States)

    Ponsford, M; Carne, E; Kingdon, C; Joyce, C; Price, C; Williams, C; El-Shanawany, T; Williams, P; Jolles, S

    2015-12-01

    There is an increasing range of therapeutic options for primary antibody-deficient patients who require replacement immunoglobulin. These include intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin (SCIg), rapid push SCIg and most recently recombinant human hyaluronidase-facilitated SCIg (fSCIg). Advantages of fSCIg include fewer needle punctures, longer infusion intervals and an improved adverse effect profile relative to IVIg. Limited real-life experience exists concerning the practical aspects of switching or starting patients on fSCIg. We describe the first 14 patients who have been treated with fSCIg at the Immunodeficiency Centre for Wales (ICW), representing more than 6 patient-years of experience. The regimen was well tolerated, with high levels of satisfaction and no increase in training requirement, including for a treatment-naive patient. Two patients discontinued fSCIg due to pain and swelling at the infusion site, and one paused therapy following post-infusion migraines. Ultrasound imaging of paired conventional and facilitated SCIg demonstrated clear differences in subcutaneous space distribution associated with a 10-fold increase in rate and volume delivery with fSCIg. Patient profiles for those choosing fSCIg fell into two main categories: those experiencing clinical problems with their current treatment and those seeking greater convenience and flexibility. When introducing fSCIg, consideration of the type and programming of infusion pump, needle gauge and length, infusion site, up-dosing schedule, home training and patient information are important, as these may differ from conventional SCIg. This paper provides guidance on practical aspects of the administration, training and outcomes to help inform decision-making for this new treatment modality.

  8. Immunoglobulins and their fragments on solid surfaces.

    NARCIS (Netherlands)

    Buijs, J.A.G.

    1995-01-01

    SummaryAdsorption of immunoglobulin G (IgG) is a common step in the production of immunological tests and biosensors. The use of IgG in these applications stems from its ability to specifically bind all kinds of molecules (antigens). In these tests the IgG molecules are immobilised

  9. Estimation of bovine colostral immunoglobulins by refractometry.

    Science.gov (United States)

    Molla, A

    1980-07-12

    The total protein of colostral whey from dairy cows as determined by a refractometer were compared with the immune globulin concentration obtained by cellulose acetate membrane electrophoresis and the immunoglobulin (IgA + IgG + IgM) contents determined by radial immunodiffusion. The coefficient of correlation between the results obtained by refractometry and electrophoresis was 0.98 (P whey.

  10. 6th International Immunoglobulin Symposium: Poster presentations

    NARCIS (Netherlands)

    Fernandez-Cruz, E.; Kaveri, S.V.; Peter, H.H.; Durandy, A.; Cantoni, N.; Quinti, I.; Sorensen, R.; Bussel, J.B.; Danieli, M.G.; Winkelmann, A.; Bayry, J.; Kaesermann, F.; Spaeth, P.; Helbert, M.; Salama, A.; van Schaik, I.N.; Yuki, N.

    2009-01-01

    P>The posters presented at the 6th International Immunoglobulin Symposium covered a wide range of fields and included both basic science and clinical research. From the abstracts accepted for poster presentation, 12 abstracts were selected for oral presentations in three parallel sessions on immunod

  11. Facilitated subcutaneous immunoglobulin administration (fSCIg)

    DEFF Research Database (Denmark)

    Blau, Igor-Wolfgang; Conlon, Niall; Petermann, Robert

    2016-01-01

    and diverse medical needs that treatments for SID management should strive to meet. In this special report, we study the opportunities provided by facilitated subcutaneous immunoglobulin administration (fSCIg) to treat patients for whom the conventional routes (intravenous and subcutaneous) are sub...

  12. Linear immunoglobulin A/immunoglobulin G bullous dermatosis associated with Vogt-Koyanagi-Harada disease.

    Science.gov (United States)

    Yanagihara, Shigeto; Mizuno, Nobuyuki; Naruse, Akiko; Tateishi, Chiharu; Tsuruta, Daisuke; Ishii, Masamitsu

    2011-08-01

    Vogt-Koyanagi-Harada disease is characterized by marked bilateral uveitis associated with symmetric vitiligo, alopecia, poliosis and dysacousia. Linear immunoglobulin (Ig)A bullous dermatosis (LABD) is characterized by small, tense, subepidermal bullae caused by IgA type autoantibody targeting the basal lamina. LABD patients sometimes show coexistence of IgG type autoantibody, termed linear IgA/IgG bullous dermatosis (LAGBD). We reported a 35-year-old Japanese male case of combined LAGBD and Vogt-Koyanagi-Harada disease. His human leukocyte antigen typing was -A24, B52, C*1202, DR*1502, DQ*0601. Immunoblot revealed that patient sera reacted to both 180- and 230-kDa proteins at the IgA and IgG level. Because Vogt-Koyanagi-Harada disease and LABD are reported to be associated with other autoimmune diseases, it is probable that Vogt-Koyanagi-Harada disease and LAGBD in our case may be associated with each other in the pathomechanism. However, we cannot exclude the possibility of this being mere coincidence.

  13. Intravenous immunoglobulin treatment of children with autism.

    Science.gov (United States)

    Plioplys, A V

    1998-02-01

    Since autism has been associated with immunologic abnormalities suggesting an autoimmune cause of autistic symptoms in a subset of patients, this study was undertaken to investigate whether intravenous immunoglobulin (i.v.Ig) would improve autistic symptoms. Ten autistic children with immunologic abnormalities, demonstrated on blood tests, were enrolled in this study. Their ages ranged from 4 to 17 years, with two girls and eight boys. Eight children (1 female and 7 male) historically had undergone autistic regression. Intravenous immunoglobulin, 200 to 400 mg/kg, was administered every 6 weeks for an intended treatment program of four infusions. In five children, there was no detectable change in behavior during the treatment program. In four children, there was a mild improvement noted in attention span and hyperactivity. In none of these children did the parents feel that the improvement was sufficient to warrant further continuation of the infusions beyond the termination of the program. Only in one child was there a very significant improvement, with almost total amelioration of autistic symptoms over the time period of the four infusions. Once the treatment program was completed, this child gradually deteriorated over a 5-month time period and fully reverted to his previous autistic state. In this treatment program, five children had no response to intravenous immunoglobulin. In the four children who showed mild improvements, those improvements may simply have been due to nonspecific effects of physician intervention and parental expectation (ie, placebo effect). However, in one child there was a very significant amelioration of autistic symptoms. There were no distinguishing historic or laboratory features in this child who improved. Given a positive response rate of only 10% in this study, along with the high economic costs of the immunologic evaluations and the intravenous immunoglobulin treatments, the use of intravenous immunoglobulin to treat autistic

  14. Immunoglobulin A in Bovine Milk: A Potential Functional Food?

    Science.gov (United States)

    Cakebread, Julie A; Humphrey, Rex; Hodgkinson, Alison J

    2015-08-26

    Immunoglobulin A (IgA) is an anti-inflammatory antibody that plays a critical role in mucosal immunity. It is found in large quantities in human milk, but there are lower amounts in bovine milk. In humans, IgA plays a significant role in providing protection from environmental pathogens at mucosal surfaces and is a key component for the establishment and maintenance of intestinal homeostasis via innate and adaptive immune mechanisms. To date, many of the dairy-based functional foods are derived from bovine colostrum, targeting the benefits of IgG. IgA has a higher pathogenic binding capacity and greater stability against proteolytic degradation when ingested compared with IgG. This provides IgA-based products greater potential in the functional food market that has yet to be realized.

  15. Disbalance of immunoglobulins the clinical importance of increased serum levels of immunoglobulin-A and -G in combination with normal or diminished immunoglobulin-M concentrations

    NARCIS (Netherlands)

    Bakker, H.D.; Imhof, J.W.; Mul, N.A.J.; Ballieux, R.E.

    1967-01-01

    A disbalance of immunoglobulin-A (IgA), immunoglobulin-G (IgG) and immunoglobulin-M (IgM) concentrations—i.e., increased IgA and IgG fractions and a normal or diminished IgM concentration—is not a specific finding but one that frequently occurs in collagen diseases which take a chronic course. In th

  16. Outcome of Intravenous Immunoglobulin-Transmitted HTLV-I, Hepatitis B, Hepatitis C, and HIV infections

    OpenAIRE

    Mohsen Foroughipour; Farahzad Jabbari Azad; Reza Farid hosseini; Abbas Shirdel; Amir Reza Khalighi; Hadis Yousefzadeh; Homa Sadri; Toktam Moghiman; Hossein Hekmatkhah

    2013-01-01

    Objective(s): Since each unit of Intravenous Immunoglobulin (IVIG) is obtained from different blood donors, blood-borne viral diseases is of high importance. We aimed at investigating the prevalence of various viral infections: Human T-cell Lymphotropic Virus Type 1 (HTLV-I), Hepatitis B (HBV), Hepatitis C (HCV), and Human Immunodeficiency Virus (HIV) among patients referred for IVIG therapy section in Mashhad University of Medical Sciences, Mashhad, Iran. Materials and Methods: A prospective...

  17. Artificial Affinity Proteins as Ligands of Immunoglobulins

    Directory of Open Access Journals (Sweden)

    Barbara Mouratou

    2015-01-01

    Full Text Available A number of natural proteins are known to have affinity and specificity for immunoglobulins. Some of them are widely used as reagents for detection or capture applications, such as Protein G and Protein A. However, these natural proteins have a defined spectrum of recognition that may not fit specific needs. With the development of combinatorial protein engineering and selection techniques, it has become possible to design artificial affinity proteins with the desired properties. These proteins, termed alternative scaffold proteins, are most often chosen for their stability, ease of engineering and cost-efficient recombinant production in bacteria. In this review, we focus on alternative scaffold proteins for which immunoglobulin binders have been identified and characterized.

  18. ABZYME ACTIVITY OF POLYCLONAL IMMUNOGLOBULINS IN SPONDYLOARTHROPATHIES

    Directory of Open Access Journals (Sweden)

    E. V. Kunder

    2009-01-01

    Full Text Available Abstract. Polyclonal immunoglobulins G (subclasses 1, 2, 4 from sera of 255 patients and 69 healthy persons were studied by a combined approach using rivanol treatment and affinity chromatography. Enzymatic reactions were carried out according to the methods that we have previously developed and validated for evaluation of abzyme activity in the patients with different disorders. The levels of DNase, proteolytic BAPNA-amidase (benzoylarginine-p-nitroanilide amidase, and superoxyde dismutase abzyme activity in spondyloarthropathies proved to be significantly higher (p = 0.001, as compared with a control group. Catalase activity of immunoglobulines in the disorders studied was compatible to control levels (p > 0.05. Analysis of relations between abzyme activity and clinical and laboratory signs of the diseases has revealed some significant correlations. Prevalence of abzyme DNAse activity is found in the patients with psoriatic arthritis, as compared to reactive arthritis and ankylosing spondilitis (p < 0.001.

  19. Virtual Reality System Offers a Wide Perspective

    Science.gov (United States)

    2008-01-01

    Robot Systems Technology Branch engineers at Johnson Space Center created the remotely controlled Robonaut for use as an additional "set of hands" in extravehicular activities (EVAs) and to allow exploration of environments that would be too dangerous or difficult for humans. One of the problems Robonaut developers encountered was that the robot s interface offered an extremely limited field of vision. Johnson robotics engineer, Darby Magruder, explained that the 40-degree field-of-view (FOV) in initial robotic prototypes provided very narrow tunnel vision, which posed difficulties for Robonaut operators trying to see the robot s surroundings. Because of the narrow FOV, NASA decided to reach out to the private sector for assistance. In addition to a wider FOV, NASA also desired higher resolution in a head-mounted display (HMD) with the added ability to capture and display video.

  20. Antarctic teleost immunoglobulins: more extreme, more interesting.

    Science.gov (United States)

    Coscia, Maria Rosaria; Varriale, Sonia; Giacomelli, Stefano; Oreste, Umberto

    2011-11-01

    We have investigated the immunoglobulin molecule and the genes encoding it in teleosts living in the Antarctic seas at the constant temperature of -1.86 °C. The majority of Antarctic teleosts belong to the suborder Notothenioidei (Perciformes), which includes only a few non-Antarctic species. Twenty-one Antarctic and two non-Antarctic Notothenioid species were included in our studies. We sequenced immunoglobulin light chains in two species and μ heavy chains, partially or totally, in twenty species. In the case of heavy chain, genomic DNA and the cDNA encoding the secreted and the membrane form were analyzed. From one species, Trematomus bernacchii, a spleen cDNA library was constructed to evaluate the diversity of VH gene segments. T. bernacchii IgM, purified from the serum and bile, was characterized. Homology Modelling and Molecular Dynamics were used to determine the molecular structure of T. bernacchii and Chionodraco hamatus immunoglobulin domains. This paper sums up the previous results and broadens them with the addition of unpublished data.

  1. 7th International Immunoglobulin Conference: Interlaken Leadership Awards.

    Science.gov (United States)

    Dalakas, M C; Löscher, W N

    2014-12-01

    The research presented in this section explores novel applications of immunoglobulin (Ig) therapy in neurological disorders. The results from the upcoming and ongoing trials of Drs Honnorat and Gamez are expected to provide meaningful insights into the treatment of two serious and disabling diseases. The results already being reported from the work of Drs Schmidt and Geis in animal models seem promising, but further proof-of-concept research is warranted to translate their significance to human diseases. Dr Goebel's work in developing animal models of complex regional pain syndrome (CRPS) may provide new insights into predicting which CRPS patients could respond to Ig therapy or other immunotherapies. The work being made possible by a number of the Interlaken Leadership Awards may provide fundamental insights in understanding neurological disorders and improving quality of life for the patients who suffer from them.

  2. 甲强龙联合人免疫球蛋白治疗小儿重症手足口病62例效果观察及护理%Observation on the effectiveness of Methylprednisolone combined with human immunoglobulin in the treatment of 62 children patients with severe hand - foot - mouth disease and nursing care

    Institute of Scientific and Technical Information of China (English)

    王芳; 冯玉梅; 汪兰云

    2011-01-01

    Objective: To explore the effectiveness of intravenous infusion of Methylprednisolone in impulse dose combined with human immunoglobulin in the treatment of children patients with severe hand - foot - mouth disease and nursing methods.Methods: 124 children patients were randomly divided into observation group and control group (62 patients for each group).The patients in both groups were treated with anti -inflammatory and anti -viral drugs and nutritional supportive therapy. In the observation group, intravenous infusion of methylprednisolone in impulse dose combined with human immunoglobulin was adopted to achieve the purpose of anti - inflammatory effect, promoting absorption of pulmonary edema, preventing cerebral edema and enhancing patient's immunity; the small doses of methylprednisolone was intravenously given to the patients in the control group.Results: The body temperature of the children patients returned to normal, appetite improved and mental symptoms disappeared,the differences between the two groups were statistically significant ( P < 0.01 ). All the other patients recovered except that one patient was transferred to a higher level hospital because of his severe condition. Conclusion: The impulse dose of Methylprednisolone combined with human immunoglobulin applied to the children patients who have premonition of severe symptoms can alleviate pulmonary edema, prevent cerebral edema and block the vicious cycle of pulmonary edema to cerebral edema so as to promote recovery of the children patients.%目的:探讨静脉滴注冲击量甲强龙联合人免疫球蛋白治疗小儿重症手足口病的效果及护理方法.方法:将124例重症手足口病患儿随机分为观察组和对照组各62例,两组均行抗炎、抗病毒及营养支持药物治疗,观察组静脉滴注冲击量甲强龙联合静脉滴注入免疫球蛋白以达到抗炎、促进肺水肿吸收、防治脑水肿、增强免疫的目的;对照组给予小剂量甲强龙静

  3. Long-term immunoglobulin therapy for chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Rajabally, Yusuf A

    2015-05-01

    Immunoglobulins are an effective but expensive treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although the goal is to improve function, use of functional scales to monitor therapy is not widespread. Limited recent evidence suggests that doses lower than those used traditionally may be as effective. There are no proven correlations of effective dose with weight, disease severity, or duration. The clinical course of CIDP is heterogeneous and includes monophasic forms and complete remissions. Careful monitoring of immunoglobulin use is necessary to avoid overtreatment. Definitive evidence for immunoglobulin superiority over steroids is lacking. Although latest trial evidence favors immunoglobulins over steroids, the latter may result in higher remission rates and longer remission periods. This article addresses the appropriateness of first-line, high-dose immunoglobulin treatment for CIDP and reviews important clinical questions regarding the need for long-term therapy protocols, adequate monitoring, treatment withdrawal, and consideration of corticosteroids as an alternative to immunoglobulin therapy.

  4. Co-evolution of Human Leukocyte Antigen (HLA) Class I Ligands with Killer-Cell Immunoglobulin-Like Receptors (KIR) in a Genetically Diverse Population of Sub-Saharan Africans

    Science.gov (United States)

    Norman, Paul J.; Hollenbach, Jill A.; Nemat-Gorgani, Neda; Guethlein, Lisbeth A.; Hilton, Hugo G.; Pando, Marcelo J.; Koram, Kwadwo A.; Riley, Eleanor M.; Abi-Rached, Laurent; Parham, Peter

    2013-01-01

    Interactions between HLA class I molecules and killer-cell immunoglobulin-like receptors (KIR) control natural killer cell (NK) functions in immunity and reproduction. Encoded by genes on different chromosomes, these polymorphic ligands and receptors correlate highly with disease resistance and susceptibility. Although studied at low-resolution in many populations, high-resolution analysis of combinatorial diversity of HLA class I and KIR is limited to Asian and Amerindian populations with low genetic diversity. At the other end of the spectrum is the West African population investigated here: we studied 235 individuals, including 104 mother-child pairs, from the Ga-Adangbe of Ghana. This population has a rich diversity of 175 KIR variants forming 208 KIR haplotypes, and 81 HLA-A, -B and -C variants forming 190 HLA class I haplotypes. Each individual we studied has a unique compound genotype of HLA class I and KIR, forming 1–14 functional ligand-receptor interactions. Maintaining this exceptionally high polymorphism is balancing selection. The centromeric region of the KIR locus, encoding HLA-C receptors, is highly diverse whereas the telomeric region encoding Bw4-specific KIR3DL1, lacks diversity in Africans. Present in the Ga-Adangbe are high frequencies of Bw4-bearing HLA-B*53:01 and Bw4-lacking HLA-B*35:01, which otherwise are identical. Balancing selection at key residues maintains numerous HLA-B allotypes having and lacking Bw4, and also those of stronger and weaker interaction with LILRB1, a KIR-related receptor. Correspondingly, there is a balance at key residues of KIR3DL1 that modulate its level of cell-surface expression. Thus, capacity to interact with NK cells synergizes with peptide binding diversity to drive HLA-B allele frequency distribution. These features of KIR and HLA are consistent with ongoing co-evolution and selection imposed by a pathogen endemic to West Africa. Because of the prevalence of malaria in the Ga-Adangbe and previous

  5. Exonuclease activity and P nucleotide addition in the generation of the expressed immunoglobulin repertoire

    Directory of Open Access Journals (Sweden)

    Sewell William

    2004-09-01

    Full Text Available Abstract Background Immunoglobulin rearrangement involves random and imprecise processes that act to both create and constrain diversity. Two such processes are the loss of nucleotides through the action of unknown exonuclease(s and the addition of P nucleotides. The study of such processes has been compromised by difficulties in reliably aligning immunoglobulin genes and in the partitioning of nucleotides between segment ends, and between N and P nucleotides. Results A dataset of 294 human IgM sequences was created and partitioned with the aid of a probabilistic model. Non-random removal of nucleotides is seen between the three IGH gene types with the IGHV gene averaging removals of 1.2 nucleotides compared to 4.7 for the other gene ends (p Conclusions The loss of nucleotides due to the action of exonucleases is not random, but is influenced by the nucleotide composition of the genes. P nucleotides do not make a significant contribution to diversity of immunoglobulin sequences. Although palindromic sequences are present in 10% of immunologlobulin rearrangements, most of the 'palindromic' nucleotides are likely to have been inserted into the junction during the process of N nucleotide addition. P nucleotides can only be stated with confidence to contribute to diversity of less than 1% of sequences. Any attempt to identify P nucleotides in immunoglobulins is therefore likely to introduce errors into the partitioning of such sequences.

  6. The determination of the rate of conjugation immunoglobuline with bifunctional chelator

    Science.gov (United States)

    Málek, Z.; Miler, V.; Budský, F.

    2006-01-01

    The work was performed under the GACR project: "Technology of preparation of radionuclides and their labelled compounds for nuclear medicine and pharmacy with the use of the reactor LVR-15" reg. no. 104/03/0499. Imaging of cell’s antigens with the use of labelled immunoglobulines allows imaging of specific receptors on cell membrane and specific tumours. It is necessary to carry out the labelling of the immunoglobulines with radionuclides of suitable physical properties, which form cations (e.g., 111In, 90Y, 177Lu) that form very strong chelates of sufficiently high stability constant preventing the dissociation of complexes or the radionuclide under “in-vivo” conditions. The immunoglobuline must be conjugated with the bifunctional chelator (BCH), which contains both chelating unit and reactive group for binding to the immunoglobuline. In our laboratory we have conjugated human IgG and monoclonal antibody CD20 with diethylenetriamine pentaacetic acid dianhydride (cDTPAA). Radionuclides 90Y and 177Lu prepared on the LVR-15 reactor in NRI Rez were used for labelling. After conjugation and labelling the yields in relation to the amount of isotopic carrier have been determined.

  7. Immunoglobulin G4-Related Pancreatic and Biliary Diseases

    Directory of Open Access Journals (Sweden)

    Hisham Al-Dhahab

    2013-01-01

    Full Text Available BACKGROUND: Autoimmune pancreatitis and autoimmune cholangitis are new clinical entities that are now recognized as the pancreaticobiliary manifestations of immunoglobulin (Ig G4-related disease.

  8. Importance of killer immunoglobulin-like receptors in allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Danilo Santana Alessio Franceschi

    2011-01-01

    Full Text Available Hematopoietic stem cell transplantation is the treatment of choice for many hematologic diseases, such as multiple myeloma, bone marrow aplasia and leukemia. Human leukocyte antigen (HLA compatibility is an important tool to prevent post-transplant complications such as graft rejection and graft-versus-host disease, but the high rates of relapse limit the survival of transplant patients. Natural Killer cells, a type of lymphocyte that is a key element in the defense against tumor cells, cells infected with viruses and intracellular microbes, have different receptors on their surfaces that regulate their cytotoxicity. Killer immunoglobulin-like receptors are the most important, interacting consistently with human leukocyte antigen class I molecules present in other cells and thus controlling the activation of natural killer cells. Several studies have shown that certain combinations of killer immunoglobulin-like receptors and human leukocyte antigens (in both donors and recipients can affect the chances of survival of transplant patients, particularly in relation to the graft-versusleukemia effect, which may be associated to decreased relapse rates in certain groups. This review aims to shed light on the mechanisms and effects of killer immunoglobulin-like receptors - human leukocyte antigen associations and their implications following hematopoietic stem cell transplantation, and to critically analyze the results obtained by the studies presented herein.

  9. THE ACCOUNTANT INFORMATION. DEMAND AND OFFER

    OpenAIRE

    Irina CHIRITA; Ioana ZAHEU

    2008-01-01

    The present paper is trying to correlate what Demand and Offer mean, from the economical point of view, which in the end tends towards the demand and offer of the accountant information. The objective of the demand and offer of accountant information is to promo te an efficient financial communication, objective that might be reached through the confrontation of the informational offer with the user’s demand. The information given by the enterprises are the basis of numerous economical and po...

  10. Determinants of High Schools' Advanced Course Offerings

    Science.gov (United States)

    Iatarola, Patrice; Conger, Dylan; Long, Mark C.

    2011-01-01

    This article examines the factors that determine a high school's probability of offering Advanced Placement (AP) and International Baccalaureate (IB) courses. The likelihood that a school offers advanced courses, and the number of sections that it offers, is largely driven by having a critical mass of students who enter high school with…

  11. The primary relevance of subconsciously offered attitudes

    DEFF Research Database (Denmark)

    Kristiansen, Tore

    2015-01-01

    ) and subconsciously (covertly) offered attitudes – because subconsciously offered attitudes appear to be a driving force in linguistic variation and change in a way that consciously offered attitudes are not. The argument is based on evidence from empirical investigations of attitudes and use in the ‘...

  12. Immunoglobulin Fc gamma receptor promotes immunoglobulin uptake, immunoglobulin-mediated calcium increase, and neurotransmitter release in motor neurons

    Science.gov (United States)

    Mohamed, Habib A.; Mosier, Dennis R.; Zou, Ling L.; Siklos, Laszlo; Alexianu, Maria E.; Engelhardt, Jozsef I.; Beers, David R.; Le, Wei-dong; Appel, Stanley H.

    2002-01-01

    Receptors for the Fc portion of immunoglobulin G (IgG; FcgammaRs) facilitate IgG uptake by effector cells as well as cellular responses initiated by IgG binding. In earlier studies, we demonstrated that amyotrophic lateral sclerosis (ALS) patient IgG can be taken up by motor neuron terminals and transported retrogradely to the cell body and can alter the function of neuromuscular synapses, such as increasing intracellular calcium and spontaneous transmitter release from motor axon terminals after passive transfer. In the present study, we examined whether FcgammaR-mediated processes can contribute to these effects of ALS patient immunoglobulins. F(ab')(2) fragments (which lack the Fc portion) of ALS patient IgG were not taken up by motor axon terminals and were not retrogradely transported. Furthermore, in a genetically modified mouse lacking the gamma subunit of the FcR, the uptake of whole ALS IgG and its ability to enhance intracellular calcium and acetylcholine release were markedly attenuated. These data suggest that FcgammaRs appear to participate in IgG uptake into motor neurons as well as IgG-mediated increases in intracellular calcium and acetylcholine release from motor axon terminals. Copyright 2002 Wiley-Liss, Inc.

  13. Prophylactic immunoglobulin therapy in secondary immune deficiency

    DEFF Research Database (Denmark)

    Agostini, Carlo; Blau, Igor-Wolfgang; Kimby, Eva

    2016-01-01

    INTRODUCTION: In primary immunodeficiency (PID), immunoglobulin replacement therapy (IgRT) for infection prevention is well-established and supported by a wealth of clinical data. On the contrary, very little evidence-based data is available on the challenges surrounding the use of Ig......RT in secondary immune deficiencies (SID), and most published guidelines are mere extrapolations from the experience in PID. AREAS COVERED: In this article, four European experts provide their consolidated opinion on open questions surrounding the prophylactic use of IgRT in SID, based on their clinical...

  14. [Dermatomyositis and Panniculitis: the function of immunoglobulins].

    Science.gov (United States)

    Abdelhafidh, Nadia Ben; Toujeni, Sana; Kefi, Asma; Bousetta, Najeh; Sayhi, Sameh; Gharsallah, Imen; Othmani, Salah

    2016-01-01

    Panniculitis is an inflammatory disease of subcutaneous adipose tissue which is rarely associated with dermatomyositis. It can occur before, after or simultaneously with muscle damage. In most cases, the evolution of panniculitis and of other dermatomyositis affections is favorable with corticosteroids and/or immunosuppressants. We report the case of a 48 year-old patient who developed panniculitis lesions 2 months before having muscular signs. Skin involvement was resistant to corticosteroid treatment associated with immunosuppressants drugs. This led to the use of polyvalent immunoglobulin treatment improving both skin and muscle damage.

  15. Immunoglobulin for necrotising soft tissue infections (INSTINCT)

    DEFF Research Database (Denmark)

    Madsen, Martin Bruun; Lange, Theis; Hjortrup, Peter Buhl;

    2016-01-01

    INTRODUCTION: Necrotising soft tissue infections (NSTI) are aggressive infections that can result in severe disability or death. Intravenous polyspecific immunoglobulin G (IVIG) is used as supplementary treatment for patients with NSTIs. The level of evidence is very low, but suggests that IVIG may....... Secondary outcomes are: mortality; time to resolution of shock; bleeding; sequential organ failure assessment scores on days 1-7; use of renal-replacement therapy, mechanical ventilation and vasopressors; days alive and out of hospital; amputation; and severe adverse reactions. CONCLUSION: This study...

  16. Immunoglobulin G4-Related Disease Mimicking Asthma

    Directory of Open Access Journals (Sweden)

    Hiroshi Sekiguchi

    2013-01-01

    Full Text Available Immunoglobulin (Ig G4-related disease (also known as ‘IgG4-related sclerosing disease’, ‘IgG4-related systemic disease’ or ‘hyper-IgG4-disease’ is a recently recognized systemic fibroinflammatory disease associated with IgG4-positive plasma cells in tissue lesions. IgG4-related disease was initially described as autoimmune pancreatitis, but it is now known to affect virtually any organ. The authors describe a patient presenting with multi-organ manifestations, including airway inflammation mimicking asthma, pulmonary parenchymal infiltrates, intrathoracic lymphadenopathy, submandibular gland swelling and a kidney mass.

  17. Frequent Intratype Neutralization by Plasma Immunoglobulin A Identified in HIV Type 2 Infection

    OpenAIRE

    Özkaya Şahin, Gülşen; Månsson, Fredrik; Palm, Angelica A.; Vincic, Elzbieta; da Silva, Zacarias; Medstrand, Patrik; Norrgren, Hans; Fenyö, Eva Maria; Jansson, Marianne

    2013-01-01

    Human immunodeficiency virus type 2 (HIV-2) is less transmissible and less pathogenic compared to HIV-1 and, when matched for CD4+ T cell count, the plasma viral load in HIV-2-infected individuals is approximately one log lower than in HIV-1-infected individuals. The explanation for these observations is elusive, but differences in virus controlling immunity generated in the two infections may be contributing factors. In the present study, we investigated neutralization by immunoglobulin A (I...

  18. Immunoglobulin Replacement Therapy: When You Need It -- and When You Don't

    Science.gov (United States)

    ... Videos Lists Search Patient Resources Immunoglobulin Replacement Therapy Immunoglobulin Replacement Therapy When you need it—and when ... enough germ-fighting antibodies. A treatment known as immunoglobulin replacement (IgG) therapy can be a lifesaver for ...

  19. The immunoglobulins of cold-blooded vertebrates.

    Science.gov (United States)

    Pettinello, Rita; Dooley, Helen

    2014-11-24

    Although lymphocyte-like cells secreting somatically-recombining receptors have been identified in the jawless fishes (hagfish and lamprey), the cartilaginous fishes (sharks, skates, rays and chimaera) are the most phylogenetically distant group relative to mammals in which bona fide immunoglobulins (Igs) have been found. Studies of the antibodies and humoral immune responses of cartilaginous fishes and other cold-blooded vertebrates (bony fishes, amphibians and reptiles) are not only revealing information about the emergence and roles of the different Ig heavy and light chain isotypes, but also the evolution of specialised adaptive features such as isotype switching, somatic hypermutation and affinity maturation. It is becoming increasingly apparent that while the adaptive immune response in these vertebrate lineages arose a long time ago, it is most definitely not primitive and has evolved to become complex and sophisticated. This review will summarise what is currently known about the immunoglobulins of cold-blooded vertebrates and highlight the differences, and commonalities, between these and more "conventional" mammalian species.

  20. Intravenous immunoglobulin therapy and systemic lupus erythematosus.

    Science.gov (United States)

    Zandman-Goddard, Gisele; Levy, Yair; Shoenfeld, Yehuda

    2005-12-01

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse manifestations. We suggest that intravenous immunoglobulin (IVIg) therapy may be beneficial and safe for various manifestations in SLE. A structured literature search of articles published on the efficacy of IVIg in the treatment of SLE between 1983 and 2005 was conducted. We searched the terms "IVIg," "intravenous immunoglobulin," "lupus," "SLE," and "systemic lupus erythematosus." The various clinical manifestations of SLE that were reported to be successfully treated by IVIg in case reports include autoimmune hemolytic anemia, acquired factor VIII inhibitors, acquired von Willebrand disease, pure red cell aplasia, thrombocytopenia, pancytopenia, myelofibrosis, pneumonitis, pleural effusion, pericarditis, myocarditis, cardiogenic shock, nephritis, end-stage renal disease, encephalitis, neuropsychiatric lupus, psychosis, peripheral neuropathy, polyradiculoneuropathy, and vasculitis. The most extensive experience is with lupus nephritis. There are only a few case series of IVIg use in patients with SLE with various manifestations, in which the response rate to IVIg therapy ranged from 33 to 100%. We suggest that IVIg devoid of sucrose, at a dose of 2 g/kg over a 5-d period given uniformly and at a slow infusion rate in patients without an increased risk for thromboembolic events or renal failure, is a safe and beneficial adjunct therapy for cases of SLE that are resistant to or refuse conventional treatment. The duration of therapy is yet to be established. Controlled trials are warranted.

  1. The Immunoglobulins of Cold-Blooded Vertebrates

    Directory of Open Access Journals (Sweden)

    Rita Pettinello

    2014-11-01

    Full Text Available Although lymphocyte-like cells secreting somatically-recombining receptors have been identified in the jawless fishes (hagfish and lamprey, the cartilaginous fishes (sharks, skates, rays and chimaera are the most phylogenetically distant group relative to mammals in which bona fide immunoglobulins (Igs have been found. Studies of the antibodies and humoral immune responses of cartilaginous fishes and other cold-blooded vertebrates (bony fishes, amphibians and reptiles are not only revealing information about the emergence and roles of the different Ig heavy and light chain isotypes, but also the evolution of specialised adaptive features such as isotype switching, somatic hypermutation and affinity maturation. It is becoming increasingly apparent that while the adaptive immune response in these vertebrate lineages arose a long time ago, it is most definitely not primitive and has evolved to become complex and sophisticated. This review will summarise what is currently known about the immunoglobulins of cold-blooded vertebrates and highlight the differences, and commonalities, between these and more “conventional” mammalian species.

  2. What Has Literature to Offer Computer Science?

    Directory of Open Access Journals (Sweden)

    Mark Dougherty

    2004-04-01

    Full Text Available In this paper I ask the question: what has literature to offer computer science? Can a bilateral programme of research be started with the aim of discovering the same kind of deep intertwining of ideas between computer science and literature, as already exists between computer science and linguistics? What practical use could such results yield? I begin by studying a classic forum for some of the most unintelligible pieces of prose ever written, the computer manual. Why are these books so hard to understand? Could a richer diet of metaphor and onomatopoeia help me get my laser printer working? I then dig down a little deeper and explore computer programs themselves as literature. Do they exhibit aesthetics, emotion and all the other multifarious aspects of true literature? If so, does this support their purpose and understandability? Finally I explore the link between computer code and the human writer. Rather than write large amounts of code directly, we encourage students to write algorithms as pseudo-code as a first step. Pseudo-code tells a story within a semi-formalised framework of conventions. Is this the intertwining we should be looking for?

  3. Cerebrospinal fluid aquaporin-4-immunoglobulin G disrupts blood brain barrier

    DEFF Research Database (Denmark)

    Asgari, Nasrin; Berg, Carsten Tue; Mørch, Marlene Thorsen;

    2015-01-01

    To clarify the significance of immunoglobulin G autoantibody specific for the astrocyte water channel aquaporin-4 in cerebrospinal fluid, aquaporin-4-immunoglobulin G from a neuromyelitis optica patient was administered intrathecally to naïve mice, and the distribution and pathogenic impact...

  4. Subcutaneous versus intravenous immunoglobulin in multifocal motor neuropathy

    DEFF Research Database (Denmark)

    Harbo, T; Andersen, Henning; Hess, A

    2009-01-01

    Background and purpose: For treatment of multifocal motor neuropathy (MMN), we hypothesized that (i) infusion of equivalent dosages of subcutaneous immunoglobulin (SCIG) is as effective as intravenous immunoglobulin (IVIG) and that (ii) subcutaneous infusion at home is associated with a better...

  5. Immunoglobulin Concentration in Tears of Contact Lens Wearers

    Directory of Open Access Journals (Sweden)

    Rajendra P Maurya

    2014-01-01

    Conclusion: The relation of immunoglobulin concentration with increasing duration of wear and material of contact lens shows that tear immunoglobulin rise accrues due to mechanical stimulation, hence contact lenses should not be used for a long period and lenses of hard nature should be discouraged. The maintenance, cleaning and deproteinization of the lenses are of high importance to avoid immunostimulation.

  6. Chemical stabilization of porous silicon for enhanced biofunctionalization with immunoglobulin

    Directory of Open Access Journals (Sweden)

    Nelson Naveas, Vicente Torres Costa, Dario Gallach, Jacobo Hernandez-Montelongo, Raul Jose Martín Palma, Josefa Predenstinacion Garcia-Ruiz and Miguel Manso-Silván

    2012-01-01

    Full Text Available Porous silicon (PSi is widely used in biological experiments, owing to its biocompatibility and well-established fabrication methods that allow tailoring its surface. Nevertheless, there are some unresolved issues such as deciding whether the stabilization of PSi is necessary for its biological applications and evaluating the effects of PSi stabilization on the surface biofunctionalization with proteins. In this work we demonstrate that non-stabilized PSi is prone to detachment owing to the stress induced upon biomolecular adsorption. Biofunctionalized non-stabilized PSi loses the interference properties characteristic of a thin film, and groove-like structures resulting from a final layer collapse were observed by scanning electron microscopy. Likewise, direct PSi derivatization with 3-aminopropyl-triethoxysilane (APTS does not stabilize PSi against immunoglobulin biofunctionalization. To overcome this problem, we developed a simple chemical process of stabilizing PSi (CoxPSi for biological applications, which has several advantages over thermal stabilization (ToxPSi. The process consists of chemical oxidation in H2O2, surface derivatization with APTS and a curing step at 120 °C. This process offers integral homogeneous PSi morphology, hydrophilic surface termination (contact angle θ = 26° and highly efficient derivatized and biofunctionalized PSi surfaces (six times more efficient than ToxPSi. All these features are highly desirable for biological applications, such as biosensing, where our results can be used for the design and optimization of the biomolecular immobilization cascade on PSi surfaces.

  7. Inverse relation between vitamin D and serum total immunoglobulin G in the Scandinavian Cystic Fibrosis Nutritional Study

    DEFF Research Database (Denmark)

    Pincikova, T; Nilsson, K; Moen, I E;

    2011-01-01

    The hallmark of cystic fibrosis (CF) is chronic lung inflammation. The severity of lung disease is closely correlated with immunoglobulin G (IgG) levels. Beyond its contribution to the bone health, the importance of vitamin D has not been fully recognized owing to the lack of human studies provid...

  8. Flow cytometric detection of neutrophil-associated immunoglobulin in patients with or without neutropenia and establishment of the reference interval.

    Science.gov (United States)

    Hwang, Keumrock; Park, Chan-Jeoung; Huh, Hee Jin; Han, Sang Hee; Jang, Seongsoo; Chi, Hyun-Sook

    2011-01-01

    We measured neutrophil-associated immunoglobulin (NAIg) levels using flow cytometry to establish the reference interval for NAIg and to estimate NAIg in patients with or without neutropenia. Peripheral blood from 152 individuals was analyzed for NAIg detection by flow cytometry. Using fluorescescent-conjugated anti-CD10 monoclonal antibody and anti-human immunoglobulins, proportions of NAIgG, NAIgA, and NAIgM bound to neutrophils were measured. Reference intervals for NAIg were set as NAIgG reference intervals defined herein, patients with neutropenia or adverse transfusion reactions may be evaluated in a clinically relevant manner.

  9. Genomic structure and expression of immunoglobulins in Squamata.

    Science.gov (United States)

    Olivieri, David N; Garet, Elina; Estevez, Olivia; Sánchez-Espinel, Christian; Gambón-Deza, Francisco

    2016-04-01

    The Squamata order represents a major evolutionary reptile lineage, yet the structure and expression of immunoglobulins in this order has been scarcely studied in detail. From the genome sequences of four Squamata species (Gekko japonicus, Ophisaurus gracilis, Pogona vitticeps and Ophiophagus hannah) and RNA-seq datasets from 18 other Squamata species, we identified the immunoglobulins present in these animals as well as the tissues in which they are found. All Squamata have at least three immunoglobulin classes; namely, the immunoglobulins M, D, and Y. Unlike mammals, however, we provide evidence that some Squamata lineages possess more than one Cμ gene which is located downstream from the Cδ gene. The existence of two evolutionary lineages of immunoglobulin Y is shown. Additionally, it is demonstrated that while all Squamata species possess the λ light chain, only Iguanidae species possess the κ light chain.

  10. Impact of vegetarian diet on serum immunoglobulin levels in children.

    Science.gov (United States)

    Gorczyca, Daiva; Prescha, Anna; Szeremeta, Karolina

    2013-03-01

    Nutrition plays an important role in immune response. We evaluated the effect of nutrient intake on serum immunoglobulin levels in vegetarian and omnivore children. Serum immunoglobulin levels and iron status were estimated in 22 vegetarian and 18 omnivore children. Seven-day food records were used to assess the diet. There were no significant differences in serum IgA, IgM, and IgG levels between groups of children. Serum immunoglobulin levels were lower in vegetarian children with iron deficiency in comparison with those without iron deficiency. In the vegetarians, IgG level correlated positively with energy, zinc, copper, and vitamin B(6) intake. In the omnivores, these correlations were stronger with IgM level. Despite negligible differences in serum immunoglobulin levels between vegetarian and omnivore children, the impact of several nutrient intakes on IgM and IgG levels differed between groups. Low iron status in vegetarian children can lead to decreased immunoglobulin levels.

  11. DUAL ROLES OF CANCER CELL-EXPRESSED IMMUNOGLOBULINS IN CANCER IMMUNOLOGY

    Directory of Open Access Journals (Sweden)

    Gregory Lee

    2014-01-01

    Full Text Available While the expression of immunoglobulins and T cell receptors on cancer cells has been well-established for decades, the potential roles and mechanisms of action of these cancerous antigen receptors have not been fully elucidated. A monoclonal antibody designated as RP215, which reacts specifically with the carbohydrate-associated epitope located on the heavy chain region of cancerous immunoglobulins and T cell receptors, was used as a unique probe to study the roles of antigen receptors in the immunology of cancer cells. Through extensive cell-based biological and immunological studies, it was found that both anti-antigen receptors and RP215 demonstrated similar actions on the gene regulations involved in the growth/proliferation of cancer cells, as well as on toll-like receptors involved in innate immunity. In addition, RP215-specific cancerous immunoglobulins are believed to capture or neutralize circulating antigen/antibodies which may be harmful to cancer cells within the human body. In contrast to normal B and T cells and their respective receptors in the conventional immune system, cancer cells co-express both immunoglobulins and T cell receptors and immune protection is exercised by unique mechanisms. For example, these cancer cell-expressed antigen receptors display a lack of class switching, limited hyper-mutation, aberrant glycosylations and a strong influence on the toll-like receptors of cancer cells. Therefore, it is hypothesized that both normal and cancerous immune systems may co-exist and operate simultaneously within the human body. The balance of these two immune factors for respective surveillance and protection may be relevant to the outcome of cancer immunotherapy in humans. A potential therapeutic strategy is being developed by using RP215 as a drug candidate to target cancer cells based on these observations.

  12. Marketing strategy to differentiate the offer

    OpenAIRE

    Miceski, Trajko; Pasovska, Silvana

    2013-01-01

    The marketing strategy for differentiation of the offers is important and accepted strategy especially by the bigger legal entities. The differentiation of the offers leads to bigger profit and bigger profitability in operation, through targeting of the demand towards the product of the enterprise. The vertical differentiation of the offers is directed towards the quality of the product itself which is observed as a something superior despite the competitive product which is observed as somet...

  13. Tourists’ expectations towards the agritourism farms’ offer

    Directory of Open Access Journals (Sweden)

    Iwona Wilk

    2013-06-01

    Full Text Available Agritourism plays an important role in multifunctional agriculture. Its development depends on agritourists’ needs identification in relation to the desired agritourism offer components which contributes to their improvement within agritourism farms market activity. The aim of the study was to determine customers preferences towards the agritourism farms offer in the Lodz region. The study was carried out on a sample of 120 respondents in 2011 (July-August and revealed that agritourists expect an offer, consisting of the components of various options offered by agritourism farm, matching their individual needs.

  14. Efficacy of subcutaneous immunoglobulins in primary immunodeficiency with Crohn's-like phenotype: report of a case.

    Science.gov (United States)

    Sanges, M; Spadaro, G; Miniero, M; Mattera, D; Sollazzo, R; D'Armiento, F P; De Palma, G D; Pecoraro, A; Borrelli, F; Genovese, A; D'Arienzo, A

    2015-01-01

    Common variable immune deficiency (CVID) is the most frequent primary immunodeficiency in adults. In CVID, the prevalence of gastrointestinal manifestations ranges between 2 and 50% with a complication-related morbidity second only to that of the respiratory tract. In some cases, clinical and endoscopic features are undistinguishable from those of inflammatory bowel disease (IBD). We describe the case of a 28-year-old man in which a diagnosis of Crohn's disease was firstly suspected. Subsequently, a diagnosis of Crohn's-like disease in a patient with CVID was made and a replacement therapy with human normal immunoglobulin intravenously was started. Unfortunately, serum IgG levels remained below 2.0 g/l in pre-infusional controls with persistence of gastrointestinal symptoms and malnutrition despite anti-inflammatory therapy (mesalazine, corticosteroids). Then, the patient began treatment with human normal immunoglobulins administered subcutaneously. The follow-up visits showed a progressive increase in serum IgG. Moreover, the patient reported improvement of gastrointestinal symptoms with reduction of diarrhoea, and laboratory tests showed a progressive and significant improvement. We confirm that therapy with subcutaneously administered immunoglobulins is safe and effective. In addition, our observations indicate that, for patients with CVID and enteropathic complications, replacement therapy with subcutaneous IgG may be the treatment of choice.

  15. Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity

    Science.gov (United States)

    Corcoran, Martin M.; Phad, Ganesh E.; Bernat, Néstor Vázquez; Stahl-Hennig, Christiane; Sumida, Noriyuki; Persson, Mats A. A.; Martin, Marcel; Hedestam, Gunilla B. Karlsson

    2016-12-01

    Comprehensive knowledge of immunoglobulin genetics is required to advance our understanding of B cell biology. Validated immunoglobulin variable (V) gene databases are close to completion only for human and mouse. We present a novel computational approach, IgDiscover, that identifies germline V genes from expressed repertoires to a specificity of 100%. IgDiscover uses a cluster identification process to produce candidate sequences that, once filtered, results in individualized germline V gene databases. IgDiscover was tested in multiple species, validated by genomic cloning and cross library comparisons and produces comprehensive gene databases even where limited genomic sequence is available. IgDiscover analysis of the allelic content of the Indian and Chinese-origin rhesus macaques reveals high levels of immunoglobulin gene diversity in this species. Further, we describe a novel human IGHV3-21 allele and confirm significant gene differences between Balb/c and C57BL6 mouse strains, demonstrating the power of IgDiscover as a germline V gene discovery tool.

  16. Anti-tumor activities of peptides corresponding to conserved complementary determining regions from different immunoglobulins.

    Science.gov (United States)

    Figueiredo, Carlos R; Matsuo, Alisson L; Massaoka, Mariana H; Polonelli, Luciano; Travassos, Luiz R

    2014-09-01

    Short synthetic peptides corresponding to sequences of complementarity-determining regions (CDRs) from different immunoglobulin families have been shown to induce antimicrobial, antiviral and antitumor activities regardless of the specificity of the original monoclonal antibody (mAb). Presently, we studied the in vitro and in vivo antitumor activity of synthetic peptides derived from conserved CDR sequences of different immunoglobulins against human tumor cell lines and murine B16F10-Nex2 melanoma aiming at the discovery of candidate molecules for cancer therapy. Four light- and heavy-chain CDR peptide sequences from different antibodies (C36-L1, HA9-H2, 1-H2 and Mg16-H2) showed cytotoxic activity against murine melanoma and a panel of human tumor cell lineages in vitro. Importantly, they also exerted anti-metastatic activity using a syngeneic melanoma model in mice. Other peptides (D07-H3, MN20v1, MS2-H3) were also protective against metastatic melanoma, without showing significant cytotoxicity against tumor cells in vitro. In this case, we suggest that these peptides may act as immune adjuvants in vivo. As observed, peptides induced nitric oxide production in bone-marrow macrophages showing that innate immune cells can also be modulated by these CDR peptides. The present screening supports the search in immunoglobulins of rather frequent CDR sequences that are endowed with specific antitumor properties and may be candidates to be developed as anti-cancer drugs.

  17. Production of immunoglobulins in gingival tissue explant cultures from juvenile periodontitis patients

    Energy Technology Data Exchange (ETDEWEB)

    Hall, E.R.; Falkler, W.A. Jr.; Suzuki, J.B. (Univ. of Maryland Dental School, Baltimore (USA))

    1990-10-01

    B lymphocytes and plasma cells are histologically observed in granulomatous periodontal tissues of juvenile periodontitis (JP) patients. Local immune processes may participate in protective or immunopathologic roles in the pathogenesis of this disease. An in vitro explant culture system was utilized to demonstrate the production of immunoglobulins by diseased JP tissues. Immunodiffusion studies using goat anti-human gamma, alpha, or mu chain serum revealed IgG to be the major immunoglobulin present in 92% of the day 1 supernatant fluids (SF) of the 47 JP gingival tissue explant cultures. IgA was present in 15% of the SF; however, no IgM was detected. Staph Protein A isolated 14C-labeled IgG from the SF, when allowed to react with goat anti-human gamma chain serum, formed lines of precipitation. Positive autoradiographs confirmed the biosynthesis of IgG by the explant cultures. The in vitro gingival tissue explant culture system described provides a useful model for the study of localized immunoglobulins produced by diseased tissues of JP patients.

  18. 16 CFR 502.101 - Introductory offers.

    Science.gov (United States)

    2010-01-01

    ... FAIR PACKAGING AND LABELING ACT Retail Sale Price Representations § 502.101 Introductory offers. (a... retail sale at a price lower than the anticipated ordinary and customary retail sale price. (b) The... duration in excess of 6 months. (4) At the time of making the introductory offer promotion, the...

  19. 16 CFR 238.2 - Initial offer.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Initial offer. 238.2 Section 238.2 Commercial Practices FEDERAL TRADE COMMISSION GUIDES AND TRADE PRACTICE RULES GUIDES AGAINST BAIT ADVERTISING § 238.2 Initial offer. (a) No statement or illustration should be used in any advertisement...

  20. 7 CFR 3560.656 - Incentives offers.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Incentives offers. 3560.656 Section 3560.656... AGRICULTURE DIRECT MULTI-FAMILY HOUSING LOANS AND GRANTS Housing Preservation § 3560.656 Incentives offers. (a....653(d), incentives to agree to the restrictive-use period in § 3560.662 if the following conditions...

  1. An offer you can’t refuse

    OpenAIRE

    Fletcher, Roland

    2001-01-01

    The general requirements of a valid contract must contain an offer, acceptance, consideration, intention, capacity and if necessary the correct formation, eg, does the contract have to be in writing. The focus of this article will be on offer, acceptance, consideration and an invitation to treat when dealing with contracts concluded during an auction.

  2. 17 CFR 230.252 - Offering statement.

    Science.gov (United States)

    2010-04-01

    ..., language and pagination. The requirements for offering statements are the same as those specified in § 230... Officer, a majority of the members of its board of directors or other governing body, and each selling... that contains the following language: This offering statement shall become qualified on the...

  3. Home-care companies' offerings take off.

    Science.gov (United States)

    Lutz, S

    1991-06-03

    Some home infusion therapy companies have been the beneficiaries of cash infusions thanks to the bullish reception of public offerings this year. The lucrative industry, reimbursed primarily by private payers and one of the fastest growing in healthcare, has long been a favorite on Wall Street. The companies plan to use proceeds from the successful offerings to pay off debt and finance expansion.

  4. True hyponatremia secondary to intravenous immunoglobulin.

    Science.gov (United States)

    Nguyen, Minhtri K; Rastogi, Anjay; Kurtz, Ira

    2006-06-01

    Hyponatremia is characterized as either "true hyponatremia," which represents a decrease in the Na(+) concentration in the water phase of plasma, or "pseudohyponatremia," which is due to an increased percentage of protein or lipid in plasma, with a normal plasma water Na(+) concentration ([Na(+)]). Pseudohyponatremia is a known complication of intravenous immunoglobulin (IVIG). Because IVIG has been reported to result in post-infusional hyperproteinemia, IVIG-induced hyponatremia has been attributed to pseudohyponatremia. In this case report, we demonstrate that IVIG therapy can result in true hyponatremia, resulting from sucrose-induced translocation of water from the intracellular compartment (ICF) to the extracellular compartment (ECF), as well as the infusion of a large volume of dilute fluid, in patients with an underlying defect in urinary free water excretion.

  5. Solar urticaria successfully treated with intravenous immunoglobulin.

    LENUS (Irish Health Repository)

    Hughes, R

    2012-02-01

    Idiopathic solar urticaria (SU) is a rare, debilitating photodermatosis, which may be difficult to treat. First-line treatment with antihistamines is effective in mild cases, but remission after phototherapeutic induction of tolerance is often short-lived. Other treatment options include plasma exchange, photopheresis and cyclosporin. We present two cases of severe, idiopathic SU, which were resistant to conventional treatment. Both patients achieved remission after administration of intravenous immunoglobulin (IVIg) and have remained in remission at 13 months and 4 years, respectively. There are only two case reports of successful treatment of solar urticaria with IVIg. In our experience IVIg given at a total dose of 2 g\\/kg over several 5-day courses about a month apart is an effective treatment option for severe idiopathic SU. It is also generally safe, even if certainly subject to significant theoretical risks, such as induction of viral infection or anaphylaxis.

  6. Rheumatoid factors, B cells and immunoglobulin genes.

    Science.gov (United States)

    Jefferis, R

    1995-04-01

    The paradigm of self, non-self discrimination in the immune system is under review as autoreactive B or T cells are increasingly delineated within normal individuals. The products of autoreactive B cells are, mostly, polyspecific IgM antibodies of low affinity. These 'natural' antibodies include rheumatoid factors (RF) encoded by unmutated germline immunoglobulin genes. In rheumatoid arthritis (RA) the RF may be of the IgM, IgG or IgA isotype, show evidence of somatic mutation and have increased affinity; consistent with maturation of an antigen driven immune response. This response could be initiated or driven by an auto-immunogenic form of IgG or an exogenous cross-reactive antigen. Changes in galactosylation of IgG have been reported to be a valuable diagnostic and prognostic indicator in RA. Speculation that these changes may precipitate some of the disease processes is critically reviewed.

  7. Single-mode tapered optical fiber loop immunosensor II: assay of anti-cholera toxin immunoglobulins

    Science.gov (United States)

    Marks, Robert S.; Hale, Zoe M.; Levine, Myron M.; Lowe, C. R.; Payne, Frank P.

    1994-07-01

    An evanescent wave immunoassay for cholera antitoxin immunoglobulins was performed using a single mode tapered optical fiber loop sensor. The transducer was silanized with 3- glycidoxypropyltrimethoxysilane and chemically modified to link covalently either cholera toxin B subunit or a synthetic peptide derived from it, CTP3. The sensor was exposed to seral fluids, obtained from human volunteers having been exposed to live virulent Vibrio cholerae 01 and shown to produce rice-water stools. Other toxins of interest, such as Clostridium botulinum toxin A, have been tested on similar systems. The bound unlabelled immunoglobulins were then exposed to a mixture of FITC-anti-IgG and TRITC-anti-IgA, without requirement for a separation step. The emanating fluorescent emissions of fluorescein and rhodamine, excited by the input laser light, were coupled back into the guided mode of the tapered fiber, and used to determine the concentrations of the complementary antigens.

  8. Immunonanogold Catalytic Resonance Scattering Spectral Assay of Trace Immunoglobulin M

    Institute of Scientific and Technical Information of China (English)

    LIANG Ai-Hui; WANG Su-Mei; JIANG Zhi-Liang

    2008-01-01

    Gold nanoparticles of 10 nm were prepared by the improved method of trisodium citrate, and used to label goat anti-human immunoglobulin M (anti-IgM) to obtain a resonance scattering spectral probe for IgM. In pH 4.5 KH2PO4-Na2HPO4 buffer solution and in the presence of polyethylene glycol, the nanogold-labeled anti-IgM was combined with IgM specifically to form immunogold complex particles. After centrifugation, the immunonanogold in the supernatant catalyzed the reduction of AuCl-4 ions by NH2OH·HCl to form larger size gold particles in pH 1.9 citrate buffer solution, making the resonance scattering intensity at 580 nm enhanced. The amount of the nanogold-labeled anti-IgM in the supernatant decreased with the addition of IgM. The decreased intensity △I580 nm was proportional to the concentration of IgM in the range of 0.06--4.80 ng·mL-1. The regression equation was △I580nm= 14.5c(IgM)+1.8, with a detection limit of 0.03 ng·mL-1 IgM. The method was applied to the determina-tion of IgM in sera of healthy humans, with satisfactory results.

  9. Natural immunoglobulins (contribution to a debate on biomedical education

    Directory of Open Access Journals (Sweden)

    Vaz Nelson M

    2000-01-01

    Full Text Available Immunology has contributed to biomedical education in many important ways since the creation of scientific medicine in the last quarter of the 19th century. Today, immunology is a major area of biomedical research. Nevertheless, there are many basic problems unresolved in immunological activities and phenomena. Solving these problems is probably necessary to devise predictable and safe ways to produce new vaccines, treat allergy and autoimmune diseases and perform safe transplants. This challenge involves not only technical developments but also changes in attitude, of which the most fundamental is to abandon the traditional stimulus-response perspective in favor of more "systemic" views. Describing immunological activities as the operation of a complex multiconnected network, raises biological and epistemological issues not usually dealt with in biomedical education. Here we point to one example of systemic approaches. A new form of immunoblot (Panama blot, by which the reaction of natural immunoglobulins with complex protein mixtures may be analyzed by a special software and multivariate statistics, has been recently used to characterize human autoimmune diseases. Our preliminary data show that Panama blots can also be used to characterize global (systemic immunogical changes in chronic human parasitic diseases, such as malaria and schistosomiasis mansoni, that correlate with the clinical status.

  10. Comparative analysis of the N-glycans of rat, mouse and human Thy-1. Site-specific oligosaccharide patterns of neural Thy-1, a member of the immunoglobulin superfamily.

    Science.gov (United States)

    Williams, A F; Parekh, R B; Wing, D R; Willis, A C; Barclay, A N; Dalchau, R; Fabre, J W; Dwek, R A; Rademacher, T W

    1993-08-01

    Protein structure and tissue type are known to influence glycosylation of proteins. We have previously investigated the N-glycans at each of the three glycosylation sites of the cell surface glycoprotein Thy-1 when isolated from rat brain and thymocytes. Here we report a comparative analysis of the site-specific N-glycosylation patterns from rat (Asn 23, 74, 98), mouse (Asn 23, 75, 99) and human (Asn 23, 60, 100) neural Thy-1. Despite considerable differences in amino acid sequence, the results show a remarkable conservation of the pattern of N-glycans at corresponding sites between the three species, as judged by chromatographic comparisons and glycosidase susceptibility. This is particularly marked for sites at Asn 74/75 in rat/mouse and the equivalent site at 60 in human Thy-1, as well as for sites at Asn 98/99 and 100, respectively. The sites at Asn 23 in rat/mouse also contained almost identical glycosylation patterns, but at this site human Thy-1 showed significantly different glycosylation patterns. These site glycosylation patterns are discussed in relation to the likely accessibility of the oligosaccharides for processing. It is known that within a species, the glycosylation of Thy-1 is tissue specific; therefore, this degree of conservation of glycosylation of Thy-1 expressed in the same tissue in different species is all the more striking, given the known variation between species in the amino acid sequence of Thy-1. It is therefore proposed that neural cells have a particular requirement for specific surface carbohydrates and that the Thy-1 polypeptide serves as an appropriate carrier for these structures.

  11. DV50纳米过滤去除静注人免疫球蛋白中的病毒时流速的影响因素%Influencing factors of velocity during removal of virus in human immunoglobulin for intravenous injection by DV50 nanofiltration

    Institute of Scientific and Technical Information of China (English)

    郑丰平; 王炳; 郑琪; 吕家成

    2012-01-01

    Objective To analyze the influencing factors of velocity during removal of virus in human immunoglobulin for intra-venous injection(IVIG) by DV50 nanofiltration. Methods The turbidity and concentration of bulk of IVIG were determined by tur-bidimeter and densimeter respectively. Five batches of bulks with similar concentrations and different turbidities, as well as five batches of bulks with similar turbidities and different concentrations, were subjected to nanofiltration by using the filter elements of the same batch, and the mean velocity was calculated. Another five batches of bulks with similar turbidities and concentrations were sub-jected to nanofiltration by using the filter elements of different batches, and the mean velocity was calculated. Results The mean velocity decreased with the increasing turbidity of bulk, while showed no linear relationship to the concentration. The mean velocity of nanofil-tration by using various filter elements showed significant difference. Conclusion The turbidity of product showed a cer-tain influ-ence, while the concentration showed no significant difference,on velocity. However, the filter element showed significant influence on velocity. The study provided a reference to controlling the velocity during removal of virus by nanofiltration and improv-ing the pro-duction procedure of IVIG.%目的 分析DV50纳米过滤去除静注入免疫球蛋白(Human immunoglobulin for intravenous injection,IVIG)病毒时流速的影响因素.方法 分别采用浊度仪、密度仪检测IVIG原液的浊度及浓度,随机选取5批浓度相近、浊度不同的IVIG原液及5批浊度相近、浓度不同的IVIG原液,分别经同一批号纳米滤芯过滤,计算平均流速;随机选取5批浊度、浓度相近的IVIG 原液,经不同批号的纳米滤芯过滤,计算平均流速.结果 随着制品浊度的升高,平均流速逐渐降低;制品浓度与平均流速不呈线性对应关系;不同批号的纳米滤芯,纳米平

  12. Vacancy Duration, Wage Offers, and Job Requirements

    DEFF Research Database (Denmark)

    Eriksson, Tor Viking; Chen, Long-Hwa

    is concerned with how vacancy durations vary with firms' minimum wage offers and minimum job requirements (regarding education, skills, age, gender and earlier work experience). The empirical analysis is based on ten employer surveys carried out by the DGBAS on Taiwan during the period 1996-2006. We estimate......Besides wage offers, credentials like education, work experience and skill requirements are key screening tools for firms in their recruitment of new employees. This paper adds some new evidence to a relatively tiny literature on firms' recruitment behaviour. In particular, our analysis...... logistic discrete hazard models with a rich set of job and firm characteristics as explanatory variables. The results show that vacancies associated with higher wage offers take, ceteris paribus, longer to be filled. The impact of firms' wage offers and credential requirements does not vary over...

  13. M.S. Offered in Industrial Chemistry

    Science.gov (United States)

    Chemical and Engineering News, 1975

    1975-01-01

    Describes graduate training geared specifically to prepare students for work in industry. Reports on schools offering such a program, and outlines the major characteristics of each school's curriculum. (GS)

  14. Mylan to Offer Generic EpiPen

    Science.gov (United States)

    ... news/fullstory_160669.html Mylan to Offer Generic EpiPen Manufacturer responds to mounting criticism about price hikes ... cheaper generic version of the emergency allergy treatment EpiPen will be made available within the next few ...

  15. Offering Spiritual Support for Family or Friends

    Science.gov (United States)

    Offering Spiritual Support for Family or Friends People who are very ill often ask spiritual questions, in seeking comfort, meaning and hope. While clergy, chaplains and other spiritual leaders may play an important role in spiritual ...

  16. Design Method Amelioration of Human Immunoglobulin Gene Primer in Heavy Chain Variable Region%人免疫球蛋白重链可变区基因引物设计方法的改良

    Institute of Scientific and Technical Information of China (English)

    姜晶; 孙颖; 刘红艳; 牟玲; 罗恩杰

    2012-01-01

    针对抗体胚系基因数据库的数据不断更新和完善,为获得人全部免疫球蛋白(Ig)重链可变区基因,改进引物设计方法,自主设计针对可变区基因高度保守的框架区1(FR1)和框架区4(FR4)的引物,提取未经免疫的健康人外周血单个核细胞,通过RT-PCR扩增重链可变区基因.其DNA序列与GenBank数据库和IMGT/V-QUEST软件比对,序列分析符合人免疫球蛋白重链基本框架结构,为胚系基因重排产生的序列.多个克隆的测序结果对比分析显示了良好的多样性.获得的重链序列为研制基因工程抗体及构建噬菌体抗体库奠定了物质基础,也为扩增其他物种Ig可变区基因的引物提供新的设计思路.%Aiming at the continuous renovation and consummation of dala of databank on antibody germ line gene, in order to obtain full gene of heavy chain variable region of human immunoglobin (Ig) , to ameliorate primer design method, a primer was independently designed aiming at variable gene highly conservative region framework 1 ( FR1) and framework 4 ( FR4) , and extracted peripheral blood mononuclear cells (PBMCs) from healthy volunteer, and amplified its heavy chain variable region gene through RT-PCR. After comparison with databank in CenBank and IMGT/V-QUEST software and sequence analysis, the DNA sequence accorded with basic framework structure of human Ig heavy chain, and was the sequence produced by the rearrangement of germ line gene. Comparative analysis of multiple clones sequencing showed a good diversity. The obtained data of heavy chain sequence had provided the material foundation for research and development of gene engineering antibodies and phage libraries, and new design ideas for amplifying Ig variable region gene primers of other species.

  17. Identification of the ancestral killer immunoglobulin-like receptor gene in primates

    Directory of Open Access Journals (Sweden)

    Coggill Penny

    2006-08-01

    Full Text Available Abstract Background Killer Immunoglobulin-like Receptors (KIR are essential immuno-surveillance molecules. They are expressed on natural killer and T cells, and interact with human leukocyte antigens. KIR genes are highly polymorphic and contribute vital variability to our immune system. Numerous KIR genes, belonging to five distinct lineages, have been identified in all primates examined thus far and shown to be rapidly evolving. Since few KIR remain orthologous between species, with only one of them, KIR2DL4, shown to be common to human, apes and monkeys, the evolution of the KIR gene family in primates remains unclear. Results Using comparative analyses, we have identified the ancestral KIR lineage (provisionally named KIR3DL0 in primates. We show KIR3DL0 to be highly conserved with the identification of orthologues in human (Homo sapiens, common chimpanzee (Pan troglodytes, gorilla (Gorilla gorilla, rhesus monkey (Macaca mulatta and common marmoset (Callithrix jacchus. We predict KIR3DL0 to encode a functional molecule in all primates by demonstrating expression in human, chimpanzee and rhesus monkey. Using the rhesus monkey as a model, we further show the expression profile to be typical of KIR by quantitative measurement of KIR3DL0 from an enriched population of natural killer cells. Conclusion One reason why KIR3DL0 may have escaped discovery for so long is that, in human, it maps in between two related leukocyte immunoglobulin-like receptor clusters outside the known KIR gene cluster on Chromosome 19. Based on genomic, cDNA, expression and phylogenetic data, we report a novel lineage of immunoglobulin receptors belonging to the KIR family, which is highly conserved throughout 50 million years of primate evolution.

  18. Intravenous immunoglobulin in symptomatic and asymptomatic children with perinatal HIV infection.

    Science.gov (United States)

    Olopoenia, L; Young, M; White, D; Barnes, S; Rahbar, F; Fomufod, A

    1997-08-01

    One hundred thirty-five children born to human immunodeficiency virus (HIV)-infected mothers were selected randomly to receive immunoglobulin (Gamimune-N, Miles Pharmaceutical Co) 200 mg/kg monthly for 1 year. All patients were seropositive by ELISA and Western blot at birth. At the time of the study, 15 symptomatic (P2) and 57 asymptomatic (P1) patients with evidence of viral infection (positive HIV culture or P24 antigen) received the immunoglobulin. Sixty-three indeterminate (PO) patients with no evidence of infection served as the control. Mean age for infants in group P2 was 32 months, 26 months for group P1, and 11 months for group PO. Significant reduction in the frequency of bacterial infections (ie, otitis media, upper respiratory tract infections, urinary tract infections, and acute gastroenteritis) was seen in the symptomatic group compared with both the asymptomatic and the control groups. Growth as measured by weight and height > 50th percentile was also markedly better in the symptomatic group than either asymptomatic or control patients. There was no significant difference in head circumference in all three groups. These results indicate that monthly intravenous immunoglobulin infusion (IVIG) appears to be beneficial to both symptomatic and asymptomatic HIV patients in reducing the frequency of bacterial infection and also enhancement of the immune response. However, symptomatic patients responded much better than the asymptomatic patients.

  19. Correlation of Immunoglobulin G Expression and Histological Subtype and Stage in Breast Cancer

    Science.gov (United States)

    Chen, Zhengshan; Yi, Weining; McNutt, Michael A.; Wang, Yun; Korteweg, Christine; Gu, Jiang

    2013-01-01

    Introduction Recently, growing evidence indicates that immunoglobulins (Igs) are not only produced by mature B lymphocytes or plasma cells, but also by various normal cells types at immune privileged sites and neoplasm, including breast cancer. However, the association of breast cancer derived IgG with genesis and development of the disease has not yet been established. Methods In this study we examined the expression of IgG in 186 breast cancers, 20 benign breast lesions and 30 normal breast tissues. Both immunohistochemistry with antibodies to Igκ (immunoglobulin G κ light chain) and Igγ (immunoglobulin G heavy chain) and in situ hybridization with an antisense probe to IgG1 heavy chain constant region gene were performed. Various clinicopathological features were also analyzed. Results We found that IgG is specifically expressed in human breast cancer cells. Both infiltrating ductal carcinoma and infiltrating lobular carcinoma had significantly greater numbers of Igκ and Igγ positive cancer cells as compared with medullary carcinoma, carcinoma in situ, and benign lesions (all pbreast cancer histological subtypes (pbreast cancer cells is correlated with malignancy and AJCC stages of the cancers. This suggests that breast cancer derived IgG may be associated with genesis, development and prognosis of the cancer. PMID:23554916

  20. Prognostic significance of serum immunoglobulin pareprotein in chronic lymphocytic leukemia

    Institute of Scientific and Technical Information of China (English)

    杨舒

    2012-01-01

    Objective To investigate the incidence of serum immunoglobulin (Ig) paraprotein in chronic lymphocytic leukemia(CLL) ,and to explore its clinical associated laboratory features and prognostic implication. Methods Serum protein electrophoresis and immunofixation

  1. Beneficial use of immunoglobulins in the treatment of Sydenham chorea

    NARCIS (Netherlands)

    T.D. van Immerzeel (Tabitha); R.M. van Gilst (Ruud); N.G. Hartwig (Nico)

    2010-01-01

    textabstractThis double case report indicates that treatment with intravenous immunoglobulins (IVIG) is effective in patients with Sydenham chorea (SC). SC is a rare but impressive clinical manifestation following streptococcal infection. This movement disorder characterised by chorea, emotional

  2. Beneficial use of immunoglobulins in the treatment of Sydenham chorea

    NARCIS (Netherlands)

    T.D. van Immerzeel (Tabitha); R.M. van Gilst (Ruud); N.G. Hartwig (Nico)

    2010-01-01

    textabstractThis double case report indicates that treatment with intravenous immunoglobulins (IVIG) is effective in patients with Sydenham chorea (SC). SC is a rare but impressive clinical manifestation following streptococcal infection. This movement disorder characterised by chorea, emotional lab

  3. Estimation of major immunoglobulins in smokers and gutkha chewers

    Directory of Open Access Journals (Sweden)

    Ketankumar Jayantilal Prajapati

    2016-01-01

    Conclusion: Higher major immunoglobulins levels in present study among the study groups indicate the use of immunoprofile estimation in etiology and pathogenesis and would prove a great asset in the proper assessment of the lesions.

  4. The molecular basis of somatic hypermutation of immunoglobulin genes.

    Science.gov (United States)

    Storb, U

    1996-04-01

    Somatic hypermutation amplifies the variable region repertoire of immunoglobulin genes. Recent experimental evidence has thrown light on various molecular models of somatic hypermutation. A link between somatic hypermutation and transcription coupled DNA repair is shaping up.

  5. Beneficial use of immunoglobulins in the treatment of Sydenham chorea

    NARCIS (Netherlands)

    T.D. van Immerzeel (Tabitha); R.M. van Gilst (Ruud); N.G. Hartwig (Nico)

    2010-01-01

    textabstractThis double case report indicates that treatment with intravenous immunoglobulins (IVIG) is effective in patients with Sydenham chorea (SC). SC is a rare but impressive clinical manifestation following streptococcal infection. This movement disorder characterised by chorea, emotional lab

  6. Self‑perceived oral health and whole salivary immunoglobulin G ...

    African Journals Online (AJOL)

    2015-04-05

    Apr 5, 2015 ... immunoglobulin G levels in habitual gutka‑chewers and nonchewers ... respondents with periodontal disease (PD) are unaware of their oral ..... virus and oral lesions in gutka eating subjects in Karachi. J Coll Physicians Surg.

  7. Immunoglobulins in granular corneal dystrophy Groenouw type I

    DEFF Research Database (Denmark)

    Møller, H U; Bojsen-Møller, M; Schrøder, H D

    1993-01-01

    Three patients with granular corneal dystrophy Groenouw type I underwent corneal grafting, and cryostat sections of the corneal buttons were examined immunohistochemically for immunoglobulins. Positive results were obtained for IgG, Kappa-, and Lambda chains with immunofluorescence technique...

  8. Cigarette promotional offers: who takes advantage?

    Science.gov (United States)

    White, Victoria M; White, Martha M; Freeman, Karen; Gilpin, Elizabeth A; Pierce, John P

    2006-03-01

    Promotional offers on cigarettes (e.g., dollar-off, multipack discounts) composed the largest share of tobacco industry marketing expenditures, totaling $8.9 billion, or 72% of the total budget in 2002. Internal industry documents indicate that young adults, potential quitters, and other price-sensitive groups are the targets of these marketing tactics. How effective they are in actually reaching these groups in the general population of smokers has not yet been investigated. Data were from 4618 current smokers responding to the large, random-digit-dialed population-based 2002 California Tobacco Survey. The characteristics were identified of smokers who reported that they used these offers "every time I see one." Thirty-five percent of smokers used promotional offers every time they saw one. Multivariate analyses identified young adults, women, African Americans, those with higher daily cigarette consumption, and those worried about cigarette costs as more likely to use promotional offers at every opportunity. Smokers most committed to quitting were no more likely to use promotional offers than those with no intention to quit. Cigarette brand was highly correlated with age and race/ethnicity, and therefore was not included in the multivariate analysis. Those who smoked menthol cigarettes and Camels, more often young adults and African Americans, were much more likely than those of other brands to use promotional offers. With the exception of smokers intending to quit, cigarette promotional offers are effectively reaching most industry-targeted groups. Importantly, young adults, who have the greatest long-term customer potential, are responding.

  9. Immunoglobulin genomics in the guinea pig (Cavia porcellus.

    Directory of Open Access Journals (Sweden)

    Yongchen Guo

    Full Text Available In science, the guinea pig is known as one of the gold standards for modeling human disease. It is especially important as a molecular and cellular biology model for studying the human immune system, as its immunological genes are more similar to human genes than are those of mice. The utility of the guinea pig as a model organism can be further enhanced by further characterization of the genes encoding components of the immune system. Here, we report the genomic organization of the guinea pig immunoglobulin (Ig heavy and light chain genes. The guinea pig IgH locus is located in genomic scaffolds 54 and 75, and spans approximately 6,480 kb. 507 V(H segments (94 potentially functional genes and 413 pseudogenes, 41 D(H segments, six J(H segments, four constant region genes (μ, γ, ε, and α, and one reverse δ remnant fragment were identified within the two scaffolds. Many V(H pseudogenes were found within the guinea pig, and likely constituted a potential donor pool for gene conversion during evolution. The Igκ locus mapped to a 4,029 kb region of scaffold 37 and 24 is composed of 349 V(κ (111 potentially functional genes and 238 pseudogenes, three J(κ and one C(κ genes. The Igλ locus spans 1,642 kb in scaffold 4 and consists of 142 V(λ (58 potentially functional genes and 84 pseudogenes and 11 J(λ -C(λ clusters. Phylogenetic analysis suggested the guinea pig's large germline V(H gene segments appear to form limited gene families. Therefore, this species may generate antibody diversity via a gene conversion-like mechanism associated with its pseudogene reserves.

  10. Immunoglobulin variable region structure and B-cell malignancies.

    Science.gov (United States)

    Kiyoi, H; Naoe, T

    2001-01-01

    The enormous diversity of immunoglobulin (Ig) variable (V) gene sequences encoding the antibody repertoire are formed by the somatic recombination of relatively few genetic elements. In B-lineage malignancies, Ig gene rearrangements have been widely used for determining clonality and cell origin. The recent development of rapid cloning and sequencing techniques has resulted in a substantial accumulation of IgV region sequences at various stages of B-cell development and has revealed stage-specific trends in the use of V, diversity, joining genes, the degree of noncoding nucleotide addition, and the rate of somatic mutations. Furthermore, sequences from B-lineage malignant cells nearly reflect the characteristics of the normal counterpart at each respective stage of development. Alternatively, from the IgV region structure of the malignant cells, it is possible to speculate at which stage of B-cell development the cells were transformed. As the complete nucleotide sequences of the human Ig heavy and Ig light V region loci have now been determined, the study of Ig genetics has entered into the super-information era.

  11. Cynomolgus macaque (Macaca fascicularis) immunoglobulin heavy chain locus description.

    Science.gov (United States)

    Yu, Guo-Yun; Mate, Suzanne; Garcia, Karla; Ward, Michael D; Brueggemann, Ernst; Hall, Matthew; Kenny, Tara; Sanchez-Lockhart, Mariano; Lefranc, Marie-Paule; Palacios, Gustavo

    2016-07-01

    Cynomolgus macaques (Macaca fascicularis) have become an important animal model for biomedical research. In particular, it is the animal model of choice for the development of vaccine candidates associated with emerging dangerous pathogens. Despite their increasing importance as animal models, the cynomolgus macaque genome is not fully characterized, hindering molecular studies for this model. More importantly, the lack of knowledge about the immunoglobulin (IG) locus organization directly impacts the analysis of the humoral response in cynomolgus macaques. Recent advances in next generation sequencing (NGS) technologies to analyze IG repertoires open the opportunity to deeply characterize the humoral immune response. However, the IG locus organization for the animal is required to completely dissect IG repertoires. Here, we describe the localization and organization of the rearranging IG heavy (IGH) genes on chromosome 7 of the cynomolgus macaque draft genome. Our annotation comprises 108 functional genes which include 63 variable (IGHV), 38 diversity (IGHD), and 7 joining (IGHJ) genes. For validation, we provide RNA transcript data for most of the IGHV genes and all of the annotated IGHJ genes, as well as proteomic data to validate IGH constant genes. The description and annotation of the rearranging IGH genes for the cynomolgus macaques will significantly facilitate scientific research. This is particularly relevant to dissect the immune response during vaccination or infection with dangerous pathogens such as Ebola, Marburg and other emerging pathogens where non-human primate models play a significant role for countermeasure development.

  12. Immunoglobulin G4-related disease with recurrent obstructive jaundice

    Directory of Open Access Journals (Sweden)

    Yu-Hsiang Chiu

    2016-03-01

    Full Text Available A 51-year-old man was referred to our clinic for recurrent obstructive jaundice and underwent pylorus-preserving pancreaticoduodenectomy for a suspected malignancy. The pathology showed immunoglobulin G4 positive plasma cell infiltrated at the pancreas and the gallbladder. We discuss the cost-effectiveness of serum immunoglobulin G4 level prior to arranging for a pancreaticoduodenectomy, which would reduce the possibility of surgical complications as well as costs.

  13. Russell body duodenitis with immunoglobulin kappa lightchain restriction

    Institute of Scientific and Technical Information of China (English)

    William R Munday; Lucy Harn Kapur; Mina Xu; Xuchen Zhang

    2015-01-01

    Russell bodies are eosinophilic intracytoplasmicglobules which are likely the result of disturbedsecretion of immunoglobulins that accumulate withinthe plasma cell. Russell body collections have beenidentified within the stomach, known as Russellbody gastritis. Similar lesions within the duodenumare referred to as Russell body duodenitis, whichis rare. Several Russell body gastritis case reportsare associated with Helicobacter pylori . However,the etiology of Russell body duodenitis remainsunclear. Here we report the first case of Russell bodyduodenitis with immunoglobulin light chain restrictionin a background of peptic duodenitis.

  14. Efficacy and tolerability of 16% subcutaneous immunoglobulin compared with 20% subcutaneous immunoglobulin in primary antibody deficiency.

    Science.gov (United States)

    Niebur, H B; Duff, C M; Shear, G F; Nguyen, D; Alberdi, T K; Dorsey, M J; Sleasman, J W

    2015-09-01

    Multiple subcutaneous immunoglobulin (SCIG) products are available to treat primary antibody deficiency (PAD). The efficacy and tolerability of 16% SCIG (Vivaglobin(®) ) was compared with 20% SCIG (Hizentra(®) ) in PAD subjects. The study was a prospective, single-centre, open-label study of PAD subjects transitioning Vivaglobin to equivalent Hizentra doses, rounded to the nearest vial size. Comparisons included immunoglobulin (Ig)G levels; tetanus, varicella and Streptococcus pneumoniae titres; adverse events (AEs), annual infection rate and quality of life during 8 weeks of Vivaglobin and 24 weeks of Hizentra. Thirty-two subjects (aged 2-75 years) participated. Rounding to the nearest Hizentra vial size resulted in a 12·8% (± 2·9%) increase in SCIG dose. Median immunoglobulin (Ig)G level following 8 weeks of Vivaglobin was similar to 24 weeks of Hizentra (1050 versus 1035 mg/dl, respectively; P = 0·77). Both products had similar protective titres to tetanus, varicella and serotypes of S. pneumoniae, which were variable but well above protective levels. After 12 weeks of Hizentra, subjects reported fewer local site reactions compared with Vivaglobin. Switching products resulted in increased systemic AEs in some subjects but, overall, not significantly higher than during Vivaglobin treatment. Average infusion time decreased from 104·7 min (3·3 sites) with Vivaglobin to 70·7 min (2·2 sites) with Hizentra (P = 0·0005). Acute serious bacterial infections were similar. Treatment satisfaction was superior with Hizentra. Hizentra and Vivaglobin have similar pharmacokinetics and efficacy. Although transition to a different SCIG product initially increased AEs, Hizentra is well tolerated and can be infused more rapidly and with fewer sites compared to Vivaglobin.

  15. Effect of intravenous human immunoglobulin G on hippocampal function of depressive model rats subjected to chronic unpredictable stress%静脉输注人免疫球蛋白G对慢性不可预料应激抑郁模型大鼠海马功能的影响

    Institute of Scientific and Technical Information of China (English)

    王晟; 徐丽芳

    2014-01-01

    目的:探讨静脉输注人免疫球蛋白G(IgG)对慢性不可预料应激抑郁模型大鼠海马功能的影响。方法对慢性不可预料应激抑郁模型大鼠分别给予静脉输注人IgG+应激( IgG组)和单纯应激( CUS组)处理,对照组不行任何处理。分别采用悬尾实验、糖水偏好实验、强迫游泳实验、自主活动实验和5-溴脱氧尿嘧啶核苷(BrdU)标记海马齿状回神经元,检测神经元再生情况。结果 IgG组及对照组糖水偏好消耗显著大于 CUS 组( P均<0.01);悬尾实验、强迫游泳实验和自主活动实验不动时间IgG组及对照组显著小于CUS组(P均<0.01);IgG组海马区域BrdU阳性细胞数与CUS组比较有统计学差异( P<0.01)。结论静脉输注人IgG对慢性不可预料应激造成的大鼠抑郁样行为具有改善作用;可保护海马的神经元再生功能。%Objective To investigate the effect of intravenous human immunoglobulin G ( IgG) on depressive model rats subjected to chronic unpredictable stress .Methods Depressive model rats subjected to chronic unpredictable stress were randomly divided into 3 groups: intravenous immunoglobulin G ( IVIG) +stress group ( IVIG group), stress-only group ( CUS group) and the control group without any treatment .Tail suspension test , sucrose preference test , forces swimming test, locomotor activity and BrdU labeling neuron of hippocampal dentate gyrus based neurogenesis were used to analyze the effect of IVIG on depressive model rats .Results Sucrose consumption in the IVIG group and control group was significantly less than that of the CUS group (P<0.01), while duration of immobility of tail suspension test , forced swimming test and lo-comotor activity was significantly shorter than that of the CUS group (all P<0.01).The difference of BrdU positive cell number in the hippocampus between the two groups was significant (P<0.01).Conclusion IVIG can improve the depres

  16. Concurrent Drug-Induced Linear Immunoglobulin A Dermatosis and Immunoglobulin A Nephropathy

    OpenAIRE

    Kim, Ji Seok; Choi, Misoo; Nam, Chan Hee; Kim, Jee Young; Park, Byung Cheol; Kim, Myung Hwa; Hong, Seung Phil

    2015-01-01

    Diseases associated with immunoglobulin A (IgA) antibody include linear IgA dermatosis, IgA nephropathy, Celiac disease, Henoch-Schönlein purpura, etc. Although usually idiopathic, IgA antibody is occasionally induced by drugs (e.g., vancomycin, carbamazepine, ceftriaxone, and cyclosporine), malignancies, infections, and other causes. So far, only a few cases of IgA bullous dermatosis coexisting with IgA nephropathy have been reported. A 64-year-old female receiving intravenous ceftriaxone an...

  17. Efficacy of Intravenous Immunoglobulin in Neurological Diseases.

    Science.gov (United States)

    Lünemann, Jan D; Quast, Isaak; Dalakas, Marinos C

    2016-01-01

    Owing to its anti-inflammatory efficacy in various autoimmune disease conditions, intravenous immunoglobulin (IVIG)-pooled IgG obtained from the plasma of several thousands individuals-has been used for nearly three decades and is proving to be efficient in a growing number of neurological diseases. IVIG therapy has been firmly established for the treatment of Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy, either as first-line therapy or adjunctive treatment. IVIG is also recommended as rescue therapy in patients with worsening myasthenia gravis and is beneficial as a second-line therapy for dermatomyositis and stiff-person syndrome. Subcutaneous rather than intravenous administration of IgG is gaining momentum because of its effectiveness in patients with primary immunodeficiency and the ease with which it can be administered independently from hospital-based infusions. The demand for IVIG therapy is growing, resulting in rising costs and supply shortages. Strategies to replace IVIG with recombinant products have been developed based on proposed mechanisms that confer the anti-inflammatory activity of IVIG, but their efficacy has not been tested in clinical trials. This review covers new developments in the immunobiology and clinical applications of IVIG in neurological diseases.

  18. Clinical applications of intravenous immunoglobulins in neurology

    Science.gov (United States)

    Hughes, R A C; Dalakas, M C; Cornblath, D R; Latov, N; Weksler, M E; Relkin, N

    2009-01-01

    Intravenous immunoglobulin (IVIg) is used increasingly in the management of patients with neurological conditions. The efficacy and safety of IVIg treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain–Barré syndrome (GBS) have been established clearly in randomized controlled trials and summarized in Cochrane systematic reviews. However, questions remain regarding the dose, timing and duration of IVIg treatment in both disorders. Reports about successful IVIg treatment in other neurological conditions exist, but its use remains investigational. IVIg has been shown to be efficacious as second-line therapy in patients with dermatomyositis and suggested to be of benefit in some patients with polymyositis. In patients with inclusion body myositis, IVIg was not shown to be effective. IVIg is also a treatment option in exacerbations of myasthenia gravis. Studies with IVIg in patients with Alzheimer's disease have reported increased plasma anti-Aβ antibody titres associated with decreased Aβ peptide levels in the cerebrospinal fluid following IVIg treatment. These changes at the molecular level were accompanied by improved cognitive function, and large-scale randomized trials are under way. PMID:19883422

  19. [Determination of serum immunoglobulins in asthmatic patients].

    Science.gov (United States)

    Cabrera Jiménez, M; Valdés Sánchez, A F; Argüelles Sobrino, D; Gómez Echevarría, A H; Lastra Alfonso, G

    1989-01-01

    One hundred eighty one asthmatic patients were evaluated at the Allergy Consultation in Hermanos Ameijeiras Clinical Surgical Hospital. A case history was made for each of the patients, where the family background and personal history of allergy was collected; possible precipitating factors (such as inhalable, food, infectious, irritant, as well as climate factors) and physical and respiratory examinations. Serum immunoglobulin tests (by means of the ultramicroanalitic system (SUMA) and the rest of Igs: IgA, IgG, IgM by means of Mancini's simple radial immunodifusion method were made. Total eosinophil count was made to all of the patients in the study as well as serial studies of the faces. An increase in the IgE and IgM figures was found in asthmatic patients related to individual controls, and in relation to the normal figures for the adult population in our country. IgA and IgG determinations were normal both in the asthmatic and control groups, related to the standard figures.

  20. The ultimatum game: Discrete vs. continuous offers

    Science.gov (United States)

    Dishon-Berkovits, Miriam; Berkovits, Richard

    2014-09-01

    In many experimental setups in social-sciences, psychology and economy the subjects are requested to accept or dispense monetary compensation which is usually given in discrete units. Using computer and mathematical modeling we show that in the framework of studying the dynamics of acceptance of proposals in the ultimatum game, the long time dynamics of acceptance of offers in the game are completely different for discrete vs. continuous offers. For discrete values the dynamics follow an exponential behavior. However, for continuous offers the dynamics are described by a power-law. This is shown using an agent based computer simulation as well as by utilizing an analytical solution of a mean-field equation describing the model. These findings have implications to the design and interpretation of socio-economical experiments beyond the ultimatum game.

  1. Vacancy Duration, Wage Offers, and Job Requirements

    DEFF Research Database (Denmark)

    Eriksson, Tor Viking; Chen, Long-Hwa

    Besides wage offers, credentials like education, work experience and skill requirements are key screening tools for firms in their recruitment of new employees. This paper adds some new evidence to a relatively tiny literature on firms' recruitment behaviour. In particular, our analysis...... is concerned with how vacancy durations vary with firms' minimum wage offers and minimum job requirements (regarding education, skills, age, gender and earlier work experience). The empirical analysis is based on ten employer surveys carried out by the DGBAS on Taiwan during the period 1996-2006. We estimate...... the business cycle. However, firms vary their skills requirements over the business cycle: our empirical analysis shows that, for a given wage offer, requirements are stricter in recessions and downturns. Separating between reasons for posting vacancies turned out important in explaining differences in vacancy...

  2. Product Offerings Testing through Customer Satisfaction

    Directory of Open Access Journals (Sweden)

    Tina Vukasovic

    2014-09-01

    Full Text Available Consumer satisfaction is imperative to a successful business, the reason for the choice of topic for this paper being explained thereby. Market changes have resulted in consumer’s enormous growth of power, which was recognized by many companies who adapted their business to meeting those expectations. Adaptation, however, also resulted in the need for constant measuring and evaluation. According to the above-mentioned, this paper measures consumer satisfaction with the product offer of the drugstore chain X The survey results have shown that X’s offer has not completely come up to the expectations of a smaller number of interviewees. In relation to the measuring ranks of consumer satisfaction defined, the greatest number of consumers has turned out to be satisfied with the product offer, whereas the percentage of those who find it excellent is smaller than the percentage of those who assess it as average.

  3. Wind offering in energy and reserve markets

    DEFF Research Database (Denmark)

    Soares, Tiago; Pinson, Pierre; Morais, Hugo

    2016-01-01

    their revenue, since currently wind turbine/farm technologies allow them to provide ancillary services. Thus, wind power producers are to develop offering strategies for participation in both energy and reserve markets, accounting for market rules, while ensuring optimal revenue. We consider a proportional...... offering strategy to optimally decide upon participation in both markets by maximizing expected revenue from day-ahead decisions while accounting for estimated regulation costs for failing to provide the services. An evaluation of considering the same proportional splitting of energy and reserve in both...

  4. Do Human Arts Really Offer a Lower Return to Education?

    DEFF Research Database (Denmark)

    Dalgaard, Carl-Johan Lars; Sørensen, Anders; Schultz, Esben

    of women in their high school. Conditional on high school fixed effects, these  characteristics are unlikely to affect post-university wages and are plausible instruments for the  educational choice. Our 2SLS estimates reveal that the gap in returns to education is negligible, implying that the wage gap...

  5. Carbon offers advantages as implant material in human body

    Science.gov (United States)

    Benson, J.

    1969-01-01

    Because of such characteristics as high strength and long-term biocompatability, aerospace carbonaceous materials may be used as surgical implants to correct pathological conditions in the body resulting from disease or injury. Examples of possible medical uses include bone replacement, implantation splints and circulatory bypass implants.

  6. Using immunoglobulin Y as an alternative antibody for the detection of hepatitis A virus in frozen liver sections

    Directory of Open Access Journals (Sweden)

    Gentil Arthur Bentes

    2015-06-01

    Full Text Available An increasing amount of research has been conducted on immunoglobulin Y (IgY because the use of IgY offers several advantages with respect to diagnostic testing, including its easy accessibility, low cost and translatability to large-scale production, in addition to the fact that it can be ethically produced. In a previous work, immunoglobulin was produced and purified from egg yolks (IgY reactive to hepatitis A virus (HAV antigens. In the present work, this anti-HAV-specific IgY was used in an indirect immunofluorescence assay to detect viral antigens in liver biopsies that were obtained from experimentally infected cynomolgus monkeys. Fields that were positive for HAV antigen were detected in liver sections using confocal microscopy. In conclusion, egg yolks from immunised hens may be a reliable source for antibody production, which can be employed for immunological studies.

  7. Using immunoglobulin Y as an alternative antibody for the detection of hepatitis A virus in frozen liver sections.

    Science.gov (United States)

    Bentes, Gentil Arthur; Lanzarini, Natália Maria; Lima, Lyana Rodrigues Pinto; Manso, Pedro Paulo de Abreu; da Silva, Alexandre Dos Santos; Mouta Junior, Sergio da Silva E; Guimarães, Juliana Rodrigues; de Moraes, Marcia Terezinha Baroni; Pelajo-Machado, Marcelo; Pinto, Marcelo Alves

    2015-06-01

    An increasing amount of research has been conducted on immunoglobulin Y (IgY) because the use of IgY offers several advantages with respect to diagnostic testing, including its easy accessibility, low cost and translatability to large-scale production, in addition to the fact that it can be ethically produced. In a previous work, immunoglobulin was produced and purified from egg yolks (IgY) reactive to hepatitis A virus (HAV) antigens. In the present work, this anti-HAV-specific IgY was used in an indirect immunofluorescence assay to detect viral antigens in liver biopsies that were obtained from experimentally infected cynomolgus monkeys. Fields that were positive for HAV antigen were detected in liver sections using confocal microscopy. In conclusion, egg yolks from immunised hens may be a reliable source for antibody production, which can be employed for immunological studies.

  8. Hair-offerings: an enigmatic Egyptian custom

    Directory of Open Access Journals (Sweden)

    G. J. Tassie

    1996-11-01

    Full Text Available The Egyptians did not record the reasons that lay behind the offering of hair. Using an holistic approach, which combines both ethnographic and ethnohistoric evidence, insights may be gained into the ancient remains of these rituals and practices.

  9. Developing an integrated offer for sustainable renovations

    NARCIS (Netherlands)

    Cré, J.; Mlecnik, E.; Kondratenko, I.; Degraeve, P.; Van der Have, J.A.; Vrijders, J.; Van Dessel, J.; Haavik, T.; Aabrekk, S.; Paiho, S.; Stenlund, O.; Svendsen, S.; Vanhoutteghem, L.; Hansen, S.

    2012-01-01

    Within an ERANET-ERACOBUILD project, this study investigates the opportunities and barriers to establish a “one stop shop” with an integrated supply side, to counteract the fragmented offer in sustainable renovation of single-family houses and to increase the level of knowledge, skills and innovatio

  10. The timing of initial public offerings

    NARCIS (Netherlands)

    Benninga, Simon; Helmantel, Mark; Sarig, Oded

    2001-01-01

    Abstract In this paper, we study the dynamics of initial public offerings (IPOs) by examining the tradeoff between an entrepreneur’s private benefits, which are lost whenever the firm is publicly traded, versus the advantages from diversification. We characterize the timing dimension of the decision

  11. Immunoglobulin heavy chain exclusion in the shark.

    Directory of Open Access Journals (Sweden)

    Karolina Malecek

    2008-06-01

    Full Text Available The adaptive immune system depends on specific antigen receptors, immunoglobulins (Ig in B lymphocytes and T cell receptors (TCR in T lymphocytes. Adaptive responses to immune challenge are based on the expression of a single species of antigen receptor per cell; and in B cells, this is mediated in part by allelic exclusion at the Ig heavy (H chain locus. How allelic exclusion is regulated is unclear; we considered that sharks, the oldest vertebrates possessing the Ig/TCR-based immune system, would yield insights not previously approachable and reveal the primordial basis of the regulation of allelic exclusion. Sharks have an IgH locus organization consisting of 15-200 independently rearranging miniloci (VH-D1-D2-JH-Cmu, a gene organization that is considered ancestral to the tetrapod and bony fish IgH locus. We found that rearrangement takes place only within a minilocus, and the recombining gene segments are assembled simultaneously and randomly. Only one or few H chain genes were fully rearranged in each shark B cell, whereas the other loci retained their germline configuration. In contrast, most IgH were partially rearranged in every thymocyte (developing T cell examined, but no IgH transcripts were detected. The distinction between B and T cells in their IgH configurations and transcription reveals a heretofore unsuspected chromatin state permissive for rearrangement in precursor lymphocytes, and suggests that controlled limitation of B cell lineage-specific factors mediate regulated rearrangement and allelic exclusion. This regulation may be shared by higher vertebrates in which additional mechanistic and regulatory elements have evolved with their structurally complex IgH locus.

  12. Immunoglobulin genes implicated in glioma risk.

    Science.gov (United States)

    Pandey, Janardan P; Kaur, Navtej; Costa, Sandra; Amorim, Julia; Nabico, Rui; Linhares, Paulo; Vaz, Rui; Viana-Pereira, Marta; Reis, Rui M

    2014-01-01

    Both genetic and environmental factors are thought to be causal in gliomagenesis. Several genes have been implicated in glioma development, but the putative role of a major immunity-related gene complex member, immunoglobulin heavy chain γ (IGHG) has not been evaluated. Prior observations that IGHG-encoded γ marker (GM) allotypes exhibit differential sensitivity to an immunoevasion strategy of cytomegalovirus, a pathogen implicated as a promoter of gliomagenesis, has lead us to hypothesize that these determinants are risk factors for glioma. To test this hypothesis, we genotyped the IGHG locus comprising the GM alleles, specifically GM alleles 3 and 17, of 120 glioma patients and 133 controls via TaqMan® genotyping assay. To assess the associations between GM genotypes and the risk of glioma, we applied an unconditional multivariate logistic regression analysis adjusted for potential confounding variables. In comparison to subjects who were homozygous for the GM 17 allele, the GM 3 homozygotes were over twice as likely, and the GM 3/17 heterozygotes were over three times as likely, to develop glioma. Similar results were achieved when analyzed by combining the data corresponding to alleles GM 3 and GM 3/17 in a dominant model. The GM 3/17 genotype and the combination of GM 3 and GM 3/17 were found to be further associated with over 3 times increased risk for high-grade astrocytoma (grades III-IV). Allele frequency analyses also showed an increased risk for gliomas and high-grade astrocytoma in association with GM 3. Our findings support the premise that the GM 3 allele may present risk for the development of glioma, possibly by modulating immunity to cytomegalovirus.

  13. Helicobacter pylori-related immunoglobulins in sarcoidosis.

    Science.gov (United States)

    Herndon, Betty L; Vlach, Victoria; Dew, Michelle; Willsie, Sandra K

    2004-03-01

    The purpose of this study was to determine serum antibody titers against a common bacterial antigen, Helicobacter pylori (H. pylon), in subjects with sarcoidosis, comparing those titers to those present in a healthy population. With the approval of the Institutional Review Board of the University of Missouri-Kansas City, patients with sarcoidosis (pulmonary and extrapulmonary) who visited the Truman Medical Center-Hospital Hill pulmonary clinic were recruited to enter the study. A serum sample was frozen at -70 degrees C for later testing (n = 20). Specific information collected on subjects included corticosteroid use, use of histamine2 blockers and antacids, date of first diagnosis, and stage of sarcoidosis. Normal controls and demographically matched individuals who lacked pulmonary diseases, including sarcoidosis, were also recruited. Serum samples were processed as above. Antibody capture enzyme immunoassay was completed for H. pylori and urease antigens by serum dilution assay for each subject, from which titers for antigen-specific immunoglobulin (Ig)G and IgA were calculated. Nonspecific serum IgE was also measured. An increased incidence of high-titer IgG antibody directed against H. pylori antigens was found in subjects with sarcoidosis compared with controls. The sarcoidosis and control groups were significantly different with respect to IgG and IgA against H. pylori, both at p = .001. IgG directed against urease was also significantly different between sarcoidosis and control patients (p = .001), but IgA directed against urease was very low in all subjects and did not yield significant differences between groups. Specific H. pylori and urease IgG antibodies exceeded those expected in the population studied. The data suggest that in pulmonary sarcoidosis, the relationship of H. pylori and its products to sarcoid granuloma formation warrants further investigation.

  14. Service Offering at Electrical Equipment Manufacturers

    Directory of Open Access Journals (Sweden)

    Lucie Kaňovská

    2015-09-01

    Full Text Available Purpose of the article: The aim of the paper is to uncover ways of managing service offering provid-ed by electrical equipment manufactures in the Czech Republic. The segment is extremely important for Czech industry nowadays, especially because of many companies being subcontractors for the car industry and mechanical engineering. The producers of electric equipment comply with the Czech in-dustry classification CZ-NACE 27. Methodology/methods: The questionnaire in the form of the Likert scale was prepared to gather in-formation about customer services. The respondents were usually directors or managers, e.g. employ-ees with high competencies of knowing customer services in this particular market. The total of 22 companies were included in the survey. Research was focused on the following industries classifica-tions belonging to CZ-NACE 27: CZ-NACE 27, CZ-NACE 271 and CZ-NACE 273. According to Czech Statistical Office the total number of companies belonging to these 3 segments is 136. It means 16,2 % companies belonging to CZ-NACE 27 participated in our research. Basic statistical methods were used to analyse the complete database. Scientific aim: The paper deals with the problem of service offering provided by today’s manufactur-ers. Global understanding of services that manufacturers really develop, sell, deliver and manage is still limited. Findings: Managing service offering provided by today‘s manufacturers shows that 1 Manufacturers not offer only tangible products, but also wide range of services and even information and support. 2 New products are not designed only according to company technicians, but also according to their cus-tomers. Their products and services are developed, tested and improved according to their needs. 3 Services provide complex customer care from time product selection to its end. Conclusions: Manufacturers of tangible products need to enlarge their product offering to be able to satisfy customers. Therefore

  15. Impact of the Molecular Form of Immunoglobulin A on Functional Activity in Defense against Streptococcus pneumoniae▿

    OpenAIRE

    Fasching, Claudine E.; Grossman, Tracy; Corthésy, Blaise; Plaut, Andrew G.; Weiser, Jeffrey N.; Janoff, Edward N.

    2007-01-01

    Antibodies of the immunoglobulin A (IgA) class react with capsular polysaccharides of Streptococcus pneumoniae and support complement-dependent opsonophagocytosis (OPC) of the organism by phagocytes. We characterized the biologic impact of the molecular forms of human monoclonal capsule-specific IgA (monomeric IgA [mIgA], polymeric IgA [pIgA], and secretory IgA [SIgA]) on OPC and susceptibility to cleavage by IgA1 protease. The efficiency of SIgA in support of OPC of S. pneumoniae was compara...

  16. The leukocyte immunoglobulin-like receptors (LIRs): a new family of immune regulators.

    Science.gov (United States)

    Fanger, N A; Borges, L; Cosman, D

    1999-08-01

    Identification of a counterstructure for the human cytomegalovirus-encoded major histocompatibility complex class I-related gene product, UL18, has led to the discovery of a novel family of immunoreceptors, termed leukocyte immunoglobulin-like receptors (LIRs). The LIRs are differentially expressed in cells of the dendritic cell, monocytic and lymphocytic lineages, and appear to mediate diverse roles in immune regulation. This review summarizes the expression, distribution, and signaling capacities of the LIRs and discusses possible roles of the LIRs in both inhibition and activation of the cellular responses.

  17. Exclusion of polymeric immunoglobulins and selective immunoglobulin Y transport that recognizes its Fc region in avian ovarian follicles.

    Science.gov (United States)

    Kitaguchi, Kohji; Osada, Kenichi; Horio, Fumihiko; Murai, Atsushi

    2008-02-15

    In avian species, blood immunoglobulin (Ig) Y, the equivalent to mammalian IgG, is selectively incorporated into ovarian follicles, but other classes, IgA and IgM, are much less abundant in the follicles. Several mammalian Igs, including IgG and IgA, are also incorporated into ovarian follicles when administered to birds. To clarify the Ig structure required for incorporation into ovarian follicles, Ig uptakes were determined after the intravenous injection of chicken and human Igs. Three chicken Igs (cIgY, cIgA and cIgM) and two human IgAs (monomeric hIgA and polymeric hIgA) were labeled with digoxigenin, and their uptakes into quail (Coturnix japonica) egg yolks were determined by ELISA and SDS-PAGE. The uptake of cIgY was the highest among the three cIgs (22% of injected cIgY was recovered from egg yolks). Chicken IgA was efficiently incorporated into egg yolk when it formed a monomeric state. Pentameric IgM was untransportable into egg yolk. We also found that the uptake of monomeric hIgA was much more efficient than that of polymeric hIgA. These results suggest that the retention of the monomeric form contributes to the efficient transport of Igs into ovarian follicles. On the other hand, Ig uptakes among monomeric Igs nevertheless differed; for example, a time-course analysis showed that the rate of monomeric cIgY uptake was approximately eight times faster than that of monomeric hIgA. The injection of cIgY fragments Fc, Fab and F(ab')(2) resulted in the largest uptake of Fc fragment, with the same level as that of cIgY. These results suggest the presence of a selective IgY transport system that recognizes its Fc region in avian ovarian follicles.

  18. FOREIGN LANGUAGE PROGRAMS OFFERED IN TURKISH UNIVERSITIES

    Directory of Open Access Journals (Sweden)

    Bengül CETINTAS

    2016-10-01

    Full Text Available n this study, the departments of philology and teaching, which take place in higher education programs in Turkey and give education in foreign language, have been examined. 23 different languages are offered to philology students who wants to attend to faculty of literature. Students can prefer classical languages besides modern languages. However, English, German, French, Arabic and Japanese are offered to the students of teaching department. To teach another foreign language, pedagogical formation is also required.This study focuses on the departments of German Language Teaching and German Language and Literature. From this point, the place and the importance of other philology and foreign language teaching departments in Turkish higher education have been examined.

  19. Distribution of the killer cell immunoglobulin-like receptors in Mexican Mestizos.

    Science.gov (United States)

    Contreras, G; Aláez, C; Murguía, A; García, D; Flores, H; Gorodezky, C

    2007-04-01

    Understanding the complex interaction between human leukocyte antigen (HLA) and killer immunoglobulin-like receptor (KIR) requires study of both HLA and KIR diversity in the same population. The presence of KIR genes 2DL1, 2, 3, 4, 5, KIR3DL1, 3DL2, 3DL3, KIR2DS1, 2DS2, 2DS3, 2DS4, 2DS5, KIR3DS1, KIR3DP1, KIR2DP1 was determined in 54 unrelated Mexican Mestizo donors. The PCR sequence-specific oligonucleotide probe One Lambda kit (Luminex) kindly given by J. Lee was used for typing. The software analyses the combination obtained for each of the five exons. Five controls (UCLA DNA exchange) were run as quality control. The gene frequency (GF) was calculated for the 16 KIR loci; the GF of individual genes was 100% for 2DL4, 3DL1, 3DL2, 3DL3, 3DP1. KIR2DL1 (76.43%), KIR2DL2 (37.64%), KIR2DL3 (76.43%), KIR2DL5 (29.29%), KIR3DS1 (23.02%), KIR2DS1 (21.83%), KIR2DS2 (37.64%), KIR2DS3 (50.93%), KIR2DS4 (86.93%), KIR2DS5 (29.29%), KIR2DP1 (86.39%). We observed similar frequencies with Caucasians and Mediterraneans, with exceptions: KIR3DL1 which was present in 100% Mexicans, ranged from 62% to 75% in Caucasians; 2DS3 (50.9%) vs 14-20% 2DS4 (86.39%) vs 65-79% and 2DS5 (29.29%) vs 11-18% in Caucasians. The finding of 23 phenotypes in 54 individuals accounting for both chromosomes, demonstrates the enormous diversity. We found 14 different combinations of stimulatory KIRs in the phenotypes; every subject had at least one stimulatory KIR; in all of them, 2DS4 existed except for one person who may have some new combination: 2DS2 2DS3. Extended family data will offer accurate and precise haplotypes to provide an insight on the significance of ethnic distribution and KIR repertoire.

  20. Complexes between nuclear factor-κB p65 and signal transducer and activator of transcription 3 are key actors in inducing activation-induced cytidine deaminase expression and immunoglobulin A production in CD40L plus interleukin-10-treated human blood B cells.

    Science.gov (United States)

    Lafarge, S; Hamzeh-Cognasse, H; Richard, Y; Pozzetto, B; Cogné, M; Cognasse, F; Garraud, O

    2011-11-01

    The signal transducer and activator of transcription 3 (STAT3) transcription factor pathway plays an important role in many biological phenomena. STAT3 transcription is triggered by cytokine-associated signals. Here, we use isolated human B cells to analyse the role of STAT3 in interleukin (IL)-10 induced terminal B cell differentiation and in immunoglobulin (Ig)A production as a characteristic readout of IL-10 signalling. We identified optimal conditions for inducing in-vitro IgA production by purified blood naive B cells using IL-10 and soluble CD40L. We show that soluble CD40L consistently induces the phosphorylation of nuclear factor (NF)-κB p65 but not of STAT3, while IL-10 induces the phosphorylation of STAT3 but not of NF-κB p65. Interestingly, while soluble CD40L and IL-10 were synergistic in driving the terminal maturation of B cells into IgA-producing plasma cells, they did not co-operate earlier in the pathway with regard to the transcription factors NF-κB p65 or STAT3. Blocking either NF-κB p65 or STAT3 profoundly altered the production of IgA and mRNA for activation-induced cytidine deaminase (AID), an enzyme strictly necessary for Ig heavy chain recombination. Finally, the STAT3 pathway was directly activated by IL-10, while IL-6, the main cytokine otherwise known for activating the STAT3 pathway, did not appear to be involved in IL-10-induced-STAT3 activation. Our results suggest that STAT3 and NF-κB pathways co-operate in IgA production, with soluble CD40L rapidly activating the NF-κB pathway, probably rendering STAT3 probably more reactive to IL-10 signalling. This novel role for STAT3 in B cell development reveals a potential therapeutic or vaccine target for eliciting IgA humoral responses at mucosal interfaces.