WorldWideScience

Sample records for human intravenous immunoglobulin

  1. Clearance of 131I-labeled murine monoclonal antibody from patients' blood by intravenous human anti-murine immunoglobulin antibody

    International Nuclear Information System (INIS)

    Stewart, J.S.; Sivolapenko, G.B.; Hird, V.; Davies, K.A.; Walport, M.; Ritter, M.A.; Epenetos, A.A.

    1990-01-01

    Five patients treated with intraperitoneal 131I-labeled mouse monoclonal antibody for ovarian cancer also received i.v. exogenous polyclonal human anti-murine immunoglobulin antibody. The pharmacokinetics of 131I-labeled monoclonal antibody in these patients were compared with those of 28 other patients receiving i.p.-radiolabeled monoclonal antibody for the first time without exogenous human anti-murine immunoglobulin, and who had no preexisting endogenous human anti-murine immunoglobulin antibody. Patients receiving i.v. human anti-murine immunoglobulin antibody demonstrated a rapid clearance of 131I-labeled monoclonal antibody from their circulation. The (mean) maximum 131I blood content was 11.4% of the injected activity in patients receiving human anti-murine immunoglobulin antibody compared to 23.3% in patients not given human anti-murine immunoglobulin antibody. Intravenous human anti-murine immunoglobulin antibody decreased the radiation dose to bone marrow (from 131I-labeled monoclonal antibody in the vascular compartment) 4-fold. Following the injection of human anti-murine immunoglobulin antibody, 131I-monoclonal/human anti-murine immunoglobulin antibody immune complexes were rapidly transported to the liver. Antibody dehalogenation in the liver was rapid, with 87% of the injected 131I excreted in 5 days. Despite the efficient hepatic uptake of immune complexes, dehalogenation of monoclonal antibody was so rapid that the radiation dose to liver parenchyma from circulating 131I was decreased 4-fold rather than increased. All patients developed endogenous human anti-murine immunoglobulin antibody 2 to 3 weeks after treatment

  2. INTRAVENOUS IMMUNOGLOBULIN IN PEDIATRIC RHEUMATOLOGY PRACTICE

    Directory of Open Access Journals (Sweden)

    E. I. Alexeeva

    2015-01-01

    Full Text Available Modern successful treatment of rheumatic diseases is impossible without the use of intravenous immunoglobulin. The use of intravenous immunoglobulin is based on strict indications developed as a result of long-term multicenter controlled studies. The article highlights the issues of using immunoglobulin in pediatric rheumatology practice, and provides the review of literature with the results from the evaluation of the efficiency of intravenous immunoglobulin confirming the efficiency of the drug only for certain rheumatic diseases. 

  3. 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.

  4. 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.

  5. 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.

  6. 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)

    Tatyana 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.

  7. Intravenous immunoglobulin and Alzheimer's disease immunotherapy.

    Science.gov (United States)

    Solomon, Beka

    2007-02-01

    Amyloid-beta peptide (Abeta) contributes to the acute progression of Alzheimer's disease (AD) and has become the main target for therapeutics. Active immunization with Abeta in individuals with AD has been efficacious; however, some patients developed side effects, possibly related to an autoimmune response. Evidence that intravenous immunoglobulin (IVIg), an FDA-approved purified immunoglobulin fraction from normal human donor blood, shows promise of passive immunotherapy for AD is reviewed. Investigations into the molecular effects of IVIg on Abeta clearance, using the BV-2 cellular microglia line, demonstrate that IVIg dissolves Abeta fibrils in vitro, increases cellular tolerance to Abeta, enhances microglial migration toward Abeta deposits, and mediates phagocytosis of Abeta. Preliminary clinical results indicate that IVIg, which contains natural antibodies against the Abeta, warrants further study into its potential to deliver a controlled immune attack on the peptide, avoiding the immune toxicities that have had a negative impact on the first clinical trials of vaccine against Abeta.

  8. Use of intravenous immunoglobulins in clinical practice

    Directory of Open Access Journals (Sweden)

    E.K. Donyush

    2011-01-01

    Full Text Available Immunoglobulins are main component of immune defense; they take part in anti-infectious resistance of organism and regulate processes of different immune reactions. Intravenous immunoglobulins are the most frequently used products made from donor blood plasma. The need in these drugs is steadily increasing during last 15–20 years, and indications are widening due to modern hightechnology methods of production and cleaning. The article presents modern data on formula, mechanisms of action and indications for different groups of intravenous immunoglobulins (standard, hyperimmune, fortified and description of possible adverse events.Key words: immuglobulines, prophylaxis, treatment, unfavorable reaction, children.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Pattern of intravenous immunoglobulins (IVIG) use in a pediatric ...

    African Journals Online (AJOL)

    Pattern of intravenous immunoglobulins (IVIG) use in a pediatric intensive care facility in a resource limited setting. ... Journal Home > Vol 13, No 2 (2013) > ... Results: The clinical diagnoses included neurology (35%), neonatology (16%), ...

  14. Pattern of intravenous immunoglobulins (IVIG) use in a pediatric ...

    African Journals Online (AJOL)

    EB

    Abstract. Background: Intravenous Immunoglobulin (IVIG) preparations are scarce biological products used for replacement or immunomodulatory effects. Guidelines have been issued by regulatory health authorities to ensure provision of the products for patients who are in severe need. Objectives: The study aimed at ...

  15. Intravenous Immunoglobulin Protects Against Severe Pandemic Influenza Infection

    Directory of Open Access Journals (Sweden)

    Steven Rockman

    2017-05-01

    Full Text Available Influenza is a highly contagious, acute, febrile respiratory infection that can have fatal consequences particularly in individuals with chronic illnesses. Sporadic reports suggest that intravenous immunoglobulin (IVIg may be efficacious in the influenza setting. We investigated the potential of human IVIg to ameliorate influenza infection in ferrets exposed to either the pandemic H1N1/09 virus (pH1N1 or highly pathogenic avian influenza (H5N1. IVIg administered at the time of influenza virus exposure led to a significant reduction in lung viral load following pH1N1 challenge. In the lethal H5N1 model, the majority of animals given IVIg survived challenge in a dose dependent manner. Protection was also afforded by purified F(ab′2 but not Fc fragments derived from IVIg, supporting a specific antibody-mediated mechanism of protection. We conclude that pre-pandemic IVIg can modulate serious influenza infection-associated mortality and morbidity. IVIg could be useful prophylactically in the event of a pandemic to protect vulnerable population groups and in the critical care setting as a first stage intervention.

  16. Intravenous Immunoglobulin in the Treatment of Primary Immunodeficiency Diseases.

    Science.gov (United States)

    De Ranieri, Deirdre; Fenny, Nana Sarkoah

    2017-01-01

    Intravenous immunoglobulin (IVIG) has been used as antibody replacement therapy in primary immunodeficiency diseases (PIDDs) for more than 50 years. Its role as a therapeutic agent has expanded over the past couple of decades as its anti-inflammatory and immune-modulatory mechanisms of action have been elucidated. It is now used "off-label" to treat other autoimmune diseases. This article focuses on the role of IVIG in the treatment of PIDDs characterized by absent or deficient antibody production. Replacement doses are given on a monthly basis in these conditions as a prophylactic measure to prevent acute and serious bacterial infections. [Pediatr Ann. 2017;46(1):e8-e12.]. Copyright 2017, SLACK Incorporated.

  17. Intravenous immunoglobulin in ABO and Rh hemolytic diseases of newborn.

    Science.gov (United States)

    Nasseri, Fatemeh; Mamouri, Gholam A; Babaei, Homa

    2006-12-01

    To evaluate whether the use of intravenous immunoglobulin in newborn infants with isoimmune hemolytic jaundice due to Rh and ABO incompatibility is an effective treatment in reducing the need for exchange transfusion. This study included all direct Coombs' test positive Rh and ABO isoimmunized babies, who admitted in the Neonatal Intensive Care Unit of Ghaem Hospital of Mashhad University of Medical Sciences, Iran, from October 2003 to October 2004. Significant hyperbilirubinemia was defined as rising by >or=0.5 mg/dl per hour. Babies were randomly assigned to received phototherapy with intravenous immunoglobulin (IVIg) 0.5 g/kg over 4 hours, every 12 hours for 3 doses (study group) or phototherapy alone (control group). Exchange transfusion was performed in any group if serum bilirubin exceeded >or=20mg/dl or rose by >or=1mg/dl/h. A total of 34 babies were eligible for this study (17 babies in each group). The number of exchange transfusion, duration of phototherapy and hospitalization days, were significant shorter in the study group versus control group. When we analyzed the outcome results in ABO and Rh hemolytic disease separately, the efficacy of IVIg was significantly better in Rh versus ABO isoimmunization. Late anemia was more common in the IVIg group 11.8% versus 0%, p=0.48. Adverse effects were not observed during IVIg administration. Administration of IVIg to newborns with significant hyperbilirubinemia due to Rh hemolytic disease reduced the need for exchange transfusion but in ABO hemolytic disease there was no significant difference between IVIg and double surface blue light phototherapy.

  18. Cytomegalovirus neutralization by hyperimmune and standard intravenous immunoglobulin preparations.

    Science.gov (United States)

    Planitzer, Christina B; Saemann, Marcus D; Gajek, Hartwig; Farcet, Maria R; Kreil, Thomas R

    2011-08-15

    Cytomegalovirus (CMV) remains one of the most important pathogens after transplantation, potentially leading to CMV disease, allograft dysfunction, acute, and chronic rejection and opportunistic infections. Immunoglobulin G (IgG) preparations with high antibody titers against CMV are a valuable adjunctive prevention and treatment option for clinicians and apart from standard intravenous immunoglobulin (IVIG), CMV hyperimmune preparations are available. The CMV antibody titer of these preparations is typically determined by Enzyme-linked immunosorbent assay (ELISA), also used for the selection of high titer plasma donors for the production of the CMV Hyperimmune product. However, CMV ELISA titers do not necessarily correlate with CMV antibody function which is determined by virus neutralization tests. CMV antibody titers were determined by both ELISA and virus neutralization assay and the IgG subclass distribution was compared between a CMV hyperimmune licensed in Europe and standard IVIG preparations. Although the expected high CMV IgG ELISA antibody titers were confirmed for three lots of a CMV hyperimmune preparation, the functionally more relevant CMV neutralizing antibody titers were significantly higher for 31 lots of standard IVIG preparations. Moreover, considerably lower IgG3 levels were found for the CMV hyperimmune preparation compared with standard IVIG preparations. The higher functional CMV neutralization titers of standard IVIG preparations and the better availability of these preparations, suggest that these products could be a valuable alternative to the CMV hyperimmune preparation.

  19. Induction of Regulatory T Cells by Intravenous Immunoglobulin: A Bridge between Adaptive and Innate Immunity.

    Science.gov (United States)

    Kaufman, Gabriel N; Massoud, Amir H; Dembele, Marieme; Yona, Madelaine; Piccirillo, Ciriaco A; Mazer, Bruce D

    2015-01-01

    Intravenous immunoglobulin (IVIg) is a polyclonal immunoglobulin G preparation with potent immunomodulatory properties. The mode of action of IVIg has been investigated in multiple disease states, with various mechanisms described to account for its benefits. Recent data indicate that IVIg increases both the number and the suppressive capacity of regulatory T cells, a subpopulation of T cells that are essential for immune homeostasis. IVIg alters dendritic cell function, cytokine and chemokine networks, and T lymphocytes, leading to development of regulatory T cells. The ability of IVIg to influence Treg induction has been shown both in animal models and in human diseases. In this review, we discuss data on the potential mechanisms contributing to the interaction between IVIg and the regulatory T-cell compartment.

  20. Clinical outcomes of intravenous immunoglobulin therapy in refractory uveitis.

    Science.gov (United States)

    Garcia-Geremias, M; Carreño, E; Epps, S J; Lee, R W J; Dick, A D

    2015-04-01

    Intravenous immunoglobulin (IVIg) therapy has multiple mechanisms of immunomodulatory action. We wished therefore to assess its efficacy in a spectrum of patients with refractory uveitis. Retrospective review of clinical charts was conducted to document response to IVIg treatment in consecutive patients with treatment-refractory uveitis. Main outcome measures were control of intraocular inflammation, visual acuity, progression of the disease, and complications. Four (two male) patients, with a mean age at the beginning of the treatment of 47 years (range: 39-64), were included in the study. Indication for treatment was patients with active non-infectious uveitis refractory to steroids and immunomodulatory therapy. All patients received a course of 0.5 g/kg per day of IVIg for three consecutive days, repeating this course at a mean of 11 week (range: 2-39 weeks) intervals when indicated clinically. The median duration of the IVIg therapy was 7 months (range: 3-14 months). In three patients treatment resulted in stabilisation and prevention of progression of the disease, and additionally in two patients it facilitated a decrease in prednisolone dose. Treatment failed to induce long-term remission in one patient with recurrence of macular oedema. IVIg was well tolerated with neither immediate nor longer-term adverse events observed. In three out of four cases IVIg was an effective adjunctive therapy and well tolerated for the management of treatment-refractory uveitis.

  1. Intravenous immunoglobulin response in treatment-naïve chronic inflammatory demyelinating polyradiculoneuropathy

    NARCIS (Netherlands)

    Kuitwaard, Krista; Hahn, Angelika F.; Vermeulen, Marinus; Venance, Shannon L.; van Doorn, Pieter A.

    2015-01-01

    There is no consensus on which treatment should be used preferentially in individual patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Patients unlikely to respond to intravenous immunoglobulin (IVIg) could be prescribed corticosteroids first to avoid high cost and a delayed

  2. Exquisite response to intravenous immunoglobulin in Susac syndrome during pregnancy

    Directory of Open Access Journals (Sweden)

    Enrique Gomez-Figueroa

    2018-03-01

    Full Text Available Introduction: From its initial report on two female patients in 1979 by J.O. Susac, Susac syndrome (SuS or SICRET (small infarctions of cochlear, retinal and encephalic tissue has persisted as an elusive entity. To date the available evidence for its treatment is based on case reports and case series. The largest systematic review described only 304 reported cases since the 1970s. Here we presented the first reported case to our knowledge in Mexican population and the unusual presentation in a pregnant patient. Case presentation: A 34-year-old Hispanic woman was brought to the ER in our hospital for apathy and behavioral changes. Upon arrival at the ER, her husband described a one-month history of behavioral changes with apathy, progressive abulia, visuospatial disorientation, and gait deterioration. The initial lab test shows no significance except by a positive qualitative hCG. An MRI was obtained and showed hyperintense periventricular white matter lesions in T2 and FLAIR sequences also involving bilateral basal ganglia and with predominant affection of the corpus callosum, in addition to infratentorial cerebellar lesions. After treatment with intravenous immunoglobulins a marked and prompt clinical and radiological improvement was observed. Conclusion: SuS is still an elusive disease. To date, no definitive score or clinical feature can predict the outcome of the disease. The presentation during pregnancy is also rare and therefore the optimal treatment and the prognosis is unknown. We hope that this article will serve as a foundation for future research. Keywords: Susac syndrome, Neuroinflammation, Corpus callosum, Demyelinating disease, Vasculitis

  3. Predictors of nonresponse to intravenous immunoglobulin therapy in Kawasaki disease

    Directory of Open Access Journals (Sweden)

    Hyo Min Park

    2013-02-01

    Full Text Available <b>Purpose:</b> It has been reported that 10% to 20% of children with Kawasaki disease (KD will not respond to intravenous immunoglobulin (IVIG treatment. In this study, we aimed to identify useful predictors of therapeutic failure in children with KD. <b>Methods:</b> We examined 309 children diagnosed with KD at the Kyungpook National University Hospital and the Inje University Busan Paik Hospital between January 2005 and June 2011. We retrospectively reviewed their medical records and analyzed multiple parameters in responders and nonresponders to IVIG. <b>Results:</b> Among the 309 children, 30 (9.7% did not respond to IVIG. They had significantly higher proportion of neutrophils, and higher levels of aspartate aminotransferase, alanine aminotransferase (ALT, total bilirubin, and N-terminal fragment of B-type natriuretic peptide than did responders. IVIGnonresponders had a significantly longer duration of hospitalization, and more frequently experienced coronary artery lesion, and sterile pyuria. No differences in the duration of fever at initial treatment or, clinical features were noted. <b>Conclusion:</b> Two independent predictors (ALT?#248;4 IU/L, total bilirubin?#240;.9 mg/dL for nonresponse were confirmed through multivariate logistic regression analysis. Thus elevated ALT and total bilirubin levels might be useful in predicting nonresponse to IVIG therapy in children with KD.

  4. Intravenous immunoglobulin to treat hyperbilirubinemia in neonates with isolated Glucose-6-Phosphate dehydrogenase deficiency

    Directory of Open Access Journals (Sweden)

    Wadah Khriesat

    2017-04-01

    Full Text Available Background Glucose-6-phosphate dehydrogenase deficiency alone or concomitant with ABO isoimmunisation is a widespread indication for neonatal exchange transfusion. Aims To evaluate the effectiveness of Intravenous Immunoglobulin in the treatment of neonatal hyperbilirubinemia due to glucose-6-phosphate dehydrogenase deficiency. Methods A retrospective cohort study was conducted between 2006 and 2014 at the Jordan University of Science and technology. The medical records of 43 infants admitted to the neonatal intensive care unit for isolated glucose-6- phosphate dehydrogenase deficiency hemolytic disease of the newborns were reviewed. Patients were divided into two groups. Group I, a historical cohort, included newborns born between 2006 and 2010, Treatment included phototherapy and exchange transfusion. Group II included newborns born between 2011 and 2014, where, in addition to phototherapy, intravenous immunoglobulin was administered. The duration of phototherapy and number of exchange transfusions were evaluated. Results Of 412 newborns that were admitted with neonatal hyperbilirubinemia, Glucose-6-phosphate dehydrogenase deficiency was present in 43. Of these, 22, did not receive intravenous immunoglobulin and served as a control group. The other 21 newborns received intravenous immunoglobulin. There was no difference in the demographic characteristics between the two groups. Infants in the control group were significantly more likely to receive exchange blood transfusion than infants in the immunoglobulin treatment group, but were significantly less likely to need phototherapy. Conclusion Intravenous immunoglobulin is an effective alternative to exchange transfusion in infants with glucose-6-phosphate dehydrogenase deficiency hemolytic disease of the newborn. It is suggested that intravenous immunoglobulin may be beneficial as a prophylaxis for infants with hyperbilirubinemia.

  5. Intravenous Immunoglobulin therapy for anti-E hemolytic disease in the newborn.

    Science.gov (United States)

    Onesimo, Roberta; Rizzo, Daniela; Ruggiero, Antonio; Valentini, Piero

    2010-09-01

    Anti-E alloimmunisation is a less common cause of haemolytic disease in the newborn (HDN) and is usually associated with mild to moderate clinical manifestations, that are often less severe than anti-D immunisation. Conventional treatments for HDN are phototherapy and exchange transfusion, the latter still representing a high-risk procedure. Currently, intravenous immunoglobulin has been used as alternative treatment for HDN to reduce the need for exchange transfusion, as well as the length of phototherapy and hospitalisation. We report a case of anti-E HDN treated successfully with intravenous immunoglobulin, as adjuvant treatment to phototherapy.

  6. Haemolytic anaemia as a complication to intravenous immunoglobulin infusion

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Harbo, Thomas; Christiansen, Ingelise

    performed before and two weeks after infusion of IVIg. Following treatment blood haemoglobin declined from 8.6±0.8 to 8.1±1.3mmol/l, p... naive patients are susceptible to develop haemolysis. Haemolytic anaemia is a severe side effect that seems to be more frequent after immunoglobulin infusions than previously recognized....

  7. Modes of Action of Intravenous Immunoglobulin in Bullous Pemphigoid.

    Science.gov (United States)

    Li, Ning; Culton, Donna; Diaz, Luis A; Liu, Zhi

    2018-06-01

    Bullous pemphigoid is an autoantibody-mediated skin blistering disease. Previous studies revealed that intravenous Ig is therapeutic in animal models of bullous pemphigoid by saturating the IgG-protective receptor FcRn, thereby accelerating degradation of pathogenic IgG. Sasaoka et al. demonstrate that the inhibitory effects of intravenous Ig on bullous pemphigoid are also associated with negative modulation of cytokine production by keratinocytes. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Hemolytic anemia following high dose intravenous immunoglobulin in patients with chronic neurological disorders

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Christiansen, I; Harbo, Thomas

    2014-01-01

    High dose intravenous immunoglobulin (IVIG) is an established treatment for various neuromuscular disorders. Recently, cases of hemolytic anemia following IVIG have been observed. The objective of this study was to determine the extent of anemia and hemolysis after IVIG and its relationship...

  9. Intravenous polyclonal human immunoglobulins in multiple sclerosis

    DEFF Research Database (Denmark)

    Sørensen, Per Soelberg

    2008-01-01

    to methylprednisolone does not make remission of symptoms faster or more complete. IVIG does not seem to be of any benefit to chronic visual or motor symptoms in MS. In secondary progressive MS, IVIG has not shown any effect on disease progression, relapses or new magnetic resonance imaging lesions. Experimental...... studies in the MS model experimental autoimmune encephalomyelitis in rats demonstrate that IVIG has to be administered at the time of induction of a relapse in order to be effective. In conclusion, IVIG can be considered as a second-line treatment to approved therapies for relapsing-remitting MS...... and magnetic resonance imaging outcome measures Udgivelsesdato: 2008...

  10. Overview of the pathogenesis and treatment of chronic inflammatory demyelinating polyneuropathy with intravenous immunoglobulins

    Directory of Open Access Journals (Sweden)

    Mohamed Mahdi-Rogers

    2010-03-01

    Full Text Available Mohamed Mahdi-Rogers, Yusuf A RajaballyNeuromuscular Clinic, Department of Neurology, University Hospitals of Leicester, Leicester, UKAbstract: Chronic inflammatory demyelinating polyneuropathy (CIDP is an acquired heterogeneous disorder of immune origin affecting the peripheral nerves, causing motor weakness and sensory symptoms and signs. The precise pathophysiology of CIDP remains uncertain although B and T cell mechanisms are believed to be implicated. Intravenous immunoglobulins (IVIg have been shown in a number of trials to be an effective treatment for CIDP. IVIg is thought to exert its immunomodulatory effects by affecting several components of the immune system including B-cells, T-cells, macrophages and complement. This article provides an overview of the pathogenesis of CIDP and of its treatment with IVIg.Keywords: chronic inflammatory demyelinating polyneuropathy, intravenous immunoglobulin, pathogenesis, treatment

  11. Perforated Appendicitis After Intravenous Immunoglobulin Therapy in a Term Neonate with Haemolytic Jaundice

    International Nuclear Information System (INIS)

    Atikan, B. Y.; Koroglu, O. A.; Yalaz, M.; Ergun, O.; Dokumcu, Z.; Doganavasrgil, B.

    2015-01-01

    Neonatal appendicitis is a rare clinical condition that may cause high morbidity and mortality if diagnosis is delayed. There is usually an underlying disease; it can also be a localized form of necrotizing enterocolitis. Here, we present a term neonate who was treated with intravenous immunoglobulin because of severe isoimmune hemolytic jaundice. The patient developed abdominal symptoms within 10 hours of therapy, was diagnosed with acute perforated appendicitis and completely recovered after surgery. (author)

  12. Clinical Efficiency of Application of Intravenous Immunoglobulin in Pregnant Women with Intrauterine Infection

    Directory of Open Access Journals (Sweden)

    O.L. Ishchenko

    2016-02-01

    Full Text Available The problem of intrauterine infection (IUI is still relevant today. Ineffective treatment of this pathology is associated with physiological decline of the immunity in these patients. We have proposed the additional use of intravenous immunoglobulin for the treatment of pregnant women with IUI. There were examined 75 patients with IUI, which was diagnosed in the II trimester. The I group consisted of 40 individuals who received conventional treatment, the II group was formed from 35 women who additionally received intravenous immunoglobulin. On the background of IUI, pregnancy was characterized by an increased incidence of threatened miscarriage and premature labor, gestosis and placental dysfunction; during delivery, premature rupture of amniotic membrane and fetal distress were more common. These patients had placenta with both ultrasonic and histological signs of infection. Among newborns, there was a significant increase in the incidence of pathology associated with intrauterine infection. Additional use of intravenous immunoglobulin in the treatment of IUI during the II trimester of pregnancy in comparison with conventional therapy leads to a significant reduction in the incidence of both obstetric complications and perinatal pathology.

  13. 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.

  14. THE ROLE OF IgM-ENRICHED INTRAVENOUS IMMUNOGLOBULIN IN TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Szabó Judit

    2014-04-01

    Full Text Available After organ transplantation, gamma globulin and intravenous immunoglobulin enriched with IgM are most frequently used in septic shock as early immune-support. If the explanted organ is infected, the transplantation, as a life-saving operation, can be performed if there is no systemic inflammation and the patient receives IgM enriched immunoglobulin prophylaxis during surgery. The period after transplantation can be divided into three parts from the infection point of view: the first month after transplantation, the first sixth months and the following six months. Infections within the first month are basically related to the surgical procedure. Because of the immunosuppressive therapy, the opportunistic and fungal infections are more common during the first sixth months. After this period, the occurrence and the type of infections are similar to that of the non-transplant population except for pulmonary infections. The latter is two to three times more frequent. This is explained by the secondary hypogammaglobulinaemia (lower blood levels of IgM and IgG which is caused by the steroids but most of mycophenolate mofetil by inhibition of the T and B lymphocyte proliferation. Septic shock develops with a continuing fall of IgM levels. Under these circumstances additional intravenous immunoglobulin therapy with IgM can be lifesaving. Besides, immunoglobulin concentrates with IgM may also be used in the case of viral infections without prophylaxis and/or without etiological therapy such as in the case of West Nile virus infection. As a result of the increase in antibiotic resistance, the application of immunotherapy, including immunoglobulins may become the mainstream in the treatment of septic shock.

  15. [Value of intravenous immunoglobulins. A case of Guillain-Barré syndrome].

    Science.gov (United States)

    Hidou, M; Olivier, J; Vivant, J F

    1992-01-01

    A case of severe Guillain-Barré syndrome (GBS) was treated with high dose intravenous immunoglobulin (IVIG), 400 mg.kg-1.days-1, over three consecutive days. The treatment was repeated once. We observed a time-related response between immunoglobulins administration and clinical improvement. The pathologic lesions of the GBS suggest that this syndrome has an immunologic basis: a humoral factor is probably not the only immunological mechanism and cellular mechanisms are also likely to be of importance. Specific mechanisms might also be present in GBS, such as anti-idiotypic suppression of autoantibodies, and elimination of circulating immune complexes. Treatment with IVIG might have several therapeutic advantages over plasmapheresis: IVIG is easily infused without any delay, is easily available and has been used widely without serious complications.

  16. Intravenous Immunoglobulin Monotherapy for Granulomatous Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency.

    Science.gov (United States)

    Hasegawa, Mizue; Sakai, Fumikazu; Okabayashi, Asako; Sato, Akitoshi; Yokohori, Naoko; Katsura, Hideki; Asano, Chihiro; Kamata, Toshiko; Koh, Eitetsu; Sekine, Yasuo; Hiroshima, Kenzo; Ogura, Takashi; Takemura, Tamiko

    2017-11-01

    Common variable immunodeficiency (CVID) is a heterogeneous subset of immunodeficiency disorders. Recurrent bacterial infection is the main feature of CVID, but various non-infectious complications can occur. A 42-year-old woman presented with cough and abnormal chest X-ray shadows. Laboratory tests showed remarkable hypogammaglobulinemia. Computed tomography revealed multiple consolidation and nodules on the bilateral lung fields, systemic lymphadenopathy, and splenomegaly. A surgical lung biopsy specimen provided the final diagnosis of lymphoproliferative disease in CVID, which was grouped under the term granulomatous lymphocytic interstitial lung disease. Interestingly, the lung lesions of this case resolved immediately after the initiation of intravenous immunoglobulin monotherapy.

  17. [Adult-onset Still's disease with pulmonary and cardiac involvement and response to intravenous immunoglobulin].

    Science.gov (United States)

    Neto, Nilton Salles Rosa; Waldrich, Leandro; de Carvalho, Jozélio Freire; Pereira, Rosa Maria Rodrigues

    2009-01-01

    Cardiopulmonary manifestations of adult-onset Still's disease (AOSD) include pericarditis, pleural effusion, transient pulmonary infiltrates, pulmonary interstitial disease and myocarditis. Serositis are common but pneumonitis and myocarditis are not and bring elevated risk of mortality. They may manifest on disease onset or flares. Previously reported cases were treated with high-dose glucocorticoids and immunosupressants and, when refractory, intravenous immunoglobulin (IVIG). We report an AOSD patient whose flare presented with severe pleupneumonitis and myopericarditis and, following nonresponse to a methylprednisolone pulse, high dose of prednisone and cyclosporine A, recovered after a 2-day 1g/kg/day IVIG infusion.

  18. Analysis and functional consequences of increased Fab-sialylation of intravenous immunoglobulin (IVIG) after lectin fractionation.

    Science.gov (United States)

    Käsermann, Fabian; Boerema, David J; Rüegsegger, Monika; Hofmann, Andreas; Wymann, Sandra; Zuercher, Adrian W; Miescher, Sylvia

    2012-01-01

    It has been proposed that the anti-inflammatory effects of intravenous immunoglobulin (IVIG) might be due to the small fraction of Fc-sialylated IgG. In this study we biochemically and functionally characterized sialic acid-enriched IgG obtained by Sambucus nigra agglutinin (SNA) lectin fractionation. Two main IgG fractions isolated by elution with lactose (E1) or acidified lactose (E2) were analyzed for total IgG, F(ab')(2) and Fc-specific sialic acid content, their pattern of specific antibodies and anti-inflammatory potential in a human in vitro inflammation system based on LPS- or PHA-stimulated whole blood. HPLC and LC-MS testing revealed an increase of sialylated IgG in E1 and more substantially in the E2 fraction. Significantly, the increased amount of sialic acid residues was primarily found in the Fab region whereas only a minor increase was observed in the Fc region. This indicates preferential binding of the Fab sialic acid to SNA. ELISA analyses of a representative range of pathogen and auto-antigens indicated a skewed antibody pattern of the sialylated IVIG fractions. Finally, the E2 fraction exerted a more profound anti-inflammatory effect compared to E1 or IVIG, evidenced by reduced CD54 expression on monocytes and reduced secretion of MCP-1 (CCL2); again these effects were Fab- but not Fc-dependent. Our results show that SNA fractionation of IVIG yields a minor fraction (approx. 10%) of highly sialylated IgG, wherein the sialic acid is mainly found in the Fab region. The tested anti-inflammatory activity was associated with Fab not Fc sialylation.

  19. Analysis and functional consequences of increased Fab-sialylation of intravenous immunoglobulin (IVIG after lectin fractionation.

    Directory of Open Access Journals (Sweden)

    Fabian Käsermann

    Full Text Available It has been proposed that the anti-inflammatory effects of intravenous immunoglobulin (IVIG might be due to the small fraction of Fc-sialylated IgG. In this study we biochemically and functionally characterized sialic acid-enriched IgG obtained by Sambucus nigra agglutinin (SNA lectin fractionation. Two main IgG fractions isolated by elution with lactose (E1 or acidified lactose (E2 were analyzed for total IgG, F(ab'(2 and Fc-specific sialic acid content, their pattern of specific antibodies and anti-inflammatory potential in a human in vitro inflammation system based on LPS- or PHA-stimulated whole blood. HPLC and LC-MS testing revealed an increase of sialylated IgG in E1 and more substantially in the E2 fraction. Significantly, the increased amount of sialic acid residues was primarily found in the Fab region whereas only a minor increase was observed in the Fc region. This indicates preferential binding of the Fab sialic acid to SNA. ELISA analyses of a representative range of pathogen and auto-antigens indicated a skewed antibody pattern of the sialylated IVIG fractions. Finally, the E2 fraction exerted a more profound anti-inflammatory effect compared to E1 or IVIG, evidenced by reduced CD54 expression on monocytes and reduced secretion of MCP-1 (CCL2; again these effects were Fab- but not Fc-dependent. Our results show that SNA fractionation of IVIG yields a minor fraction (approx. 10% of highly sialylated IgG, wherein the sialic acid is mainly found in the Fab region. The tested anti-inflammatory activity was associated with Fab not Fc sialylation.

  20. The Role of Intravenous Immunoglobulin Preparations in the Treatment of Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Marta Baleva

    2011-01-01

    Full Text Available Scleroderma is progressive autoimmune disease associated with severe disability. The major underlying pathological process in scleroderma is progressive development of fibrous tissue and obliteration of the microvasculature. Currently, there are no medical products for the treatment of scleroderma that provide both sufficient immunosuppression and low-risk side safety profile with negligible side effects. There are a large number of experimental data showing that intravenous immunoglobulin (IVIG has multiple clinical and morphological effects. On the other hand, some authors report good effect of intravenous immune globulins in patients with scleroderma. The less frequent side effects of IVIG in doses below or equal to 2 g/kg/month divided in 5 consecutive days make IVIG a promising treatment of choice in scleroderma.

  1. Rapid Resolution of Enterovirus 71-Associated Opsoclonus Myoclonus Syndrome on Intravenous Immunoglobulin

    Directory of Open Access Journals (Sweden)

    Ahmed Sahly MD

    2017-09-01

    Full Text Available Nonparaneoplastic opsoclonus–myoclonus ataxia syndrome is a rare neuroinflammatory condition featured by opsoclonus, myoclonus, ataxia, and cognitive behavioral disturbance. The authors report an observation of enterovirus 71-associated opsoclonus–myoclonus ataxia syndrome evolving toward full recovery on intravenous intravenous immunoglobulin (IG treatment. Based on this case report, enterovirus 71 should be added to the list of infectious agents likely involved in opsoclonus–myoclonus ataxia syndrome, including the emerging subgroup of opsoclonus–myoclonus ataxia syndrome recovering without aggressive or prolonged immunosuppressive intervention. Further studies are mandatory to define the precise role, incidence, treatment, and outcome of enterovirus 71 and other infectious agents in benign forms of opsoclonus–myoclonus ataxia syndrome.

  2. Adverse Effects with Ambulatory Intravenous Immunoglobulin Administration in Adult Patients with Common Variable Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Karen Alicia Rodríguez-Mireles

    2014-06-01

    Full Text Available Background: Common variable immunode ciency (CVID is the most frequent symptomatic primary immunodeficiency, affecting 1:25,000- 75,000 people. It is characterized by the absence or decrease antibody production. Treatment for CVID consists on human immunoglobulin administration, and the intravenous route is the most common route for administration, at 400-800 mg/kg of weight every 3-4 weeks. Adverse effects associated with intravenous immunoglobulin (IVIg use occur in 25% of all infusions, with severe adverse reactions presenting in less than 1% of all patients. Acute renal failure can occur as a severe adverse reaction, which presents 1-10 days after starting IVIg treatment. In our center we implemented an ambulatory scheme for IVIg administration, which allows its administration in an average of 3 hours, without severe adverse effects. Objectives: To describe adverse effects and to evaluate the frequency of renal failure secondary to ambulatory IVIg administration in patients with common variable immunode ciency. Material and method: A descriptive and prospective study was done including adult patients con de nitive diagnosis of common variable immunodeficiency, receiving IVIg at replacement dose every 3 weeks. All patients were evaluated with clinical exploration, somatometry, serum creatinine, albumin and urea determination, 24 hours creatinine clearance, glomerular ltration rate with CKD-EPI, and immediate renal function associated with accumulated IVIg. Results were analyzed with descriptive statistics. Results: We determined adverse effects in 25 patients with common variable immunode ciency (15 women and 10 men, average age 36.7 years, during a 10 months period (January-September 2013. During this period 284 IVIg infusions were administered using our scheme, frequency of adverse effects were 12.9%, with 5.2% of early adverse effects and 7.7% late adverse effects, all being mild to moderate, in some cases required analgesic and

  3. Intravenous immunoglobulin in the management of a rare cause of hemolytic disease of the newborn: Anti-SARA antibodies.

    Science.gov (United States)

    Venkataraman, Rohini; Yusuf, Kamran

    2017-01-01

    Hemolytic disease of newborn (HDN) is a condition that develops in a fetus, when the IgG molecules produced by the mother pass through the placenta and attack the fetal red blood cells. HDN can occur due to Rh and ABO incompatibilities between the mother and the fetus as well as due to other allo-immune antibodies belonging to Kell (K and k), Duffy (Fya), Kidd (Jka and Jkb), and MNS (M, N, S, and s) systems. Role of intravenous immunoglobulin in management of HDN is not clear.SARA red blood cell antigen, first discovered in 1990 is a low frequency antigen. We report, a multiparous female whose pregnancy was complicated by HDN due to anti-SARA antibodies requiring both exchange transfusion and intravenous immunoglobulin. The response was sustained after intravenous immunoglobulin (IVIG) rather than after exchange transfusion.

  4. Intravenous immunoglobulin treatment and screening for hypocretin neuron-specific autoantibodies in recent onset childhood narcolepsy with cataplexy

    DEFF Research Database (Denmark)

    Knudsen, S; Mikkelsen, J D; Bang, B

    2010-01-01

    Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC.......Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC....

  5. Analysis of anti-HLA antibodies in sensitized kidney transplant candidates subjected to desensitization with intravenous immunoglobulin and rituximab.

    Science.gov (United States)

    Lobashevsky, Andrew L; Higgins, Nancy G; Rosner, Kevin M; Mujtaba, Muhammad A; Goggins, William C; Taber, Tim E

    2013-07-27

    Preexisting donor-specific antibodies against human leukocyte antigens are major risk factors for acute antibody-mediated and chronic rejection of kidney transplant grafts. Immunomodulation (desensitization) protocols may reduce antibody concentration and improve the success of transplant. We investigated the effect of desensitization with intravenous immunoglobulin and rituximab on the antibody profile in highly sensitized kidney transplant candidates. In 31 transplant candidates (calculated panel-reactive antibody [cPRA], 34%-99%), desensitization included intravenous immunoglobulin on days 0 and 30 and a single dose of rituximab on day 15. Anti-human leukocyte antigen antibodies were analyzed before and after desensitization. Reduction of cPRA from 25% to 50% was noted for anti-class I (5 patients, within 20-60 days) and anti-class II (3 patients, within 10-20 days) antibodies. After initial reduction of cPRA, the cPRA increased within 120 days. In 24 patients, decrease in mean fluorescence intensity of antibodies by more than 50% was noted at follow-up, but there was no reduction of cPRA. Rebound occurred in 65% patients for anti-class I antibodies at 350 days and anti-class II antibodies at 101 to 200 days. Probability of rebound effect was higher in patients with mean fluorescence intensity of more than 10,700 before desensitization, anti-class II antibodies, and history of previous transplant. The desensitization protocol had limited efficacy in highly sensitized kidney transplant candidate because of the short period with antibody reduction and high frequency of rebound effect.

  6. Changes in spatiotemporal gait parameters following intravenous immunoglobulin treatment for chronic inflammatory demyelinating polyneuropathy.

    Science.gov (United States)

    Vo, Mary L; Chin, Russell L; Miranda, Caroline; Latov, Norman

    2017-10-01

    Gait impairment is a common presenting symptom in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). However, gait parameters have not previously been evaluated in detail as potential independent outcome measures. We prospectively measured changes in spatiotemporal gait parameters of 20 patients with CIDP at baseline and following treatment with intravenous immunoglobulin (IVIG), using GAITRite® a computerized walkway system with embedded sensors. Overall, study patients showed significant improvements in gait velocity, cadence, stride length, double support time, stance phase, and swing phase following IVIG treatment. Mean changes in velocity, stance phase, and swing phase, exhibited the greatest statistical significance among the subgroup that exhibited clinically meaningful improvement in Inflammatory Neuropathy Cause and Treatment disability score, Medical Research Council sum score, and grip strength. Assessment of gait parameters, in particular velocity, step phase and swing phase, is a potentially sensitive outcome measure for evaluating treatment response in CIDP. Muscle Nerve 56: 732-736, 2017. © 2017 Wiley Periodicals, Inc.

  7. Unilateral Oral Mucous Membrane Pemphigoid: Refractory Atypical Presentation Successfully Treated with Intravenous Immunoglobulins

    Directory of Open Access Journals (Sweden)

    André Laureano

    2015-01-01

    Full Text Available A 57-year-old male presented with a 6-month history of blisters and painful erosions on the right buccal mucosa. No skin or other mucosal involvement was seen. The findings of histopathological and direct immunofluorescence examinations were sufficient for the diagnosis of oral mucous membrane pemphigoid in the context of adequate clinical correlation. No response was seen after topical therapies and oral corticosteroids or dapsone. Intravenous immunoglobulin was started and repeated every three weeks. Complete remission was achieved after three cycles and no recurrence was seen after two years of follow-up. The authors report a rare unilateral presentation of oral mucous membrane pemphigoid on the right buccal and hard palate mucosa, without additional involvement during a period of five years. Local trauma or autoimmune factors are possible etiologic factors for this rare disorder, here with unique presentation.

  8. Measles Virus Neutralizing Antibodies in Intravenous Immunoglobulins: Is an Increase by Revaccination of Plasma Donors Possible?

    Science.gov (United States)

    Modrof, Jens; Tille, Björn; Farcet, Maria R; McVey, John; Schreiner, Jessica A; Borders, Charles M; Gudino, Maria; Fitzgerald, Peter; Simon, Toby L; Kreil, Thomas R

    2017-11-15

    We report a screen of plasma donors confirming that widespread use of childhood measles vaccination since 1963 resulted in a decrease in average measles virus antibody titers among plasma donors, which is reflected in intravenous immunoglobulins (IVIGs). The measles virus antibody titer, however, is a potency requirement for IVIGs, as defined in a Food and Drug Administration regulation. To mitigate the decline in measles virus antibody titers in IVIGs and to ensure consistent product release, revaccination of plasma donors was investigated as a means to boost titers. However, revaccination-induced titer increases were only about 2-fold and short-lived. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  9. Intravenous Immunoglobulins: Mode of Action and Indications in Autoimmune and Inflammatory Dermatoses

    Directory of Open Access Journals (Sweden)

    Lyubomir A. Dourmishev

    2016-01-01

    Full Text Available Intravenous immunoglobulins (IVIGs, a mixture of variable amounts of proteins (albumin, IgG, IgM, IgA, and IgE antibodies, as well as salt, sugar, solvents, and detergents, are successfully used to treat a variety of dermatological disorders. For decades, IVIGs have been administered for treatment of infectious diseases and immune deficiencies, since they contain natural antibodies that represent a first-line defense against pathogens. Today their indication has expanded, including the off-label therapy for a variety of autoimmune and inflammatory diseases. In dermatology, IVIGs are administered for treatment of different disorders at different therapeutic regimens, mostly with higher doses then those administered for treatment of infectious diseases. The aim of this prospective review is to highlight the indications, effectiveness, side effects, and perspectives of the systemic treatment with IVIGs for patients with severe, life-threatening, and resistant to conventional therapies autoimmune or inflammatory dermatoses.

  10. Scleromyxedema with Subcutaneous Nodules: Successful Treatment with Thalidomide and Intravenous Immunoglobulin

    Directory of Open Access Journals (Sweden)

    M. Dolenc-Voljč

    2013-11-01

    Full Text Available Scleromyxedema is a rare cutaneous mucinosis, usually presenting with generalized papular eruption and sclerodermoid induration, monoclonal gammopathy and systemic manifestations. An atypical clinical presentation with cutaneous and subcutaneous nodules has been reported rarely. In recent years, intravenous immunoglobulin (IVIg appears to be the therapy of choice for scleromyxedema. Treatment experiences in atypical manifestations with mucinous nodules are limited to sporadic reports. We report the case of male patient with atypical scleromyxedema without underlying paraproteinemia, presenting with generalized papular and sclerodermoid skin eruption and multiple nodular mucinous lesions on the fingers and face as well as on the eyelids, and associated systemic symptoms. Complete regression of all cutaneous lesions and extracutaneous symptoms with sustained remission was achieved by combined treatment with thalidomide and IVIg.

  11. Scleromyxedema with Subcutaneous Nodules: Successful Treatment with Thalidomide and Intravenous Immunoglobulin

    Science.gov (United States)

    Dolenc-Voljč, M.; Jurčić, V.; Hočevar, A.; Tomšič, M.

    2013-01-01

    Scleromyxedema is a rare cutaneous mucinosis, usually presenting with generalized papular eruption and sclerodermoid induration, monoclonal gammopathy and systemic manifestations. An atypical clinical presentation with cutaneous and subcutaneous nodules has been reported rarely. In recent years, intravenous immunoglobulin (IVIg) appears to be the therapy of choice for scleromyxedema. Treatment experiences in atypical manifestations with mucinous nodules are limited to sporadic reports. We report the case of male patient with atypical scleromyxedema without underlying paraproteinemia, presenting with generalized papular and sclerodermoid skin eruption and multiple nodular mucinous lesions on the fingers and face as well as on the eyelids, and associated systemic symptoms. Complete regression of all cutaneous lesions and extracutaneous symptoms with sustained remission was achieved by combined treatment with thalidomide and IVIg. PMID:24348379

  12. Non-ST Elevation Myocardial Infraction after High Dose Intravenous Immunoglobulin Infusion

    Directory of Open Access Journals (Sweden)

    Meir Mizrahi

    2009-01-01

    Full Text Available Intravenous immunoglobulins (IVIgs are used for several indications, including autoimmune conditions. IVIg treatment is associated with several possible adverse reactions including induction of a hypercoagulable state. We report a 76-year-old woman treated with IVIg for myasthenia gravis, which developed chest pain and weakness following IVIg infusion. The symptoms were associated with ST segment depression in V4–6 and elevated troponin levels. The patient was diagnosed with non-ST elevation myocardial infarction (NSTEMI. The patient had no significant risk factor besides age and a cardiac perfusion scan was interpreted as normal (the patient refused to undergo cardiac catheterization. This case is compatible with IVIg-induced hypercoagulability resulting in NSTEMI. Cardiac evaluation should therefore be considered prior to initiation of IVIg treatment especially in patients with multiple cardiovascular risks.

  13. INTRAVENOUS IMMUNOGLOBULIN ADMINISTRATION FOR DESENSITIZATION BEFORE RENAL TRANSPLANTATION AND MANAGING ANTIBODY-MEDIATED REJECTION

    Directory of Open Access Journals (Sweden)

    A. I. Sushkov

    2011-01-01

    Full Text Available Much attention has been placed recently in transplantation in highly HLA-sensitized patients. In attempts to remove these antibodies and enable successful renal transplantation, several approaches have been developed. Intravenous immunoglobulin (IVIG was found to be effective in the treatment of autoimmune and inflammatory disorders (e. g. Kawasaki disease, Guillain-Barre syndrome. Recently, a beneficial effect of IVIG on the reduc- tion of anti-HLA antibodies was described. The anti-inflammatory effect of IVIG provides hopeful opportunities in antibody-mediated rejection (AMR management. There are several protocols of IVIG administration for pre-transplant desensitization and AMR treatment: high-dose IVIG, low-dose IVIG + plasmapheresis, IVIG + plasmapheresis + rituximab. These advancements have enabled transplantation in patients previously considered untransplantable and in concert with new diagnostic techniques has resulted in new approaches to management of AMR. 

  14. Intravenous immunoglobulin therapy in a patient with lupus serositis and nephritis.

    Science.gov (United States)

    Meissner, M; Sherer, Y; Levy, Y; Chwalinska-Sadowska, H; Langevitz, P; Shoenfeld, Y

    2000-01-01

    The use of intravenous immunoglobulin (IVIg) has been reported as an immunomodulating agent in several autoimmune diseases, including systemic lupus erythematosus (SLE). Herein we report a SLE patient with severe clinical presentation that included pericarditis, pleural effusion, nephrotic range proteinuria, leukopenia, and lymphopenia. The patient received one course of high-dose IVIg (2.8 g/kg body weight), and within a week of post-IVIg therapy, her condition significantly improved. One-month post-IVIg there were decreased proteinuria, elevated leukocytes and lymphocytes count, decrease in antinuclear and anti-dsDNA antibodies, and disappearance of pericarditis and pleuritis. This case demonstrates the efficacy of IVIg in severe SLE with various clinical manifestations.

  15. Severe Periodontal Disease Associated with Long-Term Treatment with Intravenous Immunoglobulin

    Directory of Open Access Journals (Sweden)

    Jôice Dias Corrêa

    2014-01-01

    Full Text Available Intravenous immunoglobulin (IVIG is used in the treatment of neuropathy. This case report presents, for the first time, a patient with severe periodontal destruction after chronic therapy with IVIG. The patient reported having extracted his maxillary anterior teeth himself due to high mobility. Clinical examination and radiographic images show a generalized and severe periodontitis. No significant alterations in genetic or microbiological features were observed. The present case suggests that periodontal disease aggravation could be considered a new adverse effect of IVIG therapy. Postulated mechanisms are immune complexes formation, complement activation, and a direct effect in osteoclasts. In conclusion, it is important that patients that will receive IVIG treatment underwent dental evaluation.

  16. Intravenous immunoglobulin treatment and screening for hypocretin neuron-specific autoantibodies in recent onset childhood narcolepsy with cataplexy

    DEFF Research Database (Denmark)

    Knudsen, S; Mikkelsen, J D; Bang, B

    2010-01-01

    Narcolepsy with cataplexy (NC) is caused by substantial loss of hypocretin neurons. NC patients carry the HLA-DQB1*0602 allele suggesting that hypocretin neuron loss is due to an autoimmune attack. We tested intravenous immunoglobulin (IVIG) treatment in early onset NC....

  17. Optimized localization of bacterial infections with technetium-99m labelled human immunoglobulin after protein charge selection

    International Nuclear Information System (INIS)

    Welling, M.; Feitsma, H.I.J.; Calame, W.; Ensing, G.J.; Goedemans, W.; Pauwels, E.K.J.

    1994-01-01

    To improve the scintigraphic detection of bacterial infections a protein charge-purified fraction of polyclonal human immunoglobulin was applied as a radiopharmaceutical. This purification was achieved by attaching the immunoglobulin to an anion-exchanger column and by obtaining the column-bound fraction with buffer. The binding to bacteria in vitro and the target to non-target ratios of an experimental thigh infection with Staphylococcus aureus or Klebsiella pneumoniae in mice were evaluated to compare the purified and the unpurified immunoglobulin. The percentage of binding to all gram-positive and gram-negative bacteria used in this study was significantly (P 99m Tc-labelled protein charge-purified polyclonal human immunoglobulin was administered intravenously. At all time intervals the target (infected thighs) to non-target (non-infected thighs) ratios for both infections were significantly higher (P 99m Tc-labelled protein charge-purified immunoglobulin localizes both a gram-positive and a gram-negative thigh infection more intensely and faster than 99m Tc-labelled unpurified immunoglobulin. (orig.)

  18. Plasmapheresis versus intravenous immunoglobulins in guillain barre syndrome the therapeutic outcomes

    International Nuclear Information System (INIS)

    Asghar, S.P.; Mubarik, H.

    2015-01-01

    Objective: To compare the therapeutic outcomes of plasmapheresis with intravenous immunoglobulins (IVIG) for Guillain Barre syndrome. Study Design: Randomized controlled trial. Place and Duration of Study: Medicine department; PNS Shifa Hospital Karachi from Jan 2011 to Jun 2012. Patients and Methods: Adult patients admitted to internal medicine department with the diagnosis of Guillain Barre Syndrome (GBS) fulfilling the inclusion and exclusion criteria were included after taking ethical approval and informed consent. They were randomly assigned to plasmapheresis and IVIG treatment groups. Their presenting features, investigations and management plan were followed over 6 months duration. Hughes disability scale for Guillain Barre syndrome was documented and compared at admission, 4 weeks, 12 weeks and 6 months by non-parametric tests via SPSS version 17. Results: Total 36 patients (31 males and 5 females) were included. Mean age was 37 ± 15 (18-70) years, mean duration of symptoms 11.6 ± 12.7 days. Plasmapheresis and IVIG groups were comparable with respect to age and gender (p>0.05). Significant improvement of mean disability score was observed in each group from baseline score (p<0.0005). At specified intervals, comparison between the two groups in terms of mean improvement in disability scores showed significant improvement at 4 weeks (p<0.05) in IVIG group as compared to plasmapheresis group; however on further observation at 12 weeks and 6 months, mean improvement was comparable between two groups with no significant difference (p>0.05). There was no significant difference in need for assisted ventilation between two groups (p>0.05). Variants of GBS observed were AIDP (50%), AMAN (31%) and AMSAN (19%). Conclusion: Our study suggests that both plasmapheresis and intravenous immunoglobulins are useful and effective modes of treatment for Guillain Barre Syndrome. Significant short term improvement was observed in the IVIG group at 4 weeks of treatment; however

  19. Consecutive successful pregnancies subsequent to intravenous immunoglobulin therapy in a patient with recurrent spontaneous miscarriage

    Directory of Open Access Journals (Sweden)

    Diejomaoh MF

    2015-12-01

    Full Text Available Michael F Diejomaoh,1,2 Zainab Bello,2 Waleed Al Jassar,1,2 Jiri Jirous,2 Kavitha Karunakaran,2 Asiya T Mohammed11Department of Obstetrics and Gynaecology, Faculty of Medicine, Kuwait University, Safat, 2Maternity Hospital, Shuwaikh, Kuwait Background: Recurrent spontaneous miscarriage (RSM has a multifactorial etiology, mainly due to karyotype abnormalities including balanced translocation, anatomical uterine disorders, and immunological factors, although in 50%–60% the etiology is unexplained. The treatment of RSM remains challenging, and the role of intravenous immunoglobulin (IVIG in RSM is controversial. Case report: Mrs HM, 37 years old, obstetric summary: P0+1+13+1, a known case of hypothyroidism/polycystic ovary syndrome, married to an unrelated 47-year-old man, presented to our RSM clinic in early January 2014 for investigation and treatment. She has had multiple failed in vitro fertilization trials and 13 first-trimester missed miscarriages terminating at 6–7 weeks, all without IVIG therapy. Her tenth pregnancy was spontaneous, managed in London, UK, with multiple supportive therapy and courses of IVIG starting from the third to the 30th week of pregnancy. The pregnancy ended at 36 weeks of gestation with a cesarean section and a live girl baby was delivered. Mrs HM had balanced translocation, 46XX t (7:11 (p10:q10. Preimplantation genetic diagnosis/intracytoplasmic sperm injection/in vitro fertilization was performed with embryo transfer on May 29, 2014, and resulted in a successful pregnancy. She was commenced immediately on metformin, luteal support, and IVIG therapy, started at 6 weeks of gestation and at monthly intervals until 30 weeks of gestation, and also received additional therapy. The pregnancy was monitored with ultrasound, progressed uneventfully until admission at 35 weeks of gestation, with mildly elevated liver enzymes and suspected fetal growth restriction. She was managed conservatively, and in the light of

  20. Viral safety characteristics of Flebogamma DIF, a new pasteurized, solvent-detergent treated and Planova 20 nm nanofiltered intravenous immunoglobulin.

    Science.gov (United States)

    Caballero, Santiago; Nieto, Sandra; Gajardo, Rodrigo; Jorquera, Juan I

    2010-07-01

    A new human liquid intravenous immunoglobulin product, Flebogamma DIF, has been developed. This IgG is purified from human plasma by cold ethanol fractionation, PEG precipitation and ion exchange chromatography. The manufacturing process includes three different specific pathogen clearance (inactivation/removal) steps: pasteurization, solvent/detergent treatment and Planova nanofiltration with a pore size of 20 nm. This study evaluates the pathogen clearance capacity of seven steps in the production process for a wide range of viruses through spiking experiments: the three specific steps mentioned above and also four more production steps. Infectivity of samples was measured using a Tissue Culture Infectious Dose assay (log(10) TCID(50)) or Plaque Forming Units assay (log(10) PFU). Validation studies demonstrated that each specific step cleared more than 4 log(10) for all viruses assayed. An overall viral clearance between > or =13.33 log(10) and > or =25.21 log(10), was achieved depending on the virus and the number of steps studied for each virus. It can be concluded that Flebogamma DIF has a very high viral safety profile. 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

  1. Inpatient paediatric use of intravenous immunoglobulin at an academic medical centre.

    Science.gov (United States)

    Dashti-Khavidaki, S; Khalili, H; Farshadi, F; Aghamohammadi, A; Movahedi, M; Hajibabaei, M

    2008-02-01

    Intravenous immunoglobulin (IVIG) is an important research topic because of its efficacy in the management of an increasing number of diseases, its high cost and limited availability. This study was designed to evaluate the paediatric inpatient use of IVIG and identify strategies to reduce the drug expenditures. Over a six-month period, physician and nursing charts, and notes for subjects who were treated with IVIG, were reviewed to gather the required data. This included patient demographics, IVIG, indications, dosage regimen, adverse drug reactions (ADRs) and their management. 58.3 percent of IVIG infusions were ordered for labelled indications. Patients in the labelled group experienced more clinical improvement than subjects in the off-label group. Haematologists and neurologists were the most prevalent prescribers. ADRs were more prevalent in the off-label group. Hypotension, fever, headache and chills were the most common adverse effects. ADRs were managed with drugs in 22.9 percent of IVIG administrations and IVIG infusions were modified in 12.5 percent of infusions. ADRs were more prevalent in this hospital than those reported by other authors. This may be due to nursing negligence of the recommended infusion rate, higher sensitivity of our population or to the brands of IVIG which are used in the hospital. This shows the need for further evaluation of IVIG prescription and administration.

  2. Intravenous Immunoglobulin G Treatment in ABO Hemolytic Disease of the Newborn, is it Myth or Real?

    Science.gov (United States)

    Beken, Serdar; Hirfanoglu, Ibrahim; Turkyilmaz, Canan; Altuntas, Nilgun; Unal, Sezin; Turan, Ozden; Onal, Esra; Ergenekon, Ebru; Koc, Esin; Atalay, Yildiz

    2014-03-01

    Intravenous Immunoglobulin G (IVIG) therapy has been used as a component of the treatment of hemolytic disease of the newborn. There is still no consensus on its use in ABO hemolytic disease of the newborn routinely. The aim of this study is to determine whether administration of IVIG to newborns with ABO incompatibility is necessary. One hundred and seventeen patients with ABO hemolytic disease and positive Coombs test were enrolled into the study. The subjects were healthy except jaundice. Infants were divided into two groups: Group I (n = 71) received one dose of IVIG (1 g/kg) and LED phototherapy whereas Group II (n = 46) received only LED phototherapy. One patient received erythrocyte transfusion in Group I, no exchange transfusion was performed in both groups. Mean duration of phototherapy was 3.1 ± 1.3 days in Group I and 2.27 ± 0.7 days in Group II (p hemolytic disease. Meticulus follow-up of infants with ABO hemolytic disease and LED phototherapy decreases morbidity. IVIG failed to show preventing hemolysis in ABO hemolytic disease.

  3. Use of intravenous immunoglobulin in pregnancy. Report of a patient with common variable immunodeficiency

    Directory of Open Access Journals (Sweden)

    Julio César Cambray-Gutiérrez

    2016-08-01

    Full Text Available Background: Common variable immunodeficiency is the most commonly-diagnosed primary immunodeficiency in adults; it is characterized by recurrent sinopulmonary and gastrointestinal infections, and increased incidence of malignancy and autoimmune processes. Many patients begin to have clinical manifestations during reproductive age. Case report: A 34-year-old woman with 12 weeks of gestation who was diagnosed with common variable immunodeficiency after recurrent episodes of rhinosinusitis, pharyngoamygdalitis, and pneumonia. 0.6 g/kg of IVIG was prescribed every 21 days during the second trimester; the patient only presented one episode of pharyngoamygdalitis, with adequate response to treatment with antibiotics. During the third trimester the dose was adjusted to every 14 days. The patient ended the pregnancy at term without complications, with a child without defects and with proper weight and size. Conclusions: The administration of immunoglobulin is the main treatment to control common variable immunodeficiency. While the recommended starting dose is 400-800 mg/kg intravenously every 3 to 4 weeks, there is no consensus on the dose to be used in pregnant women. The recommendation is to perform serum level controls before infusion to determine and adjust it.

  4. Successful use of Intravenous Immunoglobulin For Recalcitrant Impetigo Herpetiformis: Case Report

    Directory of Open Access Journals (Sweden)

    Hayriye Sarıcaoğlu

    2012-06-01

    Full Text Available Impetigo herpetiformis (IH, if left untreated, is associated with a high rate of perinatal morbidity and mortality and may lead to the decision of termination of pregnancy. There are various and effective therapeutic agents available for the treatment of the disease. A 23-year-old woman with a history of plaque psoriasis presented with a sudden generalized pustular eruption on the 25th week of her first gestation. The diagnosis was made based on the clinical and histopathological findings. The patient was treated with systemic prednisolone (2 mg/kg/d first and, cyclosporine A (3 mg/kg/d was added to the treatment after two weeks because prednisolone was not effective alone. The lesions did not regress despite four weeks of combined treatment with prednisolone and cyclosporine. Intravenous immunoglobuline (IVIG (0.3 g/kg/d, 6 days was added on the 30th week of gestation and resulted in regression of cutaneous rashes. On the 33rd week of gestation, IVIG (0.7 g/kg/d, 3 days was repeated due to reactivation of pustules, and an improvement was observed. In this case report, we called attention to IVIG therapy in IH, for having the pregnancy continued enough for the fetal maturation before the delivery.

  5. Use of Corticosteroid in Children with Unresponsiveness to Intravenous Immunoglobulin in Kawasaki Disease

    Directory of Open Access Journals (Sweden)

    Abdolkarim Hamedi

    2017-08-01

    Full Text Available Background Kawasaki Disease (KD is a vasculitis with multi-organ involvementof unknown etiology; it is the most common cause of pediatric-heart diseases in developed countries. Treatment with Intravenous Immunoglobulin (IVIG prevents coronary artery lesions; although there are some IVIG-resistant cases, combination therapy with corticosteroids and IVIG is one of the recommendations for treatment of these cases. The aim of this study was to compare these three options for treatment of Kawasaki Disease and to evaluate their ability to deal with coronary artery complication of Kawasaki Disease. Materials and Methods A prospective cross- sectional study of hospitalized cases of Kawasaki Disease, conducted in pediatric department of Imam Reza hospital, Mashhad-Iran, during 2013 to 2015 (18 months. Based on demographic and clinical data of these patients, children with high risk of unresponsiveness to IVIG therapy (based on Harada score, were determined and treated with IVIG and corticosteroids- combination initially. Follow-up patients for heart complications were 6 weeks. Results Twenty five patients (89.2% out of total 28 hospitalized patients in this period of time who fulfilled diagnostic criteria were considered as complete Kawasaki Disease. Coronary Artery Lesions (CALs were shown in 4 patients during the follow-up period, with high risk in patients with incomplete presentation (33.3% versus 12%, P

  6. Crystalline-Like Keratopathy after Intravenous Immunoglobulin Therapy with Incomplete Kawasaki Disease: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Elif Erdem

    2013-01-01

    Full Text Available A 7-year-old girl had presented with high body temperature and joint pain which continued for 3 days. Because of the prolonged history of unexplained fever, rash, bilateral nonpurulent conjunctival injection, oropharyngeal erythema, strawberry tongue, and extreme of age, incomplete Kawasaki disease was considered and started on an intravenous immunoglobulin infusion. Six days after this treatment, patient was referred to eye clinic with decreased vision and photophobia. Visual acuity was reduced to 20/40 in both eyes. Slit-lamp examination revealed bilateral diffuse corneal punctate epitheliopathy and anterior stromal haze. Corneal epitheliopathy seemed like crystal deposits. One day after presentation, mild anterior uveitis was added to clinical picture. All ocular findings disappeared in one week with topical steroid and unpreserved artificial tear drops. We present a case who was diagnosed as incomplete Kawasaki disease along with bilateral diffuse crystalline-like keratopathy. We supposed that unusual ocular presentation may be associated with intravenous immunoglobulin treatment.

  7. Intravenous Immunoglobulins Improve Survival in Monoclonal Gammopathy-Associated Systemic Capillary-Leak Syndrome.

    Science.gov (United States)

    Pineton de Chambrun, Marc; Gousseff, Marie; Mauhin, Wladimir; Lega, Jean-Christophe; Lambert, Marc; Rivière, Sophie; Dossier, Antoine; Ruivard, Marc; Lhote, François; Blaison, Gilles; Alric, Laurent; Agard, Christian; Saadoun, David; Graveleau, Julie; Soubrier, Martin; Lucchini-Lecomte, Marie-Josée; Christides, Christine; Bosseray, Annick; Levesque, Hervé; Viallard, Jean-François; Tieulie, Nathalie; Lovey, Pierre-Yves; Le Moal, Sylvie; Bibes, Béatrice; Malizia, Giuseppe; Abgueguen, Pierre; Lifermann, François; Ninet, Jacques; Hatron, Pierre-Yves; Amoura, Zahir

    2017-10-01

    Monoclonal gammopathy-associated systemic capillary-leak syndrome, also known as Clarkson disease, is a rare condition characterized by recurrent life-threatening episodes of capillary hyperpermeability in the context of a monoclonal gammopathy. This study was conducted to better describe the clinical characteristics, natural history, and long-term outcome of monoclonal gammopathy-associated systemic capillary-leak syndrome. We conducted a cohort analysis of all patients included in the European Clarkson disease (EurêClark) registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (eg, the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months. Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%). Median (interquartile range) follow-up duration was 5.1 (2.5-9.7) years. Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Multivariate analysis found preventive treatment with IVIg (hazard ratio 0.27; 95% confidence interval, 0.10-0.70; P = .007) and terbutaline (hazard ratio 0.35; 95% confidence interval, 0.13-0.96; P = .041) to be independent predictors of mortality. We describe the largest cohort to date of patients with well-defined monoclonal gammopathy-associated systemic capillary-leak syndrome. Preventive treatment with IVIg was the strongest factor associated with survival, suggesting the use of IVIg as the first

  8. Human placental immunoglobulins show unique re-association ...

    African Journals Online (AJOL)

    Objective: To study re-association pattern of human placental eluate immunoglobulins with acid treated isologous and third party trophoblast derived placental microvesicles. Design: Laboratory based experimentation. Setting: Biological Sciences Department and Discipline for Reproductive Medicine University of ...

  9. Intravenous Immunoglobulin: A Drug Utilization Review at Shahid Sadoughi Hospital in Yazd

    Directory of Open Access Journals (Sweden)

    SeyedMojtaba Sohrevardi

    2015-10-01

    Full Text Available  Background: Drug use evaluation (DUE aims at improving the patients’ care. Studying the administration pattern of intravenous immunoglobulin (IVIG is an important research topic due to its significant role in the treatment and controlling of many disorders, high prices, and limited availability of this drug.  Methods:This observational cross-sectional study was conducted at Shahid Sadoughi Hospital in Yazd, central Iran, from May to September 2014. The orders of different wards in the hospital for IVIG given to the hospital central pharmacy were surveyed. Also, a special form developed for evaluation the method of administration. The related physician and nurse were consulted on drug complications and the causes. Finally, the gleaned data were compared to the available standards on the prescription and administration of IVIG.Results:A total of 75 patients received IVIG during this study. 58.7% of the prescriptions belonged to the cases approved by Food and Drug Administration (FDA. The most frequent cause of the use of IVIG was idiopathic thrombocytopenic purpura (ITP. The rate and dose of administration was suitable in most of the patients, yet, the measurement of laboratory parameters required for IVIG were observed in only a few cases. Complications occurred in 26.7% of the patients receiving it, which was mostly related to infusion-related reactions. On the whole, 3922 g IVIG was used during this study of which 1848 g belonged to the cases approved by FDA.Conclusion:Regarding the high costs of IVIG, complications, and limited information on the quality of the effect of this drug in the treatment of many cases, physicians should be cautious enough with its appropriate use. Besides, the presence of a clinical pharmacist in the health-care team not only improves the quality of drug therapy and treatment results, but also plays an important part in decreasing the treatment costs for the patients.

  10. Antibodies against Hepatitis A and Hepatitis B Virus in Intravenous Immunoglobulin Products.

    Science.gov (United States)

    Lee, Soyoung; Kim, Han Wool; Kim, Kyung Hyo

    2016-12-01

    The worldwide seroprevalence of hepatitis A virus (HAV) and hepatitis B virus (HBV) has changed over the last two decades, indicating a declining incidence of HAV and HBV infections. Therefore, vaccinations against HAV and HBV are recommended for unimmunized people before traveling to an endemic area. Unfortunately, primary antibody deficiency (PAD) patients can only obtain humoral immunity through intravenous immunoglobulin G (IVIG) replacement and not from vaccination because of a defect in antibody production. However, few studies have analyzed the titers of antibodies against HAV or HBV in IVIG products. In this study, the titers of anti-HAV and anti-HBs antibodies were measured in nineteen lots of IVIG products from five manufacturers from three countries (A, B from Korea; C, D from Japan; and E from the USA), and trough titers in plasma were estimated. Concentrations of anti-HAV antibody ranged from 1,888-8,927 mIU/mL and estimated trough titers exceeded the minimal protective value in all evaluated IVIG products. Concentrations of anti-HBs antibody ranged from 438-965 mIU/mL in products A and B and were 157, 123, and 1,945 mIU/mL in products C, D, and E, respectively. Estimated trough titers in products A, B, and E exceeded the minimal protective value but those in products C and D did not reach this threshold. These data demonstrated that available IVIG products generally provide sufficient antibodies against HAV and HBV to protect patients with PAD, although the trough concentrations of anti-HBs antibody in two IVIG products did not reach the minimum protective value.

  11. Intravenous immunoglobulin G (IVIG) therapy for significant hyperbilirubinemia in ABO hemolytic disease of the newborn.

    Science.gov (United States)

    Miqdad, A M; Abdelbasit, O B; Shaheed, M M; Seidahmed, M Z; Abomelha, A M; Arcala, O P

    2004-09-01

    Although intravenous immunoglobulin G (IVIG) therapy has been reported in hyperbilirubinemia of Rh hemolytic disease, its use in ABO hemolytic disease has been reported in only a few studies. In our institute we have observed that almost 30% of babies with hyperbilirubinemia due to ABO hemolytic disease required exchange transfusion. To determine whether administration of IVIG to newborns with significant hyperbilirubinemia due to ABO hemolytic disease would reduce the need for exchange transfusion as a primary goal in these babies. This was a prospective study involving all newborns with significant hyperbilirubinemia due to direct Coombs-positive ABO hemolytic disease. All healthy term babies with ABO hemolytic disease with positive direct Coombs test in the period between 2000 and 2002 were identified. Significant hyperbilirubinemia was defined as hyperbilirubinemia requiring phototherapy and/or rising by 8.5 micromol/l per h (0.5 mg/dl per h) or more to require exchange transfusion. Babies were randomly assigned into two groups: group 1 (study group) received phototherapy plus IVIG (500 mg/kg); and group 2 (control group) received phototherapy alone. Exchange transfusion was carried out in any group if at any time the bilirubin level reached 340 micromol/l (20 mg/dl) or more, or rose by 8.5 micromol/l per h (0.5 mg/dl per h) in group 2. A total of 112 babies were enrolled over 2 years, 56 in each group. Exchange transfusion was carried out in four babies in the study group, while 16 babies in the control group required exchange. Late anemia was not of concern in either group. No adverse effects related to IVIG administration were recorded. Administration of IVIG to newborns with significant hyperbilirubinemia due to ABO hemolytic disease with positive direct Coomb's test reduces the need for exchange transfusion without producing immediate adverse effects.

  12. Intravenous immunoglobulins and antiphospholipid syndrome: How, when and why? A review of the literature.

    Science.gov (United States)

    Tenti, Sara; Cheleschi, Sara; Guidelli, Giacomo Maria; Galeazzi, Mauro; Fioravanti, Antonella

    2016-03-01

    The antiphospholipid syndrome (APS) is defined by the occurrence of venous and arterial thromboses and recurrent fetal losses, frequently accompanied by a moderate thrombocytopenia, in the presence of antiphospholipid antibodies (aPL), namely lupus anticoagulant (LA), anticardiolipin antibodies (aCL), or anti-β2 glycoprotein-I (β2GPI) antibodies. The current mainstay of treatment for thrombotic APS is heparin followed by long-term anticoagulation, while in obstetric APS, the accepted first-line treatment consists in low-dose aspirin (LDA) plus prophylactic unfractionated or low-molecular-weight heparin (LMWH). Recently, new emerging treatment modalities, including intravenous immunoglobulins (IVIG), have been implemented to manage APS refractory to conventional therapy. The objective of this review is to summarize the currently available information on the IVIG therapy in APS, focusing on the use of IVIG in the obstetric form, CAPS and on primary or secondary thromboprophylaxis. We analyzed 35 studies, reporting the effects of IVIG in APS patients, and we discussed their results. IVIG in obstetric APS seem to be very useful in selected situations (patients not responsive to the conventional treatment, concomitant autoimmune manifestations or infections or patients in whom anticoagulation is contraindicated). IVIG treatment represents an important component of the combination therapy of CAPS and they could be useful, in addition to the standard therapy, to prevent recurrent thrombosis in APS patients refractory to conventional anticoagulant treatment. Anyway, in some cases we also found controversial results that claim the need of further well-designed studies to definitely state the efficacy and tolerability of IVIG in CAPS, obstetric and non-APS. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Dexamethasone, Intravenous Immunoglobulin, and Rituximab Combination Immunotherapy for Pediatric Opsoclonus-Myoclonus Syndrome.

    Science.gov (United States)

    Pranzatelli, Michael R; Tate, Elizabeth D

    2017-08-01

    Although pulse-dose dexamethasone is increasingly favored for treating pediatric opsoclonus-myoclonus syndrome (OMS), and multimodal immunotherapy is associated with improved clinical response, there have been no neuroimmunologic studies of dexamethasone-based multimodal disease-modifying therapy. In this observational retrospective study, 19 children with OMS (with or without associated neuroblastoma) underwent multibiomarker evaluation for neuroinflammation. Nine children of varying OMS severity, duration, and treatment status were treated empirically with pulse dexamethasone, intravenous immunoglobulin (IVIg), and rituximab combination immunotherapy (DEXIR-CI). Another 10 children on dexamethasone alone or with IVIg at initial evaluation only provided a comparison group. Motor severity (total score) was scored rater-blinded via videotapes using the validated OMS Evaluation Scale. DEXIR-CI was associated with a 69% reduction in group total score (P = 0.004) and was clinically well tolerated. Patients given the dexamethasone combination exhibited significantly lowered B cell frequencies in cerebrospinal fluid (-94%) and blood (-76%), normalizing the cerebrospinal fluid B cell percentage. The number of patients with positive inflammatory markers dropped 87% (P = 0.002) as did the number of markers. Cerebrospinal fluid oligoclonal bands were positive in four of nine pretreatment patients but zero of six post-treatment patients. In the comparison group, partial response to dexamethasone alone or with IVIg was associated with multiple positive markers for neuroinflammation despite an average of seven months of treatment. Multimechanistic dexamethasone-based combination immunotherapy increases the therapeutic armamentarium for OMS, providing a viable option for less severely affected individuals. Partial response to dexamethasone with or without IVIg is indicative of ongoing neuroinflammation and should be treated promptly and accordingly. Copyright © 2017

  14. Low rate of infectious complications following immunoadsorption therapy without regular substitution of intravenous immunoglobulins.

    Science.gov (United States)

    Tselmin, Sergey; Julius, Ulrich; Bornstein, Stefan R; Hohenstein, Bernd

    2017-11-01

    Immunoadsorption (IA) is increasingly used instead of plasma exchange due to lower risk of side effects and a higher selectivity. As a consequence of the reduction of immunoglobulins (Ig), the rate of infectious complications might increase in those patients. We therefore aimed to investigate the infection rate following IA without intravenous IG (IVIG) substitution in our apheresis center, where patients do not receive IVIG on a regular basis. We conducted a retrospective analysis of the IA treatments performed between 2010 and 2015 without IVIG substitution and collected data on patient age, diagnosis, number of IA treatments, serum levels of Ig, total protein, albumin, C-reactive protein (CRP) and infectious complications that occurred within 2 months after the IA treatment cycle. A total number of 52 patients (27 females) received at least 5 IA sessions using the following adsorbers: TheraSorb™-Ig (n = 3), TheraSorb™-Ig flex (n = 44), TheraSorb™ Ig pro (n = 1) and TheraSorb™-IgE (n = 5). The median number of treatment sessions was 8.8 [range 5-16], the median IgG reduction was 82 [11-99] %. Serum albumin was decreased by 8%. The median CRP levels remained normal until the end of therapy and within 2 months after that (3.10 and 4.30 mg/L respectively). Only 4 patients had infections (7.7%). Three of them received additional immunosuppressive therapy. Immunoadsorption leads to a significant reduction of IgG. CRP as inflammatory marker is not affected. Even without substitution of IVIG the complication rate directly linked with IA is low and questionable. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Endothelial Cell Amplification of Regulatory T Cells Is Differentially Modified by Immunosuppressors and Intravenous Immunoglobulin

    Directory of Open Access Journals (Sweden)

    Julien Lion

    2017-12-01

    Full Text Available Immunosuppressive treatment is a prerequisite for both organ transplantation and tolerance of the allograft. However, long-term immunosuppression has been associated with a higher incidence of malignancies and infections. Immunosuppressors mainly target circulating immune cells and little is known of their “off-target” effects, such as their impact on endothelial cells (ECs. In chronic antibody-mediated rejection (AMR, the allograft endothelium is a target of damage, histologically detected as transplant glomerulopathy, and which correlates with poor graft survival. Under inflammatory conditions, EC expression of HLA class II antigens can lead to CD4+-T lymphocyte alloactivation and selective expansion of pro-inflammatory Th17 and pro-tolerance Treg subsets. This response can be modified and preactivation of the EC by HLA-DR antibody binding promoted a proinflammatory Th17 response. However, whether or not immunosuppressors alter EC immunogenicity has not been examined. In alloimmunized patients with AMR, cyclosporine A (CsA and mycophenolic acid (MPA are often combined with intravenous immunoglobulins (IVIgs. This study reports changes in the microvascular EC phenotype and function after treatment with CsA, MPA, or IVIg. Both CsA and MPA decreased HLA-DR and increased CD54 expression, whereas IVIg increased HLA-DR expression. Interleukin 6 secretion was reduced by all three immunomodulators. Preincubation of ECs with CsA or MPA limited, while IVIg amplified, Treg expansion. Because CsA, MPA, and IVIg are known for their ability to act upon leukocytes, we confirmed that ECs maintained their immunoregulatory role when allogeneic leukocytes were pretreated with CsA, MPA, or IVIg. The results reveal that individual immunosuppressors, used in the induction and maintenance of renal allograft tolerance, had direct and distinct effects on ECs. Results of experiments associating IVIg with either CsA or MPA underlined the differences observed using

  16. Platelet associated IgG, platelet mean life span and treatment with intravenous immunoglobulin in idiopathic thrombocytopenic purpura

    International Nuclear Information System (INIS)

    Nieminen, U.; Syrjaelae, M.; Ikkala, E.; Myllylae, G.

    1988-01-01

    The clinical significance of platelet associated IgG in ITP detected by direct platelet suspension immunofluorescence test (PSIFT) was studied. The platelet mean life span (MLS) was measured with 111 In-labelled platelets in 17 adult patients. All the patients had shortened platelet MLS. The direct PSIFT was positive in 14 patients. Patients were initially treated with prednisone; 12 patients with poor response to the drug were splenectomised. 8 of these 12 patients were treated with intravenous immunoglobulin (IvIg) before splenectomy. The response to IvIg was as good or better in the 3 patients with negative PSIFT, than in the 5 patients with positive PSIFT. (author)

  17. Stability assessment of lyophilized intravenous immunoglobulin after reconstitution in glass containers and poly(vinyl chloride) bags.

    Science.gov (United States)

    Parti, R; Mankarious, S

    1997-02-01

    Human intravenous immunoglobulin (IGIV) has been in use for the past 20 years. This biological product is commonly provided in liquid or lyophilized dosage form. When the lyophilized product is rehydrated, it is usually administered within 2-3 h from time of complete dissolution. While this practice is advisable whenever possible, occasionally the patient or care-giver may need to delay the infusion. Hence, a study of the stability of lyophilized IGIV after reconstitution with water for injection was conducted. The reconstituted product was stored either in its original glass container or pooled into poly(vinyl chloride) (PVC) bags. The effect of extended storage on the active ingredient (IgG), excipients (glucose, albumin) and extractables [sodium from glass vials, and di-(2-ethyl-hexyl) phthalate and cyclohexanone from PVC bags] was evaluated. The stability of the active ingredient was evaluated by physico-chemical tests (molecularsize distribution, pH, appearance, total protein), monitoring titres of a specific antibody (hepatitis B surface antigen) and an antibody functional test (bacterial opsonization). To evaluate the risk of microbial contamination during reconstitution and pooling procedures, sterility, pyrogen and animal-safety tests were included in the protocol. The potential of IgG polymerizing in solution during storage and subsequent complement activation was evaluated by assaying for non-specific binding of complement (anti-complement activity). Results show that aseptically reconstituted IGIV is stable and remains sterile up to 48 h at 5 degrees C. The reconstituted product was also found to be stable at room temperature (25 degrees C) up to 12 h.

  18. Intravenous immunoglobulin prevents murine antibody-mediated acute lung injury at the level of neutrophil reactive oxygen species (ROS production.

    Directory of Open Access Journals (Sweden)

    John W Semple

    Full Text Available Transfusion-related acute lung injury (TRALI is a leading cause of transfusion-associated mortality that can occur with any type of transfusion and is thought to be primarily due to donor antibodies activating pulmonary neutrophils in recipients. Recently, a large prospective case controlled clinical study of cardiac surgery patients demonstrated that despite implementation of male donors, a high incidence of TRALI still occurred and suggested a need for additional interventions in susceptible patient populations. To examine if intravenous immunoglobulin (IVIg may be effective, a murine model of antibody-mediated acute lung injury that approximates human TRALI was examined. When BALB/c mice were injected with the anti-major histocompatibility complex class I antibody 34-1-2s, mild shock (reduced rectal temperature and respiratory distress (dyspnea were observed and pre-treatment of the mice with 2 g/kg IVIg completely prevented these symptoms. To determine IVIg's usefulness to affect severe lung damage, SCID mice, previously shown to be hypersensitive to 34-1-2s were used. SCID mice treated with 34-1-2s underwent severe shock, lung damage (increased wet/dry ratios and 40% mortality within 2 hours. Treatment with 2 g/kg IVIg 18 hours before 34-1-2s administration completely protected the mice from all adverse events. Treatment with IVIg after symptoms began also reduced lung damage and mortality. While the prophylactic IVIg administration did not affect 34-1-2s-induced pulmonary neutrophil accumulation, bone marrow-derived neutrophils from the IVIg-treated mice displayed no spontaneous ROS production nor could they be stimulated in vitro with fMLP or 34-1-2s. These results suggest that IVIg prevents murine antibody-mediated acute lung injury at the level of neutrophil ROS production and thus, alleviating tissue damage.

  19. Sensitive chain specific radioimmunoassay for human immunoglobulins using monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Sikora, K; Alderson, T St.J.; Ellis, J [Ludwig Institute for Cancer Research, Cambridge (UK)

    1983-02-25

    A sensitive radioimmunoassay is described for human immunoglobulins. This solid-phase assay uses commercially available monoclonal antibodies and is specific for different Ig chain types. Levels of less than 20 ng/ml Ig are detectable. The assay is suitable for the analysis of human hybridoma supernatants.

  20. Bacteriostatic enterochelin-specific immunoglobulin from normal human serum

    Energy Technology Data Exchange (ETDEWEB)

    Moore, D.G.; Yancey, R.J.; Lankford, C.E.; Earhart, C.F.

    1980-02-01

    Heat-inactivated normal human serum produces iron-reversible bacteriostasis of a number of microorganisms. This inhibitory effect was abolished by adsorption of serum with ultraviolet-killed cells of species that produce the siderophore enterochelin. Bacteriostasis also was alleviated by asorption of serum with 2,3-dihydroxy-N-benzoyl-L-serine, a degradation product of enterochelin, bound to the insoluble matrix AH-Sepharose 4B. Our results indicate that enterochelin-specific immunoglobulins exist in normal human serum. These immunoglobulins may act synergistically with transferrin to effect bacteriostasis of enterochelin-producing pathogens.

  1. Cationization of immunoglobulin G results in enhanced organ uptake of the protein after intravenous administration in rats and primate

    International Nuclear Information System (INIS)

    Triguero, D.; Buciak, J.L.; Pardridge, W.M.

    1991-01-01

    Cationization of proteins in general enhances the cellular uptake of these macromolecules, and cationized antibodies are known to retain antigen binding properties. Therefore, cationized antibodies may be therapeutic and allow for intracellular immunization. The present studies test the hypothesis that the tissue uptake of cationized immunoglobulin G (IgG) after intravenous administration may be greatly increased relative to the uptake of native proteins. The pharmacokinetics of cationized immunoglobulin G clearance from blood, and the volume of distribution of the cationized or native protein (albumin, IgG) for 10 organs was measured both in anesthetized rats and in an anesthetized adult Macaca irus cynomologous monkey. Initial studies on brain showed that serum factors inhibited uptake of 125I-cationized IgG, but not 3H-cationized IgG. The blood-brain barrier permeability surface area product for 3H-cationized IgG was 0.57 ± 0.04 microliters min-1 g-1. The ratio of the volume of distribution of the 3-H-cationized IgG compared to 3H-labeled native albumin ranged from 0.9 (testis) to 15.7 (spleen) in the rat at 3 hr after injection, and a similarly enhanced organ uptake was observed in the primate. In conclusion, these studies demonstrate that cationization of immunoglobulin greatly increases organ uptake of the plasma protein compared to native immunoglobulins, and suggest that cationization of monoclonal antibodies may represent a potential new strategy for enhancing the intracellular delivery of these proteins

  2. Intravenous immunoglobulin in relapsing-remitting multiple sclerosis: a dose-finding trial

    DEFF Research Database (Denmark)

    Fazekas, F.; Lublin, F.D.; Li, D.

    2008-01-01

    OBJECTIVE: Several studies have reported a reduction of relapses after the long-term administration of IV immunoglobulin (IVIG) to patients with relapsing-remitting multiple sclerosis (RRMS), but they were mostly small and differed in terms of predefined outcome variables and treatment regimen. W...

  3. Lack of effect of intravenous immunoglobulins on tics : A double-blind placebo-controlled study

    NARCIS (Netherlands)

    Hoekstra, PJ; Minderaa, RB; Kallenberg, CGM

    Background: Case studies and a placebo-controlled study previously suggested the effectiveness of immunomodulatory therapy in patients with tic or related disorders whose symptoms show a relationship with streptococcal infections. No data are available on the effectiveness of intravenous

  4. The human experience with intravenous levodopa

    Directory of Open Access Journals (Sweden)

    Shan H Siddiqi

    2016-01-01

    Full Text Available Objective: To compile a comprehensive summary of published human experience with levodopa given intravenously, with a focus on information required by regulatory agencies.Background: While safe intravenous (IV use of levodopa has been documented for over 50 years, regulatory supervision for pharmaceuticals given by a route other than that approved by the U.S. Food and Drug Administration (FDA has become increasingly cautious. If delivering a drug by an alternate route raises the risk of adverse events, an investigational new drug (IND application is required, including a comprehensive review of toxicity data.Methods: Over 200 articles referring to IV levodopa were examined for details of administration, pharmacokinetics, benefit and side effects.Results: We identified 142 original reports describing IVLD use in humans, beginning with psychiatric research in 1959-1960 before the development of peripheral decarboxylase inhibitors. Over 2750 subjects have received IV levodopa, and reported outcomes include parkinsonian signs, sleep variables, hormone levels, hemodynamics, CSF amino acid composition, regional cerebral blood flow, cognition, perception and complex behavior. Mean pharmacokinetic variables were summarized for 49 healthy subjects and 190 with Parkinson’s disease. Side effects were those expected from clinical experience with oral levodopa and dopamine agonists. No articles reported deaths or induction of psychosis.Conclusion: Over 2750 patients have received IV levodopa with a safety profile comparable to that seen with oral administration.

  5. Intravenous Immunoglobulins: Mechanism of Action and Limitations of Clinical Application in Pediatrics

    Directory of Open Access Journals (Sweden)

    S.O. Mokiia-Serbina

    2016-02-01

    IVIG consumption is increasing due to the fact that in many cases the drugs are being used off-label. IVIG were more likely to be used in autoimmune and systemic inflammatory diseases. However, in randomized clinical trials, a good effect was achieved only in Kawasaki disease and immune thrombocytopenic purpura. Current clinical guidelines narrowed the indications for IVIG, limiting their use in sepsis. Immunoglobulin replacement therapy is recommended for children with physiological delay of immunoglobulin production only in repeated infections, which can not be controlled or prevented with antibiotics. In secondary ID, replacement therapy must be carried out if the cause of hypogammaglobulinemia can not be eliminated or elimination is contraindicated, as well as in association with β-cell cancers, in which severe infections caused by encapsulated bacteria persist despite preventive antibiotic therapy.

  6. Subcutaneous immunoglobulin in responders to intravenous therapy with chronic inflammatory demyelinating polyradiculoneuropathy

    DEFF Research Database (Denmark)

    Markvardsen, Lars Høj; Debost, J-C; Harbo, Thomas

    2013-01-01

    BACKGROUND AND PURPOSE: We hypothesized that subcutaneous administration of immunoglobulins (SCIG) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is feasible, safe and superior to treatment with saline for the performance of muscle strength. METHODS: Thirty patients with motor...... Research Council (MRC) score, grip strength, standardized electrophysiological recordings from three nerves, and plasma IgG levels were evaluated. RESULTS: SCIG treatment was well tolerated in all 14 patients. Six patients complained of mild side-effects at the injection site. In the SCIG group...

  7. Vasoactive side effects of intravenous immunoglobulin preparations in a rat model and their treatment with recombinant platelet-activating factor acetylhydrolase

    NARCIS (Netherlands)

    Bleeker, W. K.; Teeling, J. L.; Verhoeven, A. J.; Rigter, G. M.; Agterberg, J.; Tool, A. T.; Koenderman, A. H.; Kuijpers, T. W.; Hack, C. E.

    2000-01-01

    Previously, we observed in a rat model that intravenous administration of intramuscular immunoglobulin preparations induced a long-lasting hypotension, which appeared to be associated with the presence of IgG polymers and dimers in the preparations, but unrelated to complement activation. We found

  8. Subcutaneous versus intravenous immunoglobulin in multifocal motor neuropathy: a randomized, single-blinded cross-over trial

    DEFF Research Database (Denmark)

    Harbo, Thomas; Andersen, Henning; Hess, Alexander

    2009-01-01

    at the injection sites for a few weeks. All other adverse effects during SCIG were mild and transient. No differences between treatments of health-related quality of life occurred. Conclusion: In MMN, short-term subcutaneous infusion of immunoglobulin is feasible, safe and as effective as intravenous infusion...

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

    Science.gov (United States)

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

    2014-06-21

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

  10. Qualitative and quantitative volumetric evaluation of the efficacy of intravenous immunoglobulin in multiple sclerosis: preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Teksam, M. [Department of Radiology, Gazi University Medical School, Ankara (Turkey); Department of Radiology, Medical School, University of Minnesota, MN(United States); Tali, T.; Isik, S. [Department of Radiology, Gazi University Medical School, Ankara (Turkey); Kocer, B. [Department of Neurology, Gazi University Medical School, Ankara (Turkey)

    2000-12-01

    We conducted a double-blind, placebo-controlled study in 13 patients (aged 22 to 54 years) with relapsing-remitting multiple sclerosis (MS). They were randomly assigned to receive a loading dose of immunoglobulin IgG, 0.4 g/kg body weight/day for 5 consecutive days, followed by single booster doses of 0.4 g/kg/day, or placebo, once a month for 9 months. MRI was obtained before and during the 3rd and 6th months of treatment; examinations in the 9th and 12th months were planned. Qualitative and quantitative blinded assessments were performed. There were seven patients who received active treatment and six who received placebo. Statistical analysis was performed by the Wilcoxon test. A decrease in the size and number of lesions was observed on MRI in five patients (71 %) in the treatment group, and in two (33 %) of the placebo group at 3-month follow-up. At 6 months follow-up MRI, a decrease in the amount of lesions was observed in all patients treated with IV IgG, and in two (33 %) of the placebo group; four patients (66 %) receiving placebo showed an increase. Quantitative analysis showed a statistically significant decrease in the volume of lesions in treatment group at both 3 and 6 month follow-up. There was no statistically significant change in the placebo group. (orig.)

  11. Qualitative and quantitative volumetric evaluation of the efficacy of intravenous immunoglobulin in multiple sclerosis: preliminary report

    International Nuclear Information System (INIS)

    Teksam, M.; Tali, T.; Isik, S.; Kocer, B.

    2000-01-01

    We conducted a double-blind, placebo-controlled study in 13 patients (aged 22 to 54 years) with relapsing-remitting multiple sclerosis (MS). They were randomly assigned to receive a loading dose of immunoglobulin IgG, 0.4 g/kg body weight/day for 5 consecutive days, followed by single booster doses of 0.4 g/kg/day, or placebo, once a month for 9 months. MRI was obtained before and during the 3rd and 6th months of treatment; examinations in the 9th and 12th months were planned. Qualitative and quantitative blinded assessments were performed. There were seven patients who received active treatment and six who received placebo. Statistical analysis was performed by the Wilcoxon test. A decrease in the size and number of lesions was observed on MRI in five patients (71 %) in the treatment group, and in two (33 %) of the placebo group at 3-month follow-up. At 6 months follow-up MRI, a decrease in the amount of lesions was observed in all patients treated with IV IgG, and in two (33 %) of the placebo group; four patients (66 %) receiving placebo showed an increase. Quantitative analysis showed a statistically significant decrease in the volume of lesions in treatment group at both 3 and 6 month follow-up. There was no statistically significant change in the placebo group. (orig.)

  12. FCGR2A Promoter Methylation and Risks for Intravenous Immunoglobulin Treatment Responses in Kawasaki Disease

    Directory of Open Access Journals (Sweden)

    Ho-Chang Kuo

    2015-01-01

    Full Text Available Kawasaki disease (KD is characterized by pediatric systemic vasculitis of an unknown cause. The low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A gene was reported to be involved in the susceptibility of KD. DNA methylation is one of the epigenetic mechanisms that control gene expression; thus, we hypothesized that methylation status of CpG islands in FCGR2A promoter associates with the susceptibility and therapeutic outcomes of Kawasaki disease. In this study, 36 KD patients and 24 healthy subjects from out-patient clinic were recruited. Eleven potential methylation sites within the targeted promoter region of FCGR2A were selected for investigation. We marked the eleven methylation sites from A to K. Our results indicated that methylation at the CpG sites G, H, and J associated with the risk of KD. CpG sites B, C, E, F, H, J, and K were found to associate with the outcomes of IVIG treatment. In addition, CpG sites G, J, and K were predicted as transcription factors binding sites for NF-kB, Myc-Max, and SP2, respectively. Our study reported a significant association among the promoter methylation of FCGR2A, susceptibility of KD, and the therapeutic outcomes of IVIG treatment. The methylation levels of CpG sites of FCGR2A gene promoter should be an important marker for optimizing IVIG therapy.

  13. Churg-Strauss Syndrome and pregnancy Successful treatment with intravenous immunoglobulin - Reply

    Directory of Open Access Journals (Sweden)

    M. Galeazzi

    2011-09-01

    Full Text Available La sindrome di Churg-Strauss è una malattia estremamente rara e ancora più raro è riscontrarla in una paziente in stato di gravidanza. Il trattamento iniziale della malattia consiste nella somministrazione di alte dosi di corticosteroidi. I pazienti più gravi o che rispondono poco o insoddisfacientemente ai corticosteroidi vengono solitamente trattati con farmaci citotossici. Le immunoglobuline somministrate per via endovenosa (IgEV stanno dimostrando di essere efficaci nel trattamento di questa patologia, tuttavia non esiste un consenso universale sulla loro effettiva utilità nelle vasculiti sistemiche. Noi presentiamo il caso di una donna con sindrome di Churg-Strauss resistente al trattamento con corticosteroidi e ciclofosfamide. Allorché si riscontrò che la paziente era al 3° mese di gravidanza fu iniziata una terapia con alte dosi di IgEV con ottimi risultati. Questo caso conferma l’utilità del trattamento con IgEV della sindrome di Churg-Strauss e ne dimostra l’efficacia anche in stato di gravidanza.

  14. A new manufacturing process to remove thrombogenic factors (II, VII, IX, X, and XI) from intravenous immunoglobulin gamma preparations.

    Science.gov (United States)

    Park, Dong Hwarn; Kang, Gil Bu; Kang, Dae Eun; Hong, Jeung Woon; Lee, Min Gyu; Kim, Ki Yong; Han, Jeung Whan

    2017-01-01

    Coagulation factors (II, VII, IX, X, and particularly XIa) remaining in high concentrations in intravenous immunoglobulin (IVIG) preparations can form thrombi, causing thromboembolic events, and in serious cases, result in death. Therefore, manufacturers of biological products must investigate the ability of their production processes to remove procoagulant activities. Previously, we were able to remove coagulation factors II, VII, IX, and X from our IVIG preparation through ethanol precipitation, but factor XIa, which plays an important role in thrombosis, remained in the intermediate products. Here, we used a chromatographic process using a new resin that binds with high capacity to IgG and removes procoagulant activities. The procoagulant activities were reduced to low levels as determined by the thrombin generation assay: 250 s, FXI/FXIa ELISA: <0.31 ng/mL. Even after spiking with FXIa at a concentration 32.5 times higher than the concentration in normal specimens, the procoagulant activities were below the detection limit (<0.31 ng/mL). These results demonstrate the ability of our manufacturing process to remove procoagulant activities to below the detection limit (except by NaPTT), suggesting a reduced risk of thromboembolic events that maybe potentially caused by our IVIG preparation. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  15. Intravenous immunoglobulins and rituximab therapy for severe transplant glomerulopathy in chronic antibody-mediated rejection: a pilot study.

    Science.gov (United States)

    Bachelet, Thomas; Nodimar, Celine; Taupin, Jean-Luc; Lepreux, Sebastien; Moreau, Karine; Morel, Delphine; Guidicelli, Gwendaline; Couzi, Lionel; Merville, Pierre

    2015-05-01

    Outcome of patients with transplant glomerulopathy (TG) is poor. Using B-cell targeting molecules represent a rational strategy to treat TG during chronic antibody-mediated rejection. In this pilot study, 21 patients with this diagnosis received four doses of intravenous immunoglobulins and two doses of rituximab (IVIG/RTX group). They were retrospectively compared with a untreated control group of 10 patients. At 24 months post-biopsy, graft survival was similar and poor between the treated and the untreated group, 47% vs. 40%, respectively, p = 0.69. This absence of response of IVIG/RTX treatment was observed, regardless the phenotype of TG. Baseline estimated glomerular filtration rate (eGFR) and decline in eGFR during the first six months after the treatment were risk factors associated with 24-month graft survival. The IVIG/RTX therapy had a modest effect on the kinetics of donor-specific alloantibodies at M24, compared to the untreated group, not associated with an improvement in graft survival. The mean number of adverse events per patient was higher in the IVIG/RTX group than in the control group (p = 0.03). Taken together, IVIG/RTX treatment for severe TG during chronic antibody-mediated rejection does not seem to change the natural history of TG and is associated with a high incidence of adverse events. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Safety of Intravenous Immunoglobulin (Tegeline®, Administered at Home in Patients with Autoimmune Disease: Results of a French Study

    Directory of Open Access Journals (Sweden)

    Eric Hachulla

    2018-01-01

    Full Text Available The efficacy of intravenous immunoglobulins (IVIg in patients with autoimmune diseases (AID has been known for several decades. Majority of these patients received IVIg in hospital. A retrospective study was conducted in 22 centers in France to evaluate the feasibility of the administration of Tegeline, an IVIg from LFB Biomedicaments, and assess its safety at home, compared to in hospital, in patients with AID. The included patients were at least 18 years old, suffering from AID, and treated with at least 1 cycle of Tegeline at home after receiving 3 consecutive cycles of hospital-based treatment with Tegeline at a dose between 1 and 2 g/kg/cycle. Forty-six patients with AID, in most cases immune-mediated neuropathies, received a total of 138 cycles of Tegeline in hospital and then 323 at home. Forty-five drug-related adverse events occurred in 17 patients who received their cycles at home compared to 24 adverse events in hospital in 15 patients. Serious adverse events occurred in 3 patients during home treatment, but they were not life-threatening and did not lead to discontinuation of Tegeline. Forty-five patients continued their treatment with Tegeline at home or in hospital; 39 (84.8% were still receiving home treatment at the end of the study. In conclusion, the study demonstrates the good safety profile of Tegeline administered at home at high doses in patients with AID who are eligible for home administration of Tegeline.

  17. Japanese scoring systems to predict resistance to intravenous immunoglobulin in Kawasaki disease were unreliable for Caucasian Israeli children.

    Science.gov (United States)

    Arane, Karen; Mendelsohn, Kerry; Mimouni, Michael; Mimouni, Francis; Koren, Yael; Simon, Dafna Brik; Bahat, Hilla; Helou, Mona Hanna; Mendelson, Amir; Hezkelo, Nofar; Glatstein, Miguel; Berkun, Yackov; Eisenstein, Eli; Aviel, Yonatan Butbul; Brik, Riva; Hashkes, Philip J; Uziel, Yosef; Harel, Liora; Amarilyo, Gil

    2018-05-24

    This study assessed the validity of using established Japanese risk scoring methods to predict intravenous immunoglobulin (IVIG) resistance to Kawasaki disease in Israeli children. We reviewed the medical records of 282 patients (70% male) with Kawasaki disease from six Israeli medical centres between 2004-2013. Their mean age was 2.5 years. The risk scores were calculated using the Kobayashi, Sano and Egami scoring methods and analysed to determine if a higher risk score predicted IVIG resistance in this population. Factors that predicted a lack of response to the initial IVIG dose were identified. We found that 18% did not respond to the first IVIG dose. The three scoring methods were unable to reliably predict IVIG resistance, with sensitivities of 23-32% and specificities of 67-87%. Calculating a predictive score that was specific for this population was also unsuccessful. The factors that predicted a lacked of response to the first IVIG dose included low albumin, elevated total bilirubin and ethnicity. The established risk scoring methods created for Japanese populations with Kawasaki disease were not suitable for predicting IVIG resistance in Caucasian Israeli children and we were unable to create a specific scoring method that was able to do this. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. Treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis with high-dose intravenous immunoglobulin.

    Science.gov (United States)

    Richter, C; Schnabel, A; Csernok, E; De Groot, K; Reinhold-Keller, E; Gross, W L

    1995-07-01

    In this uncontrolled study 15 patients with ANCA-associated systemic vasculitis, who were poor responders to conventional therapy, were treated with single or multiple courses of intravenous immunoglobulin (IVIG), 30 g/day over 5 days. Clinical and serological evaluation was performed before and 4 weeks after IVIG. Six of the 15 patients experienced clinically significant benefit from IVIG. Improvement was confined to single organ manifestations (skin, ENT findings), no improvement was seen with conjunctivitis and scleritis, pericarditis or nephritis. No patient experienced complete remission after IVIG. Repeated courses of IVIG at 4-week intervals were no more effective than single courses. In six anti-proteinase 3 (PR3)-positive patients pretreatment sera were incubated with F(ab')2 fragments of the IVIG preparation in vitro to measure the inhibitory effect of IVIG on anti-PR3 activity. An inhibition of anti-PR3 activity by 25-70% was observed; this did not correlate with clinical effects. Approximately 40% of patients benefited from IVIG treatment, though complete remission of disease activity did not occur. Neither clinical characteristics nor the inhibitory effect of the IVIG preparation on serum anti-PR3 activity in vitro predicted clinical response to this treatment modality.

  19. Effect of intravenous immunoglobulin in Guilain-Barre syndrome, myasthenia gravis and chronic idiopathic demyelinative polyneuropathy, A survey in Imam Khomeini Hospital

    Directory of Open Access Journals (Sweden)

    Qaffarpoor M

    1999-09-01

    Full Text Available With retrospective evaluation of 44 patients suffering from Guilan-Barre Syndrome (GBS, Chronic Idiopathic Demtyelinative Polyradiculoneuropathy (CIDP and Myasthenia Gravis (MG treated with intravenous immunoglobulin, we found following results: 1 Initial symptoms of improvement on forth or fifth days. 2 Maximum recovery for CIDP and MG were after 16-24 and 3-11 days, respectively. 3 No major complication, but mild side effects in 32% of patients. 4 In patients with GBS one grade improvement achieved after 8-30 days. 5 Intravenous immunoglobulin (IVIG plus plasmapheresis had no advantages over IVIG alone. 6 No reasonable conclusion about relapsing rate and duration of response due to follow up restrictions.

  20. Misleading hepatitis B testing in the setting of intravenous immunoglobulin [v1; ref status: indexed, http://f1000r.es/25r

    Directory of Open Access Journals (Sweden)

    Christelle M Ilboudo

    2013-11-01

    Full Text Available Intravenous immunoglobulin (IVIG is commonly used for a wide range of diagnoses, by multiple pediatric subspecialists. We report two cases of hepatitis B screening results post IVIG infusion, where positive anti-Hepatitis B core antigen serology tests indicated possible occult hepatitis infection, leading to a delay in care. However, serial antibody testing showed results consistent with the passive transfer of antibodies.

  1. Low-Dose Intravenous Immunoglobulin Treatment for Long-Standing Complex Regional Pain Syndrome: A Randomized Trial.

    Science.gov (United States)

    Goebel, Andreas; Bisla, Jatinder; Carganillo, Roy; Frank, Bernhard; Gupta, Rima; Kelly, Joanna; McCabe, Candy; Murphy, Caroline; Padfield, Nick; Phillips, Ceri; Sanders, Mark; Serpell, Mick; Shenker, Nick; Shoukrey, Karim; Wyatt, Lynne; Ambler, Gareth

    2017-10-03

    Two small trials suggest that low-dose intravenous immunoglobulin (IVIg) may improve the symptoms of complex regional pain syndrome (CRPS), a rare posttraumatic pain condition. To confirm the efficacy of low-dose IVIg compared with placebo in reducing pain during a 6-week period in adult patients who had CRPS from 1 to 5 years. 1:1 parallel, randomized, placebo-controlled, multicenter trial for 6 weeks, with an optional 6-week open extension. Patients were randomly assigned to 1 of 2 study groups between 27 August 2013 and 28 October 2015; the last patient completed follow-up on 21 March 2016. Patients, providers, researchers, and outcome assessors were blinded to treatment assignment. (ISRCTN42179756). 7 secondary and tertiary care pain management centers in the United Kingdom. 111 patients with moderate or severe CRPS of 1 to 5 years' duration. IVIg, 0.5 g/kg of body weight, or visually indistinguishable placebo of 0.1% albumin in saline on days 1 and 22 after randomization. The primary outcome was 24-hour average pain intensity, measured daily between days 6 and 42, on an 11-point (0- to 10-point) rating scale. Secondary outcomes were pain interference and quality of life. The primary analysis sample consisted of 108 eligible patients, 103 of whom had outcome data. Mean (average) pain scores were 6.9 points (SD, 1.5) for placebo and 7.2 points (SD, 1.3) for IVIg. The adjusted difference in means was 0.27 (95% CI, -0.25 to 0.80; P = 0.30), which excluded the prespecified, clinically important difference of -1.2. No statistically significant differences in secondary outcomes were found between the groups. In the open extension, 12 of the 67 patients (18%) who received 2 IVIg infusions had pain reduction of at least 2 points compared with their baseline score. Two patients in the blinded phase (1 in the placebo and 1 in the IVIg group) and 4 in the open IVIg phase had serious events. Results do not apply to patients who have had CRPS for less than 1 year or more

  2. Acute Hemorrhagic Encephalitis Responding to Combined Decompressive Craniectomy, Intravenous Immunoglobulin, and Corticosteroid Therapies: Association with Novel RANBP2 Variant

    Directory of Open Access Journals (Sweden)

    Abdulla Alawadhi

    2018-03-01

    Full Text Available BackgroundAcute hemorrhagic encephalomyelitis (AHEM is considered as a rare form of acute disseminated encephalomyelitis characterized by fulminant encephalopathy with hemorrhagic necrosis and most often fatal outcome.ObjectiveTo report the association with Ran Binding Protein (RANBP2 gene variant and the response to decompressive craniectomy and high-dose intravenous methylprednisolone (IVMP in life-threatening AHEM.DesignSingle case study.Case reportA 6-year-old girl known to have sickle cell disease (SCD presented an acquired demyelinating syndrome (ADS with diplopia due to sudden unilateral fourth nerve palsy. She received five pulses of IVMP (30 mg/kg/day. Two weeks after steroid weaning, she developed right hemiplegia and coma. Brain magnetic resonance imaging showed a left frontal necrotico-hemorrhagic lesion and new multifocal areas of demyelination. She underwent decompressive craniotomy and evacuation of an ongoing left frontoparietal hemorrhage. Comprehensive investigations ruled out vascular and infectious process. The neurological deterioration stopped concomitantly with combined neurosurgical drainage of the hematoma, decompressive craniotomy, IVMP, and intravenous immunoglobulins (IVIG. She developed during the following months Crohn disease and sclerosing cholangitis. After 2-year follow-up, there was no new neurological manifestation. The patient still suffered right hemiplegia and aphasia, but was able to walk. Cognitive/behavioral abilities significantly recovered. A heterozygous novel rare missense variant (c.4993A>G, p.Lys1665Glu was identified in RANBP2, a gene associated with acute necrotizing encephalopathy. RANBP2 is a protein playing an important role in the energy homeostasis of neuronal cells.ConclusionIn any ADS occurring in the context of SCD and/or autoimmune condition, we recommend to slowly wean steroids and to closely monitor the patient after weaning to quickly treat any recurrence of neurological symptom

  3. A preliminary randomized double blind placebo-controlled trial of intravenous immunoglobulin for Japanese encephalitis in Nepal.

    Directory of Open Access Journals (Sweden)

    Ajit Rayamajhi

    Full Text Available Japanese encephalitis (JE virus (JEV is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG's anti-inflammatory properties may also be beneficial.We performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group died during treatment and two (placebo subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2, which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group.A trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study.ClinicalTrials.gov NCT01856205.

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

    Science.gov (United States)

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

    2017-03-01

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

  5. Treatment response in Kawasaki disease is associated with sialylation levels of endogenous but not therapeutic intravenous immunoglobulin G.

    Science.gov (United States)

    Ogata, Shohei; Shimizu, Chisato; Franco, Alessandra; Touma, Ranim; Kanegaye, John T; Choudhury, Biswa P; Naidu, Natasha N; Kanda, Yutaka; Hoang, Long T; Hibberd, Martin L; Tremoulet, Adriana H; Varki, Ajit; Burns, Jane C

    2013-01-01

    Although intravenous immunoglobulin (IVIG) is highly effective in Kawasaki disease (KD), mechanisms are not understood and 10-20% of patients are treatment-resistant, manifesting a higher rate of coronary artery aneurysms. Murine models suggest that α2-6-linked sialic acid (α2-6Sia) content of IVIG is critical for suppressing inflammation. However, pro-inflammatory states also up-regulate endogenous levels of β-galactoside:α2-6 sialyltransferase-I (ST6Gal-I), the enzyme that catalyzes addition of α2-6Sias to N-glycans. We asked whether IVIG failures correlated with levels of α2-6Sia on infused IVIG or on the patient's own endogenous IgG. We quantified levels of α2-6Sia in infused IVIG and endogenous IgG from 10 IVIG-responsive and 10 resistant KD subjects using multiple approaches. Transcript levels of ST6GAL1, in patient whole blood and B cell lines were evaluated by RT-PCR. Plasma soluble (s)ST6Gal-I levels were measured by ELISA. There was no consistent difference in median sialylation levels of infused IVIG between groups. However, α2-6Sia levels in endogenous IgG, ST6GAL1 transcript levels, and ST6Gal-I protein in serum from IVIG-resistant KD subjects were lower than in responsive subjects at both pre-treatment and one-year time points (p treatment response in KD. Rather, lower sialylation of endogenous IgG and lower blood levels of ST6GALI mRNA and ST6Gal-I enzyme predict therapy resistance. These differences were stable over time, suggesting a genetic basis. Because IVIG-resistance increases risk of coronary artery aneurysms, our findings have important implications for the identification and treatment of such individuals.

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

    International Nuclear Information System (INIS)

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

    1989-01-01

    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

  7. [Study of human secretory immunoglobulin A. I. Obtaining monospecific antiserum to human secretory immunoglobulin A].

    Science.gov (United States)

    German, G P; Chernokhvostova, E V; Gol'derman, S Ia

    1975-10-01

    A method of obtaining monospecific antiserum to the human secretory IgA is described. Immunochemically pure secretory IgA (isolated from human colostrum by fractionation with ammonium sulfate and gel-filtration on Sephadex G-200) was used for immunization of rabbits or sheep. Heterologous antibodies were removed by adsorption with commercial gamma globulin, normal serum, the serum of a patient suffering from A-myeloma with the IgA polymere and purified lactoferrin. Monospecific antiserum to the secretory IgA gave a reaction of complete immunological identity with the secretory IgA and a free secretory component.

  8. Low-Dose versus Standard-Dose Intravenous Immunoglobulin to Prevent Fetal Intracranial Hemorrhage in Fetal and Neonatal Alloimmune Thrombocytopenia: A Randomized Trial.

    Science.gov (United States)

    Paridaans, Noortje P; Kamphuis, Marije M; Taune Wikman, Agneta; Tiblad, Eleonor; Van den Akker, Eline S; Lopriore, Enrico; Challis, Daniel; Westgren, Magnus; Oepkes, Dick

    2015-01-01

    Pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT) are commonly treated using weekly intravenous immunoglobulin (IVIG) at 1 g/kg maternal weight. IVIG is an expensive multidonor human blood product with dose-related side effects. Our aim was to evaluate the effectiveness of IVIG at a lower dose, i.e., 0.5 g/kg. This was a randomized controlled multicenter trial conducted in Sweden, the Netherlands and Australia. Pregnant women with human platelet antigen alloantibodies and an affected previous child without intracranial hemorrhage (ICH) were enrolled. The participants were randomized to IVIG at 0.5 or 1 g/kg per week. The analyses were per intention to treat. The primary outcome was fetal or neonatal ICH. Secondary outcomes were platelet count at birth, maternal and neonatal IgG levels, neonatal treatment and bleeding other than ICH. A total of 23 women were randomized into two groups (low dose: n = 12; standard dose: n = 11). The trial was stopped early due to poor recruitment. No ICH occurred. The median newborn platelet count was 81 × 10(9)/l (range 8-269) in the 0.5 g/kg group versus 110 × 10(9)/l (range 11-279) in the 1 g/kg group (p = 0.644). The risk of adverse outcomes in FNAIT pregnancies treated with IVIG at 0.5 g/kg is very low, similar to that using 1 g/kg, although our uncompleted trial lacked the power to conclusively prove the noninferiority of using the low dose.

  9. Treatment response in Kawasaki disease is associated with sialylation levels of endogenous but not therapeutic intravenous immunoglobulin G.

    Directory of Open Access Journals (Sweden)

    Shohei Ogata

    Full Text Available Although intravenous immunoglobulin (IVIG is highly effective in Kawasaki disease (KD, mechanisms are not understood and 10-20% of patients are treatment-resistant, manifesting a higher rate of coronary artery aneurysms. Murine models suggest that α2-6-linked sialic acid (α2-6Sia content of IVIG is critical for suppressing inflammation. However, pro-inflammatory states also up-regulate endogenous levels of β-galactoside:α2-6 sialyltransferase-I (ST6Gal-I, the enzyme that catalyzes addition of α2-6Sias to N-glycans. We asked whether IVIG failures correlated with levels of α2-6Sia on infused IVIG or on the patient's own endogenous IgG.We quantified levels of α2-6Sia in infused IVIG and endogenous IgG from 10 IVIG-responsive and 10 resistant KD subjects using multiple approaches. Transcript levels of ST6GAL1, in patient whole blood and B cell lines were evaluated by RT-PCR. Plasma soluble (sST6Gal-I levels were measured by ELISA.There was no consistent difference in median sialylation levels of infused IVIG between groups. However, α2-6Sia levels in endogenous IgG, ST6GAL1 transcript levels, and ST6Gal-I protein in serum from IVIG-resistant KD subjects were lower than in responsive subjects at both pre-treatment and one-year time points (p <0.001, respectively.Our data indicate sialylation levels of therapeutic IVIG are unrelated to treatment response in KD. Rather, lower sialylation of endogenous IgG and lower blood levels of ST6GALI mRNA and ST6Gal-I enzyme predict therapy resistance. These differences were stable over time, suggesting a genetic basis. Because IVIG-resistance increases risk of coronary artery aneurysms, our findings have important implications for the identification and treatment of such individuals.

  10. Intravenous immunoglobulin therapy leading to dramatic improvement in a patient with systemic juvenile idiopathic arthritis and severe pericarditis resistant to steroid pulse therapy.

    Science.gov (United States)

    Aizawa-Yashiro, Tomomi; Oki, Eishin; Tsuruga, Kazushi; Nakahata, Tohru; Ito, Etsuro; Tanaka, Hiroshi

    2012-05-01

    A 7-year-old Japanese boy with a 4-month history of systemic juvenile idiopathic arthritis (s-JIA) experienced disease flare with spiking fever, exanthema and arthralgia. He then developed progressive dyspnea due to severe pericarditis, and proinflammatory hypercytokinemia was suspected. Methylprednisolone pulse therapy was ineffective and echocardiography showed massive pericardial effusion had persisted. Alternatively, subsequent intravenous immunoglobulin (IVIG) therapy resulted in dramatic resolution of the pericardial effusion, and his general condition significantly improved within a few days. This case report may lend further support the use of IVIG for selected patients with s-JIA and severe pericarditis.

  11. The effect of FcγRIIA and FcγRIIB on coronary artery lesion formation and intravenous immunoglobulin treatment responses in children with Kawasaki disease

    Science.gov (United States)

    Chang, Ling-Sai; Lo, Mao-Hung; Li, Sung-Chou; Yang, Ming-Yu; Hsieh, Kai-Sheng; Kuo, Ho-Chang

    2017-01-01

    Previous research has found patients with the FcγRIIIB NA1 variant having increased risk of intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD). Our previous studies revealed that elevated FcγRIIA expression correlated with the susceptibility of KD patients. We conducted this research to determine whether and how Fcγ receptors affect the susceptibility, IVIG treatment response, and coronary artery lesions (CAL) of KD patients. The activating FcγRIIA and inhibitory FcγRIIB methylation levels of seven patients with KD and four control subjects were examined using HumanMethylation27 BeadChip. We enrolled a total of 44 KD patients and 10 control subjects with fevers. We performed real-time RT-PCR to determine the FcγRIIA and FcγRIIB expression levels, as well as a luciferase assay of FcγRIIA. We found a considerable increase in methylation of both FcγRIIA and FcγRIIB in KD patients undergoing IVIG treatment. Promoter methylation of FcγRIIA inhibited reporter activity in K562 cells using luciferase assay. The FcγRIIB mRNA expression levels were not found to increase susceptibility, CAL formation, or IVIG resistance. FcγRIIA mRNA expression levels were significantly higher in IVIG-resistant patients than in those that responded to IVIG during the pre-treatment period. Furthermore, the FcγRIIA/IIB mRNA expression ratio was considerably higher in KD patients with CAL than in those without CAL. FcγRIIA and FcγRIIB both demonstrated increased methylation levels in KD patients that underwent IVIG treatment. FcγRIIA expression influenced the IVIG treatment response of KD patients. The FcγRIIA/IIB mRNA expression ratio was greater in KD patients with CAL formation. PMID:27893416

  12. Medical resource utilization in dermatomyositis/polymyositis patients treated with repository corticotropin injection, intravenous immunoglobulin, and/or rituximab

    Directory of Open Access Journals (Sweden)

    Knight T

    2017-05-01

    Full Text Available Tyler Knight,1 T Christopher Bond,1 Breanna Popelar,2 Li Wang,3 John W Niewoehner,4 Kathryn Anastassopoulos,1 Michael Philbin4 1Covance Market Access Services Inc., Gaithersburg, MD, 2Xcenda, LLC, Palm Harbor, FL, 3STATinMED Research, Ann Arbor, MI, 4Mallinckrodt, LLC, Hazelwood, MO, USA Background: Dermatomyositis and polymyositis (DM/PM are rare, incurable inflammatory diseases that cause progressive muscle weakness and can be associated with increased medical resource use (MRU. When corticosteroid treatment is unsuccessful, patients may receive intravenous immunoglobulin (IVIg, rituximab, or repository corticotropin injection (RCI. This study compared real-world, non-medication MRU between patients treated with RCI and those treated with IVIg and/or rituximab for DM/PM.Methods: Claims of DM/PM patients were analyzed from the combination of three commercial health insurance databases in the United States from July 2009 to June 2014. Patients treated with RCI were propensity score matched to those treated with IVIg, rituximab, and both (IVIg+rituximab based on demographics, prior clinical characteristics, and prior MRU. Per-patient per-month (PPPM MRU and costs were compared using Poisson regression and generalized linear modeling, respectively.Results: One-hundred thirty-two RCI, 1,150 IVIg, and 562 rituximab patients had an average age of 52.6, 46.6, and 51.7 years, respectively, and roughly two-thirds were female. After matching, there were no significant differences in demographics or prior clinical characteristics. RCI patients had fewer PPPM hospitalizations (0.09 vs 0.17; P=0.049, shorter length of stay (LOS; 3.24 days vs 4.55 days; P=0.004, PPPM hospital outpatient department (HOPD visits (0.60 vs 1.39; P<0.001, and PPPM physician office visits (2.01 vs 2.33; P=0.035 than IVIg. RCI had fewer PPPM HOPD visits (0.56 vs 0.92; P<0.001 than rituximab. Patients treated with RCI had shorter LOS (2.18 days vs 5.15; P<0.001 and less PPPM HOPD

  13. Immunoglobulin gene usage in the human anti-pathogen response.

    Science.gov (United States)

    Newkirk, M M; Rioux, J D

    1995-09-01

    The human antibody response to foreign pathogens is generated to a relatively small number of target surface proteins and carbohydrates that nonetheless have an extensive array of epitopes. The study of human monoclonal antibodies to different pathogens shows that there are a diversity of mechanisms used to generate a sufficient repertoire of antibodies to combat the invading pathogens. Although many different immunoglobulin gene elements are used to construct the anti-pathogen response, some elements are used more often than would be expected if all elements were used randomly. For example, the immune response to Haemophilus influenzae polysaccharide appears to be quite narrow, being restricted primarily to a specific heavy-chain gene, 3-15, and a lambda light-chain family II member, 4A. In contrast, for the immune response to cytomegalovirus proteins, a wider group of gene elements is needed. It is also surprising that despite an investigator bias for IgG- rather than IgM-secreting immortal B cells (because of their high affinity and neutralizing abilities), 26% of light chains and 13% of heavy chains showed a very low level of somatic mutation, equivalent to an IgM molecule that has not undergone affinity maturation. Although some highly mutated IgG molecules are present in the anti-pathogen response, most of the monoclonal antibodies specific for viruses or bacteria have a level of somatic hypermutation similar to that of the adult IgM repertoire. A number of studies have shown that there are similarities in the antibody responses to pathogens and to self (autoantibodies).(ABSTRACT TRUNCATED AT 250 WORDS)

  14. The role of Tc-99m polyclonal human immunoglobulin G scintigraphy in Graves' ophthalmopathy

    International Nuclear Information System (INIS)

    Ortapamuk, H.; Hosal, B.; Naldoken, S.

    2002-01-01

    The aim of this study was to clarify whether Tc-99m HIG (Polyclonal Human Immunoglobulin G) can image and determine the severity of orbital involvement in patients with Graves' ophthalmopathy. Twenty-six patients between 19 and 56 years old with Graves' ophthalmopathy were examined. All patients received approximately 370 MBq Tc-99m HIG by intravenous (i.v.) injection. Planar and SPECT examination were performed 4 hours after the injection. Visual and semiquantitative evaluations were performed for both orbits by two independent observers. Clinically active ophthalmopathy patients had noticeably increased orbital accumulation of Tc-99m HIG. In patients with inactive disease, and 14 of 19 had no uptake, whereas 5 patients had orbital radioactivity accumulation. The duration of Graves' ophthalmopathy did not correlate with the presence of active ophthalmopathy and Tc-99m HIG grade. There was no correlation between clinical classification and clinical activity (r=278). There was a good correlation between clinical activity and the radioactivity grade with r=0.666 (p=0.01). The clinical classification closely correlated with Tc-99m HIG grade (r=0.423, p=0.05) Tc-99m HIG scan can clearly identified clinically active patients, and subclinical inflammation can be shown by this scintigraphic evaluation. The current preliminary results suggested that Tc-99m HIG SPECT might be useful for the assessment of disease activity in Graves' ophthalmopathy. (author)

  15. Immunoglobulin preparations for intravenous administration. A review of their biologic activities and comparison of various preparation methods

    DEFF Research Database (Denmark)

    Nielsen, H

    1994-01-01

    procedures are employed by different commercial suppliers of immunoglobulins, and from the literature it appears that various important biologic functions, e.g., opsonic activity, complement fixation, and Fc-receptor function, are subject to alterations during the preparation. The best preservation...

  16. A 70-year-old male with peripheral neuropathy, ataxia and antigliadin antibodies shows improvement in neuropathy, but not ataxia, after intravenous immunoglobulin and gluten-free diet

    Directory of Open Access Journals (Sweden)

    Dharshan Anandacoomaraswamy

    2008-10-01

    Full Text Available Dharshan Anandacoomaraswamy1, Jagdeesh Ullal2, Aaron I Vinik21Department of Internal Medicine, Coney Island Hospital, Brooklyn, NY, USA; 2Strelitz Diabetes Center, Department of Internal Medicine, Eastern Virginia Medical School, Norfolk, VA, USAAbstract: This is a case of a 70-year-old man with severe peripheral neuropathy, type 2 diabetes and progressively worsening cerebellar ataxia. He was found to have circulating antigliadin and antireticulin antibodies compatible with celiac disease in the absence of intestinal pathology. The peripheral neuropathy improved with a gluten-free diet, antioxidants and intravenous immunoglobulin, whereas the ataxia did not. This case illustrates the need to test for celiac disease in patients with idiopathic ataxia and peripheral neuropathy and the need for alternative therapies for ataxia. Keywords: celiac disease, peripheral neuropathy, autoimmune disease, cerebellar ataxia, type 2 diabetes

  17. Impact of intravenous immunoglobulin on the dopaminergic system and immune response in the acute MPTP mouse model of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    St-Amour Isabelle

    2012-10-01

    Full Text Available Abstract Intravenous immunoglobulin (IVIg is a blood-derived product, used for the treatment of immunodeficiency and autoimmune diseases. Since a range of immunotherapies have recently been proposed as a therapeutic strategy for Parkinson’s disease (PD, we investigated the effects of an IVIg treatment in a neurotoxin-induced animal model of PD. Mice received four injections of MPTP (15 mg/kg at 2-hour intervals followed by a 14-day IVIg treatment, which induced key immune-related changes such as increased regulatory T-cell population and decreased CD4+/CD8+ ratio. The MPTP treatment induced significant 80% and 84% decreases of striatal dopamine concentrations (P P P 

  18. METHODOLOGICAL APPROACHES TO EXPERT EVALUATION OF PRECLINICAL AND CLINICAL TRIALS OF HUMAN IMMUNOGLOBULIN PRODUCTS

    Directory of Open Access Journals (Sweden)

    V. B. Ivanov

    2017-01-01

    Full Text Available The article considers the experience of Russian and leading foreign regulatory agencies in organisation and conduction of preclinical and clinical trials of human immunoglobulin products. The authors suggest a classification of human immunoglobulins and provide updated information on authorization of these products in Russia. The article summarizes methodological approaches, basic scientific principles and criteria relating to expert evaluation of preclinical and clinical trials of blood products. The authors further define the expert body’s requirements for data on preclinical and clinical trials of human normal immuniglobulins and human specific immunoglobulins for the prevention and/or treatment of infectious and non-infectious diseases which are submitted as part of applications for marketing authorization or marketing authorization variation. The article suggests programs of preclinical and clinical trials for human normal immunoglobulins and human specific immunoglobulins for the prevention and/or treatment of infectious and non-infectious diseases that are aligned with the Russian legislation and Eurasian Economic Union’s regulations on medicines circulation, and have been elaborated with respect to the guidelines of the European Medicines Agency.

  19. Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes

    International Nuclear Information System (INIS)

    Grayson, J.; Dooley, N.J.; Koski, I.R.; Blaese, R.M.

    1981-01-01

    The direct effects of steroid hormones on the production of immunoglobulins and DNA synthesis by human T and B lymphocytes was evaluated in cultures of peripheral blood mononuclear cells. As detected by a reverse hemolytic plaque assay, the addition of 0.1 mM to 10 nM hydrocortisone to lymphocytes in culture in the absence of other stimulants or mitogens, resulted in the dramatic induction of immunoglobulin production with responses comparable to those seen in similar cultures stimulated with pokeweed mitogen. Steroid-stimulated immunoglobulin production was first seen after 48 h and peaked at 8-10 d of culture. The production of IgG, IgA, and IgM was induced following incubation with steroid. Glucocorticoids, but not estrogens or androgens, were capable of mediating this effect, and only compounds with affinity for the glucocorticoid receptor were active. The induction of immunoglobulin production was dependent on both T cells and monocytes; cultures depleted of either cell type did not produce immunoglobulin when stimulated with glucocorticoid hormones. Proliferation of B cells or T cells could not be detected by [/sup 3/H]thymidine incorporation or total cell recovery from steroid-stimulated cultures, even though such cultures demonstrated marked increases in immunoglobulin production. The mechanism responsible for this functional maturation of B cells to become high rate immunoglobulin producing cells is as yet undefined, although it appears to involve more than merely steroid mediated inactivation of suppressor T cells

  20. The effects of immunotherapy with intravenous immunoglobulins versus no intervention, placebo, or usual care in patients with recurrent miscarriages

    DEFF Research Database (Denmark)

    Egerup, Pia; Lindschou, Jane; Gluud, Christian

    2014-01-01

    , and publication status investigating infusions with immunoglobulins in relation to pregnancy compared to placebo, no intervention, or treatment as usual for assessments of benefits and harms. The relevant published literature will be searched using the following databases: Cochrane Central Register of Controlled...... Trials, Medline, Embase, WHO International Clinical Trials Registry Platform, and Ovid Medline In-Process and Other Non-Indexed Citations databases. Two review authors will independently extract data and assess risk of bias. We will undertake meta-analyses according to the recommendations stated...

  1. A sensitive chain specific radioimmunoassay for human immunoglobulins using monoclonal antibodies

    International Nuclear Information System (INIS)

    Sikora, K.; Alderson, T.St.J.; Ellis, J.

    1983-01-01

    A sensitive radioimmunoassay is described for human immunoglobulins. This solid-phase assay uses commercially available monoclonal antibodies and is specific for different Ig chain types. Levels of less than 20 ng/ml Ig are detectable. The assay is suitable for the analysis of human hybridoma supernatants. (Auth.)

  2. 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....

  3. Severe hemolytic disease of the newborn due to anti-Di b treated with phototherapy and intravenous immunoglobulin.

    Science.gov (United States)

    Oh, Eun-Jee; Jekarl, Dong Wook; Jang, Hyun-Sik; Park, Hae-Il; Park, Yeon-Joon; Choi, Hyun Ah; Chun, Chung-Sik; Kim, Yonggoo; Kim, Hyung Hoi

    2008-01-01

    The Di(b) antigen usually occurs with high incidence, except in certain Asian and South American Indian populations. In general, hemolysis caused by anti-Di(b) is not severe and its clinical course is benign. We report a Korean neonate with severe hemolytic disease of the newborn caused by anti-Di(b). The phenotype and genotype of the Diego blood group system of the patient and his mother were Di(a+b+) and Di(a+b-), respectively. The mother's serum and eluate from the neonate's erythrocytes contained anti-Di(b). This case was successfully managed with phototherapy and high dose iv immunoglobulin. Since most commercial antibody detection panels do not contain Di(b-) red cells, it is important to consider anti-Di(b) in cases of hemolytic disease of the newborn caused by an antibody against a high frequency antigen.

  4. Regulatory T cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to intravenous immunoglobulin therapy.

    Science.gov (United States)

    Maddur, Mohan S; Stephen-Victor, Emmanuel; Das, Mrinmoy; Prakhar, Praveen; Sharma, Varun K; Singh, Vikas; Rabin, Magalie; Trinath, Jamma; Balaji, Kithiganahalli N; Bolgert, Francis; Vallat, Jean-Michel; Magy, Laurent; Kaveri, Srini V; Bayry, Jagadeesh

    2017-03-20

    Intravenous immunoglobulin (IVIG) is a polyspecific pooled immunoglobulin G preparation and one of the commonly used therapeutics for autoimmune diseases including those of neurological origin. A recent report in murine model proposed that IVIG expands regulatory T (T reg ) cells via induction of interleukin 33 (IL-33). However, translational insight on these observations is lacking. Ten newly diagnosed Guillain-Barré syndrome (GBS) patients were treated with IVIG at the rate of 0.4 g/kg for three to five consecutive days. Clinical evaluation for muscular weakness was performed by Medical Research Council (MRC) and modified Rankin scoring (MRS) system. Heparinized blood samples were collected before and 1, 2, and 4-5 weeks post-IVIG therapy. Peripheral blood mononuclear cells were stained for surface CD4 and intracellular Foxp3, IFN-γ, and tumor necrosis factor alpha (TNF-α) and were analyzed by flow cytometry. IL-33 and prostaglandin E2 in the plasma were measured by ELISA. The fold changes in plasma IL-33 at week 1 showed no correlation with the MRC and MRS scores at weeks 1, 2, and ≥4 post-IVIG therapy. Clinical recovery following IVIG therapy appears to be associated with T reg cell response. Contrary to murine study, there was no association between the fold changes in IL-33 at week 1 and T reg cell frequency at weeks 1, 2, and ≥4 post-IVIG therapy. T reg cell-mediated clinical response to IVIG therapy in GBS patients was associated with reciprocal regulation of effector T cells-expressing TNF-α. T reg cell expansion by IVIG in patients with autoimmune diseases lack correlation with IL-33. T reg cell frequency, but not plasma IL-33 levels, represents potential immunological biomarker to predict clinical response to IVIG therapy.

  5. A 6-month mixed-effect pharmacokinetic model for post-transplant intravenous anti-hepatitis B immunoglobulin prophylaxis

    Directory of Open Access Journals (Sweden)

    Han S

    2017-07-01

    Full Text Available Seunghoon Han,1,2 Gun Hyung Na,3 Dong-Goo Kim3 1Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seocho-gu, Seoul, South Korea; 2Pharmacometrics Institute for Practical Education and Training, The Catholic University of Korea, Seocho-gu, Seoul, South Korea; 3Department of Surgery, Seoul St Mary’s Hospital, The Catholic University of Korea, Seocho-gu, Seoul, South Korea Background: Although individualized dosage regimens for anti-hepatitis B immunoglobulin (HBIG therapy have been suggested, the pharmacokinetic profile and factors influencing the basis for individualization have not been sufficiently assessed. We sought to evaluate the pharmacokinetic characteristics of anti-HBIG quantitatively during the first 6 months after liver transplantation. Methods: Identical doses of 10,000 IU HBIG were administered to adult liver transplant recipients daily during the first week, weekly thereafter until 28 postoperative days, and monthly thereafter. Blood samples were obtained at days 1, 7, 28, 84, and 168 after transplantation. Plasma HBIG titer was quantified using 4 different immunoassay methods. The titer determined by each analytical method was used for mixed-effect modeling, and the most precise results were chosen. Simulations were performed to predict the plausible immunoglobulin maintenance dose. Results: HBIG was eliminated from the body most rapidly in the immediate post-transplant period, and the elimination rate gradually decreased thereafter. In the early post-transplant period, patients with higher DNA titer tend to have lower plasma HBIG concentrations. The maintenance doses required to attain targets in 90%, 95%, and 99% of patients were ~15.3, 18.2, and 25.1 IU, respectively, multiplied by the target trough level (in IU/L. Conclusion: The variability (explained and unexplained in HBIG pharmacokinetics was relatively larger in the early post-transplant period. Dose individualization based upon

  6. The role of qualitative and quantitative MRI assessment of multiple sclerosis lesions according to their in evaluating the efficacy of intravenous immunoglobulin G

    Energy Technology Data Exchange (ETDEWEB)

    Kocer, B. [Sedat Simavi sokak 17/32 B Blok Cankaya, Sedat Simavi sokak 17/32 B Blok Cankaya, 06550, Ankara (Turkey); Department of Neurology, Gazi University Faculty of Medicine, 06510, Ankara (Turkey); Yildirim-Guerel, S.; Tali, E.T.; Isik, S. [Department of Radiology, Gazi University Faculty of Medicine, 06510, Ankara (Turkey); Irkec, C. [Department of Neurology, Gazi University Faculty of Medicine, 06510, Ankara (Turkey)

    2004-04-01

    We evaluation of the role of determining the distribution of brain-stem, cerebellar and cerebral lesions in number and volume by MRI in determining the efficiency of treatment of multiple sclerosis (MS). We studied 24 patients diagnosed as having relapsing and remitting MS, of whom 12 received intravenous immunoglobulin G; a control group of 12 were given placebo. In a double-blind study, MRI was obtained initially and at 3, 6 and 9 months, and interpreted without knowledge of clinical findings, laboratory tests or treatment. The lesions were classified according to their distribution and evaluated qualitatively and quantitatively. Each patient was also examined clinically and scored according to the expanded disability status scale (EDSS) following every MRI examination. All patients in the treatment group showed significant improvement. The lesions decreased in both in size and number in all sites. In the control group lesions increased both in number and size in all sites, but only the increase between 3and 6 months was statistically significant. In both groups, significant apparent changes were detected in the cerebellum and brain stem. Volumetric evaluation was found to be more helpful than qualitative assessment. (orig.)

  7. The role of qualitative and quantitative MRI assessment of multiple sclerosis lesions according to their in evaluating the efficacy of intravenous immunoglobulin G

    International Nuclear Information System (INIS)

    Kocer, B.; Yildirim-Guerel, S.; Tali, E.T.; Isik, S.; Irkec, C.

    2004-01-01

    We evaluation of the role of determining the distribution of brain-stem, cerebellar and cerebral lesions in number and volume by MRI in determining the efficiency of treatment of multiple sclerosis (MS). We studied 24 patients diagnosed as having relapsing and remitting MS, of whom 12 received intravenous immunoglobulin G; a control group of 12 were given placebo. In a double-blind study, MRI was obtained initially and at 3, 6 and 9 months, and interpreted without knowledge of clinical findings, laboratory tests or treatment. The lesions were classified according to their distribution and evaluated qualitatively and quantitatively. Each patient was also examined clinically and scored according to the expanded disability status scale (EDSS) following every MRI examination. All patients in the treatment group showed significant improvement. The lesions decreased in both in size and number in all sites. In the control group lesions increased both in number and size in all sites, but only the increase between 3and 6 months was statistically significant. In both groups, significant apparent changes were detected in the cerebellum and brain stem. Volumetric evaluation was found to be more helpful than qualitative assessment. (orig.)

  8. Comparisons in fluctuation of muscle strength and function in patients with immune-mediated neuropathy treated with intravenous versus subcutaneous immunoglobulin.

    Science.gov (United States)

    Christiansen, Ingelise; Markvardsen, Lars H; Jakobsen, Johannes

    2018-04-01

    Variations in muscle strength and function have not been studied in patients with chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy whose treatment regimen has been changed from intravenous to subcutaneous immunoglobulin (IVIg to SCIg). In a prospective, open-label study, patients were changed from monthly IVIg to weekly SCIg. The primary endpoint was variation in isokinetic muscle strength (cIKS). Secondary endpoints were variations in Medical Research Council (MRC) score, grip strength (GS), 9-hole-peg test (9-HPT), and 40-meter-walk test (40-MWT). The coefficient of variance of cIKS during the IVIg and SCIg treatment periods was unchanged (mean ± SD: 6.97 ± 4.83% vs. 5.50 ± 3.13%, P = 0.21). The variations in the 9-HPT and 40-MWT were significantly lower in the SCIg group (P = 0.01 and P = 0.005, respectively). When therapy was changed from IVIg to SCIg, fluctuation of muscle strength was unchanged, but performance fluctuations were diminished. Muscle Nerve 57: 610-614, 2018. © 2017 Wiley Periodicals, Inc.

  9. Intravenous immunoglobulin for chronic residual peripheral neuropathy in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome): a multicenter, double-blind trial.

    Science.gov (United States)

    Koike, Haruki; Akiyama, Kazuo; Saito, Toyokazu; Sobue, Gen

    2015-03-01

    Eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg-Strauss syndrome, frequently affects the peripheral nervous system. We conducted a multicenter, double-blind, three-arm treatment period, randomized, pre-post trial to assess the efficacy of intravenous immunoglobulin (IVIg) administration for residual peripheral neuropathy in patients with EGPA that is in remission, indicated by laboratory indices. Twenty-three patients were randomly assigned into three groups, in which the timing of IVIg and placebo administration was different. Each group received one course of intervention and two courses of placebo at 2-week intervals. Treatment effects were assessed every 2 weeks for 8 weeks. The primary outcome measure, the amount of change in the manual muscle testing sum score 2 weeks after IVIg administration, significantly increased (p = 0.002). The results over time suggested that this effect continued until the last assessment was done 8 weeks later. The number of muscles with manual muscle testing scores of three or less (p = 0.004) and the neuropathic pain scores represented by the visual analogue scale (p = 0.005) also improved significantly 2 weeks after IVIg administration. This study indicates that IVIg treatment for EGPA patients with residual peripheral neuropathy should be considered even when laboratory indices suggest remission of the disease.

  10. A Case of Alport Syndrome with Posttransplant Antiglomerular Basement Membrane Disease despite Negative Antiglomerular Basement Membrane Antibodies by EIA Treated with Plasmapheresis and Intravenous Immunoglobulin

    Directory of Open Access Journals (Sweden)

    Sumiko I. Armstead

    2013-01-01

    Full Text Available Posttransplant antiglomerular basement membrane (anti-GBM disease occurs in approximately 5% of Alport patients and usually ends in irreversible graft failure. Recent research has focused on characterizing the structure of the anti-GBM alloepitope. Here we present a case of a 22-year-old male with end-stage renal disease secondary to Alport syndrome, with a previously failed renal allograft, who received a second deceased-donor kidney transplant. Six days after transplantation, he developed acute kidney injury. The serum anti-GBM IgG was negative by enzyme immunoassay (EIA. On biopsy, he had crescentic glomerulonephritis with linear GBM fixation of IgG. With further analysis by western blotting, we were able to detect antibodies to an unidentified protein from the basement membrane. This patient was treated with plasmapheresis twice per week and monthly intravenous immunoglobulin (IVIG for a total of five months. At the end of treatment, these unknown antibodies were no longer detected. His renal function improved, and he has not required dialysis. We conclude that anti-GBM disease in patients with Alport Syndrome may be caused by circulating antibodies to other components of the basement membrane that are undetectable by routine anti-GBM EIA and may respond to treatment with plasmapheresis and IVIG.

  11. A Case of Alport Syndrome with Posttransplant Antiglomerular Basement Membrane Disease despite Negative Antiglomerular Basement Membrane Antibodies by EIA Treated with Plasmapheresis and Intravenous Immunoglobulin.

    Science.gov (United States)

    Armstead, Sumiko I; Hellmark, Thomas; Wieslander, Jorgen; Zhou, Xin J; Saxena, Ramesh; Rajora, Nilum

    2013-01-01

    Posttransplant antiglomerular basement membrane (anti-GBM) disease occurs in approximately 5% of Alport patients and usually ends in irreversible graft failure. Recent research has focused on characterizing the structure of the anti-GBM alloepitope. Here we present a case of a 22-year-old male with end-stage renal disease secondary to Alport syndrome, with a previously failed renal allograft, who received a second deceased-donor kidney transplant. Six days after transplantation, he developed acute kidney injury. The serum anti-GBM IgG was negative by enzyme immunoassay (EIA). On biopsy, he had crescentic glomerulonephritis with linear GBM fixation of IgG. With further analysis by western blotting, we were able to detect antibodies to an unidentified protein from the basement membrane. This patient was treated with plasmapheresis twice per week and monthly intravenous immunoglobulin (IVIG) for a total of five months. At the end of treatment, these unknown antibodies were no longer detected. His renal function improved, and he has not required dialysis. We conclude that anti-GBM disease in patients with Alport Syndrome may be caused by circulating antibodies to other components of the basement membrane that are undetectable by routine anti-GBM EIA and may respond to treatment with plasmapheresis and IVIG.

  12. Quantitative glycan profiling of normal human plasma derived immunoglobulin and its fragments Fab and Fc.

    Science.gov (United States)

    Anumula, Kalyan Rao

    2012-08-31

    Typical clinical grade human IgG (intravenous immunoglobulin, IVIG), used for carbohydrate analysis, is derived from thousands of healthy donors. Quantitative high-resolution glycan profiles of IgG and its Fc-Fab fragments are presented here. Glycan profiles were established following digestions with Fc specific endoglycosidase S and generic PNGase F under denaturing and non-denaturing (native) conditions. The native PNGase F glycan profile of IgG was similar (but not identical) to that of Endo S. Endo S profiles did not contain the glycans with bisecting GlcNAc. PNGase F glycan profiles were the same for Fc fragments that were isolated from pepsin and Ide S protease digests. Both isolated Fab fragments and the previously deglycosylated IVIG (native conditions) yielded the same glycan profile. Glycan profiles were established using high resolution HPLC with 2-aminobenzoic acid (2AA) labeling. An accurate determination of sialylation levels can be made by this method. Carbohydrate content in Fc and Fab was determined using an internal standard and corrected for both protein and glycan recoveries. Fab portion contained about 14% of the total carbohydrate which translates to 2.3 sugar chains per mol in IVIG where 2 chains are located in the CH2 domain of the Fc. Fc glycans consisted of neutral (N) 84.5%; mono-sialylated (S1) 15% and di-sialylated (S2) 0.5%. In contrast, Fab contained N, 21%; S1, 43% and S2, 36%. The distribution of bisecting N-acetylglucosamine and fucose was found to be very different in various glycans (N, S1 and S2) found in Fab and Fc. Total IgG glycan profile (Fab plus Fc) contained N, 78.5%; S1, 17% and S2, 4.5%. Percent distribution of glycans G0, G1 and G2 (with 0, 1 and 2 two galactoses) was 26, 49 and 25 respectively within the 78% of the neutral glycans. Glycan profiles were nearly the same for various clinical grade IVIG preparations from various manufacturers. A fast HPLC profiling method was developed for the separation and quantitation

  13. 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.

  14. A Killer Immunoglobulin - Like Receptor Gene - Content Haplotype and A Cognate Human Leukocyte Antigen Ligand are Associated with Autism

    OpenAIRE

    Torres, Anthony; Westover, Jonna; Benson, Michael; Johnson, Randall; Dykes, Annelise

    2016-01-01

    The killing activity of natural killer cells is largely regulated by the binding of class I human leukocyte antigen cognate ligands to killer cell immunoglobulin - like receptor proteins. The killer cell immunoglobulin - like receptor gene - complex contains genes that activate and others that inhibit the killing state of natural killer cells depending on the binding of specific human leukocyte antigen cognate ligands. It has been suggested in previous publications that activating human leuko...

  15. Detection of a local staphylococcal infection in mice with technetium-99m-labeled polyclonal human immunoglobulin

    International Nuclear Information System (INIS)

    Calame, W.; Feitsma, H.I.; Ensing, G.J.; Goedemans, W.T.; Camps, J.A.; van Furth, R.; Pauwels, E.K.

    1991-01-01

    The purpose of this study was to investigate both the ability of 99mTc-labeled polyclonal human immunoglobulin (HIG) to localize an infection and the modes of action involved in this process. Mice, infected with Staphylococcus aureus ATCC 25923 in a thigh muscle, received HIG intravenously. Scintigrams were made 1, 4, and 24 hr later; subsequently the mice were killed and the activity in several organs and thighs was determined. The radiopharmaceutical demonstrated a time-dependent accumulation at the site of infection. It was found that vascular permeability or Fc binding alone could not account for the mode of action of HIG. Neither the origin of Ig (human versus murine) nor the total amount of protein (0.01-1.0 mg Ig per mouse) affected the target-to-background (T/B) ratios. Ratios were not different for leukocytopenic animals. A correlation (p less than 0.001) was demonstrated between the number of bacteria at the site of infection and the T/B ratio. This was also found after antibiotic treatment (p less than 0.02)

  16. Effect of Intravenous immunoglobulin on Th1 and Th2 lymphocytes and improvement of pregnancy outcome in recurrent pregnancy loss (RPL).

    Science.gov (United States)

    Ahmadi, Majid; Abdolmohammadi-Vahid, Samaneh; Ghaebi, Mahnaz; Aghebati-Maleki, Leili; Afkham, Amir; Danaii, Shahla; Abdollahi-Fard, Sedigheh; Heidari, Lida; Jadidi-Niaragh, Farhad; Younesi, Vahid; Nouri, Mohammad; Yousefi, Mehdi

    2017-08-01

    Women with elevated natural killer (NK) cell frequency and function during pregnancy, suffer from recurrent pregnancy loss (RPL). In the present study, the possible effect of intravenous immunoglobulin (IVIG) administration on Th1 and Th2 cell frequency, cytokine secretion, and expression of transcription factors is compared between RPL patients and control group. Totally, 44 women with a history of RPL (32 women as treated group and 12 as control group) were enrolled in the study. The frequency of Th1 and Th2 lymphocytes, the expression of transcription factors related to these cells and the serum levels of associated cytokines were assessed by flowcytometry, real-time PCR and ELISA, respectively. All, assessments were performed both before and after treatment with IVIG. A significant reduction in Th1 lymphocyte frequency, transcription factor expression and cytokine levels were observed in IVIG-treated group, while all the above parameters indicated a significant increase for Th2 lymphocytes. Th1/Th2 ratio decreased significantly (p value<0.0001) at the end of treatment and 28 out of 32 (87.5%) women in IVIG-treated group had live birth in comparison with 5 out of 12 (41.6%) in untreated group. IVIG administration proves to be an efficient therapeutic strategy which is able to enhance the success rate of pregnancy through a shift in Th2 responses. Furthermore, IVIG presents efficacy for the treatment of reproduction failures especially in subjects with immune cell abnormalities and increased NK cell level and function. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Apheresis and intravenous immunoglobulins used in addition to conventional therapy to treat high-risk pregnant antiphospholipid antibody syndrome patients. A prospective study.

    Science.gov (United States)

    Ruffatti, Amelia; Favaro, Maria; Hoxha, Ariela; Zambon, Alessandra; Marson, Piero; Del Ross, Teresa; Calligaro, Antonia; Tonello, Marta; Nardelli, Giovanni B

    2016-06-01

    Pregnant women with triple antibody positive antiphospholipid syndrome (APS) who have had thrombosis or a history of early, severe pregnancy complications are generally considered at high risk of pregnancy loss. The objectives of this study were to investigate the efficacy and safety of a relatively new treatment protocol used in addition to conventional therapy in high-risk pregnant patients affected with primary APS. The study's two inclusion criteria were: (1) the presence of triple antiphospholipid positivity, (2) previous thrombosis and/or a history of one or more early, severe pregnancy complications. Eighteen pregnancies occurring between 2002 and 2015 in 14 APS patients, (mean age 34.8±3.6 SD) were monitored. All 14 (100%) patients had triple antiphospholipid positivity. In addition, six of them (42.8%) had a history of thrombosis, four (28.6%) had one or more previous early and severe pregnancy complications, and four (30.8%) met both clinical study criteria. The study protocol included weekly plasmapheresis or immunoadsorption and fortnightly 1g/kg intravenous immunoglobulins. Seventeen of the pregnancies (94.4%) produced live neonates, all born between the 26th and 37th weeks of gestation (mean 33.1±3.5 SD). One female (5.5%), born prematurely at 24 weeks, died of sepsis a week after birth. There were two cases (11.1%) of severe pregnancy complications. No treatment side effects were registered. Given the high live birth rate and the safety associated to it, the study protocol described here could be taken into consideration by medical teams treating high-risk APS pregnant patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Imunoglobulina endovenosa em crianças com síndrome de Guillain-Barré Intravenous immunoglobulin in children with Guillain-Barré syndrome

    Directory of Open Access Journals (Sweden)

    ISAC BRUCK

    2000-12-01

    Full Text Available Relatamos nossa experiência com imunoglobulina endovenosa (IGEV, plasmaferese e terapêutica de suporte no tratamento de 13 pacientes com síndrome de Guillain-Barré (SGB. Dos 13 pacientes, 7 receberam IGEV, 2 plasmaferese e 4 terapêutica de suporte. No 15° dia após a administração da IGEV, todos os pacientes deste grupo apresentaram melhora de pelo menos 1 grau na escala de Hughes et al. modificada. Dos 2 pacientes submetidos a plasmaferese, 1 apresentou melhora de 1 grau 5 dias após o procedimento. Entre os 4 pacientes que receberam tratamento de suporte, 2 apresentaram melhora dentro de 20 dias de evolução. No grupo que recebeu IGEV os escores finais foram menores e não houve recidivas. Assim, estes resultados sugerem que a IGEV diminui o tempo necessário para a melhora clínica quando comparado com tratamento suportivo.We report our experience with intravenous immunoglobulin (IVIG, plasmapheresis and supportive care in 13 patients with the Guillain-Barré syndrome. Seven of 13 patients received IVIG, 2 plasmapheresis and 4 supportive care. At 15th day after IVIG administration, all patients in this group had improved at least one disability grade. In the plasmapheresis group, 1 improved at 5th day after the procedure. Two of the 4 patients that received supportive care improved at 20th day of evaluation. In the IVIG group, the final scores were lower and had no relapses. These results suggest faster clinical improvement with IVIG when compared with supportive measures.

  19. Intravenous immunoglobulin for maintenance treatment of multifocal motor neuropathy: A multi-center, open-label, 52-week phase 3 trial.

    Science.gov (United States)

    Kuwabara, Satoshi; Misawa, Sonoko; Mori, Masahiro; Iwai, Yuta; Ochi, Kazuhide; Suzuki, Hidekazu; Nodera, Hiroyuki; Tamaoka, Akira; Iijima, Masahiro; Toda, Tatsushi; Yoshikawa, Hiroo; Kanda, Takashi; Sakamoto, Ko; Kusunoki, Susumu; Sobue, Gen; Kaji, Ryuji

    2018-04-10

    Intravenous immunoglobulin (IVIg) therapy is currently the only established treatment in patients with multifocal motor neuropathy (MMN), and many patients have an IVIg-dependent fluctuation. We aimed to investigate the efficacy and safety of every 3 week IVIg (1.0 g/kg) for 52 weeks. This study was an open-label phase 3 clinical trial, enrolling 13 MMN patients. After an induction IVIg therapy (0.4 g/kg/d for 5 consecutive days), maintenance dose (1.0 g/kg) was given every 3 weeks for 52 weeks. The major outcome measures were the Medical Research Council (MRC) sum score and hand-grip strength at week 52. This trial is registered with ClinicalTrials.gov, number NCT01827072. At week 52, 11 of the 13 patients completed the study, and all 11 had a sustained improvement. The mean (SD) MRC sum score was 85.6 (8.7) at the baseline, and 90.6 (12.8) at week 52. The mean grip strength was 39.2 (30.0) kPa at the baseline and 45.2 (32.8) kPa at week 52. Two patients dropped out because of adverse event (dysphagia) and decision of an investigator, respectively. Three patients developed coronary spasm, dysphagia, or inguinal herniation, reported as the serious adverse events, but considered not related with the study drug. The other adverse effects were mild and resolved by the end of the study period. Our results show that maintenance treatment with 1.0 g/kg IVIg every 3 week is safe and efficacious for MMN patients up to 52 weeks. Further studies are required to investigate optimal dose and duration of maintenance IVIg for MMN. © 2018 The Authors. Journal of the Peripheral Nervous System published by Wiley Periodicals, Inc. on behalf of Peripheral Nerve Society.

  20. Intravenous administration of high-dose Paclitaxel reduces gut-associated lymphoid tissue cell number and respiratory immunoglobulin A concentrations in mice.

    Science.gov (United States)

    Moriya, Tomoyuki; Fukatsu, Kazuhiko; Noguchi, Midori; Okamoto, Koichi; Murakoshi, Satoshi; Saitoh, Daizoh; Miyazaki, Masaru; Hase, Kazuo; Yamamoto, Junji

    2014-02-01

    Chemotherapy remains a mainstay of treatment for cancer patients. However, anti-cancer drugs frequently cause a wide range of side effects, including leukopenia and gastrointestinal toxicity. These adverse effects can lead to treatment delays or necessitate temporary dose reductions. Although chemotherapy-related changes in gut morphology have been demonstrated, the influences of chemotherapeutic regimens on gut immunity are understood poorly. This study aimed to examine whether the anti-cancer drug paclitaxel (PTX) impairs gut immunity in mice. Male ICR mice were randomized into three groups: Control, low-dose PTX (low PTX; 2 mg/kg), or high-dose PTX (high PTX; 4 mg/kg). A single intravenous dose was given. On day seven after the injection, lymphocytes from Peyer patches (PP), intraepithelial (IE) spaces, and the lamina propria (LP) were counted and analyzed by flow cytometry (CD4(+), CD8(+), αβTCR(+), γδTCR(+), B220(+)). Immunoglobulin A (IgA) concentrations were measured in small intestinal and respiratory tract washings. Total, CD4(+) and γδTCR(+) lymphocyte numbers in PPs were significantly lower in the high PTX than in the control group. The CD4(+) lymphocyte numbers in the IE spaces were significantly lower in both PTX groups than in the control group. Respiratory tract IgA concentrations were lower in the high PTX than in the control group. The present data suggest high-dose PTX impairs mucosal immunity, possibly rendering patients more vulnerable to infection. Careful dose selection and new therapies may be important for maintaining mucosal immunity during PTX chemotherapy.

  1. Preemptive intravenous immunoglobulin allows safe and timely administration of antineoplastic therapies in patients with multiple myeloma and parvovirus B19 disease.

    Science.gov (United States)

    Katragadda, L; Shahid, Z; Restrepo, A; Muzaffar, J; Alapat, D; Anaissie, E

    2013-08-01

    Parvovirus B19 (B19) disease is a rare cause of anemia in cancer patients and often goes unrecognized, causing delays in anticancer therapy. A retrospective review was carried out of the records of patients with multiple myeloma who underwent melphalan-based autologous stem cell transplantation (MEL-ASCT) and developed B19 infection (January 2009-December 2011). Cases were defined by the presence of clinical and laboratory findings consistent with B19 disease in patients with repeatedly positive plasma quantitative polymerase chain reaction for parvovirus. Six patients qualified as cases; 5 presented with trilineage cytopenias (chronic in 1) and 1 with anemia later progressing to pancytopenia. Transfusion-dependent thrombocytopenia led to testing in 5 patients. Two of these patients also had manifestations of autoimmune disease. Therapy with intravenous immunoglobulin (IVIG) resulted in clinical and hematologic response in all; however, 1 patient, whose white blood cell counts and serum hemoglobin levels improved, required splenectomy for persistent thrombocytopenia. All patients required additional IVIG for recurrent B19 disease. Although viral load at diagnosis did not correlate with the severity of cytopenia, its decrease was associated with response during 17 of 20 evaluable episodes (P = 0.02). Preemptive IVIG allowed the safe administration of chemotherapy in 3 patients, including MEL-ASCT in 1. Parvovirus B19 can cause severe disease in myeloma patients including ASCT recipients. Thrombocytopenia - not anemia - was the leading presentation and may be associated with autoimmune conditions. Patients with unexplained cytopenias, particularly when prolonged, should undergo testing for circulating parvovirus. A reduction in viral load was associated with response to IVIG, although additional therapy was needed for recurrent disease. Most importantly, preemptive IVIG allowed for safe and timely administration of antineoplastic therapy in patients with ongoing B

  2. Intravenous immunoglobulin treatment of the post-polio syndrome: sustained effects on quality of life variables and cytokine expression after one year follow up

    Directory of Open Access Journals (Sweden)

    Gonzalez Henrik

    2012-07-01

    Full Text Available Abstract Background Expression of inflammatory cytokines in cerebrospinal fluid (CSF has led to the hypothesis of intrathecal chronic inflammation to explain the denervation observed in post-polio syndrome (PPS. It has been shown that therapy with intravenous immunoglobulin (IVIG improves physical performance and dampens down the inflammatory process at 6 months in PPS patients. We here examined the effects of IVIG on cytokine expression and clinical outcome one year after IVIG treatment. Methods From a previous study with 135 PPS patients included, 41 patients were further evaluated before un-blinding for one year (21 placebo and 20 treated with IVIG, Xepol® 50 mg/ml, and were assessed for clinical variables by performing the Short Form-36 survey (SF-36 questionnaire assessment, the 6 minute walk distance test (6MWT and registering pain level by Visual Analogue Scale (VAS after IVIG treatment. A separate cohort of 37 PPS patients went through lumbar puncture (LP at baseline and 20 patients, treated with IVIG, repeated the LP one year later. Thirty patients affected with other neurological diseases (OND were used as control group. Inflammatory cytokines TNF, TGFβ, IFNγ, IL-23, IL-13 and IL-10 were measured in blood cells and CSF cells with RT-PCR. Results Scores of the physical components of SF-36 were significantly higher at the one year follow up time-point in the IVIG-treated patients when compared to baseline as well as to the control subjects. Pain VAS score and 6MWT improved significantly in the IVIG-treated patients when compared with baseline Relative expression of TNF and IFN-γ in both PBMCs and CSF from PPS patients were increased compared to OND subjects at baseline (p  Conclusions IVIG has effects on relevant QoL variables and inflammatory cytokines up to one year in patients with PPS. This gives a basis for scheduling IVIG in upcoming trials with this therapy.

  3. Production and purification of polyclonal antibody against F(ab')2 fragment of human immunoglobulin G

    OpenAIRE

    Nasiri, Hadi; Valedkarimi, Zahra; Aghebati-Maleki, Leili; Abdolalizadeh, Jalal; Kazemi, Tohid; Esparvarinha, Mojghan; Majidi, Jafar

    2017-01-01

    Antibodies are essential tools of biomedical and biochemical researches. Polyclonal antibodies are produced against different epitopes of antigens. Purified F(ab')2 can be used for animal’s immunization to produce polyclonal antibodies. Human immunoglobulin G (IgG) was purified by ion exchange chromatography method. In all stages verification method of the purified antibodies was sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Purified IgG was digested by pepsin enzyme a...

  4. Improved detection of a staphylococcal infection by monomeric and protein A-purified polyclonal human immunoglobulin

    International Nuclear Information System (INIS)

    Calame, W.

    1993-01-01

    The present study was undertaken to compare the technetium-99m labelled non-specific polyclonal human immunoglobulin (Ig) with 99m Tc-labelled monomeric human immunoglobulin (m-Ig), 99m Tc-labelled, protein A-purified, human immunoglobulin (A-IG) and 99m Tc-labelled monomeric, protein A-purified, human immunoglobulin (mA-Ig) as tracer agents for the detection of a thigh infection with Staphylococcus aureus. In vitro the binding of the various tracer agents to bacteria at various intervals was determined. For the in vivo evaluation, mice were infected and received one of the various labelled proteins. Scintigrams were made 0.25, 1, 4 and 24 h later. All 99m Tc-labelled Igs bound to bacteria in vitro: The percentages of binding for the m-Ig (from 1 h onwards) and A-Ig and mA-Ig (from 3 h onwards) were significantly higher than that for Ig. The in vivo target-to-non-target (T/NT) ratios were significantly higher from 4 h onwards for all purified Igs than for Ig. Protein A-purified Ig yielded higher T/NT ratios than m-Ig. Furthermore, the amount of activity in the liver was significantly lower 24 h after administration of m-Ig, A-Ig and mA-Ig than after administration of Ig. It is concluded that in this experimental infection 99m Tc-labelled monomeric Ig localizes a staphylococcal thigh infection better and faster than 99m Tc-labelled unpurified Ig. However, the accumulation obtained with protein A-purified Ig or protein A-purified monomeric Ig was the highest of all tracer agents tested. (orig.)

  5. Collaborative study for the validation of alternative in vitro potency assays for human tetanus immunoglobulins.

    Science.gov (United States)

    Gross, S; Janssen, S W J; de Vries, B; Terao, E; Daas, A; Buchheit, K-H

    2010-07-01

    An international collaborative study to validate 2 alternative in vitro methods for the potency testing of human tetanus immunoglobulin products was organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM). The study, run in the framework of the Biological Standardisation Programme (BSP) under the aegis of the European Commission and the Council of Europe, involved 21 official medicines control and industry laboratories from 15 countries. Both methods, an enzyme-linked immunoassay (EIA) and a toxoid inhibition assay (TIA), showed good reproducibility, repeatability and precision. EIA and TIA discriminated between low, medium and high potency samples. Potency estimates correlated well and both values were in close agreement with those obtained by in vivo methods. Moreover, these alternative methods allowed to resolve discrepant results between laboratories that were due to product potency loss and reporting errors. The study demonstrated that EIA and TIA are suitable quality control methods for tetanus immunoglobulin, which can be standardised in a control laboratory using a quality assurance system. Consequently, the Group of Experts on Human Blood and Blood Products of the European Pharmacopoeia revised the monograph on human tetanus immunoglobulins to include both the methods as compendial alternatives to the in vivo mouse challenge assay. 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

  6. 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 whic...

  7. A polyethylene glycol radioimmunoprecipitation assay for human immunoglobulin G

    International Nuclear Information System (INIS)

    Waller, S.J.; Taylor, R.P.; Andrews, B.S.

    1979-01-01

    A polyethylene glycol (PEG) radioimmunoprecipitation assay for human IgG is described that is sufficiently sensitive to detect 0.5 ng of IgG. This model antibody-antigen system was also used to study the stoichiometries of PEG-precipitation complexes. The results suggest that the presence of PEG may affect the stoichiometry of the complexes which precipitate from solution. (Auth.)

  8. Drug Use Evaluation of Human Intravenous Immunoglobulin (IVIG in a Teaching Hospital in East of Iran

    Directory of Open Access Journals (Sweden)

    Mandana Moradi

    2018-02-01

    Full Text Available different indications that only a few of them is now approved by the Food and Drug Administration (FDA as primary immunodeficiency, idiopathic thrombocytopenic purpura (ITP. Although it has been approved for selected indications, the list of its clinical indications, particularly off-labels, has grown considerably. Unfortunately, many of these conditions, lack sufficient clinical data of efficacy and might not always be appropriate.Method: It was a cross sectional study performed in Amir-al-momenin teaching hospital affiliated to Zabol University of medical sciences. All hospitalized patients who received IVIG during a 6 month period (autumn and winter 2015 were included in this study. We used predesigned data collection forms for data gathering as patient’s demographics, diagnoses, as well as drug related data, such as dose regimen, duration, rate of infusion, any related lab test.Results: In this study total of 49 patients received IVIG. Only in 25 cases, the mentioned indications were FDA approved (51%.Total of 189 IVIG vials (945 grams that cost 146,475,000 Tomans (39481 USD was administered during this study period, of which 560 grams (112vials (59.2% were used for FDA approved indications. From 19 ITP patients only 6 (12.2% fulfilled the criteria for IVIG therapy. Considering cases of wrong doses and whom were not indicated to receive IVIG therapy, total of (93 vials 465 grams, that cost 72,075,000 Tomans (19427 USD were spent irrationally.Conclusion: We concluded that IVIG was widely used irrationally in our institution and cost of this irrational administration is huge. This fact justifies the need for establishing multidisciplinary supervisory procedure in our hospital.

  9. Effect of Holder pasteurization on macronutrients and immunoglobulin profile of pooled donor human milk.

    Science.gov (United States)

    Adhisivam, B; Vishnu Bhat, B; Rao, Krishna; Kingsley, S M; Plakkal, Nishad; Palanivel, C

    2018-03-27

    The objective of this study was to study the effect of Holder pasteurization on macronutrients and immunoglobulin profile of pooled donor human milk. This descriptive study was conducted in a Human Milk Bank of a tertiary care teaching institute in south India. Thirty random paired pooled donor human milk samples (before and after pasteurization) were analyzed for macronutrients (protein, fat, carbohydrates) using infrared spectroscopy. Similarly, immunoglobulin profile (IgA and IgG) before and after pasteurization was quantified using ELISA. The mean values of protein, fat, and carbohydrates in pooled donor milk pre-pasteurization were 1.6, 3.6, and 6.1 g/dl compared with post-pasteurization values 1.4, 2.7, and 5.9 g/dl, respectively. Pasteurization reduced protein, fat, and energy content of pooled donor milk by 12.5%, 25%, and 16%, respectively. However, carbohydrates were not significantly reduced. Pasteurization decreased IgA by 30% and IgG by 60%. Holder pasteurization of pooled donor human milk decreases protein, fat, and energy content and also reduces the levels of IgA and IgG.

  10. Economic analysis of intravenous immunoglobulin and plasma exchange therapies for the treatment of Guillain-Barré Syndrome in a university-based hospital in the South of Brazil

    Directory of Open Access Journals (Sweden)

    Alexandre Paulo Machado de Brito

    2011-10-01

    Full Text Available Introduction: Direct costs for treating Guillain-Barré Syndrome (GBS represent a significant financial burden to public hospitals. Few studies compared the cost of plasma exchange (PE treatment with human intravenous immunoglobulin (IVIg. Objectives: To compare the cost of two therapies for GBS: IVIg and PE. Secondary objective was to evaluate compliance to IVIg prescription guidelines of the Pharmacy and Therapeutics Committee (PTC. Methods: A cross-sectional study included 25 patients with GBS admitted in a university affiliated hospital from June, 2003 through June, 2008. The costs of IVIg (n=20 and PE (n=5 were evaluated through the cost minimization method, considering direct medical costs yield by the management of the institution. Patients receiving treatments other than PE or IVIg were excluded. Data were collected by medical records review. Clinical endpoint was disability on discharge, established by the 7-point scale of Hughes. Compliance to the PTC guidelines was evaluated considering the dose and prescription regime of IVIg. Results: Twenty-five participants, ranging from 2 to 70 years of age, were included. No difference occurred in any medical variables related to the treatment or in the main clinical outcome measured by the Hughes’ scale. The mean direct cost of PE treatment was US$ 6,059± 1,701 per patient, and the same expense for IVIg was US$ 18,344±12,259 (P = 0.035. Total inpatient cost was US$ 25,730± 18,714 in the PE group, and 34,768± 27,766 (p=0.530 in the IVIg group. Conclusions: In a university-based hospital, PE is equally effective and less expensive than IVIg to treat GBS.

  11. Variations in riboflavin binding by human plasma: identification of immunoglobulins as the major proteins responsible

    International Nuclear Information System (INIS)

    Innis, W.S.; McCormick, D.B.; Merrill, A.H. Jr.

    1985-01-01

    Riboflavin binding by plasma proteins from healthy human subjects was examined by equilibrium dialysis using a physiological concentration of [2-14C]riboflavin (0.04 microM). Binding ranged from 0.080 to 0.917 pmole of riboflavin/mg of protein (with a mean +/- SD of 0.274 +/- 0.206), which corresponded to 4.14 to 49.4 pmole/ml of plasma (15.5 +/- 11.0) (N = 34). Males and females yielded similar results. Upon fractionation of plasma by gel filtration, the major riboflavin-binding components eluted with albumin and gamma-globulins. Albumin was purified and found to bind riboflavin only very weakly (Kd = 3.8 to 10.4 mM), although FMN and photochemical degradation products (e.g., lumiflavine and lumichrome) were more tightly bound. Binding in the gamma-globulin fraction was attributed to IgG and IGA because the binding protein(s) and immunoglobulins copurified using various methods were removed by treatment of plasma with protein A-agarose, and were coincident upon immunoelectrophoresis followed by autoradiography to detect [2-14C]riboflavin. Differences among the plasma samples correlated with the binding recovered with the immunoglobulins. Binding was not directly related to the total IgG or IgA levels of subjects. Hence, it appears that the binding is due to a subfraction of these proteins. These findings suggest that riboflavin-binding immunoglobulins are a major cause of variations in riboflavin binding in human circulation, and may therefore affect the utilization of this micronutrient

  12. High quality human immunoglobulin G purified from Cohn fractions by liquid chromatography

    Directory of Open Access Journals (Sweden)

    K. Tanaka

    2000-01-01

    Full Text Available In order to obtain intravenous immunoglobulin G (iv IgG of high quality from F-I+II+III or F-II+III pastes prepared by the Cohn method, we developed a chromatography process using ion exchange gels, Q-Sepharose FF and CM-Sepharose FF, and Sephacryl S-300 gel filtration. Viral inactivation was performed by incubating the preparation with pepsin at pH 4.0 at 35oC for 18 h. The characteristics of 28 batches produced by us were: yield 4.3 ± 0.2 g/l plasma, i.e., a recovery of 39.1 ± 1.8%; IgG subclasses distribution: IgG1 = 58.4%, IgG2 = 34.8%, IgG3 = 4.5% and IgG4 = 2.3%; IgG size distribution was 98.4% monomers, 1.2% dimers and 0.4% polymers and protein aggregates; anticomplement activity was less than 0.5 CH50/mg IgG, and prekallikrein activator activity (PKA was less than 5 IU/ml. These characteristics satisfied the requirements of the European Pharmacopoea edition, and the regulations of the Brazilian Health Ministry (M.S. Portaria No. 2, 30/10/1998.

  13. Pharmacokinetics of high-dose intravenous melatonin in humans

    DEFF Research Database (Denmark)

    Andersen, Lars P H; Werner, Mads U; Rosenkilde, Mette Marie

    2016-01-01

    This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60......, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments...... of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221...

  14. 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.

  15. 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.

  16. Thyroid Stimulating Immunoglobulin Bioassay Using Cultured Human Thyroid Cells; A Simplified Micromethod

    International Nuclear Information System (INIS)

    Lee, Myung Chul; Chung, June Key; Cho, Bo Youn; Koh, Chang Soon; Lee, Moon Ho; Ahn, Il Min; Ahn, Hee Kwon

    1985-01-01

    The activation of adenylate cyclase of human thymocytes in primary cell culture and the release of c-AMP into the medium are used to detect b-TSH and TSAb in sera of patients with autoimmune thyroid disease. Sera of patients are used directly as a part of cell culture without immunoglobulin precipitation. In the above TSI bioassay, TSAb pooled serum show c-AMP concentration between that of 1 mU/ml and 10 mU/ml b-TSH but normal control pooled serum doesn't show any detectable c-AMP response. Ninety five percent of untreated Graves' patients shows TSAb activity above normal range, 20% of Hashimoto's and 363/0 of euthyroid Graves' patients show detectable TSAb activity.

  17. Anti-ghrelin immunoglobulins modulate ghrelin stability and its orexigenic effect in obese mice and humans

    Science.gov (United States)

    Takagi, Kuniko; Legrand, Romain; Asakawa, Akihiro; Amitani, Haruka; François, Marie; Tennoune, Naouel; Coëffier, Moïse; Claeyssens, Sophie; do Rego, Jean-Claude; Déchelotte, Pierre; Inui, Akio; Fetissov, Sergueï O.

    2013-01-01

    Obese individuals often have increased appetite despite normal plasma levels of the main orexigenic hormone ghrelin. Here we show that ghrelin degradation in the plasma is inhibited by ghrelin-reactive IgG immunoglobulins, which display increased binding affinity to ghrelin in obese patients and mice. Co-administration of ghrelin together with IgG from obese individuals, but not with IgG from anorectic or control patients, increases food intake in rats. Similarly, chronic injections of ghrelin together with IgG from ob/ob mice increase food intake, meal frequency and total lean body mass of mice. These data reveal that in both obese humans and mice, IgG with increased affinity for ghrelin enhances ghrelin’s orexigenic effect, which may contribute to increased appetite and overeating. PMID:24158035

  18. Separation of hemagglutination-inhibiting immunoglobulin M antibody to rubella virus in human serum by high-performance liquid chromatography.

    OpenAIRE

    Kobayashi, N; Suzuki, M; Nakagawa, T; Matumoto, M

    1986-01-01

    High-performance liquid chromatography was successfully used to separate hemagglutination-inhibiting immunoglobulin M (IgM) rubella virus antibody from IgG rubella virus antibody in human serum. The fractionation by high-performance liquid chromatography was as effective as sucrose density gradient centrifugation in separating IgM antibody from IgG antibody.

  19. Immunochromatographic Brucella-specific immunoglobulin M and G lateral flow assays for rapid serodiagnosis of human brucellosis

    NARCIS (Netherlands)

    Smits, Henk L.; Abdoel, Theresia H.; Solera, Javier; Clavijo, Encarnacion; Diaz, Ramon

    2003-01-01

    To fulfill the need for a simple and rapid diagnostic test for human brucellosis, we used the immunochromatographic lateral flow assay format to develop two assays, one for the detection of Brucella-specific immunoglobulin M (IgM) antibodies and one for the detection of Brucella-specific IgG

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

    NARCIS (Netherlands)

    Lauc, G.; Huffman, J.E.; Pucic, M.; Zgaga, L.; Adamczyk, B.; Muzinic, A.; Novokmet, M.; Polasek, O.; Gornik, O.; Kristic, J.; Keser, T.; Vitart, V.; Scheijen, B.; Uh, H.W.; Molokhia, M.; Patrick, A.L.; McKeigue, P.; Kolcic, I.; Lukic, I.K.; Swann, O.; Leeuwen, F.N. van; Ruhaak, L.R.; Houwing-Duistermaat, J.J.; Slagboom, P.E.; Beekman, M.; Craen, A.J. de; Deelder, A.M.; Zeng, Q.; Wang, W.; Hastie, N.D.; Gyllensten, U.; Wilson, J.F.; Wuhrer, M.; Wright, A.F.; Rudd, P.M.; Hayward, C.; Aulchenko, Y.; Campbell, H.; Rudan, I.

    2013-01-01

    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

  1. Effective intravenous immunoglobulin therapy for Churg-Strauss syndrome (allergic granulomatous angiitis complicated by neuropathy of the eighth cranial nerve: a case report

    Directory of Open Access Journals (Sweden)

    Ozaki Yoshio

    2012-09-01

    Full Text Available Abstract Introduction We report the case of a patient with Churg-Strauss syndrome with eighth cranial nerve palsy. Vestibulocochlear nerve palsy is extremely rare in Churg-Strauss syndrome. To the best of our knowledge, only one case of complicated neuropathy of the eighth cranial nerve has been described in a previous report presenting an aggregate calculation, but no differentiation between polyarteritis nodosa and Churg-Strauss syndrome was made. High-dose immunoglobulin was administered to our patient, and her neuropathy of the eighth cranial nerve showed improvement. Case presentation At the age of 46, a Japanese woman developed Churg-Strauss syndrome that later became stable with low-dose prednisolone treatment. At the age of 52, she developed sudden difficulty of hearing in her left ear, persistent severe rotary vertigo, and mononeuritis multiplex. At admission, bilateral perceptive deafness of about 80dB and eosinophilia of 4123/μL in peripheral blood were found. A diagnosis of cranial neuropathy of the eighth cranial nerve associated with exacerbated Churg-Strauss syndrome was made. Although high doses of steroid therapy alleviated the inflammatory symptoms and markers, the vertigo and bilateral hearing loss remained. Addition of a high-dose immunoglobulin finally resulted in marked alleviation of the symptoms associated with neuropathy of the eighth cranial nerve. Conclusions A high dose of immunoglobulin therapy shows favorable effects in neuropathy of the eighth cranial nerve, but no reports regarding its efficacy in cranial neuropathy have been published.

  2. 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

  3. Effects of low concentrations of cadmium on immunoglobulin E production by human B lymphocytes in vitro

    International Nuclear Information System (INIS)

    Jelovcan, Sandra; Gutschi, Andrea; Kleinhappl, Barbara; Sedlmayr, Peter; Barth, Sonja; Marth, Egon

    2003-01-01

    Exposure to cadmium (Cd) can cause a variety of biological effects including alterations of immune responses in animals and humans. Both immunosuppression and immunoenhancement have been reported. The present study was aimed at investigating the consequences of exposure to Cd on the human immunoglobulin (Ig) E synthesis, using purified peripheral blood B lymphocytes and IL-4 and anti-human CD40 monoclonal antibody (a-CD40 mAb) as stimuli. Low concentrations of Cd (0.1-10 μM) markedly inhibited production of IgE in a concentration-dependent manner. IgG production, in contrast to IgE, showed a tendency towards being enhanced by Cd, although with a certain individual variability; IgM production was not affected. Cd failed to alter immediate surface expression of the activation markers CD69 and CD23 indicating that early activation events were not impaired. However, the portion of activated B cells was diminished by Cd after stimulation for more than 24 h, paralleled by a concomitant decrease in viability and a subsequent reduction in proliferation. These data suggest that the mechanism of Cd action on activated B cells involved pathways that interrupted an effectively initiated cell activation and induced a cytotoxic signal. Results from this study thus provide further evidence for and new information on the immunotoxic and immunomodulatory effects of Cd on human immune responses

  4. Characterization of immunoglobulin A kappa autoantibodies to human lactate dehydrogenase isoenzyme-3

    NARCIS (Netherlands)

    Weijers, R. N.; Oude Elferink, R. P.; Mulder, J.; Kruijswijk, H.

    1987-01-01

    We have purified with a cumulative recovery of 48% from the serum of a patient the immunoglobulin A kappa subunit of the lactate dehydrogenase-immunoglobulin A kappa (LD-IgA kappa) complex. It appears that the pI range of the complex is 5.4-5.8. The Ig part of the complex showed a monoclonal

  5. CP-25 Attenuates the Activation of CD4+ T Cells Stimulated with Immunoglobulin D in Human.

    Science.gov (United States)

    Wu, Yu-Jing; Chen, Heng-Shi; Chen, Wen-Sheng; Dong, Jin; Dong, Xiao-Jie; Dai, Xing; Huang, Qiong; Wei, Wei

    2018-01-01

    Researchers have shown that the level of immunoglobulin D (IgD) is often elevated in patients with autoimmune diseases. The possible roles of IgD on the function of human T cell activation are still unclear. Paeoniflorin-6'- O -benzene sulfonate (code: CP-25), the chemistry structural modifications of paeoniflorin, was a novel drug of anti-inflammation and immunomodulation. The aims of this study were to determine if human CD4 + T cells could be activated by IgD via the IgD receptor (IgDR)-Lck pathway and whether the novel compound CP-25 could affect the activation of T cells by regulating Lck. Human CD4 + T cells were purified from peripheral blood mononuclear cells using microbeads. T cell viability and proliferation were detected by Cell Counting Kit-8 and CFSE Cell Proliferation Kit. Cytokines secreted by T cells were assessed with the Quantibody Human Inflammation Array. The binding affinity and expression of IgDR on T cells were detected by flow cytometry, and protein expression of IgDR, Lck, and P-Lck were analyzed by western blot. IgD was shown to bind to IgDR on CD4 + T cells in a concentration-dependent manner and stimulate the activation and proliferation of these cells by enhancing phosphorylation of the activating tyrosine residue of Lck (Tyr 394 ). CP-25 inhibited the IgD-stimulated activation and proliferation of CD4 + T cells, as well as the production of inflammatory cytokines; it was thus suggested that this process might be related to the downregulation of Lck (Tyr 394 ) phosphorylation. These results demonstrate that IgD amplifies the activation of CD4 + T cells, which could be mediated by Lck phosphorylation. Further, CP-25, via its ability to modulate Lck, is a novel potential therapeutic agent for the treatment of human autoimmune diseases.

  6. 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.

  7. 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.

  8. Immunomodulatory treatment with intravenous immunoglobulin and prednisone in patients with recurrent miscarriage and implantation failure after in vitro fertilization/intracytoplasmic sperm injection

    DEFF Research Database (Denmark)

    Nyborg, Kathinka Marie; Kolte, Astrid Marie; Larsen, Elisabeth Clare

    2014-01-01

    OBJECTIVE: To assess outcome in terms of live-birth rate after fresh or frozen IVF/intracytoplasmic sperm injection assisted reproductive technology (ART) cycles where immunomodulation was given to patients with recurrent pregnancy loss after prior ART treatments. DESIGN: Retrospective cohort study....... SETTING: Tertiary care university hospital. PATIENT(S): Fifty-two patients with a history of at least three consecutive pregnancy losses after ART who underwent at least one further ART cycle with concurrent immunomodulation in 2003-2012. INTERVENTION(S): Immunomodulation with IV immunoglobulin...... and prednisone starting from before ET and continuing in the first trimester if pregnancy was established. MAIN OUTCOME MEASURE(S): Live-birth rate per ET and cumulative live-birth rate after up to five ETs. RESULT(S): Nineteen patients (36.5%) achieved a live birth after the first ET with immunomodulation...

  9. 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...... cytokines inhibited the production of IgA and IgG induced by anti-CD40 Ab alone. In combination with anti-CD40 Ab and IL-4, IgG4 were inhibited in cultures stimulated with IL-20, IL-22, IL-26, IL-28 and IL-29 compared with IL-4 and anti-CD40 Ab alone, whereas all IL-10 analogues increased the production...

  10. Unsuspected human immunodeficiency virus infection presenting as immunoglobulin G4-related lymphadenopathy: a case report.

    Science.gov (United States)

    Yu, Hsing-Tse; Lee, Chen-Hsiang; Huang, Shun-Chen; Yu, Shan-Fu

    2018-01-01

    Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated condition characterized by infiltration of the involved organs by IgG4-bearing plasma cells. The prevalence of autoimmune diseases, associated with or occurring in patients with human immunodeficiency virus (HIV) infection, has been increasing. We describe a 58-year-old man with an undiagnosed HIV infection, which presented as chronic cervical lymphadenopathy with an elevated serum IgG4 and a very high IgE. Histologically, lymph nodes showed expanded sinusoids and burnt-out germinal centers with increased plasmacytic infiltration and collagen fiber deposition. The absolute number of IgG4+ plasma cells and the IgG4+/IgG+ plasma cell ratio was increased. The lymph nodes were enlarged and clinically the patient improved after steroid treatment. Nine months later, he was diagnosed with acquired immune deficiency syndrome, following presentation with a cavitary left lung lesion. Immunohistochemical studies on the previously resected lymph node revealed complete absence of CD4+ T-lymphocytes and increased CD8+ T-lymphocytes. The pathologic findings met the criteria of both HIV infection and IgG4-related lymphadenopathy. Our case demonstrates that further investigations for underlying HIV infection in a case of IgG4-RD are critical, especially when extremely elevated IgE is concomitantly present.

  11. Decreased immunoglobulin production by a human lymphoid cell line following melphalan treatment

    Energy Technology Data Exchange (ETDEWEB)

    Griffin, G.D. (Oak Ridge National Lab., TN); Owen, B.A.; Atchley, C.E.; Novelli, G.D.; Solomon, A.

    1982-11-01

    The effect of melphalan on immunoglobulin G (IgG) production by a human lymphoblastoid cell line (BF) was studied. The amount of secreted IgG and the percentage of cells containing cytoplasmic IgG were measured by immunoassay and cytofluorometry, respectively. Dose-response studies indicated that melphalan concentrations of 2 x 10/sup -8/ M had no effect, while concentrations of 8 x 10/sup -7/ M were totally toxic, after 72-h exposures to the drug. Statistically significant, persistent, alterations in both synthesis and secretion of IgG by BF cells were observed following treatment for 72 h with 4 x 10/sup -7/ M melphalan, and there was an increase in population-doubling time from 24 to 72 h in these drug-treated cells. The percentage of IgG-containing cells in melphalan-treated cultures was significantly decreased as compared to control cultures. IgG secretion was also decreased in these cultures, and the variation in IgG secretion as a function of cellular growth was significantly altered following melphalan treatment. Decreased IgG production following melphalan treatment may be related to altered cell cycle kinetics. Based on immunological analysis, there was no evident alteration in the IgG secreted by melphalan-treated cells, nor did melphalan treatment produce a cellular population lacking IgG entirely.

  12. 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...

  13. Intravenous immunoglobulin use in managing severe, perioperative peristomal pyoderma gangrenosum following subtotal colectomy with end ileostomy for medically refractory chronic ulcerative colitis

    Science.gov (United States)

    Behm, Kevin; Larson, David W.; Colibaseanu, Dorin

    2015-01-01

    Peristomal pyoderma gangrenosum (PPG) is a rare subtype of pyoderma gangrenosum that is characterized by painful, necrotic ulcerations occurring in the area surrounding an abdominal stoma. PPG is typically seen in younger patients with active inflammatory bowel disease. The etiology and pathogenesis is largely unknown and risk factors are not well defined. Therapy typically involves a combination of aggressive local wound care and systemic medications. Diagnosis and management of PPG can be difficult and data on treatment are limited. We present a case of severe postoperative peristomal recalcitrant to conventional therapy successfully treated with intravenous immune globulin. PMID:25802252

  14. 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

  15. Genetic regulation of immunoglobulin E level in different pathological states: integration of mouse and human genetics

    Czech Academy of Sciences Publication Activity Database

    Gusareva, Elena; Kurey, Irina; Grekov, Igor; Lipoldová, Marie

    2014-01-01

    Roč. 89, č. 2 (2014), s. 375-405 ISSN 1464-7931 R&D Projects: GA ČR GA310/08/1697; GA MŠk LH12049 Institutional support: RVO:68378050 Keywords : Genetic control of complex diseases * Immunoglobulin E * Epistasis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 9.670, year: 2014

  16. Chimeric immunoglobulin E reactive with tumor-associated antigen activates human Fc epsilon RI bearing cells

    NARCIS (Netherlands)

    Luiten, R. M.; Warnaar, S. O.; Schuurman, J.; Pasmans, S. G.; Latour, S.; Daëron, M.; Fleuren, G. J.; Litvinov, S. V.

    1997-01-01

    Crosslinking of immunoglobulin E molecules that are bound to the Fc epsilon receptors expressed on mast cells or basophils triggers activation of these cells, resulting in the development of a type I hypersensitivity. Targeting this potent immune reaction towards tumors by using IgE that reacts with

  17. Normal human immunoglobulin G4 is bispecific: it has two different antigen-combining sites

    NARCIS (Netherlands)

    Schuurman, J.; van Ree, R.; Perdok, G. J.; van Doorn, H. R.; Tan, K. Y.; Aalberse, R. C.

    1999-01-01

    Unlike other immunoglobulin G (IgG) subclasses, IgG4 antibodies in plasma have been reported to be functionally monovalent. In this paper we show that the apparent monovalency of circulating IgG4 is caused by asymmetry of plasma IgG4. A large fraction of plasma IgG4 molecules have two different

  18. Signals sustaining human immunoglobulin V gene hypermutation in isolated germinal centre B cells

    NARCIS (Netherlands)

    K. Dahlenborg; J.D. Pound (J.); J. Gordon (Jocelynne); C.A.K. Borrebaeck (C. A K); R. Carlsson (R.)

    2000-01-01

    textabstractAffinity maturation of antibody responses depends on somatic hypermutation of the immunoglobulin V genes. Hypermutation is initiated specifically in proliferating B cells in lymphoid germinal centres but the signals driving this process remain unknown. This study identifies signals that

  19. Importance of neonatal immunoglobulin transfer for hippocampal development and behaviour in the newborn pig.

    Directory of Open Access Journals (Sweden)

    Kateryna Goncharova

    Full Text Available Neurological disorders are among the main clinical problems affecting preterm children and often result in the development of communication and learning disabilities later in life. Several factors are of importance for brain development, however the role of immunoglobulins (passive immunity transfer has not yet been investigated. Piglets are born agammaglobulinemic, as a result of the lack of transfer of maternal immunoglobulins in utero, thus, they serve as an ideal model to mimic the condition of immunoglobulin deficiency in preterm infants. Thirty six, unsuckled newborn piglets were fed an infant formula or colostrum and supplemented orally or intravenously with either species-specific or foreign immunoglobulin and then compared to both newborn and sow-reared piglets. Two days after the piglets were born behavioural tests (novel recognition and olfactory discrimination of conspecifics scent were performed, after which the piglets were sacrificed and blood, cerebrospinal fluid and hippocampi samples were collected for analyses. Both parameters of neuronal plasticity (neuronal maturation and synapse-associated proteins and behavioural test parameters appeared to be improved by the appearance of species-specific porcine immunoglulin in the circulation and cerebrospinal fluid of the piglets. In conclusion, we postulate possible positive clinical effects following intravenous infusion of human immunoglobulin in terms of neuronal plasticity and cognitive function in preterm infants born with low blood immunoglobulin levels.

  20. Expression of immunoglobulin G in human podocytes, and its role in cell viability and adhesion.

    Science.gov (United States)

    Jing, Ziyang; Deng, Hui; Ma, Junfan; Guo, Yanhong; Liang, Yaoxian; Wu, Rui; A, Lata; Geng, Zihan; Qiu, Xiaoyan; Wang, Yue

    2018-06-01

    Podocyte injury occurs during the initiation and development of numerous forms of glomerular disease, and antibodies targeting podocytes have become a biomarker for diagnosis and monitoring treatment response. Accumulating evidence has suggested that immunoglobulin (Ig) is expressed in non‑B lineage cells, including epithelial cancer cells, myeloid cells and several types of normal cells. The main aim of the present study was to ascertain the expression of IgG in human podocytes and to determine its potential role in cellular bioactivity. The present study detected positive staining for IgG heavy chain (Igγ) and its subtype γ4, and the light chains κ and λ in the cytoplasm or on the membrane by immunofluorescence. In addition, positive bands were detected for Igγ, γ1, γ3, γ4, κ and λ in the lysates of a podocyte cell line by western blotting. Mass spectrometry confirmed IgG1 as an intact tetramer in the culture supernatant. Constant region transcripts of Igγ, γ1, γ3, γ4, κ and λ were identified by reverse transcription‑polymerase chain reaction, and DNA sequencing of these transcripts revealed 96‑99% similarity with Ig mRNAs in the National Center for Biotechnology Information database. Compared with the diverse gene rearrangements from B cell-derived Ig, podocyte‑derived Ig exhibited conservative V(D)J patterns in the variable regions of Igγ and κ chains. Furthermore, the present study investigated the mechanism underlying IgG production in these cells by examining the expression of recombination activating gene (RAG)1, RAG2 and activation‑induced cytidine deaminase. The expression levels of these proteins suggested that podocyte‑derived Ig and traditional Ig may be generated in a similar manner. Furthermore, small interfering RNA‑mediated downregulation of IgG expression reduced podocyte viability and adhesive capabilities. These findings suggested that IgG is expressed in podocytes and that this expression may be associated

  1. A sensitive electrochemical immunosensor based on poly(2-aminobenzylamine) film modified screen-printed carbon electrode for label-free detection of human immunoglobulin G.

    Science.gov (United States)

    Putnin, Thitirat; Jumpathong, Watthanachai; Laocharoensuk, Rawiwan; Jakmunee, Jaroon; Ounnunkad, Kontad

    2018-08-01

    This work focuses on fabricating poly(2-aminobenzylamine)-modified screen-printed carbon electrode as an electrochemical immunosensor for the label-free detection of human immunoglobulin G. To selectively detect immunoglobulin G, the anti-immunoglobulin G antibody with high affinity to immunoglobulin G was covalently linked with the amine group of poly(2-aminobenzylamine) film-deposited screen-printed carbon electrode. The selectivity for immunoglobulin G was subsequently assured by being challenged with redox-active interferences and adventitious adsorption did not significantly interfere the analyte signal. To obviate the use of costly secondary antibody, the [Fe(CN) 6 ] 4-/3- redox probe was instead applied to measure the number of human immunoglobulin G through the immunocomplex formation that is quantitatively related to the level of the differential pulse voltammetric current. The resulting immunosensor exhibited good sensitivity with the detection limit of 0.15 ng mL -1 , limit of quantitation of 0.50 ng mL -1 and the linear range from 1.0 to 50 ng mL -1 . Given those striking analytical performances and the affordability arising from using cheap screen-printed carbon electrode with label-free detection, the immunosensor serves as a promising model for the next-step development of a diagnostic tool.

  2. Serum immunoglobulin levels in humans exposed to therapeutic total-body gamma irradiation

    International Nuclear Information System (INIS)

    Chaskes, S.; Kingdon, G.C.; Balish, E.

    1975-01-01

    Reduced serum immunoglobulin (IgA, IgG, IgM) levels developed in the majority of 27 patients with hematologic disorders after treatment with 100 to 350 R total-body gamma-ray exposures at a dose rate of either 1.5 R/min to 1.5 R/hr. A reduction in IgA of 20 percent or more was found in 66 percent of the cases, while 56 percent showed an IgM decrease, and 49 percent an IgG decrease of 20 percent. The severity of immunoglobulin depression was influenced by the total radiation dose and the patient's primary disease. The occurrence of IgG and IgM depression was greater when the radiation was given at 1.5 R/hr than when the dose rate was 1.5 R/min. Substantial but incomplete recovery toward preirradiation immunoglobulin levels was found for most patients by 7 wk after total-body irradiation (TBI). (U.S.)

  3. 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. Copyright © 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  4. First-pass metabolism of ethanol in human beings: effect of intravenous infusion of fructose

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Billinger, MH; Schäfer, C.

    2004-01-01

    Intravenous infusion of fructose has been shown to enhance reduced form of nicotinamide adenine dinucleotide reoxidation and, thereby, to enhance the metabolism of ethanol. In the current study, the effect of fructose infusion on first-pass metabolism of ethanol was studied in human volunteers....... A significantly higher first-pass metabolism of ethanol was obtained after administration of fructose in comparison with findings for control experiments with an equimolar dose of glucose. Because fructose is metabolized predominantly in the liver and can be presumed to have virtually no effects in the stomach...

  5. 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.

  6. Treatment of Alzheimer disease using combination therapy with plasma exchange and haemapheresis with albumin and intravenous immunoglobulin: Rationale and treatment approach of the AMBAR (Alzheimer Management By Albumin Replacement) study.

    Science.gov (United States)

    Boada, M; Ramos-Fernández, E; Guivernau, B; Muñoz, F J; Costa, M; Ortiz, A M; Jorquera, J I; Núñez, L; Torres, M; Páez, A

    2016-09-01

    There is a growing interest in new therapeutic strategies for the treatment of Alzheimer disease (AD) which focus on reducing the beta-amyloid peptide (Aβ) burden in the brain by sequestering plasma Aβ, a large proportion of which is bound to albumin and other proteins. This review discusses the concepts of interaction between Aβ and albumin that have given rise to AMBAR (Alzheimer's Disease Management by Albumin Replacement) project, a new multicentre, randomised, controlled clinical trial for the treatment of AD. Results from preliminary research suggest that Albutein(®) (therapeutic albumin, Grifols) contains no quantifiable levels of Aβ. Studies also show that Albutein(®) has Aβ binding capacity. On the other hand, AD entails a high level of nitro-oxidative stress associated with fibrillar aggregates of Aβ that can induce albumin modification, thus affecting its biological functions. Results from the phase ii study confirm that using therapeutic apheresis to replace endogenous albumin with Albutein(®) 5% is feasible and safe in patients with AD. This process resulted in mobilisation of Aβ and cognitive improvement in treated patients. The AMBAR study will test combination therapy with therapeutic apheresis and haemopheresis with the possible leverage effect of Albutein(®) with intravenous immunoglobulin replacement (Flebogamma(®) DIF). Cognitive, functional, and behavioural changes in patients with mild to moderate AD will be assessed. the AMBAR study represents a new therapeutic perspective for AD. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. 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

  8. Evaluation of 99mTc labelled human immunoglobulin (99mTc-HIG) in infection/inflammatory foci imaging. Final report for the period 15 December 1996 - 15 August 1997

    International Nuclear Information System (INIS)

    Shimpi, H.H.

    1997-10-01

    The aim of the study was to investigate whether the labelling efficiency biodistribution and inflammatory focus detection are dependent on the source of the human immunoglobulin G (HIG) and the chelating agent used in the labelling of the HIG with 99mTc. Three forms of immunoglobulins; Gamma venin P, Intraglobulin F and Sandoglobulin were used in this study. Reduction of HIG was done by 2-mercaptoethanol at molar ratio 1000:1, with 30 minutes reaction time at room temperature. The reduced HIG was then purified, membrane filtered aliquoted and lyophilised. Lyophilised HIG was dissolved in sterile normal saline and chelated with one of the following ligands Sn-MDP, SN PYP, Sn DTPA, SN-GH and Sn-citrate and then added 99m Tc04 for labelling. The radiochemical purity of the labelled compound was 90%. The biodistribution studies were done wistar rats where in the experimental groups were sacrifised at 3,5 and 24 hours following 99mTc HIG injection intravenously. Imaging studies were carried out in rabbits. Sterile inflammatory lesions were produced in the thigh muscle of these animals by injection of turpentine oil and the contralateral thigh muscle served as-controls. The results showed that there was no significant difference in biodistribution and inflammatory focus uptake of 9gmTc HIG with respect to the sources of HIG. There was favourable biodistribution characteristics when the ligands used were Sn MDP and Sn-Citrate

  9. 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. © 2015 International Society for Neurochemistry.

  10. Contemporary management of neonatal alloimmune thrombocytopenia: good outcomes in the intravenous immunoglobulin era: results from the Australian neonatal alloimmune thrombocytopenia registry.

    Science.gov (United States)

    Crighton, Gemma L; Scarborough, Ri; McQuilten, Zoe K; Phillips, Louise E; Savoia, Helen F; Williams, Bronwyn; Holdsworth, Rhonda; Henry, Amanda; Wood, Erica M; Cole, Stephen A

    2017-10-01

    To describe the natural history, antenatal and postnatal therapy, and clinical outcomes of Australian patients with fetomaternal/neonatal alloimmune thrombocytopenia (NAIT) recorded in the Australian NAIT registry. Analysis of registry data of Australian mothers treated antenatally for NAIT and any fetus/newborn with thrombocytopenia (TCP) and maternal human platelet antigen (HPA) antibodies. Ninety four potential cases (91 pregnancies; three twin pregnancies) were registered between December 2004 and September 2015 with 76 confirmed or treated as NAIT. NAIT was frequently unanticipated (44 cases, 58%), whilst 32 cases (42%) were anticipated due to personal or family history. In 70/76 cases, the diagnosis of NAIT was made based on HPA antibody results; anti-HPA-1a was most commonly detected (58/70, 82%), followed by anti-HPA-5b (5/70, 7%). Intracranial haemorrhage (ICH) was detected in seven cases (9%). Maternal antenatal therapy resulted in improved clinical outcomes. For antenatally treated cases, whilst 10/29 (34%) neonates had severe TCP, only one ICH was detected. This study provides data on contemporary "real world" management of Australian mothers and babies with NAIT. Antenatal IVIG therapy was associated with better neonatal outcomes. Maternal side-effects and treatment costs were substantial.

  11. Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk.

    Science.gov (United States)

    Van den Hout, Johanna M P; Kamphoven, Joep H J; Winkel, Léon P F; Arts, Willem F M; De Klerk, Johannes B C; Loonen, M Christa B; Vulto, Arnold G; Cromme-Dijkhuis, Adri; Weisglas-Kuperus, Nynke; Hop, Wim; Van Hirtum, Hans; Van Diggelen, Otto P; Boer, Marijke; Kroos, Marian A; Van Doorn, Pieter A; Van der Voort, Edwin; Sibbles, Barbara; Van Corven, Emiel J J M; Brakenhoff, Just P J; Van Hove, Johan; Smeitink, Jan A M; de Jong, Gerard; Reuser, Arnold J J; Van der Ploeg, Ans T

    2004-05-01

    Recent reports warn that the worldwide cell culture capacity is insufficient to fulfill the increasing demand for human protein drugs. Production in milk of transgenic animals is an attractive alternative. Kilogram quantities of product per year can be obtained at relatively low costs, even in small animals such as rabbits. We tested the long-term safety and efficacy of recombinant human -glucosidase (rhAGLU) from rabbit milk for the treatment of the lysosomal storage disorder Pompe disease. The disease occurs with an estimated frequency of 1 in 40,000 and is designated as orphan disease. The classic infantile form leads to death at a median age of 6 to 8 months and is diagnosed by absence of alpha-glucosidase activity and presence of fully deleterious mutations in the alpha-glucosidase gene. Cardiac hypertrophy is characteristically present. Loss of muscle strength prevents infants from achieving developmental milestones such as sitting, standing, and walking. Milder forms of the disease are associated with less severe mutations and partial deficiency of alpha-glucosidase. In the beginning of 1999, 4 critically ill patients with infantile Pompe disease (2.5-8 months of age) were enrolled in a single-center open-label study and treated intravenously with rhAGLU in a dose of 15 to 40 mg/kg/week. Genotypes of patients were consistent with the most severe form of Pompe disease. Additional molecular analysis failed to detect processed forms of alpha-glucosidase (95, 76, and 70 kDa) in 3 of the 4 patients and revealed only a trace amount of the 95-kDa biosynthetic intermediate form in the fourth (patient 1). With the more sensitive detection method, 35S-methionine incorporation, we could detect low-level synthesis of -glucosidase in 3 of the 4 patients (patients 1, 2, and 4) with some posttranslation modification from 110 kDa to 95 kDa in 1 of them (patient 1). One patient (patient 3) remained totally deficient with both detection methods (negative for cross

  12. Hepatic glycogen in humans. II. Gluconeogenetic formation after oral and intravenous glucose

    International Nuclear Information System (INIS)

    Radziuk, J.

    1989-01-01

    The amount of glycogen that is formed by gluconeogenetic pathways during glucose loading was quantitated in human subjects. Oral glucose loading was compared with its intravenous administration. Overnight-fasted subjects received a constant infusion or [3- 3 H]glucose and a marker for gluconeogenesis, [U- 14 C]lactate or sodium [ 14 C]bicarbonate [ 14 C]bicarbonate. An unlabeled glucose load was then administered. Postabsorptively, or after glucose infusion was terminated, a third tracer ([6- 3 H]glucose) infusion was initiated along with a three-step glucagon infusion. Without correcting for background stimulation of [ 14 C]glucose production or for dilution of 14 C with citric acid cycle carbon in the oxaloacetate pool, the amount of glycogen mobilized by the glucagon infusion that was produced by gluconeogenesis during oral glucose loading was 2.9 +/- 0.7 g calculated from [U- 14 C]-lactate incorporation and 7.4 +/- 1.3 g calculated using [ 14 C]bicarbonate as a gluconeogenetic marker. During intravenous glucose administration the latter measurement also yielded 7.2 +/- 1.1 g. When the two corrections above are applied, the respective quantities became 5.3 +/- 1.7 g for [U- 14 C]lactate as tracer and 14.7 +/- 4.3 and 13.9 +/- 3.6 g for oral and intravenous glucose with [ 14 C]bicarbonate as tracer (P less than 0.05, vs. [ 14 C]-lactate as tracer). When [2- 14 C]acetate was infused, the same amount of label was incorporated into mobilized glycogen regardless of which route of glucose administration was used. Comparison with previous data also suggests that 14 CO 2 is a potentially useful marker for the gluconeogenetic process in vivo

  13. Expression of members of immunoglobulin gene family in somatic cell hybrids between human B and T cells

    International Nuclear Information System (INIS)

    Kozbor, D.; Burioni, R.; Ar-Rushdi, A.; Zmijewski, C.; Croce, C.M.

    1987-01-01

    Somatic cell hybrids were obtained between human T and B cells and tested for the expression of differentiated traits of both cell lineages. The T-cell parent SUP-T1 is CD3 - , CD4 + , CD1 + , CD8 + , is weakly positive for HLA class I determinants, and has an inversion of chromosome 14 due to a site-specific recombination event between an immunoglobulin heavy-chain variable gene and the joining segment of the T-cell receptor α chain. The B-cell parent, the 6-thioguanine- and ouabain-resistant mutant GM1500, is a lymphoblastoid cell line that secretes IgG2, K chains, and expresses B1, B532, and HLA class I and II antigens. All hybrids expressed characteristics of B cells (Ig + , B1 + , B532 + , EBNA + , HLA antigens), whereas only CD4 among the T-cell markers was expressed. The level of T-cell receptor β-chain transcript was greatly reduced and no RNA of the chimeric T-cell receptor α-chain joining segment-immunoglobulin heavy-chain variable region was detected. Southern blot analysis indicated that absence of T-cell differentiation markers in the hybrids was not due to chromosomal loss. Rather, some B-cell-specific factor present in the hybrids may account for the suppression

  14. Implicit transitive inference and the human hippocampus: does intravenous midazolam function as a reversible hippocampal lesion?

    Directory of Open Access Journals (Sweden)

    Greene Anthony J

    2007-09-01

    Full Text Available Abstract Recent advances have led to an understanding that the hippocampus is involved more broadly than explicit or declarative memory alone. Tasks which involve the acquisition of complex associations involve the hippocampus whether the learning is explicit or implicit. One hippocampal-dependent implicit task is transitive inference (TI. Recently it was suggested that implicit transitive inference does not depend upon the hippocampus (Frank, M. J., O'Reilly, R. C., & Curran, T. 2006. When memory fails, intuition reigns: midazolam enhances implicit inference in humans. Psychological Science, 17, 700–707. The authors demonstrated that intravenous midazolam, which is thought to inactivate the hippocampus, may enhance TI performance. Three critical assumptions are required but not met: 1 that deactivations of other regions could not account for the effect 2 that intravenous midazolam does indeed deactivate the hippocampus and 3 that midazolam influences explicit but not implicit memory. Each of these assumptions is seriously flawed. Consequently, the suggestion that implicit TI does not depend upon the hippocampus is unfounded.

  15. Generation of Immunoglobulin diversity in human gut-associated lymphoid tissue.

    Science.gov (United States)

    Spencer, Jo; Barone, Francesca; Dunn-Walters, Deborah

    2009-06-01

    The organised gut associated lymphoid tissue (GALT) exists adjacent to an extensive and diverse luminal flora. The follicle associated epithelium and associated dendritic cells and lymphocytes form a tightly fortified gateway between the flora and the host that permits connectivity between them and chronic activation of the lymphoid compartment. As a consequence, plasma cell precursors are generated continuously, and in abundance, in GALT by clonal proliferation. Clonal proliferation alone on this scale would reduce the spectrum of B cell specificity. To compensate, GALT also houses molecular machinery that diversifies the receptor repertoire by somatic hypermutation, class switch recombination and receptor revision. These three processes of enhancing the diversity of mature B cells ensure that although clonally related plasma cells may secrete immunoglobulin side by side in the mucosa they rarely have identical antigen binding sites.

  16. Intravenous immunoglobulin prophylaxis in neonates on artificial ...

    African Journals Online (AJOL)

    Bone heap formed as the urrent ediate. 1. ging in analysis. ra;my in r Med pected. ,ng ,n ... antibody action, or to induce an opsonophagocytic effect, as shown in vitro in ... possible, a milk formula was given. The diagnosis of ..... to group Srreprococcus reactivity ano m VJVO protection agains1 multiple serotypes. J Exp Med ...

  17. Intravenous immunoglobulin prophylaxis in neonates on artificial ...

    African Journals Online (AJOL)

    There were no significant differences in the treated and placebo groups with regard to the frequency of positive blood cultures 28.6% and 14.3%), endotracheal cultures ... Analyses of subgroups of patients with different diagnoses revealed no differences except a trend suggesting fewer infections in term babies treated with ...

  18. Rotavirus specific plasma secretory immunoglobulin in children with acute gastroenteritis and children vaccinated with an attenuated human rotavirus vaccine

    Science.gov (United States)

    Herrera, Daniel; Vásquez, Camilo; Corthésy, Blaise; Franco, Manuel A; Angel, Juana

    2013-01-01

    Rotavirus (RV)–specific secretory immunoglobulin (RV-SIg) has been previously detected in serum of naturally RV infected children and shown to reflect the intestinal Ig immune response. Total plasma SIgA and plasma RV-SIg were evaluated by ELISA in children with gastroenteritis due or not due to RV infection and in 50 children vaccinated with the attenuated RIX4414 human RV vaccine and 62 placebo recipients. RV-SIg was only detected in children with evidence of previous RV infection or with acute RV gastroenteritis. Vaccinees had higher RV-SIg titers than placebo recipients and RV-SIg titers increased after the second vaccine dose. RV-SIg measured after the second dose correlated with protection when vaccinees and placebo recipients were analyzed jointly. RV-SIg may serve as a valuable correlate of protection for RV vaccines. PMID:23839157

  19. 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

  20. Fish Immunoglobulins

    OpenAIRE

    Sara Mashoof; Michael F. Criscitiello

    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 immunoglob...

  1. Anti-influenza Hyperimmune Immunoglobulin Enhances Fc-functional Antibody Immunity during Human Influenza Infection.

    Science.gov (United States)

    Vanderven, Hillary A; Wragg, Kathleen; Ana-Sosa-Batiz, Fernanda; Kristensen, Anne B; Jegaskanda, Sinthujan; Wheatley, Adam K; Wentworth, Deborah; Wines, Bruce D; Hogarth, P Mark; Rockman, Steve; Kent, Stephen J

    2018-05-31

    New treatments for severe influenza are needed. Passive transfer of influenza-specific hyperimmune pooled immunoglobulin (Flu-IVIG) boosts neutralising antibody responses to past strains in influenza-infected subjects. The effect of Flu-IVIG on antibodies with Fc-mediated functions, which may target diverse influenza strains, is unclear. We studied the capacity of Flu-IVIG, relative to standard IVIG, to bind to Fc receptors and mediate antibody-dependent cellular cytotoxicity in vitro. The effect of Flu-IVIG infusion, compared to placebo infusion, was examined in serial plasma samples from 24 subjects with confirmed influenza infection in the INSIGHT FLU005 pilot study. Flu-IVIG contains higher concentrations of Fc-functional antibodies than IVIG against a diverse range of influenza hemagglutinins. Following infusion of Flu-IVIG into influenza-infected subjects, a transient increase in Fc-functional antibodies was present for 1-3 days against infecting and non-infecting strains of influenza. Flu-IVIG contains antibodies with Fc-mediated functions against influenza virus and passive transfer of Flu-IVIG increases anti-influenza Fc-functional antibodies in the plasma of influenza-infected subjects. Enhancement of Fc-functional antibodies to a diverse range of influenza strains suggests that Flu-IVIG infusion could prove useful in the context of novel influenza virus infections, when there may be minimal or no neutralising antibodies in the Flu-IVIG preparation.

  2. 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

    2014-04-08

    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.

  3. Micro-bead injection spectroscopy for label-free automated determination of immunoglobulin G in human serum.

    Science.gov (United States)

    Ramos, Inês I; Magalhães, Luís M; Barreiros, Luisa; Reis, Salette; Lima, José L F C; Segundo, Marcela A

    2018-01-01

    Immunoglobulin G (IgG) represents the major fraction of antibodies in healthy adult human serum, and deviations from physiological levels are a generic marker of disease corresponding to different pathologies. Therefore, screening methods for IgG evaluation are a valuable aid to diagnostics. The present work proposes a rapid, automatic, and miniaturized method based on UV-vis micro-bead injection spectroscopy (μ-BIS) for the real-time determination of human serum IgG with label-free detection. Relying on attachment of IgG in rec-protein G immobilized in Sepharose 4B, a bioaffinity column is automatically assembled, where IgG is selectively retained and determined by on-column optical density measurement. A "dilution-and-shoot" approach (50 to 200 times) was implemented without further sample treatment because interferences were flushed out of the column upon sample loading, with minimization of carryover and cross-contamination by automatically discarding the sorbent (0.2 mg) after each determination. No interference from human serum albumin at 60 mg mL -1 in undiluted sample was found. The method allowed IgG determination in the range 100-300 μg mL -1 (corresponding to 5.0-60 mg mL -1 in undiluted samples), with a detection limit of 33 μg mL -1 (1.7 mg mL -1 for samples, dilution factor of 50). RSD values were time-to-result decreased from several hours to times, showing the potential of the proposed approach as a point-of-care method. Graphical abstract Micro-Bead Injection Spectroscopy method for real time, automated and label-free determination of total serum human Immunoglobulin G (IgG). The method was designed for Lab-on-Valve (LOV) platforms using a miniaturised protein G bioaffinity separative approach. IgG are separated from serum matrix components upon quantification with low non-specific binding in less than 5 min.

  4. 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

  5. Effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Fuglsang, Stefan; Graff, J

    2006-01-01

    : To examine the effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function after a meal in healthy humans. METHODS: Nine healthy volunteers participated in a placebo-controlled, double-blind, crossover study. Each volunteer was examined during intravenous infusion...... of glyceryl trinitrate 1 microg/kg x min or saline. A gamma camera technique was used to measure gastric emptying and small intestinal transit after a 1600-kJ mixed liquid and solid meal. Furthermore, duodenal motility was assessed by manometry. RESULTS: Glyceryl trinitrate did not change gastric mean...... emptying time, gastric half emptying time, gastric retention at 15 min or small intestinal mean transit time. Glyceryl trinitrate did not influence the frequency of duodenal contractions, the amplitude of duodenal contractions or the duodenal motility index. CONCLUSIONS: Intravenous infusion of glyceryl...

  6. 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.

  7. Pharmacokinetics and pharmacodynamics of eltanolone (pregnanolone), a new steroid intravenous anaesthetic, in humans

    DEFF Research Database (Denmark)

    Carl, Peder; Høgskilde, S; Lang-Jensen, T

    1994-01-01

    Eltanolone, a new intravenous steroid anaesthetic agent was administered intravenously in a dose of 0.6 mg.kg-1 over 45 s to eight healthy male volunteers to evaluate some of its pharmacokinetic and pharmacodynamic effects. Drug concentration-time data were analysed by PCNONLIN, a non...

  8. The interaction between calreticulin and 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...

  9. 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

    protein adsorption from diluted human serum solutions with relatively low protein concentrations, but the nonfouling character was weakened when less diluted human serum solutions with higher protein concentrations were used. The observed adsorption trend is independent of adsorption time, indicating...

  10. A radiolabeled antiglobulin assay to identify human cervical mucus immunoglobulin (Ig) A and IgG antisperm antibodies

    International Nuclear Information System (INIS)

    Haas, G.G. Jr.; D'Cruz, O.J.

    1989-01-01

    Antisperm immunoglobulin (Ig) A and IgG antibodies in human cervical mucus (CM) were identified by a radiolabeled antiglobulin assay. Cervical mucus samples from fertile and infertile women were exposed to a 1:3,200 dilution of 2-mercaptoethanol (2-ME), and 5 micrograms of the solubilized CM protein were assayed for the presence of IgA and IgG antisperm and anti-Candida activity by the radiolabeled antiglobulin assay. Purified human secretory IgA and IgG exposed to 2-ME retained the molecular integrity and functional activity of the untreated antibody molecules. CM aliquots collected after high-performance liquid chromatography (HPLC) fractionation were assessed for antisperm antibody activity; antisperm antibody activity was retained in the appropriate IgA or IgG CM fractions. The incidence of CM antisperm antibodies was minimally affected when the radiolabeled antiglobulin assay was performed with a motile sperm population. Approximately 70% of the CM IgA antisperm antibodies were of the IgA1 subclass; CM IgG was primarily of the IgG4 subclass. When Candida antigen was substituted for sperm in the radiolabeled antiglobulin assay, the CM antisperm antibodies were found to be exclusively sperm-specific. These data indicate that the radiolabeled antiglobulin assay using 2-ME to extract CM antibodies is a specific method for the assay of antisperm antibodies in CM

  11. Binding of 99mTc-labelled polyclonal human immunoglobulin to bacteria as a mechanism for scintigraphic detection of infection

    International Nuclear Information System (INIS)

    Calame, W.; Furth, R. van

    1991-01-01

    The aim of the present study was to determine whether 99m Tc-labelled polyclonal human immunoglobulin ( 99m Tc-HIG) binds to bacteria in vitro as well as in vivo. In vitro, the binding of 99m Tc-HIG to various gram-positive and gram-negative bacteria was determined. In vivo, mice were infected with Staphylococcus aureus Cowan I (protein A rich) or S. aureus EMS (protein A deficient) in a tigh muscle and then 99m Tc-HIG or 99m Tc-labelled human serum albumin ( 99m Tc-HSA) was administered; scintigrams were made 1, 4 and 18 h later. In vitro binding of 99m Tc-HIG to bacteria was higher for gram-positive than for gram-negative forms. A positive correlation was found between the protein A content and the degree of binding to S. aureus. This was also found in vivo. The accumulation of 99m Tc-HIG at the site of infection was significantly (P 99m Tc-HSA, for both strains of S. aureus. It is concluded that vascular permeability cannot fully explain the accumulation of 99m Tc-HIG at the site of infection and that binding of 99m Tc-HIG to bacteria plays a role in this respect. (orig.)

  12. 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

  13. 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...

  14. Immunoglobulin lambda light chain gene rearrangements in human B-cell malignancies

    NARCIS (Netherlands)

    T. Tümkaya (Talip)

    1997-01-01

    textabstractLymphocytes form the specific immune system, capable of recognizing and responding to any foreign antigen, while remaining indifferent to self components. Throughout human life, lymphocytes are continuously generated from pluripotent hematopoietic stem cells. These hematopoietic stem

  15. 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...

  16. Treatment with HPMA copolymer-based doxorubicin conjugate containing human immunoglobulin induces long-lasting systemic anti-tumour immunity in mice

    Czech Academy of Sciences Publication Activity Database

    Šírová, Milada; Strohalm, Jiří; Šubr, Vladimír; Plocová, Daniela; Rossmann, Pavel; Mrkvan, Tomáš; Ulbrich, Karel; Říhová, Blanka

    2007-01-01

    Roč. 56, - (2007), s. 35-47 ISSN 0340-7004 R&D Projects: GA MŠk 1M0505; GA ČR GA305/05/2268 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z40500505 Keywords : targered tumour therapy * hpma * human immunoglobulin Subject RIV: EE - Microbiology, Virology Impact factor: 3.728, year: 2007

  17. 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.

  18. Soluble suppressor supernatants elaborated by concanavalin A-activated human mononuclear cells. Characterization of a soluble suppressor of B cell immunoglobulin production

    International Nuclear Information System (INIS)

    Fleisher, T.A.; Greene, W.C.; Blaese, R.M.; Waldmann, T.A.

    1981-01-01

    Human peripheral blood mononuclear cells (PBMC) activated with the mitogenic lectin concanavalin A (Con A) elaborate a soluble immune suppressor supernatant (SISS) that contains at least 2 distinct suppressor factors. One of these, SISS-B, inhibits polyclonal B cell immunoglobulin production, whereas the other, SISS-T, suppresses T cell proliferation to both mitogens and antigens. The latter mediator is discussed in the companion paper. Characteristics of the human soluble suppressor of B cell immunoglobulin production (SISS-B) include: 1) inhibition by a noncytotoxic mechanism, 2) loss of activity in the presence of the monosaccharide L-rhamnose, 3) appearance within 8 to 16 hr after the addition of Con A, 4) elaboration by cells irradiated with 500 or 2000 rads, 5) production by highly purified T cells, 6) stability at pH 2.5 but instability at 56/sup o/C, and 7) m.w. of 60 to 80,000. These data indicate that after Con A activation, selected T cells not only become potent suppressor cells, but also generate a soluble saccharide-specific factor(s) that inhibits polyclonal immunoglobulin production by human B cells

  19. Systemic administration of antiretrovirals prior to exposure prevents rectal and intravenous HIV-1 transmission in humanized BLT mice.

    Directory of Open Access Journals (Sweden)

    Paul W Denton

    2010-01-01

    Full Text Available Successful antiretroviral pre-exposure prophylaxis (PrEP for mucosal and intravenous HIV-1 transmission could reduce new infections among targeted high-risk populations including discordant couples, injection drug users, high-risk women and men who have sex with men. Targeted antiretroviral PrEP could be particularly effective at slowing the spread of HIV-1 if a single antiretroviral combination were found to be broadly protective across multiple routes of transmission. Therefore, we designed our in vivo preclinical study to systematically investigate whether rectal and intravenous HIV-1 transmission can be blocked by antiretrovirals administered systemically prior to HIV-1 exposure. We performed these studies using a highly relevant in vivo model of mucosal HIV-1 transmission, humanized Bone marrow/Liver/Thymus mice (BLT. BLT mice are susceptible to HIV-1 infection via three major physiological routes of viral transmission: vaginal, rectal and intravenous. Our results show that BLT mice given systemic antiretroviral PrEP are efficiently protected from HIV-1 infection regardless of the route of exposure. Specifically, systemic antiretroviral PrEP with emtricitabine and tenofovir disoproxil fumarate prevented both rectal (Chi square = 8.6, df = 1, p = 0.003 and intravenous (Chi square = 13, df = 1, p = 0.0003 HIV-1 transmission. Our results indicate that antiretroviral PrEP has the potential to be broadly effective at preventing new rectal or intravenous HIV transmissions in targeted high risk individuals. These in vivo preclinical findings provide strong experimental evidence supporting the potential clinical implementation of antiretroviral based pre-exposure prophylactic measures to prevent the spread of HIV/AIDS.

  20. Radioimmunoassay to quantitatively measure cell surface immunoglobulins

    International Nuclear Information System (INIS)

    Krishman, E.C.; Jewell, W.R.

    1975-01-01

    A radioimmunoassay techniques developed to quantitatively measure the presence of immunoglobulins on the surface of cells, is described. The amount of immunoglobulins found on different tumor cells varied from 200 to 1140 ng/10 6 cells. Determination of immunoglobulins on the peripheral lymphocytes obtained from different cancer patients varied between 340 to 1040 ng/10 6 cells. Cultured tumor cells, on the other hand, were found to contain negligible quantities of human IgG [pt

  1. Conjugation of hydroxyapatite nanocrystals with human immunoglobulin G for nanomedical applications.

    Science.gov (United States)

    Iafisco, Michele; Varoni, Elena; Di Foggia, Michele; Pietronave, Stefano; Fini, Milena; Roveri, Norberto; Rimondini, Lia; Prat, Maria

    2012-02-01

    Inorganic nanosized drug carriers are a promising field in nanomedicine applied to cancer. Their conjugation with antibodies combines the properties of the nanoparticles themselves with the specific and selective recognition ability of the antibodies to antigens. Biomimetic carbonate-hydroxyapatite (HA) nanoparticles were synthesized and fully characterized; human IgGs, used as model antibodies, were coupled to these nanocrystals. The maximum loading amount, the interaction modelling, the preferential orientation and the secondary structure modifications were evaluated using theoretical models (Langmuir, Freundlich and Langmuir-Freundlich) spectroscopic (UV-Vis, Raman), calorimetric (TGA), and immunochemical techniques (ELISA, Western Blot). HA nanoparticles of about 30 nm adsorbed human IgGs, in a dose-dependent, saturable and stable manner with micromolar affinity and adsorption capability around 2.3 mg/m(2). Adsorption isotherm could be described by Langmuir-Freundlich model, and was due to both energetically homogeneous and heterogeneous binding sites on HA surface, mainly of electrostatic nature. Binding did not induce secondary structure modification of IgGs. A preferential IgG end-on orientation with the involvement of IgG Fc moiety in the adsorption seems most probable due to the steric hindrance of their Fab domains. Biomimetic HA nanocrystals are suitable substrates to produce nanoparticles which can be functionalized with antibodies for efficient targeted drug delivery to tumours. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function in healthy humans

    DEFF Research Database (Denmark)

    Madsen, Jan Lysgård; Fuglsang, Stefan; Graff, J

    2006-01-01

    of glyceryl trinitrate 1 microg/kg x min or saline. A gamma camera technique was used to measure gastric emptying and small intestinal transit after a 1600-kJ mixed liquid and solid meal. Furthermore, duodenal motility was assessed by manometry. RESULTS: Glyceryl trinitrate did not change gastric mean......BACKGROUND: Glyceryl trinitrate is a donor of nitric oxide that relaxes smooth muscle cells of the gastrointestinal tract. Little is known about the effect of glyceryl trinitrate on gastric emptying and no data exist on the possible effect of glyceryl trinitrate on small intestinal transit. AIM......: To examine the effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function after a meal in healthy humans. METHODS: Nine healthy volunteers participated in a placebo-controlled, double-blind, crossover study. Each volunteer was examined during intravenous infusion...

  3. The nanoscale spatial organization of B-cell receptors on immunoglobulin M- and G-expressing human B-cells.

    Science.gov (United States)

    Lee, Jinmin; Sengupta, Prabuddha; Brzostowski, Joseph; Lippincott-Schwartz, Jennifer; Pierce, Susan K

    2017-02-15

    B-cell activation is initiated by the binding of antigen to the B-cell receptor (BCR). Here we used dSTORM superresolution imaging to characterize the nanoscale spatial organization of immunoglobulin M (IgM) and IgG BCRs on the surfaces of resting and antigen--activated human peripheral blood B-cells. We provide insights into both the fundamental process of antigen-driven BCR clustering and differences in the spatial organization of IgM and IgG BCRs that may contribute to the characteristic differences in the responses of naive and memory B-cells to antigen. We provide evidence that although both IgM and IgG BCRs reside in highly heterogeneous protein islands that vary in size and number of BCR single-molecule localizations, both resting and activated B-cells intrinsically maintain a high -frequency of single isolated BCR localizations, which likely represent BCR monomers. IgG BCRs are more clustered than IgM BCRs on resting cells and form larger protein islands after antigen activation. Small, dense BCR clusters likely formed via protein-protein interactions are present on the surface of resting cells, and antigen activation induces these to come together to form less dense, larger islands, a process likely governed, at least in part, by protein-lipid interactions. © 2017 Lee, Sengupta, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  4. 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...

  5. Structural Basis of Human Parechovirus Neutralization by Human Monoclonal Antibodies

    NARCIS (Netherlands)

    Shakeel, Shabih; Westerhuis, Brenda M.; Ora, Ari; Koen, Gerrit; Bakker, Arjen Q.; Claassen, Yvonne; Wagner, Koen; Beaumont, Tim; Wolthers, Katja C.; Butcher, Sarah J.

    2015-01-01

    Since it was first recognized in 2004 that human parechoviruses (HPeV) are a significant cause of central nervous system and neonatal sepsis, their clinical importance, primarily in children, has started to emerge. Intravenous immunoglobulin treatment is the only treatment available in such

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

    Science.gov (United States)

    Hsieh, Ching-Lin; Tseng, Andrew; He, Hongxuan; Kuo, Chih-Jung; Wang, Xuannian; Chang, Yung-Fu

    2017-01-01

    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.

  7. 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.

  8. The antigen-binding fragment of human gamma immunoglobulin prevents amyloid β-peptide folding into β-sheet to form oligomers

    Science.gov (United States)

    Valls-Comamala, Victòria; Guivernau, Biuse; Bonet, Jaume; Puig, Marta; Perálvarez-Marín, Alex; Palomer, Ernest; Fernàndez-Busquets, Xavier; Altafaj, Xavier; Tajes, Marta; Puig-Pijoan, Albert; Vicente, Rubén; Oliva, Baldomero; Muñoz, Francisco J.

    2017-01-01

    The amyloid beta-peptide (Aβ) plays a leading role in Alzheimer's disease (AD) physiopathology. Even though monomeric forms of Aβ are harmless to cells, Aβ can aggregate into β-sheet oligomers and fibrils, which are both neurotoxic. Therefore, one of the main therapeutic approaches to cure or delay AD onset and progression is targeting Aβ aggregation. In the present study, we show that a pool of human gamma immunoglobulins (IgG) protected cortical neurons from the challenge with Aβ oligomers, as assayed by MTT reduction, caspase-3 activation and cytoskeleton integrity. In addition, we report the inhibitory effect of IgG on Aβ aggregation, as shown by Thioflavin T assay, size exclusion chromatography and atomic force microscopy. Similar results were obtained with Palivizumab, a human anti-sincitial virus antibody. In order to dissect the important domains, we cleaved the pool of human IgG with papain to obtain Fab and Fc fragments. Using these cleaved fragments, we functionally identified Fab as the immunoglobulin fragment inhibiting Aβ aggregation, a result that was further confirmed by an in silico structural model. Interestingly, bioinformatic tools show a highly conserved structure able to bind amyloid in the Fab region. Overall, our data strongly support the inhibitory effect of human IgG on Aβ aggregation and its neuroprotective role. PMID:28467807

  9. 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

  10. Enhanced opsonisation of Rhesus D-positive human red blood cells by recombinant polymeric immunoglobulin G anti-G antibodies.

    Science.gov (United States)

    Díaz-Solano, Dylana; Fuenmayor, Jaheli; Montaño, Ramon F

    2018-02-01

    Anti-RhD antibodies (anti-D) are important in the prophylaxis of haemolytic disease of the foetus and newborn (HDFN) due to RhD incompatibility. Current preparations of anti-D are sourced from hyperimmune human plasma, so its production carries a risk of disease and is dependent on donor availability. Despite the efforts to develop a monoclonal preparation with similar prophylactic properties to the plasma-derived anti-D, no such antibody is yet available. Here we studied the agglutinating, opsonic and haemolytic activities of two recombinant polymeric immunoglobulins (Ig) against the G antigen of the Rh complex. Recombinant polymeric anti-G IgG1 (IgG1μtp) and IgG3 (IgG3μtp) were produced in vitro, purified by protein G-affinity chromatography, and analysed by gel electrophoresis. Their agglutinating, opsonic and haemolytic activities were evaluated using haemagglutination, erythrophagocytosis, and complement activation assays. The recombinant IgG1μtp and IgG3μtp anti-G antibodies ranged from 150,000 to 1,000,000 Da in molecular weight, indicating the formation of polymeric IgG. No complement activation or haemolytic activity was detected upon incubation of RhD-positive red-blood cells with the polymeric anti-G IgG. Both polymers were better opsonins than a prophylactic preparation of plasma-derived anti-D. The enhanced opsonic properties of the polymeric anti-G IgG1μtp and IgG3μtp could allow them to mediate the clearance of RhD-positive red blood cells from circulation more efficiently than natural or other synthetic prophylactic anti-D options. Their inability to induce complement-mediated haemolysis would be prophylactically convenient and is comparable in vitro to that of the available plasma-derived polyclonal anti-D preparations. The described properties suggest that polymeric antibodies like these (but with anti-D specificity) may be testable candidates for prophylaxis of HDFN caused by anti-D.

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

    OpenAIRE

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

    2016-01-01

    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 amin...

  12. Dose-Dependent Effect of Intravenous Administration of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Neonatal Stroke Mice

    Science.gov (United States)

    Tanaka, Emi; Ogawa, Yuko; Mukai, Takeo; Sato, Yoshiaki; Hamazaki, Takashi; Nagamura-Inoue, Tokiko; Harada-Shiba, Mariko; Shintaku, Haruo; Tsuji, Masahiro

    2018-01-01

    Neonatal brain injury induced by stroke causes significant disability, including cerebral palsy, and there is no effective therapy for stroke. Recently, mesenchymal stem cells (MSCs) have emerged as a promising tool for stem cell-based therapies. In this study, we examined the safety and efficacy of intravenously administered human umbilical cord-derived MSCs (UC-MSCs) in neonatal stroke mice. Pups underwent permanent middle cerebral artery occlusion at postnatal day 12 (P12), and low-dose (1 × 104) or high-dose (1 × 105) UC-MSCs were administered intravenously 48 h after the insult (P14). To evaluate the effect of the UC-MSC treatment, neurological behavior and cerebral blood flow were measured, and neuroanatomical analysis was performed at P28. To investigate the mechanisms of intravenously injected UC-MSCs, systemic blood flowmetry, in vivo imaging and human brain-derived neurotrophic factor (BDNF) measurements were performed. Functional disability was significantly improved in the high-dose UC-MSC group when compared with the vehicle group, but cerebral blood flow and cerebral hemispheric volume were not restored by UC-MSC therapy. The level of exogenous human BDNF was elevated only in the cerebrospinal fluid of one pup 24 h after UC-MSC injection, and in vivo imaging revealed that most UC-MSCs were trapped in the lungs and disappeared in a week without migration toward the brain or other organs. We found that systemic blood flow was stable over the 10 min after cell administration and that there were no differences in mortality among the groups. Immunohistopathological assessment showed that the percent area of Iba1-positive staining in the peri-infarct cortex was significantly reduced with the high-dose UC-MSC treatment compared with the vehicle treatment. These results suggest that intravenous administration of UC-MSCs is safe for a mouse model of neonatal stroke and improves dysfunction after middle cerebral artery occlusion by modulating

  13. Dose-Dependent Effect of Intravenous Administration of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Neonatal Stroke Mice

    Directory of Open Access Journals (Sweden)

    Emi Tanaka

    2018-03-01

    Full Text Available Neonatal brain injury induced by stroke causes significant disability, including cerebral palsy, and there is no effective therapy for stroke. Recently, mesenchymal stem cells (MSCs have emerged as a promising tool for stem cell-based therapies. In this study, we examined the safety and efficacy of intravenously administered human umbilical cord-derived MSCs (UC-MSCs in neonatal stroke mice. Pups underwent permanent middle cerebral artery occlusion at postnatal day 12 (P12, and low-dose (1 × 104 or high-dose (1 × 105 UC-MSCs were administered intravenously 48 h after the insult (P14. To evaluate the effect of the UC-MSC treatment, neurological behavior and cerebral blood flow were measured, and neuroanatomical analysis was performed at P28. To investigate the mechanisms of intravenously injected UC-MSCs, systemic blood flowmetry, in vivo imaging and human brain-derived neurotrophic factor (BDNF measurements were performed. Functional disability was significantly improved in the high-dose UC-MSC group when compared with the vehicle group, but cerebral blood flow and cerebral hemispheric volume were not restored by UC-MSC therapy. The level of exogenous human BDNF was elevated only in the cerebrospinal fluid of one pup 24 h after UC-MSC injection, and in vivo imaging revealed that most UC-MSCs were trapped in the lungs and disappeared in a week without migration toward the brain or other organs. We found that systemic blood flow was stable over the 10 min after cell administration and that there were no differences in mortality among the groups. Immunohistopathological assessment showed that the percent area of Iba1-positive staining in the peri-infarct cortex was significantly reduced with the high-dose UC-MSC treatment compared with the vehicle treatment. These results suggest that intravenous administration of UC-MSCs is safe for a mouse model of neonatal stroke and improves dysfunction after middle cerebral artery occlusion by

  14. 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.

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

    International Nuclear Information System (INIS)

    Huseynli, Sabina; Baydemir, Gözde; Sarı, Esma; Elkak, Assem; Denizli, Adil

    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 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

  16. Human kinetics of orally and intravenously administered low-dose 1,2-(13)C-dichloroacetate.

    Science.gov (United States)

    Jia, Minghong; Coats, Bonnie; Chadha, Monisha; Frentzen, Barbara; Perez-Rodriguez, Javier; Chadik, Paul A; Yost, Richard A; Henderson, George N; Stacpoole, Peter W

    2006-12-01

    Dichloroacetate (DCA) is a putative environmental hazard, owing to its ubiquitous presence in the biosphere and its association with animal and human toxicity. We sought to determine the kinetics of environmentally relevant concentrations of 1,2-(13)C-DCA administered to healthy adults. Subjects received an oral or intravenous dose of 2.5 microg/kg of 1,2-(13)C-DCA. Plasma and urine concentrations of 1,2-(13)C-DCA were measured by a modified gas chromatography-tandem mass spectrometry method. 1,2-(13)C-DCA kinetics was determined by modeling using WinNonlin 4.1 software. Plasma concentrations of 1,2-(13)C-DCA peaked 10 minutes and 30 minutes after intravenous or oral administration, respectively. Plasma kinetic parameters varied as a function of dose and duration. Very little unchanged 1,2-(13)C-DCA was excreted in urine. Trace amounts of DCA alter its own kinetics after short-term exposure. These findings have important implications for interpreting the impact of this xenobiotic on human health.

  17. Immunoglobulins in Cerebrospinal Fluid

    DEFF Research Database (Denmark)

    Sellebjerg, Finn Thorup

    2015-01-01

    immunoglobulin synthesis. Intrathecally synthesised immunoglobulins are usually of restricted clonality, and electrophoresis-based methods can be used for detecting this in the form of oligoclonal bands. These methods depend on comparing paired CSF and blood samples. Qualitative analyses for the assessment......The assessment of intrathecally synthesised immunoglobulin is an important part of routine cerebrospinal fl uid (CSF) analysis. Immunoglobulins can be detected in normal CSF and are derived from plasma. The appearance of immunoglobulins in normal CSF is readily explained by size-dependent diffusion...

  18. Hepatic glycogen in humans. I. Direct formation after oral and intravenous glucose or after a 24-h fast

    International Nuclear Information System (INIS)

    Radziuk, J.

    1989-01-01

    The formation of hepatic glycogen by the direct pathway is assessed in humans after a 12-h fast and oral loading (100 g) or intravenous infusion (90 g) and after a 24-h fast and the same oral glucose load. The methodology used is based on the double tracer method. [3- 3 H]glucose is infused at a constant rate for the determination of the metabolic clearance of glucose. [1- 14 C]glucose is administered with the glucose load. One hour after absorption or the intravenous glucose infusion is terminated, a glucagon infusion is initiated to mobilize the glycogen labeled with [1- 14 C]glucose and formed during the absorptive period. At this time a third tracer, [6- 3 H]glucose, is administered to measure glucose clearance. It was found that after the 12-h fast and oral glucose loading 7.2 +/- 1.1 g of hepatic glycogen appears to be formed directly from glucose compared with 8.4 +/- 1.0 g after the same load and a 24-h fast and 8.5 +/- 0.4 g after a 12-h fast and an equivalent intravenous glucose infusion. When the amount of label ([ 14 C]glucose) mobilized that was not corrected for metabolic recycling was calculated, the data suggested that the amount of glycogen formed by gluconeogenic pathways was probably at least equal to that formed by direct uptake. It was also approximately 60% greater after a 24-h fast. It can be concluded that the amount of hepatic glycogen formed directly from glucose during glucose loading is not significantly altered by the route of entry or the extension of the fasting period to 24 h. The data suggest, however, that gluconeogenetic formation of glycogen increases with fasting

  19. 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.

  20. Differential production of immunoglobulin classes and subclasses by mucosal-type human B-lymphocytes exposed in vitro to CpG oligodeoxynucleotides.

    Science.gov (United States)

    Cognasse, Fabrice; Acquart, Sophie; Beniguel, Lydie; Sabido, Odile; Chavarin, Patricia; Genin, Christian; Garraud, Olivier

    2005-01-01

    As B-lymphocytes play an important role in innate and adaptive immunity, we aimed to examine the effects of CpG oligodeoxynucleotides (ODNs) on purified tonsil-originating CD19+ B-cells, representing mucosal B-cells. We screened various K-type ODNs, reactive with human B-cells, and tested for the production of immunoglobulins in vitro. Using one CpG-ODN, DSP30, we observed that it could upregulate not only Toll-like receptor 9 (TLR9) mRNA expression in activated B-cells, but also the early expression of CD69 followed by the sequential expression of CD80, CD86 and the nuclear factor (NF)-kappaB pathway. Furthermore, mRNA expression of certain B-cell-derived cytokines was influenced by exposure to DSP30, with a strong upregulation of interleukin 6 (IL-6) and downregulation of IL1-beta. Stimulation of B-cells, co-stimulated with IL-2, IL-10 and soluble CD40 ligand (sCD40L) with different CpG-ODNs, had differing effects on the terminal differentiation in vitro of B-cells into immunoglobulin-secreting cells. TLR9 is involved in innate immunity and the recognition of bound CpG DNA from invading bacterial pathogens. As tonsillar B-cells are mucosal-type B-lymphocytes, this study suggests that CpG-ODNs show promise as mucosal adjuvants in modulating the local production of immunoglobulins of certain classes and subclasses, a crucial issue in vaccine perspectives.

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

    International Nuclear Information System (INIS)

    Xue, Jiangnan; Zhang, Xiaoshu; Zhao, Haiya; Fu, Qiang; Cao, Yanning; Wang, Yuesi; Feng, Xiaoying; Fu, Aili

    2011-01-01

    Research highlights: → LAIR-1 is expressed on human megakaryocytes from an early stage. → Up-regulation of LAIR-1 negatively regulates megakaryocytic differentiation of cell line. → 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 + CD41a + and CD41a + CD42b + cells. LAIR-1 is also detectable in a fraction of human cord blood CD34 + 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 + 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.

  2. Effects of intravenous glucose on dopaminergic function in the human brain in vivo.

    Science.gov (United States)

    Haltia, Lauri T; Rinne, Juha O; Merisaari, Harri; Maguire, Ralph P; Savontaus, Eriika; Helin, Semi; Någren, Kjell; Kaasinen, Valtteri

    2007-09-01

    Dopamine is known to regulate food intake by modulating food reward via the mesolimbic circuitry of the brain. The objective of this study was to compare the effects of high energy input (i.v. glucose) on striatal and thalamic dopamine release in overweight and lean individuals. We hypothesized that glucose would induce dopamine release and positive ratings (e.g., satiety) in Behavioral Analog Scales, particularly in food-deprived lean subjects. [(11)C]raclopride PET was performed for 12 lean (mean BMI = 22 kg/m(2)) and 12 overweight (mean BMI = 33 kg/m(2)) healthy subjects. Each subject was imaged twice in a blinded counter-balanced setting, after 300 mg/kg i.v. glucose and after i.v. placebo. Dopamine D2 receptor binding potentials (BPs) were estimated. The voxel-based analysis of the baseline scans indicated lower striatal BPs in the overweight group and a negative correlation between BMIs and BPs. Intravenous glucose did not have a significant effect on BPs in overweight or lean subjects (male and female groups combined). However, BP changes were opposite in the two gender groups. In male subjects, significant BP reductions after glucose were seen in the right and left caudate nucleus, left putamen, and right thalamus. In female subjects, increases in BP secondary to glucose were seen in the right caudate nucleus and right and left putamen. The sexually dimorphic effect of glucose was seen in both overweight and lean subjects. Although gender differences were not among the a priori hypotheses of the present study and, therefore, they must be considered to be preliminary findings, we postulate that this observation is a reflection of an interaction between glucose, sex steroids (estrogen), leptin, and dopamine.

  3. Noninvasive quantification of human brain antioxidant concentrations after an intravenous bolus of vitamin C

    Science.gov (United States)

    Background: Until now, antioxidant based initiatives for preventing dementia have lacked a means to detect deficiency or measure pharmacologic effect in the human brain in situ. Objective: Our objective was to apply a novel method to measure key human brain antioxidant concentrations throughout the ...

  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. Intravenous Lipid Emulsion as an Antidote for the Treatment of Acute Poisoning: A Bibliometric Analysis of Human and Animal Studies.

    Science.gov (United States)

    Zyoud, Sa'ed H; Waring, W Stephen; Al-Jabi, Samah W; Sweileh, Waleed M; Rahhal, Belal; Awang, Rahmat

    2016-11-01

    In recent years, there has been increasing interest in the role of intravenous lipid formulations as potential antidotes in patients with severe cardiotoxicity caused by drug toxicity. The aim of this study was to conduct a comprehensive bibliometric analysis of all human and animal studies featuring lipid emulsion as an antidote for the treatment of acute poisoning. The Scopus database search was performed on 5 February 2016 to analyse the research output related to intravenous lipid emulsion as an antidote for the treatment of acute poisoning. Research indicators used for analysis included total number of articles, date (year) of publication, total citations, value of the h-index, document types, countries of publication, journal names, collaboration patterns and institutions. A total of 594 articles were retrieved from Scopus database for the period of 1955-2015. The percentage share of global intravenous lipid emulsion research output showed that research output was 85.86% in 2006-2015 with yearly average growth in this field of 51 articles per year. The USA, United Kingdom (UK), France, Canada, New Zealand, Germany, Australia, China, Turkey and Japan accounted for 449 (75.6%) of all the publications. The total number of citations for all documents was 9,333, with an average of 15.7 citations per document. The h-index of the retrieved documents for lipid emulsion research as antidote for the treatment of acute poisoning was 49. The USA and the UK achieved the highest h-indices, 34 and 14, respectively. New Zealand produced the greatest number of documents with international collaboration (51.9%) followed by Australia (50%) and Canada (41.4%) out of the total number of publications for each country. In summary, we found an increase in the number of publications in the field of lipid emulsion after 2006. The results of this study demonstrate that the majority of publications in the field of lipid emulsion were published by high-income countries. Researchers from

  6. A pharmacokinetic evaluation of five H(1) antagonists after an oral and intravenous microdose to human subjects.

    Science.gov (United States)

    Madan, Ajay; O'Brien, Zhihong; Wen, Jianyun; O'Brien, Chris; Farber, Robert H; Beaton, Graham; Crowe, Paul; Oosterhuis, Berend; Garner, R Colin; Lappin, Graham; Bozigian, Haig P

    2009-03-01

    To evaluate the pharmacokinetics (PK) of five H(1) receptor antagonists in human volunteers after a single oral and intravenous (i.v.) microdose (0.1 mg). Five H(1) receptor antagonists, namely NBI-1, NBI-2, NBI-3, NBI-4 and diphenhydramine, were administered to human volunteers as a single 0.1-mg oral and i.v. dose. Blood samples were collected up to 48 h, and the parent compound in the plasma extract was quantified by high-performance liquid chromatography and accelerator mass spectroscopy. The median clearance (CL), apparent volume of distribution (V(d)) and apparent terminal elimination half-life (t(1/2)) of diphenhydramine after an i.v. microdose were 24.7 l h(-1), 302 l and 9.3 h, and the oral C(max) and AUC(0-infinity) were 0.195 ng ml(-1) and 1.52 ng h ml(-1), respectively. These data were consistent with previously published diphenhydramine data at 500 times the microdose. The rank order of oral bioavailability of the five compounds was as follows: NBI-2 > NBI-1 > NBI-3 > diphenhydramine > NBI-4, whereas the rank order for CL was NBI-4 > diphenhydramine > NBI-1 > NBI-3 > NBI-2. Human microdosing provided estimates of clinical PK of four structurally related compounds, which were deemed useful for compound selection.

  7. A pharmacokinetic evaluation of five H1 antagonists after an oral and intravenous microdose to human subjects

    Science.gov (United States)

    Madan, Ajay; O'Brien, Zhihong; Wen, Jianyun; O'Brien, Chris; Farber, Robert H; Beaton, Graham; Crowe, Paul; Oosterhuis, Berend; Garner, R Colin; Lappin, Graham; Bozigian, Haig P

    2009-01-01

    AIMS To evaluate the pharmacokinetics (PK) of five H1 receptor antagonists in human volunteers after a single oral and intravenous (i.v.) microdose (0.1 mg). METHODS Five H1 receptor antagonists, namely NBI-1, NBI-2, NBI-3, NBI-4 and diphenhydramine, were administered to human volunteers as a single 0.1-mg oral and i.v. dose. Blood samples were collected up to 48 h, and the parent compound in the plasma extract was quantified by high-performance liquid chromatography and accelerator mass spectroscopy. RESULTS The median clearance (CL), apparent volume of distribution (Vd) and apparent terminal elimination half-life (t1/2) of diphenhydramine after an i.v. microdose were 24.7 l h−1, 302 l and 9.3 h, and the oral Cmax and AUC0–∞ were 0.195 ng ml−1 and 1.52 ng h ml−1, respectively. These data were consistent with previously published diphenhydramine data at 500 times the microdose. The rank order of oral bioavailability of the five compounds was as follows: NBI-2 > NBI-1 > NBI-3 > diphenhydramine > NBI-4, whereas the rank order for CL was NBI-4 > diphenhydramine > NBI-1 > NBI-3 > NBI-2. CONCLUSIONS Human microdosing provided estimates of clinical PK of four structurally related compounds, which were deemed useful for compound selection. PMID:19523012

  8. Acute effect of intravenously applied alcohol in the human striatal and extrastriatal D2 /D3 dopamine system.

    Science.gov (United States)

    Pfeifer, Philippe; Tüscher, Oliver; Buchholz, Hans Georg; Gründer, Gerhard; Vernaleken, Ingo; Paulzen, Michael; Zimmermann, Ulrich S; Maus, Stephan; Lieb, Klaus; Eggermann, Thomas; Fehr, Christoph; Schreckenberger, Mathias

    2017-09-01

    Investigations on the acute effects of alcohol in the human mesolimbic dopamine D 2 /D 3 receptor system have yielded conflicting results. With respect to the effects of alcohol on extrastriatal D 2 /D 3 dopamine receptors no investigations have been reported yet. Therefore we applied PET imaging using the postsynaptic dopamine D 2 /D 3 receptor ligand [ 18 F]fallypride addressing the question, whether intravenously applied alcohol stimulates the extrastriatal and striatal dopamine system. We measured subjective effects of alcohol and made correlation analyses with the striatal and extrastriatal D 2 /D 3 binding potential. Twenty-four healthy male μ-opioid receptor (OPRM1)118G allele carriers underwent a standardized intravenous and placebo alcohol administration. The subjective effects of alcohol were measured with a visual analogue scale. For the evaluation of the dopamine response we calculated the binding potential (BP ND ) by using the simplified reference tissue model (SRTM). In addition, we calculated distribution volumes (target and reference regions) in 10 subjects for which metabolite corrected arterial samples were available. In the alcohol condition no significant dopamine response in terms of a reduction of BP ND was observed in striatal and extrastriatal brain regions. We found a positive correlation for 'liking' alcohol and the BP ND in extrastriatal brain regions (Inferior frontal cortex (IFC) (r = 0.533, p = 0.007), orbitofrontal cortex (OFC) (r = 0.416, p = 0.043) and prefrontal cortex (PFC) (r = 0.625, p = 0.001)). The acute alcohol effects on the D 2 /D 3 dopamine receptor binding potential of the striatal and extrastriatal system in our experiment were insignificant. A positive correlation of the subjective effect of 'liking' alcohol with cortical D 2 /D 3 receptors may hint at an addiction relevant trait. © 2016 Society for the Study of Addiction.

  9. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Differential antibody isotype reactivity to specific antigens in human lymphatic filariasis: gp15/400 preferentially induces immunoglobulin E (IgE), IgG4, and IgG2

    NARCIS (Netherlands)

    Yazdanbakhsh, M.; Paxton, W. A.; Brandenburg, A.; van Ree, R.; Lens, M.; Partono, F.; Maizels, R. M.; Selkirk, M. E.

    1995-01-01

    Lymphatic filarial infection in humans is associated with a strong skewing of the immune response towards the TH2 arm, with prominent interleukin 4-producing cells and elevated levels of immunoglobulin G4 (IgG4) and IgE antibodies in peripheral blood. To determine how such a generalized TH2

  11. Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk.

    NARCIS (Netherlands)

    Hout, J.M. van den; Kamphoven, J.H.; Winkel, L.P.; Arts, W.F.M.; Klerk, J.B.C. de; Loonen, M.C.B.; Vulto, A.G.; Cromme-Dijkhuis, A.H.; Weisglas-Kuperus, N.; Hop, W.C.J.; Hirtum, H. van; Diggelen, O.P. van; Boer, M. de; Kroos, M.A.; Doorn, P.A. van; Voort, E.I. van der; Sibbles, B.; Corven, E.J. van; Brakenhoff, J.P.; Hove, J.L. van; Smeitink, J.A.M.; Jong, G. de; Reuser, A.J.J.; Ploeg, A.T. van der

    2004-01-01

    OBJECTIVE: Recent reports warn that the worldwide cell culture capacity is insufficient to fulfill the increasing demand for human protein drugs. Production in milk of transgenic animals is an attractive alternative. Kilogram quantities of product per year can be obtained at relatively low costs,

  12. Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk

    NARCIS (Netherlands)

    J.M.P. van den Hout (Johanna); B. Sibbles (Barbara); J.P. Brakenhoff (Just); A.H. Cromme-Dijkhuis (Adri); N. Weisglas-Kuperus (Nynke); A.J.J. Reuser (Arnold); M.A. Boer (Marijke); J.A.M. Smeitink (Jan); O.P. van Diggelen (Otto); E. van der Voort (Edwin); E.J.J.M. van Corven (Emiel); H. van Hirtum (Hans); J.H.J. Kamphoven (Joep); A.T. van der Ploeg (Ans); J. van Hove (Johan); W.F.M. Arts (Willem Frans); P.A. van Doorn (Pieter); J.B.C. de Klerk (Johannes); M.C.B. Loonen (Christa); A.G. Vulto (Arnold); M.A. Kroos (Marian); W.C.J. Hop (Wim); L.P.F. Winkel (Léon); G. de Jong (Gerard)

    2004-01-01

    textabstractOBJECTIVE: Recent reports warn that the worldwide cell culture capacity is insufficient to fulfill the increasing demand for human protein drugs. Production in milk of transgenic animals is an attractive alternative. Kilogram quantities of product per year can be

  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. Aspirin and salicylate bind to immunoglobulin heavy chain binding protein (BiP) and inhibit its ATPase activity in human fibroblasts.

    Science.gov (United States)

    Deng, W G; Ruan, K H; Du, M; Saunders, M A; Wu, K K

    2001-11-01

    Salicylic acid (SA), an endogenous signaling molecule of plants, possesses anti-inflammatory and anti-neoplastic actions in human. Its derivative, aspirin, is the most commonly used anti-inflammatory and analgesic drug. Aspirin and sodium salicylate (salicylates) have been reported to have multiple pharmacological actions. However, it is unclear whether they bind to a cellular protein. Here, we report for the first time the purification from human fibroblasts of a approximately 78 kDa salicylate binding protein with sequence identity to immunoglobulin heavy chain binding protein (BiP). The Kd values of SA binding to crude extract and to recombinant BiP were 45.2 and 54.6 microM, respectively. BiP is a chaperone protein containing a polypeptide binding site recognizing specific heptapeptide sequence and an ATP binding site. A heptapeptide with the specific sequence displaced SA binding in a concentration-dependent manner whereas a control heptapeptide did not. Salicylates inhibited ATPase activity stimulated by this specific heptapeptide but did not block ATP binding or induce BiP expression. These results indicate that salicylates bind specifically to the polypeptide binding site of BiP in human cells that may interfere with folding and transport of proteins important in inflammation.

  15. Dosimetry of intravenously administered oxygen-15 labelled water in man: a model based on experimental human data from 21 subjects

    International Nuclear Information System (INIS)

    Smith, T.; Tong, C.; Lammertsma, A.A.; Butler, K.R.; Schnorr, L.; Watson, J.D.G.; Ramsay, S.; Clark, J.C.; Jones, T.

    1994-01-01

    Models based on uniform distribution of tracer in total body water underestimate the absorbed dose from H 2 15 O because of the short half-life (2.04 min) of 15 O, which leads to non-uniform distribution of absorbed dose and also complicates the direct measurement of organ retention curves. However, organ absorbed doses can be predicted by the present kinetic model based on the convolution technique. The measured time course of arterial H 2 15 O concentration following intravenous administration represents the input function to organs. The impulse response of a given organ is its transit time function determined by blood flow and the partition of water between tissue and blood. Values of these two parameters were taken from the literature. Integrals of the arterial input function and organ transit time functions were used to derive integrals of organ retention functions (organ residence times). The latter were used with absorbed dose calculation software (MIRDOSE-2) to obtain estimates for 24 organs. From the mean values of organ absorbed doses, the effective dose equivalent (EDE) and effective dose (ED) were calculated. From measurements on 21 subjects, the average value for both EDE and ED was calculated to be 1.2 μSv.MBq -1 compared with a value of about 0.5 μSv.MBq -1 predicted by uniform water distribution models. Based on the human data, a method of approximating H 2 15 O absorbed dose values from body surface area is described. (orig.)

  16. Estimation of absorbed doses in humans due to intravenous administration of fluorine-18-fluorodeoxyglucose in PET studies

    International Nuclear Information System (INIS)

    Mejia, A.A.; Nakamura, T.; Masatoshi, I.; Hatazawa, J.; Masaki, M.; Watanuki, S.

    1991-01-01

    Radiation absorbed doses due to intravenous administration of fluorine-18-fluorodeoxyglucose in positron emission tomography (PET) studies were estimated in normal volunteers. The time-activity curves were obtained for seven human organs (brain, heart, kidney, liver, lung, pancreas, and spleen) by using dynamic PET scans and for bladder content by using a single detector. These time-activity curves were used for the calculation of the cumulative activity in these organs. Absorbed doses were calculated by the MIRD method using the absorbed dose per unit of cumulated activity, 'S' value, transformed for the Japanese physique and the organ masses of the Japanese reference man. The bladder wall and the heart were the organs receiving higher doses of 1.2 x 10(-1) and 4.5 x 10(-2) mGy/MBq, respectively. The brain received a dose of 2.9 x 10(-2) mGy/MBq, and other organs received doses between 1.0 x 10(-2) and 3.0 x 10(-2) mGy/MBq. The effective dose equivalent was estimated to be 2.4 x 10(-2) mSv/MBq. These results were comparable to values of absorbed doses reported by other authors on the radiation dosimetry of this radiopharmaceutical

  17. Effects of Intravenous Administration of Human Umbilical Cord Blood Stem Cells in 3-Acetylpyridine-Lesioned Rats

    Science.gov (United States)

    Calatrava-Ferreras, Lucía; Gonzalo-Gobernado, Rafael; Herranz, Antonio S.; Reimers, Diana; Montero Vega, Teresa; Jiménez-Escrig, Adriano; Richart López, Luis Alberto; Bazán, Eulalia

    2012-01-01

    Cerebellar ataxias include a heterogeneous group of infrequent diseases characterized by lack of motor coordination caused by disturbances in the cerebellum and its associated circuits. Current therapies are based on the use of drugs that correct some of the molecular processes involved in their pathogenesis. Although these treatments yielded promising results, there is not yet an effective therapy for these diseases. Cell replacement strategies using human umbilical cord blood mononuclear cells (HuUCBMCs) have emerged as a promising approach for restoration of function in neurodegenerative diseases. The aim of this work was to investigate the potential therapeutic activity of HuUCBMCs in the 3-acetylpyridine (3-AP) rat model of cerebellar ataxia. Intravenous administered HuUCBMCs reached the cerebellum and brain stem of 3-AP ataxic rats. Grafted cells reduced 3-AP-induced neuronal loss promoted the activation of microglia in the brain stem, and prevented the overexpression of GFAP elicited by 3-AP in the cerebellum. In addition, HuUCBMCs upregulated the expression of proteins that are critical for cell survival, such as phospho-Akt and Bcl-2, in the cerebellum and brain stem of 3-AP ataxic rats. As all these effects were accompanied by a temporal but significant improvement in motor coordination, HuUCBMCs grafts can be considered as an effective cell replacement therapy for cerebellar disorders. PMID:23150735

  18. 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

  19. Radiolabeled, nonspecific, polyclonal human immunoglobulin in the detection of focal inflammation by scintigraphy: Comparison with gallium-67 citrate and technetium-99m-labeled albumin

    International Nuclear Information System (INIS)

    Rubin, R.H.; Fischman, A.J.; Needleman, M.; Wilkinson, R.; Callahan, R.J.; Khaw, B.A.; Hansen, W.P.; Kramer, P.B.; Strauss, H.W.

    1989-01-01

    The accumulation of nonspecific polyclonal human immunoglobulin (IgG) radiolabeled with 125 I or 111 In was compared to that of [ 67 Ga]citrate and [ 99m Tc]albumin in rats with deep thigh inflammation due to Escherichia coli infection. Serial scintigrams were acquired at 1, 3, 24, and in some cases, 48 hr after injection. As early as 3 hr postinjection, [ 111 In]IgG showed greater accumulation at the lesion than [ 99m Tc]HSA (p less than 0.01). Both [ 125 I]IgG and [ 111 In]IgG showed greater accumulation than [ 67 Ga]citrate (p less than 0.01). At 24 hr, IgG image definition increased, while HSA image definition decreased, and the intensity of accumulation of both IgG preparations was greater than that of [ 67 Ga]citrate or [ 99m Tc]HSA (p less than 0.01). At all imaging times, [ 67 Ga]citrate accumulation was surprisingly low. In inflammation produced by Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans, or turpentine, [ 111 In]IgG accumulation was similar to the results obtained with Escherichia coli. These studies suggest that focal sites of inflammation can be detected with radiolabeled nonspecific human polyclonal IgG

  20. 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...

  1. Immunoglobulin therapy for enteroviral meningitides in children

    Directory of Open Access Journals (Sweden)

    O. G. Kimirilova

    2016-01-01

    Full Text Available The authors give the material of their own observations on the clinical and laboratory efficacy of the Russian intravenous immunoglobulin Gabriglobin for the treatment of enteroviral meningitides in children.The performed trials indicated that the use of Gabriglobin in the combination therapy of severe enteroviral meningitides in children reduced the duration of intoxication, global cerebral symptoms, meningeal syndrome, the time of cerebrospinal fluid sanitation by 1,5 times, and that of in-hospital treatment by 5,8±1,8 days as compared to those who received conventional basic therapy.

  2. Characterization of ornidazole metabolites in human bile after intraveneous doses by ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry

    Directory of Open Access Journals (Sweden)

    Jiangbo Du

    2012-04-01

    Full Text Available Ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS was used to characterize ornidazole metabolites in human bile after intravenous doses. A liquid chromatography tandem mass spectrometry (LC–MS/MS assay was developed for the determination of the bile level of ornidazole. Bile samples, collected from four patients with T-tube drainage after biliary tract surgery, were prepared by protein precipitation with acetonitrile before analysis. A total of 12 metabolites, including 10 novel metabolites, were detected and characterized. The metabolites of ornidazole in human bile were the products of hydrochloride (HCl elimination, oxidative dechlorination, hydroxylation, sulfation, diastereoisomeric glucuronation, and substitution of NO2 or Cl atom by cysteine or N-acetylcysteine, and oxidative dechlorination followed by further carboxylation. The bile levels of ornidazole at 12 h after multiple intravenous infusions were well above its minimal inhibitory concentration for common strains of anaerobic bacteria.

  3. Early Intravenous Delivery of Human Brain Stromal Cells Modulates Systemic Inflammation and Leads to Vasoprotection in Traumatic Spinal Cord Injury.

    Science.gov (United States)

    Badner, Anna; Vawda, Reaz; Laliberte, Alex; Hong, James; Mikhail, Mirriam; Jose, Alejandro; Dragas, Rachel; Fehlings, Michael

    2016-08-01

    : Spinal cord injury (SCI) is a life-threatening condition with multifaceted complications and limited treatment options. In SCI, the initial physical trauma is closely followed by a series of secondary events, including inflammation and blood spinal cord barrier (BSCB) disruption, which further exacerbate injury. This secondary pathology is partially mediated by the systemic immune response to trauma, in which cytokine production leads to the recruitment/activation of inflammatory cells. Because early intravenous delivery of mesenchymal stromal cells (MSCs) has been shown to mitigate inflammation in various models of neurologic disease, this study aimed to assess these effects in a rat model of SCI (C7-T1, 35-gram clip compression) using human brain-derived stromal cells. Quantitative polymerase chain reaction for a human-specific DNA sequence was used to assess cell biodistribution/clearance and confirmed that only a small proportion (approximately 0.001%-0.002%) of cells are delivered to the spinal cord, with the majority residing in the lung, liver, and spleen. Intriguingly, although cell populations drastically declined in all aforementioned organs, there remained a persistent population in the spleen at 7 days. Furthermore, the cell infusion significantly increased splenic and circulating levels of interleukin-10-a potent anti-inflammatory cytokine. Through this suppression of the systemic inflammatory response, the cells also reduced acute spinal cord BSCB permeability, hemorrhage, and lesion volume. These early effects further translated into enhanced functional recovery and tissue sparing 10 weeks after SCI. This work demonstrates an exciting therapeutic approach whereby a minimally invasive cell-transplantation procedure can effectively reduce secondary damage after SCI through systemic immunomodulation. Central nervous system pericytes (perivascular stromal cells) have recently gained significant attention within the scientific community. In addition to

  4. Rapid intravenous infusion of 20 mL/kg saline alters the distribution of perfusion in healthy supine humans.

    Science.gov (United States)

    Henderson, A C; Sá, R C; Barash, I A; Holverda, S; Buxton, R B; Hopkins, S R; Prisk, G K

    2012-03-15

    Rapid intravenous saline infusion, a model meant to replicate the initial changes leading to pulmonary interstitial edema, increases pulmonary arterial pressure in humans. We hypothesized that this would alter lung perfusion distribution. Six healthy subjects (29 ± 6 years) underwent magnetic resonance imaging to quantify perfusion using arterial spin labeling. Regional proton density was measured using a fast-gradient echo sequence, allowing blood delivered to the slice to be normalized for density and quantified in mL/min/g. Contributions from flow in large conduit vessels were minimized using a flow cutoff value (blood delivered > 35% maximum in mL/min/cm(3)) in order to obtain an estimate of blood delivered to the capillary bed (perfusion). Images were acquired supine at baseline, after infusion of 20 mL/kg saline, and after a short upright recovery period for a single sagittal slice in the right lung during breath-holds at functional residual capacity. Thoracic fluid content measured by impedance cardiography was elevated post-infusion by up to 13% (pchanges in conduit vessels, there were no significant changes in perfusion in dependent lung following infusion (7.8 ± 1.9 mL/min/g baseline, 7.9 ± 2.0 post, 8.5 ± 2.1 recovery, p=0.36). There were no significant changes in lung density. These data suggest that saline infusion increased perfusion to nondependent lung, consistent with an increase in intravascular pressures. Dependent lung may have been "protected" from increases in perfusion following infusion due to gravitational compression of the pulmonary vasculature. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Immunoregulatory activities of human immunodeficiency virus (HIV) proteins: Effect of HIV recombinant and synthetic peptides on immunoglobulin synthesis and proliferative responses by normal lymphocytes

    International Nuclear Information System (INIS)

    Nair, M.P.N.; Pottathil, R.; Heimer, E.P.; Schwartz, S.A.

    1988-01-01

    Recombinant and synthetic peptides corresponding to envelope proteins of the human immunodeficiency virus (HIV) were examined for their effects on the activities of lymphocytes from normal donors in vitro. Although lymphocytes cultured with env-gag peptides produced significant amounts of IgG, addition of env-gag peptides to a pokeweed mitogen-induced B-cell activation system resulted in suppression of immunoglobulin synthesis by normal lymphocytes. Recombinant antigens, env-gag and env-80 dihydrofolate reductase (DHFR), produced a substantial proliferative response by peripheral blood mononuclear cells (PBMC) as determined by [ 3 H]thymidine incorporation. PBMC precultured with HIV synthetic peptide env 578-608 also manifested significant proliferative responses as compared to control cultures. CD3 + lymphocytes precultured with recombinant HIV antigens, env-gag and env-80 DHFR, and synthetic HIV peptide, env 487-511, showed moderate but significant proliferative responses. Both recombinant antigens and synthetic peptides also produced a dose-dependent stimulatory effect on proliferation by CD3 - lymphocytes. These studies demonstrate that recombinant and synthetic peptides of the HIV genome express immunoregulatory T- and B-cell epitopes. Identification of unique HIV epitopes with immunogenic and immunoregulatory activities is necessary for the development of an effective vaccine against HIV infection

  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. A new approach for generating bispecific antibodies based on a common light chain format and the stable architecture of human immunoglobulin G1.

    Science.gov (United States)

    De Nardis, Camilla; Hendriks, Linda J A; Poirier, Emilie; Arvinte, Tudor; Gros, Piet; Bakker, Alexander B H; de Kruif, John

    2017-09-01

    Bispecific antibodies combine two different antigen-binding sites in a single molecule, enabling more specific targeting, novel mechanisms of action, and higher clinical efficacies. Although they have the potential to outperform conventional monoclonal antibodies, many bispecific antibodies have issues regarding production, stability, and pharmacokinetic properties. Here, we describe a new approach for generating bispecific antibodies using a common light chain format and exploiting the stable architecture of human immunoglobulin G 1 We used iterative experimental validation and computational modeling to identify multiple Fc variant pairs that drive efficient heterodimerization of the antibody heavy chains. Accelerated stability studies enabled selection of one Fc variant pair dubbed "DEKK" consisting of substitutions L351D and L368E in one heavy chain combined with L351K and T366K in the other. Solving the crystal structure of the DEKK Fc region at a resolution of 2.3 Å enabled detailed analysis of the interactions inducing CH3 interface heterodimerization. Local shifts in the IgG backbone accommodate the introduction of lysine side chains that form stabilizing salt-bridge interactions with substituted and native residues in the opposite chain. Overall, the CH3 domain adapted to these shifts at the interface, yielding a stable Fc conformation very similar to that in wild-type IgG. Using the DEKK format, we generated the bispecific antibody MCLA-128, targeting human EGF receptors 2 and 3. MCLA-128 could be readily produced and purified at industrial scale with a standard mammalian cell culture platform and a routine purification protocol. Long-term accelerated stability assays confirmed that MCLA-128 is highly stable and has excellent biophysical characteristics. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Physical linkage of a human immunoglobulin heavy chain variable region gene segment to diversity and joining region elements

    International Nuclear Information System (INIS)

    Schroeder, H.W. Jr.; Walter, M.A.; Hofker, M.H.; Ebens, A.; Van Dijk, K.W.; Liao, L.C.; Cox, D.W.; Milner, E.C.B.; Perlmutter, R.M.

    1988-01-01

    Antibody genes are assembled from a series of germ-line gene segments that are juxtaposed during the maturation of B lymphocytes. Although diversification of the adult antibody repertoire results in large part from the combinatorial joining of these gene segments, a restricted set of antibody heavy chain variable (V H ), diversity (D H ), and joining (J H ) region gene segments appears preferentially in the human fetal repertoire. The authors report here that one of these early-expressed V H elements (termed V H 6) is the most 3' V H gene segment, positioned 77 kilobases on the 5' side of the J H locus and immediately adjacent to a set of previously described D H sequences. In addition to providing a physical map linking human V H , D H , and J H elements, these results support the view that the programmed development of the antibody V H repertoire is determined in part by the chromosomal position of these gene segments

  9. Fundamental characteristics of the immunoglobulin VH repertoire of chickens in comparison with those of humans, mice, and camelids.

    Science.gov (United States)

    Wu, Leeying; Oficjalska, Katarzyna; Lambert, Matthew; Fennell, Brian J; Darmanin-Sheehan, Alfredo; Ní Shúilleabháin, Deirdre; Autin, Bénédicte; Cummins, Emma; Tchistiakova, Lioudmila; Bloom, Laird; Paulsen, Janet; Gill, Davinder; Cunningham, Orla; Finlay, William J J

    2012-01-01

    Examination of 1269 unique naive chicken V(H) sequences showed that the majority of positions in the framework (FW) regions were maintained as germline, with high mutation rates observed in the CDRs. Many FW mutations could be clearly related to the modulation of CDR structure or the V(H)-V(L) interface. CDRs 1 and 2 of the V(H) exhibited frequent mutation in solvent-exposed positions, but conservation of common structural residues also found in human CDRs at the same positions. In comparison with humans and mice, the chicken CDR3 repertoire was skewed toward longer sequences, was dominated by small amino acids (G/S/A/C/T), and had higher cysteine (chicken, 9.4%; human, 1.6%; and mouse, 0.25%) but lower tyrosine content (chicken, 9.2%; human, 16.8%; and mouse 26.4%). A strong correlation (R(2) = 0.97) was observed between increasing CDR3 length and higher cysteine content. This suggests that noncanonical disulfides are strongly favored in chickens, potentially increasing CDR stability and complexity in the topology of the combining site. The probable formation of disulfide bonds between CDR3 and CDR1, FW2, or CDR2 was also observed, as described in camelids. All features of the naive repertoire were fully replicated in the target-selected, phage-displayed repertoire. The isolation of a chicken Fab with four noncanonical cysteines in the V(H) that exhibits 64 nM (K(D)) binding affinity for its target proved these constituents to be part of the humoral response, not artifacts. This study supports the hypothesis that disulfide bond-constrained CDR3s are a structural diversification strategy in the restricted germline v-gene repertoire of chickens.

  10. Mouse to human comparative genetics reveals a novel immunoglobulin E-controlling locus on Hsa8q12

    Czech Academy of Sciences Publication Activity Database

    Gusareva, Elena; Havelková, Helena; Blažková, Hana; Kosařová, Marcela; Kučera, P.; Král, V.; Salyakina, D.; Mulller-Myhsok, b.; Lipoldová, Marie

    2009-01-01

    Roč. 61, č. 1 (2009), s. 15-25 ISSN 0093-7711 R&D Projects: GA ČR GA310/06/1745; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z50520514 Keywords : atopy * specific IgE * genetic loci * mouse-human homology * Czech population * 8q12 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.988, year: 2009

  11. High dose intravenous immunoglobulin in Rh and ABO hemolytic ...

    African Journals Online (AJOL)

    Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 12, No 1 (2014) >. Log in or Register to get access to full text downloads.

  12. High dose intravenous immunoglobulin in Rh and ABO hemolytic ...

    African Journals Online (AJOL)

    Ehab

    suggested as an alternative therapy to ET for rhesus. HDN.11-13 ... (HD-IVIG) in reducing the need for exchange transfusion, duration of phototherapy and/or hospitalization in ... blood group A and 34 neonates with blood group B, distributed ...

  13. Intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy

    NARCIS (Netherlands)

    P.A. van Doorn (Pieter)

    1990-01-01

    textabstractPatients with a chronic inflammatory demyelinating polyneuropathy (CIDP) may respond to treatment with corticosteroids and to plasmapheresis, which was demonstrated in controlled clinical studies. In an uncontrolled study it was found that 13/17 CIDP patients had a rapid and

  14. Immunoglobulins for preventing hepatitis A

    DEFF Research Database (Denmark)

    Liu, Jian Ping; Nikolova, Dimitrinka; Fei, Yutong

    2009-01-01

    Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention.......Hepatitis A (infectious hepatitis) is a common epidemic disease. Immunoglobulins for passive immunisation are used as prevention....

  15. Immunoglobulin production in human mixed lymphocyte cultures: implications for co-cultures of cells from patients and healthy donors

    International Nuclear Information System (INIS)

    Ruemke, H.C.; Terpstra, F.G.; Huis, B.; Out, T.A.; Zeijlemaker, W.P.

    1982-01-01

    When human peripheral blood lymphocytes (PBL) are cultured in the presence of irradiated allogeneic lymphocytes, the resulting mixed lymphocyte reaction (MLR) leads to the secretion into the supernatant of substantial amounts of IgM and IgG, derived from nonirradiated responder B lymphocytes. Our data indicate that stimulation to Ig production by responder B cells may result from different types of of interactions. First, B cells and monocytes among the irradiated stimulator cells activate T responder B cells to produce Ig; second, ''responder'' B cells activate irradiated ''stimulator'' T cells, leading to a ''helper'' signal, back to the responder B cells and leading to Ig production. The latter system is radiosensitive, because allogeneic T cells, irradiated at a dose of 4000 rad or more, failed to induce Ig production by responder B cells. In some combinations of human allogeneic lymphocytes, the co-culture of the cells leads to inhibition of Ig production, both in the presence and in the absence of PWM. Thus, co-culture of allogeneic cells may cause ''positive'' as well as ''negative'' allogeneic effects. The implications of these findings for the interpretation of co-cultures that are aimed at establishing defects in lymphocytes from patients with, for example, immunodeficiencies, who fail to produce Ig in the presence of PWM are discussed

  16. The Immunobiology of Immunoglobulin G4

    NARCIS (Netherlands)

    Lighaam, Laura C.; Rispens, Theo

    2016-01-01

    Human immunoglobulin G4 (IgG4) antibodies are in many ways unusual. In this review, an overview is given of the structural and functional aspects of IgG4 antibodies, the consequences of IgG4 antibody formation in various disease settings, and the factors involved in the regulation of IgG4 responses.

  17. 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...

  18. Traces of pFc' in IVIG interact with human IgG Fc domains and counteract aggregation

    NARCIS (Netherlands)

    Rispens, Theo; Himly, Martin; Ooievaar-de Heer, Pleuni; den Bleker, Tamara H.; Aalberse, Rob C.

    2010-01-01

    To prevent multimer formation, intravenous immunoglobulin (IVIG) is often treated with traces of pepsin. So far, the mechanism behind this treatment has been unclear. Recently, we reported that human IgG4 binds other IgG molecules via Fc-Fc interactions. Here we show that IVIG treated with traces of

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

    Science.gov (United States)

    Aminu, M; Gwafan, Jz; Inabo, Hi; Oguntayo, Ao; Ella, Ee; Koledade, Ak

    2014-01-01

    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. 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. 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 (Pwomen. 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). Further studies are needed to determine the HPV serotypes and evaluate the risk of natural development of HPV-related malignancies among women in the study area.

  20. 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

  1. Intraarticular and intravenous administration of 99MTc-HMPAO-labeled human mesenchymal stem cells (99MTC-AH-MSCS): In vivo imaging and biodistribution

    International Nuclear Information System (INIS)

    Meseguer-Olmo, Luis; Montellano, Antonio Jesús; Martínez, Teresa; Martínez, Carlos M.; Revilla-Nuin, Beatriz; Roldán, Marta; Mora, Cristina Fuente; López-Lucas, Maria Dolores; Fuente, Teodomiro

    2017-01-01

    Introduction: Therapeutic application of intravenous administered (IV) human bone marrow-derived mesenchymal stem cells (ahMSCs) appears to have as main drawback the massive retention of cells in the lung parenchyma, questioning the suitability of this via of administration. Intraarticular administration (IAR) could be considered as an alternative route for therapy in degenerative and traumatic joint lesions. Our work is outlined as a comparative study of biodistribution of 99m Tc-ahMSCs after IV and IAR administration, via scintigraphic study in an animal model. Methods: Isolated primary culture of adult human mesenchymal stem cells was labeled with 99m Tc-HMPAO for scintigraphic study of in vivo distribution after intravenous and intra-articular (knee) administration in rabbits. Results: IV administration of radiolabeled ahMSCs showed the bulk of radioactivity in the lung parenchyma while IAR images showed activity mainly in the injected cavity and complete absence of uptake in pulmonary bed. Conclusions: Our study shows that IAR administration overcomes the limitations of IV injection, in particular, those related to cells destruction in the lung parenchyma. After IAR administration, cells remain within the joint cavity, as expected given its size and adhesion properties. Advances in knowledge: Intra-articular administration of adult human mesenchymal stem cells could be a suitable route for therapeutic effect in joint lesions. Implications for patient care: Local administration of adult human mesenchymal stem cells could improve their therapeutic effects, minimizing side effects in patients.

  2. 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....

  3. Treatment of neonatal sepsis with intravenous immune globulin

    DEFF Research Database (Denmark)

    Brocklehurst, Peter; Farrell, Barbara; King, Andrew

    2011-01-01

    Neonatal sepsis is a major cause of death and complications despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in endogenous immunoglobulin. Meta-analyses of trials of intravenous immune globulin for suspected or proven neonatal sepsis...

  4. Serological blind spots for variants of human IgG3 and IgG4 by a commonly used anti-immunoglobulin reagent.

    Science.gov (United States)

    Howie, Heather L; Delaney, Meghan; Wang, Xiaohong; Er, Lay See; Vidarsson, Gestur; Stegmann, Tamara C; Kapp, Linda; Lebedev, Jenna N; Wu, Yanyun; AuBuchon, James P; Zimring, James C

    2016-12-01

    Human immunoglobulin G (IgG) includes four different subtypes (IgG1, IgG2, IgG3, and IgG4), and it is also now appreciated that there are genetic variations within IgG subtypes (called isoallotypes). Twenty-nine different isoallotypes have been described, with 7, 4, 15, and 3 isoallotypes described for IgG1, IgG2, IgG3, and IgG4, respectively. The reactivity of anti-IgG with different isoallotypes has not been characterized. A novel monoclonal anti-K antibody (PugetSound Monoclonal Antibody 1 [PUMA1]) was isolated and sequenced, and a panel of PUMA1 variants was expressed, consisting of the 29 known IgG isoallotypes. The resulting panel of antibodies was preincubated with K-positive red blood cells (RBCs) and then subjected to testing with currently approved anti-IgG by flow cytometry, solid phase systems, gel cards, and tube testing. A US Food and Drug Administration (FDA)-approved monoclonal anti-IgG (gamma-clone) failed to recognize 2 of 15 IgG3 isoallotypes (IgG3-03 and IgG3-13) and 3 of 3 IgG4 isoallotypes (IgG4-01, IgG4-02, and IgG4-03). In contrast, an FDA-approved rabbit polyclonal anti-IgG recognized each of the known human IgG isoallotypes. These findings demonstrate "blind spots" in isoalloantibody detection by a monoclonal anti-IgG. If a patient has anti-RBC antibodies predominantly of an IgG3 subtype (the IgG3-03 and/or IgG3-13 variety), then it is possible that a clinically significant alloantibody would be missed. IgG-03 and IgG-13 have an estimated frequency of 1% to 3% in Caucasian populations and 20% to 30% in certain African populations. Nonreactivity with IgG4 is a known characteristic of this monoclonal anti-IgG, but IgG4 isoallotypes have not been previously reported. © 2016 AABB.

  5. Unconjugated oestetrol in plasma in response to an intravenous load of dehydroepiandrosterone sulphate (DHAS) in uncomplicated and complicated human pregnancy

    International Nuclear Information System (INIS)

    Axelsson, Ove

    1978-01-01

    A non-chromatographic radioimmunoassay for estimation of unconjugated oestetrol in plasma from pregnant women is described. The antiserum has a high specificity to oestetrol. The technical procedure is simple and rapid. Only small amounts of plasma (0.2-0.4 ml) are needed for the analysis. The method has been applied to the measurement of oestetrol in plasma from pregnant women before and after an intravenous injection of 50 mg DHAS. In women with uncomplicated pregnancies a rise of plasma oestetrol was found 60 min after the injection. From 120 to 360 min there was a plateau level, at 600 min a decrease from this level was observed. No changes in the oestetrol response were found with advancing gestational age from the 33rd to the 40th week of pregnancy. A great spread in the individual responses were recorded. Patients with pre-eclampsia and intrauterine growth retardation had a tendency to a lower increase and patients with diabetes a tendency to a higher increase of plasma oestetrol after the DHAS administration. From the data obtained it is concluded that the increase of plasma oestetrol after an intraveneous injection of DHAS in most cases is secondary to the increase of plasma oestradiol. The results suggest that measurement of unconjugated oestetrol in plasma after an intravenous load of DHAS is no safe way to assess foetal wellbeing. In women with intrauterine growth retardation (IUGR) the simultaneous measurement of plasma oestradiol and oestetrol after an injection of DHAS indicates a possibility to distinguish placental from foetal causes of this syndrome. (author)

  6. Immunoglobulin transfusion in hemolytic disease of the newborn: place in therapy

    Directory of Open Access Journals (Sweden)

    Mundy CA

    2015-06-01

    Full Text Available Cynthia A Mundy, Jatinder Bhatia Department of Pediatrics, Division of Neonatology, Georgia Regents University, Children's Hospital of Georgia, GA, USA Abstract: Hemolytic disease of the newborn continues to be a common neonatal disorder that requires a comprehensive understanding on the part of those caring for infants. Common treatments include hydration and phototherapy. Exchange transfusion is used in severe hemolytic disease, but infants undergoing this treatment are exposed to many adverse effects. Intravenous immunoglobulin is a newer strategy that is showing promise in the treatment of the disease. This review discusses the current use and future expectations of intravenous immunoglobulin therapy in newborns. Keywords: hyperbilirubinemia, ABO incompatibility, neonatal jaundice 

  7. Influence of Human Leukocyte Antigen (HLA) Alleles and Killer Cell Immunoglobulin-Like Receptors (KIR) Types on Heparin-Induced Thrombocytopenia (HIT).

    Science.gov (United States)

    Karnes, Jason H; Shaffer, Christian M; Cronin, Robert; Bastarache, Lisa; Gaudieri, Silvana; James, Ian; Pavlos, Rebecca; Steiner, Heidi E; Mosley, Jonathan D; Mallal, Simon; Denny, Joshua C; Phillips, Elizabeth J; Roden, Dan M

    2017-09-01

    Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT. HIT cases and heparin-exposed controls were identified in BioVU, an electronic health record coupled to a DNA biobank. HLA sequencing and KIR type imputation using Illumina OMNI-Quad data were performed. Odds ratios for HLA alleles and KIR types and HLA*KIR interactions using conditional logistic regressions were determined in the overall population and by race/ethnicity. Analysis was restricted to KIR types and HLA alleles with a frequency greater than 0.01. The p values for HLA and KIR association were corrected by using a false discovery rate qHIT cases and 350 matched controls were identified. No statistical differences in baseline characteristics were observed between cases and controls. The HLA-DRB3*01:01 allele was significantly associated with HIT in the overall population (odds ratio 2.81 [1.57-5.02], p=2.1×10 -4 , q=0.02) and in individuals with European ancestry, independent of other alleles. No KIR types were associated with HIT, although a significant interaction was observed between KIR2DS5 and the HLA-C1 KIR binding group (p=0.03). The HLA-DRB3*01:01 allele was identified as a potential risk factor for HIT. This class II HLA gene and allele represent biologically plausible candidates for influencing HIT pathogenesis. We found limited evidence of the role of KIR types in HIT pathogenesis. Replication and further study of the HLA-DRB3*01:01 association is necessary. © 2017 Pharmacotherapy Publications, Inc.

  8. Kinetics of intravenous radiographic contrast medium injections as used on CT: simulation with time delay differential equations in a basic human cardiovascular multicompartment model.

    Science.gov (United States)

    Violon, D

    2012-12-01

    To develop a multicompartment model of only essential human body components that predicts the contrast medium concentration vs time curve in a chosen compartment after an intravenous injection. Also to show that the model can be used to time adequately contrast-enhanced CT series. A system of linked time delay instead of ordinary differential equations described the model and was solved with a Matlab program (Matlab v. 6.5; The Mathworks, Inc., Natick, MA). All the injection and physiological parameters were modified to cope with normal or pathological situations. In vivo time-concentration curves from the literature were recalculated to validate the model. The recalculated contrast medium time-concentration curves and parameters are given. The results of the statistical analysis of the study findings are expressed as the median prediction error and the median absolute prediction error values for both the time delay and ordinary differential equation systems; these are situated well below the generally accepted maximum 20% limit. The presented program correctly predicts the time-concentration curve of an intravenous contrast medium injection and, consequently, allows an individually tailored approach of CT examinations with optimised use of the injected contrast medium volume, as long as time delay instead of ordinary differential equations are used. The presented program offers good preliminary knowledge of the time-contrast medium concentration curve after any intravenous injection, allowing adequate timing of a CT examination, required by the short scan time of present-day scanners. The injected volume of contrast medium can be tailored to the individual patient with no more contrast medium than is strictly needed.

  9. [Production, specificity and structure of immunoglobulins].

    Science.gov (United States)

    Goujard, C; Delfraissy, J F

    1991-03-21

    Immunoglobulin is a key factor of the immune response resulting from B-cell activation and associated with T-cell stimulation. Because of its structure, this antibody has a dual function: it specifically recognizes the inducer antigen in the variable region and eliminates it by a constant portion which is responsible for effector properties. Surface immunoglobulin, therefore, is the B-cell antigen receptor; it differs from the T-cell receptor in that it recognizes the antigen unbound to the major istocompatibility complex; binding the antigen results in direct signal transduction first in the cytoplasm, then in the nucleus. This receptor can be secreted in the body: it is made up of circulating immunoglobulins. Human immunoglobulins are divided into 5 classes, each of them with its own response kinetics, distribution and functions. The variability of the antibody response accounts for a genetic organization involving numerous genes which may be associated with each other, or mutate, or recombine during maturation of the lymphocytes. Altogether, this system has a theoretical capacity of response to three hundred million different antigens.

  10. Pharmacokinetics of flomoxef in mucosal tissue of the middle ear and mastoid following intravenous administration in humans.

    Science.gov (United States)

    Saito, H; Kimura, T; Takeda, T; Kishimoto, S; Oguma, T; Shimamura, K

    1990-01-01

    The pharmacokinetics of flomoxef in serum and in the mucosal tissue of the middle ear and mastoid were studied in 9 patients undergoing tympanoplasties. All patients received 1 g of flomoxef intravenously. Flomoxef levels in serum and in mucosal tissue were determined by a bioassay method. The peak value of mean concentrations of flomoxef in the mucosal tissue was 30.3 +/- 11.7 micrograms/ml at 10 min after the administrations. Pharmacokinetic analyses showed that the concentration of flomoxef in the mucosal tissue was over 1.56 micrograms/ml (which is the MIC90 for the common pathogens of otitis media) for more than 2 h and decreased parallel with serum concentration with a half-life of about 40 min.

  11. Reduction of microhemorrhages in the spinal cord of symptomatic ALS mice after intravenous human bone marrow stem cell transplantation accompanies repair of the blood-spinal cord barrier

    Science.gov (United States)

    Eve, David J.; Steiner, George; Mahendrasah, Ajay; Sanberg, Paul R.; Kurien, Crupa; Thomson, Avery; Borlongan, Cesar V.; Garbuzova-Davis, Svitlana

    2018-01-01

    Blood-spinal cord barrier (BSCB) alterations, including capillary rupture, have been demonstrated in animal models of amyotrophic lateral sclerosis (ALS) and ALS patients. To date, treatment to restore BSCB in ALS is underexplored. Here, we evaluated whether intravenous transplantation of human bone marrow CD34+ (hBM34+) cells into symptomatic ALS mice leads to restoration of capillary integrity in the spinal cord as determined by detection of microhemorrhages. Three different doses of hBM34+ cells (5 × 104, 5 × 105 or 1 × 106) or media were intravenously injected into symptomatic G93A SOD1 mice at 13 weeks of age. Microhemorrhages were determined in the cervical and lumbar spinal cords of mice at 4 weeks post-treatment, as revealed by Perls’ Prussian blue staining for ferric iron. Numerous microhemorrhages were observed in the gray and white matter of the spinal cords in media-treated mice, with a greater number of capillary ruptures within the ventral horn of both segments. In cell-treated mice, microhemorrhage numbers in the cervical and lumbar spinal cords were inversely related to administered cell doses. In particular, the pervasive microvascular ruptures determined in the spinal cords in late symptomatic ALS mice were significantly decreased by the highest cell dose, suggestive of BSCB repair by grafted hBM34+ cells. The study results provide translational outcomes supporting transplantation of hBM34+ cells at an optimal dose as a potential therapeutic strategy for BSCB repair in ALS patients. PMID:29535831

  12. Spiral CT and optimization of the modalities of the iodinated intravenous contrast material: Experimental studies in human pathology

    International Nuclear Information System (INIS)

    Bonaldi, V.

    1998-01-01

    Spiral (or helical) CT represents the most recent improvement in the field of computed assisted tomography (CAT scan). The capabilities of this new imaging modality are much superior to these of conventional CT scanning; then result from the rapid acquisition and from the volumetric nature of the derived data set. The short time of data acquisition had made mandatory the revision of protocols for intravenous administration of iodinated contrast material. By the means of several studies, carried out on pathologic and healthy patients, we have attempted to improve knowledge in factors influencing CT attenuation values after injection of contrast material, in the aim of improving contrast administration performed during spiral CT scanning. Anatomical landmarks that we have studied till now have been liver, the pancreas, the kidney and the cervical spine. In addition, a paired based methodology has been used. The volumetric set of data derived from spiral CT scanning leads to optimal post-processing tasks, the most interesting being related to cine-display and multiplanar reformatting; both modalities have been evaluated, about the pancreas and the musculo-skeletal system respectively. Conversely, this new modality, as for other imaging modalities, is responsible for additional costs derived from restless increase in the number of images to be dealt with and from the occurrence of new tasks (in post-processing particularly). The place of spiral CT in diagnostic strategies among other modern imaging modalities should be assessed, especially with respect to Magnetic Resonance Imaging (MRI). (author)

  13. Differential patterns of human immunoglobulin G subclass responses to distinct regions of a single protein, the merozoite surface protein 1 of Plasmodium falciparum

    DEFF Research Database (Denmark)

    Cavanagh, D R; Dobaño, C; Elhassan, I M

    2001-01-01

    Comparisons of immunoglobulin G (IgG) subclass responses to the major polymorphic region and to a conserved region of MSP-1 in three cohorts of African villagers exposed to Plasmodium falciparum revealed that responses to Block 2 are predominantly IgG3 whereas antibodies to MSP-1(19) are mainly IgG......1. The striking dominance of IgG3 to Block 2 may explain the short duration of this response and also the requirement for continuous stimulation by malaria infection to maintain clinical immunity....

  14. Pulse methylprednisolone therapy for impending cardiac tamponade in immunoglobulin-resistant Kawasaki disease

    NARCIS (Netherlands)

    Dahlem, P. G.; von Rosenstiel, I. A.; Lam, J.; Kuijpers, T. W.

    1999-01-01

    We describe a boy with Kawasaki disease (KD) whose clinical course was marked by a rapid improvement upon treatment with intravenous immunoglobulin (IVIG) and oral aspirin, which - within 14 days - was followed by the development of a large pericardial effusion with symptoms of impending cardiac

  15. Control of polyclonal immunoglobulin production from human lymphocytes by leukotrienes; leukotriene B4 induces an OKT8(+), radiosensitive suppressor cell from resting, human OKT8(-) T cells

    International Nuclear Information System (INIS)

    Atluru, D.; Goodwin, J.S.

    1984-01-01

    We report that leukotriene B4 (LTB4), a 5-lipoxygenase metabolite of arachidonic acid, is a potent suppressor of polyclonal Ig production in pokeweed mitogen (PWM)-stimulated cultures of human peripheral blood lymphocytes, while LTC4 and LTD4 have little activity in this system. Preincubation of T cells with LTB4 in nanomolar to picomolar concentrations rendered these cells suppressive of Ig production in subsequent PWM-stimulated cultures of fresh, autologous B + T cells. This LTB4-induced suppressor cell was radiosensitive, and its generation could be blocked by cyclohexamide but not by mitomycin C. The LTB4-induced suppressor cell was OKT8(+), while the precursor for the cell could be OKT8(-). The incubation of OKT8(-) T cells with LTB4 for 18 h resulted in the appearance of the OKT8(+) on 10-20% of the cells, and this could be blocked by cyclohexamide but not by mitomycin C. Thus, LTB4 in very low concentrations induces a radiosensitive OKT8(+) suppressor cell from OKT8(-) cells. In this regard, LTB4 is three to six orders of magnitude more potent than any endogenous hormonal inducer of suppressor cells previously described. Glucocorticosteroids, which block suppressor cell induction in many systems, may act by inhibiting endogenous production of LTB4

  16. Reduction of microhemorrhages in the spinal cord of symptomatic ALS mice after intravenous human bone marrow stem cell transplantation accompanies repair of the blood-spinal cord barrier.

    Science.gov (United States)

    Eve, David J; Steiner, George; Mahendrasah, Ajay; Sanberg, Paul R; Kurien, Crupa; Thomson, Avery; Borlongan, Cesar V; Garbuzova-Davis, Svitlana

    2018-02-13

    Blood-spinal cord barrier (BSCB) alterations, including capillary rupture, have been demonstrated in animal models of amyotrophic lateral sclerosis (ALS) and ALS patients. To date, treatment to restore BSCB in ALS is underexplored. Here, we evaluated whether intravenous transplantation of human bone marrow CD34 + (hBM34 + ) cells into symptomatic ALS mice leads to restoration of capillary integrity in the spinal cord as determined by detection of microhemorrhages. Three different doses of hBM34 + cells (5 × 10 4 , 5 × 10 5 or 1 × 10 6 ) or media were intravenously injected into symptomatic G93A SOD1 mice at 13 weeks of age. Microhemorrhages were determined in the cervical and lumbar spinal cords of mice at 4 weeks post-treatment, as revealed by Perls' Prussian blue staining for ferric iron. Numerous microhemorrhages were observed in the gray and white matter of the spinal cords in media-treated mice, with a greater number of capillary ruptures within the ventral horn of both segments. In cell-treated mice, microhemorrhage numbers in the cervical and lumbar spinal cords were inversely related to administered cell doses. In particular, the pervasive microvascular ruptures determined in the spinal cords in late symptomatic ALS mice were significantly decreased by the highest cell dose, suggestive of BSCB repair by grafted hBM34 + cells. The study results provide translational outcomes supporting transplantation of hBM34 + cells at an optimal dose as a potential therapeutic strategy for BSCB repair in ALS patients.

  17. A new high molecular weight immunoglobulin class from the carcharhine shark: implications for the properties of the primordial immunoglobulin.

    Science.gov (United States)

    Berstein, R M; Schluter, S F; Shen, S; Marchalonis, J J

    1996-04-16

    All immunoglobulins and T-cell receptors throughout phylogeny share regions of highly conserved amino acid sequence. To identify possible primitive immunoglobulins and immunoglobulin-like molecules, we utilized 3' RACE (rapid amplification of cDNA ends) and a highly conserved constant region consensus amino acid sequence to isolate a new immunoglobulin class from the sandbar shark Carcharhinus plumbeus. The immunoglobulin, termed IgW, in its secreted form consists of 782 amino acids and is expressed in both the thymus and the spleen. The molecule overall most closely resembles mu chains of the skate and human and a new putative antigen binding molecule isolated from the nurse shark (NAR). The full-length IgW chain has a variable region resembling human and shark heavy-chain (VH) sequences and a novel joining segment containing the WGXGT motif characteristic of H chains. However, unlike any other H-chain-type molecule, it contains six constant (C) domains. The first C domain contains the cysteine residue characteristic of C mu1 that would allow dimerization with a light (L) chain. The fourth and sixth domains also contain comparable cysteines that would enable dimerization with other H chains or homodimerization. Comparison of the sequences of IgW V and C domains shows homology greater than that found in comparisons among VH and C mu or VL, or CL thereby suggesting that IgW may retain features of the primordial immunoglobulin in evolution.

  18. Development of a translational model to screen medications for cocaine use disorder II: Choice between intravenous cocaine and money in humans

    Science.gov (United States)

    Lile, Joshua A.; Stoops, William W.; Rush, Craig R.; Negus, S. Stevens; Glaser, Paul E. A.; Hatton, Kevin W.; Hays, Lon R.

    2016-01-01

    Background A medication for treating cocaine use disorder has yet to be approved. Laboratory-based evaluation of candidate medications in animals and humans is a valuable means to demonstrate safety, tolerability and initial efficacy of potential medications. However, animal-to-human translation has been hampered by a lack of coordination. Therefore, we designed homologous cocaine self-administration studies in rhesus monkeys (see companion article) and human subjects in an attempt to develop linked, functionally equivalent procedures for research on candidate medications for cocaine use disorder. Methods Eight (N=8) subjects with cocaine use disorder completed 12 experimental sessions in which they responded to receive money ($0.01, $1.00 and $3.00) or intravenous cocaine (0, 3, 10 and 30 mg/70 kg) under independent, concurrent progressive-ratio schedules. Prior to the completion of 9 choice trials, subjects sampled the cocaine dose available during that session and were informed of the monetary alternative value. Results The allocation of behavior varied systematically as a function of cocaine dose and money value. Moreover, a similar pattern of cocaine choice was demonstrated in rhesus monkeys and humans across different cocaine doses and magnitudes of the species-specific alternative reinforcers. The subjective and cardiovascular responses to IV cocaine were an orderly function of dose, although heart rate and blood pressure remained within safe limits. Conclusions These coordinated studies successfully established drug vs. non-drug choice procedures in humans and rhesus monkeys that yielded similar cocaine choice behavior across species. This translational research platform will be used in future research to enhance the efficiency of developing interventions to reduce cocaine use. PMID:27269368

  19. A randomized clinical trial of recombinant human hyaluronidase-facilitated subcutaneous versus intravenous rehydration in mild to moderately dehydrated children in the emergency department.

    Science.gov (United States)

    Spandorfer, Philip R; Mace, Sharon E; Okada, Pamela J; Simon, Harold K; Allen, Coburn H; Spiro, David M; Friend, Keith; Harb, George; Lebel, Francois

    2012-11-01

    Alternative treatment of dehydration is needed when intravenous (IV) or oral rehydration therapy fails. Subcutaneous (SC) hydration facilitated by recombinant human hyaluronidase offers an alternative treatment for dehydration. This clinical trial is the first to compare recombinant human hyaluronidase-facilitated SC (rHFSC) rehydration with standard IV rehydration for use in dehydrated children. This Phase IV noninferiority trial evaluated whether rHFSC fluid administration can be given safely and effectively, with volumes similar to those delivered intravenously, to children who have mild to moderate dehydration. The study included mild to moderately dehydrated children (Gorelick dehydration score) aged 1 month to 10 years. They were randomized to receive 20 mL/kg of isotonic fluids using rHFSC or IV therapy over 1 hour and then as needed until clinically rehydrated. The primary outcome was total volume of fluid administered (emergency department [ED] plus inpatient hospitalization). Secondary outcomes included mean volume infused in the ED alone, postinfusion dehydration scores and weight changes, line placement success and time, safety, and provider and parent/guardian questionnaire. 148 patients (mean age, 2.3 [1.91] years]; white, 53.4%; black, 31.8%) were enrolled in the intention-to-treat population (73 rHFSC; 75 IV). The primary outcome, mean total volume infused, was 365.0 (324.6) mL in the rHFSC group over 3.1 hours versus 455.8 (597.4) mL in the IV group over 6.6 hours (P = 0.51). The secondary outcome of mean volume infused in the ED alone was 334.3 (226.40) mL in the rHFSC group versus 299.6 (252.33) mL in the IV group (P = 0.03). Dehydration scores and weight changes postinfusion were similar. Successful line placement occurred in all 73 rHFSC-treated patients and 59 of 75 (78.7%) IV-treated patients (P dehydrated children, rHFSC was inferior to IV hydration for the primary outcome measure. However, rHFSC was noninferior in the ED phase of hydration

  20. GH receptor signaling in skeletal muscle and adipose tissue in human subjects following exposure to an intravenous GH bolus

    DEFF Research Database (Denmark)

    Jørgensen, Jens O L; Jessen, Niels; Pedersen, Steen Bønløkke

    2006-01-01

    Growth hormone (GH) regulates muscle and fat metabolism, which impacts on body composition and insulin sensitivity, but the underlying GH signaling pathways have not been studied in vivo in humans. We investigated GH signaling in biopsies from muscle and abdominal fat obtained 30 (n = 3) or 60 (n...... was measured by in vitro phosphorylation of PI. STAT5 DNA binding activity was assessed with EMSA, and the expression of IGF-I and SOCS mRNA was measured by real-time RT-PCR. GH induced a 52% increase in circulating FFA levels with peak values after 155 min (P = 0.03). Tyrosine-phosphorylated STAT5...... tended to increase after GH in muscle and fat, respectively. We conclude that 1) STAT5 is acutely activated in human muscle and fat after a GH bolus, but additional downstream GH signaling was significant only in fat; 2) the direct GH effects in muscle need further characterization; and 3) this human...

  1. Human Schistosoma haematobium antifecundity immunity is dependent on transmission intensity and associated with immunoglobulin G1 to worm-derived antigens

    DEFF Research Database (Denmark)

    Wilson, Shona; Jones, Frances M.; van Dam, Govert J.

    2014-01-01

    BACKGROUND: Immunity that reduces worm fecundity and, in turn, reduces morbidity is proposed for Schistosoma haematobium, a parasite of major public health importance. Mathematical models of epidemiological trends suggest that antifecundity immunity is dependent on antibody responses to adult......-worm-derived antigen. METHODS: For a Malian cohort (age, 5-29 years) residing in high-transmission fishing villages or a moderate-transmission village, worm fecundity was assessed using the ratio of urinary egg excretion to levels of circulating anodic antigen, a Schistosoma-specific antigen that is steadily secreted......, host age and transmission were negatively associated with worm fecundity. A significant interaction term between host age and transmission indicates that antifecundity immunity develops earlier in high-transmission areas. SWA immunoglobulin G1 (IgG1) levels explained the effect of transmission...

  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...... infection was attenuated, as evidenced by altered viral kinetics in comparison with five control IgG-treated animals. Plasma samples obtained from the mice at viral challenge neutralized H77C-HCVpp at dilutions as high as 1/400. Infection was completely prevented when, before administration to naïve...

  3. Immunoglobulin G for patients with necrotising soft tissue infection (INSTINCT)

    DEFF Research Database (Denmark)

    Madsen, Martin B.; Hjortrup, Peter B.; Hansen, Marco B.

    2017-01-01

    Purpose: The aim of the INSTINCT trial was to assess the effect of intravenous polyspecific immunoglobulin G (IVIG) compared with placebo on self-reported physical function in intensive care unit (ICU) patients with necrotising soft tissue infection (NSTI). Methods: We randomised 100 patients...... with NSTI 1:1 to masked infusion of 25 g of IVIG (Privigen, CSL Behring) or an equal volume of 0.9% saline once daily for the first 3 days of ICU admission. The primary outcome was the physical component summary (PCS) score of the 36-item short form health survey (SF-36) 6 months after randomisation...

  4. Distribution of 131I-labeled recombinant human erythropoietin in maternal and fetal organs following intravenous administration in pregnant rats

    International Nuclear Information System (INIS)

    Yilmaz, O.; Lambrecht, F.Y.; Durkan, K.; Gokmen, N.; Erbayraktar, S.

    2007-01-01

    The aim of the present study was to demonstrate the possible transplacental transmission of 131 I labeled recombinant human erythropoietin ( 131 I-rh-EPO) in pregnant rats and its distribution through maternal and fetal organs. Six Wistar Albino Rats in their pregnancy of 18 days were used 131 I labeled recombinant human erythropoietin (specific activity = 2.4 μCi/IU) was injected into the tail vein of rats. After 30 minutes labeled erythropoietin infusion maternal stomach, kidney, lung, liver, brain and heart as well as fetus were removed. Then, the same organs were removed from each fetus. Measuring weight of maternal and fetal organs as well as placenta were followed by radioactivity count via Cd(Te) detector. 131 I labeled recombinant human erythropoietin was found to be able to pass rat placenta and its distribution order in fetal organs was similar to those of maternal organs. Besides, as measurements were performed closer to cornu uteri, uptakes were decreasing in every fetus and its corresponding placenta. (author)

  5. Pharmacokinetic-Pharmacodynamic Modelling of the Analgesic and Antihyperalgesic Effects of Morphine after Intravenous Infusion in Human Volunteers

    DEFF Research Database (Denmark)

    Ravn, Pernille; Foster, David J. R.; Kreilgaard, Mads

    2014-01-01

    Using a modelling approach, this study aimed to (i) examine whether the pharmacodynamics of the analgesic and antihyperalgesic effects of morphine differ; (ii) investigate the influence of demographic, pain sensitivity and genetic (OPRM1) variables on between-subject variability of morphine...... pharmacokinetics and pharmacodynamics in human experimental pain models. The study was a randomized, double-blind, 5-arm, cross-over, placebo-controlled study. The psychophysical cutaneous pain tests, electrical pain tolerance (EPTo) and secondary hyperalgesia areas (2HA) were studied in 28 healthy individuals (15...

  6. Intentional intravenous mercury injection

    African Journals Online (AJOL)

    In this case report, intravenous complications, treatment strategies and possible ... Mercury toxicity is commonly associated with vapour inhalation or oral ingestion, for which there exist definite treatment options. Intravenous mercury ... personality, anxiousness, irritability, insomnia, depression and drowsi- ness.[1] However ...

  7. The plasma and cerebrospinal fluid pharmacokinetics of erlotinib and its active metabolite (OSI-420) after intravenous administration of erlotinib in non-human primates.

    Science.gov (United States)

    Meany, Holly J; Fox, Elizabeth; McCully, Cynthia; Tucker, Chris; Balis, Frank M

    2008-08-01

    Erlotinib hydrochloride is a small molecule inhibitor of epidermal growth factor receptor (EGFR). EGFR is over-expressed in primary brain tumors and solid tumors that metastasize to the central nervous system. We evaluated the plasma and cerebrospinal fluid (CSF) pharmacokinetics of erlotinib and its active metabolite OSI-420 after an intravenous (IV) dose in a non-human primate model. Erlotinib was administered as a 1 h IV infusion to four adult rhesus monkeys. Serial blood and CSF samples were drawn over 48 h and erlotinib and OSI-420 were quantified with an HPLC/tandem mass spectroscopic assay. Pharmacokinetic parameters were estimated using non-compartmental and compartmental methods. CSF penetration was calculated from the AUC(CSF):AUC(plasma). Erlotinib disappearance from plasma after a short IV infusion was biexponential with a mean terminal half-life of 5.2 h and a mean clearance of 128 ml/min per m(2). OSI-420 exposure (AUC) in plasma was 30% (range 12-59%) of erlotinib, and OSI-420 clearance was more than 5-fold higher than erlotinib. Erlotinib and OSI-420 were detectable in CSF. The CSF penetration (AUC(CSF):AUC(plasma)) of erlotinib and OSI-420 was OSI-420 are measurable in CSF after an IV dose. The drug exposure (AUC) in the CSF is limited relative to total plasma concentrations but is substantial relative the free drug exposure in plasma.

  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. Human plasma-derived immunoglobulin G fractionated by an aqueous two-phase system, caprylic acid precipitation, and membrane chromatography has a high purity level and is free of detectable in vitro thrombogenic activity.

    Science.gov (United States)

    Vargas, M; Segura, Á; Wu, Y-W; Herrera, M; Chou, M-L; Villalta, M; León, G; Burnouf, T

    2015-02-01

    Instituto Clodomiro Picado has developed an immunoglobulin G (IgG) plasma fractionation process combining a polyethylene glycol/phosphate aqueous two-phase system (ATPS), caprylic acid precipitation and anion-exchange membrane chromatography. We evaluated the purity and in vitro thrombogenicity of such IgG, in line with current international requirements. Contributions of the different production steps to reduce thrombogenicity were assessed at 0·2 l-scale, and then the methodology was scaled-up to a 10 l-scale and final products (n = 3) were analysed. Purity, immunoglobulin composition, and subclass distribution were determined by electrophoretic and immunochemical methods. The in vitro thrombogenic potential was determined by a thrombin generation assay (TGA) using a Technothrombin fluorogenic substrate. Prekallikrein activator (PKA), plasmin, factor Xa, thrombin and thrombin-like activities were assessed using S-2302, S-2251, S-2222, S-2238 and S-2288 chromogenic substrates, respectively, and FXI by an ELISA. The thrombogenicity markers were reduced mostly during the ATPS step and were found to segregate mostly into the discarded liquid upper phase. The caprylic acid precipitation eliminated the residual procoagulant activity. The IgG preparations made from the 10 l-batches contained 100% gamma proteins, low residual IgA and undetectable IgM. The IgG subclass distribution was not substantially affected by the process. TGA and amidolytic activities revealed an undetectable in vitro thrombogenic risk and the absence of proteolytic enzymes in the final product. Fractionating human plasma by an ATPS combined with caprylic acid and membrane chromatography resulted in an IgG preparation of high purity and free of a detectable in vitro thrombogenic risk. © 2014 International Society of Blood Transfusion.

  10. Phase I dose escalation pharmacokinetic assessment of intravenous humanized anti-MUC1 antibody AS1402 in patients with advanced breast cancer.

    Science.gov (United States)

    Pegram, Mark D; Borges, Virginia F; Ibrahim, Nuhad; Fuloria, Jyotsna; Shapiro, Charles; Perez, Susan; Wang, Karen; Schaedli Stark, Franziska; Courtenay Luck, Nigel

    2009-01-01

    MUC1 is a cell-surface glycoprotein that establishes a molecular barrier at the epithelial surface and engages in morphogenetic signal transduction. Alterations in MUC1 glycosylation accompany the development of cancer and influence cellular growth, differentiation, transformation, adhesion, invasion, and immune surveillance. A 20-amino-acid tandem repeat that forms the core protein of MUC1 is overexpressed and aberrantly glycosylated in the majority of epithelial tumors. AS1402 (formerly R1550) is a humanized IgG1k monoclonal antibody that binds to PDTR sequences within this tandem repeat that are not exposed in normal cells. AS1402 is a potent inducer of antibody-dependent cellular cytotoxicity (ADCC), specifically against MUC1-expressing tumor cells. The objective of this study was to determine the safety, tolerability, and pharmacokinetic (PK) characteristics of AS1402 monotherapy in patients with locally advanced or metastatic MUC1-positive breast cancer that had progressed after anthracyclines- and taxane-based therapy. Patients received AS1402 over a 1- to 3-hour intravenous (i.v.) infusion at doses between 1 and 16 mg/kg, with repeated dosing every 1 to 3 weeks (based on patient-individualized PK assessment) until disease progression. Serum AS1402 levels were measured at multiple times after i.v. administration. Human anti-human antibody (HAHA) responses were measured to determine the immunogenicity of AS1402. Noncompartmental pharmacokinetic parameters were determined and were used to assess dose dependency across the dose range studied. Twenty-six patients were treated. AS1402 was generally well tolerated. Two grade 3/4 drug-related adverse events were reported, both at the 3-mg/kg dose. Neither was observed in expanded or subsequent dosing cohorts. No anti-human antibodies were detected. Plasma concentrations of AS1402 appeared to be proportional to dose within the 1- to 16-mg/kg dose range assessed, with a mean terminal half-life of 115.4 +/- 37.1 hours

  11. Isolation of a human anti-epidermal growth factor receptor Fab antibody, EG-19-11, with subnanomolar affinity from naïve immunoglobulin repertoires using a hierarchical antibody library system.

    Science.gov (United States)

    Hur, Byung-ung; Yoon, Jae-bong; Liu, Li-Kun; Cha, Sang-hoon

    2010-11-30

    Specific antibodies that possess a subnanomolar affinity are very difficult to obtain from human naïve immunoglobulin repertoires without the use of lengthy affinity optimization procedures. Here, we designed a hierarchical phage-displayed antibody library system to generate an enormous diversity of combinatorial Fab fragments (6×10(17)) and attempted to isolate high-affinity Fabs against the human epidermal growth factor receptor (EGFR). A primary antibody library, designated HuDVFab-8L, comprising 4.5×10(9) human naïve heavy chains and eight unspecified human naïve light chains was selected against the EGFR-Fc protein by biopanning, and four anti-EGFR Fab clones were isolated. Because one of the Fab clones, denoted EG-L2-11, recognized a native EGFR expressed on A431 cells, the heavy chain of the Fab was shuffled with a human naïve light chain repertoire with a diversity of 1.4×10(8) and selected a second time against the EGFR-Fc protein again. One EG-L2-11 variant, denoted EG-19-11, recognized an EGFR epitope that was almost the same as that bound by cetuximab and had a K(D) of approximately 540 pM for soluble EGFR, which is about 7-fold higher than that of the FabC225 derived from cetuximab. This variant was also internalized by A431 cells, likely via receptor-mediated endocytosis, and it efficiently inhibited EGF-mediated tyrosine phosphorylation of the EGFR. These results demonstrate that the use of our hierarchical antibody library system is advantageous in generating fully human antibodies especially with a therapeutic purpose. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. Mechanism of immunoglobulin G4 Fab-arm exchange

    NARCIS (Netherlands)

    Rispens, Theo; Ooijevaar-de Heer, Pleuni; Bende, Onno; Aalberse, Rob C.

    2011-01-01

    Immunoglobulin G (IgG) antibodies are symmetrical molecules that may be regarded as covalent dimers of 2 half-molecules, each consisting of a light chain and a heavy chain. Human IgG4 is an unusually dynamic antibody, with half-molecule exchange ("Fab-arm exchange") resulting in asymmetrical,

  13. Quantifying the reduction in immunoglobulin use over time in patients with chronic immune thrombocytopenic purpura receiving romiplostim (AMG 531)

    NARCIS (Netherlands)

    Pullarkat, Vinod A.; Gernsheirner, Terry B.; Wasser, Jeffrey S.; Newland, Adrian; Guthrie, Troy H.; de Wolf, Joost Th. M.; Stewart, Ron; Berger, Dietmar

    Patients with Immune thrombocytopenic purpura (ITP) often require immunoglobulin (Ig) therapy with intravenous 19 (IVIG) or anti-D to prevent or treat the serious bleeding events. Because the thrombopoietin (TPO) mimetic romiplostim (AMG 531; Nplate) elevates platelet counts in patients with chronic

  14. Development of graphene oxide/poly(3,4-ethylenedioxythiophene)/poly(styrene sulfonate) thin film-based electrochemical surface plasmon resonance immunosensor for detection of human immunoglobulin G

    Science.gov (United States)

    Pothipor, Chammari; Lertvachirapaiboon, Chutiparn; Shinbo, Kazunari; Kato, Keizo; Kaneko, Futao; Ounnunkad, Kontad; Baba, Akira

    2018-02-01

    An electrochemically synthesized graphene oxide (GO)/poly(3,4-ethylenedioxythiophene) (PEDOT)/poly(styrene sulfonate) (PSS) thin film-based electrochemical surface plasmon resonance (EC-SPR) sensor chip was developed and employed for the detection of human immunoglobulin G (IgG). GO introduced the carboxylic group on the film surface, which also allowed electrochemical control, for the immobilization of the anti-IgG antibody via covalent bonding through amide coupling reaction. The SPR sensitivity of the detection was improved under the control by applying an electrochemical potential, by which the sensitivity was increased by the increment in applied potential. Among the open-circuit and different applied potentials in the range of -1.0 to 0.50 V, the EC-SPR immunosensor at an applied potential of 0.50 V exhibited the highest sensitivity of 6.08 × 10-3 mL µg-1 cm-2 and linearity in the human IgG concentration range of 1.0 to 10 µg mL-1 with a relatively low detection limit of 0.35 µg mL-1. The proposed sensor chip is promising for immunosensing at the physiological level.

  15. Immunoglobulin adsorption on modified surfaces

    NARCIS (Netherlands)

    Bremer, M.G.E.G.

    2001-01-01

    Preservation of biological functioning of proteins during immobilisation is of special interest in various biomedical and biotechnical applications. In industry physical adsorption of immunoglobulins (IgGs) onto solid surfaces is still the predominant immobilisation procedure because it is

  16. Dose-Related Modulation of Event-Related Potentials to Novel and Target Stimuli by Intravenous Δ9-THC in Humans

    Science.gov (United States)

    D'Souza, Deepak Cyril; Fridberg, Daniel J; Skosnik, Patrick D; Williams, Ashley; Roach, Brian; Singh, Nagendra; Carbuto, Michelle; Elander, Jacqueline; Schnakenberg, Ashley; Pittman, Brian; Sewell, R Andrew; Ranganathan, Mohini; Mathalon, Daniel

    2012-01-01

    Cannabinoids induce a host of perceptual alterations and cognitive deficits in humans. However, the neural correlates of these deficits have remained elusive. The current study examined the acute, dose-related effects of delta-9-tetrahydrocannabinol (Δ9-THC) on psychophysiological indices of information processing in humans. Healthy subjects (n=26) completed three test days during which they received intravenous Δ9-THC (placebo, 0.015 and 0.03 mg/kg) in a within-subject, double-blind, randomized, cross-over, and counterbalanced design. Psychophysiological data (electroencephalography) were collected before and after drug administration while subjects engaged in an event-related potential (ERP) task known to be a valid index of attention and cognition (a three-stimulus auditory ‘oddball' P300 task). Δ9-THC dose-dependently reduced the amplitude of both the target P300b and the novelty P300a. Δ9-THC did not have any effect on the latency of either the P300a or P300b, or on early sensory-evoked ERP components preceding the P300 (the N100). Concomitantly, Δ9-THC induced psychotomimetic effects, perceptual alterations, and subjective ‘high' in a dose-dependent manner. Δ9-THC -induced reductions in P3b amplitude correlated with Δ9-THC-induced perceptual alterations. Lastly, exploratory analyses examining cannabis use status showed that whereas recent cannabis users had blunted behavioral effects to Δ9-THC, there were no dose-related effects of Δ9-THC on P300a/b amplitude between cannabis-free and recent cannabis users. Overall, these data suggest that at doses that produce behavioral and subjective effects consistent with the known properties of cannabis, Δ9-THC reduced P300a and P300b amplitudes without altering the latency of these ERPs. Cannabinoid agonists may therefore disrupt cortical processes responsible for context updating and the automatic orientation of attention, while leaving processing speed and earlier sensory ERP components intact

  17. Immunoassay of serum polypeptide hormones by using 125I-labelled anti(-immunoglobulin G) antibodies.

    Science.gov (United States)

    Beck, P; Nicholas, H

    1975-03-01

    1. A technique for indirectly labelling antibodies to polypeptide hormones, by combining them with radioactively labelled anti-(immunoglobulin G) is described. (a) 125I-labelled anti-(rabbit immunoglobulin G) and anti-(guinea-pig immunoglobulin G) antibodies with high specific radioactivity were prepared after purification of the antibodies on immunoadsorbents containing the respective antigens. (b) Rabbit immunoglobulin G antibodies to human growth hormone, porcine glucagon and guinea-pig immunoglobulin G antibodies to bovine insulin and bovine parathyroid hormone were combined with immunoadsorbents containing the respective polypeptide hormone antigen. (c) The immunoglobulin G antibodies to the polypeptide hormones were reacted with 125-I-labelled anti-(immunoglobulin G) antibodies directed against the appropriate species of immunoglobulin G,and the anti-hormone antibodies were combined with the hormone-containing immunoadsorbent. (d) 125I-labelled anti-(immunoglobulin G) antibodies and anti-hormone antibodies were simultaneously eluted from the hormone-containing immunoadsorbent by dilute HCl, pH 2.0. After elution the anti-(immunoglobulin G) antibodies and antihormone antibodies were allowed to recombine at pH 8.0 and 4 degrees C. 2. The resultant immunoglobulin G-anti-immunoglobulin G complex was used in immunoradiometric (labelled antibody) and two-site assays of the respective polypeptide hormone. 3. By using these immunoassays, concentrations down to 90pg of human growth hormone/ml, 100 pg of bovine insulin/ml, 80 pg of bovine parathyroid hormone/ml and 150 pg of glucagon/ml were readily detected. Assays of human plasma for growth hormone and insulin by these methods showed good agreement with results obtained by using a directly 125I-labelled anti-hormone antibody in an immunoradiometric assay of human growth hormone or by radioimmunoassay of human insulin. 4. The method described allows immunoradiometric or two-site assays to be performed starting with as

  18. Dynamics of Inter-heavy Chain Interactions in Human Immunoglobulin G (IgG) Subclasses Studied by Kinetic Fab Arm Exchange

    NARCIS (Netherlands)

    Rispens, Theo; Davies, Anna M.; Ooijevaar-de Heer, Pleuni; Absalah, Samira; Bende, Onno; Sutton, Brian J.; Vidarsson, Gestur; Aalberse, Rob C.

    2014-01-01

    Background: Fab arm exchange requires weak interactions between CH3 domains, such as in human IgG4. Results: CH3-CH3 interactions differ >1,000,000-fold between human subclasses and allotypes due to variations Lys/Asn-392, Val/Met-397, and Lys/Arg-409. Conclusion: For IgG2 and IgG3, but not IgG1,

  19. 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.

  20. Comparative mapping of DNA probes derived from the V{sub k} immunoglobulin gene regions on human and great ape chromosomes by fluorescence in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Arnold, N.; Wienberg, J.; Ermert, K. [Universitaet Muenchen (Germany)] [and others

    1995-03-01

    Fluorescence in situ hybridization (FISH) of cosmid clones of human V{sub K} gene regions to human and primate chromosomes contributed to the dating of chromosome reorganizations in evolution. A clone from the K locus at 2p11-p12 (cos 106) hybridized to the assumed homologous chromosome bands in the chimpanzees Pan troglodytes (PTR) and P. paniscus (PPA), the Gorilla gorilla (GGO), and the orangutan Pongo Pygmaeus (PPY). Human and both chimpanzees differed from gorilla and orangutan by the mapping of cos 170, a clone derived from chromosome 2cen-q11.2; the transposition of this orphon to the other side of the centromere can, therefore, be dated after the human/chimpanzee and gorilla divergence. Hybridization to homologous bands was also found with a cosmid clone containing a V{sub K}I orphon located on chromosome 1 (cos 115, main signal at 1q31-q32), although the probe is not fully unique. Also, a clone derived from the orphon V{sub K} region on chromosome 22q11 (cos 121) hybridized to the homologous bands in the great apes. This indicates that the orphons on human chromosomes 1 and 22 had been translocated early in primate evolution. 18 refs., 2 figs.

  1. Primary structure of and immunoglobulin E response to the repeat subunit of gp15/400 from human lymphatic filarial parasites

    NARCIS (Netherlands)

    Paxton, W. A.; Yazdanbakhsh, M.; Kurniawan, A.; Partono, F.; Maizels, R. M.; Selkirk, M. E.

    1993-01-01

    We have isolated and sequenced clones encoding the repeated subunit of the surface-associated glycoprotein gp15/400 from the two nematode species predominantly responsible for lymphatic filariasis in humans: Brugia malayi and Wuchereria bancrofti. The amino acid sequence of the 15-kDa subunit,

  2. Immunoglobulin variable region sequences of two human monoclonal antibodies directed to an onco-developmental carbohydrate antigen, lactotetraosylceramide (LcOse4Cer).

    Science.gov (United States)

    Yago, K; Zenita, K; Ohwaki, I; Harada, R; Nozawa, S; Tsukazaki, K; Iwamori, M; Endo, N; Yasuda, N; Okuma, M

    1993-11-01

    A human monoclonal antibody, 11-50, was generated and was shown to recognize an onco-developmental carbohydrate antigen, LcOse4Cer. The isotype of this antibody was IgM, lambda, similar to the previously known human anti-LcOse4 antibodies, such as IgMWOO and HMST-1. We raised a murine anti-idiotypic antibody G3 (IgG1, kappa) against 11-50, and tested its reactivity towards the affinity purified human polyclonal anti-LcOse4 antibodies prepared from pooled human sera using a Gal beta 1-->3GlcNAc beta-immobilized column. The results indicated that at least a part of the human polyclonal anti-LcOse4 antibodies shared the G3 idiotype with 11-50. We further analyzed the sequence of variable regions of the two anti-LcOse4 antibodies, 11-50 and HMST-1. Sequence analysis of the heavy chain variable regions indicated that the VH regions of these two antibodies were highly homologous to each other (93.5% at the nucleic acid level), and these antibodies utilized the germline genes VH1.9III and hv3005f3 as the VH segments, which are closely related germline genes of the VHIII family. It was noted that these germline VH genes are frequently utilized in fetal B cells. The JH region of both antibodies was encoded by the JH4 gene. For the light chain, the V lambda segments of the two antibodies were 96.3% homologous to each other at the nucleic acid level. The V lambda segments of both antibodies showed the highest homology to the rearranged V lambda gene called V lambda II.DS among reported V lambda genes, while the exact germline V lambda genes encoding the two antibodies were not yet registered in available sequence databanks. The amino acid sequences of the J lambda segments of both antibodies were identical. These results indicate that the two human antibodies recognizing the onco-developmental carbohydrate antigen Lc4 are encoded by the same or very homologous germline genes.

  3. Immunoglobulin for alloimmune hemolytic disease in neonates.

    Science.gov (United States)

    Zwiers, Carolien; Scheffer-Rath, Mirjam Ea; Lopriore, Enrico; de Haas, Masja; Liley, Helen G

    2018-03-18

    Exchange transfusion and phototherapy have traditionally been used to treat jaundice and avoid the associated neurological complications. Because of the risks and burdens of exchange transfusion, intravenous immunoglobulin (IVIg) has been suggested as an alternative therapy for alloimmune hemolytic disease of the newborn (HDN) to reduce the need for exchange transfusion. To assess the effect and complications of IVIg in newborn infants with alloimmune HDN on the need for and number of exchange transfusions. We performed electronic searches of CENTRAL, PubMed, Embase (Ovid), Web of Science, CINAHL (EBSCOhost), Academic Search Premier, and the trial registers ClinicalTrials.gov and controlled-trials.com in May 2017. We also searched reference lists of included and excluded trials and relevant reviews for further relevant studies. We considered all randomized and quasi-randomized controlled trials of IVIg in the treatment of alloimmune HDN. Trials must have used predefined criteria for the use of IVIg and exchange transfusion therapy to be included. We used the standard methods of Cochrane and its Neonatal Review Group. We assessed studies for inclusion and two review authors independently assessed quality and extracted data. We discussed any differences of opinion to reach consensus. We contacted investigators for additional or missing information. We calculated risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) for categorical outcomes. We calculated mean difference (MD) for continuous variables. We used GRADE criteria to assess the risk of bias for major outcomes and to summarize the level of evidence. Nine studies with 658 infants fulfilled the inclusion criteria. Term and preterm infants with Rh or ABO (or both) incompatibility were included. The use of exchange transfusion decreased significantly in the immunoglobulin treated group (typical RR 0.35, 95% CI 0.25 to 0.49; typical RD -0.22, 95% CI -0.27 to

  4. 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.

  5. Structural repertoire of immunoglobulin λ light chains

    KAUST Repository

    Chailyan, Anna; Marcatili, Paolo; Cirillo, Davide; Tramontano, Anna

    2011-01-01

    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.

  6. Potential Confounding of Diagnosis of Rabies in Patients with Recent Receipt of Intravenous Immune Globulin.

    Science.gov (United States)

    Vora, Neil M; Orciari, Lillian A; Bertumen, J Bradford; Damon, Inger; Ellison, James A; Fowler, Vance G; Franka, Richard; Petersen, Brett W; Satheshkumar, P S; Schexnayder, Stephen M; Smith, Todd G; Wallace, Ryan M; Weinstein, Susan; Williams, Carl; Yager, Pamela; Niezgoda, Michael

    2018-02-09

    Rabies is an acute encephalitis that is nearly always fatal. It is caused by infection with viruses of the genus Lyssavirus, the most common of which is Rabies lyssavirus. The Council of State and Territorial Epidemiologists (CSTE) defines a confirmed human rabies case as an illness compatible with rabies that meets at least one of five different laboratory criteria.* Four of these criteria do not depend on the patient's rabies vaccination status; however, the remaining criterion, "identification of Lyssavirus-specific antibody (i.e. by indirect fluorescent antibody…test or complete [Rabies lyssavirus] neutralization at 1:5 dilution) in the serum," is only considered diagnostic in unvaccinated patients. Lyssavirus-specific antibodies include Rabies lyssavirus-specific binding immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies and Rabies lyssavirus neutralizing antibodies (RLNAs). This report describes six patients who were tested for rabies by CDC and who met CSTE criteria for confirmed human rabies because they had illnesses compatible with rabies, had not been vaccinated for rabies, and were found to have serum RLNAs (with complete Rabies lyssavirus neutralization at a serum dilution of 1:5). An additional four patients are described who were tested for rabies by CDC who were found to have serum RLNAs (with incomplete Rabies lyssavirus neutralization at a serum dilution of 1:5) despite having not been vaccinated for rabies. None of these 10 patients received a rabies diagnosis; rather, they were considered to have been passively immunized against rabies through recent receipt of intravenous immune globulin (IVIG). Serum RLNA test results should be interpreted with caution in patients who have not been vaccinated against rabies but who have recently received IVIG.

  7. Clinical Evaluation of Ciprofloxacin Intravenous Preparation ...

    African Journals Online (AJOL)

    The most common site of bacteria infection in humans is the urinary tract. For nosocomial infections it is the catheterized urinary tract. Compromised immune responses in hospitalized patients contribute to the difficulties encountered in treating their infections. In these patients, administration of intravenous antibiotic is ...

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

    International Nuclear Information System (INIS)

    Sui, Weiguo; Che, Wenti; Guimai, Zuo; Chen, Jiejing; Li, Liping; Li, Wuxian; Dai, Yong

    2012-01-01

    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 2 -CH = O), L5 lipids (-CH 2 -C = O), and L3 lipids (-CH 2 -CH 2 -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 research

  9. 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

  10. 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.

  11. Detection of toxoplasma-specific immunoglobulin G in human sera: performance comparison of in house Dot-ELISA with ECLIA and ELISA.

    Science.gov (United States)

    Teimouri, Aref; Modarressi, Mohammad Hossein; Shojaee, Saeedeh; Mohebali, Mehdi; Zouei, Nima; Rezaian, Mostafa; Keshavarz, Hossein

    2018-05-08

    In the current study, performance of electrochemiluminescence immunoassay (ECLIA) in detection of anti-toxoplasma IgG in human sera was compared with that of enzyme-linked immunosorbent assay (ELISA). Furthermore, performance of an in house Dot-ELISA in detection of anti-toxoplasma IgG was compared with that of ECLIA and ELISA. In total, 219 human sera were tested to detect anti-toxoplasma IgG using Dynex DS2® and Roche Cobas® e411 Automated Analyzers. Discordant results rechecked using immunofluorescence assay (IFA). Then, sera were used in an in house Dot-ELISA to assess toxoplasma-specific IgG. Of the 219 samples, two samples were found undetermined using ECLIA but reactive using ELISA. Using IFA, the two sera were reported unreactive. Furthermore, two samples were found reactive using ECLIA and unreactive using ELISA. These samples were reported reactive using IFA. The overall agreement for the two former methods was 98% (rZ0.98.1; P house Dot-ELISA included sensitivity of 79.5, specificity of 78.2, and accuracy of 78.9%, compared to ECLIA and ELISA. Positive and negative predictive values included 82.9 and 74.2%, respectively. A 100% sensitivity was found in in house Dot-ELISA for highly reactive sera in ECLIA and ELISA. ECLIA is appropriate for the first-line serological screening tests and can replace ELISA due to high speed, sensitivity, and specificity, particularly in large laboratories. Dot-ELISA is a rapid, sensitive, specific, cost-effective, user-friendly, and field-portable technique and hence can be used for screening toxoplasmosis, especially in rural fields or less equipped laboratories.

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

    International Nuclear Information System (INIS)

    Kostopoulos, C.; Toubanakis, C.; Mamoulakis, C.; Gialafos, E.; Mavrikakis, M.; Koutsikos, J.; Zerva, C.; Leondi, A.; Moulopoulos, L.A.; Sfikakis, P.P.

    2008-01-01

    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.)

  13. Streptococcus pyogenes Infection and the Human Proteome with a Special Focus on the Immunoglobulin G-cleaving Enzyme IdeS.

    Science.gov (United States)

    Karlsson, Christofer A Q; Järnum, Sofia; Winstedt, Lena; Kjellman, Christian; Björck, Lars; Linder, Adam; Malmström, Johan A

    2018-06-01

    Infectious diseases are characterized by a complex interplay between host and pathogen, but how these interactions impact the host proteome is unclear. Here we applied a combined mass spectrometry-based proteomics strategy to investigate how the human proteome is transiently modified by the pathogen Streptococcus pyogenes , with a particular focus on bacterial cleavage of IgG in vivo In invasive diseases, S. pyogenes evokes a massive host response in blood, whereas superficial diseases are characterized by a local leakage of several blood plasma proteins at the site of infection including IgG. S. pyogenes produces IdeS, a protease cleaving IgG in the lower hinge region and we find highly effective IdeS-cleavage of IgG in samples from local IgG poor microenvironments. The results show that IdeS contributes to the adaptation of S. pyogenes to its normal ecological niches. Additionally, the work identifies novel clinical opportunities for in vivo pathogen detection. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Computed tomography intravenous cholangiography

    International Nuclear Information System (INIS)

    Nascimento, S.; Murray, W.; Wilson, P.

    1997-01-01

    Indications for direct visualization of the bile ducts include bile duct dilatation demonstrated by ultrasound or computed tomography (CT) scanning, where the cause of the bile duct dilatation is uncertain or where the anatomy of bile duct obstruction needs further clarification. Another indication is right upper quadrant pain, particularly in a post-cholecystectomy patient, where choledocholithiasis is suspected. A possible new indication is pre-operative evaluation prior to laparoscopic cholecystectomy. The bile ducts are usually studied by endoscopic retrograde cholangiopancreatography (ERCP), or, less commonly, trans-hepatic cholangiography. The old technique of intravenous cholangiography has fallen into disrepute because of inconsistent bile-duct opacification. The advent of spiral CT scanning has renewed interest in intravenous cholangiography. The CT technique is very sensitive to the contrast agent in the bile ducts, and angiographic and three-dimensional reconstructions of the biliary tree can readily be obtained using the CT intravenous cholangiogram technique (CT IVC). Seven patients have been studied using this CT IVC technique, between February 1995 and June 1996, and are the subject of the present report. Eight further studies have since been performed. The results suggest that CT IVC could replace ERCP as the primary means of direct cholangiography, where pancreatic duct visualization is not required. (authors)

  15. Immunoglobulins and C3 in the P. brasiliensis granuloma

    Directory of Open Access Journals (Sweden)

    Lilian M. V. Biagioni

    1987-04-01

    Full Text Available The experimental model of paracoccidioidomycosis induced in mice by the intravenous injection of yeast-forms of P. brasiliensis (Bt2 strain; 1 x 10(6 viable fungi/animal was used to evaluate sequentially 2, 4, 8, 16 and 20 weeks after inoculation: 1. The presence of immunoglobulins and C3 in the pulmonary granuloma-ta, by direct immunofluorescence; 2. The humoral (immunodiffusion test and the cellular (footpad sweeling test immune response; 3. The histopathology of lesions. The cell-immune response was positive since week 2, showing a transitory depression at week 16. Specific antibodies were first detected at week 4 and peaked at week 16. At histology, epithelioid granulomas with numerous fungi and polymorphonuclear agreggates were seen. The lungs showed progressive involvement up to week 16, with little decrease at week 20. From week 2 on, there were deposits of IgG and C3 around fungal walls within the granulomas and IgG stained cells among the mononuclear cell peripheral halo. Interstitital immunoglobulins and C3 deposits in the granulomas were not letected. IgG and C3 seen to play an early an important role in. the host defenses against P. brasiliensis by possibly cooperating in the killing of parasites and blocking the antigenic diffusion.

  16. EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases: EFNS task force on the use of intravenous immunoglobulin in treatment of neurological diseases

    DEFF Research Database (Denmark)

    Elovaara, I.; Apostolski, S.; Doorn, P. van

    2008-01-01

    and consensus recommendations are given according to EFNS guidance regulations. The efficacy of IVIG has been proven in Guillain-Barre syndrome (level A), chronic inflammatory demyelinating polyradiculoneuropathy (level A), multifocal mononeuropathy (level A), acute exacerbations of myasthenia gravis (MG...

  17. Antigen-specific human NKT cells from tuberculosis patients produce IL-21 to help B cells for the production of immunoglobulins.

    Science.gov (United States)

    Wu, Changyou; Li, Zitao; Fu, Xiaoying; Yu, Sifei; Lao, Suihua; Yang, Binyan

    2015-10-06

    Natural killer T (NKT) cells from mouse and human play an important role in the immune responses against Mycobacterium tuberculosis. However, the function of CD3(+)TCRvβ11(+) NKT cells at the local site of M. tuberculosis infection remains poorly defined. In the present study, we found that after stimulation with M. tuberculosis antigens, NKT cells isolated from tuberculosis (TB) pleural fluid mononuclear cells (PFMCs) produced IL-21 and other cytokines including IFN-γ, TNF-α, IL-2 and IL-17. IL-21-expressing NKT cells in PFMCs displayed effector memory phenotype, expressing CD45RO(high)CD62L(low)CCR7(low). Moreover, NKT cells expressed high levels of CXCR5 and all of IL-21-expressing NKT cells co-expressed CXCR5. The frequency of BCL-6-expression was higher in IL-21-expressing but not in non-IL-21-expressing CD3(+)TCRvβ11(+) NKT cells. Sorted CD3(+)TCRvβ11(+) NKT cells from PFMCs produced IFN-γ and IL-21 after stimulation, which expressed CD40L. Importantly, CD3(+)TCRvβ11(+) NKT cells provided help to B cells for the production of IgG and IgA. Taken together, our data demonstrate that CD3(+)TCRvβ11(+) NKT cells from a local site of M. tuberculosis infection produce IL-21, express CXCR5 and CD40L, help B cells to secrete IgG and IgA, and may participate in local immune responses against M. tuberculosis infection.

  18. The Fab Conformations in the Solution Structure of Human Immunoglobulin G4 (IgG4) Restrict Access to Its Fc Region

    Science.gov (United States)

    Rayner, Lucy E.; Hui, Gar Kay; Gor, Jayesh; Heenan, Richard K.; Dalby, Paul A.; Perkins, Stephen J.

    2014-01-01

    Human IgG4 antibody shows therapeutically useful properties compared with the IgG1, IgG2, and IgG3 subclasses. Thus IgG4 does not activate complement and shows conformational variability. These properties are attributable to its hinge region, which is the shortest of the four IgG subclasses. Using high throughput scattering methods, we studied the solution structure of wild-type IgG4(Ser222) and a hinge mutant IgG4(Pro222) in different buffers and temperatures where the proline substitution suppresses the formation of half-antibody. Analytical ultracentrifugation showed that both IgG4 forms were principally monomeric with sedimentation coefficients s20,w0 of 6.6–6.8 S. A monomer-dimer equilibrium was observed in heavy water buffer at low temperature. Scattering showed that the x-ray radius of gyration Rg was unchanged with concentration in 50–250 mm NaCl buffers, whereas the neutron Rg values showed a concentration-dependent increase as the temperature decreased in heavy water buffers. The distance distribution curves (P(r)) revealed two peaks, M1 and M2, that shifted below 2 mg/ml to indicate concentration-dependent IgG4 structures in addition to IgG4 dimer formation at high concentration in heavy water. Constrained x-ray and neutron scattering modeling revealed asymmetric solution structures for IgG4(Ser222) with extended hinge structures. The IgG4(Pro222) structure was similar. Both IgG4 structures showed that their Fab regions were positioned close enough to the Fc region to restrict C1q binding. Our new molecular models for IgG4 explain its inability to activate complement and clarify aspects of its stability and function for therapeutic applications. PMID:24876381

  19. Association of serum anti-rotavirus immunoglobulin A antibody seropositivity and protection against severe rotavirus gastroenteritis: analysis of clinical trials of human rotavirus vaccine.

    Science.gov (United States)

    Cheuvart, Brigitte; Neuzil, Kathleen M; Steele, A Duncan; Cunliffe, Nigel; Madhi, Shabir A; Karkada, Naveen; Han, Htay Htay; Vinals, Carla

    2014-01-01

    Clinical trials of the human rotavirus vaccine Rotarix™ (RV1) have demonstrated significant reductions in severe rotavirus gastroenteritis (RVGE) in children worldwide. However, no correlate of vaccine efficacy (VE) has yet been established. This paper presents 2 analyses which aimed to investigate whether serum anti-RV IgA measured by ELISA 1 or 2 mo post-vaccination can serve as a correlate of efficacy against RVGE: (1) In a large Phase III efficacy trial (Rota-037), the Prentice criteria for surrogate endpoints was applied to anti-RV IgA seropositivity 1 mo post-vaccination. These criteria determine whether a significant vaccine group effect can be predicted from the surrogate, namely seropositivity (anti-RV IgA concentration>20 U/mL); (2) Among other GSK-sponsored RV1 VE studies, 8 studies which assessed immunogenicity at 1 or 2 mo post-vaccination in all or a sub-cohort of enrolled subjects and had at least 10 RVGE episodes were included in a meta-analysis to measure the regression between clinical VE and VE predicted from immunogenicity (VE1). In Rota-037, anti-RV IgA seropositivity post-vaccination was associated with a lower incidence of any or severe RVGE, however, the proportion of vaccine group effect explained by seropositivity was only 43.6% and 32.7% respectively. This low proportion was due to the vaccine group effect observed in seronegative subjects. In the meta-analysis, the slope of the regression between clinical VE and VE1 was statistically significant. These two independent analyses support the hypothesis that post-vaccination anti-RV IgA seropositivity (antibody concentration ≥20 U/mL) may serve as a useful correlate of efficacy in clinical trials of RV1 vaccines.

  20. 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. © The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  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 sy...

  2. Detection of inflammatory lesions with radiolabelled immunoglobulins

    International Nuclear Information System (INIS)

    Blok, D.; Rijksuniversiteit Leiden; Ogtrop, M. van; Arndt, J.W.; Camps, J.A.J.; Feitsma, R.I.J.; Pauwels, E.K.J.

    1990-01-01

    Previous reports on the use of radiolabelled immunoglobulins led us to undertake a pilot experiment in an animal model to investigate the potentials sodium pertechnate Tc 99m-immunoglobulin scintigraphy in the detection of infectious foci. Mice infected in one leg with staphylococcus infection in were injected with sodium pertechnote Tc 99m-immunoglobulin, albumin aggregated technetium Tc 99m or gallium citrate Ga 67. The results obtained by scintigraphy suggested a specific accumulation of radiolabelled immunoglobulin at the site of infection. Visualization of the infection and the image quality, especially the 6- and 24-h images, were clearly enhanced after the use of immunoglobulin preparations as compared with those labelled with gallium. (orig.)

  3. Comparison of techniques of detecting immunoglobulin-binding protein reactivity to immunoglobulin produced by different avian and mammalian species.

    Science.gov (United States)

    Justiz-Vaillant, A A; Akpaka, P E; McFarlane-Anderson, N; Smikle, M F

    2013-01-01

    The rationale of this study was to use several immunological assays to investigate the reactivity of immunoglobulin binding protein (IBP) to immunoglobulins from various avian and mammalian species. The IBP studied were Staphylococcal protein A (SpA), Streptococcal protein G (SpG), Peptostreptococcal protein L (SpL) and recombinant protein LA (SpLA). The various immunological techniques used were double immunodiffusion (Ouchterlony technique) that tested positive high protein reactivities, direct and competitive enzyme-linked immunosorbent assays (ELISAs) that tested moderate and low positive protein binding capacities, respectively. In addition to sandwich ELISAs, immunoblot analyses and Ig-purification by SpA-affinity chromatography, which were sensitive tests and helpful in the screening and confirmatory tests were also used. The Ouchterlony technique showed that compared to the other proteins, SpLA had the highest range of reactivity with animal sera and purified immunoglobulins while SpL was least reactive. With the direct ELISA, SpL reacted with the raccoon sera, rabbit IgG and with IgY from bantam hens and pigeons. While with the direct ELISA, SpA reacted with sera from skunk, coyote, raccoon, mule, donkey and human. The sandwich ELISA revealed high reactivity of both SpG and SpLA with mammalian sera titres ranging from 1:32 (raccoon serum) to 1:1024 (mule and donkey sera). These results suggest that IBP can be used for the detection of immunoglobulin using various immunological assays and this is important for the diagnosis of infectious diseases in animal and bird populations studied and in the purification of immunoglobulins.

  4. Quantitation of Fc receptors and surface immunoglobulin is affected by cell isolation procedures using plasmagel and ficoll-hypaque.

    Science.gov (United States)

    Alexander, E L; Titus, J A; Segal, D M

    1978-01-01

    When mononuclear leukocytes are isolated directly from whole human blood using Ficoll-Hypaque or Plasmagel, cytophilic immunoglobulin is detected on cell surfaces. Upon incubation at 37 degrees C, this cell-associated immunoglobulin is shed slowly into the medium. However, when cells are prewashed in phosphate-buffered saline prior to isolation, they appear to be free of cytophilic immunoglobulin. Compared to prewashed cells, populations retaining cytophilic immunoglobulin on their surfaces demonstrate a decreased binding of soluble immune complexes and radiolabelled trimeric rabbit IgG. The data suggest that Ficoll-Hypaque and Plasmagel cause serum IgG to bind with abnormally high affinity to human mononuclear leukocytes, probably via Fc receptors. This artifact of preparation can lead to erroneous estimates of the numbers of cells bearing Fc receptors or intrinsic membrane immunoglobulin within a given population of cells and to an inaccurate assessment of the average number of Fc receptors per cell.

  5. Enrichment of sialylated IgG by lectin fractionation does not enhance the efficacy of immunoglobulin G in a murine model of immune thrombocytopenia

    NARCIS (Netherlands)

    Guhr, T.; Bloem, J.; Derksen, N.I.L.; Wuhrer, M.; Koenderman, A.H.L.; Aalberse, R.C.; Rispens, T.

    2011-01-01

    Intravenous immunoglobulin G (IVIg) is widely used against a range of clinical symptoms. For its use in immune modulating therapies such as treatment of immune thrombocytopenic purpura high doses of IVIg are required. It has been suggested that only a fraction of IVIg causes this anti immune

  6. Intravenous high-dose immunotherapy: practical recommendations for use in the treatment of neurological disimmune diseases

    Directory of Open Access Journals (Sweden)

    N. A. Suponeva

    2015-01-01

    Full Text Available Current publication summarizes main indications and benefits of intravenous high-dose immunotherapy (IHI in the treatment of various autoimmune diseases of the peripheral nervous system. Available products of intravenous immunoglobulin (IVIG on the Russian market are reviewed. Tactics for choosing optimal medication for IHI based on its effectiveness and safety are analyzed. Dosage calculation and way of administration of IVIG are described, beeing of a high practical value in neurologist’s daily work.

  7. [Effect of compound danshen dripping pill combined with intravenous transplantation of human umbilical cord blood mononuclear cells on local inflammatory response in the myocardium of rabbits with acute myocardial infarction].

    Science.gov (United States)

    Deng, Liu-xia; Yu, Guo-long; Al, Qi; Yuan, Chun-ju

    2013-11-01

    To investigate effect of Compound Danshen Dripping Pill (CDDP) on the inflammatory response of the myocardium of acute myocardial infarction (AMI) rabbits, to observe the therapeutic effect of CDDP combined intravenous transplantation of human umbilical cord blood mononuclear cells (HUCBMCs) on inflammatory response, pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) , and heart function in the myocardium of AMI rabbits, and to explore the possible protective mechanisms of the combined therapy. The AMI model was successfully established by ligation of the left anterior coronary artery (LAD) in 40 healthy rabbits.Then they were randomly divided into four groups, i.e., the control group, the CDDP group, the transplantation group, and the combined group, 10 in each group. Rabbits in the control group received intravenous injection of 0.5 mL normal saline via ear vein within 24 h after AMI and then intragastric infusion of normal saline at 5 mL per day. Rabbits in the CDDP group received intravenous injection of 0.5 mL normal saline via ear vein within 24 h after AMI and then intragastric infusion of solution obtained by solving 270 mg CDDP in 5 mL normal saline per day. Rabbits in the transplantation group received intravenous injection of 0.5 mL normal saline labeled with green fluorescent protein (GFP) containing 3 x 10(7) of HUCBMCs via ear vein within 24 h after AMI and then intragastric infusion of normal saline at 5 mL per day. Rabbits in the combined group received intravenous injection of 0.5 mL normal saline labeled with GFP containing 3 x 10(7) of HUCBMCs via ear vein within 24 h after AMI and then intragastric infusion of solution obtained by solving 270 mg CDDP in 5 mL normal saline per day. At week 1 and 4 after treatment, cardiac function indices such as left ventricular fractional shorting (LVFS) and left ventricular ejection fraction (LVEF) were performed by echocardiography; the number of transplanted cells in the myocardium was found

  8. The Prospect of Immunoglobulin Y for Therapy of Canine parvovirus Infection in Dogs

    Directory of Open Access Journals (Sweden)

    I Gusti Ayu Agung Suartini

    2015-06-01

    Full Text Available Canine parvovirus (CPV is a highly infectious virus. The virus causes death in dogs worldwide. The mortality rate due to infection of CPV in dog reaches 91%. Prevention of CPV infection in puppies has been done by vaccination which is effectively proven. Protective mechanisms of maternal antibodies contribute to the failure of vaccination. Highly stable characteristics of parvovirus enable the virus still exist in the environment. Various therapies are performed only to suppress the clinical symptoms but can not reduce puppy mortalities. This review discusses CPV alternative therapy and the advantages using immunoglobulin Y (IgY specific antibodies isolated from chicken egg yolk. Immunoglobulin Y will neutralize the virus, so it can not infect host cells. Intravenous IgY therapy has shown to suppress the spread of CPV infection and prevent death.

  9. Intravenous versus oral etoposide

    DEFF Research Database (Denmark)

    Ali, Abir Salwa; Grönberg, Malin; Langer, Seppo W.

    2018-01-01

    High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs, G3) are aggressive cancers of the digestive system with poor prognosis and survival. Platinum-based chemotherapy (cisplatin/carboplatin + etoposide) is considered the first-line palliative treatment. Etoposide is frequently...... administered intravenously; however, oral etoposide may be used as an alternative. Concerns for oral etoposide include decreased bioavailability, inter- and intra-patient variability and patient compliance. We aimed to evaluate possible differences in progression-free survival (PFS) and overall survival (OS......) in patients treated with oral etoposide compared to etoposide given as infusion. Patients (n = 236) from the Nordic NEC study were divided into three groups receiving etoposide as a long infusion (24 h, n = 170), short infusion (≤ 5 h, n = 33) or oral etoposide (n = 33) according to hospital tradition. PFS...

  10. Intraarterial reteplase and intravenous abciximab for treatment of acute ischemic stroke. A preliminary feasibility and safety study in a non-human primate model

    International Nuclear Information System (INIS)

    Qureshi, Adnan I.; Suri, M. Fareed K.; Ali, Zulfiqar; Ringer, Andrew J.; Boulos, Alan S.; Guterman, Lee R.; Hopkins, L. Nelson; Nakada, Marian T.; Alberico, Ronald A.; Martin, Lisa B.E.

    2005-01-01

    We performed a preliminary feasibility and safety study using intravenous (IV) administration of a platelet glycoprotein IIb/IIIa inhibitor (abciximab) in conjunction with intraarterial (IA) administration of a thrombolytic agent (reteplase) in a primate model of intracranial thrombosis. We introduced thrombus through superselective catheterization of the intracranial segment of the internal carotid artery in 16 primates. The animals were randomly assigned to receive IA reteplase and IV abciximab (n =4), IA reteplase and IV placebo (n =4), IA placebo and IV abciximab (n =4) or IA and IV placebo (n =4). Recanalization was assessed by serial angiography during the 6-h period after initiation of treatment. Postmortem magnetic resonance (MR) imaging was performed to determine the presence of cerebral infarction or intracranial hemorrhage. Partial or complete recanalization at 6 h after initiation of treatment (decrease of two or more points in pre-treatment angiographic occlusion grade) was observed in two animals treated with IA reteplase and IV abciximab, three animals treated with IA reteplase alone and one animal treated with IV abciximab alone. No improvement in perfusion was observed in animals that received IV and IA placebo. Cerebral infarction was demonstrated on postmortem MR imaging in three animals that received IA and IV placebo and in one animal each from the groups that received IA reteplase and IV abciximab or IV abciximab alone. One animal that received IV abciximab alone had a small intracerebral hemorrhage on MR imaging. (orig.)

  11. Enhancement of polymeric immunoglobulin receptor transcytosis by biparatopic VHH.

    Directory of Open Access Journals (Sweden)

    Chris D Emmerson

    Full Text Available The polymeric immunoglobulin receptor (pIgR ensures the transport of dimeric immunoglobulin A (dIgA and pentameric immunoglobulin M (pIgM across epithelia to the mucosal layer of for example the intestines and the lungs via transcytosis. Per day the human pIgR mediates the excretion of 2 to 5 grams of dIgA into the mucosa of luminal organs. This system could prove useful for therapies aiming at excretion of compounds into the mucosa. Here we investigated the use of the variable domain of camelid derived heavy chain only antibodies, also known as VHHs or Nanobodies®, targeting the human pIgR, as a transport system across epithelial cells. We show that VHHs directed against the human pIgR are able to bind the receptor with high affinity (∼1 nM and that they compete with the natural ligand, dIgA. In a transcytosis assay both native and phage-bound VHH were only able to get across polarized MDCK cells that express the human pIgR gene in a basolateral to apical fashion. Indicating that the VHHs are able to translocate across epithelia and to take along large particles of cargo. Furthermore, by making multivalent VHHs we were able to enhance the transport of the compounds both in a MDCK-hpIgR and Caco-2 cell system, probably by inducing receptor clustering. These results show that VHHs can be used as a carrier system to exploit the human pIgR transcytotic system and that multivalent compounds are able to significantly enhance the transport across epithelial monolayers.

  12. 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.

  13. Clinical applications of immunoglobulin in neuromuscular diseases: focus on inflammatory myopathies

    Directory of Open Access Journals (Sweden)

    Paulo Victor Sgobbi de Souza

    2014-12-01

    Full Text Available During recent years, an increasing number of neuromuscular diseases have been recognized either to be caused primarily by autoimmune mechanisms, or to have important autoimmune components. The involved pathophysiological mechanisms and clinical manifestations have been better recognized and many of these disorders are potentially treatable by immunosuppression or by immunomodulation with intravenous immunoglobulin (IVIg. IVIg has been tried in a variety of immune-mediated neurological diseases, being target of widespread use in central and peripheral nervous systems diseases. Objective To give an overview of the main topics regarding the mechanism of action and different therapeutic uses of IVIg in neurological practice, mainly in neuromuscular diseases.

  14. Acute Toxicity of Intravenously Administered Titanium Dioxide Nanoparticles in Mice

    OpenAIRE

    Xu, Jiaying; Shi, Hongbo; Ruth, Magaye; Yu, Hongsheng; Lazar, Lissy; Zou, Baobo; Yang, Cui; Wu, Aiguo; Zhao, Jinshun

    2013-01-01

    BACKGROUND: With a wide range of applications, titanium dioxide (TiO₂) nanoparticles (NPs) are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO₂ nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans. METHODS: In this study, mice were injected intravenously with a single dose of TiO₂ NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg). Animal mortality, blood biochem...

  15. Ultrasonography versus intravenous urography

    International Nuclear Information System (INIS)

    Aslaksen, A.

    1991-01-01

    The present study was performed to compare the clinical value of urography and ultrasonography in a non-selected group of patients referred for urography to a university hospital. The conslusions and clinical implications of the study are as follows: Intravenous urography remains the cornerstone imaging examination in the evaluation of ureteral calculi. Ultrasonography is a valuable adjunct in cases of non- visualization of the kidneys, in distal obstruction and known contrast media allergy. When women with recurrent urinary tract infection are referred for imaging of the urinary tract, ultrasonography should be used. Ultrasonography should replace urography for screening of non-acute hydronephrosis like in female genital cancer and benign prostate hyperplasia. There is good correlation between urography and ultrasonography in assessing the degree of hydronephrosis. However, more researh on the relationship between hydronephrosis and obstruction is necessary. Ultrasonography should be used as the only imaging method of the upper urinary tract in patients with microscopic hematuria. In patients less than 50 years with macroscopic hematuria, ultrasonography should be used as the only imaging of the upper urinary tract, and an examination of the urinary bladder should be included. In patients over 50 years, urography supplied with ultrasonography should be used, but more research is necessary on the subject of imaging method and age. 158 refs

  16. Immunoglobulin E-Mediated Autoimmunity

    Directory of Open Access Journals (Sweden)

    Marcus Maurer

    2018-04-01

    Full Text Available The study of autoimmunity mediated by immunoglobulin E (IgE autoantibodies, which may be termed autoallergy, is in its infancy. It is now recognized that systemic lupus erythematosus, bullous pemphigoid (BP, and chronic urticaria, both spontaneous and inducible, are most likely to be mediated, at least in part, by IgE autoantibodies. The situation in other conditions, such as autoimmune uveitis, rheumatoid arthritis, hyperthyroid Graves’ disease, autoimmune pancreatitis, and even asthma, is far less clear but evidence for autoallergy is accumulating. To be certain of an autoallergic mechanism, it is necessary to identify both IgE autoantibodies and their targets as has been done with the transmembrane protein BP180 and the intracellular protein BP230 in BP and IL-24 in chronic spontaneous urticaria. Also, IgE-targeted therapies, such as anti-IgE, must have been shown to be of benefit to patients as has been done with both of these conditions. This comprehensive review of the literature on IgE-mediated autoallergy focuses on three related questions. What do we know about the prevalence of IgE autoantibodies and their targets in different diseases? What do we know about the relevance of IgE autoantibodies in different diseases? What do we know about the cellular and molecular effects of IgE autoantibodies? In addition to providing answers to these questions, based on a broad review of the literature, we outline the current gaps of knowledge in our understanding of IgE autoantibodies and describe approaches to address them.

  17. On the Dark Side of Therapies with Immunoglobulin Concentrates: The Adverse Events

    OpenAIRE

    Sp?th, Peter J.; Granata, Guido; La Marra, Fabiola; Kuijpers, Taco W.; Quinti, Isabella

    2015-01-01

    Abstract to the dark side of therapies with human immunoglobulin G concentratesTherapy by human immunoglobulin G (IgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A p...

  18. Granulomatous interstitial pneumonia in a miniature swine associated with repeated intravenous injections of Tc-99m human serum albumin: concise communication

    International Nuclear Information System (INIS)

    Whinnery, J.E.; Young, J.T.

    1980-01-01

    Albumin lung-scanning agents have a proven high degree of safety, with the only contraindication to their use being allergic hypersensitivity. We have used these agents to investigate the physiologic effects of high G/sub z/ acceleratory forces on pulmonary perfusion using the miniature swine. Multiple doses of human macroaggregated albumin and human-albumin microspheres were given to a miniature swine at various levels of centrifugal acceleration over a 6-wk period. The dosages given were the same per kilogram as those used for routine clinical human studies. The animal subsequently died from a severe granulomatous interstitial pneumonia. The granulomatous lesions suggest that the pathogenesis may have involved a cell-mediated delayed hypersensitivity. This interstitial pneumonia may represent the end point in a chronic hypersensitivity response to the human-albumin lung-scanning agents

  19. CERTIFICATION REPORT The certification of the mass concentration of immunoglobulin G proteinase 3 anti-neutrophil cytoplasmic autoantibodies (IgG PR3 ANCA) in human serum: ERM® - DA483/IFCC

    OpenAIRE

    MONOGIOUDI EVANTHIA; HUTU DANA PETRONELA; CHAROUD-GOT JEAN; SHELDON JOANNA; SCHIMMEL HEINZ; TRAPMANN STEFANIE; MERONI PIERLUIGI; EMONS HENDRIK; ZEGERS INGRID

    2017-01-01

    This report describes the production and certification of ERM-DA483/IFCC, a serum protein reference material intended for the standardisation of measurements of immunoglobulin G proteinase 3 anti-neutrophil cytoplasmic autoantibodies (IgG PR3 ANCA). The material was produced according to ISO Guide 34:2009 [ ] and is certified in accordance with ISO Guide 35:2006. The raw material used to prepare ERM-DA483/IFCC was a plasmapheresis material containing a high concentration of IgG PR3 ANCA. A...

  20. Tumor tropism of intravenously injected human-induced pluripotent stem cell-derived neural stem cells and their gene therapy application in a metastatic breast cancer model.

    Science.gov (United States)

    Yang, Jing; Lam, Dang Hoang; Goh, Sally Sallee; Lee, Esther Xingwei; Zhao, Ying; Tay, Felix Chang; Chen, Can; Du, Shouhui; Balasundaram, Ghayathri; Shahbazi, Mohammad; Tham, Chee Kian; Ng, Wai Hoe; Toh, Han Chong; Wang, Shu

    2012-05-01

    Human pluripotent stem cells can serve as an accessible and reliable source for the generation of functional human cells for medical therapies. In this study, we used a conventional lentiviral transduction method to derive human-induced pluripotent stem (iPS) cells from primary human fibroblasts and then generated neural stem cells (NSCs) from the iPS cells. Using a dual-color whole-body imaging technology, we demonstrated that after tail vein injection, these human NSCs displayed a robust migratory capacity outside the central nervous system in both immunodeficient and immunocompetent mice and homed in on established orthotopic 4T1 mouse mammary tumors. To investigate whether the iPS cell-derived NSCs can be used as a cellular delivery vehicle for cancer gene therapy, the cells were transduced with a baculoviral vector containing the herpes simplex virus thymidine kinase suicide gene and injected through tail vein into 4T1 tumor-bearing mice. The transduced NSCs were effective in inhibiting the growth of the orthotopic 4T1 breast tumor and the metastatic spread of the cancer cells in the presence of ganciclovir, leading to prolonged survival of the tumor-bearing mice. The use of iPS cell-derived NSCs for cancer gene therapy bypasses the sensitive ethical issue surrounding the use of cells derived from human fetal tissues or human embryonic stem cells. This approach may also help to overcome problems associated with allogeneic transplantation of other types of human NSCs. Copyright © 2012 AlphaMed Press.

  1. Immunomodulatory Mechanisms of Intravenous Immunoglobulin : Towards Safer Immunosuppression after Liver Transplantation

    NARCIS (Netherlands)

    S.W.A. Tjon (Angela)

    2014-01-01

    markdownabstract__Abstract__ Immunity originates from the Latin term immunis, meaning “exempt”, which refers to all the mechanisms used by the body as protection against invasion by agents that are foreign to the body. These agents may be infectious pathogens, foods, chemicals, drugs, and, in

  2. Headache and Nausea after Treatment with High-Dose Subcutaneous versus Intravenous Immunoglobulin

    DEFF Research Database (Denmark)

    Markvardsen, Lars H; Christiansen, Ingelise; Andersen, Henning

    2015-01-01

    and could be an alternative in patients experiencing side effects. Fifty-nine patients diagnosed with neurological disorders (chronic inflammatory demyelinating polyneuropathy (CIDP), multi-focal motor neuropathy (MMN) or post-polio syndrome) were treated with IVIG, and 27 CIDP or MMN patients with SCIG...

  3. Serum albumin level predicts initial intravenous immunoglobulin treatment failure in Kawasaki disease.

    Science.gov (United States)

    Kuo, Ho-Chang; Liang, Chi-Di; Wang, Chih-Lu; Yu, Hong-Ren; Hwang, Kao-Pin; Yang, Kuender D

    2010-10-01

    Kawasaki disease (KD) is a systemic vasculitis primarily affecting children who are initial IVIG treatment. This study was conducted to investigate the risk factors for initial IVIG treatment failure in KD. Children who met KD diagnosis criteria and were admitted for IVIG treatment were retrospectively enrolled for analysis. Patients were divided into IVIG-responsive and IVIG-resistant groups. Initial laboratory data before IVIG treatment were collected for analysis. A total of 131 patients were enrolled during the study period. At 48 h after completion of initial IVIG treatment, 20 patients (15.3%) had an elevated body temperature. Univariate analysis showed that patients who had initial findings of high neutrophil count, abnormal liver function, low serum albumin level (≤2.9 g/dL) and pericardial effusion were at risk for IVIG treatment failure. Multivariate analysis with a logistic regression procedure showed that serum albumin level was considered the independent predicting factor of IVIG resistance in patients with KD (p = 0.006, OR = 40, 95% CI: 52.8-562). There was no significant correlation between age, gender, fever duration before IVIG treatment, haemoglobin level, total leucocyte and platelet counts, C-reactive protein level, or sterile pyuria and initial IVIG treatment failure. The specificity and sensitivity for prediction of IVIG treatment failure in this study were 96% and 34%, respectively. Pre-IVIG treatment serum albumin levels are a useful predictor of IVIG resistance in patients with KD. © 2010 The Author(s)/Journal Compilation © 2010 Foundation Acta Paediatrica.

  4. Timing of Intravenous Immunoglobulin Treatment and Risk of Coronary Artery Abnormalities in Children with Kawasaki Disease

    Directory of Open Access Journals (Sweden)

    Aswine K. Bal

    2014-10-01

    Conclusion: The results of this study suggest that although IVIG treatment within 10 days is important to minimize development of cardiac pathology, neither occurrence of CA lesions in IVIG-treated children nor the time frame for resolution of established CA abnormalities was associated with the timing of IVIG administration. Age 40 mm/hour predict a delay in resolution of CA lesions among children with KD.

  5. Retreatment with intravenous immunoglobulin (IVIG of refractory Guillain Barre syndrome in children

    Directory of Open Access Journals (Sweden)

    Rivas Larrauri Francisco

    2014-07-01

    Full Text Available Guillain-Barré syndrome (GBS is an acute symmetrical pa- ralyzing disease due to a demyelinating polyrradiculoneuropathy, often induced by a preceding infection 1. The main modalities for the treatment of GBS include plasmapheresis and intrave- nous immune globulin. Reports of the use of IVIG in children with GBS are limited: 1 g/kg for two days or 400 mg/kg for five days. While these studies in children are not definitive because of design limitations, their results are consistent with the larger randomized trials in adults 2,3.

  6. Tick-borne encephalitis virus neutralization by high dose intravenous immunoglobulin

    Czech Academy of Sciences Publication Activity Database

    Elsterová, Jana; Palus, Martin; Širmarová, J.; Kopecký, J.; Niller, H.H.; Růžek, Daniel

    2017-01-01

    Roč. 8, č. 2 (2017), s. 253-258 ISSN 1877-959X R&D Projects: GA MZd(CZ) NV16-34238A Institutional support: RVO:60077344 Keywords : flavivirus * ticks * neutralizing antibodies * ivig * antibody-dependent enhancement * ammunotherapy Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 3.230, year: 2016

  7. In vitro regulation of immunoglobulin synthesis after human marrow transplantation. II. Deficient T and non-T lymphocyte function within 3-4 months of allogeneic, syngeneic, or autologous marrow grafting for hematologic malignancy

    International Nuclear Information System (INIS)

    Witherspoon, R.P.; Lum, L.G.; Storb, R.; Thomas, E.D.

    1982-01-01

    Immunoglobulin secretion was studied in 37 patients between 19 and 106 days after allogeneic HLA-identical (30 patients), allogeneic one HLA-haplotype-identical (three patients), syngeneic (three patients), or autologous (one patient) marrow grafting. E rosette-positive (T) and E rosette-negative (non-T) peripheral blood mononuclear cells were cocultured with pokeweed mitogen for 6 days. Polyvalent immunoglobulin secretion was determined by counting plaque forming cells in a reverse hemolytic plaque assay. The number of antibody secreting cells in cocultures of autologous T and non-T lymphocytes was low in 40 of 44 tests conducted on samples from the 37 patients. Mononuclear or non-T cells from 38 of 40 tests failed to produce antibody when cultured with normal helper T cells. T cells from 23 of 37 tests failed to help normal non-T cells secrete antibody. T lymphocytes from 23 of 41 tests suppressed antibody production greater than 80% by normal T and non-T cells. The suppressor cells were radiosensitive in 17 of the 25 tests. The abnormal function of lymphocyte subpopulations in patients during the first 3 mo after syngeneic, allogeneic or autologous marrow grafting was similar regardless of the type of graft or the presence of acute graft versus host disease

  8. Analysis of Serum proteom before and after Intravenous Injection of wild ginseng herbal acupuncture

    Directory of Open Access Journals (Sweden)

    Tae-Sik Kang

    2004-12-01

    Full Text Available Objectives : To observe changes in the serum proteins before and after intravenous injection of wild ginseng herbal acupuncture. Methods : Blood was collected before and after the administration of wild ginseng herbal acupuncture and only the serum was centrifuged. Then differences in the spots on the scanned image after running 2-Dimensional electrophoresis were located and conducted mass analysis and protein identification. Results : Following results were obtained from the comparative analysis of serum proteins before and after the administration of wild ginseng herbal acupuncture. 1. 28 spots were identified before and after the administration. 2. In confirming manifestation degree, spots with more than two-times increase were 204, 803, 1505, 2205, 3105, 7104, 9001 spots, with more than one-time increase were 1101, 1302, 2013, 3009, 3010, 4002, 4009, 6706, 7103, 8006, 8101, and spots with decrease were 205, 801, 3205, 5202, 6105. 3. After conducting protein identification, proteins 205, 804, 1302, 4009, 6105, 6106 are unidentified yet, and 1101 is unnamed protein. Protein 204 is identified as complement receptor CR2-C3d, 801 as YAP1 protein, 803 as antitrypsin polymer, 1505 as PRO0684, 2013 and 3010 as proapolipoprotein, 2205 as USP48, 2403 as vitamin D binding protein, 3009 as complement component 4A preprotein, 3105 as immunoglobulin lambda chain, 3205 as transthyretin, 4002 as Ras-related protein Ral-A, 4204 as beta actin, 5202 and 7104 as apolipoprotein L1, 6704 as alpha 2 macroglobulin precursor, 7103 as complement component 3 precursor, 8006 as testis-specific protein Y, 8101 as transferrin, 9001 as (Alpha-Oxy, Beta-(C112gdeoxy T-State Human Hemoglobin, and 9003 as human hemoglobin. 4. Immune protein CR2-C3d, which acts against microbes and pathogenic organisms, and Antitrypsin(803, which is secreted with inflammatory response in the lungs, were increased by more than 200% after the administration of herbal acupuncture. 5

  9. A novel double-tracer technique to characterize absorption, distribution, metabolism and excretion (ADME) of [14C]tofogliflozin after oral administration and concomitant intravenous microdose administration of [13C]tofogliflozin in humans.

    Science.gov (United States)

    Schwab, Dietmar; Portron, Agnes; Backholer, Zoe; Lausecker, Berthold; Kawashima, Kosuke

    2013-06-01

    Human mass balance studies and the assessment of absolute oral bioavailability (F) are usually assessed in separate studies. Intravenous microdose administration of an isotope tracer concomitant to an unlabeled oral dose is an emerging technique to assess F. We report a novel double-tracer approach implemented for tofogliflozin combining oral administration of a radiolabel tracer with concomitant intravenous administration of a stable isotope tracer. Tofogliflozin is a potent and selective sodium/glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus currently in clinical development. The objectives of the present study were to assess the systemic exposure of major circulating metabolites, excretion balance, F and contribution of renal clearance (CLR) to total clearance (CL) of tofogliflozin in healthy subjects within one study applying a novel double-tracer technique. Six healthy male subjects received 20 mg [(12)C/(14)C]tofogliflozin (3.73 MBq) orally and a concomitant microdose of 0.1 mg [(13)C]tofogliflozin intravenously. Pharmacokinetics of tofogliflozin were determined for the oral and intravenous route; the pharmacokinetics of the metabolites M1 and M5 were determined for the oral route. Quantification of [(12)C]tofogliflozin in plasma and urine and [(13)C]tofogliflozin in plasma was performed by selective LC-MS/MS methods. For the pre-selected metabolites of tofogliflozin, M1 and M5, a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to plasma and urine samples. Total radioactivity was assessed in plasma, urine and feces. Pharmacokinetic analysis was conducted by non-compartmental methods. The pharmacokinetics of tofogliflozin in healthy subjects were characterized by an F of 97.5 ± 12.3 %, CL of 10.0 ± 1.3 l/h and volume of distribution at steady-state (V(ss)) of 50.6 ± 6.7 l. The main route of elimination of total drug-related material was by excretion into urine (77.0 ± 4.1 % of the dose). The

  10. Methods of preparing and using intravenous nutrient compositions

    International Nuclear Information System (INIS)

    Beigler, M.A.; Koury, A.J.

    1983-01-01

    A method for preparing a stable, dry-packaged, sterile, nutrient composition which upon addition of sterile, pyrogen-free water is suitable for intravenous administration to a mammal, including a human, is described. The method comprises providing the nutrients in a specific dry form and state of physical purity acceptable for intravenous administration, sealing the nutrients in a particular type of container adapted to receive and dispense sterile fluids and subjecting the container and its sealed contents to a sterilizing, nondestructive dose of ionizing radiation. The method results in a packaged, sterile nutrient composition which may be dissolved by the addition of sterile pyrogen-free water. The resulting aqueous intravenous solution may be safely administered to a mammal in need of nutrient therapy. The packaged nutrient compositions of the invention exhibit greatly extended storage life and provide an economical method of providing intravenous solutions which are safe and efficacious for use. (author)

  11. Experience with polyclonal immunoglobulin therapy in poly trauma patients with severe sepsis

    International Nuclear Information System (INIS)

    Janjua, S.K.; Hussain, R.M.; Mohsin, S.T.; Iqbal, A.; Mishwani, A.H.

    2011-01-01

    To evaluate the effects of intravenous immunoglobulin therapy on progression of severe sepsis in patients of poly trauma. Design: Quasi-experimental study. Place and Duration of Study: Combined Military Hospital Peshawar from June 2008 to Dec 2009. Patients and Methods: Forty six patients of poly trauma with severe sepsis were included. Along with the standard management i.e., surgical management, fluid resuscitation, antibiotics, analgesics, ionotropic, ventilatory and nutritional support, IVIG 5% (intravenous immunoglobulin) was infused over a period of 6 hours and repeated for three consecutive days. Sequential Organ Failure Assessment (SOFA) score was used to assess the progress in all the patients. Results: At the time of enrolment mean SOFA score was 5.41+- 1.127 and on the 15 day it was 1.62 +- 2.24, mean age was 39.21+10.26 years. Thirty four patients (73.91%) developed gram negative sepsis and eighteen patients (39.13%) developed septic shock. Mean duration of stay in ICU and on ventilatory support was 20.80+9.61 and 10.52 + 5.52 days respectively. Thirty five days mortality rate of these patients was 30.43%. Conclusion: The IVIG administration, when used along with the standard management appears to improve significantly the prognosis in patients of poly trauma with severe sepsis. (author)

  12. Using Mass Spectrometry to Quantify Rituximab and Perform Individualized Immunoglobulin Phenotyping in ANCA-Associated Vasculitis

    NARCIS (Netherlands)

    Mills, John R.; Cornec, Divi; Dasari, Surendra; Ladwig, Paula M.; Hummel, Amber M.; Cheu, Melissa; Murray, David L.; Willrich, Maria A.; Snyder, Melissa R.; Hoffman, Gary S.; Kallenberg, Cees G. M.; Langford, Carol A.; Merkel, Peter A.; Monach, Paul A.; Seo, Philip; Spiera, Robert F.; St Cair, E. William; Stone, John H.; Specks, Ulrich; Barnidge, David R.

    2016-01-01

    Therapeutic monoclonal immunoglobulins (mAbs) are used to treat patients with a wide range of disorders including autoimmune diseases. As pharmaceutical companies bring more fully humanized therapeutic mAb drugs to the healthcare market analytical platforms that perform therapeutic drug monitoring

  13. On the dark side of therapies with immunoglobulin concentrates: the adverse events

    NARCIS (Netherlands)

    Späth, Peter J.; Granata, Guido; La Marra, Fabiola; Kuijpers, Taco W.; Quinti, Isabella

    2015-01-01

    Therapy by human immunoglobulin G (lgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase

  14. 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...

  15. 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

  16. Ancient Phylogenetic Beginnings of Immunoglobulin Hypermutation

    Czech Academy of Sciences Publication Activity Database

    Kubrycht, J.; Sigler, Karel; Růžička, Michal; Souček, P.; Borecký, J.; Ježek, Petr

    2006-01-01

    Roč. 63, - (2006), s. 691-706 ISSN 0022-2844 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z50110509 Keywords : immunoglobulin * hypermutation * antigen Subject RIV: EE - Microbiology, Virology Impact factor: 2.767, year: 2006

  17. Immunoglobulins and their fragments on solid surfaces

    NARCIS (Netherlands)

    Buijs, J.A.G.

    1995-01-01

    Summary

    Adsorption 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

  18. Orthostatic stability with intravenous levodopa

    Directory of Open Access Journals (Sweden)

    Shan H. Siddiqi

    2015-08-01

    Full Text Available Intravenous levodopa has been used in a multitude of research studies due to its more predictable pharmacokinetics compared to the oral form, which is used frequently as a treatment for Parkinson’s disease (PD. Levodopa is the precursor for dopamine, and intravenous dopamine would strongly affect vascular tone, but peripheral decarboxylase inhibitors are intended to block such effects. Pulse and blood pressure, with orthostatic changes, were recorded before and after intravenous levodopa or placebo—after oral carbidopa—in 13 adults with a chronic tic disorder and 16 tic-free adult control subjects. Levodopa caused no statistically or clinically significant changes in blood pressure or pulse. These data add to previous data that support the safety of i.v. levodopa when given with adequate peripheral inhibition of DOPA decarboxylase.

  19. Serum immunoglobulin E and immunoglobulin G reactivity to Agaricus bisporus proteins in mushroom cultivation workers.

    Science.gov (United States)

    Khakzad, Z; Hedayati, M T; Mahdian, S; Mayahi, S

    2015-06-01

    Although molds are regarded as the main fungal allergen sources, evidence indicates that spores of Basidiomycota including Agaricus bisporus ( A. bisporus ) can be also found at high concentrations in the environment and may cause as many respiratory allergies as molds. The aim of the present study was to evaluate specific immunoglobulin E (IgE) and immunoglobulin G (IgG) antibodies against A. bisporus via immunoblotting technique in individuals working at mushroom cultivation centers. In this study, 72 workers involved in the cultivation and harvest of button mushrooms were enrolled. For the analysis of serum IgE and IgG, A. bisporus grown in Sabouraud dextrose broth was harvested and ruptured by liquid nitrogen and glass beads. The obtained sample was centrifuged and the supernatant was collected as "crude extract" (CE). CE was separated via Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE). The separated proteins were transferred to a nitrocellulose filter and the bands responsive to IgE and IgG were identified by anti-human conjugated antibodies. All participants were screened in terms of total IgE level. Among 72 workers, 18 (25%) had a total IgE level higher than 188 IU/mL. In SDS-PAGE, the CE of A. bisporus showed 23 different protein bands with a molecular weight range of 13-80 kDa. The sera of 23.6% and 55.5% of participants showed positive response, with specific IgE and IgG antibodies against A. bisporus in the blot, respectively. The bands with molecular weights of 62 and 68 kDa were the most reactive protein components of A. bisporus to specific IgE antibodies. Moreover, bands with molecular weights of 57 and 62 kDa showed the highest reactivity to IgG, respectively. Also, 62 and 68 kDa components were the most reactive bands with both specific IgG and IgE antibodies. The obtained findings revealed that A. bisporus has different allergens and antigens, which contribute to its potential as an aeroallergen in hypersensitivity

  20. Evaluation of adsorption selectivity of immunoglobulins M, A and G and purification of immunoglobulin M with mixed-mode resins.

    Science.gov (United States)

    Luo, Ying-Di; Zhang, Qi-Lei; Yao, Shan-Jing; Lin, Dong-Qiang

    2018-01-19

    This study investigated adsorption selectivity of immunoglobulin M (IgM), immunoglobulin A (IgA) and immunoglobulin (IgG) on four mixed-mode resins with the functional ligands of 4-mercatoethyl-pyridine (MEP), 2-mercapto-1-methylimidazole (MMI), 5-aminobenzimidazole (ABI) and tryptophan-5-aminobenzimidazole (W-ABI), respectively. IgM purification processes with mixed-mode resins were also proposed. All resins showed typical pH-dependent adsorption, and high adsorption capacity was found at pH 5.0-8.0 with low adsorption capacity under acidic conditions. Meanwhile, high selectivity of IgM/IgA and IgM/IgG was obtained with ABI-4FF and MMI-4FF resins at pH 4.0-5.0, which was used to develop a method for IgM, IgA and IgG separation by controlling loading and elution pH. Capture of monoclonal IgM from cell culture supernatant with ABI-4FF resins was studied and high purity (∼99%) and good recovery (80.8%) were obtained. Moreover, IgM direct separation from human serum with combined two-step chromatography (ABI-4FF and MMI-4FF) was investigated, and IgM purity of 65.2% and a purification factor of 28.3 were obtained after optimization. The antibody activity of IgM was maintained after purification. The results demonstrated that mixed-mode chromatography with specially-designed ligands is a promising way to improve adsorption selectivity and process efficiency of IgM purification from complex feedstock. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Noninvasive assessment of coronary stenoses by myocardial imaging during pharmacologic coronary vasodilation. VI. Detection of coronary artery disease in human beings with intravenous N-13 ammonia and positron computed tomography

    International Nuclear Information System (INIS)

    Schelbert, H.R.; Wisenberg, G.; Phelps, M.E.; Gould, K.L.; Henze, E.; Hoffman, E.J.; Gomes, A.; Kuhl, D.E.

    1982-01-01

    The possibility of detecting mild coronary stenoses with positron computed tomography and nitrogen (N-13) ammonia administered during pharmacologic coronary vasodilation was previously demonstrated in chronically instrumented dogs. The feasibility of using this technique in human beings and its sensitivity in determining the degree and extent of coronary artery disease were examined in 13 young normal healthy volunteers and 32 patients with angiographically documented coronary artery disease. N-13 ammonia was administered intravenously and its distribution in the left ventricular myocardium recorded at rest and during dipyridamole-induced coronary hyperemia. In the 13 volunteers, N-13 activity was homogeneous at rest and during hyperemia, whereas 31 of the 32 patients had regional defects on the hyperemic images not present during rest. All six patients with double, all 10 with triple and 15 of 16 patients with single vessel disease (97 percent) were correctly identified with the technique. Two vessel involvement was correctly identified in five of the six patients with double vessel disease and three vessel disease in six of 10 patients. Of all 58 coronary stenoses, 52 (90 percent) were correctly identified. In a subgroup of 11 patients, the technique was compared with exercise thallium-201 planar images, which were abnormal in 10 (91 percent) whereas N-13 images were abnormal in all 11. Of the 19 stenosed coronary arteries in this subgroup, 11 (58 percent) were correctly identified with thallium-201 and 17 (89 percent) with tomography (p less than 0.01). It is concluded that cross-sectional imaging of the myocardial distribution of N-13 ammonia administered during pharmacologic coronary vasodilation is a highly sensitive and accurate means for noninvasive detection of coronary stenoses in human beings and for estimating the extent of coronary artery disease

  2. The optimal choice of medication administration route regarding intravenous, intramuscular, and subcutaneous injection

    Directory of Open Access Journals (Sweden)

    Jin JF

    2015-07-01

    Full Text Available Jing-fen Jin,1 Ling-ling Zhu,2 Meng Chen,3 Hui-min Xu,3 Hua-fen Wang,1 Xiu-qin Feng,1 Xiu-ping Zhu,3 Quan Zhou31Division of Nursing, 2VIP Care Ward, Division of Nursing, 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaBackground: Intravenous (IV, intramuscular (IM, and subcutaneous (SC are the three most frequently used injection routes in medication administration. Comparative studies of SC versus IV, IM versus IV, or IM versus SC have been sporadically conducted, and some new findings are completely different from the dosage recommendation as described in prescribing information. However, clinicians may still be ignorant of such new evidence-based findings when choosing treatment methods.Methods: A literature search was performed using PubMed, MEDLINE, and Web of Sciences™ Core Collection to analyze the advantages and disadvantages of SC, IV, and IM administration in head-to-head comparative studies.Results: “SC better than IV” involves trastuzumab, rituximab, antitumor necrosis factor medications, bortezomib, amifostine, recombinant human granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, recombinant interleukin-2, immunoglobulin, epoetin alfa, heparin, and opioids. “IV better than SC” involves ketamine, vitamin K1, and abatacept. With respect to insulin and ketamine, whether IV has advantages over SC is determined by specific clinical circumstances. “IM better than IV” involves epinephrine, hepatitis B immunoglobulin, pegaspargase, and some antibiotics. “IV better than IM” involves ketamine, morphine, and antivenom. “IM better than SC” involves epinephrine. “SC better than IM” involves interferon-beta-1a, methotrexate, human chorionic gonadotropin, hepatitis B immunoglobulin, hydrocortisone, and morphine. Safety, efficacy, patient preference, and pharmacoeconomics are four principles

  3. Comparsion between Intravenous Delivered Human Fetal Bone Marrow Mesenchymal Stromal Cells and Mononuclear Cells in the Treatment of Rat Cerebral Infarct.

    Science.gov (United States)

    Huang, Ai-Hua; Zhang, Ping-Ping; Zhang, Bin; Ma, Bu-Qing; Guan, Yun-Qian; Zhou, Yi-Dan

    2016-10-10

    Objective To compare the effecacy of human mesenchymal stromal cell (hMSC) with human mononuclear cell (hMNC) in treating rat cerebral infarct.Methods The SD rat models of cerebral infarct were established by distal middle cerebral artery occlusion (dMCAO). Rats were divided into four groups: sham,ischemia vehicle,MSC,and MNC transplantation groups. For the transplantation group,1×10 6 hMSCs or hMNCs were intravascularly transplanted into the tail vein 1 hour after the ischemia onset. The ischemia vehicle group received dMCAO surgery and intravascular saline injection 1,3,5,and 7 days after the ischemia onset,and then behavioral tests were performed. At 48 h after the ischemia onset,the abundance of Iba- 1,the symbol of activated microglia,was evaluated in the peri-ischemia striatum area; meanwhile,the neurotrophic factors such as glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) in ipsilateral peri-ischemia striatum area were also measured. Results The relative infarct volume in ischemia vehicle group,hMSC group,and hMNC transplantation group were (37.85±4.40)%,(33.41±3.82)%,and (30.23±3.63)%,respectively. The infarct volumes of MSC group (t=2.100,P=0.034) and MNC group (t=2.109,P=0.0009) were significantly smaller than that of ischemia vehicle group,and that of MNC group was significantly smaller than that of MSC group (t=1.743,P=0.043). One day after transplantation,the score of ischemia vehicle group in limb placing test was (4.32±0.71)%,which was significantly lower than that in sham group (9.73±0.36)% (t=2.178,P=8.61×10 -11 ). The scores of MSC and MNC group,which were (5.09±0.62)% (t=2.1009,P=0.024) and (5.90±0.68)% (t=2.1008,P=0.0001),respectively,were significantly higher than that of ischemia vehicle group; also,the score of MNC group was significantly higher than that of MSC group(t=2.1009,P=0.0165). The contralateral forelimb scores of MSC and MNC groups in beam walking test were (5.56±0.86)% (t=2

  4. intravenous infusion of chlorimipramine (anafranil)

    African Journals Online (AJOL)

    the already extensive outpatient facilities at Johannesburg. Hospital as well as the Tara Neuro-Psychiatric Hospital for long-term therapy. Technique of Chlorimipramine Infusion. Initially 1 ampoule of chlorimipramine 25 mg in 250 mg of 5°~ dextrose saline was administered intravenously at the rate of 60 drops per minute.

  5. Killer Cell Immunoglobulin-like Receptors and their Ligands

    Directory of Open Access Journals (Sweden)

    Tajik N.

    2010-09-01

    Full Text Available The Natural killer (NK cells are a subset of lymphocytes comprising around 10% of total lymphocytes in peripheral blood. Due to their role in the innate response, NK cells provide a ‘first line of defense’ against infectious agents and cancer and are also thought to play a role in autoimmunity. The killer cell immunoglobulin-like receptors (KIR are regulatory surface molecules, found on NK cells and on a subset of T lymphocytes. The genes for KIR are present on chromosome 19 in the leukocyte receptor complex and show a major difference for both the type and number of KIR genes present among different ethnic groups. They have been divided into two groups of 2D or 3D, depending on the number of external immunoglobulin domains. The presence of a long cytoplasmic tail with two immune tyrosine-based inhibitory motifs (ITIM allows the transduction of inhibitory signals and characterizes the inhibitory KIRs (2DL and 3DL, whereas the presence of short cytoplasmic tails corresponds to the activating KIR receptors (2DS and 3DS.These polymorphic receptors interact with specific motifs on human leukocyte antigen (HLA class I molecules, modulate NK cytolytic activity. Some KIRs are known to interact with HLA-C molecules of target cells, HLA-Bw4 molecules and HLA-A3/11. For some KIRs the corresponding ligands are still unknown.

  6. Neuromyelitis Optica Immunoglobulin G in a Child

    OpenAIRE

    Hudson, Lynsee A.; Bernard, Timothy J.; Tseng, Brian S.; Miller, Bradford R.; Corboy, John R.

    2006-01-01

    Neuromyelitis optica or Devic’s syndrome is an uncommon demyelinating disorder that preferentially attacks the spinal cord and optic nerves. Although it is well described in adults, childhood neuromyelitis optica has rarely been reported in the literature and is frequently misdiagnosed as severe multiple sclerosis. Recently, a serum immunoglobulin G test for neuromyelitis optica has become available which may clarify and accelerate the diagnosis. This report describes a child with recurrent m...

  7. Phase 1A safety assessment of intravenous amitriptyline

    NARCIS (Netherlands)

    Fridrich, Peter; Colvin, Hans Peter; Zizza, Anthony; Wasan, Ajay D.; Lukanich, Jean; Lirk, Philipp; Saria, Alois; Zernig, Gerald; Hamp, Thomas; Gerner, Peter

    2007-01-01

    The antidepressant amitriptyline is used as an adjuvant in the treatment of chronic pain. Among its many actions, amitriptyline blocks Na+ channels and nerves in several animal and human models. As perioperative intravenous lidocaine has been suggested to decrease postoperative pain, amitriptyline,

  8. Intravenous immunglobulin binds beta amyloid and modifies its aggregation, neurotoxicity and microglial phagocytosis in vitro.

    Directory of Open Access Journals (Sweden)

    Susann Cattepoel

    Full Text Available Intravenous Immunoglobulin (IVIG has been proposed as a potential therapeutic for Alzheimer's disease (AD and its efficacy is currently being tested in mild-to-moderate AD. Earlier studies reported the presence of anti-amyloid beta (Aβ antibodies in IVIG. These observations led to clinical studies investigating the potential role of IVIG as a therapeutic agent in AD. Also, IVIG is known to mediate beneficial effects in chronic inflammatory and autoimmune conditions by interfering with various pathological processes. Therefore, we investigated the effects of IVIG and purified polyclonal Aβ-specific antibodies (pAbs-Aβ on aggregation, toxicity and phagocytosis of Aβ in vitro, thus elucidating some of the potential mechanisms of action of IVIG in AD patients. We report that both IVIG and pAbs-Aβ specifically bound to Aβ and inhibited its aggregation in a dose-dependent manner as measured by Thioflavin T assay. Additionally, IVIG and the purified pAbs-Aβ inhibited Aβ-induced neurotoxicity in the SH-SY5Y human neuroblastoma cell line and prevented Aβ binding to rat primary cortical neurons. Interestingly, IVIG and pAbs-Aβ also increased the number of phagocytosing cells as well as the amount of phagocytosed fibrillar Aβ by BV-2 microglia. Phagocytosis of Aβ depended on receptor-mediated endocytosis and was accompanied by upregulation of CD11b expression. Importantly, we could also show that Privigen dose-dependently reversed Aβ-mediated LTP inhibition in mouse hippocampal slices. Therefore, our in vitro results suggest that IVIG may have an impact on different processes involved in AD pathogenesis, thereby promoting further understanding of the effects of IVIG observed in clinical studies.

  9. Intravenous Therapy: Hazards, Complications and Their Prevention ...

    African Journals Online (AJOL)

    Breaks in aseptic techniques, faulty handling of parenteral fluid containers, failure to discard out-dated intravenous solutions and tubings contribute to occurrence of intravenous-associated sepsis. Improper technique and lack of pharmaceutical knowledge when adding drugs into intravenous fluids contribute to ...

  10. A tomographic approach to intravenous coronary arteriography

    International Nuclear Information System (INIS)

    Ritman, E.L.; Bove, A.A.

    1986-01-01

    Coronary artery anatomy can be visualized using high speed, volume scanning X-ray CT. A single scan during a bolus injection of contrast medium provides image data for display of all angles of view of the opacified coronary arterial tree. Due to the tomographic nature of volume image data the superposition of contrast filled cardiac chambers, such as would occur in the levophase of an intravenous injection of contrast agent, can be eliminated. Data are presented which support these statements. The Dynamic Spatial Reconstructor (DSR) was used to scan a life-like radiologic phantom of an adult human thorax in which the left atrial and ventricular chambers and the major epicardial coronary arteries were opacified so as to simulate the levophase of an intravenous injection of contrast agent. A catheter filled with diluted contrast agent and with regions of luminal narrowing (i.e. 'stenoses') was advanced along a tract equivalent to a right ventricular catheterization. Ease of visualization of the catheter 'stenoses' and the accuracy with which they can be measured are presented. (Auth.)

  11. Intravenous Antiepileptic Drugs in Russia

    Directory of Open Access Journals (Sweden)

    P. N. Vlasov

    2014-01-01

    Full Text Available Launching four intravenous antiepileptic drugs: valproate (Depakene and Convulex, lacosamide (Vimpat, and levetiracetam (Keppra – into the Russian market has significantly broadened the possibilities of rendering care to patients in seizure emergency situations. The chemi- cal structure, mechanisms of action, indications/contraindications, clinical effectiveness and tolerability, advantages/disadvantages, and adverse events of using these drugs in urgent and elective neurology are discussed. 

  12. Immunoglobulin subclass in experimental murine Toxocara cati infection

    Directory of Open Access Journals (Sweden)

    Kusnoto

    2017-11-01

    Full Text Available Aim: The aim of this study was to detect specific immunoglobulin (Ig that could be used to determine monoclonal antibody in conjugate-making an effort for the indirect enzyme-linked immunosorbent assay (ELISA diagnostic kit of toxocariasis in human. Materials and Methods: The study was conducted to assess the Ig profile, based on ELISA-isotyping, in mice infected with second stage larvae eggs of Toxocara cati. The optical density values of anti-T. cati mice serum IgG subclasses were analyzed by applying ANOVA factorial. Results: The specific IgG subclass in mice infected with T. cati mice was found to be IgG2β. Conclusion: Subclass of IgG, especially IgG2β, can provide leads about the use of the monoclonal antibody in conjugate making an effort for the indirect ELISA diagnostic kit.

  13. Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation.

    Science.gov (United States)

    Jeong, Jong Cheol; Jambaldorj, Enkthuya; Kwon, Hyuk Yong; Kim, Myung-Gyu; Im, Hye Jin; Jeon, Hee Jung; In, Ji Won; Han, Miyeun; Koo, Tai Yeon; Chung, Junho; Song, Eun Young; Ahn, Curie; Yang, Jaeseok

    2016-02-01

    Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate.This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2  g/kg), a single dose of rituximab (375  mg/m), and 4 doses of bortezomib (1.3  mg/m). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients.There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83  ±  16.0 (14952  ±  5820) and 63  ±  36.0 (10321  ±  7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468-634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group.In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients.

  14. Serum-derived bovine immunoglobulin/ protein isolate: postulated mechanism of action for management of enteropathy

    Directory of Open Access Journals (Sweden)

    Petschow BW

    2014-05-01

    Full Text Available Bryon W Petschow, Bruce Burnett, Audrey L Shaw, Eric M Weaver, Gerald L Klein Entera Health, Inc., Cary, NC, USA Abstract: The health and performance of the gastrointestinal tract is influenced by the interaction of a variety of factors, including diet, nutritional status, genetics, environment, stress, the intestinal microbiota, immune status, and gut barrier. Disruptions in one or more of these factors can lead to enteropathy or intestinal disorders that are known to occur in concert with certain disease states or conditions such as irritable bowel syndrome or human immunodeficiency virus (HIV infection. Nutritional support in the form of a medical food along with current therapies could help manage the adverse effects of enteropathy, which include effects on nutrient digestion, absorption, and metabolism, as well as utilization of nutrients from foodstuffs. Numerous studies have demonstrated that oral administration of plasma- or serum-derived protein concentrates containing high levels of immunoglobulins can improve weight management, normalize gut barrier function, and reduce the severity of enteropathy in animals. Recent trials in humans provide preliminary evidence that a serum-derived bovine immunoglobulin/protein isolate is safe and improves symptoms, nutritional status, and various biomarkers associated with enteropathy in patients with HIV infection or diarrhea-predominant irritable bowel syndrome. This review summarizes data from preclinical and clinical studies with immunoglobulin-containing plasma/serum protein concentrates, with a focus on the postulated mode of action of serum-derived bovine immunoglobulin/protein isolate for patients with enteropathy. Keywords: bovine immunoglobulins, nutrient, gut barrier, microbiota

  15. Carotenoid supplementation and retinoic acid in immunoglobulin A regulation of the gut microbiota dysbiosis.

    Science.gov (United States)

    Lyu, Yi; Wu, Lei; Wang, Fang; Shen, Xinchun; Lin, Dingbo

    2018-04-01

    Dysbiosis, a broad spectrum of imbalance of the gut microbiota, may progress to microbiota dysfunction. Dysbiosis is linked to some human diseases, such as inflammation-related disorders and metabolic syndromes. However, the underlying mechanisms of the pathogenesis of dysbiosis remain elusive. Recent findings suggest that the microbiome and gut immune responses, like immunoglobulin A production, play critical roles in the gut homeostasis and function, and the progression of dysbiosis. In the past two decades, much progress has been made in better understanding of production of immunoglobulin A and its association with commensal microbiota. The present minireview summarizes the recent findings in the gut microbiota dysbiosis and dysfunction of immunoglobulin A induced by the imbalance of pathogenic bacteria and commensal microbiota. We also propose the potentials of dietary carotenoids, such as β-carotene and astaxanthin, in the improvement of the gut immune system maturation and immunoglobulin A production, and the consequent promotion of the gut health. Impact statement The concept of carotenoid metabolism in the gut health has not been well established in the literature. Here, we review and discuss the roles of retinoic acid and carotenoids, including pro-vitamin A carotenoids and xanthophylls in the maturation of the gut immune system and IgA production. This is the first review article about the carotenoid supplements and the metabolites in the regulation of the gut microbiome. We hope this review would provide a new direction for the management of the gut microbiota dysbiosis by application of bioactive carotenoids and the metabolites.

  16. 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.

    Directory of Open Access Journals (Sweden)

    Paul J Norman

    2013-10-01

    Full Text Available 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

  17. Hydrometer test for estimation of immunoglobulin concentration in bovine colostrum.

    Science.gov (United States)

    Fleenor, W A; Stott, G H

    1980-06-01

    A practical field method for measuring immunoglobulin concentration in bovine colostrum has been developed from the linear relationship between colostral specific gravity and immunoglobulin concentration. Fourteen colostrums were collected within 24 h postpartum from nursed and unnursed cows and were assayed for specific gravity and major colostral constituents. Additionally, 15 colostrums were collected immediately postpartum prior to suckling and assayed for specific gravity and immunoglobulin concentration. Regression analysis provided an equation to estimate colostral immunoglobulin concentration from the specific gravity of fresh whole colostrum. From this, a colostrometer was developed for practical field use.

  18. Successful Immunoglobulin Treatment in Severe Cryptogenic Organizing Pneumonia Caused by Dermatomyositis

    Directory of Open Access Journals (Sweden)

    Dong Hoon Lee

    2015-08-01

    Full Text Available In connective tissue diseases, autoantibodies cause pulmonary interstitial inflammation and fibrosis, and patients require treatment with an immunosuppressive agent such as a steroid. Dermatomyositis is an incurable, uncommon form of connective tissue disease that occasionally causes diffuse pulmonary inflammation leading to acute severe respiratory failure. In such cases, the prognosis is very poor despite treatment with high-dose steroid. In the present case, a 46-year-old man was admitted to our hospital with dyspnea. He was diagnosed with dermatomyositis combined with cryptogenic organizing pneumonia (COP with respiratory failure and underwent treatment with steroid and an immunosuppressive agent, but the COP was not improved. However, the respiratory failure did improve after treatment with intravenous immunoglobulin, which therefore can be considered a treatment option in cases where steroids and immunosuppressive agents are ineffective.

  19. Screening for congenital toxoplasmosis: accuracy of immunoglobulin M and immunoglobulin A tests after birth

    DEFF Research Database (Denmark)

    Gilbert, Ruth E; Thalib, Lukman; Tan, Hooi Kuan

    2007-01-01

    OBJECTIVES: To determine the accuracy of postnatal screening for toxoplasma-specific immunoglobulin (Ig) M and IgA. SETTING: Ten centres in three European countries. METHODS: We compared results of the first postnatal IgM or IgA test in infants with infected mothers identified by prenatal screeni...

  20. 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.

  1. [Clinical effect of anti-D immunoglobulin in treatment of childhood immune thrombocytopenia: a Meta analysis].

    Science.gov (United States)

    Qin, Wei; Huang, Shao-Ling; Li, Ting-Ting

    2017-10-01

    To investigate the clinical effect and safety of anti-D immunoglobulin (anti-D) in the treatment of children with newly diagnosed acute immune thrombocytopenia (ITP) through a Meta analysis. PubMed, EMBASE, Cohrane Library, Ovid, CNKI, and Wanfang Data were searched for randomized controlled trials (RCTs) published up to April 2017. Review Manager 5.3 was used for the Meta analysis. Seven RCTs were included. The Meta analysis showed that after 72 hours and 7 days of treatment, the intravenous immunoglobulin (IVIG) group had a significantly higher percentage of children who achieved platelet count >20×10 9 /L than the anti-D group (Panti-D (50 μg/kg) group and the IVIG group (P>0.05), and there were also no significant differences in platelet count after 24 hours and 7 days of treatment between the 50 μg/kg and 75 μg/kg anti-D groups (P>0.05). The anti-D group had a significantly greater reduction in the hemoglobin level than the IVIG group after treatment, but did not need transfusion. No children in the anti-D group or the IVIG group experienced serious adverse reactions. Intravenous injection of anti-D may have a similar effect as IVIG in improving platelet count in children with acute ITP, but it may be slightly inferior to IVIG in the rate of platelet increase after treatment. The anti-D dose of 50 μg/kg may have a similar effect as 75 μg/kg. The recommended dose of anti-D for treatment of ITP is safe.

  2. Peptide and nucleotide sequences of rat CD4 (W3/25) antigen: evidence for derivation from a structure with four immunoglobulin-related domains

    International Nuclear Information System (INIS)

    Clark, S.J.; Jefferies, W.A.; Barclay, A.N.; Gagnon, J.; Williams, A.F.

    1987-01-01

    The rat W3/25 antigen was the first marker antigen of helper T lymphocytes to be identified. Subsequently, the human OKT4 antigen (now called CD4) was described, and cell distribution and functional data suggested that W3/25 and OKT4 antigens were homologous. This is now confirmed by the matching of peptide sequences from W3/25 antigen with sequence predicted from rat cDNA clones detected by cross-hybridization with a cDNA probe for human CD4. Analysis of the two sequences suggests an evolutionary origin from a structure with four immunoglobulin-related domains, although only domain 1 at the NH 2 terminus meets the standard criteria for an immunoglobulin-related sequence. CD4 domains 2 and 4 contain disulfide bonds but seem like truncated immunoglobulin domains, whereas domain 3 may have a pattern of β-strands like an immunoglobulin variable domain, but without the disulfide bond

  3. Serology and immunoglobulin profile in rheumatoid arthritis.

    Science.gov (United States)

    Adhya, S; Chakraborty, G; Hajra, B; Bhattacharya, S; Sikdar, P K; Sinha, S; Banerjee, P P; Ghosh, E; Chakraborty, P

    1998-01-01

    One hundred and twenty cases of clinically diagnosed rheumatoid arthritis, 80 non-rheumatoid cases suffering from various other diseases and 40 healthy individuals were investigated for the presence of rheumatoid factor, quantitation of serum immunoglobulin, demonstration of ANA and LE cell phenomenon. Microlatex agglutination test of serum for rheumatoid factor showed 56.6% positivity in rheumatoid group and 3.7% positivity in non-rheumatoid group. All three serum immunoglobulins (IgG, IgM, IgA) were raised in serum in significant titre in cases of rheumatoid arthritis, whereas only IgA lever was elevated in the group of non-rheumatoid diseases. ANA and LE cell phenomenon were observed in 11.7% and 4.4% cases of rheumatoid arthritis who had severe underlying disease. In non-rheumatoid group, only one of 6 cases of systemic lupus erythematosus showed rheumatoid factor and that too in an insignificant titre (less than 1:20). Synovium and synovial fluid contained plenty of plasma cells and lymphocytes. It has been observed that RF appears first in synovial fluid and it may take several months to a year to attain detectable level in serum.

  4. Levels of serum immunoglobulins in apparently healthy children and ...

    African Journals Online (AJOL)

    The results also confirm suggestions that levels of some immunoglobulin types seen amongst African adults may have possibly been attained during childhood. Our study could be of value since previous reports in this regard have been relatively scanty especially in this part of Nigeria. Keywords: Immunoglobulin, Immunity ...

  5. Levels of serum immunoglobulins in apparently healthy children and ...

    African Journals Online (AJOL)

    olayemitoyin

    suggestions that levels of some immunoglobulin types seen amongst African adults may have possibly been attained during childhood. Our study could be of value since previous reports in this regard have been relatively scanty especially in this part of Nigeria. Keywords: Immunoglobulin, Immunity, IgA, IgG, IgM.

  6. 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.

  7. INTERACTION OF ALBUMIN AND IMMUNOGLOBULIN G WITH SYNTHETIC HYDROXYAPATITE

    Directory of Open Access Journals (Sweden)

    E. Pylypchuk

    2012-12-01

    Full Text Available It was shown by X-ray phase analysis, IR spectra analysis and MALDI-ToF mass spectrometry methods that interaction of synthetic hydroxyapatite with a solution of immunoglobulin G leads to its partial dissolution due to leaching from the surface of calcium triphosphate which, in our opinion, forms complexes with immunoglobulin G.

  8. Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty.

    Science.gov (United States)

    Golpanian, Samuel; DiFede, Darcy L; Pujol, Marietsy V; Lowery, Maureen H; Levis-Dusseau, Silvina; Goldstein, Bradley J; Schulman, Ivonne H; Longsomboon, Bangon; Wolf, Ariel; Khan, Aisha; Heldman, Alan W; Goldschmidt-Clermont, Pascal J; Hare, Joshua M

    2016-03-15

    Frailty is a syndrome associated with reduced physiological reserves that increases an individual's vulnerability for developing increased morbidity and/or mortality. While most clinical trials have focused on exercise, nutrition, pharmacologic agents, or a multifactorial approach for the prevention and attenuation of frailty, none have studied the use of cell-based therapies. We hypothesize that the application of allogeneic human mesenchymal stem cells (allo-hMSCs) as a therapeutic agent for individuals with frailty is safe and efficacious. The CRATUS trial comprises an initial non-blinded phase I study, followed by a blinded, randomized phase I/II study (with an optional follow-up phase) that will address the safety and pre-specified beneficial effects in patients with the aging frailty syndrome. In the initial phase I protocol, allo-hMSCs will be administered in escalating doses via peripheral intravenous infusion (n=15) to patients allocated to three treatment groups: Group 1 (n=5, 20 million allo-hMSCs), Group 2 (n=5, 100 million allo-hMSCs), and Group 3 (n=5, 200 million allo-hMSCs). Subsequently, in the randomized phase, allo-hMSCs or matched placebo will be administered to patients (n=30) randomly allocated in a 1:1:1 ratio to one of two doses of MSCs versus placebo: Group A (n=10, 100 million allo-hMSCs), Group B (n=10, 200 million allo-hMSCs), and Group C (n=10, placebo). Primary and secondary objectives are, respectively, to demonstrate the safety and efficacy of allo-hMSCs administered in frail older individuals. This study will determine the safety of intravenous infusion of stem cells and compare phenotypic outcomes in patients with aging frailty.

  9. Human immunodeficiency virus seroconversion presenting with acute inflammatory demyelinating polyneuropathy: a case report

    Directory of Open Access Journals (Sweden)

    Sloan Derek J

    2008-12-01

    Full Text Available Abstract Introduction Acute Human Immunodeficiency Virus infection is associated with a range of neurological conditions. Guillain-Barré syndrome is a rare presentation; acute inflammatory demyelinating polyneuropathy is the commonest form of Guillain-Barré syndrome. Acute inflammatory demyelinating polyneuropathy has occasionally been reported in acute Immunodeficiency Virus infection but little data exists on frequency, management and outcome. Case presentation We describe an episode of Guillain-Barré syndrome presenting as acute inflammatory demyelinating polyneuropathy in a 30-year-old man testing positive for Immunodeficiency Virus, probably during acute seroconversion. Clinical suspicion was confirmed by cerebrospinal fluid analysis and nerve conduction studies. Rapid clinical deterioration prompted intravenous immunoglobulin therapy and early commencement of highly active anti-retroviral therapy. All symptoms resolved within nine weeks. Conclusion Unusual neurological presentations in previously fit patients are an appropriate indication for Immunodeficiency-Virus testing. Highly active anti-retroviral therapy with adequate penetration of the central nervous system should be considered as an early intervention, alongside conventional therapies such as intravenous immunoglobulin.

  10. Swine plasma immunoglobulins for prevention and treatment of post-weaning diarrhoea: Optimizing stability towards gut conditions

    DEFF Research Database (Denmark)

    Hedegaard, Chris Juul; Ballegaard, Anne-Sofie; Røjel, Nanna

    Brief description of research area: A common problem in swine production is diarrhoea in newly weaned piglets, and huge quantities of antibiotics go to treat post-weaning diarrhoeas in piglets. The use of antibiotics can lead to the development of multi- and fully resistant bacteria, which...... consequently pose a great threat to human health. Therefore, sustainable alternatives for treating post-weaning diarrhoea without using antibiotics are in demand. Swine that are old (and big) enough for slaughter have during their upbringing been challenges by many different pathogens and thus have developed...... know: It is possible to multimerise immunoglobulins, which results in an advantage when binding to their respective antigens in comparison to the non-multimerised immunoglobulins, but too high degree of multimerisation abates immunoglobulin reactivity. Unfortunately, a preliminary study showed...

  11. Immunoglobulin G4-Related Disease: An Update

    Directory of Open Access Journals (Sweden)

    Abdullah Al-Mujaini

    2018-03-01

    Full Text Available Immunoglobulin G4-related disease (IgG4-RD is an increasingly recognized immune-mediated condition comprised of a collection of disorders that share specific pathological, serological, and clinical features. IgG4-RD is a fibroinflammatory condition with a tendency to form tumors with inflammatory infiltrate with IgG4 rich plasma cells and elevation of serum IgG4, which may affect virtually every organ and tissue. IgG4-related ophthalmic disease may present as dacryoadenitis, myositis, or involvement of other orbital tissue. Hypophysitis or pachymeningitis may manifest as cranial neuropathies. The diagnosis of IgG4-RD is based on a typical clinical scenario, supportive laboratory test, expected radiological characteristics, and distinct histopathological and immunohistochemical features. Corticosteroids and immunosuppressives form the mainline treatment.

  12. Today and tomorrow of intravenous coronary angiography programme in Japan

    International Nuclear Information System (INIS)

    Ando, Masami; Hyodo, Kazuyuki

    1994-01-01

    Development of an intravenous coronary angiography system using monochromated synchrotron radiation at the Photon Factory is described. This comprises an asymmetric cut silicon monochromator crystal to get a larger exposure area, a two dimensional imaging system using an imaging intensifier coupled to a CCD TV camera and a fast video data acquisition system. The whole system is under development using alive dogs. A future system including a dedicated insertion device applicable to alive humans is also proposed. (author)

  13. HIV antibodies among intravenous drug users in Bahrain.

    Science.gov (United States)

    al-Haddad, M K; Khashaba, A S; Baig, B Z; Khalfan, S

    1994-09-01

    A 12-month study was conducted to identify risk factors for human immunodeficiency virus (HIV) infections among intravenous drug users (IDU) attending drug rehabilitation clinic of the Psychiatric Hospital, Manama, Bahrain. Patients provided demographic and behavioural information based on a questionnaire. Two hundred and forty male IDUs participated in the study on voluntary basis. The seroprevalence of HIV was 21.1 per cent. The presence of HIV antibody was associated with educational status, frequency of injecting drugs and needle sharing.

  14. Euthanasia of Small Animals with Nitrogen; Comparison with Intravenous Pentobarbital

    OpenAIRE

    Quine, John P.; Buckingham, William; Strunin, Leo

    1988-01-01

    Intravenous pentobarbital (with or without addition of saturated potassium chloride) was compared with nitrogen gas exposure for euthanasia of small animals (dogs, cats, and rabbits) in a humane society environment. Initially, electrocardiographic) and electroencephalographic monitoring were used to establish the time of death in presedated animals given either pentobarbital or exposed to nitrogen; later, nitrogen euthanasia alone was studied. Sedation with acepromazine delayed the effects of...

  15. Production of immunoglobulins in gingival tissue explant cultures from juvenile periodontitis patients

    International Nuclear Information System (INIS)

    Hall, E.R.; Falkler, W.A. Jr.; Suzuki, J.B.

    1990-01-01

    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

  16. 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.

  17. Structure of filamin A immunoglobulin-like repeat 10 from Homo sapiens

    International Nuclear Information System (INIS)

    Page, Richard C.; Clark, Jeffrey G.; Misra, Saurav

    2011-01-01

    The structure of immunoglobulin-like repeat 10 from human filamin A solved at 2.44 Å resolution suggests the potential effects of mutations correlated with otopalatodigital syndrome spectrum disorders. Filamin A (FlnA) plays a critical role in cytoskeletal organization, cell motility and cellular signaling. FlnA utilizes different binding sites on a series of 24 immunoglobulin-like domains (Ig repeats) to interact with diverse cytosolic proteins and with cytoplasmic portions of membrane proteins. Mutations in a specific domain, Ig10 (FlnA-Ig10), are correlated with two severe forms of the otopalatodigital syndrome spectrum disorders Melnick–Needles syndrome and frontometaphyseal dysplasia. The crystal structure of FlnA-Ig10 determined at 2.44 Å resolution provides insight into the perturbations caused by these mutations

  18. 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.

  19. Intentional intravenous mercury injection | Yudelowitz | South African ...

    African Journals Online (AJOL)

    Intravenous mercury injection is rarely seen, with few documented cases. Treatment strategies are not clearly defined for such cases, although a few options do show benefit. This case report describes a 29-year-old man suffering from bipolar disorder, who presented following self-inflicted intravenous injection of mercury.

  20. Acute Inflammatory Demyelinating Neuropathy : Immunoglobulin And Immune Complex Profile

    Directory of Open Access Journals (Sweden)

    Shripad A

    2003-01-01

    Full Text Available Serum immunoglobulins (IgG, IgA and IgM and immune complexes IgG (IcG were measured in 58 cases of acute inflammatory demyelinating neuropathy, popularly known as Guillian Barre′ syndrome, and in 30 healthy controls using single radial immunodiffusion assay. Immunoglobulin and immune complex levels were significantly elevated in patients as compared to controls. The increased levels of immunoglobulins and immune complexes may contribute to the pathogenesis of the disease and provide rationale for therapeutic plasmapheresis.

  1. The role of antiviral and immunoglobulin therapy in the prevention of Epstein-Barr virus infection and post-transplant lymphoproliferative disease following solid organ transplantation.

    Science.gov (United States)

    Green, M; Reyes, J; Webber, S; Rowe, D

    2001-06-01

    The recognition of the importance of Epstein-Barr virus (EBV) infection, including EBV-associated post-transplant lymphoproliferative disease (PTLD), has led to a new focus on the prevention of this problem. This paper reviews the scientific rationale behind, and clinical experience with, the use of chemoprophylaxis (using acyclovir or ganciclovir) and immunoprophylaxis (using intravenous immunoglobulin) in the prevention of EBV/PTLD. While some centers have already introduced the use of one or both of these agents as standard prophylaxis against the development of this complication, published data in support of these protocols are currently lacking. Well designed clinical trials are necessary to evaluate the potential role of both antiviral and immunoglobulin agents in the prevention of EBV/PTLD in organ transplant recipients.

  2. 7(th) International Immunoglobulin Conference: Poster presentations.

    Science.gov (United States)

    Warnatz, K; Ballow, M; Stangel, M; Bril, V

    2014-12-01

    Immunoglobulin (Ig) therapy is the mainstay of treatment for primary antibody deficiency disorders and has proved to be efficacious in specific autoimmune and inflammatory diseases. Additionally, due to the role of Ig in complement activation, it is being used increasingly in solid organ transplantation. Furthermore, Ig is the primary or secondary treatment in some immune-mediated neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) or multifocal motor neuropathy (MMN). This session discusses trends of Ig use in Europe, proposed mechanisms of action, adverse effects and the potential role of Ig therapy in transplantation. Dr Šedivá reported that Ig therapy is available in all European countries, although dosing is not always optimal, due partly to reimbursement plans. Subcutaneous immunoglobulin (SCIg) has become increasingly accessible in recent years; however, the chosen route of administration still varies widely between countries. Dr Berger's presentation on optimization of Ig therapy in neuropathies, and Dr Rojavin's report on a pharmacometric model to determine the serum IgG levels achieved by different dosing regimens in primary antibody deficiency (PAD) patients, led to the challenging concept of using individualized dosing strategies. Dr Klehmet reported on the potential benefit of using antigen-specific T cell responses as a biomarker of IVIg responsiveness in CIDP patients, while Dr von Gunten provided an insight into the mechanisms of action of Ig preparations, suggesting that the immunoregulatory effects of IgG may be mediated by IgG antibodies against glycans. Dr Basta reported on the potential thrombogenic adverse effects associated with Ig therapy. Although these adverse events are rare, further studies are needed to clarify the relationship between Ig replacement and immunomodulatory therapy and these adverse reactions. In transplantation, Dr Carbone described that prophylactic IVIg treatment was found to decrease the

  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

    associated with blood-borne horseradish peroxidase leakage indicating blood-brain barrier breakdown. The cerebrospinal fluid aquaporin-4-immunoglobulin G therefore distributes widely in brain to initiate astrocytopathy and blood-brain barrier breakdown....... was evaluated. A distinct distribution pattern of aquaporin-4-immunoglobulin G deposition was observed in the subarachnoid and subpial spaces where vessels penetrate the brain parenchyma, via a paravascular route with intraparenchymal perivascular deposition. Perivascular astrocyte-destructive lesions were...

  4. Purification, characterization and ELISA detection of mink immunoglobulins

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Aasted, Bent

    2008-01-01

    the estimated molecular weights of the immunoglobulin gamma, alpha and mu heavy chains were found to be 54 kDa, 69 kDa and 83 kDa respectively. The purities of purified IgG, IgM and IgA were estimated by immunoglobulin class specific ELISAs to be more than 90% for IgG and IgM, and more than 80% for IgA....

  5. Gut microbiota utilize immunoglobulin A for mucosal colonization.

    Science.gov (United States)

    Donaldson, G P; Ladinsky, M S; Yu, K B; Sanders, J G; Yoo, B B; Chou, W-C; Conner, M E; Earl, A M; Knight, R; Bjorkman, P J; Mazmanian, S K

    2018-05-18

    The immune system responds vigorously to microbial infection while permitting lifelong colonization by the microbiome. Mechanisms that facilitate the establishment and stability of the gut microbiota remain poorly described. We found that a regulatory system in the prominent human commensal Bacteroides fragilis modulates its surface architecture to invite binding of immunoglobulin A (IgA) in mice. Specific immune recognition facilitated bacterial adherence to cultured intestinal epithelial cells and intimate association with the gut mucosal surface in vivo. The IgA response was required for B. fragilis (and other commensal species) to occupy a defined mucosal niche that mediates stable colonization of the gut through exclusion of exogenous competitors. Therefore, in addition to its role in pathogen clearance, we propose that IgA responses can be co-opted by the microbiome to engender robust host-microbial symbiosis. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  6. Immunoglobulin Genomics in the Guinea Pig (Cavia porcellus)

    Science.gov (United States)

    Guo, Yongchen; Bao, Yonghua; Meng, Qingwen; Hu, Xiaoxiang; Meng, Qingyong; Ren, Liming; Li, Ning; Zhao, Yaofeng

    2012-01-01

    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 VH segments (94 potentially functional genes and 413 pseudogenes), 41 DH segments, six JH segments, four constant region genes (μ, γ, ε, and α), and one reverse δ remnant fragment were identified within the two scaffolds. Many VH 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 Vκ (111 potentially functional genes and 238 pseudogenes), three Jκ and one Cκ genes. The Igλ locus spans 1,642 kb in scaffold 4 and consists of 142 Vλ (58 potentially functional genes and 84 pseudogenes) and 11 Jλ -Cλ clusters. Phylogenetic analysis suggested the guinea pig’s large germline VH 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. PMID:22761756

  7. Intravenous Iron Carboxymaltose as a Potential Therapeutic in Anemia of Inflammation.

    Directory of Open Access Journals (Sweden)

    Niklas Lofruthe

    Full Text Available Intravenous iron supplementation is an effective therapy in iron deficiency anemia (IDA, but controversial in anemia of inflammation (AI. Unbound iron can be used by bacteria and viruses for their replication and enhance the inflammatory response. Nowadays available high molecular weight iron complexes for intravenous iron substitution, such as ferric carboxymaltose, might be useful in AI, as these pharmaceuticals deliver low doses of free iron over a prolonged period of time. We tested the effects of intravenous iron carboxymaltose in murine AI: Wild-type mice were exposed to the heat-killed Brucella abortus (BA model and treated with or without high molecular weight intravenous iron. 4h after BA injection followed by 2h after intravenous iron treatment, inflammatory cytokines were upregulated by BA, but not enhanced by iron treatment. In long term experiments, mice were fed a regular or an iron deficient diet and then treated with intravenous iron or saline 14 days after BA injection. Iron treatment in mice with BA-induced AI was effective 24h after iron administration. In contrast, mice with IDA (on iron deficiency diet prior to BA-IA required 7d to recover from AI. In these experiments, inflammatory markers were not further induced in iron-treated compared to vehicle-treated BA-injected mice. These results demonstrate that intravenous iron supplementation effectively treated the murine BA-induced AI without further enhancement of the inflammatory response. Studies in humans have to reveal treatment options for AI in patients.

  8. Analysis of Serum Proteom after Intravenous Injection of cultivated wild ginseng pharmacopuncture

    Directory of Open Access Journals (Sweden)

    Dong-Hee,Lee

    2006-06-01

    Full Text Available Objectives : To observe the changes in the serum proteins after intravenous injection of cultivated wild ginseng pharmacopuncture. Methods : Blood was collected before and after the administration of cultivated wild ginseng pharmacopuncture and only the serum was taken. Then differences in the spots on the scanned image after carrying out 2-Dimensional electrophoresis were located and conducted mass analysis and protein identification. Results : Following results were obtained from the comparative analysis of serum proteins before and after the administration of cultivated wild ginseng pharmacopuncture. 1. 28 spots were identified before and after the administration. 2. In confirming manifestation degree, spots with more than two-times increase were 204, 1302, 2205, 3105, 7104, 8006, spots with more than one-time increase were 1101, 1505, 2013, 2403, 3009, 3010, 4002, 4009, 6704, 8101, and spots with decrease were 205, 801, 803, 3205, 5202, 6105, 6106, 7103, 9001, 9003. 3. After conducting protein identification, proteins 205, 804, 1302, 4009, 6105, 6106 are unidentified yet, and 1l01 is unnamed protein. Protein 204 is identified as complement receptor CR2-C3d, 801 as YAPl protein, 803 as antitrypsin polymer, 1505 as PRO0684, 2013 and 3010 as proapolipoprotein, 2205 as USP48, 2403 as vitamin D binding protein, 3009 as complement component 4A preprotein, 3105 as immunoglobulin lambda chain, 3205 as transthyretin, 4002 as Ras-related protein Ral-A, 4204 as beta actin, 5202 and 7104 as apolipoprotein Ll, 6704 as alpha 2 macroglobulin precursor, 7103 as complement component 3 precursor, 8006 as testis-specific protein Y, 8101 as transferrin, 9001 as (Alpha-Oxy, Beta-(Cl12gdeoxy T-State Human Hemoglobin, and 9003 as human hemoglobin. 4. Immune protein CR2-C3d(204, which acts against microbes and pathogenic organisms, was increased by more than two-times after the administration of pharmacopuncture. 5. Antitrypsin(803, which is secreted with

  9. Rectal dihydroartemisinin versus intravenous quinine in the ...

    African Journals Online (AJOL)

    Rectal dihydroartemisinin versus intravenous quinine in the treatment of severe malaria: A randomised clinical trial. F Esamai, P Ayuo, W Owino-Ongor, J Rotich, A Ngindu, A Obala, F Ogaro, L Quoqiao, G Xingbo, L Guangqian ...

  10. INFECTIVE ENDOCARDITIS IN INTRAVENOUS DRUGS ABUSED PATIENT

    Directory of Open Access Journals (Sweden)

    E. Y. Ponomareva

    2014-07-01

    Full Text Available Three-year observation of acute tricuspid infective endocarditis in intravenous drug abused patient: diagnosis, clinical features, visceral lesions, the possibility of cardiac surgery and conservative treatment, outcome.

  11. INFECTIVE ENDOCARDITIS IN INTRAVENOUS DRUGS ABUSED PATIENT

    Directory of Open Access Journals (Sweden)

    E. Y. Ponomareva

    2011-01-01

    Full Text Available Three-year observation of acute tricuspid infective endocarditis in intravenous drug abused patient: diagnosis, clinical features, visceral lesions, the possibility of cardiac surgery and conservative treatment, outcome.

  12. First-in-Human Study of PF-05212384 (PKI-587), a Small-Molecule, Intravenous, Dual Inhibitor of PI3K and mTOR in Patients with Advanced Cancer.

    Science.gov (United States)

    Shapiro, Geoffrey I; Bell-McGuinn, Katherine M; Molina, Julian R; Bendell, Johanna; Spicer, James; Kwak, Eunice L; Pandya, Susan S; Millham, Robert; Borzillo, Gary; Pierce, Kristen J; Han, Lixin; Houk, Brett E; Gallo, Jorge D; Alsina, Maria; Braña, Irene; Tabernero, Josep

    2015-04-15

    To evaluate safety (primary endpoint), tolerability, pharmacokinetics, pharmacodynamic profile, and preliminary activity of the intravenous, pan-class I isoform PI3K/mTOR inhibitor PF-05212384 in patients with advanced solid tumors. Part 1 of this open-label phase I study was designed to estimate the maximum-tolerated dose (MTD) in patients with nonselected solid tumors, using a modified continual reassessment method to guide dose escalation. Objectives of part 2 were MTD confirmation and assessment of preliminary activity in patients with selected tumor types and PI3K pathway dysregulation. Seventy-seven of the 78 enrolled patients received treatment. The MTD for PF-05212384, administered intravenously once weekly, was estimated to be 154 mg. The most common treatment-related adverse events (AE) were mucosal inflammation/stomatitis (58.4%), nausea (42.9%), hyperglycemia (26%), decreased appetite (24.7%), fatigue (24.7%), and vomiting (24.7%). The majority of patients treated at the MTD experienced only grade 1 treatment-related AEs. Grade 3 treatment-related AEs occurred in 23.8% of patients at the MTD. No treatment-related grade 4-5 AEs were reported at any dose level. Antitumor activity was noted in this heavily pretreated patient population, with two partial responses (PR) and an unconfirmed PR. Eight patients had long-lasting stable disease (>6 months). Pharmacokinetic analyses showed a biphasic concentration-time profile for PF-05212384 (half-life, 30-37 hours after multiple dosing). PF-05212384 inhibited downstream effectors of the PI3K pathway in paired tumor biopsies. These findings demonstrate the manageable safety profile and antitumor activity of the PI3K/mTOR inhibitor PF-05212384, supporting further clinical development for patients with advanced solid malignancies. ©2015 American Association for Cancer Research.

  13. Intravenous iron-containing products: EMA procrastination.

    Science.gov (United States)

    2014-07-01

    A European reassessment has led to identical changes in the summaries of product characteristics (SPCs) for all intravenous iron-containing products: the risk of serious adverse effects is now highlighted, underlining the fact that intravenous iron-containing products should only be used when the benefits clearly outweigh the harms. Unfortunately, iron dextran still remains on the market despite a higher risk of hypersensitivity reactions than with iron sucrose.

  14. The effect of high antigen density on solid-phase radioimmunoassays for antibody regardless of immunoglobulin class

    International Nuclear Information System (INIS)

    Rubin, R.L.; Hardtke, M.A.; Carr, R.I.

    1980-01-01

    Human sera containing antibody to casein or to bovine serum albumin were used to assess the validity and utility of a solid-phase assay for quantitating antibody activity. Rabbit anti-human immunoglobulin radiolabeled with 125 I and capable of reacting with all human immunoglobulin classes was used to detect antibody bound to antigen immobilized to polystyrene tubes by a new covalent technique. This method results in very high antigen concentrations in highly stable association with polystyrene tubes. Kinetic and absorption studies demonstrated that low avidity antibodies are better detected when antigen is immobilized by the covalent method than when passively adsorbed. Conditions are described for minimizing artifactual interactions and for obtaining results similar to those obtained with conventional, liquid-phase assays. Failure to reach equilibrium in solid-phase assays and other problems are proposed to explain, in part, the inability to obtain a better correlation between solid- and liquid-phase immunoassays. (Auth.)

  15. Manufacture of immunoglobulin products for patients with primary antibody deficiencies – the effect of processing conditions on product safety and efficacy

    Directory of Open Access Journals (Sweden)

    Albert eFarrugia

    2014-12-01

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

  16. Optimal composition of intravenous lipids

    African Journals Online (AJOL)

    fatty acids. All these fatty acids present a source of energy with a ..... Phagocytosis and killing of Candida albicans by human. Figure 4: ... Mechanisms of increased survival after lipopolysaccharide- induced .... Dietary alpha-linolenic acid and.

  17. Comparisons in fluctuation of muscle strength and function in patients with immune mediated neuropathy treated with intravenous versus subcutaneous immunoglobulin

    DEFF Research Database (Denmark)

    Christiansen, Ingelise; Markvardsen, Lars; Jakobsen, Johannes

    2018-01-01

    : In a prospective, open-label study, patients were changed from monthly IVIg to weekly SCIg. The primary endpoint was variation in isokinetic muscle strength (cIKS). Secondary endpoints were variations in Medical Research Council (MRC) score, grip strength (GS), 9-hole-peg test (9-HPT), and 40-meter-walk test (40...

  18. 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.

  19. Serum immunoglobulin G4 levels and Graves' disease phenotype.

    Science.gov (United States)

    Martin, Carmen Sorina; Sirbu, Anca Elena; Betivoiu, Minodora Andreea; Florea, Suzana; Barbu, Carmen Gabriela; Fica, Simona Vasilica

    2017-02-01

    We investigated, at diagnosis, the relationship between serum immunoglobulin G4 levels and the main characteristics of Graves' disease: hyperthyroidism severity, goiter size, presence of active Graves' ophthalmopathy, antithyroid antibodies status, and titer. This prospective study included 80 newly diagnosed Graves' disease patients. The main parameters measured at diagnosis: thyroid-stimulating hormone, free thyroxine, free triiodothyronine, total triiodothyronine, thyroglobulin, antithyroid peroxidase antibodies, anti-thyroglobulin antibodies, thyroid-stimulating hormone receptor antibodies, immunoglobulin G4. In Graves' disease patients, serum immunoglobulin G4 levels were higher than in general population (p = 0.028) and higher in men compared to women (p = 0.002). Only one female patient with intense hypoechoic goiter, high anti-thyroglobulin antibody, and antithyroid peroxidase antibody titers had an elevated serum immunoglobulin G4 level at diagnosis. Patients with immunoglobulin G4 levels above the 75th percentile (>237.52 mg/dl, N = 20) were younger at Graves' ophthalmopathy onset (p 286.28 mg/dl, N = 8) had lower total triiodothyronine values (p = 0.001) than patients with IgG below the 90th percentile. No significant correlations were found between smoking status (p = 0.58), goiter size (p = 0.50), the presence of ophthalmopathy (p = 0.42) or thyroid-stimulating hormone receptor antibody titers (p = 0.45) and the mean value of immunoglobulin G4 levels at diagnosis. Our data suggest that Graves' disease patients with elevated immunoglobulin G4 levels at diagnosis have a phenotype characterized by higher anti-thyroglobulin antibody and antithyroid peroxidase antibody titers, less severe T3 hyperthyroidism, younger age at ophthalmopathy onset and require a shorter duration of the first methimazole treatment cycle.

  20. Current treatment options with immunoglobulin G for the individualization of care in patients with primary immunodeficiency disease.

    Science.gov (United States)

    Jolles, S; Orange, J S; Gardulf, A; Stein, M R; Shapiro, R; Borte, M; Berger, M

    2015-02-01

    Primary antibody deficiencies require lifelong replacement therapy with immunoglobulin (Ig)G to reduce the incidence and severity of infections. Both subcutaneous and intravenous routes of administering IgG can be effective and well tolerated. Treatment regimens can be individualized to provide optimal medical and quality-of-life outcomes in infants, children, adults and elderly people. Frequency, dose, route of administration, home or infusion-centre administration, and the use of self- or health-professional-administered infusion can be tailored to suit individual patient needs and circumstances. Patient education is needed to understand the disease and the importance of continuous therapy. Both the subcutaneous and intravenous routes have advantages and disadvantages, which should be considered in selecting each patient's treatment regimen. The subcutaneous route is attractive to many patients because of a reduced incidence of systemic adverse events, flexibility in scheduling and its comparative ease of administration, at home or in a clinic. Self-infusion regimens, however, require independence and self-reliance, good compliance on the part of the patient/parent and the confidence of the physician and the nurse. Intravenous administration in a clinic setting may be more appropriate in patients with reduced manual dexterity, reluctance to self-administer or a lack of self-reliance, and intravenous administration at home for those with good venous access who prefer less frequent treatments. Both therapy approaches have been demonstrated to provide protection from infections and improve health-related quality of life. Data supporting current options in IgG replacement are presented, and considerations in choosing between the two routes of therapy are discussed. © 2014 British Society for Immunology.

  1. Human antibodies to immunoglobulin A (IgA)

    International Nuclear Information System (INIS)

    Munster, P.J.J. van; Nadorp, J.H.S.M.; Shuurman, H.J.

    1978-01-01

    In the sera of 12 out of 27 individuals with IgA deficiency (serum level below 0.02 mg IgA/m) class-specific anti-IgA antibodies were demonstrated by haemagglutination. These sera showed false-positive results in a solid-phase inhibition radioimmunoassay (RIST) (apparent IgA concentration between 0.6 and 13.7 μg IgA/ml) indicating that the RIST is not an appropriate test for the analysis of serum of IgA seficient individuals. A modification of the RIST is proposed (titration RIA) that permits differentiation between low levels of IgA and class-specific anti-IgA antibodies. With this test IgA deficient individuals could be classified as those with low but detectable levels of IgA and those with class-specific anti-IgA antibodies. A computer procedure was developed to calculate both the amount and the avidity (K) of the anti-IgA antibodies and to simulate the assay system. The K value calculated from experimental points proved to be an overestimation of the K value which fitted most adequately in the simulation. The comparison of the results with clinical findings indicated a possible correlation between the amount and the avidity of the anti-IgA antibodies and the appearence of anaphylactic reactions after transfusion of IgA. (Auth.)

  2. Subcutaneous immunoglobulin as first-line therapy in treatment-naive patients with chronic inflammatory demyelinating polyneuropathy

    DEFF Research Database (Denmark)

    Markvardsen, L H; Sindrup, S H; Christiansen, I

    2017-01-01

    BACKGROUND AND PURPOSE: Subcutaneous immunoglobulin (SCIG) is effective as maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). We investigated whether multiple subcutaneous infusions are as effective as conventional therapy with intravenous loading doses in treatment...... treatment arm and followed for a further 10 weeks. All participants were evaluated at weeks 0, 2, 5 and 10 during both therapies. Primary outcome was combined isokinetic muscle strength (cIKS). Secondary outcomes were disability, clinical evaluation of muscle strength and the performance of various function...... tests. RESULTS: All participants received both therapies, 14 completing the protocol. Overall, cIKS increased by 7.4 ± 14.5% (P = 0.0003) during SCIG and by 6.9 ± 16.8% (P = 0.002) during IVIG, the effect being similar (P = 0.80). Improvement of cIKS peaked 2 weeks after IVIG and 5 weeks after SCIG...

  3. Simple immunoglobulin G sensor based on thin core single-mode fiber

    Science.gov (United States)

    Zheng, Yingfang; Lang, Tingting; Shen, Tingting; Shen, Changyu

    2018-03-01

    In this paper, a simple fiber biosensor (FOB) for immunoglobulin G (IgG) detection is designed and experimentally verified. The FOB is constructed by a 20 mm long thin core single-mode fiber (TCSMF) sandwiched between two single-mode optical fibers (SMFs). First, the refractive index (RI) sensitivity of the fiber structures is calculated by the beam propagation method. The refractive index sensing experiment is performed using different concentrations of glycerol solutions, and the experimental results are mostly consistent with the simulation predictions. The experimental RI sensitivity increases with the surrounding RI and reaches 82.7 nm/RIU. Then the surface of the FOB is functionalized by APTES for covalent bonding. The human IgG and goat anti-human IgG are chosen as a bioconjugated pair to examine the bio-sensing effectiveness of this FOB. The sensitivity of IgG detection is determined to be 10.4 nm/(mg/ml). And the serum IgG concentration in normal adults lies within the range of 6-16 mg/ml (Worsfold et al., 1985), so the sensor is applicable to human IgG monitoring. The specificity of the FOB is also verified by a contrast experiment conducted using rabbit immunoglobulin G. The proposed FOB is simple, low loss, cost-effective, and can be used for various biological and chemical applications.

  4. SCM, the M Protein of Streptococcus canis Binds Immunoglobulin G.

    Science.gov (United States)

    Bergmann, Simone; Eichhorn, Inga; Kohler, Thomas P; Hammerschmidt, Sven; Goldmann, Oliver; Rohde, Manfred; Fulde, Marcus

    2017-01-01

    The M protein of Streptococcus canis (SCM) is a virulence factor and serves as a surface-associated receptor with a particular affinity for mini-plasminogen, a cleavage product of the broad-spectrum serine protease plasmin. Here, we report that SCM has an additional high-affinity immunoglobulin G (IgG) binding activity. The ability of a particular S. canis isolate to bind to IgG significantly correlates with a scm -positive phenotype, suggesting a dominant role of SCM as an IgG receptor. Subsequent heterologous expression of SCM in non-IgG binding S. gordonii and Western Blot analysis with purified recombinant SCM proteins confirmed its IgG receptor function. As expected for a zoonotic agent, the SCM-IgG interaction is species-unspecific, with a particular affinity of SCM for IgGs derived from human, cats, dogs, horses, mice, and rabbits, but not from cows and goats. Similar to other streptococcal IgG-binding proteins, the interaction between SCM and IgG occurs via the conserved Fc domain and is, therefore, non-opsonic. Interestingly, the interaction between SCM and IgG-Fc on the bacterial surface specifically prevents opsonization by C1q, which might constitute another anti-phagocytic mechanism of SCM. Extensive binding analyses with a variety of different truncated SCM fragments defined a region of 52 amino acids located in the central part of the mature SCM protein which is important for IgG binding. This binding region is highly conserved among SCM proteins derived from different S. canis isolates but differs significantly from IgG-Fc receptors of S. pyogenes and S. dysgalactiae sub. equisimilis , respectively. In summary, we present an additional role of SCM in the pathogen-host interaction of S. canis . The detailed analysis of the SCM-IgG interaction should contribute to a better understanding of the complex roles of M proteins in streptococcal pathogenesis.

  5. A phase 3 trial of IV immunoglobulin for Alzheimer disease.

    Science.gov (United States)

    Relkin, Norman R; Thomas, Ronald G; Rissman, Robert A; Brewer, James B; Rafii, Michael S; van Dyck, Christopher H; Jack, Clifford R; Sano, Mary; Knopman, David S; Raman, Rema; Szabo, Paul; Gelmont, David M; Fritsch, Sandor; Aisen, Paul S

    2017-05-02

    We tested biweekly infusions of IV immunoglobulin (IVIg) as a possible treatment for mild to moderate Alzheimer disease (AD) dementia. In a phase 3, double-blind, placebo-controlled trial, we randomly assigned 390 participants with mild to moderate AD to receive placebo (low-dose albumin) or IVIg (Gammagard Liquid; Baxalta, Bannockburn, IL) administered IV at doses of 0.2 or 0.4 g/kg every 2 weeks for 18 months. The primary cognitive outcome was change from baseline to 18 months on the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale; the primary functional outcome was 18-month change on the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory. Safety and tolerability data, as well as serial MRIs and plasma samples, were collected throughout the study from all enrolled participants. No beneficial effects were observed in the dual primary outcome measures for the 2 IVIg doses tested. Significant decreases in plasma Aβ42 (but not Aβ40) levels were observed in IVIg-treated participants. Analysis of safety data showed no difference between IVIg and placebo in terms of the rate of occurrence of amyloid-related imaging abnormalities (brain edema or microhemorrhage). IVIg-treated participants had more systemic reactions (chills, rashes) but fewer respiratory infections than participants receiving placebo. Participants with mild to moderate AD showed good tolerability of treatment with low-dose human IVIg for 18 months but did not show beneficial effects on cognition or function relative to participants who received placebo. NCT00818662. This study provides Class II evidence that IVIg infusions performed every 2 weeks do not improve cognition or function at 18 months in patients with mild to moderate AD. © 2017 American Academy of Neurology.

  6. [Peripheral intravenous catheter-related phlebitis].

    Science.gov (United States)

    van der Sar-van der Brugge, Simone; Posthuma, E F M Ward

    2011-01-01

    Phlebitis is a very common complication of the use of intravenous catheters. Two patients with an i.v. catheter complicated by thrombophlebitis are described. Patient A was immunocompromised due to chronic lymphatic leukaemia and developed septic thrombophlebitis with positive blood cultures for S. Aureus. Patient B was being treated with flucloxacillin because of an S. Aureus infection and developed chemical phlebitis. Septic phlebitis is rare, but potentially serious. Chemical or mechanical types of thrombophlebitis are usually less severe, but happen very frequently. Risk factors include: female sex, previous episode of phlebitis, insertion at (ventral) forearm, emergency placement and administration of antibiotics. Until recently, routine replacement of peripheral intravenous catheters after 72-96 h was recommended, but randomised controlled trials have not shown any benefit of this routine. A recent Cochrane Review recommends replacement of peripheral intravenous catheters when clinically indicated only.

  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...... providing evidence of its benefit. In the context of the recently described immunomodulatory functions of vitamin D, we aimed to assess the relationship between vitamin D and IgG levels....

  8. Specific egg yolk immunoglobulin as a new preventive approach for Shiga-toxin-mediated diseases.

    Directory of Open Access Journals (Sweden)

    Paola Neri

    Full Text Available Shiga toxins (Stxs are involved in the development of severe systemic complications associated with enterohemorrhagic Escherichia coli (EHEC infection. Various neutralizing agents against Stxs are under investigation for management of EHEC infection. In this study, we immunized chickens with formalin-inactivated Stx-1 or Stx-2, and obtained immunoglobulin Y (IgY from the egg yolk. Anti-Stx-1 IgY and anti-Stx-2 IgY recognized the corresponding Stx A subunit and polymeric but not monomeric B subunit. Anti-Stx-1 IgY and anti-Stx-2 IgY suppressed the cytotoxicity of Stx-1 and Stx-2 to HeLa 229 cells, without cross-suppressive activity. The suppressive activity of these IgY was abrogated by pre-incubation with the corresponding recombinant B subunit, which suggests that the antibodies directed to the polymeric B subunits were predominantly involved in the suppression. In vivo, the intraperitoneal or intravenous administration of these IgY rescued mice from death caused by intraperitoneal injection of the corresponding toxin at a lethal dose. Moreover, oral administration of anti-Stx-2 IgY reduced the mortality of mice infected intestinally with EHEC O157:H7. Our results therefore suggest that anti-Stx IgY antibodies may be considered as preventive agents for Stx-mediated diseases in EHEC infection.

  9. Generation and characterization of ABT-981, a dual variable domain immunoglobulin (DVD-Ig(TM)) molecule that specifically and potently neutralizes both IL-1α and IL-1β.

    Science.gov (United States)

    Lacy, Susan E; Wu, Chengbin; Ambrosi, Dominic J; Hsieh, Chung-Ming; Bose, Sahana; Miller, Renee; Conlon, Donna M; Tarcsa, Edit; Chari, Ravi; Ghayur, Tariq; Kamath, Rajesh V

    2015-01-01

    Interleukin-1 (IL-1) cytokines such as IL-1α, IL-1β, and IL-1Ra contribute to immune regulation and inflammatory processes by exerting a wide range of cellular responses, including expression of cytokines and chemokines, matrix metalloproteinases, and nitric oxide synthetase. IL-1α and IL-1β bind to IL-1R1 complexed to the IL-1 receptor accessory protein and induce similar physiological effects. Preclinical and clinical studies provide significant evidence for the role of IL-1 in the pathogenesis of osteoarthritis (OA), including cartilage degradation, bone sclerosis, and synovial proliferation. Here, we describe the generation and characterization of ABT-981, a dual variable domain immunoglobulin (DVD-Ig) of the IgG1/k subtype that specifically and potently neutralizes IL-1α and IL-1β. In ABT-981, the IL-1β variable domain resides in the outer domain of the DVD-Ig, whereas the IL-1α variable domain is located in the inner position. ABT-981 specifically binds to IL-1α and IL-1β, and is physically capable of binding 2 human IL-1α and 2 human IL-1β molecules simultaneously. Single-dose intravenous and subcutaneous pharmacokinetics studies indicate that ABT-981 has a half-life of 8.0 to 10.4 d in cynomolgus monkey and 10.0 to 20.3 d in rodents. ABT-981 exhibits suitable drug-like-properties including affinity, potency, specificity, half-life, and stability for evaluation in human clinical trials. ABT-981 offers an exciting new approach for the treatment of OA, potentially addressing both disease modification and symptom relief as a disease-modifying OA drug.

  10. Anaemia and fever in kidney transplant. The role of human parvovirus B19

    Directory of Open Access Journals (Sweden)

    Yanet Parodis López

    2017-03-01

    We report the case of a 65 year-old man with a history of deceased donor renal transplant in September 2014. At 38 days after the transplant, the patient presented progressive anaemia that was resistant to erythropoiesis-stimulating agents. At 64 days after transplant, hyperthermia occurred with progressive deterioration of the patient's general condition. The viral serology and the first blood PCR for human parvovirus B19 were both negative. At 4 months and 19 days after, a bone marrow biopsy was conducted, showing giant erythroblasts with nuclear viral inclusions that were compatible with parvovirus; a PCR in the tissue confirmed the diagnosis. A second blood PCR was positive for parvovirus. After treatment with intravenous immunoglobulin and the temporary discontinuation of mycophenolate mofetil, a complete remission of the disease occurred, although the blood PCR for parvovirus B19 remained positive, so monitoring is necessary for future likely recurrence.

  11. General applicability of chicken egg yolk antibodies: the performance of IgY immunoglobulins raised against the hypoxia-inducible factor 1alpha

    OpenAIRE

    Camenisch, G; Tini, M; Chilov, D; Kvietikova, I; Srinivas, V; Caro, J; Spielmann, P; Wenger, R H; Gassmann, M

    1999-01-01

    Avian embryos and neonates acquire passive immunity by transferring maternal immunoglobulins from serum to egg yolk. Despite being a convenient source of antibodies, egg yolk immunoglobulins (IgY) from immunized hens have so far received scant attention in research. Here we report the generation and rapid isolation of IgY from the egg yolk of hens immunized against the alpha subunit of the human hypoxia-inducible factor 1 (HIF-1alpha). Anti-HIF-1alpha IgY antibodies were affinity purified and...

  12. On the dark side of therapies with immunoglobulin concentrates. The adverse events

    Directory of Open Access Journals (Sweden)

    Peter J. Spaeth

    2015-02-01

    Full Text Available Abstract to the dark side of therapies with human immunoglobulin G concentratesTherapy by human immunoglobulin G (IgG concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A part of the success is the adverse event (AE profile of IgG concentrates which, even at life-long need for therapy, is excellent. Transmission of pathogens in the last decade could be entirely controlled through the antecedent introduction by authorities of a regulatory network and installing quality standards by the plasma fractionation industry. The cornerstone of the regulatory network is current Good Manufacturing practice. Non-infectious AEs occur rarely and mainly are mild to moderate. However, in recent times the increase in frequency of hemolytic and thrombotic AEs raised worrying questions on the possible background for these AEs. Below we review elements of non-infectious AEs , and particularly focus on hemolysis and thrombosis. We discuss how the introduction of plasma fractionation by ion-exchange chromatography and polishing by immunoaffinity chromatographic steps might alter repertoire of specificities and influence AE profiles and efficacy of IgG concentrates.

  13. Nasal secretions from patients with polyps and healthy individuals, collected with a new aspiration system: evaluation of total protein and immunoglobulin concentrations

    NARCIS (Netherlands)

    Biewenga, J.; Stoop, A. E.; Baker, H. E.; Swart, S. J.; Nauta, J. J.; van Kamp, G. J.; van der Baan, S.

    1991-01-01

    This study was designed, first, to test a new system for aspiration of human nasal secretions and, secondly, to evaluate protein and immunoglobulin concentrations in these secretions at different levels of secretory activity. The direct aspiration system combines the advantages of minimal irritation

  14. The adverse effects of inadvertent intraoperative intravenous ...

    African Journals Online (AJOL)

    Inadvertent intravenous injection of 1% phenylephrine (10 mg) induced severe hypertension and tachycardia in a previously healthy female patient undergoing elective gynaecological surgery. This medical error was investigated using the criticalincident technique that is available in our department. This case report ...

  15. [Phlebitis associated to intravenous/infusional therapy].

    Science.gov (United States)

    Nicotera, Raffaela

    2011-01-01

    Phlebitis is a common problem associated to intravenous therapies, it may cause pain, sepsis and increased duration of hospitalization. Several factors can increase the risk of phlebitis. The literature review addresses the mechanisms of chemical phlebitis, the characteristics of drugs likely to cause a phlebitis and the main measures to be adopted for prevention and treatment.

  16. Intravenous iron supplementation in children on hemodialysis.

    NARCIS (Netherlands)

    Leijn, E.; Monnens, L.A.H.; Cornelissen, E.A.M.

    2004-01-01

    BACKGROUND: Children with end-stage renal disease (ESRD) on hemodialysis (HD) are often absolute or functional iron deficient. There is little experience in treating these children with intravenous (i.v.) iron-sucrose. In this prospective study, different i.v. iron-sucrose doses were tested in

  17. Campaign best practice in intravenous therapy.

    Science.gov (United States)

    Baldwin, Wayne; Murphy, Jayne; Shakespeare, David; Kelly, Chris; Fox, Louise; Kelly, Matthew

    Intravenous therapy is an integral part of nursing care but is associated with a high risk of infection. This article outlines a campaign that aimed to increase awareness of best practice for IV therapy and reduce the risks of healthcare-associated IV infections in hospital and community settings.

  18. Intravenous voriconazole after toxic oral administration

    NARCIS (Netherlands)

    Alffenaar, J.W.C.; Van Assen, S.; De Monchy, J.G.R.; Uges, D.R.A.; Kosterink, J.G.W.; Van Der Werf, T.S.

    In a male patient with rhinocerebral invasive aspergillosis, prolonged high-dosage oral administration of voriconazole led to hepatotoxicity combined with a severe cutaneous reaction while intravenous administration in the same patient did not. High concentrations in the portal blood precipitate

  19. Complex intravenous anesthesia in interventional procedures

    International Nuclear Information System (INIS)

    Xie Zonggui; Hu Yuanming; Huang Yunlong; You Yong; Wu Juan; Huang Zengping; Li Jian

    2006-01-01

    Objective: To evaluate the value and safety of Diprivan and Fentany intravenous administration of analgesia in interventional procedures. Methods: Diprivan with Fentany intravenous administration for analgesia was used in eighty interventional procedures of sixty-five patients, without tracheal tube insertion. Vital signs including HR, BP, arterial oxygen saturation (SpO 2 ) and patients' reaction to operating were recorded. Results: Intravenous anesthesia was cared out successfully in eighty interventional procedures, with patients under sleeping condition during the operation, together with no pain and no agony memory of the procedure. The amount of Diprivan was 500±100 mg and Fentany was 0.2±0.025 mg. Mean arterial pressure and SpO 2 were 11.4±2.2 kPa, 10.6±2.1 kPa and 98±1.0, 96±1.5 respectively before and after ten minutes of the operation, with no significant difference. Conclusions: Diprivan with Fentany intravenous administration for interventional procedure analgesia possess good safety, painless and no agony memory of the procedure; therefor ought to be recommended. (authors)

  20. Intravenous paracetamol overdose in a paediatric patient

    NARCIS (Netherlands)

    Broeks, Ilse J.; Van Roon, Eric N.; Van Pinxteren-Nagler, Evelyn; De Vries, Tjalling W.

    2013-01-01

    BACKGROUND: Paracetamol is a widely used drug in children. In therapeutic doses, paracetamol has an excellent safety profile. Since the introduction of the intravenous form in 2004, only three reports of accidental overdose in children have been published. The low number probably is due to

  1. Administration and monitoring of intravenous anesthetics

    NARCIS (Netherlands)

    Sahinovic, Marko M.; Absalom, Anthony R.; Struys, Michel M. R. F.

    2010-01-01

    Purpose of review The importance of accuracy in controlling the dose-response relation for intravenous anesthetics is directly related to the importance of optimizing the efficacy and quality of anesthesia while minimizing adverse drug effects. Therefore, it is important to measure and control all

  2. A double-tracer technique to characterize absorption, distribution, metabolism and excretion (ADME) of [14C]-basimglurant and absolute bioavailability after oral administration and concomitant intravenous microdose administration of [13C6]-labeled basimglurant in humans.

    Science.gov (United States)

    Guerini, Elena; Schadt, Simone; Greig, Gerard; Haas, Ruth; Husser, Christophe; Zell, Manfred; Funk, Christoph; Hartung, Thomas; Gloge, Andreas; Mallalieu, Navita L

    2017-02-01

    1. The emerging technique of employing intravenous microdose administration of an isotope tracer concomitantly with an [ 14 C]-labeled oral dose was used to characterize the disposition and absolute bioavailability of a novel metabotropic glutamate 5 (mGlu5) receptor antagonist under clinical development for major depressive disorder (MDD). 2. Six healthy volunteers received a single 1 mg [ 12 C/ 14 C]-basimglurant (2.22 MBq) oral dose and a concomitant i.v. tracer dose of 100 μg of [ 13 C 6 ]-basimglurant. Concentrations of [ 12 C]-basimglurant and the stable isotope [ 13 C 6 ]-basimglurant were determined in plasma by a specific LC/MS-MS method. Total [ 14 C] radioactivity was determined in whole blood, plasma, urine and feces by liquid scintillation counting. Metabolic profiling was conducted in plasma, urine, blood cell pellet and feces samples. 3. The mean absolute bioavailability after oral administration (F) of basimglurant was ∼67% (range 45.7-77.7%). The major route of [ 14 C]-radioactivity excretion, primarily in form of metabolites, was in urine (mean recovery 73.4%), with the remainder excreted in feces (mean recovery 26.5%). The median t max for [ 12 C]-basimglurant after the oral administration was 0.71 h (range 0.58-1.00) and the mean terminal half-life was 77.2 ± 38.5 h. Terminal half-life for the [ 14 C]-basimglurant was 178 h indicating presence of metabolites with a longer terminal half-life. Five metabolites were identified with M1-Glucuronide as major and the others in trace amounts. There was minimal binding of drug to RBCs. IV pharmacokinetics was characterized with a mean ± SD CL of 11.8 ± 7.4 mL/h and a Vss of 677 ± 229 L. 4. The double-tracer technique used in this study allowed to simultaneously characterize the absolute bioavailability and disposition characteristics of the new oral molecular entity in a single study.

  3. 21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fab fragment specific... Test Systems § 866.5520 Immunoglobulin G (Fab fragment specific) immunological test system. (a) Identification. An immunoglobulin G (Fab fragment specific) immunological test system is a device that consists...

  4. 21 CFR 866.5540 - Immunoglobulin G (Fd fragment specific) immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fd fragment specific... Test Systems § 866.5540 Immunoglobulin G (Fd fragment specific) immunological test system. (a) Identification. An immunoglobulin G (Fd fragment specific) immunological test system is a device that consists of...

  5. 21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fc fragment specific... Test Systems § 866.5530 Immunoglobulin G (Fc fragment specific) immunological test system. (a) Identification. An immunoglobulin G (Fc fragment specific) immunological test system is a device that consists of...

  6. Acute phase proteins and immunoglobulin classes in newly ...

    African Journals Online (AJOL)

    Background: No single organic cause has been found for schizophrenia and its management has been difficult. More so, there are few data on the immune parameters of Nigerian schizophrenic patients on drug treatment and those that are not on treatment. Methodology: This study determines the levels of immunoglobulin

  7. Rhesus anti-D immunoglobulin in chronic autoimmune neuropathy

    NARCIS (Netherlands)

    de Jager, AEJ; van der Hoeven, JH

    Objective - To investigate the effect of Rhesus anti-D immunoglobulin (anti-D) in patients with an autoimmune demyelinating neuropathy. Material and methods - Three patients with an autoimmune mediated neuropathy received 1000 IU anti-D weekly for 2 months. Results - Two patients worsened gradually

  8. Immunoglobulin therapy in hematologic neoplasms and after hematopoietic cell transplantation.

    Science.gov (United States)

    Ueda, Masumi; Berger, Melvin; Gale, Robert Peter; Lazarus, Hillard M

    2018-03-01

    Immunoglobulins are used to prevent or reduce infection risk in primary immune deficiencies and in settings which exploit its anti-inflammatory and immune-modulatory effects. Rigorous proof of immunoglobulin efficacy in persons with lympho-proliferative neoplasms, plasma cell myeloma, and persons receiving hematopoietic cell transplants is lacking despite many clinical trials. Further, there are few consensus guidelines or algorithms for use in these conditions. Rapid development of new therapies targeting B-cell signaling and survival pathways and increased use of chimeric antigen receptor T-cell (CAR-T) therapy will likely result in more acquired deficiencies of humoral immunity and infections in persons with cancer. We review immunoglobulin formulations and discuss efficacy and potential adverse effects in the context of preventing infections and in graft-versus-host disease. We suggest an algorithm for evaluating acquired deficiencies of humoral immunity in persons with hematologic neoplasms and recommend appropriate use of immunoglobulin therapy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Alpha chain determinants on the membrane of immunoglobulin synthesizing cells

    NARCIS (Netherlands)

    Hijmans, W.; Schuit, H.R.E.; Radl, J.; Vossen, J.M.J.J.

    1974-01-01

    In a study of surface immunoglobulins (Ig) on lymphocytes from patients with paraproteinemia (1), we observed that a variable number of plasma cells not only contained intracellular Ig, but also had Ig on their surface, as shown in the vital technique of immunofluorescence. Moreover, in the bone

  10. Bacteremia and immunoglobulin classes in Nigerian women with ...

    African Journals Online (AJOL)

    Apart from antiphospholipid- and thyroid- autoantibodies which were reported as underlying causes of recurrent pregnancy loss, specific IgG to patermal MHC and Rh was proposed. This raises the possibility of other classes of immunoglobulin in recurrent abortion. Twenty-four pregnant women with recurrent abortion ...

  11. serum immunoglobulin levels in white, asiatic and bantu blood donors

    African Journals Online (AJOL)

    all assays were calculated as a percentage of the mean of. TABLE I. RESULTS OF IMMUNOGLOBULIN ASSAYS OF tOO WHITE, tOO ASIATIC AND 100 BANTU DONORS, EXPRESSED AS A. PERCENTAGE OF A CONTROL SERUM. Parameter. Range. Mean. Variance. Standard deviation. CoefI. of variation.

  12. Effect of continuous milking on immunoglobulin concentrations in bovine colostrum

    NARCIS (Netherlands)

    Verweij, J.J.; Koets, A.P.; Eisenberg, S.W.F.

    2014-01-01

    Continuous milking is defined as a dairy cattle management system without a planned dry period for cows in late gestation. Continuous milking has been described to reduce health problems common in periparturient cattle, but may affect colostrum immunoglobulin (Ig) concentration and subsequently calf

  13. Diverse binding site structures revealed in homology models of polyreactive immunoglobulins

    Science.gov (United States)

    Ramsland, Paul A.; Guddat, Luke W.; Edmundson, Allen B.; Raison, Robert L.

    1997-09-01

    We describe here computer-assisted homology models of the combiningsite structure of three polyreactive immunoglobulins. Template-based modelsof Fv (VL-VH) fragments were derived forthe surface IgM expressed by the malignant CD5 positive B cells from threepatients with chronic lymphocytic leukaemia (CLL). The conserved frameworkregions were constructed using crystal coordinates taken from highlyhomologous human variable domain structures (Pot and Hil). Complementaritydetermining regions (CDRs) were predicted by grafting loops, taken fromknown immunoglobulin structures, onto the Fv framework models. The CDRtemplates were chosen, where possible, to be of the same length and of highresidue identity or similarity. LCDR1, 2 and 3 as well as HCDR1 and 2 forthe Fv were constructed using this strategy. For HCDR3 prediction, adatabase containing the Cartesian coordinates of 30 of these loops wascompiled from unliganded antibody X-ray crystallographic structures and anHCDR3 of the same length as that of the B CLL Fv was selected as a template.In one case (Yar), the resulting HCDR3 model gave unfavourable interactionswhen incorporated into the Fv model. This HCDR3 was therefore modelled usingan alternative strategy of construction of the loop stems, using apreviously described HCDR3 conformation (Pot), followed by chain closurewith a β-turn. The template models were subjected to positionalrefinement using energy minimisation and molecular dynamics simulations(X-PLOR). An electrostatic surface description (GRASP) did not reveal acommon structural feature within the binding sites of the three polyreactiveFv. Thus, polyreactive immunoglobulins may recognise similar and multipleantigens through a diverse array of binding site structures.

  14. Molecular Analysis of Activation-Induced Cytidine Deaminase Gene in Immunoglobulin-E Deficient Patients

    Directory of Open Access Journals (Sweden)

    Sergio Roa

    2008-01-01

    Full Text Available Understanding how class switch recombination (CSR is regulated to produce immunoglobulin E (IgE has become fundamental because of the dramatic increase in the prevalence of IgE-mediated hypersensitivity reactions. CSR requires the induction of the enzyme AICDA in B cells. Mutations in AICDA have been linked to Hyper-IgM syndrome (HIGM2, which shows absence of switching to IgE as well as to IgG and IgA. Although isolated IgE deficiency is a rare entity, here we show some individuals with normal serum IgM, IgG, and IgA levels that had undetectable total serum IgE levels. We have analyzed the AICDA gene in these individuals to determine if there are mutations in AICDA that could lead to selective IgE deficiency. Conformational sensitive gel electrophoresis (CSGE and sequencing analysis of AICDA coding sequences demonstrated sequence heterogeneity due to 5923A/G and 7888C/T polymorphisms, but did not reveal any novel mutation that might explain the selective IgE deficit.

  15. Intravenous/oral ciprofloxacin therapy versus intravenous ceftazidime therapy for selected bacterial infections.

    Science.gov (United States)

    Gaut, P L; Carron, W C; Ching, W T; Meyer, R D

    1989-11-30

    The efficacy and toxicity of sequential intravenous and oral ciprofloxacin therapy was compared with intravenously administered ceftazidime in a prospective, randomized, controlled, non-blinded trial. Thirty-two patients (16 patients receiving ciprofloxacin and 16 patients receiving ceftazidime) with 38 infections caused by susceptible Pseudomonas aeruginosa, enteric gram-negative rods, Salmonella group B, Serratia marcescens, Pseudomonas cepacia, and Xanthomonas maltophilia at various sites were evaluable for determination of efficacy. Length of therapy varied from seven to 25 days. Concomitant antimicrobials included intravenously administered beta-lactams for gram-positive organisms, intravenous/oral metronidazole and clindamycin for anaerobes, and intravenous/local amphotericin B for Candida albicans. Intravenous administration of 200 mg ciprofloxacin every 12 hours to 11 patients produced peak serum levels between 1.15 and 3.12 micrograms/ml; trough levels ranged between 0.08 and 0.86 micrograms/ml. Overall response rates were similar for patients receiving ciprofloxacin and ceftazidime. Emergence of resistance was similar in both groups--one Enterobacter cloacae and two P. aeruginosa became resistant after ciprofloxacin therapy and two P. aeruginosa became resistant after ceftazidime therapy. The frequency of superinfection with a variety of organisms was also similar in both groups. Adverse events related to ciprofloxacin included transient pruritus at the infusion site and generalized rash leading to drug discontinuation (one patient each), and with ceftazidime adverse effects included pain at the site of infusion and the development of allergic interstitial nephritis (one patient each). Overall, intravenous/oral ciprofloxin therapy appears to be as safe and effective as intravenous ceftazidime therapy in the treatment of a variety of infections due to susceptible aerobic gram-negative organisms.

  16. Disposition of nasal, intravenous, and oral methadone in healthy volunteers.

    Science.gov (United States)

    Dale, Ola; Hoffer, Christine; Sheffels, Pamela; Kharasch, Evan D

    2002-11-01

    Nasal administration of many opioids demonstrates rapid uptake and fast onset of action. Nasal administration may be an alternative to intravenous and oral administration of methadone and was therefore studied in human volunteers. The study was approved by the Institutional Review Board of the University of Washington, Seattle. Eight healthy volunteers (6 men and 2 women) aged 19 to 33 years were enrolled after informed written consent was obtained. Subjects received 10 mg methadone hydrochloride nasally, orally, or intravenously on 3 separate occasions in a crossover design. Nasal methadone (50 mg/mL in aqueous solution) was given as a 100-microL spray in each nostril (Pfeiffer BiDose sprayer). Blood samples for liquid chromatography-mass spectrometry analyses of methadone and the metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolinium were drawn for up to 96 hours. The methadone effect was measured by noninvasive infrared pupilometry coincident with blood sampling. Nasal uptake of methadone was rapid, with maximum plasma concentrations occurring within 7 minutes. The maximum effects of intravenous, nasal, and oral methadone, on the basis of dark-adapted pupil diameter, were reached in about 15 minutes, 30 minutes, and 2 hours, respectively. The respective durations were 24, 10, and 8 hours. Both nasal and oral bioavailabilities were 0.85. Subjects reported that nasal methadone caused a burning sensation. Nasal administration of methadone results in rapid absorption and onset of effect and high bioavailability, which was greater than that reported for other nasal opioids, with a similar duration of effect. Nasal administration may be an alternative route of methadone administration; however, improved formulations are desirable to reduce nasal irritation.

  17. Acute toxicity of intravenously administered titanium dioxide nanoparticles in mice.

    Directory of Open Access Journals (Sweden)

    Jiaying Xu

    Full Text Available BACKGROUND: With a wide range of applications, titanium dioxide (TiO₂ nanoparticles (NPs are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO₂ nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans. METHODS: In this study, mice were injected intravenously with a single dose of TiO₂ NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg. Animal mortality, blood biochemistry, hematology, genotoxicity and histopathology were investigated 14 days after treatment. RESULTS: Death of mice in the highest dose (1387 mg/kg group was observed at day two after TiO₂ NPs injection. At day 7, acute toxicity symptoms, such as decreased physical activity and decreased intake of food and water, were observed in the highest dose group. Hematological analysis and the micronucleus test showed no significant acute hematological or genetic toxicity except an increase in the white blood cell (WBC count among mice 645 mg/kg dose group. However, the spleen of the mice showed significantly higher tissue weight/body weight (BW coefficients, and lower liver and kidney coefficients in the TiO₂ NPs treated mice compared to control. The biochemical parameters and histological tissue sections indicated that TiO₂ NPs treatment could induce different degrees of damage in the brain, lung, spleen, liver and kidneys. However, no pathological effects were observed in the heart in TiO₂ NPs treated mice. CONCLUSIONS: Intravenous injection of TiO₂ NPs at high doses in mice could cause acute toxicity effects in the brain, lung, spleen, liver, and kidney. No significant hematological or genetic toxicity was observed.

  18. Spongiform leucoencephalopathy following intravenous heroin abuse: Radiological and histopathological findings

    International Nuclear Information System (INIS)

    Robertson, A.S.; Jain, S.; O'Neil, R.A.

    2001-01-01

    A case of spongiform leucoencephalopathy in a known intravenous heroin abuser is presented. To our knowledge, this is the only case of heroin-related spongiform leucoencephalopathy reported in Australia. The relationship to intravenous rather than inhaled heroin is particularly unusual with only one other possible case documented in the literature. The imaging and histopathological findings are described. Neurological examination revealed disorientation in time and place, memory loss and cognitive impairment but no focal signs. Biochemical and haematological profiles were normal. Viral serology was positive for hepatitis C but negative for hepatitis B and human immunodeficiency virus (HIV). Cerebral CT revealed diffuse symmetrical hypodensity of the cerebral white matter. The ventricles and subarachnoid spaces were of normal size. Magnetic resonance imaging showed diffuse symmetrical signal abnormality in the cerebral white matter. These changes were hyperintense on proton density, T2-weighted, modified T2-weighted (FLAIR) and diffusion-weighted images. T1 -weighted scans showed corresponding hypointensity. There was no enhancement after intravenous gadolinium. Cerebral spinal fluid (CSF) specimens were negative for a variety of virological, immunological and bacteriological markers. No viral or bacterial growth was demonstrated. Oligoclonal bands for multiple sclerosis and Protein 134 for Wilson's disease were negative. Right frontal brain biopsy showed spongiform white matter and degenerative change with prominent fibrous gliosis. In severely affected areas, loss of normal myelin staining and axonal loss were present, accompanied by scattered foamy macrophages. Loss of oligodendroglial nuclei was also present. There was no evidence of inflammation or progressive multifocal leucoencephalopathy. No bacteria or virus particles were seen on electron microscopic examination of the brain tissue. Following the biopsy, the patient discharged himself from hospital and the

  19. Immunoglobulin concentration in blood serum of postcolostral calves: Ratio between immunoglobulin level and appearance of enzootic pneumonia

    Directory of Open Access Journals (Sweden)

    Jonić Branko

    2007-01-01

    Full Text Available The timely supply of newborn calves with optimal quantities of colostrum has a key role in the process of immune protection in the early phase of their lives. Passively acquired antibodies can protect the digestive organs from infection caused by E.coli bacteria, and it seems also from the appearance of diseases of the respiratory tract. These examinations were performed on a cattle farm where bronchopneumonia was one of the most significant health problems, and a group of 39 calves were selected for the investigations. The calves were fed with their mothers’ colostrum after birth, and then with collective milk. Immunoglobulin concentration was determined in blood samples taken during the postcolostral period, with the method using zinc-sulphate. At the age of 40 days, the calves were administered a polyvalent inactivated vaccine, and revaccinated 20 days after that (Vibak, Veterinary Department Subotica. In 74.34% calves, the immunoglobulin G concentration ranged from 26 to 40 g/l. In 25.66% calves, the immunoglobulin concentration was lower, from 8 to 25 g/l. The calves found to have a lower concentration of immunoglobulin in blood contracted bronchopneumonia more frequently, and the outcome of the disease in some cases was mortality, even.

  20. Intravenous cidofovir for resistant cutaneous warts in a patient with psoriasis treated with monoclonal antibodies.

    LENUS (Irish Health Repository)

    McAleer, M A

    2012-02-01

    Human papilloma virus is a common and often distressing cutaneous disease. It can be therapeutically challenging, especially in immunocompromised patients. We report a case of recalcitrant cutaneous warts that resolved with intravenous cidofovir treatment. The patient was immunocompromised secondary to monoclonal antibody therapy for psoriasis.

  1. Incarcerated intravenous heroin users: predictors of post-release utilization of methadone maintenance treatment.

    Science.gov (United States)

    Lin, Huang-Chi; Wang, Peng-Wei; Yang, Yi-Hsin; Tsai, Jih-Jin; Yen, Cheng-Fang

    2016-01-01

    Incarcerated intravenous heroin users have more problematic patterns of heroin use, but are less likely to access methadone maintenance treatment by their own initiative than heroin users in the community. The present study examined predictors for receiving methadone maintenance treatment post-release among incarcerated intravenous heroin users within a 24-month period. This cohort study recruited 315 incarcerated intravenous heroin users detained in 4 prisons in southern Taiwan and followed up within the 24-month period post-release. Cox proportional hazards regression analysis was applied to determine the predictive effects of sociodemographic and drug-use characteristics, attitude toward methadone maintenance treatment, human immunodeficiency virus serostatus, perceived family support, and depression for access to methadone maintenance treatment after release. There were 295 (93.7%) incarcerated intravenous heroin users released that entered the follow-up phase of the study. During the 24-month follow-up period, 50.8% of them received methadone maintenance treatment. After controlling for the effects of the detainment period before and after recruitment by Cox proportional hazards regression analysis, incarcerated intravenous heroin users who had positive human immunodeficiency virus serostatus (HR = 2.85, 95% CI = 1.80-4.52, p maintenance treatment before committal (HR = 1.94, 95% CI = 1.23-3.05, p maintenance treatment within the 24-month follow-up period. Positive human immunodeficiency virus serostatus with fully subsidized treatment and previous methadone maintenance treatment experiences predicted access of methadone maintenance treatment post-release. Strategies for getting familiar with methadone maintenance treatment during detainment, including providing methadone maintenance treatment prior to release and lowering the economic burden of receiving treatment, may facilitate entry of methadone maintenance treatment for incarcerated intravenous heroin

  2. Large-scale in vitro expansion of polyclonal human switched-memory B lymphocytes.

    Directory of Open Access Journals (Sweden)

    Sonia Néron

    Full Text Available Polyclonal preparations of therapeutic immunoglobulins, namely intravenous immunoglobulins (IVIg, are essential in the treatment of immunodeficiency and are increasingly used for the treatment of autoimmune and inflammatory diseases. Currently, patients' accessibility to IVIg depends exclusively upon volunteer blood donations followed by the fractionation of pooled human plasma obtained from thousands of individuals. Presently, there are no in vitro cell culture procedures allowing the preparation of polyclonal human antibodies. All in vitro human therapeutic antibodies that are currently generated are based on monoclonal antibodies, which are mostly issued from genetic engineering or single cell antibody technologies. Here, we describe an in vitro cell culture system, using CD40-CD154 interactions, that leads to a 1×10(6-fold expansion of switched memory B lymphocytes in approximately 50 days. These expanded cells secrete polyclonal IgG, which distribution into IgG(1, IgG(2, IgG(3 and IgG(4 is similar to that of normal human serum. Such in vitro generated IgG showed relatively low self-reactivity since they interacted moderately with only 24 human antigens among a total of 9484 targets. Furthermore, up to one liter of IgG secreting cells can be produced in about 40 days. This experimental model, providing large-scale expansion of human B lymphocytes, represents a critical step toward the in vitro production of polyclonal human IgG and a new method for the ex vivo expansion of B cells for therapeutic purposes.

  3. Optimal timing for intravenous administration set replacement.

    Science.gov (United States)

    Gillies, D; O'Riordan, L; Wallen, M; Morrison, A; Rankin, K; Nagy, S

    2005-10-19

    Administration of intravenous therapy is a common occurrence within the hospital setting. Routine replacement of administration sets has been advocated to reduce intravenous infusion contamination. If decreasing the frequency of changing intravenous administration sets does not increase infection rates, a change in practice could result in considerable cost savings. The objective of this review was to identify the optimal interval for the routine replacement of intravenous administration sets when infusate or parenteral nutrition (lipid and non-lipid) solutions are administered to people in hospital via central or peripheral venous catheters. We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, CINAHL, EMBASE: all from inception to February 2004; reference lists of identified trials, and bibliographies of published reviews. We also contacted researchers in the field. We did not have a language restriction. We included all randomized or quasi-randomized controlled trials addressing the frequency of replacing intravenous administration sets when parenteral nutrition (lipid and non-lipid containing solutions) or infusions (excluding blood) were administered to people in hospital via a central or peripheral catheter. Two authors assessed all potentially relevant studies. We resolved disagreements between the two authors by discussion with a third author. We collected data for the outcomes; infusate contamination; infusate-related bloodstream infection; catheter contamination; catheter-related bloodstream infection; all-cause bloodstream infection and all-cause mortality. We identified 23 references for review. We excluded eight of these studies; five because they did not fit the inclusion criteria and three because of inadequate data. We extracted data from the remaining 15 references (13 studies) with 4783 participants. We conclude that there is no evidence that changing intravenous administration sets more often than every 96 hours

  4. Production and Purification Immunoglobulin against E. coli in Egg Yolk

    Directory of Open Access Journals (Sweden)

    Mohammadreza Nassiri

    2016-08-01

    Full Text Available Introduction Chicken is the only avian species in which polyclonal antibodies, like IgG is transported from the hen to the egg yolk in a similar manner as the transport of mammalian IgG from the mother to the fetus. Immunoglobulin Y in the chicken is transported to the egg and accumulates in the egg yolk in large quantities. IgY is an egg yolk antibody that has been used widely for treatment and prevention of infections in humans and animal. IgY is used for passive protection of the pathogen infections such as Escherichia coli, bovine and human rotavirus, bovine coronavirus, salmonella, staphylococcus and Pseudomonas. IgY is a promising candidate as an alternative to antibiotics. Eschericha coli strains of serotype O157: H7 belongs to a family of pathogenic E. coli called enterohemorrhagic E. coli (EHEC strains responsible for hemorrhagic colitis, bloody or non-bloody diarrhea, and hemolytic uremic syndrome in humans. This strain of E. coli pathogenises by adhering to host intestinal epithelium and forming bacterial colonies. The purpose of this study was to produce and purify immunoglobulin Y against E. coli O157:H7 and develop specific polyclonal anti E. coli antibody in the egg yolk. Materials and Methods Sixteen-week-old laying hens (Mashhad, Iran were kept in individual cages with food and water ad libitum. Immunization of hens was performed by intramuscularly injecting killed E. coli O157: H7 with an equal volume of Freund’s complete adjuvant into two sides of chest area (Sigma, USA for the first immunization. Two booster immunizations followed up using complete and incomplete Freund’s adjuvants in two weeks interval. Freund’s adjuvant without antigen was injected to the control group. Two weeks after the last injection, the eggs were collected daily for eight weeks, marked and stored at 4 ºC. In order to IgY purification, eggs were collected. Purification of IgY from egg yolk was based on Polson and using PEG6000. Finally, the

  5. [Use of monoclonal antibodies against horse immunoglobulin in an enzyme immunoassay of bacterial toxins and anatoxins].

    Science.gov (United States)

    Burkin, M A; Gal'vidis, I A; Iakovleva, I V; Sviridov, V V

    2007-01-01

    Immunization of BALB/c mice by horse antiserum against diphtheria made it possible to obtain IgG1 monoclonal antibodies (MoAbs) 2B7E4 specific for light chains of horse immunoglobulin (Ig). Unlike commercial preparations of anti-horse immunoglobulin antibodies, which are specific for the whole Ig molecule or its Fc-fragment, the peroxidase (HRP) conjugate of the MoAb, 2B7E4-HRP did not interact with human, mouse, rabbit, and sheep Igs, or horse albumin. The conjugate obtained was used with MoAbs against bacterial toxins and commercial horse anatoxins, as a universal reagent in sandwich enzyme immunoassay (ELISA) for bacterial toxins and anatoxins. The detection sensitivity of diphtheria toxin/anatoxin equaled 0.0005 Lf/ml; tetanus toxin and anatoxin were detected with sensitivities of 20 LD50/ml and 0.005 UI/ml, respectively. A similar sandwich ELISA for botulinum anatoxins (group measurement) allowed types A, B, and E to be detected at 0.02, 0.002, and 0.001 UI/ml, respectively; selective measurement was only possible in the case of type E anatoxin (0.001 UI/ml).

  6. Technology of DTPA and immunoglobulins conjugation and their attachment to 90Y and 177Lu radionuclides

    International Nuclear Information System (INIS)

    Rekova, M.; Jedinakova-Krizova, V.

    2010-01-01

    The aim of the study of labeling of ligand-antibody conjugates was to find optimal conditions of preparing of these conjugates and appropriate radioactivity of selected nuclide for applications in nuclear medicine. Conjugation of the γ-immunoglobulin G (human or bovine IgG, polyclonal antibodies) and bifunctional chelating agent, diethylenetriaminepentaacetic acid dianhydride (cDTPAA), was carried out. Various values of the cDTPAA/antibody ratio, the weight concentration of polyclonal or monoclonal antibodies (MEM-97) and buffers were used. Further, the labeling conditions of the DTPA-IgG conjugate by radionuclides 90 Y and 177 Lu were optimized, and the labeling yield and the conjugation ratio of prepared radionuclide-DTPA-IgG conjugates was determined. Optimal incubation time of the immunoglobulin conjugation was obtained at 30 min from mixing of individual components. The labeling yield of radionuclide-DTPA-antibody conjugate higher than 95% was achieved. Higher values of conjugation ratio of radionuclide-DTPA-antibody conjugate were achieved in 0.1 mol L -1 carbonate buffer, pH 8.5, and the 0.1 mol L -1 carbonate buffer is suitable for studied conjugation systems. This study showed that the labeling yield as well as the conjugation ratio of tested systems depend on the amount of antibody substance, bifunctional chelating agent/antibody molar ratio and pH value of the buffer used. (author)

  7. T-cell independent reconstitution of the immunoglobulin levels in nu/nu mice

    International Nuclear Information System (INIS)

    Mannhardt, W.; Schulte-Wissermann, H.; Gardilcic, S.; Leon, F. de

    1982-01-01

    Nude mice were transplanted under the renal capsule either with allogeneic or human thymus that were long-term precultured or pretreated in vitro with Carrageenan for three days. None of the thymus tissue transplants showed lymphatic repopulation 9 wk after transplantation. Histological investigation of the peripheral lymphatic tissue did not reveal any change in the thymus-dependent area. On the other hand, plasma cells and germinal centers could be found in significantly increased numbers. In addition, a normalization of the serum immunoglobulin concentrations could be found, as no specific antibodies against thymus-dependent antigens were present after immunization and T-cell function did not improve. Similar results were obtained 9 wk after injection of irradiated thymocyte suspensions or of peritoneal macrophages from immunocompetent donors. It is concluded that thymus epithelial cells could act via macrophages on the polyclonal maturation and differentiation of B cells without involvement of T cells. This would be in agreement with the experience in some patients with severe combined immunodeficiency (SCID) in which reconstitution of the immunoglobulin levels is observed after transplantation of cultured thymus tissue before T-cell reconstitution can be demonstrated. (Auth.)

  8. Characterizing immunoglobulin repertoire from whole blood by a personal genome sequencer.

    Directory of Open Access Journals (Sweden)

    Fan Gao

    Full Text Available In human immune system, V(DJ recombination produces an enormously large repertoire of immunoglobulins (Ig so that they can tackle different antigens from bacteria, viruses and tumor cells. Several studies have demonstrated the utility of next-generation sequencers such as Roche 454 and Illumina Genome Analyzer to characterize the repertoire of immunoglobulins. However, these techniques typically require separation of B cell population from whole blood and require a few weeks for running the sequencers, so it may not be practical to implement them in clinical settings. Recently, the Ion Torrent personal genome sequencer has emerged as a tabletop personal genome sequencer that can be operated in a time-efficient and cost-effective manner. In this study, we explored the technical feasibility to use multiplex PCR for amplifying V(DJ recombination for IgH, directly from whole blood, then sequence the amplicons by the Ion Torrent sequencer. The whole process including data generation and analysis can be completed in one day. We tested the method in a pilot study on patients with benign, atypical and malignant meningiomas. Despite the noisy data, we were able to compare the samples by their usage frequencies of the V segment, as well as their somatic hypermutation rates. In summary, our study suggested that it is technically feasible to perform clinical monitoring of V(DJ recombination within a day by personal genome sequencers.

  9. Immunoglobulin levels in dogs after total-body irradiation and bone marrow transplantation

    International Nuclear Information System (INIS)

    Vriesendorp, H.M.; Halliwell, R.E.; Johnson, P.M.; Fey, T.A.; McDonough, C.M.

    1985-01-01

    The influence of total-body irradiation (TBI) and autologous or allogeneic bone marrow transplantation on serum immunoglobulin subclasses was determined in a dog model. Only IgG1 levels decreased after low-dose (+/- 4.5 Gy) TBI, but levels of all immunoglobulin classes fell after high-dose TBI (8.5 GyX1 or 2X6.0 Gy). After autologous bone marrow transplantation IgM levels were the first and IgE levels were the last to return to normal. After successful allogeneic bone marrow transplantation prolonged low IgM and IgE levels were found but IgA levels increased rapidly to over 150% of pretreatment values. A comparison of dogs with or without clinical signs or graft-versus-host disease (GVHD), revealed no differences in IgM levels. Dogs with GVHD had higher IgA but lower IgE levels. Dogs that rejected their allogeneic bone marrow cells showed significant early rises in IgE and IgA levels in comparison with dogs with GVHD. These results differ from the observations made on Ig levels in human bone marrow transplant patients. No significant differences in phytohemagglutinin stimulation tests were found between dogs with or without GVHD or dogs receiving an autologous transplant for the first four months after TBI and transplantation. An early primary or secondary involvement of humoral immunity in GVHD and graft rejection in dogs is postulated

  10. [Reducing fear in preschool children receiving intravenous injections].

    Science.gov (United States)

    Hsieh, Yi-Chuan; Liu, Hui-Tzu; Cho, Yen-Hua

    2012-06-01

    Our pediatric medical ward administers an average of 80 intravenous injections to preschool children. We found that 91.1% exhibit behavior indicative of fear and anxiety. Over three-quarters (77.8%) of this number suffer severe fear and actively resist receiving injections. Such behavior places a greater than normal burden on human and material resources and often gives family members negative impressions that lower their trust in the healthcare service while raising nurse-patient tensions. Using observation and interviews, we found primary factors in injection fear to be: Past negative experiences, lack of adequate prior communication, measures taken to preemptively control child resistance, and default cognitive behavioral strategies from nursing staff. This project worked to develop a strategy to reduce cases of severe injection fear in preschool children from 77.8% to 38.9% and achieve a capacity improvement target for members of 50%. Our team identified several potential strategy solutions from research papers and books between August 1st, 2009 and April 30th, 2010. Our proposed method included therapeutic games, self-selection of injection position, and cognitive behavioral strategies to divert attention. Other measures were also specified as standard operating procedures for administering pediatric intravenous injections. We applied the strategy on 45 preschool children and identified a post-injection "severe fear" level of 37.8%. This project was designed to reduce fear in children to make them more accepting of vaccinations and to enhance children's positive treatment experience in order to raise nursing care quality.

  11. Cardiovascular effects of intravenous ghrelin infusion in healthy young men

    DEFF Research Database (Denmark)

    Vestergaard, Esben Thyssen; Andersen, Niels Holmark; Hansen, Troels Krarup

    2007-01-01

    Ghrelin infusion improves cardiac function in patients suffering from cardiac failure, and bolus administration of ghrelin increases cardiac output in healthy subjects. The cardiovascular effects of more continuous intravenous ghrelin exposure remain to be studied. We therefore studied the cardio......Ghrelin infusion improves cardiac function in patients suffering from cardiac failure, and bolus administration of ghrelin increases cardiac output in healthy subjects. The cardiovascular effects of more continuous intravenous ghrelin exposure remain to be studied. We therefore studied...... the cardiovascular effects of a constant infusion of human ghrelin at a rate of 5 pmol/kg per minute for 180 min. Fifteen healthy, young (aged 23.2 ± 0.5 yr), normal-weight (23.0 ± 0.4 kg/m2) men volunteered in a randomized double-blind, placebo-controlled crossover study. With the subjects remaining fasting, peak...... myocardial systolic velocity S′, tissue tracking TT, left ventricular ejection fraction EF, and endothelium-dependent flow-mediated vasodilatation were measured. Ghrelin infusion increased S′ 9% (P = 0.002) and TT 10% (P

  12. Characterization of an intravenously injected bolus

    International Nuclear Information System (INIS)

    Samuel, A.M.; Raikar, U.R.; Atmaram, S.H.; Ganatra, R.D.

    1976-01-01

    A study of some parameters affecting the time activity histogram of an intravenous bolus injection of radioactivity was performed. A scoring system for bolus compactness was attempted. A score of 2 and above was considered to be a satisfactory bolus. Volumes less than 1 ml tended to result in a satisfactory bolus. The nature of radiopharmaceutical injected, different injecters and age of the patient did not affect the score. Thyrotoxic patients gave the best bolus score. (orig.) [de

  13. Successful outcome after intravenous gasoline injection.

    Science.gov (United States)

    Domej, Wolfgang; Mitterhammer, Heike; Stauber, Rudolf; Kaufmann, Peter; Smolle, Karl Heinz

    2007-12-01

    Gasoline, ingested intentionally or accidentally, is toxic. The majority of reported cases of gasoline intoxication involve oral ingestion or inhalation. Data are scarce on complications and outcomes following hydrocarbon poisoning by intravenous injection. Following a suicide attempt by intravenous self-injection of 10 ml of gasoline, a 26-year-old medical student was admitted to the intensive care unit (ICU) with hemoptysis, symptoms of acute respiratory failure, chest pain, and severe abdominal cramps. Gas exchange was severely impaired and a chest x-ray indicated chemical pneumonitis. Initial treatment consisted of mechanical ventilation, supportive hyperventilation, administration of nitrogen oxide (NO), and prednisone. Unfortunately, the patient developed multi-organ dysfunction syndrome (MODS) complicated by life-threatening severe vasoplegia within 24 hours after gasoline injection. High doses of vasopressors along with massive amounts of parenteral fluids were necessary. Despite fluid replacement, renal function worsened and required hemofiltration on 5 sequential days. After 12 days of intensive care management, the patient recovered completely and was discharged to a psychiatric care facility. Intravenous gasoline injection causes major injury to the lungs, the organ bearing the first capillary bed encountered. Treatment of gasoline poisoning is symptomatic because no specific antidote is available. Early and aggressive supportive care may be conducive to a favorable outcome with minimal residual pulmonary sequelae.

  14. Contrast agent choice for intravenous coronary angiography

    International Nuclear Information System (INIS)

    Zeman, H.D.; Siddons, D.P.

    1989-01-01

    The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with monochromatic synchrotron radiation x-rays and an iodine containing contrast agent at the Stanford Synchrotron Radiation Laboratory have shown that such an intravenous angiography procedure would be possible with an adequately intense monochromatic x-ray source. Because of the size and cost of synchrotron radiation facilities it would be desirable to make the most efficient use of the intensity available, while reducing as much as possible the radiation dose experienced by the patient. By choosing contrast agents containing elements with a higher atomic number than iodine, it is possible to both improve the image quality and reduce the patient radiation dose, while using the same synchrotron source. By using Si monochromator crystals with a small mosaic spread, it is possible to increase the x-ray flux available for imaging by over an order of magnitude, without any changes in the storage ring or wiggler magnet. The most critical imaging task for intravenous coronary angiography utilizing synchrotron radiation x-rays is visualizing a coronary artery through the left ventricle or aorta which also contains a contrast agent. Calculations have been made of the signal to noise ratio expected for this imaging task for various contrast agents with atomic numbers between that of iodine and bismuth

  15. Intravenous Lipids for Preterm Infants: A Review

    Directory of Open Access Journals (Sweden)

    Ghassan S. A. Salama

    2015-01-01

    Full Text Available Extremely low birth weight infants (ELBW are born at a time when the fetus is undergoing rapid intrauterine brain and body growth. Continuation of this growth in the first several weeks postnatally during the time these infants are on ventilator support and receiving critical care is often a challenge. These infants are usually highly stressed and at risk for catabolism. Parenteral nutrition is needed in these infants because most cannot meet the majority of their nutritional needs using the enteral route. Despite adoption of a more aggressive approach with amino acid infusions, there still appears to be a reluctance to use early intravenous lipids. This is based on several dogmas that suggest that lipid infusions may be associated with the development or exacerbation of lung disease, displace bilirubin from albumin, exacerbate sepsis, and cause CNS injury and thrombocytopena. Several recent reviews have focused on intravenous nutrition for premature neonate, but very little exists that provides a comprehensive review of intravenous lipid for very low birth and other critically ill neonates. Here, we would like to provide a brief basic overview, of lipid biochemistry and metabolism of lipids, especially as they pertain to the preterm infant, discuss the origin of some of the current clinical practices, and provide a review of the literature, that can be used as a basis for revising clinical care, and provide some clarity in this controversial area, where clinical care is often based more on tradition and dogma than science.

  16. Influences on physicians' choices of intravenous colloids.

    Science.gov (United States)

    Miletin, Michael S; Stewart, Thomas E; Norton, Peter G

    2002-07-01

    Controversy over the optimal intravenous fluid for volume resuscitation continues unabated. Our objectives were to characterize the demographics of physicians who prescribe intravenous colloids and determine factors that enter into their decision to choose a colloid. Questionnaire with 61 items. Ten percent ( n = 364) of frequent intravenous fluid prescribers in the province of Ontario, Canada. The response rate was 74%. Colloid use in the past year was reported by 79% of the responding physicians. Important reasons for choosing a colloid included blood loss and manipulation of oncotic pressure. Physicians tended to prefer either albumin or pentastarch, but no important reasons were found for choosing between the two. Albumin with or without crystalloid was preferred in 5/13 scenarios by more than 50% of the respondents, whereas pentastarch was not favored by more than 50% of respondents in any scenario. Physicians practising in critical care areas and teaching hospitals generally preferred pentastarch to albumin. Physicians reporting pentastarch as representing greater than 90% of total colloid use were more likely to have been visited by a drug detailer for pentastarch than those who used less synthetic colloid (54 vs 22%, p distribution. Although albumin appeared to be preferred in more clinical niches, most physicians did not state reasons for choosing between products. Marketing, specialty, location of practice and clinical scenario appear to play significant roles in the utilization of colloid products.

  17. [Detection of split products of the immunoglobulins IgG, IgA and IgM during chronic otitis media (author's transl)].

    Science.gov (United States)

    Kastenbauer, E R; Hochgesand, K; Hochstrasser, K; Tappermann, G

    1975-07-01

    Proteolytic enzymes such as pepsine or papaine are able to split IgG antibodies into large fragments in vitro. These immunoglobulin fragments (IgG, IgA, IgM) were now detected in vivo from the purulent secretions of cholesteatoma, chronic otitis media and radical mastoid cavities. During chronic otitis media the intact immunoglobulins are split due to the proteolytic activity of neutral proteinases. These fragments were qualitatively and quantitatively investigated by means of various immunological procedures. After the immunoelectrophoretic separation of the purulent middle-ear-secretions and after diffusion against anti-IgG-, anti-IgA- and anti-IgM- serum double precipitate lines could be observed especially in middle-ear-secretion with a bacterial flora of pseudomonas aeruginosa (pyocyanea) and of the proteus-providencia-group. This was the first proof of the presence of split products of the immunoglobulins. The exact demonstration of these split products could be carried out by gel-filtration and fractionation of the intact and split immunoglobulins. During chronic otitis media intact immunoglobulins are split by leucocytic and extracellular bacterial proteinases into fragments of different molecular weight. The most malignant extracellular proteinases with the greatest proteolytic activity against intact immunoglobulins are the bacterial proteinases of pseudomonas aeruginosa. These proteinases can not be inhibited by the other serum proteinaseinhibitors except for alpha-2-macroglobulin of the human blood serum. This inhibitor has a very high molecular weight so that we can not find it in a higher concentration in the middle-ear-secretion. We can liberate this inhibitor by injuring the blood vessels during a tympanoplasty. In this way we get an inhibitory effect against these proteinases and combined with an appropriate antibiotic therapy we can cure a chronic otitis media.

  18. High levels of immunoglobulin E and a continuous increase in immunoglobulin G and immunoglobulin M by age in children with newly diagnosed type 1 diabetes

    DEFF Research Database (Denmark)

    Svensson, Jannet; Eising, Stefanie; Mortensen, Henrik Bindesbøl

    2012-01-01

    The incidence of type 1 diabetes (T1D) is increasing, either because of environmental factors accelerating onset of the disease or because of inducement of autoimmune diabetes in children who previously were at lower risk. High levels of immunoglobulin (Ig), specifically, IgM and IgA, and a low...... level of IgG were reported in adult patients; however no studies have analyzed the increasing incidence in relation to Ig levels. Our aim was to describe Ig in children newly diagnosed with diabetes and in their healthy siblings. Children with T1D expressed significantly lower IgG (p

  19. Autoantibodies and immunoglobulins in alcoholic steatosis and cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Tage-Jensen, Ulrik Viggo

    1983-01-01

    increased (p less than 0.005) concentrations of immunoglobulins G, A, and M when compared to patients with steatosis. These results indicate that the degree of liver damage has more effect than chronic alcoholism on the humoral immune system. Whether this influence is direct or indirect remains......Antinuclear antibodies were significantly more prevalent (p less than 0.01) in 143 patients with alcoholic cirrhosis than in 64 patients with alcoholic steatosis and in 94 controls. Smooth muscle antibodies were significantly more prevalent (p less than 0.05) in patients with alcoholic steatosis...... and cirrhosis than in controls. The prevalence of antimitochondrial antibodies and IgG liver membrane antibodies did not differ significantly between the three groups. Immunoglobulin G, A, and M concentrations were only occasionally increased in patients with steatosis. Patients with cirrhosis had significantly...

  20. A role for PCNA ubiquitination in immunoglobulin hypermutation.

    Directory of Open Access Journals (Sweden)

    Hiroshi Arakawa

    2006-11-01

    Full Text Available Proliferating cell nuclear antigen (PCNA is a DNA polymerase cofactor and regulator of replication-linked functions. Upon DNA damage, yeast and vertebrate PCNA is modified at the conserved lysine K164 by ubiquitin, which mediates error-prone replication across lesions via translesion polymerases. We investigated the role of PCNA ubiquitination in variants of the DT40 B cell line that are mutant in K164 of PCNA or in Rad18, which is involved in PCNA ubiquitination. Remarkably, the PCNA(K164R mutation not only renders cells sensitive to DNA-damaging agents, but also strongly reduces activation induced deaminase-dependent single-nucleotide substitutions in the immunoglobulin light-chain locus. This is the first evidence, to our knowledge, that vertebrates exploit the PCNA-ubiquitin pathway for immunoglobulin hypermutation, most likely through the recruitment of error-prone DNA polymerases.